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Sample records for human primary somatosensory

  1. Four-dimensional maps of the human somatosensory system.

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    Avanzini, Pietro; Abdollahi, Rouhollah O; Sartori, Ivana; Caruana, Fausto; Pelliccia, Veronica; Casaceli, Giuseppe; Mai, Roberto; Lo Russo, Giorgio; Rizzolatti, Giacomo; Orban, Guy A

    2016-03-29

    A fine-grained description of the spatiotemporal dynamics of human brain activity is a major goal of neuroscientific research. Limitations in spatial and temporal resolution of available noninvasive recording and imaging techniques have hindered so far the acquisition of precise, comprehensive four-dimensional maps of human neural activity. The present study combines anatomical and functional data from intracerebral recordings of nearly 100 patients, to generate highly resolved four-dimensional maps of human cortical processing of nonpainful somatosensory stimuli. These maps indicate that the human somatosensory system devoted to the hand encompasses a widespread network covering more than 10% of the cortical surface of both hemispheres. This network includes phasic components, centered on primary somatosensory cortex and neighboring motor, premotor, and inferior parietal regions, and tonic components, centered on opercular and insular areas, and involving human parietal rostroventral area and ventral medial-superior-temporal area. The technique described opens new avenues for investigating the neural basis of all levels of cortical processing in humans.

  2. Intraoperative intrinsic optical imaging of human somatosensory cortex during neurosurgical operations.

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    Sato, Katsushige; Nariai, Tadashi; Momose-Sato, Yoko; Kamino, Kohtaro

    2017-07-01

    Intrinsic optical imaging as developed by Grinvald et al. is a powerful technique for monitoring neural function in the in vivo central nervous system. The advent of this dye-free imaging has also enabled us to monitor human brain function during neurosurgical operations. We briefly describe our own experience in functional mapping of the human somatosensory cortex, carried out using intraoperative optical imaging. The maps obtained demonstrate new additional evidence of a hierarchy for sensory response patterns in the human primary somatosensory cortex.

  3. Metaplasticity in human primary somatosensory cortex: effects on physiology and tactile perception.

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    Jones, Christina B; Lulic, Tea; Bailey, Aaron Z; Mackenzie, Tanner N; Mi, Yi Qun; Tommerdahl, Mark; Nelson, Aimee J

    2016-05-01

    Theta-burst stimulation (TBS) over human primary motor cortex evokes plasticity and metaplasticity, the latter contributing to the homeostatic balance of excitation and inhibition. Our knowledge of TBS-induced effects on primary somatosensory cortex (SI) is limited, and it is unknown whether TBS induces metaplasticity within human SI. Sixteen right-handed participants (6 females, mean age 23 yr) received two TBS protocols [continuous TBS (cTBS) and intermittent TBS (iTBS)] delivered in six different combinations over SI in separate sessions. TBS protocols were delivered at 30 Hz and were as follows: a single cTBS protocol, a single iTBS protocol, cTBS followed by cTBS, iTBS followed by iTBS, cTBS followed by iTBS, and iTBS followed by cTBS. Measures included the amplitudes of the first and second somatosensory evoked potentials (SEPs) via median nerve stimulation, their paired-pulse ratio (PPR), and temporal order judgment (TOJ). Dependent measures were obtained before TBS and at 5, 25, 50, and 90 min following stimulation. Results indicate similar effects following cTBS and iTBS; increased amplitudes of the second SEP and PPR without amplitude changes to SEP 1, and impairments in TOJ. Metaplasticity was observed such that TOJ impairments following a single cTBS protocol were abolished following consecutive cTBS protocols. Additionally, consecutive iTBS protocols altered the time course of effects when compared with a single iTBS protocol. In conclusion, 30-Hz cTBS and iTBS protocols delivered in isolation induce effects consistent with a TBS-induced reduction in intracortical inhibition within SI. Furthermore, cTBS- and iTBS-induced metaplasticity appear to follow homeostatic and nonhomeostatic rules, respectively. Copyright © 2016 the American Physiological Society.

  4. Encoding of Touch Intensity But Not Pleasantness in Human Primary Somatosensory Cortex

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    Laubacher, Claire M.; Olausson, Håkan; Wang, Binquan; Spagnolo, Primavera A.; Bushnell, M. Catherine

    2016-01-01

    Growing interest in affective touch has delineated a neural network that bypasses primary somatosensory cortex (S1). Several recent studies, however, have cast doubt on the segregation of touch discrimination and affect, suggesting that S1 also encodes affective qualities. We used functional magnetic resonance imaging (fMRI) and repetitive transcranial magnetic stimulation (rTMS) to examine the role of S1 in processing touch intensity and pleasantness. Twenty-six healthy human adults rated brushing on the hand during fMRI. Intensity ratings significantly predicted activation in S1, whereas pleasantness ratings predicted activation only in the anterior cingulate cortex. Nineteen subjects also received inhibitory rTMS over right hemisphere S1 and the vertex (control). After S1 rTMS, but not after vertex rTMS, sensory discrimination was reduced and subjects with reduced sensory discrimination rated touch as more intense. In contrast, rTMS did not alter ratings of touch pleasantness. Our findings support divergent neural processing of touch intensity and pleasantness, with affective touch encoded outside of S1. SIGNIFICANCE STATEMENT Growing interest in affective touch has identified a neural network that bypasses primary somatosensory cortex (S1). Several recent studies, however, cast doubt on the separation of touch discrimination and affect. We used functional magnetic resonance imaging and repetitive transcranial magnetic stimulation to demonstrate the representation of touch discrimination and intensity in S1, but the representation of pleasantness in the anterior cingulate cortex, not S1. Our findings support divergent neural processing of touch intensity and pleasantness, with affective touch encoded outside of S1. Our study contributes to growing delineation of the affective touch system, a crucial step in understanding its dysregulation in numerous clinical conditions such as autism, eating disorders, depression, and chronic pain. PMID:27225773

  5. Theta-Burst Stimulation-Induced Plasticity over Primary Somatosensory Cortex Changes Somatosensory Temporal Discrimination in Healthy Humans

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    Conte, Antonella; Rocchi, Lorenzo; Nardella, Andrea; Dispenza, Sabrina; Scontrini, Alessandra; Khan, Nashaba; Berardelli, Alfredo

    2012-01-01

    Background The somatosensory temporal discrimination threshold (STDT) measures the ability to perceive two stimuli as being sequential. Precisely how the single cerebral structures contribute in controlling the STDT is partially known and no information is available about whether STDT can be modulated by plasticity-inducing protocols. Methodology/Principal Findings To investigate how the cortical and cerebellar areas contribute to the STDT we used transcranial magnetic stimulation and a neuronavigation system. We enrolled 18 healthy volunteers and 10 of these completed all the experimental sessions, including the control experiments. STDT was measured on the left hand before and after applying continuous theta-burst stimulation (cTBS) on the right primary somatosensory area (S1), pre-supplementary motor area (pre-SMA), right dorsolateral prefrontal cortex (DLPFC) and left cerebellar hemisphere. We then investigated whether intermittent theta-burst stimulation (iTBS) on the right S1 improved the STDT. After right S1 cTBS, STDT values increased whereas after iTBS to the same cortical site they decreased. cTBS over the DLPFC and left lateral cerebellum left the STDT statistically unchanged. cTBS over the pre-SMA also left the STDT statistically unchanged, but it increased the number of errors subjects made in distinguishing trials testing a single stimulus and those testing paired stimuli. Conclusions/Significance Our findings obtained by applying TBS to the cortical areas involved in processing sensory discrimination show that the STDT is encoded in S1, possibly depends on intrinsic S1 neural circuit properties, and can be modulated by plasticity-inducing TBS protocols delivered over S1. Our findings, giving further insight into mechanisms involved in somatosensory temporal discrimination, help interpret STDT abnormalities in movement disorders including dystonia and Parkinson's disease. PMID:22412964

  6. Theta-burst stimulation-induced plasticity over primary somatosensory cortex changes somatosensory temporal discrimination in healthy humans.

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    Antonella Conte

    Full Text Available BACKGROUND: The somatosensory temporal discrimination threshold (STDT measures the ability to perceive two stimuli as being sequential. Precisely how the single cerebral structures contribute in controlling the STDT is partially known and no information is available about whether STDT can be modulated by plasticity-inducing protocols. METHODOLOGY/PRINCIPAL FINDINGS: To investigate how the cortical and cerebellar areas contribute to the STDT we used transcranial magnetic stimulation and a neuronavigation system. We enrolled 18 healthy volunteers and 10 of these completed all the experimental sessions, including the control experiments. STDT was measured on the left hand before and after applying continuous theta-burst stimulation (cTBS on the right primary somatosensory area (S1, pre-supplementary motor area (pre-SMA, right dorsolateral prefrontal cortex (DLPFC and left cerebellar hemisphere. We then investigated whether intermittent theta-burst stimulation (iTBS on the right S1 improved the STDT. After right S1 cTBS, STDT values increased whereas after iTBS to the same cortical site they decreased. cTBS over the DLPFC and left lateral cerebellum left the STDT statistically unchanged. cTBS over the pre-SMA also left the STDT statistically unchanged, but it increased the number of errors subjects made in distinguishing trials testing a single stimulus and those testing paired stimuli. CONCLUSIONS/SIGNIFICANCE: Our findings obtained by applying TBS to the cortical areas involved in processing sensory discrimination show that the STDT is encoded in S1, possibly depends on intrinsic S1 neural circuit properties, and can be modulated by plasticity-inducing TBS protocols delivered over S1. Our findings, giving further insight into mechanisms involved in somatosensory temporal discrimination, help interpret STDT abnormalities in movement disorders including dystonia and Parkinson's disease.

  7. Reorganization of the Human Somatosensory Cortex in Hand Dystonia

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    Maria Jose Catalan

    2012-05-01

    Full Text Available Background and Purpose: Abnormalities of finger representations in the somatosensory cortex have been identified in patients with focal hand dystonia. Measuring blood flow with positron emission tomography (PET can be use to demonstrate functional localization of receptive fields. Methods: A vibratory stimulus was applied to the right thumb and little finger of six healthy volunteers and six patients with focal hand dystonia to map their receptive fields using H215O PET. Results: The cortical finger representations in the primary somatosensory cortex were closer to each other in patients than in normal subjects. No abnormalities were found in secondary somatosensory cortex, but the somatotopy there is less well distinguished. Conclusions: These data confirm prior electrophysiological and functional neuroimaging observations showing abnormalities of finger representations in somatosensory cortex of patients with focal hand dystonia.

  8. Effects of mastication on human somatosensory processing: A study using somatosensory-evoked potentials.

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    Nakata, Hiroki; Aoki, Mai; Sakamoto, Kiwako

    2017-04-01

    The aim of the present study was to investigate the effects of mastication on somatosensory processing using somatosensory-evoked potentials (SEPs). Fourteen healthy subjects received a median nerve stimulation at the right wrist under two conditions: Mastication and Control. SEPs were recorded in five sessions for approximately seven minutes: Pre, Post 1, 2, 3, and 4. Subjects were asked to chew gum for five minutes after one session in Mastication. Control included the same five sessions. The amplitudes and latencies of P14, N20, P25, N35, P45, and N60 components at C3', frontal N30 component at Fz, and P100 and N140 components at Pz were analyzed. The amplitude of P45-N60 was significantly smaller at Post 1, 2, 3, and 4 than at Pre in Control, but not in Mastication. The latency of P25 was significantly longer at Post 2, 3, and 4 than at Pre in Control, but not in Mastication. The latency of P100 was significantly longer at Post 2 than at Pre in Control, but not in Mastication. These results suggest the significant effects of mastication on the neural activity of human somatosensory processing. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  9. Human perception of electrical stimulation on the surface of somatosensory cortex.

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    Shivayogi V Hiremath

    Full Text Available Recent advancement in electrocorticography (ECoG-based brain-computer interface technology has sparked a new interest in providing somatosensory feedback using ECoG electrodes, i.e., cortical surface electrodes. We conducted a 28-day study of cortical surface stimulation in an individual with arm paralysis due to brachial plexus injury to examine the sensation produced by electrical stimulation of the somatosensory cortex. A high-density ECoG grid was implanted over the somatosensory and motor cortices. Stimulation through cortical surface electrodes over the somatosensory cortex successfully elicited arm and hand sensations in our participant with chronic paralysis. There were three key findings. First, the intensity of perceived sensation increased monotonically with both pulse amplitude and pulse frequency. Second, changing pulse width changed the type of sensation based on qualitative description provided by the human participant. Third, the participant could distinguish between stimulation applied to two neighboring cortical surface electrodes, 4.5 mm center-to-center distance, for three out of seven electrode pairs tested. Taken together, we found that it was possible to modulate sensation intensity, sensation type, and evoke sensations across a range of locations from the fingers to the upper arm using different stimulation electrodes even in an individual with chronic impairment of somatosensory function. These three features are essential to provide effective somatosensory feedback for neuroprosthetic applications.

  10. Abnormal activation of the primary somatosensory cortex in spasmodic dysphonia: an fMRI study.

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    Simonyan, Kristina; Ludlow, Christy L

    2010-11-01

    Spasmodic dysphonia (SD) is a task-specific focal dystonia of unknown pathophysiology, characterized by involuntary spasms in the laryngeal muscles during speaking. Our aim was to identify symptom-specific functional brain activation abnormalities in adductor spasmodic dysphonia (ADSD) and abductor spasmodic dysphonia (ABSD). Both SD groups showed increased activation extent in the primary sensorimotor cortex, insula, and superior temporal gyrus during symptomatic and asymptomatic tasks and decreased activation extent in the basal ganglia, thalamus, and cerebellum during asymptomatic tasks. Increased activation intensity in SD patients was found only in the primary somatosensory cortex during symptomatic voice production, which showed a tendency for correlation with ADSD symptoms. Both SD groups had lower correlation of activation intensities between the primary motor and sensory cortices and additional correlations between the basal ganglia, thalamus, and cerebellum during symptomatic and asymptomatic tasks. Compared with ADSD patients, ABSD patients had larger activation extent in the primary sensorimotor cortex and ventral thalamus during symptomatic task and in the inferior temporal cortex and cerebellum during symptomatic and asymptomatic voice production. The primary somatosensory cortex shows consistent abnormalities in activation extent, intensity, correlation with other brain regions, and symptom severity in SD patients and, therefore, may be involved in the pathophysiology of SD.

  11. Anticipation increases tactile stimulus processing in the ipsilateral primary somatosensory cortex.

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    van Ede, Freek; de Lange, Floris P; Maris, Eric

    2014-10-01

    Stimulus anticipation improves perception. To account for this improvement, we investigated how stimulus processing is altered by anticipation. In contrast to a large body of previous work, we employed a demanding perceptual task and investigated sensory responses that occur beyond early evoked activity in contralateral primary sensory areas: Stimulus-induced modulations of neural oscillations. For this, we recorded magnetoencephalography in 19 humans while they performed a cued tactile identification task involving the identification of either a proximal or a distal stimulation on the fingertips. We varied the cue-target interval between 0 and 1000 ms such that tactile targets occurred at various degrees of anticipation. This allowed us to investigate the influence of anticipation on stimulus processing in a parametric fashion. We observed that anticipation increases the stimulus-induced response (suppression of beta-band oscillations) originating from the ipsilateral primary somatosensory cortex. This occurs in the period in which the tactile memory trace is analyzed and is correlated with the anticipation-induced improvement in tactile perception. We propose that this ipsilateral response indicates distributed processing across bilateral primary sensory cortices, of which the extent increases with anticipation. This constitutes a new and potentially important mechanism contributing to perception and its improvement following anticipation. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Frequency specific modulation of human somatosensory cortex

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    Matteo eFeurra

    2011-02-01

    Full Text Available Oscillatory neuronal activities are commonly observed in response to sensory stimulation. However, their functional roles are still the subject of debate. One way to probe the roles of oscillatory neural activities is to deliver alternating current to the cortex at biologically relevant frequencies and examine whether such stimulation influences perception and cognition. In this study, we tested whether transcranial alternating current stimulation (tACS over the primary somatosensory cortex (SI could elicit tactile sensations in humans in a frequency dependent manner. We tested the effectiveness of tACS over SI at frequency bands ranging from 2 to 70 Hz. Our results show that stimulation in alpha (10-14 Hz and high gamma (52-70 Hz frequency range produces a tactile sensation in the contralateral hand. A weaker effect was also observed for beta (16-20 Hz stimulation. These findings highlight the frequency-dependency of effective tACS over SI with the effective frequencies corresponding to those observed in previous EEG/MEG studies of tactile perception. Our present study suggests that tACS could be used as a powerful online stimulation technique to reveal the causal roles of oscillatory brain activities.

  13. Glutamate-Mediated Primary Somatosensory Cortex Excitability Correlated with Circulating Copper and Ceruloplasmin

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    Franca Tecchio

    2011-01-01

    Full Text Available Objective. To verify whether markers of metal homeostasis are related to a magnetoencephalographic index representative of glutamate-mediated excitability of the primary somatosensory cortex. The index is identified as the source strength of the earliest component (M20 of the somatosensory magnetic fields (SEFs evoked by right median nerve stimulation at wrist. Method. Thirty healthy right-handed subjects (51±22 years were enrolled in the study. A source reconstruction algorithm was applied to assess the amount of synchronously activated neurons subtending the M20 and the following SEF component (M30, which is generated by two independent contributions of gabaergic and glutamatergic transmission. Serum copper, ceruloplasmin, iron, transferrin, transferrin saturation, and zinc levels were measured. Results. Total copper and ceruloplasmin negatively correlated with the M20 source strength. Conclusion. This pilot study suggests that higher level of body copper reserve, as marked by ceruloplasmin variations, parallels lower cortical glutamatergic responsiveness.

  14. Simultaneous acoustic stimulation of human primary and secondary somatosensory cortices using transcranial focused ultrasound.

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    Lee, Wonhye; Chung, Yong An; Jung, Yujin; Song, In-Uk; Yoo, Seung-Schik

    2016-10-26

    Transcranial focused ultrasound (FUS) is gaining momentum as a novel non-invasive brain stimulation method, with promising potential for superior spatial resolution and depth penetration compared to transcranial magnetic stimulation or transcranial direct current stimulation. We examined the presence of tactile sensations elicited by FUS stimulation of two separate brain regions in humans-the primary (SI) and secondary (SII) somatosensory areas of the hand, as guided by individual-specific functional magnetic resonance imaging data. Under image-guidance, acoustic stimulations were delivered to the SI and SII areas either separately or simultaneously. The SII areas were divided into sub-regions that are activated by four types of external tactile sensations to the palmar side of the right hand-vibrotactile, pressure, warmth, and coolness. Across the stimulation conditions (SI only, SII only, SI and SII simultaneously), participants reported various types of tactile sensations that arose from the hand contralateral to the stimulation, such as the palm/back of the hand or as single/neighboring fingers. The type of tactile sensations did not match the sensations that are associated with specific sub-regions in the SII. The neuro-stimulatory effects of FUS were transient and reversible, and the procedure did not cause any adverse changes or discomforts in the subject's mental/physical status. The use of multiple FUS transducers allowed for simultaneous stimulation of the SI/SII in the same hemisphere and elicited various tactile sensations in the absence of any external sensory stimuli. Stimulation of the SII area alone could also induce perception of tactile sensations. The ability to stimulate multiple brain areas in a spatially restricted fashion can be used to study causal relationships between regional brain activities and their cognitive/behavioral outcomes.

  15. Regional structural differences across functionally parcellated Brodmann areas of human primary somatosensory cortex.

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    Sánchez-Panchuelo, Rosa-María; Besle, Julien; Mougin, Olivier; Gowland, Penny; Bowtell, Richard; Schluppeck, Denis; Francis, Susan

    2014-06-01

    Ultra-high-field (UHF) MRI is ideally suited for structural and functional imaging of the brain. High-resolution structural MRI can be used to map the anatomical boundaries between functional domains of the brain by identifying changes related to the pattern of myelination within cortical gray matter, opening up the possibility to study the relationship between functional domains and underlying structure in vivo. In a recent study, we demonstrated the correspondence between functional (based on retinotopic mapping) and structural (based on changes in T2(⁎)-weighted images linked to myelination) parcellations of the primary visual cortex (V1) in vivo at 7T (Sanchez-Panchuelo et al., 2012b). Here, we take advantage of the improved BOLD CNR and high spatial resolution achievable at 7T to study regional structural variations across the functionally defined areas within the primary somatosensory cortex (S1) in individual subjects. Using a traveling wave fMRI paradigm to map the internal somatotopic representation of the index, middle, and ring fingers in S1, we were able to identify multiple map reversals at the tip and base, corresponding to the boundaries between Brodmann areas 3a, 3b, 1 and 2. Based on high resolution structural MRI data acquired in the same subjects, we inspected these functionally-parcellated Brodmann areas for differences in cortical thickness and MR contrast measures (magnetization transfer ratio (MTR) and signal intensity in phase sensitive inversion recovery (PSIR) images) that are sensitive to myelination. Consistent area-related differences in cortical thickness and MTR/PSIR measurements were found across subjects. However these measures did not have sufficient sensitivity to allow definition of areal boundaries. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Beta oscillations define discrete perceptual cycles in the somatosensory domain.

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    Baumgarten, Thomas J; Schnitzler, Alfons; Lange, Joachim

    2015-09-29

    Whether seeing a movie, listening to a song, or feeling a breeze on the skin, we coherently experience these stimuli as continuous, seamless percepts. However, there are rare perceptual phenomena that argue against continuous perception but, instead, suggest discrete processing of sensory input. Empirical evidence supporting such a discrete mechanism, however, remains scarce and comes entirely from the visual domain. Here, we demonstrate compelling evidence for discrete perceptual sampling in the somatosensory domain. Using magnetoencephalography (MEG) and a tactile temporal discrimination task in humans, we find that oscillatory alpha- and low beta-band (8-20 Hz) cycles in primary somatosensory cortex represent neurophysiological correlates of discrete perceptual cycles. Our results agree with several theoretical concepts of discrete perceptual sampling and empirical evidence of perceptual cycles in the visual domain. Critically, these results show that discrete perceptual cycles are not domain-specific, and thus restricted to the visual domain, but extend to the somatosensory domain.

  17. Rapid-rate paired associative stimulation over the primary somatosensory cortex.

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    Philemon Tsang

    Full Text Available Rapid-rate paired associative stimulation (rPAS involves repeat pairing of peripheral nerve stimulation and Transcranial magnetic stimulation (TMS pulses at a 5 Hz frequency. RPAS over primary motor cortex (M1 operates with spike-timing dependent plasticity such that increases in corticospinal excitability occur when the nerve and TMS pulse temporally coincide in cortex. The present study investigates the effects of rPAS over primary somatosensory cortex (SI which has not been performed to date. In a series of experiments, rPAS was delivered over SI and M1 at varying timing intervals between the nerve and TMS pulse based on the latency of the N20 somatosensory evoked potential (SEP component within each participant (intervals for SI-rPAS: N20, N20-2.5 ms, N20 + 2.5 ms, intervals for M1-rPAS: N20, N20+5 ms. Changes in SI physiology were measured via SEPs (N20, P25, N20-P25 and SEP paired-pulse inhibition, and changes in M1 physiology were measured with motor evoked potentials and short-latency afferent inhibition. Measures were obtained before rPAS and at 5, 25 and 45 minutes following stimulation. Results indicate that paired-pulse inhibition and short-latency afferent inhibition were reduced only when the SI-rPAS nerve-TMS timing interval was set to N20-2.5 ms. SI-rPAS over SI also led to remote effects on motor physiology over a wider range of nerve-TMS intervals (N20-2.5 ms - N20+2.5 ms during which motor evoked potentials were increased. M1-rPAS increased motor evoked potentials and reduced short-latency afferent inhibition as previously reported. These data provide evidence that, similar to M1, rPAS over SI is spike-timing dependent and is capable of exerting changes in SI and M1 physiology.

  18. Weak but Critical Links between Primary Somatosensory Centers and Motor Cortex during Movement

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    Pengxu Wei

    2018-01-01

    Full Text Available Motor performance is improved by stimulation of the agonist muscle during movement. However, related brain mechanisms remain unknown. In this work, we perform a functional magnetic resonance imaging (fMRI study in 21 healthy subjects under three different conditions: (1 movement of right ankle alone; (2 movement and simultaneous stimulation of the agonist muscle; or (3 movement and simultaneous stimulation of a control area. We constructed weighted brain networks for each condition by using functional connectivity. Network features were analyzed using graph theoretical approaches. We found that: (1 the second condition evokes the strongest and most widespread brain activations (5147 vs. 4419 and 2320 activated voxels; and (2 this condition also induces a unique network layout and changes hubs and the modular structure of the brain motor network by activating the most “silent” links between primary somatosensory centers and the motor cortex, particularly weak links from the thalamus to the left primary motor cortex (M1. Significant statistical differences were found when the strength values of the right cerebellum (P < 0.001 or the left thalamus (P = 0.006 were compared among the three conditions. Over the years, studies reported a small number of projections from the thalamus to the motor cortex. This is the first work to present functions of these pathways. These findings reveal mechanisms for enhancing motor function with somatosensory stimulation, and suggest that network function cannot be thoroughly understood when weak ties are disregarded.

  19. Assessing Somatosensory Utilization during Unipedal Postural Control

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    Goel, Rahul; De Dios, Yiri E.; Gadd, Nichole E.; Caldwell, Erin E.; Peters, Brian T.; Reschke, Millard F.; Bloomberg, Jacob J.; Oddsson, Lars I. E.; Mulavara, Ajitkumar P.

    2017-01-01

    Multisensory—visual, vestibular and somatosensory information is integrated for appropriate postural control. The primary goal of this study was to assess somatosensory utilization during a functional motor task of unipedal postural control, in normal healthy adults. Assessing individual bias in the utilization of individual sensory contributions during postural control may help customization of rehabilitation protocols. In this study, a test paradigm of unipedal stance control in supine orie...

  20. Within-digit functional parcellation of Brodmann areas of the human primary somatosensory cortex using functional magnetic resonance imaging at 7 tesla.

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    Sanchez-Panchuelo, Rosa M; Besle, Julien; Beckett, Alex; Bowtell, Richard; Schluppeck, Denis; Francis, Susan

    2012-11-07

    The primary somatosensory cortex (S1) can be subdivided cytoarchitectonically into four distinct Brodmann areas (3a, 3b, 1, and 2), but these areas have never been successfully delineated in vivo in single human subjects. Here, we demonstrate the functional parcellation of four areas of S1 in individual human subjects based on high-resolution functional MRI measurements made at 7 T using vibrotactile stimulation. By stimulating four sites along the length of the index finger, we were able to identify and locate map reversals of the base to tip representation of the index finger in S1. We suggest that these reversals correspond to the areal borders between the mirrored representations in the four Brodmann areas, as predicted from electrophysiology measurements in nonhuman primates. In all subjects, maps were highly reproducible across scanning sessions and stable over weeks. In four of the six subjects scanned, four, mirrored, within-finger somatotopic maps defining the extent of the Brodmann areas could be directly observed on the cortical surface. In addition, by using multivariate classification analysis, the location of stimulation on the index finger (four distinct sites) could be decoded with a mean accuracy of 65% across subjects. Our measurements thus show that within-finger topography is present at the millimeter scale in the cortex and is highly reproducible. The ability to identify functional areas of S1 in vivo in individual subjects will provide a framework for investigating more complex aspects of tactile representation in S1.

  1. Detection of optogenetic stimulation in somatosensory cortex by non-human primates--towards artificial tactile sensation.

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    May, Travis; Ozden, Ilker; Brush, Benjamin; Borton, David; Wagner, Fabien; Agha, Naubahar; Sheinberg, David L; Nurmikko, Arto V

    2014-01-01

    Neuroprosthesis research aims to enable communication between the brain and external assistive devices while restoring lost functionality such as occurs from stroke, spinal cord injury or neurodegenerative diseases. In future closed-loop sensorimotor prostheses, one approach is to use neuromodulation as direct stimulus to the brain to compensate for a lost sensory function and help the brain to integrate relevant information for commanding external devices via, e.g. movement intention. Current neuromodulation techniques rely mainly of electrical stimulation. Here we focus specifically on the question of eliciting a biomimetically relevant sense of touch by direct stimulus of the somatosensory cortex by introducing optogenetic techniques as an alternative to electrical stimulation. We demonstrate that light activated opsins can be introduced to target neurons in the somatosensory cortex of non-human primates and be optically activated to create a reliably detected sensation which the animal learns to interpret as a tactile sensation localized within the hand. The accomplishment highlighted here shows how optical stimulation of a relatively small group of mostly excitatory somatosensory neurons in the nonhuman primate brain is sufficient for eliciting a useful sensation from data acquired by simultaneous electrophysiology and from behavioral metrics. In this first report to date on optically neuromodulated behavior in the somatosensory cortex of nonhuman primates we do not yet dissect the details of the sensation the animals exerience or contrast it to those evoked by electrical stimulation, issues of considerable future interest.

  2. Detection of optogenetic stimulation in somatosensory cortex by non-human primates--towards artificial tactile sensation.

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    Travis May

    Full Text Available Neuroprosthesis research aims to enable communication between the brain and external assistive devices while restoring lost functionality such as occurs from stroke, spinal cord injury or neurodegenerative diseases. In future closed-loop sensorimotor prostheses, one approach is to use neuromodulation as direct stimulus to the brain to compensate for a lost sensory function and help the brain to integrate relevant information for commanding external devices via, e.g. movement intention. Current neuromodulation techniques rely mainly of electrical stimulation. Here we focus specifically on the question of eliciting a biomimetically relevant sense of touch by direct stimulus of the somatosensory cortex by introducing optogenetic techniques as an alternative to electrical stimulation. We demonstrate that light activated opsins can be introduced to target neurons in the somatosensory cortex of non-human primates and be optically activated to create a reliably detected sensation which the animal learns to interpret as a tactile sensation localized within the hand. The accomplishment highlighted here shows how optical stimulation of a relatively small group of mostly excitatory somatosensory neurons in the nonhuman primate brain is sufficient for eliciting a useful sensation from data acquired by simultaneous electrophysiology and from behavioral metrics. In this first report to date on optically neuromodulated behavior in the somatosensory cortex of nonhuman primates we do not yet dissect the details of the sensation the animals exerience or contrast it to those evoked by electrical stimulation, issues of considerable future interest.

  3. Clinical application of somatosensory amplification in psychosomatic medicine

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    Nakao Mutsuhiro

    2007-10-01

    Full Text Available Abstract Many patients with somatoform disorders are frequently encountered in psychosomatic clinics as well as in primary care clinics. To assess such patients objectively, the concept of somatosensory amplification may be useful. Somatosensory amplification refers to the tendency to experience a somatic sensation as intense, noxious, and disturbing. It may have a role in a variety of medical conditions characterized by somatic symptoms that are disproportionate to demonstrable organ pathology. It may also explain some of the variability in somatic symptomatology found among different patients with the same serious medical disorder. It has been assessed with a self-report questionnaire, the Somatosensory Amplification Scale. This instrument was developed in a clinical setting in the U.S., and the reliability and validity of the Japanese and Turkish versions have been confirmed as well. Many studies have attempted to clarify the specific role of somatosensory amplification as a pathogenic mechanism in somatization. It has been reported that somatosensory amplification does not correlate with heightened sensitivity to bodily sensations and that emotional reactivity exerts its influence on somatization via a negatively biased reporting style. According to our recent electroencephalographic study, somatosensory amplification appears to reflect some aspects of long-latency cognitive processing rather than short-latency interoceptive sensitivity. The concept of somatosensory amplification can be useful as an indicator of somatization in the therapy of a broad range of disorders, from impaired self-awareness to various psychiatric disorders. It also provides useful information for choosing appropriate pharmacological or psychological therapy. While somatosensory amplification has a role in the presentation of somatic symptoms, it is closely associated with other factors, namely, anxiety, depression, and alexithymia that may also influence the same

  4. Influence of dopaminergically mediated reward on somatosensory decision-making.

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    Burkhard Pleger

    2009-07-01

    Full Text Available Reward-related dopaminergic influences on learning and overt behaviour are well established, but any influence on sensory decision-making is largely unknown. We used functional magnetic resonance imaging (fMRI while participants judged electric somatosensory stimuli on one hand or other, before being rewarded for correct performance at trial end via a visual signal, at one of four anticipated financial levels. Prior to the procedure, participants received either placebo (saline, a dopamine agonist (levodopa, or an antagonist (haloperidol.higher anticipated reward improved tactile decisions. Visually signalled reward reactivated primary somatosensory cortex for the judged hand, more strongly for higher reward. After receiving a higher reward on one trial, somatosensory activations and decisions were enhanced on the next trial. These behavioural and neural effects were all enhanced by levodopa and attenuated by haloperidol, indicating dopaminergic dependency. Dopaminergic reward-related influences extend even to early somatosensory cortex and sensory decision-making.

  5. Voxel-based lesion-symptom mapping of stroke lesions underlying somatosensory deficits

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    Sarah Meyer

    2016-01-01

    Full Text Available The aim of this study was to investigate the relationship between stroke lesion location and the resulting somatosensory deficit. We studied exteroceptive and proprioceptive somatosensory symptoms and stroke lesions in 38 patients with first-ever acute stroke. The Erasmus modified Nottingham Sensory Assessment was used to clinically evaluate somatosensory functioning in the arm and hand within the first week after stroke onset. Additionally, more objective measures such as the perceptual threshold of touch and somatosensory evoked potentials were recorded. Non-parametric voxel-based lesion-symptom mapping was performed to investigate lesion contribution to different somatosensory deficits in the upper limb. Additionally, structural connectivity of brain areas that demonstrated the strongest association with somatosensory symptoms was determined, using probabilistic fiber tracking based on diffusion tensor imaging data from a healthy age-matched sample. Voxels with a significant association to somatosensory deficits were clustered in two core brain regions: the central parietal white matter, also referred to as the sensory component of the superior thalamic radiation, and the parietal operculum close to the insular cortex, representing the secondary somatosensory cortex. Our objective recordings confirmed findings from clinical assessments. Probabilistic tracking connected the first region to thalamus, internal capsule, brain stem, postcentral gyrus, cerebellum, and frontal pathways, while the second region demonstrated structural connections to thalamus, insular and primary somatosensory cortex. This study reveals that stroke lesions in the sensory fibers of the superior thalamocortical radiation and the parietal operculum are significantly associated with multiple exteroceptive and proprioceptive deficits in the arm and hand.

  6. Voxel-based lesion-symptom mapping of stroke lesions underlying somatosensory deficits.

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    Meyer, Sarah; Kessner, Simon S; Cheng, Bastian; Bönstrup, Marlene; Schulz, Robert; Hummel, Friedhelm C; De Bruyn, Nele; Peeters, Andre; Van Pesch, Vincent; Duprez, Thierry; Sunaert, Stefan; Schrooten, Maarten; Feys, Hilde; Gerloff, Christian; Thomalla, Götz; Thijs, Vincent; Verheyden, Geert

    2016-01-01

    The aim of this study was to investigate the relationship between stroke lesion location and the resulting somatosensory deficit. We studied exteroceptive and proprioceptive somatosensory symptoms and stroke lesions in 38 patients with first-ever acute stroke. The Erasmus modified Nottingham Sensory Assessment was used to clinically evaluate somatosensory functioning in the arm and hand within the first week after stroke onset. Additionally, more objective measures such as the perceptual threshold of touch and somatosensory evoked potentials were recorded. Non-parametric voxel-based lesion-symptom mapping was performed to investigate lesion contribution to different somatosensory deficits in the upper limb. Additionally, structural connectivity of brain areas that demonstrated the strongest association with somatosensory symptoms was determined, using probabilistic fiber tracking based on diffusion tensor imaging data from a healthy age-matched sample. Voxels with a significant association to somatosensory deficits were clustered in two core brain regions: the central parietal white matter, also referred to as the sensory component of the superior thalamic radiation, and the parietal operculum close to the insular cortex, representing the secondary somatosensory cortex. Our objective recordings confirmed findings from clinical assessments. Probabilistic tracking connected the first region to thalamus, internal capsule, brain stem, postcentral gyrus, cerebellum, and frontal pathways, while the second region demonstrated structural connections to thalamus, insular and primary somatosensory cortex. This study reveals that stroke lesions in the sensory fibers of the superior thalamocortical radiation and the parietal operculum are significantly associated with multiple exteroceptive and proprioceptive deficits in the arm and hand.

  7. The Influence of Eye Closure on Somatosensory Discrimination: A Trade-off Between Simple Perception and Discrimination.

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    Götz, Theresa; Hanke, David; Huonker, Ralph; Weiss, Thomas; Klingner, Carsten; Brodoehl, Stefan; Baumbach, Philipp; Witte, Otto W

    2017-06-01

    We often close our eyes to improve perception. Recent results have shown a decrease of perception thresholds accompanied by an increase in somatosensory activity after eye closure. However, does somatosensory spatial discrimination also benefit from eye closure? We previously showed that spatial discrimination is accompanied by a reduction of somatosensory activity. Using magnetoencephalography, we analyzed the magnitude of primary somatosensory (somatosensory P50m) and primary auditory activity (auditory P50m) during a one-back discrimination task in 21 healthy volunteers. In complete darkness, participants were requested to pay attention to either the somatosensory or auditory stimulation and asked to open or close their eyes every 6.5 min. Somatosensory P50m was reduced during a task requiring the distinguishing of stimulus location changes at the distal phalanges of different fingers. The somatosensory P50m was further reduced and detection performance was higher during eyes open. A similar reduction was found for the auditory P50m during a task requiring the distinguishing of changing tones. The function of eye closure is more than controlling visual input. It might be advantageous for perception because it is an effective way to reduce interference from other modalities, but disadvantageous for spatial discrimination because it requires at least one top-down processing stage. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Phantom somatosensory evoked potentials following selective intraneural electrical stimulation in two amputees.

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    Granata, Giuseppe; Di Iorio, Riccardo; Romanello, Roberto; Iodice, Francesco; Raspopovic, Stanisa; Petrini, Francesco; Strauss, Ivo; Valle, Giacomo; Stieglitz, Thomas; Čvančara, Paul; Andreu, David; Divoux, Jean-Louis; Guiraud, David; Wauters, Loic; Hiairrassary, Arthur; Jensen, Winnie; Micera, Silvestro; Rossini, Paolo Maria

    2018-06-01

    The aim of the paper is to objectively demonstrate that amputees implanted with intraneural interfaces are truly able to feel a sensation in the phantom hand by recording "phantom" somatosensory evoked potentials from the corresponding brain areas. We implanted four transverse intrafascicular multichannel electrodes, available with percutaneous connections to a multichannel electrical stimulator, in the median and ulnar nerves of two left trans-radial amputees. Two channels of the implants that were able to elicit sensations during intraneural nerve stimulation were chosen, in both patients, for recording somatosensory evoked potentials. We recorded reproducible evoked responses by stimulating the median and the ulnar nerves in both cases. Latencies were in accordance with the arrival of somatosensory information to the primary somatosensory cortex. Our results provide evidence that sensations generated by intraneural stimulation are truly perceived by amputees and located in the phantom hand. Moreover, our results strongly suggest that sensations perceived in different parts of the phantom hand result in different evoked responses. Somatosensory evoked potentials obtained by selective intraneural electrical stimulation in amputee patients are a useful tool to provide an objective demonstration of somatosensory feedback in new generation bidirectional prostheses. Copyright © 2018. Published by Elsevier B.V.

  9. Auditory-somatosensory bimodal stimulation desynchronizes brain circuitry to reduce tinnitus in guinea pigs and humans.

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    Marks, Kendra L; Martel, David T; Wu, Calvin; Basura, Gregory J; Roberts, Larry E; Schvartz-Leyzac, Kara C; Shore, Susan E

    2018-01-03

    The dorsal cochlear nucleus is the first site of multisensory convergence in mammalian auditory pathways. Principal output neurons, the fusiform cells, integrate auditory nerve inputs from the cochlea with somatosensory inputs from the head and neck. In previous work, we developed a guinea pig model of tinnitus induced by noise exposure and showed that the fusiform cells in these animals exhibited increased spontaneous activity and cross-unit synchrony, which are physiological correlates of tinnitus. We delivered repeated bimodal auditory-somatosensory stimulation to the dorsal cochlear nucleus of guinea pigs with tinnitus, choosing a stimulus interval known to induce long-term depression (LTD). Twenty minutes per day of LTD-inducing bimodal (but not unimodal) stimulation reduced physiological and behavioral evidence of tinnitus in the guinea pigs after 25 days. Next, we applied the same bimodal treatment to 20 human subjects with tinnitus using a double-blinded, sham-controlled, crossover study. Twenty-eight days of LTD-inducing bimodal stimulation reduced tinnitus loudness and intrusiveness. Unimodal auditory stimulation did not deliver either benefit. Bimodal auditory-somatosensory stimulation that induces LTD in the dorsal cochlear nucleus may hold promise for suppressing chronic tinnitus, which reduces quality of life for millions of tinnitus sufferers worldwide. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  10. Effects of face/head and whole body cooling during passive heat stress on human somatosensory processing.

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    Nakata, Hiroki; Namba, Mari; Kakigi, Ryusuke; Shibasaki, Manabu

    2017-06-01

    We herein investigated the effects of face/head and whole body cooling during passive heat stress on human somatosensory processing recorded by somatosensory-evoked potentials (SEPs) at C4' and Fz electrodes. Fourteen healthy subjects received a median nerve stimulation at the left wrist. SEPs were recorded at normothermic baseline (Rest), when esophageal temperature had increased by ~1.2°C (heat stress: HS) during passive heating, face/head cooling during passive heating (face/head cooling: FHC), and after HS (whole body cooling: WBC). The latencies and amplitudes of P14, N20, P25, N35, P45, and N60 at C4' and P14, N18, P22, and N30 at Fz were evaluated. Latency indicated speed of the subcortical and cortical somatosensory processing, while amplitude reflected the strength of neural activity. Blood flow in the internal and common carotid arteries (ICA and CCA, respectively) and psychological comfort were recorded in each session. Increases in esophageal temperature due to HS significantly decreased the amplitude of N60, psychological comfort, and ICA blood flow in the HS session, and also shortened the latencies of SEPs (all, P body temperature. Copyright © 2017 the American Physiological Society.

  11. More than skin deep: body representation beyond primary somatosensory cortex.

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    Longo, Matthew R; Azañón, Elena; Haggard, Patrick

    2010-02-01

    The neural circuits underlying initial sensory processing of somatic information are relatively well understood. In contrast, the processes that go beyond primary somatosensation to create more abstract representations related to the body are less clear. In this review, we focus on two classes of higher-order processing beyond somatosensation. Somatoperception refers to the process of perceiving the body itself, and particularly of ensuring somatic perceptual constancy. We review three key elements of somatoperception: (a) remapping information from the body surface into an egocentric reference frame, (b) exteroceptive perception of objects in the external world through their contact with the body, and (c) interoceptive percepts about the nature and state of the body itself. Somatorepresentation, in contrast, refers to the essentially cognitive process of constructing semantic knowledge and attitudes about the body, including: (d) lexical-semantic knowledge about bodies generally and one's own body specifically, (e) configural knowledge about the structure of bodies, (f) emotions and attitudes directed towards one's own body, and (g) the link between physical body and psychological self. We review a wide range of neuropsychological, neuroimaging and neurophysiological data to explore the dissociation between these different aspects of higher somatosensory function. 2009 Elsevier Ltd. All rights reserved.

  12. Activity in the primary somatosensory cortex induced by reflexological stimulation is unaffected by pseudo-information: a functional magnetic resonance imaging study.

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    Miura, Naoki; Akitsuki, Yuko; Sekiguchi, Atsushi; Kawashima, Ryuta

    2013-05-27

    Reflexology is an alternative medical practice that produces beneficial effects by applying pressure to specific reflex areas. Our previous study suggested that reflexological stimulation induced cortical activation in somatosensory cortex corresponding to the stimulated reflex area; however, we could not rule out the possibility of a placebo effect resulting from instructions given during the experimental task. We used functional magnetic resonance imaging (fMRI) to investigate how reflexological stimulation of the reflex area is processed in the primary somatosensory cortex when correct and pseudo-information about the reflex area is provided. Furthermore, the laterality of activation to the reflexological stimulation was investigated. Thirty-two healthy Japanese volunteers participated. The experiment followed a double-blind design. Half of the subjects received correct information, that the base of the second toe was the eye reflex area, and pseudo-information, that the base of the third toe was the shoulder reflex area. The other half of the subjects received the opposite information. fMRI time series data were acquired during reflexological stimulation to both feet. The experimenter stimulated each reflex area in accordance with an auditory cue. The fMRI data were analyzed using a conventional two-stage approach. The hemodynamic responses produced by the stimulation of each reflex area were assessed using a general linear model on an intra-subject basis, and a two-way repeated-measures analysis of variance was performed on an intersubject basis to determine the effect of reflex area laterality and information accuracy. Our results indicated that stimulation of the eye reflex area in either foot induced activity in the left middle postcentral gyrus, the area to which tactile sensation to the face projects, as well as in the postcentral gyrus contralateral foot representation area. This activity was not affected by pseudo information. The results also indicate

  13. Activity in the primary somatosensory cortex induced by reflexological stimulation is unaffected by pseudo-information: a functional magnetic resonance imaging study

    Science.gov (United States)

    2013-01-01

    Background Reflexology is an alternative medical practice that produces beneficial effects by applying pressure to specific reflex areas. Our previous study suggested that reflexological stimulation induced cortical activation in somatosensory cortex corresponding to the stimulated reflex area; however, we could not rule out the possibility of a placebo effect resulting from instructions given during the experimental task. We used functional magnetic resonance imaging (fMRI) to investigate how reflexological stimulation of the reflex area is processed in the primary somatosensory cortex when correct and pseudo-information about the reflex area is provided. Furthermore, the laterality of activation to the reflexological stimulation was investigated. Methods Thirty-two healthy Japanese volunteers participated. The experiment followed a double-blind design. Half of the subjects received correct information, that the base of the second toe was the eye reflex area, and pseudo-information, that the base of the third toe was the shoulder reflex area. The other half of the subjects received the opposite information. fMRI time series data were acquired during reflexological stimulation to both feet. The experimenter stimulated each reflex area in accordance with an auditory cue. The fMRI data were analyzed using a conventional two-stage approach. The hemodynamic responses produced by the stimulation of each reflex area were assessed using a general linear model on an intra-subject basis, and a two-way repeated-measures analysis of variance was performed on an intersubject basis to determine the effect of reflex area laterality and information accuracy. Results Our results indicated that stimulation of the eye reflex area in either foot induced activity in the left middle postcentral gyrus, the area to which tactile sensation to the face projects, as well as in the postcentral gyrus contralateral foot representation area. This activity was not affected by pseudo information

  14. [Neurophysiological investigations of information processing in the somato-sensory system].

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    Kunesch, E

    2009-08-01

    The ability of the human hand to perform complex sensorimotor tasks such as tactile exploration and grasping is based on 1. exact encoding of somatosensory information by cutaneous mechanoreceptors, 2. elaborated processing of afferent signals in somatosensory relay stations and cortex fields, 3. rapid and effective interaction of sensory feedback with motor programs, and 4. different modes of sensory control, which can be switched over. (c) Georg Thieme Verlag KG Stuttgart-New York.

  15. Somatosensory discrimination deficits following pediatric cerebral malaria.

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    Dugbartey, A T; Spellacy, F J; Dugbartey, M T

    1998-09-01

    Pathologic studies of central nervous system damage in human falciparum malaria indicate primary localization in the cerebral white matter. We report a sensory-perceptual investigation of 20 Ghanaian children with a recent history of cerebral malaria who were age-, gender-, and education-matched with 20 healthy control subjects. Somatosensory examinations failed to show any evidence of hemianesthesia, pseudohemianesthesia, or extinction to double simultaneous tactile stimulation. While unilateral upper limb testing revealed intact unimanual tactile roughness discrimination, bimanual tactile discrimination, however, was significantly impaired in the cerebral malaria group. A strong negative correlation (r = -0.72) between coma duration and the bimanual tactile roughness discrimination test was also found. An inefficiency in the integrity of callosal fibers appear to account for our findings, although alternative subcortical mechanisms known to be involved in information transfer across the cerebral hemispheres may be compromised as well.

  16. Anatomical and functional properties of the foot and leg representation in areas 3b, 1 and 2 of primary somatosensory cortex in humans: A 7T fMRI study.

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    Akselrod, Michel; Martuzzi, Roberto; Serino, Andrea; van der Zwaag, Wietske; Gassert, Roger; Blanke, Olaf

    2017-10-01

    Primary somatosensory cortex (S1) processes somatosensory information and is composed of multiple subregions. In particular, tactile information from the skin is encoded in three subregions, namely Brodmann areas (BAs) 3b, 1 and 2, with each area representing a complete map of the contralateral body. Although, much is known about the somatotopic organization of the hand in human S1, less research has been carried out regarding the somatotopic maps of the foot and leg in S1. Moreover, a latero-medial S1 organization along the superior part of the postcentral gyrus has been reported when moving from hip to toes, yet to date there is no study investigating leg/foot maps within the different subregions of S1. Using ultra-high field MRI (7T), we mapped six cortical representations of the lower limb (hip to toes) at the single subject level and performed this analysis separately for BAs 3b, 1 and 2. Analyzing the BOLD responses associated with tactile stimulations of the mapped foot and leg regions on each side, we quantified the extent and the strength of activation to determine somatotopic organization. In addition, we investigated whether each mapped representation also responded to the stimulation of other body parts (i.e. response selectivity) and conducted dissimilarity analysis relating these anatomical and functional properties of S1 to the physical structure of the lower limbs. Our data reveal somatotopy for the leg, but not for the foot in all investigated BAs, with large inter-subject variability. We found only minor differences between the properties of the three investigated BAs, suggesting that S1 maps for the lower limbs differ from those described for the hand. We also describe greater extent/strength of S1 activation for the big toe representation (compared to the other mapped representations) within all BAs, suggesting a possible homology between the first digit of upper and lower extremity in humans, and report different patterns of selectivity in the

  17. Somatosensory Representations Link the Perception of Emotional Expressions and Sensory Experience.

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    Kragel, Philip A; LaBar, Kevin S

    2016-01-01

    Studies of human emotion perception have linked a distributed set of brain regions to the recognition of emotion in facial, vocal, and body expressions. In particular, lesions to somatosensory cortex in the right hemisphere have been shown to impair recognition of facial and vocal expressions of emotion. Although these findings suggest that somatosensory cortex represents body states associated with distinct emotions, such as a furrowed brow or gaping jaw, functional evidence directly linking somatosensory activity and subjective experience during emotion perception is critically lacking. Using functional magnetic resonance imaging and multivariate decoding techniques, we show that perceiving vocal and facial expressions of emotion yields hemodynamic activity in right somatosensory cortex that discriminates among emotion categories, exhibits somatotopic organization, and tracks self-reported sensory experience. The findings both support embodied accounts of emotion and provide mechanistic insight into how emotional expressions are capable of biasing subjective experience in those who perceive them.

  18. Experience-induced plasticity of cutaneous maps in the primary somatosensory cortex of adult monkeys and rats.

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    Xerri, C; Coq, J O; Merzenich, M M; Jenkins, W M

    1996-01-01

    In a first study, the representations of skin surfaces of the hand in the primary somatosensory cortex, area 3b, were reconstructed in owl monkeys and squirrel monkeys trained to pick up food pellets from small, shallow wells, a task which required skilled use of the digits. Training sessions included limited manual exercise over a total period of a few hours of practice. From an early clumsy performance in which many retrieval attempts were required for each successful pellet retrieval, the monkeys exhibited a gradual improvement. Typically, the animals used various combinations of digits before developing a successful retrieval strategy. As the behavior came to be stereotyped, monkeys consistently engaged surfaces of the distal phalanges of one or two digits in the palpation and capture of food pellets from the smallest wells. Microelectrode mapping of the hand surfaces revealed that the glabrous skin of the fingertips predominantly involved in the dexterity task was represented over topographically expanded cortical sectors. Furthermore, cutaneous receptive fields which covered the most frequently stimulated digital tip surfaces were less than half as large as were those representing the corresponding surfaces of control digits. In a second series of experiments, Long-Evans rats were assigned to environments promoting differential tactile experience (standard, enriched, and impoverished) for 80 to 115 days from the time of weaning. A fourth group of young adult rat experienced a severe restriction of forepaw exploratory movement for either 7 or 15 days. Cortical maps derived in the primary somatosensory cortex showed that environmental enrichment induced a substantial enlargement of the cutaneous forepaw representation, and improved its spatial resolution (smaller glabrous receptive fields). In contrast, tactile impoverishment resulted in a degradation of the forepaw representation that was characterized by larger cutaneous receptive fields and the emergence of

  19. Primary somatosensory cortex in chronic low back pain – a 1H-MRS study

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    Sharma KN

    2011-05-01

    Full Text Available Neena K Sharma1, Kenneth McCarson2, Linda Van Dillen5, Angela Lentz1, Talal Khan3, Carmen M Cirstea1,41Department of Physical Therapy and Rehabilitation Science, 2Department of Pharmacology, Toxicology and Therapeutics, 3Department of Anesthesiology, 4Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, KS, USA; 5Program in Physical Therapy and Department of Orthopedic Surgery, Washington University School of Medicine, St Louis, MO, USAAbstract: The goal of this study was to investigate whether certain metabolites, specific to neurons, glial cells, and the neuronal-glial neurotransmission system, in the primary somatosensory cortex (SSC, are altered and correlated with clinical characteristics of pain in patients with chronic low back pain (LBP. Eleven LBP patients and eleven age-matched healthy controls were included. N-acetylaspartate (NAA, choline (Cho, myo-inositol (mI, and glutamine/glutamate (Glx were measured with proton magnetic resonance spectroscopy (1H-MRS in left and right SSC. Differences in metabolite concentrations relative to those of controls were evaluated as well as analyses of metabolite correlations within and between SSCs. Relationships between metabolite concentrations and pain characteristics were also evaluated. We found decreased NAA in the left SSC (P = 0.001 and decreased Cho (P = 0.04 along with lower correlations between all metabolites in right SSC (P = 0.007 in LBP compared to controls. In addition, we found higher and significant correlations between left and right mI (P < 0.001 in LBP vs P = 0.1 in controls and between left mI and right Cho (P = 0.048 vs P = 0.6. Left and right NAA levels were negatively correlated with pain duration (P = 0.04 and P = 0.02 respectively while right Glx was positively correlated with pain severity (P = 0.04. Our preliminary results demonstrated significant altered neuronal-glial interactions in SSC, with left neural alterations related to pain duration

  20. Assessing Somatosensory Utilization during Unipedal Postural Control.

    Science.gov (United States)

    Goel, Rahul; De Dios, Yiri E; Gadd, Nichole E; Caldwell, Erin E; Peters, Brian T; Reschke, Millard F; Bloomberg, Jacob J; Oddsson, Lars I E; Mulavara, Ajitkumar P

    2017-01-01

    Multisensory-visual, vestibular and somatosensory information is integrated for appropriate postural control. The primary goal of this study was to assess somatosensory utilization during a functional motor task of unipedal postural control, in normal healthy adults. Assessing individual bias in the utilization of individual sensory contributions during postural control may help customization of rehabilitation protocols. In this study, a test paradigm of unipedal stance control in supine orientation with and without vision was assessed. Postural control in this test paradigm was hypothesized to utilize predominantly contributions of somatosensory information from the feet and ankle joint, with minimal vestibular input. Fourteen healthy subjects "stood" supine on their dominant leg while strapped to a backpack frame that was freely moving on air-bearings, to remove available otolith tilt cues with respect to gravity that influences postural control when standing upright. The backpack was attached through a cable to a pneumatic cylinder that provided a gravity-like load. Subjects performed three trials each with Eyes-open (EO) and Eyes-closed (EC) while loaded with 60% body weight. There was no difference in unipedal stance time (UST) across the two conditions with EC condition challenging the postural control system greater than the EO condition. Stabilogram-diffusion analysis (SDA) indicated that the critical mean square displacement was significantly different between the two conditions. Vestibular cues, both in terms of magnitude and the duration for which relevant information was available for postural control in this test paradigm, were minimized. These results support our hypothesis that maintaining unipedal stance in supine orientation without vision, minimizes vestibular contribution and thus predominantly utilizes somatosensory information for postural control.

  1. Reduction of pain sensitivity after somatosensory therapy in adults with cerebral palsy

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    Inmaculada eRiquelme

    2013-06-01

    Full Text Available Objective. Pain and deficits in somatosensory processing seem to play a relevant role in cerebral palsy (CP. Rehabilitation techniques based on neuroplasticity mechanisms may induce powerful changes in the organization of the primary somatosensory cortex and have been proved to reduce levels of pain and discomfort in neurological pathologies. However, little is known about the efficacy of such interventions for pain sensitivity in CP individuals. Methods. Adults with cerebral palsy participated in the study and were randomly assigned to the intervention (n=17 or the control group (n=20. The intervention group received a somatosensory therapy including 4 types of exercises (touch, proprioception, vibration, and stereognosis. All participants were asked to continue their standardized motor therapy during the study period. Several somatosensory (pain and touch thresholds, stereognosis, propioception, texture recognition and motor parameters (fine motor skills were assessed before, immediately after and three months after the therapy (follow-up. Results. Participants of the intervention group showed a significant reduction on pain sensitivity after treatment and at follow-up after three months, whereas participants in the control group displayed increasing pain sensitivity over time. No improvements were found on touch sensitivity, proprioception, texture recognition or fine motor skills. Conclusions. Data suggest the possibility that somatosensory therapy was effective in eliciting changes in central somatosensory processing. This hypothesis may have implications for future neuromodulatory treatment of pain complaints in children and adults with cerebral palsy.

  2. Human umbilical cord blood cells restore brain damage induced changes in rat somatosensory cortex.

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    Maren Geissler

    Full Text Available Intraperitoneal transplantation of human umbilical cord blood (hUCB cells has been shown to reduce sensorimotor deficits after hypoxic ischemic brain injury in neonatal rats. However, the neuronal correlate of the functional recovery and how such a treatment enforces plastic remodelling at the level of neural processing remains elusive. Here we show by in-vivo recordings that hUCB cells have the capability of ameliorating the injury-related impairment of neural processing in primary somatosensory cortex. Intact cortical processing depends on a delicate balance of inhibitory and excitatory transmission, which is disturbed after injury. We found that the dimensions of cortical maps and receptive fields, which are significantly altered after injury, were largely restored. Additionally, the lesion induced hyperexcitability was no longer observed in hUCB treated animals as indicated by a paired-pulse behaviour resembling that observed in control animals. The beneficial effects on cortical processing were reflected in an almost complete recovery of sensorimotor behaviour. Our results demonstrate that hUCB cells reinstall the way central neurons process information by normalizing inhibitory and excitatory processes. We propose that the intermediate level of cortical processing will become relevant as a new stage to investigate efficacy and mechanisms of cell therapy in the treatment of brain injury.

  3. Seeing is not feeling: posterior parietal but not somatosensory cortex engagement during touch observation.

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    Chan, Annie W-Y; Baker, Chris I

    2015-01-28

    Observing touch has been reported to elicit activation in human primary and secondary somatosensory cortices and is suggested to underlie our ability to interpret other's behavior and potentially empathy. However, despite these reports, there are a large number of inconsistencies in terms of the precise topography of activation, the extent of hemispheric lateralization, and what aspects of the stimulus are necessary to drive responses. To address these issues, we investigated the localization and functional properties of regions responsive to observed touch in a large group of participants (n = 40). Surprisingly, even with a lenient contrast of hand brushing versus brushing alone, we did not find any selective activation for observed touch in the hand regions of somatosensory cortex but rather in superior and inferior portions of neighboring posterior parietal cortex, predominantly in the left hemisphere. These regions in the posterior parietal cortex required the presence of both brush and hand to elicit strong responses and showed some selectivity for the form of the object or agent of touch. Furthermore, the inferior parietal region showed nonspecific tactile and motor responses, suggesting some similarity to area PFG in the monkey. Collectively, our findings challenge the automatic engagement of somatosensory cortex when observing touch, suggest mislocalization in previous studies, and instead highlight the role of posterior parietal cortex. Copyright © 2015 the authors 0270-6474/15/351468-13$15.00/0.

  4. Somatosensory abnormalities in knee OA.

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    Wylde, Vikki; Palmer, Shea; Learmonth, Ian D; Dieppe, Paul

    2012-03-01

    The aim of this study was to use quantitative sensory testing (QST) to explore the range and prevalence of somatosensory abnormalities demonstrated by patients with advanced knee OA. One hundred and seven knee OA patients and 50 age- and sex-matched healthy participants attended a 1-h QST session. Testing was performed on the medial side of the knee and the pain-free forearm. Light-touch thresholds were assessed using von Frey filaments, pressure pain thresholds using a digital pressure algometer, and thermal sensation and pain thresholds using a Thermotest MSA. Significant differences in median threshold values from knee OA patients and healthy participants were identified using Mann-Whitney U-tests. The z-score transformations were used to determine the prevalence of the different somatosensory abnormalities in knee OA patients. Testing identified 70% of knee OA patients as having at least one somatosensory abnormality. Comparison of median threshold values between knee OA patients and healthy participants revealed that patients had localized thermal and tactile hypoaesthesia and pressure hyperalgesia at the osteoarthritic knee. Tactile hypoaesthesia and pressure hyperalgesia were also present at the pain-free forearm. The most prevalent somatosensory abnormalities were tactile hypoaesthesia and pressure hyperalgesia, evident in between 20 and 34% of patients. This study found that OA patients demonstrate an array of somatosensory abnormalities, of which the most prevalent were tactile hypoaesthesia and pressure hyperalgesia. Further research is now needed to establish the clinical implications of these somatosensory abnormalities.

  5. Influence of body position on cortical pain-related somatosensory processing: an ERP study.

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    Chiara Spironelli

    Full Text Available BACKGROUND: Despite the consistent information available on the physiological changes induced by head down bed rest, a condition which simulates space microgravity, our knowledge on the possible perceptual-cortical alterations is still poor. The present study investigated the effects of 2-h head-down bed rest on subjective and cortical responses elicited by electrical, pain-related somatosensory stimulation. METHODOLOGY/PRINCIPAL FINDINGS: Twenty male subjects were randomly assigned to two groups, head-down bed rest (BR or sitting control condition. Starting from individual electrical thresholds, Somatosensory Evoked Potentials were elicited by electrical stimuli administered randomly to the left wrist and divided into four conditions: control painless condition, electrical pain threshold, 30% above pain threshold, 30% below pain threshold. Subjective pain ratings collected during the EEG session showed significantly reduced pain perception in BR compared to Control group. Statistical analysis on four electrode clusters and sLORETA source analysis revealed, in sitting controls, a P1 component (40-50 ms in the right somatosensory cortex, whereas it was bilateral and differently located in BR group. Controls' N1 (80-90 ms had widespread right hemisphere activation, involving also anterior cingulate, whereas BR group showed primary somatosensory cortex activation. The P2 (190-220 ms was larger in left-central locations of Controls compared with BR group. CONCLUSIONS/SIGNIFICANCE: Head-down bed rest was associated to an overall decrease of pain sensitivity and an altered pain network also outside the primary somatosensory cortex. Results have implications not only for astronauts' health and spaceflight risks, but also for the clinical aspects of pain detection in bedridden patients at risk of fatal undetected complications.

  6. Discriminability of Single and Multichannel Intracortical Microstimulation within Somatosensory Cortex

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    Cynthia Kay Overstreet

    2016-12-01

    Full Text Available The addition of tactile and proprioceptive feedback to neuroprosthetic limbs is expected to significantly improve the control of these devices. Intracortical microstimulation (ICMS of somatosensory cortex is a promising method of delivering this sensory feedback. To date, the main focus of somatosensory ICMS studies has been to deliver discriminable signals, corresponding to varying intensity, to a single location in cortex. However, multiple independent and simultaneous streams of sensory information will need to be encoded by ICMS to provide functionally relevant feedback for a neuroprosthetic limb (e.g. encoding contact events and pressure on multiple digits.In this study, we evaluated the ability of an awake, behaving non-human primate (Macaca mulatta to discriminate ICMS stimuli delivered on multiple electrodes spaced within somatosensory cortex. We delivered serial stimulation on single electrodes to evaluate the discriminability of sensations corresponding to ICMS of distinct cortical locations. Additionally, we delivered trains of multichannel stimulation, derived from a tactile sensor, synchronously across multiple electrodes. Our results indicate that discrimination of multiple ICMS stimuli is a challenging task, but that discriminable sensory percepts can be elicited by both single and multichannel ICMS on electrodes spaced within somatosensory cortex.

  7. Volumetric localization of somatosensory cortex in children using synthetic aperture magnetometry

    International Nuclear Information System (INIS)

    Xiang, Jing; Holowka, Stephanie; Chuang, Sylvester; Sharma, Rohit; Hunjan, Amrita; Otsubo, Hiroshi

    2003-01-01

    Magnetic signal from the human brain can be measured noninvasively by using magnetoencephalography (MEG). This study was designed to localize and reconstruct the neuromagnetic activity in the somatosensory cortex in children Twenty children were studied using a 151-channel MEG system with electrical stimulation applied to median nerves. Data were analyzed using synthetic aperture magnetometry (SAM). A clear deflection (M1) was clearly identified in 18 children (90%, 18/20). Two frequency bands, 30-60 Hz and 60-120 Hz, were found to be related to somatosensory cortex. Magnetic activity was localized in the posterior bank of the central sulcus in 16 children. The extent of the reconstructed neuromagnetic activity of the left hemisphere was significantly larger than that of the right hemisphere (P<0.01). Somatosensory cortex was accurately localized by using SAM. The extent of the reconstructed neuromagnetic activity suggested that the left hemisphere was the dominant side in the somatosensory system in children. We postulate that the volumetric characteristics of the reconstructed neuromagnetic activity are able to indicate the functionality of the brain. (orig.)

  8. Effect of Somatosensory Impairments on Balance Control

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    Alireza Hassanpour

    2012-10-01

    Full Text Available Background and Aim: The somatosensory system is one of the most effective systems in balance control. It consists of peripheral and central components. Knowing the role of these components in balance control assists the developing of effective rehabilitation protocols. In some diseases peripheral components and in others central components are impaired. This paper reviews the effect of impairment of peripheral and central components of the somatosensory system on balance control.Methods: In this study publication about somatosensory impairments from 1983 through 2011 in PubMed, Scopus, ProQuest, Google Scholar, Iran Medex, Iran Doc and Magiran were reviewed. Medical subject headings terms and keywords related to balance, somatosensory, somatosensory loss, and sensory integration/processing were used to perform the searches.Conclusion: Somatosensory impairments either with peripheral or central origin, can cause problems in balance control. However, these problems are not considered in some patients. In these impairments, balance training is recommended to be used alongside other routine treatments in the patients' rehabilitation programs.

  9. Posterior Thalamic Nucleus Modulation of Tactile Stimuli Processing in Rat Motor and Primary Somatosensory Cortices

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    Diana Casas-Torremocha

    2017-09-01

    Full Text Available Rodents move rhythmically their facial whiskers and compute differences between signals predicted and those resulting from the movement to infer information about objects near their head. These computations are carried out by a large network of forebrain structures that includes the thalamus and the primary somatosensory (S1BF and motor (M1wk cortices. Spatially and temporally precise mechanorreceptive whisker information reaches the S1BF cortex via the ventroposterior medial thalamic nucleus (VPM. Other whisker-related information may reach both M1wk and S1BF via the axons from the posterior thalamic nucleus (Po. However, Po axons may convey, in addition to direct sensory signals, the dynamic output of computations between whisker signals and descending motor commands. It has been proposed that this input may be relevant for adjusting cortical responses to predicted vs. unpredicted whisker signals, but the effects of Po input on M1wk and S1BF function have not been directly tested or compared in vivo. Here, using electrophysiology, optogenetics and pharmacological tools, we compared in adult rats M1wk and S1BF in vivo responses in the whisker areas of the motor and primary somatosensory cortices to passive multi-whisker deflection, their dependence on Po activity, and their changes after a brief intense activation of Po axons. We report that the latencies of the first component of tactile-evoked local field potentials in M1wk and S1BF are similar. The evoked potentials decrease markedly in M1wk, but not in S1BF, by injection in Po of the GABAA agonist muscimol. A brief high-frequency electrical stimulation of Po decreases the responsivity of M1wk and S1BF cells to subsequent whisker stimulation. This effect is prevented by the local application of omega-agatoxin, suggesting that it may in part depend on GABA release by fast-spiking parvalbumin (PV-expressing cortical interneurons. Local optogenetic activation of Po synapses in different

  10. Atrophy and Primary Somatosensory Cortical Reorganization after Unilateral Thoracic Spinal Cord Injury: A Longitudinal Functional Magnetic Resonance Imaging Study

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    Jia-Sheng Rao

    2013-01-01

    Full Text Available The effects of traumatic spinal cord injury (SCI on the changes in the central nervous system (CNS over time may depend on the dynamic interaction between the structural integrity of the spinal cord and the capacity of the brain plasticity. Functional magnetic resonance imaging (fMRI was used in a longitudinal study on five rhesus monkeys to observe cerebral activation during upper limb somatosensory tasks in healthy animals and after unilateral thoracic SCI. The changes in the spinal cord diameters were measured, and the correlations among time after the lesion, structural changes in the spinal cord, and primary somatosensory cortex (S1 reorganization were also determined. After SCI, activation of the upper limb in S1 shifted to the region which generally dominates the lower limb, and the rostral spinal cord transverse diameter adjacent to the lesion exhibited obvious atrophy, which reflects the SCI-induced changes in the CNS. A significant correlation was found among the time after the lesion, the spinal cord atrophy, and the degree of contralateral S1 reorganization. The results indicate the structural changes in the spinal cord and the dynamic reorganization of the cerebral activation following early SCI stage, which may help to further understand the neural plasticity in the CNS.

  11. Direct electrical stimulation of human cortex evokes high gamma activity that predicts conscious somatosensory perception

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    Muller, Leah; Rolston, John D.; Fox, Neal P.; Knowlton, Robert; Rao, Vikram R.; Chang, Edward F.

    2018-04-01

    Objective. Direct electrical stimulation (DES) is a clinical gold standard for human brain mapping and readily evokes conscious percepts, yet the neurophysiological changes underlying these percepts are not well understood. Approach. To determine the neural correlates of DES, we stimulated the somatosensory cortex of ten human participants at frequency-amplitude combinations that both elicited and failed to elicit conscious percepts, meanwhile recording neural activity directly surrounding the stimulation site. We then compared the neural activity of perceived trials to that of non-perceived trials. Main results. We found that stimulation evokes distributed high gamma activity, which correlates with conscious perception better than stimulation parameters themselves. Significance. Our findings suggest that high gamma activity is a reliable biomarker for perception evoked by both natural and electrical stimuli.

  12. Bilateral somatosensory evoked potentials following intermittent theta-burst repetitive transcranial magnetic stimulation.

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    Premji, Azra; Ziluk, Angela; Nelson, Aimee J

    2010-08-05

    Intermittent theta-burst stimulation (iTBS) is a form of repetitive transcranial magnetic stimulation that may alter cortical excitability in the primary somatosensory cortex (SI). The present study investigated the effects of iTBS on subcortical and early cortical somatosensory evoked potentials (SEPs) recorded over left, iTBS stimulated SI and the right-hemisphere non-stimulated SI. SEPs were recorded before and at 5, 15, and 25 minutes following iTBS. Compared to pre-iTBS, the amplitude of cortical potential N20/P25 was significantly increased for 5 minutes from non-stimulated SI and for 15 to 25 minutes from stimulated SI. Subcortical potentials recorded bilaterally remained unaltered following iTBS. We conclude that iTBS increases the cortical excitability of SI bilaterally and does not alter thalamocortical afferent input to SI. ITBS may provide one avenue to induce cortical plasticity in the somatosensory cortex.

  13. Persistent Neuronal Firing in Primary Somatosensory Cortex in the Absence of Working Memory of Trial-Specific Features of the Sample Stimuli in a Haptic Working Memory Task

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    Wang, Liping; Li, Xianchun; Hsiao, Steven S.; Bodner, Mark; Lenz, Fred; Zhou, Yong-Di

    2012-01-01

    Previous studies suggested that primary somatosensory (SI) neurons in well-trained monkeys participated in the haptic-haptic unimodal delayed matching-to-sample (DMS) task. In this study, 585 SI neurons were recorded in monkeys performing a task that was identical to that in the previous studies but without requiring discrimination and active…

  14. Temporal factors affecting somatosensory-auditory interactions in speech processing

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    Takayuki eIto

    2014-11-01

    Full Text Available Speech perception is known to rely on both auditory and visual information. However, sound specific somatosensory input has been shown also to influence speech perceptual processing (Ito et al., 2009. In the present study we addressed further the relationship between somatosensory information and speech perceptual processing by addressing the hypothesis that the temporal relationship between orofacial movement and sound processing contributes to somatosensory-auditory interaction in speech perception. We examined the changes in event-related potentials in response to multisensory synchronous (simultaneous and asynchronous (90 ms lag and lead somatosensory and auditory stimulation compared to individual unisensory auditory and somatosensory stimulation alone. We used a robotic device to apply facial skin somatosensory deformations that were similar in timing and duration to those experienced in speech production. Following synchronous multisensory stimulation the amplitude of the event-related potential was reliably different from the two unisensory potentials. More importantly, the magnitude of the event-related potential difference varied as a function of the relative timing of the somatosensory-auditory stimulation. Event-related activity change due to stimulus timing was seen between 160-220 ms following somatosensory onset, mostly around the parietal area. The results demonstrate a dynamic modulation of somatosensory-auditory convergence and suggest the contribution of somatosensory information for speech processing process is dependent on the specific temporal order of sensory inputs in speech production.

  15. The interaction between felt touch and tactile consequences of observed actions: an action-based somatosensory congruency paradigm.

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    Deschrijver, Eliane; Wiersema, Jan R; Brass, Marcel

    2016-07-01

    Action observation leads to a representation of both the motor aspect of an observed action (motor simulation) and its somatosensory consequences (action-based somatosensory simulation) in the observer's brain. In the current electroencephalography-study, we investigated the neuronal interplay of action-based somatosensory simulation and felt touch. We presented index or middle finger tapping movements of a human or a wooden hand, while simultaneously presenting 'tap-like' tactile sensations to either the corresponding or non-corresponding fingertip of the participant. We focused on an early stage of somatosensory processing [P50, N100 and N140 sensory evoked potentials (SEPs)] and on a later stage of higher-order processing (P3-complex). The results revealed an interaction effect of animacy and congruency in the early P50 SEP and an animacy effect in the N100/N140 SEPs. In the P3-complex, we found an interaction effect indicating that the influence of congruency was larger in the human than in the wooden hand. We argue that the P3-complex may reflect higher-order self-other distinction by signaling simulated action-based touch that does not match own tactile information. As such, the action-based somatosensory congruency paradigm might help understand higher-order social processes from a somatosensory point of view. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  16. Bilateral somatosensory evoked potentials following intermittent theta-burst repetitive transcranial magnetic stimulation

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    Ziluk Angela

    2010-08-01

    Full Text Available Abstract Background Intermittent theta-burst stimulation (iTBS is a form of repetitive transcranial magnetic stimulation that may alter cortical excitability in the primary somatosensory cortex (SI. The present study investigated the effects of iTBS on subcortical and early cortical somatosensory evoked potentials (SEPs recorded over left, iTBS stimulated SI and the right-hemisphere non-stimulated SI. SEPs were recorded before and at 5, 15, and 25 minutes following iTBS. Results Compared to pre-iTBS, the amplitude of cortical potential N20/P25 was significantly increased for 5 minutes from non-stimulated SI and for 15 to 25 minutes from stimulated SI. Subcortical potentials recorded bilaterally remained unaltered following iTBS. Conclusion We conclude that iTBS increases the cortical excitability of SI bilaterally and does not alter thalamocortical afferent input to SI. ITBS may provide one avenue to induce cortical plasticity in the somatosensory cortex.

  17. Predictability of painful stimulation modulates the somatosensory-evoked potential in the rat

    NARCIS (Netherlands)

    Schaap, M.W.H.; van Oostrom, H.; Doornenbal, A.; Baars, A.M.; Arndt, S.S.; Hellebrekers, L.J.

    2013-01-01

    Abstract Somatosensory-evoked potentials (SEPs) are used in humans and animals to increase knowledge about nociception and pain. Since the SEP in humans increases when noxious stimuli are administered unpredictably, predictability potentially influences the SEP in animals as well. To assess the

  18. Prefrontal cortex and somatosensory cortex in tactile crossmodal association: an independent component analysis of ERP recordings.

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    Yixuan Ku

    2007-08-01

    Full Text Available Our previous studies on scalp-recorded event-related potentials (ERPs showed that somatosensory N140 evoked by a tactile vibration in working memory tasks was enhanced when human subjects expected a coming visual stimulus that had been paired with the tactile stimulus. The results suggested that such enhancement represented the cortical activities involved in tactile-visual crossmodal association. In the present study, we further hypothesized that the enhancement represented the neural activities in somatosensory and frontal cortices in the crossmodal association. By applying independent component analysis (ICA to the ERP data, we found independent components (ICs located in the medial prefrontal cortex (around the anterior cingulate cortex, ACC and the primary somatosensory cortex (SI. The activity represented by the IC in SI cortex showed enhancement in expectation of the visual stimulus. Such differential activity thus suggested the participation of SI cortex in the task-related crossmodal association. Further, the coherence analysis and the Granger causality spectral analysis of the ICs showed that SI cortex appeared to cooperate with ACC in attention and perception of the tactile stimulus in crossmodal association. The results of our study support with new evidence an important idea in cortical neurophysiology: higher cognitive operations develop from the modality-specific sensory cortices (in the present study, SI cortex that are involved in sensation and perception of various stimuli.

  19. Morphometric analysis of feedforward pathways from the primary somatosensory area (S1 of rats

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    A.L. de Sá

    2016-01-01

    Full Text Available We used biotinylated dextran amine (BDA to anterogradely label individual axons projecting from primary somatosensory cortex (S1 to four different cortical areas in rats. A major goal was to determine whether axon terminals in these target areas shared morphometric similarities based on the shape of individual terminal arbors and the density of two bouton types: en passant (Bp and terminaux (Bt. Evidence from tridimensional reconstructions of isolated axon terminal fragments (n=111 did support a degree of morphological heterogeneity establishing two broad groups of axon terminals. Morphological parameters associated with the complexity of terminal arbors and the proportion of beaded Bp vs stalked Bt were found to differ significantly in these two groups following a discriminant function statistical analysis across axon fragments. Interestingly, both groups occurred in all four target areas, possibly consistent with a commonality of presynaptic processing of tactile information. These findings lay the ground for additional work aiming to investigate synaptic function at the single bouton level and see how this might be associated with emerging properties in postsynaptic targets.

  20. Electrophysiological Evidence for a Sensory Recruitment Model of Somatosensory Working Memory.

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    Katus, Tobias; Grubert, Anna; Eimer, Martin

    2015-12-01

    Sensory recruitment models of working memory assume that information storage is mediated by the same cortical areas that are responsible for the perceptual processing of sensory signals. To test this assumption, we measured somatosensory event-related brain potentials (ERPs) during a tactile delayed match-to-sample task. Participants memorized a tactile sample set at one task-relevant hand to compare it with a subsequent test set on the same hand. During the retention period, a sustained negativity (tactile contralateral delay activity, tCDA) was elicited over primary somatosensory cortex contralateral to the relevant hand. The amplitude of this component increased with memory load and was sensitive to individual limitations in memory capacity, suggesting that the tCDA reflects the maintenance of tactile information in somatosensory working memory. The tCDA was preceded by a transient negativity (N2cc component) with a similar contralateral scalp distribution, which is likely to reflect selection of task-relevant tactile stimuli at the encoding stage. The temporal sequence of N2cc and tCDA components mirrors previous observations from ERP studies of working memory in vision. The finding that the sustained somatosensory delay period activity varies as a function of memory load supports a sensory recruitment model for spatial working memory in touch. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Neural mechanisms of selective attention in the somatosensory system.

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    Gomez-Ramirez, Manuel; Hysaj, Kristjana; Niebur, Ernst

    2016-09-01

    Selective attention allows organisms to extract behaviorally relevant information while ignoring distracting stimuli that compete for the limited resources of their central nervous systems. Attention is highly flexible, and it can be harnessed to select information based on sensory modality, within-modality feature(s), spatial location, object identity, and/or temporal properties. In this review, we discuss the body of work devoted to understanding mechanisms of selective attention in the somatosensory system. In particular, we describe the effects of attention on tactile behavior and corresponding neural activity in somatosensory cortex. Our focus is on neural mechanisms that select tactile stimuli based on their location on the body (somatotopic-based attention) or their sensory feature (feature-based attention). We highlight parallels between selection mechanisms in touch and other sensory systems and discuss several putative neural coding schemes employed by cortical populations to signal the behavioral relevance of sensory inputs. Specifically, we contrast the advantages and disadvantages of using a gain vs. spike-spike correlation code for representing attended sensory stimuli. We favor a neural network model of tactile attention that is composed of frontal, parietal, and subcortical areas that controls somatosensory cells encoding the relevant stimulus features to enable preferential processing throughout the somatosensory hierarchy. Our review is based on data from noninvasive electrophysiological and imaging data in humans as well as single-unit recordings in nonhuman primates. Copyright © 2016 the American Physiological Society.

  2. Alpha, beta and gamma electrocorticographic rhythms in somatosensory, motor, premotor and prefrontal cortical areas differ in movement execution and observation in humans.

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    Babiloni, Claudio; Del Percio, Claudio; Vecchio, Fabrizio; Sebastiano, Fabio; Di Gennaro, Giancarlo; Quarato, Pier P; Morace, Roberta; Pavone, Luigi; Soricelli, Andrea; Noce, Giuseppe; Esposito, Vincenzo; Rossini, Paolo Maria; Gallese, Vittorio; Mirabella, Giovanni

    2016-01-01

    In the present study, we tested the hypothesis that both movement execution and observation induce parallel modulations of alpha, beta, and gamma electrocorticographic (ECoG) rhythms in primary somatosensory (Brodmann area 1-2, BA1-2), primary motor (BA4), ventral premotor (BA6), and prefrontal (BA44 and BA45, part of putative human mirror neuron system underlying the understanding of actions of other people) areas. ECoG activity was recorded in drug-resistant epileptic patients during the execution of actions to reach and grasp common objects according to their affordances, as well as during the observation of the same actions performed by an experimenter. Both action execution and observation induced a desynchronization of alpha and beta rhythms in BA1-2, BA4, BA6, BA44 and BA45, which was generally higher in amplitude during the former than the latter condition. Action execution also induced a major synchronization of gamma rhythms in BA4 and BA6, again more during the execution of an action than during its observation. Human primary sensorimotor, premotor, and prefrontal areas do generate alpha, beta, and gamma rhythms and differently modulate them during action execution and observation. Gamma rhythms of motor areas are especially involved in action execution. Oscillatory activity of neural populations in sensorimotor, premotor and prefrontal (part of human mirror neuron system) areas represents and distinguishes own actions from those of other people. This methodological approach might be used for a neurophysiological diagnostic imaging of social cognition in epileptic patients. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  3. Evaluation of the synuclein-y (SNCG) gene as a PPARy target in murine adipocytes, dorsal root ganglia somatosensory neurons, and human adipose tissue

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    Synuclein-gamma is highly expressed in both adipocytes and peripheral nervous system (PNS) somatosensory neurons. Its mRNA is induced during adipogenesis, increased in obese human white adipose tissue (WAT), may be coordinately regulated with leptin, and is decreased following treatment of murine 3T...

  4. Subliminal stimulation and somatosensory signal detection.

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    Ferrè, Elisa Raffaella; Sahani, Maneesh; Haggard, Patrick

    2016-10-01

    Only a small fraction of sensory signals is consciously perceived. The brain's perceptual systems may include mechanisms of feedforward inhibition that protect the cortex from subliminal noise, thus reserving cortical capacity and conscious awareness for significant stimuli. Here we provide a new view of these mechanisms based on signal detection theory, and gain control. We demonstrated that subliminal somatosensory stimulation decreased sensitivity for the detection of a subsequent somatosensory input, largely due to increased false alarm rates. By delivering the subliminal somatosensory stimulus and the to-be-detected somatosensory stimulus to different digits of the same hand, we show that this effect spreads across the sensory surface. In addition, subliminal somatosensory stimulation tended to produce an increased probability of responding "yes", whether the somatosensory stimulus was present or not. Our results suggest that subliminal stimuli temporarily reduce input gain, avoiding excessive responses to further small inputs. This gain control may be automatic, and may precede discriminative classification of inputs into signals or noise. Crucially, we found that subliminal inputs influenced false alarm rates only on blocks where the to-be-detected stimuli were present, and not on pre-test control blocks where they were absent. Participants appeared to adjust their perceptual criterion according to a statistical distribution of stimuli in the current context, with the presence of supraliminal stimuli having an important role in the criterion-setting process. These findings clarify the cognitive mechanisms that reserve conscious perception for salient and important signals. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Modulation of Somatosensory Alpha Rhythm by Transcranial Alternating Current Stimulation at Mu-Frequency

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    Christopher Gundlach

    2017-08-01

    Full Text Available Introduction: Transcranial alternating current stimulation (tACS is emerging as an interventional tool to modulate different functions of the brain, potentially by interacting with intrinsic ongoing neuronal oscillations. Functionally different intrinsic alpha oscillations are found throughout the cortex. Yet it remains unclear whether tACS is capable of specifically modulating the somatosensory mu-rhythm in amplitude.Objectives: We used tACS to modulate mu-alpha oscillations in amplitude. When compared to sham stimulation we expected a modulation of mu-alpha oscillations but not visual alpha oscillations by tACS.Methods: Individual mu-alpha frequencies were determined in 25 participants. Subsequently, blocks of tACS with individual mu-alpha frequency and sham stimulation were applied over primary somatosensory cortex (SI. Electroencephalogram (EEG was recorded before and after either stimulation or sham. Modulations of mu-alpha and, for control, visual alpha amplitudes were then compared between tACS and sham.Results: Somatosensory mu-alpha oscillations decreased in amplitude after tACS was applied at participants’ individual mu-alpha frequency. No changes in amplitude were observed for sham stimulation. Furthermore, visual alpha oscillations were not affected by tACS or sham, respectively.Conclusion: Our results demonstrate the capability of tACS to specifically modulate the targeted somatosensory mu-rhythm when the tACS frequency is tuned to the individual endogenous rhythm and applied over somatosensory areas. Our results are in contrast to previously reported amplitude increases of visual alpha oscillations induced by tACS applied over visual cortex. Our results may point to a specific interaction between our stimulation protocol and the functional architecture of the somatosensory system.

  6. The effect of water immersion on short-latency somatosensory evoked potentials in human

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    Sato Daisuke

    2012-01-01

    Full Text Available Abstract Background Water immersion therapy is used to treat a variety of cardiovascular, respiratory, and orthopedic conditions. It can also benefit some neurological patients, although little is known about the effects of water immersion on neural activity, including somatosensory processing. To this end, we examined the effect of water immersion on short-latency somatosensory evoked potentials (SEPs elicited by median nerve stimuli. Short-latency SEP recordings were obtained for ten healthy male volunteers at rest in or out of water at 30°C. Recordings were obtained from nine scalp electrodes according to the 10-20 system. The right median nerve at the wrist was electrically stimulated with the stimulus duration of 0.2 ms at 3 Hz. The intensity of the stimulus was fixed at approximately three times the sensory threshold. Results Water immersion significantly reduced the amplitudes of the short-latency SEP components P25 and P45 measured from electrodes over the parietal region and the P45 measured by central region. Conclusions Water immersion reduced short-latency SEP components known to originate in several cortical areas. Attenuation of short-latency SEPs suggests that water immersion influences the cortical processing of somatosensory inputs. Modulation of cortical processing may contribute to the beneficial effects of aquatic therapy. Trial Registration UMIN-CTR (UMIN000006492

  7. A new psychometric questionnaire for reporting of somatosensory percepts

    Science.gov (United States)

    Kim, L. H.; McLeod, R. S.; Kiss, Z. H. T.

    2018-02-01

    Objective. There have been remarkable advances over the past decade in neural prostheses to restore lost motor function. However, restoration of somatosensory feedback, which is essential for fine motor control and user acceptance, has lagged behind. With an increasing interest in using electrical stimulation to restore somatosensory sensations within the peripheral (PNS) and central nervous systems (CNS), it is critical to characterize the percepts evoked by electrical stimulation in a standardized manner with a validated psychometric questionnaire. This will allow comparison of results from applications at various nervous system levels in multiple settings. Approach. We compiled a summary of published reports of somatosensory percepts that were elicited by electrical stimulation in humans and used these to develop a new psychometric questionnaire. Results. This new questionnaire was able to characterize subjective evoked sensations with good test-retest reliability (Spearman’s correlation coefficients ranging 0.716  ⩽  ρ  ⩽  1.000, p  ⩽  0.005) in 13 subjects receiving stimulation through neural implants in both the CNS and PNS. Furthermore, the new questionnaire captured more descriptors (M  =  2.65, SD  =  0.91) that would have been missed by being categorized as ‘other sensations’, using a previous questionnaire (M  =  1.40, SD  =  0.77, t(12)  =  -10.24, p  psychometric questionnaire will aid in establishing consistency and standardization of reporting in future studies of somatosensory neural prostheses.

  8. COMMUNICATION Designing a somatosensory neural prosthesis: percepts evoked by different patterns of thalamic stimulation

    Science.gov (United States)

    Heming, Ethan; Sanden, Andrew; Kiss, Zelma H. T.

    2010-12-01

    Although major advances have been made in the development of motor prostheses, fine motor control requires intuitive somatosensory feedback. Here we explored whether a thalamic site for a somatosensory neural prosthetic could provide natural somatic sensation to humans. Different patterns of electrical stimulation (obtained from thalamic spike trains) were applied in patients undergoing deep brain stimulation surgery. Changes in pattern produced different sensations, while preserving somatotopic representation. While most percepts were reported as 'unnatural', some stimulations produced more 'natural' sensations than others. However, the additional patterns did not elicit more 'natural' percepts than high-frequency (333 Hz) electrical stimulation. These features suggest that despite some limitations, the thalamus may be a feasible site for a somatosensory neural prosthesis and different stimulation patterns may be useful in its development.

  9. Corticofugal projections induce long-lasting effects on somatosensory responses in the trigeminal complex of the rat

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    Angel eNunez

    2014-05-01

    Full Text Available The sensory information flow at subcortical relay stations is controlled by the action of topographic connections from the neocortex. To determinate the functional properties of the somatosensory corticofugal projections to the principal (Pr5 and caudal spinal (Sp5C trigeminal nuclei, we performed unitary recordings in anesthetized rats. To examine the effect of these cortical projections we used tactile stimulation of the whisker and electrical stimulation of somatosensory cortices. Corticofugal anatomical projections to Pr5 and Sp5C nuclei were detected by using retrograde fluorescent tracers. Neurons projecting exclusively to Pr5 were located in the cingulate cortex while neurons projecting to both Sp5C and Pr5 nuclei were located in the somatosensory and insular cortices (>75% of neurons. Physiological results indicated that primary somatosensory cortex produced a short-lasting facilitating or inhibiting effects (< 5 minutes of tactile responses in Pr5 nucleus through activation of NMDA glutamatergic or GABAA receptors since effects were blocked by iontophoretically application of APV and bicuculline, respectively. In contrast, stimulation of secondary somatosensory cortex did not affect most of the Pr5 neurons; however both cortices inhibited the nociceptive responses in the Sp5C nucleus through activation of glycinergic or GABAA receptors because effects were blocked by iontophoretically application of strychnine and bicuculline, respectively. These and anatomical results demonstrated that the somatosensory cortices projects to Pr5 nucleus to modulate tactile responses by excitatory and inhibitory actions, while projections to the Sp5C nucleus control nociceptive sensory transmission by only inhibitory effects. Thus, somatosensory cortices may modulate innocuous and noxious inputs simultaneously, contributing to the perception of specifically tactile or painful sensations.

  10. Novel assessment of cortical response to somatosensory stimuli in children with hemiparetic cerebral palsy.

    Science.gov (United States)

    Maitre, Nathalie L; Barnett, Zachary P; Key, Alexandra P F

    2012-10-01

    The brain's response to somatosensory stimuli is essential to experience-driven learning in children. It was hypothesized that advances in event-related potential technology could quantify the response to touch in somatosensory cortices and characterize the responses of hemiparetic children. In this prospective study of 8 children (5-8 years old) with hemiparetic cerebral palsy, both event-related potential responses to sham or air puff trials and standard functional assessments were used. Event-related potential technology consistently measured signals reflecting activity in the primary and secondary somatosensory cortices as well as complex cognitive processing of touch. Participants showed typical early responses but less efficient perceptual processes. Significant differences between affected and unaffected extremities correlated with sensorimotor testing, stereognosis, and 2-point discrimination (r > 0.800 and P = .001 for all). For the first time, a novel event-related potential paradigm shows that hemiparetic children have slower and less efficient tactile cortical perception in their affected extremities.

  11. Inhibitory Mechanisms in Primary Somatosensory Cortex Mediate the Effects of Peripheral Electrical Stimulation on Tactile Spatial Discrimination.

    Science.gov (United States)

    Saito, Kei; Otsuru, Naofumi; Inukai, Yasuto; Kojima, Sho; Miyaguchi, Shota; Tsuiki, Shota; Sasaki, Ryoki; Onishi, Hideaki

    2018-06-01

    Selective afferent activation can be used to improve somatosensory function, possibly by altering cortical inhibitory circuit activity. Peripheral electrical stimulation (PES) is widely used to induce selective afferent activation, and its effect may depend on PES intensity. Therefore, we investigated the effects of high- and low-intensity PES applied to the right index finger on tactile discrimination performance and cortical sensory-evoked potential paired-pulse depression (SEP-PPD) in 25 neurologically healthy subjects. In Experiment 1, a grating orientation task (GOT) was performed before and immediately after local high- and low-intensity PES (both delivered as 1-s, 20-Hz trains of 0.2-ms electrical pulses at 5-s intervals). In Experiment 2, PPD of SEP components N20/P25_SEP-PPD and N20_SEP-PPD, respectively, were assessed before and immediately after high- and low-intensity PES. Improved GOT discrimination performance after high-intensity PES (reduced discrimination threshold) was associated with lower baseline performance (higher baseline discrimination threshold). Subjects were classified into low and high (baseline) GOT performance groups. Improved GOT discrimination performance in the low GOT performance group was significantly associated with a greater N20_SEP-PPD decrease (weaker PPD). Subjects were also classified into GOT improvement and GOT decrement groups. High-intensity PES decreased N20_SEP-PPD in the GOT improvement group but increased N20_SEP-PPD in the GOT decrement group. Furthermore, a greater decrease in GOT discrimination threshold was significantly associated with a greater N20_SEP-PPD decrease in the GOT improvement group. These results suggest that high-intensity PES can improve sensory perception in subjects with low baseline function by modulating cortical inhibitory circuits in primary somatosensory cortex. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  12. The third-stimulus temporal discrimination threshold: focusing on the temporal processing of sensory input within primary somatosensory cortex.

    Science.gov (United States)

    Leodori, Giorgio; Formica, Alessandra; Zhu, Xiaoying; Conte, Antonella; Belvisi, Daniele; Cruccu, Giorgio; Hallett, Mark; Berardelli, Alfredo

    2017-10-01

    The somatosensory temporal discrimination threshold (STDT) has been used in recent years to investigate time processing of sensory information, but little is known about the physiological correlates of somatosensory temporal discrimination. The objective of this study was to investigate whether the time interval required to discriminate between two stimuli varies according to the number of stimuli in the task. We used the third-stimulus temporal discrimination threshold (ThirdDT), defined as the shortest time interval at which an individual distinguishes a third stimulus following a pair of stimuli delivered at the STDT. The STDT and ThirdDT were assessed in 31 healthy subjects. In a subgroup of 10 subjects, we evaluated the effects of the stimuli intensity on the ThirdDT. In a subgroup of 16 subjects, we evaluated the effects of S1 continuous theta-burst stimulation (S1-cTBS) on the STDT and ThirdDT. Results show that ThirdDT is shorter than STDT. We found a positive correlation between STDT and ThirdDT values. As long as the stimulus intensity was within the perceivable and painless range, it did not affect ThirdDT values. S1-cTBS significantly affected both STDT and ThirdDT, although the latter was affected to a greater extent and for a longer period of time. We conclude that the interval needed to discriminate between time-separated tactile stimuli is related to the number of stimuli used in the task. STDT and ThirdDT are encoded in S1, probably by a shared tactile temporal encoding mechanism whose performance rapidly changes during the perception process. ThirdDT is a new method to measure somatosensory temporal discrimination. NEW & NOTEWORTHY To investigate whether the time interval required to discriminate between stimuli varies according to changes in the stimulation pattern, we used the third-stimulus temporal discrimination threshold (ThirdDT). We found that the somatosensory temporal discrimination acuity varies according to the number of stimuli in the

  13. MOBIUS-STRIP-LIKE COLUMNAR FUNCTIONAL CONNECTIONS ARE REVEALED IN SOMATO-SENSORY RECEPTIVE FIELD CENTROIDS.

    Directory of Open Access Journals (Sweden)

    James Joseph Wright

    2014-10-01

    Full Text Available Receptive fields of neurons in the forelimb region of areas 3b and 1 of primary somatosensory cortex, in cats and monkeys, were mapped using extracellular recordings obtained sequentially from nearly radial penetrations. Locations of the field centroids indicated the presence of a functional system, in which cortical homotypic representations of the limb surfaces are entwined in three-dimensional Mobius-strip-like patterns of synaptic connections. Boundaries of somatosensory receptive field in nested groups irregularly overlie the centroid order, and are interpreted as arising from the superposition of learned connections upon the embryonic order. Since the theory of embryonic synaptic self-organisation used to model these results was devised and earlier used to explain findings in primary visual cortex, the present findings suggest the theory may be of general application throughout cortex, and may reveal a modular functional synaptic system, which, only in some parts of the cortex, and in some species, is manifest as anatomical ordering into columns.

  14. Feedforward somatosensory inhibition is normal in cervical dystonia.

    Science.gov (United States)

    Ferrè, Elisa R; Ganos, Christos; Bhatia, Kailash P; Haggard, Patrick

    2015-03-01

    Insufficient cortical inhibition is a key pathophysiological finding in dystonia. Subliminal sensory stimuli were reported to transiently inhibit somatosensory processing. Here we investigated whether such subliminal feedforward inhibition is reduced in patients with cervical dystonia. Sixteen cervical dystonia patients and 16 matched healthy controls performed a somatosensory detection task. We measured the drop in sensitivity to detect a threshold-level digital nerve shock when it was preceded by a subliminal conditioning shock, compared to when it was not. Subliminal conditioning shocks reduced sensitivity to threshold stimuli to a similar extent in both patients and controls, suggesting that somatosensory subliminal feedforward inhibition is normal in cervical dystonia. Somatosensory feedforward inhibition was normal in this group of cervical dystonia patients. Our results qualify previous concepts of a general dystonic deficit in sensorimotor inhibitory processing. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Making sense out of spinal cord somatosensory development

    Science.gov (United States)

    Seal, Rebecca P.

    2016-01-01

    The spinal cord integrates and relays somatosensory input, leading to complex motor responses. Research over the past couple of decades has identified transcription factor networks that function during development to define and instruct the generation of diverse neuronal populations within the spinal cord. A number of studies have now started to connect these developmentally defined populations with their roles in somatosensory circuits. Here, we review our current understanding of how neuronal diversity in the dorsal spinal cord is generated and we discuss the logic underlying how these neurons form the basis of somatosensory circuits. PMID:27702783

  16. HAL® exoskeleton training improves walking parameters and normalizes cortical excitability in primary somatosensory cortex in spinal cord injury patients.

    Science.gov (United States)

    Sczesny-Kaiser, Matthias; Höffken, Oliver; Aach, Mirko; Cruciger, Oliver; Grasmücke, Dennis; Meindl, Renate; Schildhauer, Thomas A; Schwenkreis, Peter; Tegenthoff, Martin

    2015-08-20

    Reorganization in the sensorimotor cortex accompanied by increased excitability and enlarged body representations is a consequence of spinal cord injury (SCI). Robotic-assisted bodyweight supported treadmill training (BWSTT) was hypothesized to induce reorganization and improve walking function. To assess whether BWSTT with hybrid assistive limb® (HAL®) exoskeleton affects cortical excitability in the primary somatosensory cortex (S1) in SCI patients, as measured by paired-pulse somatosensory evoked potentials (ppSEP) stimulated above the level of injury. Eleven SCI patients took part in HAL® assisted BWSTT for 3 months. PpSEP were conducted before and after this training period, where the amplitude ratios (SEP amplitude following double pulses - SEP amplitude following single pulses) were assessed and compared to eleven healthy control subjects. To assess improvement in walking function, we used the 10-m walk test, timed-up-and-go test, the 6-min walk test, and the lower extremity motor score. PpSEPs were significantly increased in SCI patients as compared to controls at baseline. Following training, ppSEPs were increased from baseline and no longer significantly differed from controls. Walking parameters also showed significant improvements, yet there was no significant correlation between ppSEP measures and walking parameters. The findings suggest that robotic-assisted BWSTT with HAL® in SCI patients is capable of inducing cortical plasticity following highly repetitive, active locomotive use of paretic legs. While there was no significant correlation of excitability with walking parameters, brain areas other than S1 might reflect improvement of walking functions. EEG and neuroimaging studies may provide further information about supraspinal plastic processes and foci in SCI rehabilitation.

  17. Somatosensory BOLD fMRI reveals close link between salient blood pressure changes and the murine neuromatrix.

    Science.gov (United States)

    Reimann, Henning Matthias; Todiras, Mihail; Hodge, Russ; Huelnhagen, Till; Millward, Jason Michael; Turner, Robert; Seeliger, Erdmann; Bader, Michael; Pohlmann, Andreas; Niendorf, Thoralf

    2018-05-15

    The neuromatrix, or "pain matrix", is a network of cortical brain areas which is activated by noxious as well as salient somatosensory stimulation. This has been studied in mice and humans using blood oxygenation level-dependent (BOLD) fMRI. Here we demonstrate that BOLD effects observed in the murine neuromatrix in response to salient somatosensory stimuli are prone to reflect mean arterial blood pressure (MABP) changes, rather than neural activity. We show that a standard electrostimulus typically used in murine somatosensory fMRI can induce substantial elevations in MABP. Equivalent drug-induced MABP changes - without somatosensory stimulation - evoked BOLD patterns in the neuromatrix strikingly similar to those evoked by electrostimulation. This constitutes a serious caveat for murine fMRI. The regional specificity of these BOLD patterns can be attributed to the co-localization of the neuromatrix with large draining veins. Based on these findings we propose a cardiovascular support mechanism whereby abrupt elevations in MABP provide additional energy supply to the neuromatrix and other essential brain areas in fight-or-flight situations. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. The Processing of Somatosensory Information shifts from an early parallel into a serial processing mode: a combined fMRI/MEG study.

    Directory of Open Access Journals (Sweden)

    Carsten Michael Klingner

    2016-12-01

    Full Text Available The question regarding whether somatosensory inputs are processed in parallel or in series has not been clearly answered. Several studies that have applied dynamic causal modeling (DCM to fMRI data have arrived at seemingly divergent conclusions. However, these divergent results could be explained by the hypothesis that the processing route of somatosensory information changes with time. Specifically, we suggest that somatosensory stimuli are processed in parallel only during the early stage, whereas the processing is later dominated by serial processing. This hypothesis was revisited in the present study based on fMRI analyses of tactile stimuli and the application of DCM to magnetoencephalographic (MEG data collected during sustained (260 ms tactile stimulation. Bayesian model comparisons were used to infer the processing stream. We demonstrated that the favored processing stream changes over time. We found that the neural activity elicited in the first 100 ms following somatosensory stimuli is best explained by models that support a parallel processing route, whereas a serial processing route is subsequently favored. These results suggest that the secondary somatosensory area (SII receives information regarding a new stimulus in parallel with the primary somatosensory area (SI, whereas later processing in the SII is dominated by the preprocessed input from the SI.

  19. The Processing of Somatosensory Information Shifts from an Early Parallel into a Serial Processing Mode: A Combined fMRI/MEG Study.

    Science.gov (United States)

    Klingner, Carsten M; Brodoehl, Stefan; Huonker, Ralph; Witte, Otto W

    2016-01-01

    The question regarding whether somatosensory inputs are processed in parallel or in series has not been clearly answered. Several studies that have applied dynamic causal modeling (DCM) to fMRI data have arrived at seemingly divergent conclusions. However, these divergent results could be explained by the hypothesis that the processing route of somatosensory information changes with time. Specifically, we suggest that somatosensory stimuli are processed in parallel only during the early stage, whereas the processing is later dominated by serial processing. This hypothesis was revisited in the present study based on fMRI analyses of tactile stimuli and the application of DCM to magnetoencephalographic (MEG) data collected during sustained (260 ms) tactile stimulation. Bayesian model comparisons were used to infer the processing stream. We demonstrated that the favored processing stream changes over time. We found that the neural activity elicited in the first 100 ms following somatosensory stimuli is best explained by models that support a parallel processing route, whereas a serial processing route is subsequently favored. These results suggest that the secondary somatosensory area (SII) receives information regarding a new stimulus in parallel with the primary somatosensory area (SI), whereas later processing in the SII is dominated by the preprocessed input from the SI.

  20. A functional MRI study of somatotopic representation of somatosensory stimulation in the cerebellum

    Energy Technology Data Exchange (ETDEWEB)

    Takanashi, M.; Abe, K.; Yanagihara, T.; Sakoda, S. [Dept. of Neurology D4, Osaka Univ. Graduate School of Medicine, Suita City, Osaka (Japan); Tanaka, H.; Hirabuki, N.; Nakamura, H.; Fujita, N. [Dept. of Radiology, Osaka Univ. Graduate School of Medicine, Suita City, Osaka (Japan)

    2003-03-01

    Somatotopic representation in the cerebral cortex of somatosensory stimulation has been widely reported, but that in the cerebellum has not. We investigated the latter in the human cerebellum by functional MRI (fMRI). Using a 1.5 tesla imager, we obtained multislice blood oxygen level-dependent fMRI with single-shot gradient-echo echoplanar imaging in seven right-handed volunteers during electrical stimulation of the left index finger and big toe. In the anterior and posterior cerebellum, activated pixels for the index finger were separate from those for the toe. This suggests that somatosensory stimulation of different parts of the body may involve distinct areas of in the cerebellum as well as the cerebral cortex. (orig.)

  1. A functional MRI study of somatotopic representation of somatosensory stimulation in the cerebellum

    International Nuclear Information System (INIS)

    Takanashi, M.; Abe, K.; Yanagihara, T.; Sakoda, S.; Tanaka, H.; Hirabuki, N.; Nakamura, H.; Fujita, N.

    2003-01-01

    Somatotopic representation in the cerebral cortex of somatosensory stimulation has been widely reported, but that in the cerebellum has not. We investigated the latter in the human cerebellum by functional MRI (fMRI). Using a 1.5 tesla imager, we obtained multislice blood oxygen level-dependent fMRI with single-shot gradient-echo echoplanar imaging in seven right-handed volunteers during electrical stimulation of the left index finger and big toe. In the anterior and posterior cerebellum, activated pixels for the index finger were separate from those for the toe. This suggests that somatosensory stimulation of different parts of the body may involve distinct areas of in the cerebellum as well as the cerebral cortex. (orig.)

  2. Vestibular-somatosensory interactions: effects of passive whole-body rotation on somatosensory detection.

    Directory of Open Access Journals (Sweden)

    Elisa Raffaella Ferrè

    Full Text Available Vestibular signals are strongly integrated with information from several other sensory modalities. For example, vestibular stimulation was reported to improve tactile detection. However, this improvement could reflect either a multimodal interaction or an indirect interaction driven by vestibular effects on spatial attention and orienting. Here we investigate whether natural vestibular activation induced by passive whole-body rotation influences tactile detection. In particular, we assessed the ability to detect faint tactile stimuli to the fingertips of the left and right hand during spatially congruent or incongruent rotations. We found that passive whole-body rotations significantly enhanced sensitivity to faint shocks, without affecting response bias. Critically, this enhancement of somatosensory sensitivity did not depend on the spatial congruency between the direction of rotation and the hand stimulated. Thus, our results support a multimodal interaction, likely in brain areas receiving both vestibular and somatosensory signals.

  3. MEG reveals a fast pathway from somatosensory cortex to occipital areas via posterior parietal cortex in a blind subject.

    Science.gov (United States)

    Ioannides, Andreas A; Liu, Lichan; Poghosyan, Vahe; Saridis, George A; Gjedde, Albert; Ptito, Maurice; Kupers, Ron

    2013-01-01

    Cross-modal activity in visual cortex of blind subjects has been reported during performance of variety of non-visual tasks. A key unanswered question is through which pathways non-visual inputs are funneled to the visual cortex. Here we used tomographic analysis of single trial magnetoencephalography (MEG) data recorded from one congenitally blind and two sighted subjects after stimulation of the left and right median nerves at three intensities: below sensory threshold, above sensory threshold and above motor threshold; the last sufficient to produce thumb twitching. We identified reproducible brain responses in the primary somatosensory (S1) and motor (M1) cortices at around 20 ms post-stimulus, which were very similar in sighted and blind subjects. Time-frequency analysis revealed strong 45-70 Hz activity at latencies of 20-50 ms in S1 and M1, and posterior parietal cortex Brodmann areas (BA) 7 and 40, which compared to lower frequencies, were substantially more pronounced in the blind than the sighted subjects. Critically, at frequencies from α-band up to 100 Hz we found clear, strong, and widespread responses in the visual cortex of the blind subject, which increased with the intensity of the somatosensory stimuli. Time-delayed mutual information (MI) revealed that in blind subject the stimulus information is funneled from the early somatosensory to visual cortex through posterior parietal BA 7 and 40, projecting first to visual areas V5 and V3, and eventually V1. The flow of information through this pathway occurred in stages characterized by convergence of activations into specific cortical regions. In sighted subjects, no linked activity was found that led from the somatosensory to the visual cortex through any of the studied brain regions. These results provide the first evidence from MEG that in blind subjects, tactile information is routed from primary somatosensory to occipital cortex via the posterior parietal cortex.

  4. Negative BOLD signal changes in ipsilateral primary somatosensory cortex are associated with perfusion decreases and behavioral evidence for functional inhibition

    DEFF Research Database (Denmark)

    Schäfer, Katharina; Blankenburg, Felix; Kupers, Ron

    2012-01-01

    that the negative BOLD signal is associated with functional inhibition. Electrical stimulation of the median nerve at 7Hz evoked robust negative BOLD signals in the primary somatosensory cortex (SI) ipsilateral to stimulation, and positive BOLD signals in contralateral SI. The negative BOLD signal in ipsilateral SI......) at the ipsilateral finger during concomitant stimulation of the contralateral median nerve increased significantly, suggesting augmented functional inhibition. Since the CPT in the ipsilateral hallux did not significantly change in response to median nerve stimulation, it is more likely that the CPT......-increase for the finger is due to functional inhibition (Kastrup et al., 2008) than to changes in selective attention. In conclusion, our data provide evidence that stimulus-induced reductions in relative rCBF may underlie the negative BOLD signal, which in turn may reflect increments in functional inhibition....

  5. Direct and crossed effects of somatosensory stimulation on neuronal excitability and motor performance in humans

    NARCIS (Netherlands)

    Veldman, M. P.; Maffiuletti, N. A.; Hallett, M.; Zijdewind, I.; Hortobagyi, T.

    2014-01-01

    This analytic review reports how prolonged periods of somatosensory electric stimulation (SES) with repetitive transcutaneous nerve stimulation can have 'direct' and 'crossed' effects on brain activation, corticospinal excitability, and motor performance. A review of 26 studies involving 315 healthy

  6. Predicting Spike Occurrence and Neuronal Responsiveness from LFPs in Primary Somatosensory Cortex

    Science.gov (United States)

    Storchi, Riccardo; Zippo, Antonio G.; Caramenti, Gian Carlo; Valente, Maurizio; Biella, Gabriele E. M.

    2012-01-01

    Local Field Potentials (LFPs) integrate multiple neuronal events like synaptic inputs and intracellular potentials. LFP spatiotemporal features are particularly relevant in view of their applications both in research (e.g. for understanding brain rhythms, inter-areal neural communication and neronal coding) and in the clinics (e.g. for improving invasive Brain-Machine Interface devices). However the relation between LFPs and spikes is complex and not fully understood. As spikes represent the fundamental currency of neuronal communication this gap in knowledge strongly limits our comprehension of neuronal phenomena underlying LFPs. We investigated the LFP-spike relation during tactile stimulation in primary somatosensory (S-I) cortex in the rat. First we quantified how reliably LFPs and spikes code for a stimulus occurrence. Then we used the information obtained from our analyses to design a predictive model for spike occurrence based on LFP inputs. The model was endowed with a flexible meta-structure whose exact form, both in parameters and structure, was estimated by using a multi-objective optimization strategy. Our method provided a set of nonlinear simple equations that maximized the match between models and true neurons in terms of spike timings and Peri Stimulus Time Histograms. We found that both LFPs and spikes can code for stimulus occurrence with millisecond precision, showing, however, high variability. Spike patterns were predicted significantly above chance for 75% of the neurons analysed. Crucially, the level of prediction accuracy depended on the reliability in coding for the stimulus occurrence. The best predictions were obtained when both spikes and LFPs were highly responsive to the stimuli. Spike reliability is known to depend on neuron intrinsic properties (i.e. on channel noise) and on spontaneous local network fluctuations. Our results suggest that the latter, measured through the LFP response variability, play a dominant role. PMID:22586452

  7. Index finger somatosensory evoked potentials in blind Braille readers.

    Science.gov (United States)

    Giriyappa, Dayananda; Subrahmanyam, Roopakala Mysore; Rangashetty, Srinivasa; Sharma, Rajeev

    2009-01-01

    Traditionally, vision has been considered the dominant modality in our multi-sensory perception of the surrounding world. Sensory input via non-visual tracts becomes of greater behavioural relevance in totally blind individuals to enable effective interaction with the world around them. These include audition and tactile perceptions, leading to an augmentation in these perceptions when compared with normal sighted individuals. The objective of the present work was to study the index finger somatosensory evoked potentials (SEPs) in totally blind and normal sighted individuals. SEPs were recorded in 15 Braille reading totally blind females and compared with 15 age-matched normal sighted females. Latency and amplitudes of somatosensory evoked potential waveforms (N9, N13, and N20) were measured. Amplitude of N20 SEP (a cortical somatosensory evoked potential) was significantly larger in the totally blind than in normal sighted individuals (p Braille reading right index finger. Totally blind Braille readers have larger N20 amplitude, suggestive of greater somatosensory cortical representation of the Braille reading index finger.

  8. MEG reveals a fast pathway from somatosensory cortex to occipital areas via posterior parietal cortex in a blind subject

    Directory of Open Access Journals (Sweden)

    Andreas A Ioannides

    2013-08-01

    Full Text Available Cross-modal activity in visual cortex of blind subjects has been reported during performance of variety of non-visual tasks. A key unanswered question is through which pathways non-visual inputs are funneled to the visual cortex. Here we used tomographic analysis of single trial magnetoencephalography (MEG data recorded from one congenitally blind and two sighted subjects after stimulation of the left and right median nerves at three intensities: below sensory threshold, above sensory threshold and above motor threshold; the last sufficient to produce thumb twitching. We identified reproducible brain responses in the primary somatosensory (S1 and motor (M1 cortices at around 20 ms post-stimulus, which were very similar in sighted and blind subjects. Time-frequency analysis revealed strong 45 to 70 Hz activity at latencies of 20 to 50 ms in S1 and M1, and posterior parietal cortex Brodmann areas (BA 7 and 40, which compared to lower frequencies, were substantially more pronounced in the blind than the sighted subjects. Critically, at frequencies from α-band up to 100 Hz we found clear, strong and widespread responses in the visual cortex of the blind subject, which increased with the intensity of the somatosensory stimuli. Time-delayed mutual information (MI revealed that in blind subject the stimulus information is funneled from the early somatosensory to visual cortex through posterior parietal BA 7 and 40, projecting first to visual areas V5 and V3, and eventually V1. The flow of information through this pathway occured in stages characterized by convergence of activations into specific cortical regions. In sighted subjects, no linked activity was found that led from the somatosensory to the visual cortex through any of the studied brain regions. These results provide the first evidence from MEG that in blind subjects, tactile information is routed from primary somatosensory to occipital cortex via the posterior parietal cortex.

  9. A cognitive neuroprosthetic that uses cortical stimulation for somatosensory feedback

    Science.gov (United States)

    Klaes, Christian; Shi, Ying; Kellis, Spencer; Minxha, Juri; Revechkis, Boris; Andersen, Richard A.

    2014-10-01

    Objective. Present day cortical brain-machine interfaces (BMIs) have made impressive advances using decoded brain signals to control extracorporeal devices. Although BMIs are used in a closed-loop fashion, sensory feedback typically is visual only. However medical case studies have shown that the loss of somesthesis in a limb greatly reduces the agility of the limb even when visual feedback is available. Approach. To overcome this limitation, this study tested a closed-loop BMI that utilizes intracortical microstimulation to provide ‘tactile’ sensation to a non-human primate. Main result. Using stimulation electrodes in Brodmann area 1 of somatosensory cortex (BA1) and recording electrodes in the anterior intraparietal area, the parietal reach region and dorsal area 5 (area 5d), it was found that this form of feedback can be used in BMI tasks. Significance. Providing somatosensory feedback has the poyential to greatly improve the performance of cognitive neuroprostheses especially for fine control and object manipulation. Adding stimulation to a BMI system could therefore improve the quality of life for severely paralyzed patients.

  10. Somatosensory tinnitus: Current evidence and future perspectives

    Science.gov (United States)

    Greco, Antonio; Turchetta, Rosaria; Altissimi, Giancarlo; de Vincentiis, Marco; Cianfrone, Giancarlo

    2017-01-01

    In some individuals, tinnitus can be modulated by specific maneuvers of the temporomandibular joint, head and neck, eyes, and limbs. Neuroplasticity seems to play a central role in this capacity for modulation, suggesting that abnormal interactions between the sensory modalities, sensorimotor systems, and neurocognitive and neuroemotional networks may contribute to the development of somatosensory tinnitus. Current evidence supports a link between somatic disorders and higher modulation of tinnitus, especially in patients with a normal hearing threshold. Patients with tinnitus who have somatic disorders seems to have a higher chance of modulating their tinnitus with somatic maneuvers; consistent improvements in tinnitus symptoms have been observed in patients with temporomandibular joint disease following targeted therapy for temporomandibular disorders. Somatosensory tinnitus is often overlooked by otolaryngologists and not fully investigated during the diagnostic process. Somatic disorders, when identified and treated, can be a valid therapeutic target for tinnitus; however, somatic screening of subjects for somatosensory tinnitus is imperative for correct selection of patients who would benefit from a multidisciplinary somatic approach. PMID:28553764

  11. Somatosensory tinnitus: Current evidence and future perspectives.

    Science.gov (United States)

    Ralli, Massimo; Greco, Antonio; Turchetta, Rosaria; Altissimi, Giancarlo; de Vincentiis, Marco; Cianfrone, Giancarlo

    2017-06-01

    In some individuals, tinnitus can be modulated by specific maneuvers of the temporomandibular joint, head and neck, eyes, and limbs. Neuroplasticity seems to play a central role in this capacity for modulation, suggesting that abnormal interactions between the sensory modalities, sensorimotor systems, and neurocognitive and neuroemotional networks may contribute to the development of somatosensory tinnitus. Current evidence supports a link between somatic disorders and higher modulation of tinnitus, especially in patients with a normal hearing threshold. Patients with tinnitus who have somatic disorders seems to have a higher chance of modulating their tinnitus with somatic maneuvers; consistent improvements in tinnitus symptoms have been observed in patients with temporomandibular joint disease following targeted therapy for temporomandibular disorders. Somatosensory tinnitus is often overlooked by otolaryngologists and not fully investigated during the diagnostic process. Somatic disorders, when identified and treated, can be a valid therapeutic target for tinnitus; however, somatic screening of subjects for somatosensory tinnitus is imperative for correct selection of patients who would benefit from a multidisciplinary somatic approach.

  12. Asymmetric Functional Connectivity of the Contra- and Ipsilateral Secondary Somatosensory Cortex during Tactile Object Recognition

    Directory of Open Access Journals (Sweden)

    Yinghua Yu

    2018-01-01

    Full Text Available In the somatosensory system, it is well known that the bilateral secondary somatosensory cortex (SII receives projections from the unilateral primary somatosensory cortex (SI, and the SII, in turn, sends feedback projections to SI. Most neuroimaging studies have clearly shown bilateral SII activation using only unilateral stimulation for both anatomical and functional connectivity across SII subregions. However, no study has unveiled differences in the functional connectivity of the contra- and ipsilateral SII network that relates to frontoparietal areas during tactile object recognition. Therefore, we used event-related functional magnetic resonance imaging (fMRI and a delayed match-to-sample (DMS task to investigate the contributions of bilateral SII during tactile object recognition. In the fMRI experiment, 14 healthy subjects were presented with tactile angle stimuli on their right index finger and asked to encode three sample stimuli during the encoding phase and one test stimulus during the recognition phase. Then, the subjects indicated whether the angle of test stimulus was presented during the encoding phase. The results showed that contralateral (left SII activity was greater than ipsilateral (right SII activity during the encoding phase, but there was no difference during the recognition phase. A subsequent psycho-physiological interaction (PPI analysis revealed distinct connectivity from the contra- and ipsilateral SII to other regions. The left SII functionally connected to the left SI and right primary and premotor cortex, while the right SII functionally connected to the left posterior parietal cortex (PPC. Our findings suggest that in situations involving unilateral tactile object recognition, contra- and ipsilateral SII will induce an asymmetrical functional connectivity to other brain areas, which may occur by the hand contralateral effect of SII.

  13. Adaptation in human somatosensory cortex as a model of sensory memory construction: a study using high-density EEG.

    Science.gov (United States)

    Bradley, Claire; Joyce, Niamh; Garcia-Larrea, Luis

    2016-01-01

    Adaptation in sensory cortices has been seen as a mechanism allowing the creation of transient memory representations. Here we tested the adapting properties of early responses in human somatosensory areas SI and SII by analysing somatosensory-evoked potentials over the very first repetitions of a stimulus. SI and SII generators were identified by well-defined scalp potentials and source localisation from high-density 128-channel EEG. Earliest responses (~20 ms) from area 3b in the depth of the post-central gyrus did not show significant adaptation to stimuli repeated at 300 ms intervals. In contrast, responses around 45 ms from the crown of the gyrus (areas 1 and 2) rapidly lessened to a plateau and abated at the 20th stimulation, and activities from SII in the parietal operculum at ~100 ms displayed strong adaptation with a steady amplitude decrease from the first repetition. Although responses in both SI (1-2) and SII areas showed adapting properties and hence sensory memory capacities, evidence of sensory mismatch detection has been demonstrated only for responses reflecting SII activation. This may index the passage from an early form of sensory storage in SI to more operational memory codes in SII, allowing the prediction of forthcoming input and the triggering of a specific signal when such input differs from the previous sequence. This is consistent with a model whereby the length of temporal receptive windows increases with progression in the cortical hierarchy, in parallel with the complexity and abstraction of neural representations.

  14. Are there abnormalities in peripheral and central components of somatosensory evoked potentials in non - specific chronic low back pain ?

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    Christian Puta

    2016-10-01

    Full Text Available Chronic low back pain (CLBP was shown to be associated with longer reflex response latencies of trunk muscles during external upper limb perturbations. One theoretical, but rarely investigated possibility for longer reflex latencies might be related to modulated somatosensory information processing. Therefore, the present study investigated somatosensory evoked potentials (SEPs to median nerve stimulation in CLBP patients and healthy controls (HC. Latencies of the peripheral N9 SEP component were used as primary outcome. In addition, latencies and amplitudes of the central N20 SEP component, sensory thresholds, motor thresholds, and nerve conduction velocity were also analyzed in CLBP patients and HC. There is a trend for the CLBP patients to exhibited longer N9 latencies at the ipsilateral Erb’s point compared to HC. This trend is substantiated by significantly longer N9 latencies in CLBP patients compared to normative data. None of the other parameters showed any significant difference between CLBP patients and HC. Overall, our data indicate small differences of the peripheral N9 SEP component; however, these differences cannot explain the reflex delay observed in CLBP patients. While it was important to rule out the contribution of early somatosensory processing and to elucidate its contribution to the delayed reflex responses in CLBP patients, further research is needed to find the primary source(s of time-delayed reflexes in CLBP.

  15. Structural and functional changes in the somatosensory cortex in euthymic females with bipolar disorder.

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    Minuzzi, Luciano; Syan, Sabrina K; Smith, Mara; Hall, Alexander; Hall, Geoffrey Bc; Frey, Benicio N

    2017-12-01

    Current evidence from neuroimaging data suggests possible dysfunction of the fronto-striatal-limbic circuits in individuals with bipolar disorder. Somatosensory cortical function has been implicated in emotional recognition, risk-taking and affective responses through sensory modalities. This study investigates anatomy and function of the somatosensory cortex in euthymic bipolar women. In total, 68 right-handed euthymic women (bipolar disorder = 32 and healthy controls = 36) between 16 and 45 years of age underwent high-resolution anatomical and functional magnetic resonance imaging during the mid-follicular menstrual phase. The somatosensory cortex was used as a seed region for resting-state functional connectivity analysis. Voxel-based morphometry was used to evaluate somatosensory cortical gray matter volume between groups. We found increased resting-state functional connectivity between the somatosensory cortex and insular cortex, inferior prefrontal gyrus and frontal orbital cortex in euthymic bipolar disorder subjects compared to healthy controls. Voxel-based morphometry analysis showed decreased gray matter in the left somatosensory cortex in the bipolar disorder group. Whole-brain voxel-based morphometry analysis controlled by age did not reveal any additional significant difference between groups. This study is the first to date to evaluate anatomy and function of the somatosensory cortex in a well-characterized sample of euthymic bipolar disorder females. Anatomical and functional changes in the somatosensory cortex in this population might contribute to the pathophysiology of bipolar disorder.

  16. Somatosensory evoked potentials and dynamic postural assessment in adolescent idiopathic scoliosis

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    Dalia Mohamed Ezz El Mikkawy

    2016-01-01

    Conclusion The study demonstrates abnormal somatosensory and postural function in patients with AIS, and a significant inter-relationship between the scoliotic angle, the somatosensory system, and posture. Thus, optimum assessment and treatment of neurological pathway and balance are important in these patients.

  17. [Maturation of cerebral somatosensory evoked potentials].

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    Cadilhac, J; Zhu, Y; Georgesco, M; Echenne, B; Rodiere, M

    1985-07-01

    Cerebral somatosensory evoked potentials (SEPs) were elicited by stimulation of the median nerve and/or posterior tibial nerve in 117 children of 1 day to 16 years old. A major negative wave (N) was consistently recorded from the parietal region of the scalp when the arm was stimulated. The peak latency, the onset latency, the rising time and the duration of H wave are closely correlated with age and body length. The latencies are shortest in the subjects of 1-3 years old. SEPs to lower extremity stimulation were inconstant in the infants before the age of one. The major positive wave (P) has a variable topographic distribution along the middle line, over the scalp. The latencies are also very variable in the different subjects of the same age as well as in the same subject with different locations of active electrode. Among the parameters studied as for N wave, only the rising time of P wave is significantly correlated with age. The latencies of P wave have the shortest value in the subjects of 1-3 years old. The comparison of SEPs to upper and to lower limb stimulations shows that there is no relationship between them in respect to their morphology and amplitude. The minimum value of the latencies of N and P waves was observed at the same age but the difference between the peak latencies of P and N waves in the same subject increases considerably after 2 years of age and reaches the adult value after 5 years of age. These resultats indicate that the maturation of the peripheral somatosensory pathways proceeds at a higher rate than that of the central somatosensory pathways, that the maturation of the somatosensory pathways of the upper limb precedes that of the lower limb, and that the rising time of N or P waves is a good index of cortical maturation. The clinical utility of these SEPs in pediatrics is discussed.

  18. Descending projections from the dysgranular zone of rat primary somatosensory cortex processing deep somatic input.

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    Lee, Taehee; Kim, Uhnoh

    2012-04-01

    In the mammalian somatic system, peripheral inputs from cutaneous and deep receptors ascend via different subcortical channels and terminate in largely separate regions of the primary somatosensory cortex (SI). How these inputs are processed in SI and then projected back to the subcortical relay centers is critical for understanding how SI may regulate somatic information processing in the subcortex. Although it is now relatively well understood how SI cutaneous areas project to the subcortical structures, little is known about the descending projections from SI areas processing deep somatic input. We examined this issue by using the rodent somatic system as a model. In rat SI, deep somatic input is processed mainly in the dysgranular zone (DSZ) enclosed by the cutaneous barrel subfields. By using biotinylated dextran amine (BDA) as anterograde tracer, we characterized the topography of corticostriatal and corticofugal projections arising in the DSZ. The DSZ projections terminate mainly in the lateral subregions of the striatum that are also known as the target of certain SI cutaneous areas. This suggests that SI processing of deep and cutaneous information may be integrated, to a certain degree, in this striatal region. By contrast, at both thalamic and prethalamic levels as far as the spinal cord, descending projections from DSZ terminate in areas largely distinguishable from those that receive input from SI cutaneous areas. These subcortical targets of DSZ include not only the sensory but also motor-related structures, suggesting that SI processing of deep input may engage in regulating somatic and motor information flow between the cortex and periphery. Copyright © 2011 Wiley-Liss, Inc.

  19. Modality-Based Organization of Ascending Somatosensory Axons in the Direct Dorsal Column Pathway

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    Niu, Jingwen; Ding, Long; Li, Jian J.; Kim, Hyukmin; Liu, Jiakun; Li, Haipeng; Moberly, Andrew; Badea, Tudor C.; Duncan, Ian D.; Son, Young-Jin; Scherer, Steven S.

    2013-01-01

    The long-standing doctrine regarding the functional organization of the direct dorsal column (DDC) pathway is the “somatotopic map” model, which suggests that somatosensory afferents are primarily organized by receptive field instead of modality. Using modality-specific genetic tracing, here we show that ascending mechanosensory and proprioceptive axons, two main types of the DDC afferents, are largely segregated into a medial–lateral pattern in the mouse dorsal column and medulla. In addition, we found that this modality-based organization is likely to be conserved in other mammalian species, including human. Furthermore, we identified key morphological differences between these two types of afferents, which explains how modality segregation is formed and why a rough “somatotopic map” was previously detected. Collectively, our results establish a new functional organization model for the mammalian direct dorsal column pathway and provide insight into how somatotopic and modality-based organization coexist in the central somatosensory pathway. PMID:24198362

  20. Primary somatosensory/motor cortical thickness distinguishes paresthesia-dominant from pain-dominant carpal tunnel syndrome.

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    Maeda, Yumi; Kettner, Norman; Kim, Jieun; Kim, Hyungjun; Cina, Stephen; Malatesta, Cristina; Gerber, Jessica; McManus, Claire; Libby, Alexandra; Mezzacappa, Pia; Mawla, Ishtiaq; Morse, Leslie R; Audette, Joseph; Napadow, Vitaly

    2016-05-01

    Paresthesia-dominant and pain-dominant subgroups have been noted in carpal tunnel syndrome (CTS), a peripheral neuropathic disorder characterized by altered primary somatosensory/motor (S1/M1) physiology. We aimed to investigate whether brain morphometry dissociates these subgroups. Subjects with CTS were evaluated with nerve conduction studies, whereas symptom severity ratings were used to allocate subjects into paresthesia-dominant (CTS-paresthesia), pain-dominant (CTS-pain), and pain/paresthesia nondominant (not included in further analysis) subgroups. Structural brain magnetic resonance imaging data were acquired at 3T using a multiecho MPRAGE T1-weighted pulse sequence, and gray matter cortical thickness was calculated across the entire brain using validated, automated methods. CTS-paresthesia subjects demonstrated reduced median sensory nerve conduction velocity (P = 0.05) compared with CTS-pain subjects. In addition, cortical thickness in precentral and postcentral gyri (S1/M1 hand area) contralateral to the more affected hand was significantly reduced in CTS-paresthesia subgroup compared with CTS-pain subgroup. Moreover, in CTS-paresthesia subjects, precentral cortical thickness was negatively correlated with paresthesia severity (r(34) = -0.40, P = 0.016) and positively correlated with median nerve sensory velocity (r(36) = 0.51, P = 0.001), but not with pain severity. Conversely, in CTS-pain subjects, contralesional S1 (r(9) = 0.62, P = 0.042) and M1 (r(9) = 0.61, P = 0.046) cortical thickness were correlated with pain severity, but not median nerve velocity or paresthesia severity. This double dissociation in somatotopically specific S1/M1 areas suggests a neuroanatomical substrate for symptom-based CTS subgroups. Such fine-grained subgrouping of CTS may lead to improved personalized therapeutic approaches, based on superior characterization of the linkage between peripheral and central neuroplasticity.

  1. Cortical thickness development of human primary visual cortex related to the age of blindness onset.

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    Li, Qiaojun; Song, Ming; Xu, Jiayuan; Qin, Wen; Yu, Chunshui; Jiang, Tianzi

    2017-08-01

    Blindness primarily induces structural alteration in the primary visual cortex (V1). Some studies have found that the early blind subjects had a thicker V1 compared to sighted controls, whereas late blind subjects showed no significant differences in the V1. This implies that the age of blindness onset may exert significant effects on the development of cortical thickness of the V1. However, no previous research used a trajectory of the age of blindness onset-related changes to investigate these effects. Here we explored this issue by mapping the cortical thickness trajectory of the V1 against the age of blindness onset using data from 99 blind individuals whose age of blindness onset ranged from birth to 34 years. We found that the cortical thickness of the V1 could be fitted well with a quadratic curve in both the left (F = 11.59, P = 3 × 10 -5 ) and right hemispheres (F = 6.54, P = 2 × 10 -3 ). Specifically, the cortical thickness of the V1 thinned rapidly during childhood and adolescence and did not change significantly thereafter. This trend was not observed in the primary auditory cortex (A1), primary motor cortex (M1), or primary somatosensory cortex (S1). These results provide evidence that an onset of blindness before adulthood significantly affects the cortical thickness of the V1 and suggest a critical period for cortical development of the human V1.

  2. Brownian Optogenetic-Noise-Photostimulation on the Brain Amplifies Somatosensory-Evoked Field Potentials

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    Nayeli Huidobro

    2017-08-01

    Full Text Available Stochastic resonance (SR is an inherent and counter-intuitive mechanism of signal-to-noise ratio (SNR facilitation in biological systems associated with the application of an intermediate level of noise. As a first step to investigate in detail this phenomenon in the somatosensory system, here we examined whether the direct application of noisy light on pyramidal neurons from the mouse-barrel cortex expressing a light-gated channel channelrhodopsin-2 (ChR2 can produce facilitation in somatosensory evoked field potentials. Using anesthetized Thy1-ChR2-YFP transgenic mice, and a new neural technology, that we called Brownian optogenetic-noise-photostimulation (BONP, we provide evidence for how BONP directly applied on the barrel cortex modulates the SNR in the amplitude of whisker-evoked field potentials (whisker-EFP. In all transgenic mice, we found that the SNR in the amplitude of whisker-EFP (at 30% of the maximal whisker-EFP exhibited an inverted U-like shape as a function of the BONP level. As a control, we also applied the same experimental paradigm, but in wild-type mice, as expected, we did not find any facilitation effects. Our results show that the application of an intermediate intensity of BONP on the barrel cortex of ChR2 transgenic mice amplifies the SNR of somatosensory whisker-EFPs. This result may be relevant to explain the improvements found in sensory detection in humans produced by the application of transcranial-random-noise-stimulation (tRNS on the scalp.

  3. Distribution and morphology of nitridergic neurons across functional domains of the rat primary somatosensory cortex

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    Anaelli A Nogueira-Campos

    2012-11-01

    Full Text Available The rat primary somatosensory cortex (S1 is remarkable for its conspicuous vertical compartmentalization in barrels and septal columns, which are additionally stratified in horizontal layers. Whereas excitatory neurons from each of these compartments perform different types of processing, the role of interneurons is much less clear. Among the numerous types of GABAergic interneurons, those producing nitric oxide (NO are especially puzzling, since this gaseous messenger can modulate neural activity, synaptic plasticity and neurovascular coupling. We used a quantitative morphological approach to investigate whether nitrergic interneurons, which might therefore be considered both as NO volume diffusers and as elements of local circuitry, display features that could relate to barrel cortex architecture. In fixed brain sections, nitrergic interneurons can be revealed by histochemical processing for NADPH-diaphorase (NADPHd. Here, the dendritic arbors of nitrergic neurons from different compartments of area S1 were 3D reconstructed from serial 200-μm thick sections, using 100x objective and the Neurolucida system. Standard morphological parameters were extracted for all individual arbors and compared across columns and layers. Wedge analysis was used to compute dendritic orientation indices. Supragranular layers displayed the highest density of nitrergic neurons, whereas layer IV contained nitrergic neurons with largest soma area. The highest nitrergic neuronal density was found in septa, where dendrites were previously characterized as more extense and ramified than in barrels. Dendritic arbors were not confined to the boundaries of the column nor layer of their respective soma, being mostly double-tufted and vertically oriented, except in supragranular layers. These data strongly suggest that nitrergic interneurons adapt their morphology to the dynamics of processing performed by cortical compartments.

  4. Deletion of ENTPD3 does not impair nucleotide hydrolysis in primary somatosensory neurons or spinal cord [v1; ref status: indexed, http://f1000r.es/3rm

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    Eric McCoy

    2014-07-01

    Full Text Available Ectonucleotidases are membrane-bound or secreted proteins that hydrolyze extracellular nucleotides.  Recently, we identified three ectonucleotidases that hydrolyze extracellular adenosine 5’-monophosphate (AMP to adenosine in primary somatosensory neurons.  Currently, it is unclear which ectonucleotidases hydrolyze ATP and ADP in these neurons.  Ectonucleoside triphosphate diphosphohydrolases (ENTPDs comprise a class of enzymes that dephosphorylate extracellular ATP and ADP.  Here, we found that ENTPD3 (also known as NTPDase3 or CD39L3 was located in nociceptive and non-nociceptive neurons of the dorsal root ganglion (DRG, in the dorsal horn of the spinal cord, and in free nerve endings in the skin.  To determine if ENTPD3 contributes directly to ATP and ADP hydrolysis in these tissues, we generated and characterized an Entpd3 knockout mouse.  This mouse lacks ENTPD3 protein in all tissues examined, including the DRG, spinal cord, skin, and bladder.  However, DRG and spinal cord tissues from Entpd3-/- mice showed no reduction in histochemical staining when ATP, ADP, AMP, or UTP were used as substrates.  Additionally, using fast-scan cyclic voltammetry (FSCV, adenosine production was not impaired in the dorsal spinal cord of Entpd3-/- mice when the substrate ADP was applied.  Further, Entpd3-/- mice did not differ in nociceptive behaviors when compared to wild-type mice, although Entpd3-/- mice showed a modest reduction in β-alanine-mediated itch.  Taken together, our data indicate that deletion of Entpd3 does not impair ATP or ADP hydrolysis in primary somatosensory neurons or in dorsal spinal cord.  Moreover, our data suggest there could be multiple ectonucleotidases that act redundantly to hydrolyze nucleotides in these regions of the nervous system.

  5. Deletion of ENTPD3 does not impair nucleotide hydrolysis in primary somatosensory neurons or spinal cord [v2; ref status: indexed, http://f1000r.es/4dl

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    Eric McCoy

    2014-09-01

    Full Text Available Ectonucleotidases are membrane-bound or secreted proteins that hydrolyze extracellular nucleotides.  Recently, we identified three ectonucleotidases that hydrolyze extracellular adenosine 5’-monophosphate (AMP to adenosine in primary somatosensory neurons.  Currently, it is unclear which ectonucleotidases hydrolyze ATP and ADP in these neurons.  Ectonucleoside triphosphate diphosphohydrolases (ENTPDs comprise a class of enzymes that dephosphorylate extracellular ATP and ADP.  Here, we found that ENTPD3 (also known as NTPDase3 or CD39L3 was located in nociceptive and non-nociceptive neurons of the dorsal root ganglion (DRG, in the dorsal horn of the spinal cord, and in free nerve endings in the skin.  To determine if ENTPD3 contributes directly to ATP and ADP hydrolysis in these tissues, we generated and characterized an Entpd3 knockout mouse.  This mouse lacks ENTPD3 protein in all tissues examined, including the DRG, spinal cord, skin, and bladder.  However, DRG and spinal cord tissues from Entpd3-/- mice showed no reduction in histochemical staining when ATP, ADP, AMP, or UTP were used as substrates.  Additionally, using fast-scan cyclic voltammetry (FSCV, adenosine production was not impaired in the dorsal spinal cord of Entpd3-/- mice when the substrate ADP was applied.  Further, Entpd3-/- mice did not differ in nociceptive behaviors when compared to wild-type mice, although Entpd3-/- mice showed a modest reduction in β-alanine-mediated itch.  Taken together, our data indicate that deletion of Entpd3 does not impair ATP or ADP hydrolysis in primary somatosensory neurons or in dorsal spinal cord.  Moreover, our data suggest there could be multiple ectonucleotidases that act redundantly to hydrolyze nucleotides in these regions of the nervous system.

  6. ASYMMETRY OF SOMATOSENSORY CORTICAL PLASTICITY IN PATIENT WITH BILATERAL CARPAL TUNNEL SYNDROME

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    Hikmat Hadoush

    2017-09-01

    Full Text Available Background: Following peripheral nerve lesion, the adult somatosensory system showedcortical reorganizational abilities.Previous studies identified the digits' somatotopy map changes and somatosensory cortical plasticity in response to the Carpal Tunnel Syndrome (CTS that affected the dominant hand only. Objective: Answering the remained question is that what the extent of the cortical plasticity would be in left and right somatosensory cortices in response to CTS affecting the right and left hands simultaneously. Methods: Cortical representations activated by tactile stimulation of median nerve (index and ulnar nerve (little of both dominant and non-dominant hands were evaluated by Magnetoencephalography (MEG systemfor healthy participants and patient with bilateral moderate CTS. index – little fingers'somatotopy map and inter-digit cortical distance was then mapped and calculated for each participant on the real MRI data and the 3D brain surface image. Results: in healthy participants, index – little inter-digit somatosensory cortical distance of right hand (dominant was significantly larger than the index – little inter-digitsomatosensory cortical distance of left hand (11.2±2.1mm vs.7.0±2.9mm, P = 0.006. However, in patient with bilateral CTS, the index – little inter-digit somatosensory cortical distance of righthand (dominant was significantly smaller than the index – little inter-digit somatosensory cortical distance of left hand (5.8mm vs. 7.4mm. Conclusion: our data could be interpreted as the hand use – dependency served more median nerve – cortical territory from the ulnar nerve invasion in the right somatotopy map (left hand than the left somatotopy map of the right hand.

  7. Impaired somatosensory discrimination of shape in Parkinson's disease : Association with caudate nucleus dopaminergic function

    NARCIS (Netherlands)

    Weder, BJ; Leenders, KL; Vontobel, P; Nienhusmeier, M; Keel, A; Zaunbauer, W; Vonesch, T; Ludin, HP

    1999-01-01

    Tactile discrimination of macrogeometric objects in a two-alternative forced-choice procedure represents a demanding task involving somatosensory pathways and higher cognitive processing. The objects for somatosensory discrimination, i.e., rectangular parallelepipeds differing only in oblongness,

  8. Reduced somatosensory impairment by piezosurgery during orthognathic surgery of the mandible.

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    Brockmeyer, Phillipp; Hahn, Wolfram; Fenge, Stefan; Moser, Norman; Schliephake, Henning; Gruber, Rudolf Matthias

    2015-09-01

    This clinical trial aimed to test the hypothesis that piezosurgery causes reduced nerval irritations and, thus, reduced somatosensory impairment when used in orthognathic surgery of the mandible. To this end, 37 consecutive patients with Angle Class II and III malocclusion were treated using bilateral sagittal split osteotomies (BSSO) of the mandible. In a split mouth design, randomized one side of the mandible was operated using a conventional saw, while a piezosurgery device was used on the contralateral side. In order to test the individual qualities of somatosensory function, quantitative sensory testings (QSTs) were performed 1 month, 6 months and 1 year after surgery. A comparison of the data using a two-way analysis of variance (ANOVA) revealed a significant reduction in postoperative impairment in warm detection threshold (WDT) (P = 0.046), a decreased dynamic mechanical allodynia (ALL) (P = 0.002) and a decreased vibration detection threshold (VDT) (P = 0.030) on the piezosurgery side of the mandible as opposed to the conventionally operated control side. In the remaining QSTs, minor deviations from the preoperative baseline conditions and a more rapid regression could be observed. Piezosurgery caused reduced somatosensory impairment and a faster recovery of somatosensory functions in the present investigation.

  9. Somatosensory cortices are required for the acquisition of morphine-induced conditioned place preference.

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    Zhiqiang Meng

    Full Text Available BACKGROUND: Sensory system information is thought to play an important role in drug addiction related responses. However, how somatic sensory information participates in the drug related behaviors is still unclear. Many studies demonstrated that drug addiction represents a pathological usurpation of neural mechanisms of learning and memory that normally relate to the pursuit of rewards. Thus, elucidate the role of somatic sensory in drug related learning and memory is of particular importance to understand the neurobiological mechanisms of drug addiction. PRINCIPAL FINDINGS: In the present study, we investigated the role of somatosensory system in reward-related associative learning using the conditioned place preference model. Lesions were made in somatosensory cortices either before or after conditioning training. We found that lesion of somatosensory cortices before, rather than after morphine conditioning impaired the acquisition of place preference. CONCLUSION: These results demonstrate that somatosensory cortices are necessary for the acquisition but not retention of morphine induced place preference.

  10. Cortical somatosensory reorganization in children with spastic cerebral palsy: a multimodal neuroimaging study

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    CHRISTOS ePAPADELIS

    2014-09-01

    Full Text Available Although cerebral palsy (CP is among the most common causes of physical disability in early childhood, we know little about the functional and structural changes of this disorder in the developing brain. Here, we investigated with three different neuroimaging modalities (magnetoencephalography (MEG, diffusion tension imaging (DTI, and resting state fMRI whether spastic CP is associated with functional and anatomical abnormalities in the sensorimotor network. Ten children participated in the study: four with diplegic CP (DCP, three with hemiplegic CP (HCP, and three typically-developing (TD children. Somatosensory evoked fields (SEFs were recorded in response to pneumatic stimuli applied to digits D1, D3, and D5 of both hands. Several parameters of water diffusion were calculated from DTI between the thalamus and the precentral and postcentral gyri in both hemispheres. The sensorimotor resting state networks (RSNs were examined by using an independent component analysis method. Tactile stimulation of the fingers elicited the first prominent cortical response at ~50 ms, in all except one child, localized over the primary somatosensory cortex (S1. In five CP children, abnormal somatotopic organization was observed in the affected (or more affected hemisphere. Euclidean distances were markedly different between the two hemispheres in the HCP children, and between DCP and TD children for both hemispheres. DTI analysis revealed decreased fractional anisotropy and increased apparent diffusion coefficient for the thalamocortical pathways in the more affected compared to less affected hemisphere in CP children. Rs-fMRI results indicated absent and/or abnormal sensorimotor RSNs for children with HCP and DCP consistent with the severity and location of their lesions. Our findings suggest an abnormal somatosensory processing mechanism in the sensorimotor network of children with CP possibly as a result of diminished thalamocortical projections.

  11. Somatosensory mismatch response in young and elderly adults

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    Juho M. Strömmer

    2014-10-01

    Full Text Available Aging is associated with cognitive decline and alterations in early perceptual processes. Studies in the auditory and visual modalities have shown that the mismatch negativity (or the mismatch response, MMR, an event-related potential (ERP elicited by a deviant stimulus in a background of homogenous events, diminishes with aging and cognitive decline. However, the effects of aging on the somatosensory MMR are not known. In the current study, we recorded ERPs to electrical pulses to different fingers of the left hand in a passive oddball experiment in young (22–36 years and elderly (66–95 years adults engaged in a visual task. The MMR was found to deviants as compared to standards at two latency ranges: 180–220 ms and 250–290 ms post-stimulus onset. At 180–220 ms, within the young, the MMR was found at medial electrode sites, whereas aged did not show any amplitude difference between the stimulus types at the same latency range. At 250–290 ms, the MMR was evident with attenuated amplitude and narrowed scalp distribution among aged (Fz compared to young (fronto-centrally and lateral parietal sites. Hence, the results reveal that the somatosensory change detection mechanism is altered in aging. The somatosensory MMR can be used as a reliable measure of age-related changes in sensory-cognitive functions.

  12. High-order motor cortex in rats receives somatosensory inputs from the primary motor cortex via cortico-cortical pathways.

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    Kunori, Nobuo; Takashima, Ichiro

    2016-12-01

    The motor cortex of rats contains two forelimb motor areas; the caudal forelimb area (CFA) and the rostral forelimb area (RFA). Although the RFA is thought to correspond to the premotor and/or supplementary motor cortices of primates, which are higher-order motor areas that receive somatosensory inputs, it is unknown whether the RFA of rats receives somatosensory inputs in the same manner. To investigate this issue, voltage-sensitive dye (VSD) imaging was used to assess the motor cortex in rats following a brief electrical stimulation of the forelimb. This procedure was followed by intracortical microstimulation (ICMS) mapping to identify the motor representations in the imaged cortex. The combined use of VSD imaging and ICMS revealed that both the CFA and RFA received excitatory synaptic inputs after forelimb stimulation. Further evaluation of the sensory input pathway to the RFA revealed that the forelimb-evoked RFA response was abolished either by the pharmacological inactivation of the CFA or a cortical transection between the CFA and RFA. These results suggest that forelimb-related sensory inputs would be transmitted to the RFA from the CFA via the cortico-cortical pathway. Thus, the present findings imply that sensory information processed in the RFA may be used for the generation of coordinated forelimb movements, which would be similar to the function of the higher-order motor cortex in primates. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  13. Effect of somatosensory and neurofeedback training on balance in older healthy adults: a preliminary investigation.

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    Azarpaikan, Atefeh; Taheri Torbati, Hamidreza

    2017-10-23

    The aim of this study was to assess the effectiveness of balance training with somatosensory and neurofeedback training on dynamic and static balance in healthy, elderly adults. The sample group consisted of 45 healthy adults randomly assigned to one of the three test groups: somatosensory, neurofeedback, and a control. Individualization of the balance program started with pre-tests for static and dynamic balances. Each group had 15- and 30-min training sessions. All groups were tested for static (postural stability) and dynamic balances (Berg Balance Scale) in acquisition and transfer tests (fall risk of stability and timed up and go). Improvements in static and dynamic balances were assessed by somatosensory and neurofeedback groups and then compared with the control group. Results indicated significant improvements in static and dynamic balances in both test groups in the acquisition test. Results revealed a significant improvement in the transfer test in the neurofeedback and somatosensory groups, in static and dynamic conditions, respectively. The findings suggest that these methods of balance training had a significant influence on balance. Both the methods are appropriate to prevent falling in adults. Neurofeedback training helped the participants to learn static balance, while somatosensory training was effective on dynamic balance learning. Further research is needed to assess the effects of longer and discontinuous stimulation with somatosensory and neurofeedback training on balance in elderly adults.

  14. SOMATOSENSORY EVOKED POTENTIALS IN DIABETES MELLITUS TYPE - 2

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    Rekha

    2015-10-01

    Full Text Available Diabetes mellitus is the most common metabolic disorder affecting majority of population. It is estimated that over 400 million people throughout the world have diabetes. It has progressed to be a pandemic from an epidemic causing morbidity and mortality in the population. Among the many complications of diabetes, diabetic neuropathies contribute majorly to the morbidity associated with the disease. Axonal conduction is affected by elevated levels of protein kinase c causing neuronal ischemia; decreased ce llular myoinositol affecting sodium potassium ATPase pump leads to decreased nerve conduction; Somatosensory E voked P otentials (SSEPs reflect the activity of somatosensory pathways mediated through the dorsal columns of the spinal cord and the specific so matosensory cortex. Recording of Somatosensory Evoked Potentials in diabetics is done to assess the sensory involvement of spinal cord. Presence of SEPs provides clear evidence for axonal continuity and by using different stimulation sites, the rate of reg eneration can be determined. Both onset and peak latencies of all SEP components are prolonged in patients with diabetes. Present study is done to compare somatosensory evoked potentials in diabetics and normal subjects. MATERIALS AND METHOD S: The present study was undertaken at the Upgraded Department of Physiology, Osmania Medical College, Koti, Hyderabad. The study was conducted on subjects, both male and female in the age group of 45 to 55 years, suffering from type II diabetes excluding other neurologi cal disorders. Non - invasive method of estimation of nerve conduction studies using SFEMG/EP — Electromyography or evoked potential system (Nicolet systems — USA using surface electrodes with automated computerized monitor attached with printer is used. RESUL TS : ANOVA showed statistically significant N9 latency (right & left sides. Latencies of all the components of SSEPs were more significant than amplitudes in Diabetic

  15. Pain from Dental Implant Placement, Inflammatory Pulpitis Pain, and Neuropathic Pain Present Different Somatosensory Profiles.

    Science.gov (United States)

    Porporatti, André Luís; Bonjardim, Leonardo Rigoldi; Stuginski-Barbosa, Juliana; Bonfante, Estevam Augusto; Costa, Yuri Martins; Rodrigues Conti, Paulo César

    2017-01-01

    To address the two following questions: (1) What kind of somatosensory abnormalities may be characterized in patients receiving dental implants (IMP), in ongoing inflammatory dental pulpitis (IP) patients, and in neuropathic pain (atypical odontalgia [AO]) patients? and (2) What sort of sensory and neural changes may result from dental implant placement surgery and pulpectomy? A total of 60 subjects were divided into three groups: the IMP (n = 20), IP (n = 20), and AO groups (n = 20). Quantitative sensory testing (QST) was performed preoperatively (baseline) for all three groups and postoperatively at 1 month and 3 months after dental implant placement or pulpectomy (in the IMP group and IP group, respectively). Statistical analyses were completed with one-way and two-way analysis of variance and z score transformations (α = 5%). The main findings of this study indicated that: (1) Elevations in mechanical detection threshold (MDT) and in current perception threshold (CPT) related to C-fiber activation, indicating a loss of function, were found at baseline in IP patients; (2) Somatosensory abnormalities such as allodynia, reduced MDT and mechanical pain threshold (MPT), and impaired pain modulation were found in AO patients; (3) No somatosensory alterations after implant placement were found in the IMP group; and (4) Somatosensory alterations in the form of reduction in the CPT related to C-fiber activation were reported 3 months after pulpectomy in the IP group. This study showed that somatosensory abnormalities were evident in AO and IP patients, and somatosensory alterations were seen in IP patients even 3 months after pulpectomy. However, no somatosensory alterations were seen after implant placement.

  16. BOLD responses in somatosensory cortices better reflect heat sensation than pain.

    Science.gov (United States)

    Moulton, Eric A; Pendse, Gautam; Becerra, Lino R; Borsook, David

    2012-04-25

    The discovery of cortical networks that participate in pain processing has led to the common generalization that blood oxygen level-dependent (BOLD) responses in these areas indicate the processing of pain. Physical stimuli have fundamental properties that elicit sensations distinguishable from pain, such as heat. We hypothesized that pain intensity coding may reflect the intensity coding of heat sensation during the presentation of thermal stimuli during fMRI. Six 3T fMRI heat scans were collected for 16 healthy subjects, corresponding to perceptual levels of "low innocuous heat," "moderate innocuous heat," "high innocuous heat," "low painful heat," "moderate painful heat," and "high painful heat" delivered by a contact thermode to the face. Subjects rated pain and heat intensity separately after each scan. A general linear model analysis detected different patterns of brain activation for the different phases of the biphasic response to heat. During high painful heat, the early phase was associated with significant anterior insula and anterior cingulate cortex activation. Persistent responses were detected in the right dorsolateral prefrontal cortex and inferior parietal lobule. Only the late phase showed significant correlations with perceptual ratings. Significant heat intensity correlated activation was identified in contralateral primary and secondary somatosensory cortices, motor cortex, and superior temporal lobe. These areas were significantly more related to heat ratings than pain. These results indicate that heat intensity is encoded by the somatosensory cortices, and that pain evaluation may either arise from multimodal evaluative processes, or is a distributed process.

  17. MEG reveals a fast pathway from somatosensory cortex to occipital areas via posterior parietal cortex in a blind subject

    DEFF Research Database (Denmark)

    Ioannides, Andreas A; Liu, Lichan; Poghosyan, Vahe

    2013-01-01

    magnetoencephalography (MEG) data recorded from one congenitally blind and two sighted subjects after stimulation of the left and right median nerves at three intensities: below sensory threshold, above sensory threshold and above motor threshold; the last sufficient to produce thumb twitching. We identified...... reproducible brain responses in the primary somatosensory (S1) and motor (M1) cortices at around 20 ms post-stimulus, which were very similar in sighted and blind subjects. Time-frequency analysis revealed strong 45-70 Hz activity at latencies of 20-50 ms in S1 and M1, and posterior parietal cortex Brodmann...... of information through this pathway occurred in stages characterized by convergence of activations into specific cortical regions. In sighted subjects, no linked activity was found that led from the somatosensory to the visual cortex through any of the studied brain regions. These results provide the first...

  18. Psychotherapy With Somatosensory Stimulation for Endometriosis-Associated Pain: A Randomized Controlled Trial.

    Science.gov (United States)

    Meissner, Karin; Schweizer-Arau, Annemarie; Limmer, Anna; Preibisch, Christine; Popovici, Roxana M; Lange, Isabel; de Oriol, Barbara; Beissner, Florian

    2016-11-01

    To evaluate whether psychotherapy with somatosensory stimulation is effective for the treatment of pain and quality of life in patients with endometriosis-related pain. Patients with a history of endometriosis and chronic pelvic pain were randomized to either psychotherapy with somatosensory stimulation (ie, different techniques of acupuncture point stimulation) or wait-list control for 3 months, after which all patients were treated. The primary outcome was brain connectivity assessed by functional magnetic resonance imaging. Prespecified secondary outcomes included pain on 11-point numeric rating scales (maximal and average global pain, pelvic pain, dyschezia, and dyspareunia) and physical and mental quality of life. A sample size of 30 per group was planned to compare outcomes in the treatment group and the wait-list control group. From March 2010 through March 2012, 67 women (mean age 35.6 years) were randomly allocated to intervention (n=35) or wait-list control (n=32). In comparison with wait-list controls, treated patients showed improvements after 3 months in maximal global pain (mean group difference -2.1, 95% confidence interval [CI] -3.4 to -0.8; P=.002), average global pain (-2.5, 95% CI -3.5 to -1.4; P<.001), pelvic pain (-1.4, 95% CI -2.7 to -0.1; P=.036), dyschezia (-3.5, 95% CI -5.8 to -1.3; P=.003), physical quality of life (3.8, 95% CI 0.5-7.1, P=.026), and mental quality of life (5.9, 95% CI 0.6-11.3; P=.031); dyspareunia improved nonsignificantly (-1.8, 95% CI -4.4 to 0.7; P=.150). Improvements in the intervention group remained stable at 6 and 24 months, and control patients showed comparable symptom relief after delayed intervention. Psychotherapy with somatosensory stimulation reduced global pain, pelvic pain, and dyschezia and improved quality of life in patients with endometriosis. After 6 and 24 months, when all patients were treated, both groups showed stable improvements. ClinicalTrials.gov, https://clinicaltrials.gov, NCT01321840.

  19. Sub-threshold cross-modal sensory interaction in the thalamus: lemniscal auditory response in the medial geniculate nucleus is modulated by somatosensory stimulation.

    Science.gov (United States)

    Donishi, T; Kimura, A; Imbe, H; Yokoi, I; Kaneoke, Y

    2011-02-03

    Recent studies have highlighted cross-modal sensory modulations in the primary sensory areas in the cortex, suggesting that cross-modal sensory interactions occur at early stages in the hierarchy of sensory processing. Multi-modal sensory inputs from non-lemniscal thalamic nuclei and cortical inputs from the secondary sensory and association areas are considered responsible for the modulations. On the other hand, there is little evidence of cross-sensory modal sensitivities in lemniscal thalamic nuclei. In the present study, we were interested in a possibility that somatosensory stimulation may affect auditory response in the ventral division (MGV) of the medial geniculate nucleus (MG), a lemniscal thalamic nucleus that is considered to be dedicated to auditory uni-modal processing. Experiments were performed on anesthetized rats. Transcutaneous electrical stimulation of the hindpaw, which is thought to evoke nociception and seems unrelated to auditory processing, modulated unit discharges in response to auditory stimulation (noise bursts). The modulation was observed in the MGV and non-lemniscal auditory thalamic nuclei such as the dorsal and medial divisions of the MG. The major effect of somatosensory stimulation was suppression. The most robust suppression was induced by electrical stimuli given simultaneously with noise bursts or preceding noise bursts by 10 to 20 ms. The results indicate that the lemniscal (MGV) and non-lemniscal auditory nuclei are subject to somatosensory influence. In everyday experience intense somatosensory stimuli such as pain interrupt our ongoing hearing or interfere with clear recognition of sound. The modulation of lemniscal auditory response by somatosensory stimulation may underlie such cross-modal disturbance of auditory perception as a form of cross-modal switching of attention. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Functional connectivity between somatosensory and motor brain areas predicts individual differences in motor learning by observing.

    Science.gov (United States)

    McGregor, Heather R; Gribble, Paul L

    2017-08-01

    Action observation can facilitate the acquisition of novel motor skills; however, there is considerable individual variability in the extent to which observation promotes motor learning. Here we tested the hypothesis that individual differences in brain function or structure can predict subsequent observation-related gains in motor learning. Subjects underwent an anatomical MRI scan and resting-state fMRI scans to assess preobservation gray matter volume and preobservation resting-state functional connectivity (FC), respectively. On the following day, subjects observed a video of a tutor adapting her reaches to a novel force field. After observation, subjects performed reaches in a force field as a behavioral assessment of gains in motor learning resulting from observation. We found that individual differences in resting-state FC, but not gray matter volume, predicted postobservation gains in motor learning. Preobservation resting-state FC between left primary somatosensory cortex and bilateral dorsal premotor cortex, primary motor cortex, and primary somatosensory cortex and left superior parietal lobule was positively correlated with behavioral measures of postobservation motor learning. Sensory-motor resting-state FC can thus predict the extent to which observation will promote subsequent motor learning. NEW & NOTEWORTHY We show that individual differences in preobservation brain function can predict subsequent observation-related gains in motor learning. Preobservation resting-state functional connectivity within a sensory-motor network may be used as a biomarker for the extent to which observation promotes motor learning. This kind of information may be useful if observation is to be used as a way to boost neuroplasticity and sensory-motor recovery for patients undergoing rehabilitation for diseases that impair movement such as stroke. Copyright © 2017 the American Physiological Society.

  1. Somatosensory evoked potentials in children with autism | Azouz ...

    African Journals Online (AJOL)

    SSEPs) changesamong children with autism, and their relation to somatosensory manifestations and severity of autism. Subjects: Thirty children with autism aged 2–12 years were included in the study, all of them fulfilling criteria of the Diagnostic ...

  2. Decoding stimulus features in primate somatosensory cortex during perceptual categorization

    Science.gov (United States)

    Alvarez, Manuel; Zainos, Antonio; Romo, Ranulfo

    2015-01-01

    Neurons of the primary somatosensory cortex (S1) respond as functions of frequency or amplitude of a vibrotactile stimulus. However, whether S1 neurons encode both frequency and amplitude of the vibrotactile stimulus or whether each sensory feature is encoded by separate populations of S1 neurons is not known, To further address these questions, we recorded S1 neurons while trained monkeys categorized only one sensory feature of the vibrotactile stimulus: frequency, amplitude, or duration. The results suggest a hierarchical encoding scheme in S1: from neurons that encode all sensory features of the vibrotactile stimulus to neurons that encode only one sensory feature. We hypothesize that the dynamic representation of each sensory feature in S1 might serve for further downstream processing that leads to the monkey’s psychophysical behavior observed in these tasks. PMID:25825711

  3. Skill-Specific Changes in Somatosensory Nogo Potentials in Baseball Players.

    Directory of Open Access Journals (Sweden)

    Koya Yamashiro

    Full Text Available Athletic training is known to induce neuroplastic alterations in specific somatosensory circuits, which are reflected by changes in somatosensory evoked potentials and event-related potentials. The aim of this study was to clarify whether specific athletic training also affects somatosensory Nogo potentials related to the inhibition of movements. The Nogo potentials were recorded at nine cortical electrode positions (Fz, Cz, Pz, F3, F4, C3, C4, P3 and P4 in 12 baseball players (baseball group and in 12 athletes in sports, such as track and field events and swimming, that do not require response inhibition, such as batting for training or performance (sports group. The Nogo potentials and Go/Nogo reaction times (Go/Nogo RTs were measured under a somatosensory Go/Nogo paradigm in which subjects were instructed to rapidly push a button in response to stimulus presentation. The Nogo potentials were obtained by subtracting the Go trial from the Nogo trial. The peak Nogo-N2 was significantly shorter in the baseball group than that in the sports group. In addition, the amplitude of Nogo-N2 in the frontal area was significantly larger in the baseball group than that in the sports group. There was a significant positive correlation between the latency of Nogo-N2 and Go/Nogo RT. Moreover, there were significant correlations between the Go/Nogo RT and both the amplitude of Nogo-N2 and Nogo-P3 (i.e., amplitude of the Nogo-potentials increases with shorter RT. Specific athletic training regimens may induce neuroplastic alterations in sensorimotor inhibitory processes.

  4. c-Kit expression in somatosensory nuclei of lower medulla oblongata.

    Science.gov (United States)

    Pop, Elena; Mărdărescu, Mariana; Lazăr, M; Rusu, M C; Ion, Daniela Adriana

    2013-01-01

    Protein kinase signal-transduction pathways play critical roles in regulating nociception. The c-kit receptor contributes to pain regulation in the spinal cord and is present on both peripheral and central terminals. Expression of c-kit was demonstrated in human trigeminal and spinal ganglia. However, the brainstem expression of c-kit was overlooked. We aimed to evaluate it by immunohistochemistry, on eight samples of human lower medulla oblongata. We used two clones of CD117/c-kit antibodies, from different manufacturers, and neurofilament antibodies. Positive expression of CD117/c-kit was found within the spinal trigeminal nucleus, the gracilis, cuneate, and lateral cuneate nuclei, and within the olivary complex. CD117/c-kit positive interstitial networks of these nuclei were positively labeled with neurofilaments. CD117/c-kit labeled the olivary neurons, but not the magnocellular neurons of the trigeminal, gracilis and cuneate nuclei. c-kit interstitial systems of brainstem could play so an important role for the functional status along the somatosensory neural circuits.

  5. Loss of Ensemble Segregation in Dentate Gyrus, but Not in Somatosensory Cortex, during Contextual Fear Memory Generalization

    Directory of Open Access Journals (Sweden)

    Marie Yokoyama

    2016-11-01

    Full Text Available The details of contextual or episodic memories are lost and generalized with the passage of time. Proper generalization may underlie the formation and assimilation of semantic memories and enable animals to adapt to ever-changing environments, whereas overgeneralization of fear memory evokes maladaptive fear responses to harmless stimuli, which is a symptom of anxiety disorders such as post-traumatic stress disorder (PTSD. To understand the neural basis of fear memory generalization, we investigated the patterns of neuronal ensemble reactivation during memory retrieval when contextual fear memory expression is generalized using transgenic mice that allowed us to visualize specific neuronal ensembles activated during memory encoding and retrieval. We found preferential reactivations of neuronal ensembles in the primary somatosensory cortex, when mice were returned to the conditioned context to retrieve their memory 1 day after conditioning. In the hippocampal dentate gyrus (DG, exclusively separated ensemble reactivation was observed when mice were exposed to a novel context. These results suggest that the DG as well as the somatosensory cortex were likely to distinguish the two different contexts at the ensemble activity level when memory is not generalized at the behavioral level. However, 9 days after conditioning when animals exhibited generalized fear, the unique reactivation pattern in the DG, but not in the somatosensory cortex, was lost. Our results suggest that the alternations in the ensemble representation within the DG, or in upstream structures that link the sensory cortex to the hippocampus, may underlie generalized contextual fear memory expression.

  6. Airway somatosensory deficits and dysphagia in Parkinson's disease.

    Science.gov (United States)

    Hammer, Michael J; Murphy, Caitlin A; Abrams, Trisha M

    2013-01-01

    Individuals with Parkinson's disease (PD) often experience substantial impairment of swallow control, and are typically unaware of the presence or severity of their impairments suggesting that these individuals may also experience airway sensory deficits. However, the degree to which impaired swallow function in PD may relate to airway sensory deficits has yet to be formally tested. The purpose of this study was to examine whether airway sensory function is associated with swallow impairment in PD. Eighteen PD participants and 18 healthy controls participated in this study and underwent endoscopic assessment of airway somatosensory function, endoscopic assessment of swallow function, and clinical ratings of swallow and disease severity. PD participants exhibited abnormal airway somatosensory function and greater swallow impairment compared with healthy controls. Swallow and sensory deficits in PD were correlated with disease severity. Moreover, PD participants reported similar self-rated swallow function as healthy controls, and swallow deficits were correlated with sensory function suggesting an association between impaired sensory function and poor self-awareness of swallow deficits in PD. These results suggest that control of swallow is influenced by airway somatosensory function, that swallow-related deficits in PD are related to abnormal somatosensation, and that swallow and airway sensory function may degrade as a function of disease severity. Therefore, the basal ganglia and related neural networks may play an important role to integrate airway sensory input for swallow-related motor control. Furthermore, the airway deficits observed in PD suggest a disintegration of swallow-related sensory and motor control.

  7. Inhibition of somatosensory-evoked cortical responses by a weak leading stimulus.

    Science.gov (United States)

    Nakagawa, Kei; Inui, Koji; Yuge, Louis; Kakigi, Ryusuke

    2014-11-01

    We previously demonstrated that auditory-evoked cortical responses were suppressed by a weak leading stimulus in a manner similar to the prepulse inhibition (PPI) of startle reflexes. The purpose of the present study was to investigate whether a similar phenomenon was present in the somatosensory system, and also whether this suppression reflected an inhibitory process. We recorded somatosensory-evoked magnetic fields following stimulation of the median nerve and evaluated the extent by which they were suppressed by inserting leading stimuli at an intensity of 2.5-, 1.5-, 1.1-, or 0.9-fold the sensory threshold (ST) in healthy participants (Experiment 1). The results obtained demonstrated that activity in the secondary somatosensory cortex in the hemisphere contralateral to the stimulated side (cSII) was significantly suppressed by a weak leading stimulus with the intensity larger than 1.1-fold ST. This result implied that the somatosensory system had an inhibitory process similar to that of PPI. We then presented two successive leading stimuli before the test stimulus, and compared the extent of suppression between the test stimulus-evoked responses and those obtained with the second prepulse alone and with two prepulses (first and second) (Experiment 2). When two prepulses were preceded, cSII responses to the second prepulse were suppressed by the first prepulse, whereas the ability of the second prepulse to suppress the test stimulus remained unchanged. These results suggested the presence of at least two individual pathways; response-generating and inhibitory pathways. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Inhibitory rTMS applied on somatosensory cortex in Wilson's disease patients with hand dystonia.

    Science.gov (United States)

    Lozeron, Pierre; Poujois, Aurélia; Meppiel, Elodie; Masmoudi, Sana; Magnan, Thierry Peron; Vicaut, Eric; Houdart, Emmanuel; Guichard, Jean-Pierre; Trocello, Jean-Marc; Woimant, France; Kubis, Nathalie

    2017-10-01

    Hand dystonia is a common complication of Wilson's disease (WD), responsible for handwriting difficulties and disability. Alteration of sensorimotor integration and overactivity of the somatosensory cortex have been demonstrated in dystonia. This study investigated the immediate after effect of an inhibitory repetitive transcranial magnetic stimulation (rTMS) applied over the somatosensory cortex on the writing function in WD patients with hand dystonia. We performed a pilot prospective randomized double-blind sham-controlled crossover rTMS study. A 20-min 1-Hz rTMS session, stereotaxically guided, was applied over the left somatosensory cortex in 13 WD patients with right dystonic writer's cramp. After 3 days, each patient was crossed-over to the alternative treatment. Patients were clinically evaluated before and immediately after each rTMS session with the Unified Wilson's Disease rating scale (UWDRS), the Writers' Cramp Rating Scale (WCRS), a specifically designed scale for handwriting difficulties in Wilson's disease patients (FAR, flow, accuracy, and rhythmicity evaluation), and a visual analog scale (VAS) for handwriting discomfort. No significant change in UWDRS, WCRS, VAS, or FAR scores was observed in patients treated with somatosensory inhibitory rTMS compared to the sham protocol. The FAR negatively correlated with UWDRS (r = -0.6; P = 0.02), but not with the WCRS score, disease duration, MRI diffusion lesions, or with atrophy scores. In our experimental conditions, a single inhibitory rTMS session applied over somatosensory cortex did not improve dystonic writer cramp in WD patients.

  9. Reliability of Visual and Somatosensory Feedback in Skilled Movement: The Role of the Cerebellum.

    Science.gov (United States)

    Mizelle, J C; Oparah, Alexis; Wheaton, Lewis A

    2016-01-01

    The integration of vision and somatosensation is required to allow for accurate motor behavior. While both sensory systems contribute to an understanding of the state of the body through continuous updating and estimation, how the brain processes unreliable sensory information remains to be fully understood in the context of complex action. Using functional brain imaging, we sought to understand the role of the cerebellum in weighting visual and somatosensory feedback by selectively reducing the reliability of each sense individually during a tool use task. We broadly hypothesized upregulated activation of the sensorimotor and cerebellar areas during movement with reduced visual reliability, and upregulated activation of occipital brain areas during movement with reduced somatosensory reliability. As specifically compared to reduced somatosensory reliability, we expected greater activations of ipsilateral sensorimotor cerebellum for intact visual and somatosensory reliability. Further, we expected that ipsilateral posterior cognitive cerebellum would be affected with reduced visual reliability. We observed that reduced visual reliability results in a trend towards the relative consolidation of sensorimotor activation and an expansion of cerebellar activation. In contrast, reduced somatosensory reliability was characterized by the absence of cerebellar activations and a trend towards the increase of right frontal, left parietofrontal activation, and temporo-occipital areas. Our findings highlight the role of the cerebellum for specific aspects of skillful motor performance. This has relevance to understanding basic aspects of brain functions underlying sensorimotor integration, and provides a greater understanding of cerebellar function in tool use motor control.

  10. Somatosensory impairment and its association with balance limitation in people with multiple sclerosis.

    Science.gov (United States)

    Jamali, Akram; Sadeghi-Demneh, Ebrahim; Fereshtenajad, Niloufar; Hillier, Susan

    2017-09-01

    Somatosensory impairments are common in multiple sclerosis. However, little data are available to characterize the nature and frequency of these problems in people with multiple sclerosis. To investigate the frequency of somatosensory impairments and identify any association with balance limitations in people with multiple sclerosis. The design was a prospective cross-sectional study, involving 82 people with multiple sclerosis and 30 healthy controls. Tactile and proprioceptive sensory acuity were measured using the Rivermead Assessment of Somatosensory Performance. Vibration duration was assessed using a tuning fork. Duration for the Timed Up and Go Test and reaching distance of the Functional Reach Test were measured to assess balance limitations. The normative range of sensory modalities was defined using cut-off points in the healthy participants. The multivariate linear regression was used to identify the significant predictors of balance in people with multiple sclerosis. Proprioceptive impairments (66.7%) were more common than tactile (60.8%) and vibration impairments (44.9%). Somatosensory impairments were more frequent in the lower limb (78.2%) than the upper limb (64.1%). All sensory modalities were significantly associated with the Timed Up and Go and Functional Reach tests (plimitation. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Neuromagnetic beta and gamma oscillations in the somatosensory cortex after music training in healthy older adults and a chronic stroke patient.

    Science.gov (United States)

    Jamali, Shahab; Fujioka, Takako; Ross, Bernhard

    2014-06-01

    Extensive rehabilitation training can lead to functional improvement even years after a stroke. Although neuronal plasticity is considered as a main origin of such ameliorations, specific subtending mechanisms need further investigation. Our aim was to obtain objective neuromagnetic measures sensitive to brain reorganizations induced by a music-supported training. We applied 20-Hz vibrotactile stimuli to the index finger and the ring finger, recorded somatosensory steady-state responses with magnetoencephalography, and analyzed the cortical sources displaying oscillations synchronized with the external stimuli in two groups of healthy older adults before and after musical training or without training. In addition, we applied the same analysis for an anecdotic report of a single chronic stroke patient with hemiparetic arm and hand problems, who received music-supported therapy (MST). Healthy older adults showed significant finger separation within the primary somatotopic map. Beta dipole sources were more anterior located compared to gamma sources. An anterior shift of sources and increases in synchrony between the stimuli and beta and gamma oscillations were observed selectively after music training. In the stroke patient a normalization of somatotopic organization was observed after MST, with digit separation recovered after training and stimulus induced gamma synchrony increased. The proposed stimulation paradigm captures the integrity of primary somatosensory hand representation. Source position and synchronization between the stimuli and gamma activity are indices, sensitive to music-supported training. Responsiveness was also observed in a chronic stroke patient, encouraging for the music-supported therapy. Notably, changes in somatosensory responses were observed, even though the therapy did not involve specific sensory discrimination training. The proposed protocol can be used for monitoring changes in neuronal organization during training and will improve

  12. Genetic influence demonstrated for MEG-recorded somatosensory evoked responses

    NARCIS (Netherlands)

    van 't Ent, D.; van Soelen, I.L.C.; Stam, K.J.; de Geus, E.J.C.; Boomsma, D.I.

    2010-01-01

    We tested for a genetic influence on magnetoencephalogram (MEG)-recorded somatosensory evoked fields (SEFs) in 20 monozygotic (MZ) and 14 dizygotic (DZ) twin pairs. Previous electroencephalogram (EEG) studies that demonstrated a genetic contribution to evoked responses generally focused on

  13. Cortical plasticity induced by spike-triggered microstimulation in primate somatosensory cortex.

    Directory of Open Access Journals (Sweden)

    Weiguo Song

    Full Text Available Electrical stimulation of the nervous system for therapeutic purposes, such as deep brain stimulation in the treatment of Parkinson's disease, has been used for decades. Recently, increased attention has focused on using microstimulation to restore functions as diverse as somatosensation and memory. However, how microstimulation changes the neural substrate is still not fully understood. Microstimulation may cause cortical changes that could either compete with or complement natural neural processes, and could result in neuroplastic changes rendering the region dysfunctional or even epileptic. As part of our efforts to produce neuroprosthetic devices and to further study the effects of microstimulation on the cortex, we stimulated and recorded from microelectrode arrays in the hand area of the primary somatosensory cortex (area 1 in two awake macaque monkeys. We applied a simple neuroprosthetic microstimulation protocol to a pair of electrodes in the area 1 array, using either random pulses or pulses time-locked to the recorded spiking activity of a reference neuron. This setup was replicated using a computer model of the thalamocortical system, which consisted of 1980 spiking neurons distributed among six cortical layers and two thalamic nuclei. Experimentally, we found that spike-triggered microstimulation induced cortical plasticity, as shown by increased unit-pair mutual information, while random microstimulation did not. In addition, there was an increased response to touch following spike-triggered microstimulation, along with decreased neural variability. The computer model successfully reproduced both qualitative and quantitative aspects of the experimental findings. The physiological findings of this study suggest that even simple microstimulation protocols can be used to increase somatosensory information flow.

  14. Keeping in Touch With the Visual System: Spatial Alignment and Multisensory Integration of Visual-Somatosensory Inputs

    Directory of Open Access Journals (Sweden)

    Jeannette Rose Mahoney

    2015-08-01

    Full Text Available Correlated sensory inputs coursing along the individual sensory processing hierarchies arrive at multisensory convergence zones in cortex where inputs are processed in an integrative manner. The exact hierarchical level of multisensory convergence zones and the timing of their inputs are still under debate, although increasingly, evidence points to multisensory integration at very early sensory processing levels. The objective of the current study was to determine, both psychophysically and electrophysiologically, whether differential visual-somatosensory integration patterns exist for stimuli presented to the same versus opposite hemifields. Using high-density electrical mapping and complementary psychophysical data, we examined multisensory integrative processing for combinations of visual and somatosensory inputs presented to both left and right spatial locations. We assessed how early during sensory processing visual-somatosensory (VS interactions were seen in the event-related potential and whether spatial alignment of the visual and somatosensory elements resulted in differential integration effects. Reaction times to all VS pairings were significantly faster than those to the unisensory conditions, regardless of spatial alignment, pointing to engagement of integrative multisensory processing in all conditions. In support, electrophysiological results revealed significant differences between multisensory simultaneous VS and summed V+S responses, regardless of the spatial alignment of the constituent inputs. Nonetheless, multisensory effects were earlier in the aligned conditions, and were found to be particularly robust in the case of right-sided inputs (beginning at just 55ms. In contrast to previous work on audio-visual and audio-somatosensory inputs, the current work suggests a degree of spatial specificity to the earliest detectable multisensory integrative effects in response to visual-somatosensory pairings.

  15. Non-invasive modulation of somatosensory evoked potentials by the application of static magnetic fields over the primary and supplementary motor cortices.

    Science.gov (United States)

    Kirimoto, Hikari; Asao, Akihiko; Tamaki, Hiroyuki; Onishi, Hideaki

    2016-10-04

    This study was performed to investigate the possibility of non-invasive modulation of SEPs by the application of transcranial static magnetic field stimulation (tSMS) over the primary motor cortex (M1) and supplementary motor cortex (SMA), and to measure the strength of the NdFeB magnetic field by using a gaussmeter. An NdFeB magnet or a non-magnetic stainless steel cylinder (for sham stimulation) was settled on the scalp over M1 and SMA of 14 subjects for periods of 15 min. SEPs following right median nerve stimulation were recorded before and immediately after, 5 min after, and 10 min after tSMS from sites C3' and F3. Amplitudes of the N33 component of SEPs at C3' significantly decreased immediately after tSMS over M1 by up to 20%. However, tSMS over the SMA did not affect the amplitude of any of the SEP components. At a distance of 2-3 cm (rough depth of the cortex), magnetic field strength was in the range of 110-190 mT. Our results that tSMS over M1 can reduce the amplitude of SEPs are consistent with those of low-frequency repeated TMS and cathodal tDCS studies. Therefore, tSMS could be a useful tool for modulating cortical somatosensory processing.

  16. Global patterns in human consumption of net primary production

    Science.gov (United States)

    Imhoff, Marc L.; Bounoua, Lahouari; Ricketts, Taylor; Loucks, Colby; Harriss, Robert; Lawrence, William T.

    2004-06-01

    The human population and its consumption profoundly affect the Earth's ecosystems. A particularly compelling measure of humanity's cumulative impact is the fraction of the planet's net primary production that we appropriate for our own use. Net primary production-the net amount of solar energy converted to plant organic matter through photosynthesis-can be measured in units of elemental carbon and represents the primary food energy source for the world's ecosystems. Human appropriation of net primary production, apart from leaving less for other species to use, alters the composition of the atmosphere, levels of biodiversity, energy flows within food webs and the provision of important ecosystem services. Here we present a global map showing the amount of net primary production required by humans and compare it to the total amount generated on the landscape. We then derive a spatial balance sheet of net primary production `supply' and `demand' for the world. We show that human appropriation of net primary production varies spatially from almost zero to many times the local primary production. These analyses reveal the uneven footprint of human consumption and related environmental impacts, indicate the degree to which human populations depend on net primary production `imports' and suggest policy options for slowing future growth of human appropriation of net primary production.

  17. Evaluation of various somatosensory stimulations for functional MRI

    International Nuclear Information System (INIS)

    Hara, Kazushi; Nakasato, Nobukazu; Mizoi, Kazuo; Yoshimoto, Takashi; Shimizu, Hiroaki.

    1997-01-01

    The aim of this functional magnetic resonance imaging (fMRI) study was to test detectability of activated area using various somatosensory stimulations. The following stimulations were performed in normal volunteers: regular or irregular electrical median nerve stimulation (n=5, each), tactile stimulation to the palm and fingers (n=8), pain stimulation to the index finger (n=5) or to the palm and fingers (n=5). fMRI was acquired with a spoiled gradient echo sequence at 1.5 T. Detectability of activated area was the highest when the pain stimulation was applied to the palm and fingers (80%). A successful rate for the tactile stimulation was 25%, and the other stimulations failed to demonstrate any activation. When successful, the highest signal activation on fMRI was seen on a sulcus, which presumably arose from a vein. The sulcus was defined as the central sulcus by somatosensory evoked field using a median nerve stimulation. Our study indicates that the pain stimulation to the palm and fingers may be a choice for the sensory fMRI. (author)

  18. Neuron Types in the Presumptive Primary Somatosensory Cortex of the Florida Manatee (Trichechus manatus latirostris).

    Science.gov (United States)

    Reyes, Laura D; Stimpson, Cheryl D; Gupta, Kanika; Raghanti, Mary Ann; Hof, Patrick R; Reep, Roger L; Sherwood, Chet C

    2015-01-01

    Within afrotherians, sirenians are unusual due to their aquatic lifestyle, large body size and relatively large lissencephalic brain. However, little is known about the neuron type distributions of the cerebral cortex in sirenians within the context of other afrotherians and aquatic mammals. The present study investigated two cortical regions, dorsolateral cortex area 1 (DL1) and cluster cortex area 2 (CL2), in the presumptive primary somatosensory cortex (S1) in Florida manatees (Trichechus manatus latirostris) to characterize cyto- and chemoarchitecture. The mean neuron density for both cortical regions was 35,617 neurons/mm(3) and fell within the 95% prediction intervals relative to brain mass based on a reference group of afrotherians and xenarthrans. Densities of inhibitory interneuron subtypes labeled against calcium-binding proteins and neuropeptide Y were relatively low compared to afrotherians and xenarthrans and also formed a small percentage of the overall population of inhibitory interneurons as revealed by GAD67 immunoreactivity. Nonphosphorylated neurofilament protein-immunoreactive (NPNFP-ir) neurons comprised a mean of 60% of neurons in layer V across DL1 and CL2. DL1 contained a higher percentage of NPNFP-ir neurons than CL2, although CL2 had a higher variety of morphological types. The mean percentage of NPNFP-ir neurons in the two regions of the presumptive S1 were low compared to other afrotherians and xenarthrans but were within the 95% prediction intervals relative to brain mass, and their morphologies were comparable to those found in other afrotherians and xenarthrans. Although this specific pattern of neuron types and densities sets the manatee apart from other afrotherians and xenarthrans, the manatee isocortex does not appear to be explicitly adapted for an aquatic habitat. Many of the features that are shared between manatees and cetaceans are also shared with a diverse array of terrestrial mammals and likely represent highly conserved

  19. Long-term neuroplasticity of the face primary motor cortex and adjacent somatosensory cortex induced by tooth loss can be reversed following dental implant replacement in rats.

    Science.gov (United States)

    Avivi-Arber, Limor; Lee, Jye-Chang; Sood, Mandeep; Lakschevitz, Flavia; Fung, Michelle; Barashi-Gozal, Maayan; Glogauer, Michael; Sessle, Barry J

    2015-11-01

    Tooth loss is common, and exploring the neuroplastic capacity of the face primary motor cortex (face-M1) and adjacent primary somatosensory cortex (face-S1) is crucial for understanding how subjects adapt to tooth loss and their prosthetic replacement. The aim was to test if functional reorganization of jaw and tongue motor representations in the rat face-M1 and face-S1 occurs following tooth extraction, and if subsequent dental implant placement can reverse this neuroplasticity. Rats (n = 22) had the right maxillary molar teeth extracted under local and general anesthesia. One month later, seven rats had dental implant placement into healed extraction sites. Naive rats (n = 8) received no surgical treatment. Intracortical microstimulation (ICMS) and recording of evoked jaw and tongue electromyographic responses were used to define jaw and tongue motor representations at 1 month (n = 8) or 2 months (n = 7) postextraction, 1 month postimplant placement, and at 1-2 months in naive rats. There were no significant differences across study groups in the onset latencies of the ICMS-evoked responses (P > 0.05), but in comparison with naive rats, tooth extraction caused a significant (P rats. These novel findings suggest that face-M1 and adjacent face-S1 may play a role in adaptive mechanisms related to tooth loss and their replacement with dental implants. © 2015 Wiley Periodicals, Inc.

  20. Alexithymia and Somatosensory Amplification Link Perceived Psychosocial Stress and Somatic Symptoms in Outpatients with Psychosomatic Illness

    Directory of Open Access Journals (Sweden)

    Mutsuhiro Nakao

    2018-05-01

    Full Text Available Background: Psychosomatic patients often complain of a variety of somatic symptoms. We sought to clarify the role of clinical predictors of complaints of somatic symptoms. Methods: We enrolled 604 patients visiting a psychosomatic outpatient clinic. The outcome was the total number of somatic symptoms, and the candidate clinical predictors were perceived psychosocial stress, alexithymia, somatosensory amplification, adaptation, anxiety, and depression. All participants completed questionnaires assessing the outcome and the predictors. Results: The average number of reported somatic symptoms was 4.8; the most frequent was fatigue (75.3%, followed by insomnia (56.1%, low-back pain (49.5%, headache (44.7%, and palpitations (43.1%. Multiple regression analysis showed that the total number of somatic symptoms was significantly associated with the degree of perceived psychosocial stress, alexithymia, somatosensory amplification, and depression. Also, structural equation models indicated links between excessive adaptation (via perceived psychosocial stress, alexithymia, and somatosensory amplification and the total number of somatic symptoms. Conclusion: The results suggested that the association between psychosocial stress and reported somatic symptoms is mediated by alexithymia and somatosensory amplification in psychosomatic patients.

  1. Ehlers-Danlos Syndrome, Hypermobility Type: Impact of Somatosensory Orthoses on Postural Control (A Pilot Study

    Directory of Open Access Journals (Sweden)

    Emma G. Dupuy

    2017-06-01

    Full Text Available Elhers-Danlos syndrome (EDS is the clinical manifestation of connective tissue disorders, and comprises several clinical forms with no specific symptoms and selective medical examinations which result in a delay in diagnosis of about 10 years. The EDS hypermobility type (hEDS is characterized by generalized joint hypermobility, variable skin hyperextensibility and impaired proprioception. Since somatosensory processing and multisensory integration are crucial for both perception and action, we put forth the hypothesis that somatosensory deficits in hEDS patients may lead, among other clinical symptoms, to misperception of verticality and postural instability. Therefore, the purpose of this study was twofold: (i to assess the impact of somatosensory deficit on subjective visual vertical (SVV and postural stability; and (ii to quantify the effect of wearing somatosensory orthoses (i.e., compressive garments and insoles on postural stability. Six hEDS patients and six age- and gender-matched controls underwent a SVV (sitting, standing, lying on the right side evaluation and a postural control evaluation on a force platform (Synapsys, with or without visual information (eyes open (EO/eyes closed (EC. These two latter conditions performed either without orthoses, or with compression garments (CG, or insoles, or both. Results showed that patients did not exhibit a substantial perceived tilt of the visual vertical in the direction of the body tilt (Aubert effect as did the control subjects. Interestingly, such differential effects were only apparent when the rod was initially positioned to the left of the vertical axis (opposite the longitudinal body axis. In addition, patients showed greater postural instability (sway area than the controls. The removal of vision exacerbated this instability, especially in the mediolateral (ML direction. The wearing of orthoses improved postural stability, especially in the eyes-closed condition, with a particularly

  2. MEG event-related desynchronization and synchronization deficits during basic somatosensory processing in individuals with ADHD

    Directory of Open Access Journals (Sweden)

    Wang Frank

    2008-02-01

    Full Text Available Abstract Background Attention-Deficit/Hyperactivity Disorder (ADHD is a prevalent, complex disorder which is characterized by symptoms of inattention, hyperactivity, and impulsivity. Convergent evidence from neurobiological studies of ADHD identifies dysfunction in fronto-striatal-cerebellar circuitry as the source of behavioural deficits. Recent studies have shown that regions governing basic sensory processing, such as the somatosensory cortex, show abnormalities in those with ADHD suggesting that these processes may also be compromised. Methods We used event-related magnetoencephalography (MEG to examine patterns of cortical rhythms in the primary (SI and secondary (SII somatosensory cortices in response to median nerve stimulation, in 9 adults with ADHD and 10 healthy controls. Stimuli were brief (0.2 ms non-painful electrical pulses presented to the median nerve in two counterbalanced conditions: unpredictable and predictable stimulus presentation. We measured changes in strength, synchronicity, and frequency of cortical rhythms. Results Healthy comparison group showed strong event-related desynchrony and synchrony in SI and SII. By contrast, those with ADHD showed significantly weaker event-related desynchrony and event-related synchrony in the alpha (8–12 Hz and beta (15–30 Hz bands, respectively. This was most striking during random presentation of median nerve stimulation. Adults with ADHD showed significantly shorter duration of beta rebound in both SI and SII except for when the onset of the stimulus event could be predicted. In this case, the rhythmicity of SI (but not SII in the ADHD group did not differ from that of controls. Conclusion Our findings suggest that somatosensory processing is altered in individuals with ADHD. MEG constitutes a promising approach to profiling patterns of neural activity during the processing of sensory input (e.g., detection of a tactile stimulus, stimulus predictability and facilitating our

  3. Precise chronology of differentiation of developing human primary dentition.

    Science.gov (United States)

    Hu, Xuefeng; Xu, Shan; Lin, Chensheng; Zhang, Lishan; Chen, YiPing; Zhang, Yanding

    2014-02-01

    While correlation of developmental stage with embryonic age of the human primary dentition has been well documented, the available information regarding the differentiation timing of the primary teeth was largely based on the observation of initial mineralization and varies significantly. In this study, we aimed to document precise differentiation timing of the developing human primary dentition. We systematically examined the expression of odontogenic differentiation markers along with the formation of mineralized tissue in each developing maxillary and mandibular teeth from human embryos with well-defined embryonic age. We show that, despite that all primary teeth initiate development at the same time, odontogenic differentiation begins in the maxillary incisors at the 15th week and in the mandibular incisors at the 16th week of gestation, followed by the canine, the first primary premolar, and the second primary premolar at a week interval sequentially. Despite that the mandibular primary incisors erupt earlier than the maxillary incisors, this distal to proximal sequential differentiation of the human primary dentition coincides in general with the sequence of tooth eruption. Our results provide an accurate chronology of odontogenic differentiation of the developing human primary dentition, which could be used as reference for future studies of human tooth development.

  4. Spinal N13 versus cortical N20 and dermatomal somatosensory ...

    African Journals Online (AJOL)

    Mohamed Imam

    2013-04-06

    Apr 6, 2013 ... Spinal N13 versus cortical N20 and dermatomal somatosensory .... recording point for the right upper limb stimulation and the. C40 for the left upper limb stimulation. The reference ..... Brain 1992;115:1209–34. 298. M. Imam ...

  5. Effects of white noise on event-related potentials in somatosensory Go/No-go paradigms.

    Science.gov (United States)

    Ohbayashi, Wakana; Kakigi, Ryusuke; Nakata, Hiroki

    2017-09-06

    Exposure to auditory white noise has been shown to facilitate human cognitive function. This phenomenon is termed stochastic resonance, and a moderate amount of auditory noise has been suggested to benefit individuals in hypodopaminergic states. The present study investigated the effects of white noise on the N140 and P300 components of event-related potentials in somatosensory Go/No-go paradigms. A Go or No-go stimulus was presented to the second or fifth digit of the left hand, respectively, at the same probability. Participants performed somatosensory Go/No-go paradigms while hearing three different white noise levels (45, 55, and 65 dB conditions). The peak amplitudes of Go-P300 and No-go-P300 in ERP waveforms were significantly larger under 55 dB than 45 and 65 dB conditions. White noise did not affect the peak latency of N140 or P300, or the peak amplitude of N140. Behavioral data for the reaction time, SD of reaction time, and error rates showed the absence of an effect by white noise. This is the first event-related potential study to show that exposure to auditory white noise at 55 dB enhanced the amplitude of P300 during Go/No-go paradigms, reflecting changes in the neural activation of response execution and inhibition processing.

  6. Reduced resting state functional connectivity of the somatosensory cortex predicts psychopathological symptoms in women with bulimia nervosa

    Directory of Open Access Journals (Sweden)

    Luca eLavagnino

    2014-08-01

    Full Text Available BackgroundAlterations in the resting state functional connectivity (rs-FC of several brain networks have been demonstrated in eating disorders. However, very few studies are currently available on brain network dysfunctions in bulimia nervosa (BN. The somatosensory network is central in processing body-related stimuli and it may be altered in BN. The present study therefore aimed to investigate rs-FC in the somatosensory network in bulimic women. MethodsSixteen medication-free women with BN (age=23±5 years and 18 matched controls (age=23±3 years underwent a functional magnetic resonance resting state scan and assessment of eating disorder symptoms. Within-network and seed-based functional connectivity analyses were conducted to assess rs-FC within the somatosensory network and to other areas of the brain. ResultsBN patients showed a decreased resting state functional connectivity both within the somatosensory network (t=9.0, df=1, P=0.005 and with posterior cingulate cortex (PCC and two visual areas (the right middle occipital gyrus and the right cuneus(P=0.05 corrected for multiple comparison. The region in the right middle occipital gyrus is implicated in body processing and is known as extrastriate body area, or EBA. The rs-FC of the left paracentral lobule with the EBA correlated with psychopathology measures like bulimia (r=-0.4; P=0.02 and interoceptive awareness (r=-0.4; P=0.01. Analyses were conducted using age, BMI (body mass index and depressive symptoms as covariates. ConclusionsOur findings show a specific alteration of the rs-FC of the somatosensory cortex in BN patients, which correlates with eating disorder symptoms. The connectivity between the somatosensory cortex and the EBA might be related to dysfunctions in body image processing. The results should be considered preliminary due to the small sample size.

  7. Reduced resting-state functional connectivity of the somatosensory cortex predicts psychopathological symptoms in women with bulimia nervosa.

    Science.gov (United States)

    Lavagnino, Luca; Amianto, Federico; D'Agata, Federico; Huang, Zirui; Mortara, Paolo; Abbate-Daga, Giovanni; Marzola, Enrica; Spalatro, Angela; Fassino, Secondo; Northoff, Georg

    2014-01-01

    Alterations in the resting-state functional connectivity (rs-FC) of several brain networks have been demonstrated in eating disorders. However, very few studies are currently available on brain network dysfunctions in bulimia nervosa (BN). The somatosensory network is central in processing body-related stimuli and it may be altered in BN. The present study therefore aimed to investigate rs-FC in the somatosensory network in bulimic women. Sixteen medication-free women with BN (age = 23 ± 5 years) and 18 matched controls (age = 23 ± 3 years) underwent a functional magnetic resonance resting-state scan and assessment of eating disorder symptoms. Within-network and seed-based functional connectivity analyses were conducted to assess rs-FC within the somatosensory network and to other areas of the brain. Bulimia nervosa patients showed a decreased rs-FC both within the somatosensory network (t = 9.0, df = 1, P = 0.005) and with posterior cingulate cortex and two visual areas (the right middle occipital gyrus and the right cuneus) (P = 0.05 corrected for multiple comparison). The rs-FC of the left paracentral lobule with the right middle occipital gyrus correlated with psychopathology measures like bulimia (r = -0.4; P = 0.02) and interoceptive awareness (r = -0.4; P = 0.01). Analyses were conducted using age, BMI (body mass index), and depressive symptoms as covariates. Our findings show a specific alteration of the rs-FC of the somatosensory cortex in BN patients, which correlates with eating disorder symptoms. The region in the right middle occipital gyrus is implicated in body processing and is known as extrastriate body area (EBA). The connectivity between the somatosensory cortex and the EBA might be related to dysfunctions in body image processing. The results should be considered preliminary due to the small sample size.

  8. Magnetoencephalographic Imaging of Auditory and Somatosensory Cortical Responses in Children with Autism and Sensory Processing Dysfunction

    Directory of Open Access Journals (Sweden)

    Carly Demopoulos

    2017-05-01

    Full Text Available This study compared magnetoencephalographic (MEG imaging-derived indices of auditory and somatosensory cortical processing in children aged 8–12 years with autism spectrum disorder (ASD; N = 18, those with sensory processing dysfunction (SPD; N = 13 who do not meet ASD criteria, and typically developing control (TDC; N = 19 participants. The magnitude of responses to both auditory and tactile stimulation was comparable across all three groups; however, the M200 latency response from the left auditory cortex was significantly delayed in the ASD group relative to both the TDC and SPD groups, whereas the somatosensory response of the ASD group was only delayed relative to TDC participants. The SPD group did not significantly differ from either group in terms of somatosensory latency, suggesting that participants with SPD may have an intermediate phenotype between ASD and TDC with regard to somatosensory processing. For the ASD group, correlation analyses indicated that the left M200 latency delay was significantly associated with performance on the WISC-IV Verbal Comprehension Index as well as the DSTP Acoustic-Linguistic index. Further, these cortical auditory response delays were not associated with somatosensory cortical response delays or cognitive processing speed in the ASD group, suggesting that auditory delays in ASD are domain specific rather than associated with generalized processing delays. The specificity of these auditory delays to the ASD group, in addition to their correlation with verbal abilities, suggests that auditory sensory dysfunction may be implicated in communication symptoms in ASD, motivating further research aimed at understanding the impact of sensory dysfunction on the developing brain.

  9. Auditory-somatosensory temporal sensitivity improves when the somatosensory event is caused by voluntary body movement

    Directory of Open Access Journals (Sweden)

    Norimichi Kitagawa

    2016-12-01

    Full Text Available When we actively interact with the environment, it is crucial that we perceive a precise temporal relationship between our own actions and sensory effects to guide our body movements.Thus, we hypothesized that voluntary movements improve perceptual sensitivity to the temporal disparity between auditory and movement-related somatosensory events compared to when they are delivered passively to sensory receptors. In the voluntary condition, participants voluntarily tapped a button, and a noise burst was presented at various onset asynchronies relative to the button press. The participants made either 'sound-first' or 'touch-first' responses. We found that the performance of temporal order judgment (TOJ in the voluntary condition (as indexed by the just noticeable difference was significantly better (M=42.5 ms ±3.8 s.e.m than that when their finger was passively stimulated (passive condition: M=66.8 ms ±6.3 s.e.m. We further examined whether the performance improvement with voluntary action can be attributed to the prediction of the timing of the stimulation from sensory cues (sensory-based prediction, kinesthetic cues contained in voluntary action, and/or to the prediction of stimulation timing from the efference copy of the motor command (motor-based prediction. When the participant’s finger was moved passively to press the button (involuntary condition and when three noise bursts were presented before the target burst with regular intervals (predictable condition, the TOJ performance was not improved from that in the passive condition. These results suggest that the improvement in sensitivity to temporal disparity between somatosensory and auditory events caused by the voluntary action cannot be attributed to sensory-based prediction and kinesthetic cues. Rather, the prediction from the efference copy of the motor command would be crucial for improving the temporal sensitivity.

  10. Beta 2-adrenergic receptors are colocalized and coregulated with whisker barrels in rat somatosensory cortex

    International Nuclear Information System (INIS)

    Vos, P.; Kaufmann, D.; Hand, P.J.; Wolfe, B.B.

    1990-01-01

    Autoradiography has been used to visualize independently the subtypes of beta-adrenergic receptors in rat somatosensory cortex. Beta 2-adrenergic receptors, but not beta 1-adrenergic receptors colocalize with whisker barrels in this tissue. Thus, each whisker sends a specific multisynaptic pathway to the somatosensory cortex that can be histochemically visualized and only one subtype of beta-adrenergic receptor is specifically associated with this cortical representation. Additionally, neonatal lesion of any or all of the whisker follicles results in loss of the corresponding barrel(s) as shown by histochemical markers. This loss is paralleled by a similar loss in the organization of beta 2-adrenergic receptors in the somatosensory cortex. Other results indicate that these beta 2-adrenergic receptors are not involved in moment-to-moment signal transmission in this pathway and, additionally, are not involved in a gross way in the development of whisker-barrel array

  11. Multimodal and widespread somatosensory abnormalities in persistent shoulder pain in the first 6 months after stroke: an exploratory study

    NARCIS (Netherlands)

    Roosink, M.; van Dongen, R.T.; Buitenweg, J.R.; Renzenbrink, G.J.; Geurts, A.C.H.; IJzerman, M.J.

    2012-01-01

    Roosink M, Van Dongen RT, Buitenweg JR, Renzenbrink GJ, Geurts AC, IJzerman MJ. Multimodal and widespread somatosensory abnormalities in persistent shoulder pain in the first 6 months after stroke: an exploratory study. OBJECTIVE: To explore the role of multimodal and widespread somatosensory

  12. Vibration and muscle contraction affect somatosensory evoked potentials

    OpenAIRE

    Cohen, LG; Starr, A

    1985-01-01

    We recorded potentials evoked by specific somatosensory stimuli over peripheral nerve, spinal cord, and cerebral cortex. Vibration attenuated spinal and cerebral potentials evoked by mixed nerve and muscle spindle stimulation; in one subject that was tested, there was no effect on cutaneous input. Presynaptic inhibition of Ia input in the spinal cord and muscle spindle receptor occupancy are probably the responsible mechanisms. In contrast, muscle contraction attenuated cerebral potentials to...

  13. Body Topography Parcellates Human Sensory and Motor Cortex.

    Science.gov (United States)

    Kuehn, Esther; Dinse, Juliane; Jakobsen, Estrid; Long, Xiangyu; Schäfer, Andreas; Bazin, Pierre-Louis; Villringer, Arno; Sereno, Martin I; Margulies, Daniel S

    2017-07-01

    The cytoarchitectonic map as proposed by Brodmann currently dominates models of human sensorimotor cortical structure, function, and plasticity. According to this model, primary motor cortex, area 4, and primary somatosensory cortex, area 3b, are homogenous areas, with the major division lying between the two. Accumulating empirical and theoretical evidence, however, has begun to question the validity of the Brodmann map for various cortical areas. Here, we combined in vivo cortical myelin mapping with functional connectivity analyses and topographic mapping techniques to reassess the validity of the Brodmann map in human primary sensorimotor cortex. We provide empirical evidence that area 4 and area 3b are not homogenous, but are subdivided into distinct cortical fields, each representing a major body part (the hand and the face). Myelin reductions at the hand-face borders are cortical layer-specific, and coincide with intrinsic functional connectivity borders as defined using large-scale resting state analyses. Our data extend the Brodmann model in human sensorimotor cortex and suggest that body parts are an important organizing principle, similar to the distinction between sensory and motor processing. © The Author 2017. Published by Oxford University Press.

  14. Projections of Somatosensory Cortex and Frontal Eye Fields onto Incertotectal Neurons in the Cat

    Science.gov (United States)

    Perkins, Eddie; Warren, Susan; Lin, Rick C.-S.; May, Paul J.

    2014-01-01

    The goal of this study was to determine whether the input-output characteristics of the zona incerta (ZI) are appropriate for it to serve as a conduit for cortical control over saccade-related activity in the superior colliculus. The study utilized the neuronal tracers wheat germ agglutinin-horseradish peroxidase (WGA-HRP) and biotinylated dextran amine (BDA) in the cat. Injections of WGA-HRP into primary somatosensory cortex (SI) revealed sparse, widespread nontopographic projections throughout ZI. In addition, region-specific areas of more intense termination were present in ventral ZI, although strict topography was not observed. In comparison, the frontal eye fields (FEF) also projected sparsely throughout ZI, but terminated more heavily, medially, along the border between the two sublaminae. Furthermore, retrogradely labeled incertocortical neurons were observed in both experiments. The relationship of these two cortical projections to incertotectal cells was also directly examined by retrogradely labeling incertotectal cells with WGA-HRP in animals that had also received cortical BDA injections. Labeled axonal arbors from both SI and FEF had thin, sparsely branched axons with numerous en passant boutons. They formed numerous close associations with the somata and dendrites of WGA-HRP-labeled incertotectal cells. In summary, these results indicate that both sensory and motor cortical inputs to ZI display similar morphologies and distributions. In addition, both display close associations with incertotectal cells, suggesting direct synaptic contact. From these data, we conclude that inputs from somatosensory and FEF cortex both play a role in controlling gaze-related activity in the superior colliculus by way of the inhibitory incertotectal projection. PMID:17083121

  15. CGRP in human models of primary headaches

    DEFF Research Database (Denmark)

    Ashina, Håkan; Schytz, Henrik Winther; Ashina, Messoud

    2018-01-01

    experiments are likely due to assay variation; therefore, proper validation and standardization of an assay is needed. To what extent CGRP is involved in tension-type headache and cluster headache is unknown. CONCLUSION: Human models of primary headaches have elucidated the role of CGRP in headache...... pathophysiology and sparked great interest in developing new treatment strategies using CGRP antagonists and antibodies. Future studies applying more refined human experimental models should identify biomarkers of CGRP-induced primary headache and reveal whether CGRP provocation experiments could be used......OBJECTIVE: To review the role of CGRP in human models of primary headaches and to discuss methodological aspects and future directions. DISCUSSION: Provocation experiments demonstrated a heterogeneous CGRP migraine response in migraine patients. Conflicting CGRP plasma results in the provocation...

  16. Vestibular-Somatosensory Convergence in Head Movement Control During Locomotion after Long-Duration Space Flight

    Science.gov (United States)

    Mulavara, Ajitkumar; Ruttley, Tara; Cohen, Helen; Peters, Brian; Miller, Chris; Brady, Rachel; Merkle, Lauren; Bloomberg, Jacob

    2010-01-01

    Exposure to the microgravity conditions of space flight induces adaptive modification in the control of vestibular-mediated reflexive head movement during locomotion after space flight. Space flight causes astronauts to be exposed to somatosensory adaptation in both the vestibular and body load-sensing (BLS) systems. The goal of these studies was to examine the contributions of vestibular and BLS-mediated somatosensory influences on head movement control during locomotion after long-duration space flight. Subjects were asked to walk on a treadmill driven at 1.8 m/s while performing a visual acuity task. Data were collected using the same testing protocol from three independent subject groups; 1) normal subjects before and after exposure to 30 minutes of 40% bodyweight unloaded treadmill walking, 2) bilateral labyrinthine deficient (LD) patients and 3) astronauts who performed the protocol before and after long duration space flight. Motion data from head and trunk segmental motion data were obtained to calculate the angular head pitch (HP) movements during walking trials while subjects performed the visual task, to estimate the contributions of vestibular reflexive mechanisms in HP movements. Results showed that exposure to unloaded locomotion caused a significant increase in HP movements, whereas in the LD patients the HP movements were significantly decreased. Astronaut subjects results showed a heterogeneous response of both increases and decreases in the amplitude of HP movement. We infer that BLS-mediated somatosensory input centrally modulates vestibular input and can adaptively modify head-movement control during locomotion. Thus, space flight may cause a central adaptation mediated by the converging vestibular and body load-sensing somatosensory systems.

  17. Chronic stress and peripheral pain: Evidence for distinct, region-specific changes in visceral and somatosensory pain regulatory pathways.

    Science.gov (United States)

    Zheng, Gen; Hong, Shuangsong; Hayes, John M; Wiley, John W

    2015-11-01

    Chronic stress alters the hypothalamic-pituitary-adrenal (HPA) axis and enhances visceral and somatosensory pain perception. It is unresolved whether chronic stress has distinct effects on visceral and somatosensory pain regulatory pathways. Previous studies reported that stress-induced visceral hyperalgesia is associated with reciprocal alterations of endovanilloid and endocannabinoid pain pathways in DRG neurons innervating the pelvic viscera. In this study, we compared somatosensory and visceral hyperalgesia with respect to differential responses of peripheral pain regulatory pathways in a rat model of chronic, intermittent stress. We found that chronic stress induced reciprocal changes in the endocannabinoid 2-AG (increased) and endocannabinoid degradation enzymes COX-2 and FAAH (decreased), associated with down-regulation of CB1 and up-regulation of TRPV1 receptors in L6-S2 DRG but not L4-L5 DRG neurons. In contrast, sodium channels Nav1.7 and Nav1.8 were up-regulated in L4-L5 but not L6-S2 DRGs in stressed rats, which was reproduced in control DRGs treated with corticosterone in vitro. The reciprocal changes of CB1, TRPV1 and sodium channels were cell-specific and observed in the sub-population of nociceptive neurons. Behavioral assessment showed that visceral hyperalgesia persisted, whereas somatosensory hyperalgesia and enhanced expression of Nav1.7 and Nav1.8 sodium channels in L4-L5 DRGs normalized 3 days after completion of the stress phase. These data indicate that chronic stress induces visceral and somatosensory hyperalgesia that involves differential changes in endovanilloid and endocannabinoid pathways, and sodium channels in DRGs innervating the pelvic viscera and lower extremities. These results suggest that chronic stress-induced visceral and lower extremity somatosensory hyperalgesia can be treated selectively at different levels of the spinal cord. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Disruption of visuospatial and somatosensory functional connectivity in anorexia nervosa.

    Science.gov (United States)

    Favaro, Angela; Santonastaso, Paolo; Manara, Renzo; Bosello, Romina; Bommarito, Giulia; Tenconi, Elena; Di Salle, Francesco

    2012-11-15

    Although body image disturbance is considered one of the core characteristics of anorexia nervosa (AN), the exact nature of this complex feature is poorly understood. Task-related functional magnetic resonance imaging studies can only partially explore the multimodal complexity of body consciousness, which is a complex cognition underpinned by aspects of visual perception, proprioception, and touch. The aim of the present study was to explore the functional connectivity of networks involved in visuospatial and somatosensory processing in AN. Twenty-nine subjects with AN, 16 women who had recovered from it, and 26 healthy women underwent a resting-state functional magnetic resonance imaging scan and neuropsychological assessment of their visuospatial abilities using the Rey-Osterrieth Complex Figure Test. Both AN groups showed areas of decreased connectivity in the ventral visual network, a network involved in the "what?" pathway of visual perception. Even more interestingly, the AN group, but not the recovered AN group, displayed increased coactivation in the left parietal cortex, encompassing the somatosensory cortex, in an area implicated in long-term multimodal spatial memory and representation, even in the absence of visual information. A neuropsychological assessment of visuospatial abilities revealed that aspects of detail processing and global integration (central coherence) showed correlations with connectivity of this brain area in the AN group. Our findings show that AN is associated with double disruption of brain connectivity, which shows a specific association with visuospatial difficulties and may explain the failure of the integration process between visual and somatosensory perceptual information that might sustain body image disturbance. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  19. Changing practice in the assessment and treatment of somatosensory loss in stroke survivors: protocol for a knowledge translation study.

    Science.gov (United States)

    Cahill, Liana S; Lannin, Natasha A; Mak-Yuen, Yvonne Y K; Turville, Megan L; Carey, Leeanne M

    2018-01-23

    The treatment of somatosensory loss in the upper limb after stroke has been historically overshadowed by therapy focused on motor recovery. A double-blind randomized controlled trial has demonstrated the effectiveness of SENSe (Study of the Effectiveness of Neurorehabilitation on Sensation) therapy to retrain somatosensory discrimination after stroke. Given the acknowledged prevalence of upper limb sensory loss after stroke and the evidence-practice gap that exists in this area, effort is required to translate the published research to clinical practice. The aim of this study is to determine whether evidence-based knowledge translation strategies change the practice of occupational therapists and physiotherapists in the assessment and treatment of sensory loss of the upper limb after stroke to improve patient outcomes. A pragmatic, before-after study design involving eight (n = 8) Australian health organizations, specifically sub-acute and community rehabilitation facilities. Stroke survivors (n = 144) and occupational therapists and physiotherapists (~10 per site, ~n = 80) will be involved in the study. Stroke survivors will be provided with SENSe therapy or usual care. Occupational therapists and physiotherapists will be provided with a multi-component approach to knowledge translation including i) tailoring of the implementation intervention to site-specific barriers and enablers, ii) interactive group training workshops, iii) establishing and fostering champion therapists and iv) provision of written educational materials and online resources. Outcome measures for occupational therapists and physiotherapists will be pre- and post-implementation questionnaires and audits of medical records. The primary outcome for stroke survivors will be change in upper limb somatosensory function, measured using a standardized composite measure. This study will provide evidence and a template for knowledge translation in clinical, organizational and policy contexts

  20. Visuotactile motion congruence enhances gamma-band activity in visual and somatosensory cortices.

    Science.gov (United States)

    Krebber, Martin; Harwood, James; Spitzer, Bernhard; Keil, Julian; Senkowski, Daniel

    2015-08-15

    When touching and viewing a moving surface our visual and somatosensory systems receive congruent spatiotemporal input. Behavioral studies have shown that motion congruence facilitates interplay between visual and tactile stimuli, but the neural mechanisms underlying this interplay are not well understood. Neural oscillations play a role in motion processing and multisensory integration. They may also be crucial for visuotactile motion processing. In this electroencephalography study, we applied linear beamforming to examine the impact of visuotactile motion congruence on beta and gamma band activity (GBA) in visual and somatosensory cortices. Visual and tactile inputs comprised of gratings that moved either in the same or different directions. Participants performed a target detection task that was unrelated to motion congruence. While there were no effects in the beta band (13-21Hz), the power of GBA (50-80Hz) in visual and somatosensory cortices was larger for congruent compared with incongruent motion stimuli. This suggests enhanced bottom-up multisensory processing when visual and tactile gratings moved in the same direction. Supporting its behavioral relevance, GBA was correlated with shorter reaction times in the target detection task. We conclude that motion congruence plays an important role for the integrative processing of visuotactile stimuli in sensory cortices, as reflected by oscillatory responses in the gamma band. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Co-occurrence of Pain Symptoms and Somatosensory Sensitivity in Burning Mouth Syndrome: A Systematic Review

    Science.gov (United States)

    Moisset, Xavier; Calbacho, Valentina; Torres, Pilar; Gremeau-Richard, Christelle; Dallel, Radhouane

    2016-01-01

    Background Burning mouth syndrome (BMS) is a chronic and spontaneous oral pain with burning quality in the tongue or other oral mucosa without any identifiable oral lesion or laboratory finding. Pathogenesis and etiology of BMS are still unknown. However, BMS has been associated with other chronic pain syndromes including other idiopathic orofacial pain, the dynias group and the family of central sensitivity syndromes. This would imply that BMS shares common mechanisms with other cephalic and/or extracephalic chronic pains. The primary aim of this systematic review was to determine whether BMS is actually associated with other pain syndromes, and to analyze cephalic and extracephalic somatosensory sensitivity in these patients. Methods This report followed the PRISMA Statement. An electronic search was performed until January 2015 in PubMed, Cochrane library, Wiley and ScienceDirect. Searched terms included “burning mouth syndrome OR stomatodynia OR glossodynia OR burning tongue OR oral burning”. Studies were selected according to predefined inclusion criteria (report of an association between BMS and other pain(s) symptoms or of cutaneous cephalic and/or extracephalic quantitative sensory testing in BMS patients), and a descriptive analysis conducted. Results The search retrieved 1512 reports. Out of these, twelve articles met criteria for co-occurring pain symptoms and nine studies for quantitative sensory testing (QST) in BMS patients. The analysis reveals that in BMS patients co-occurring pain symptoms are rare, assessed by only 0.8% (12 of 1512) of the retrieved studies. BMS was associated with headaches, TMD, atypical facial pain, trigeminal neuralgia, post-herpetic facial pain, back pain, fibromyalgia, joint pain, abdominal pain, rectal pain or vulvodynia. However, the prevalence of pain symptoms in BMS patients is not different from that in the age-matched general population. QST studies reveal no or inconsistent evidence of abnormal cutaneous cephalic

  2. Co-occurrence of Pain Symptoms and Somatosensory Sensitivity in Burning Mouth Syndrome: A Systematic Review.

    Directory of Open Access Journals (Sweden)

    Xavier Moisset

    Full Text Available Burning mouth syndrome (BMS is a chronic and spontaneous oral pain with burning quality in the tongue or other oral mucosa without any identifiable oral lesion or laboratory finding. Pathogenesis and etiology of BMS are still unknown. However, BMS has been associated with other chronic pain syndromes including other idiopathic orofacial pain, the dynias group and the family of central sensitivity syndromes. This would imply that BMS shares common mechanisms with other cephalic and/or extracephalic chronic pains. The primary aim of this systematic review was to determine whether BMS is actually associated with other pain syndromes, and to analyze cephalic and extracephalic somatosensory sensitivity in these patients.This report followed the PRISMA Statement. An electronic search was performed until January 2015 in PubMed, Cochrane library, Wiley and ScienceDirect. Searched terms included "burning mouth syndrome OR stomatodynia OR glossodynia OR burning tongue OR oral burning". Studies were selected according to predefined inclusion criteria (report of an association between BMS and other pain(s symptoms or of cutaneous cephalic and/or extracephalic quantitative sensory testing in BMS patients, and a descriptive analysis conducted.The search retrieved 1512 reports. Out of these, twelve articles met criteria for co-occurring pain symptoms and nine studies for quantitative sensory testing (QST in BMS patients. The analysis reveals that in BMS patients co-occurring pain symptoms are rare, assessed by only 0.8% (12 of 1512 of the retrieved studies. BMS was associated with headaches, TMD, atypical facial pain, trigeminal neuralgia, post-herpetic facial pain, back pain, fibromyalgia, joint pain, abdominal pain, rectal pain or vulvodynia. However, the prevalence of pain symptoms in BMS patients is not different from that in the age-matched general population. QST studies reveal no or inconsistent evidence of abnormal cutaneous cephalic and extracephalic

  3. Somatosensory sensitivity in patients with persistent idiopathic orofacial pain is associated with pain relief from hypnosis and relaxation.

    Science.gov (United States)

    Baad-Hansen, Lene; Abrahamsen, Randi; Zachariae, Robert; List, Thomas; Svensson, Peter

    2013-06-01

    In a recent study hypnosis has been found to relieve persistent idiopathic orofacial pain. Quantitative sensory testing (QST) is widely used to evaluate somatosensory sensitivity, which has been suggested as a possible predictor of management outcome. The objectives of this study were to examine: (1) possible associations between clinical pain relief and baseline somatosensory sensitivity and (2) the effect of hypnosis management on QST parameters. Forty-one patients with persistent idiopathic orofacial pain completed this randomized controlled study in 1 of 2 groups: hypnosis (hypnotic analgesia suggestions) or control (relaxation). QST at 2 intraoral (pain region and contralateral mirror image region) and 3 extraoral (hand and both cheeks) sites was performed at baseline and after the hypnosis/control management, together with pressure pain thresholds and pressure pain tolerance thresholds determined bilaterally at the masseter and temporalis muscles, the temporomandibular joints, and the third finger. Degree of pain relief was negatively correlated with a summary statistic of baseline somatosensory sensitivity (summed z-score), that is, high baseline somatosensory sensitivity was associated with low pain relief (r=-0.372, P=0.020). Hypnosis had no major effect on any QST measure compared with relaxation (P>0.063). High pain sensitivity at baseline may predict poor pain management outcome. In addition, despite clear clinical pain relief, hypnosis did not significantly or specifically influence somatosensory sensitivity. Future studies should further explore QST measures as possible predictors of different management response in orofacial pain conditions.

  4. Postnatal Development of CB1 Receptor Expression in Rodent Somatosensory Cortex

    Science.gov (United States)

    Deshmukh, Suvarna; Onozuka, Kaori; Bender, Kevin J.; Bender, Vanessa A.; Lutz, Beat; Mackie, Ken; Feldman, Daniel E.

    2007-01-01

    Endocannabinoids are powerful modulators of synaptic transmission that act on presynaptic cannabinoid receptors. Cannabinoid receptor type 1 (CB1) is the dominant receptor in the CNS, and is present in many brain regions, including sensory cortex. To investigate the potential role of CB1 receptors in cortical development, we examined the developmental expression of CB1 in rodent primary somatosensory (barrel) cortex, using immunohistochemistry with a CB1-specific antibody. We found that before postnatal day (P) 6, CB1 receptor staining was present exclusively in the cortical white matter, and that CB1 staining appeared in the grey matter between P6 and P20 in a specific laminar pattern. CB1 staining was confined to axons, and was most prominent in cortical layers 2/3, 5a, and 6. CB1 null (−/−) mice showed altered anatomical barrel maps in layer 4, with enlarged inter-barrel septa, but normal barrel size. These results indicate that CB1 receptors are present in early postnatal development and influence development of sensory maps. PMID:17210229

  5. Attentional Modulation of Somatosensory Processing During the Anticipation of Movements Accompanying Pain: An Event-Related Potential Study.

    Science.gov (United States)

    Clauwaert, Amanda; Torta, Diana M; Danneels, Lieven; Van Damme, Stefaan

    2018-02-01

    Attending to pain-relevant information is crucial to protect us from physical harm. Behavioral studies have already suggested that during anticipation of pain somatosensory input at the body location under threat is prioritized. However, research using daily life cues for pain, especially movements, is lacking. Furthermore, to our knowledge, no studies have investigated cortical processing associated with somatosensory processing during threatened movements. The current study aims to investigate whether movements accompanying pain automatically steer attention toward somatosensory input at the threatened location, affecting somatosensory evoked potentials (SEPs). Healthy volunteers were cued to perform movements with the left or the right hand, and one of these movements could be accompanied by pain on the moving hand. During movement anticipation, a task-irrelevant tactile stimulus was presented to the threatened or pain-free hand to evoke SEPs. During anticipation of movements accompanying pain, the N120 component was increased for tactile stimuli at the threatened relative to the hand without pain. Moreover, the P200 SEP was enhanced during anticipation of movements accompanying pain relative to movements without pain, irrespective of which hand was stimulated. These findings show that the anticipation of pain-accompanying movements may affect the processing of somatosensory input, and that this is likely to be driven by attentional processes. This study shows that the anticipation of pain-related movements automatically biases attention toward stimuli at a pain-related location, measured according to SEPs. The present study provides important new insights in the interplay between pain and attention, and its consequences at the cortical level. Copyright © 2017 The American Pain Society. Published by Elsevier Inc. All rights reserved.

  6. Somatosensory amplification mediates sex differences in psychological distress among cardioverter-defibrillator patients

    DEFF Research Database (Denmark)

    Versteeg, Henneke; Baumert, Jens; Kolb, Christof

    2010-01-01

    The present study examined whether female patients with an implantable cardioverter defibrillator (ICD) report more psychological distress than male patients, and whether somatosensory amplification mediates this relationship. Design: Consecutive ICD patients (N = 241; 33% women) participating in...

  7. Quantifying interhemispheric symmetry of somatosensory evoked potentials with the intraclass correlation coefficient

    NARCIS (Netherlands)

    van de Wassenberg, Wilma J. G.; van der Hoeven, Johannes H.; Leenders, Klaus L.; Maurits, Natasha M.

    Although large intersubject variability is reported for cortical somatosensory evoked potentials (SEPs), variability between hemispheres within one subject is thought to be small. Therefore, interhemispheric comparison of SEP waveforms might be clinically useful to detect unilateral abnormalities in

  8. Steady-state evoked potentials to study the processing of tactile and nociceptive somatosensory input in the human brain.

    Science.gov (United States)

    Colon, E; Legrain, V; Mouraux, A

    2012-10-01

    The periodic presentation of a sensory stimulus induces, at certain frequencies of stimulation, a sustained electroencephalographic response of corresponding frequency, known as steady-state evoked potentials (SS-EP). In visual, auditory and vibrotactile modalities, studies have shown that SS-EP reflect mainly activity originating from early, modality-specific sensory cortices. Furthermore, it has been shown that SS-EP have several advantages over the recording of transient event-related brain potentials (ERP), such as a high signal-to-noise ratio, a shorter time to obtain reliable signals, and the capacity to frequency-tag the cortical activity elicited by concurrently presented sensory stimuli. Recently, we showed that SS-EP can be elicited by the selective activation of skin nociceptors and that nociceptive SS-EP reflect the activity of a population of neurons that is spatially distinct from the somatotopically-organized population of neurons underlying vibrotactile SS-EP. Hence, the recording of SS-EP offers a unique opportunity to study the cortical representation of nociception and touch in humans, and to explore their potential crossmodal interactions. Here, (1) we review available methods to achieve the rapid periodic stimulation of somatosensory afferents required to elicit SS-EP, (2) review previous studies that have characterized vibrotactile and nociceptive SS-EP, (3) discuss the nature of the recorded signals and their relationship with transient event-related potentials and (4) outline future perspectives and potential clinical applications of this technique. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  9. Relationship between somatosensory event-related potential N140 aberrations and hemispatial agnosia in patients with stroke: a preliminary study.

    Science.gov (United States)

    Ueno, Tomoyuki; Hada, Yasushi; Shimizu, Yukiyo; Yamada, Thoru

    2018-06-01

    The somatosensory event-related potential N140 is thought to be related to selective attention. This study aimed to compare the somatosensory event-related potential N140 in healthy subjects to that in patients with stroke to determine whether N140 and attentiveness are associated in patients with stroke with or without hemispatial agnosia. Normal somatosensory event-related potential N140 values were determined using data from ten healthy subjects. Fifteen patients with stroke were divided into two groups based on the presence of hemispatial neglect. Somatosensory event-related potential N140 components were compared between the two groups. Stimulation of the affected limb in the hemispatial agnosia group resulted in significantly longer N140 latency at the contralateral vs. the ipsilateral electrode. This was the inverse of the relationship observed in normal subjects, with stimulation of the intact side in patients with hemispatial agnosia, and with stimulation of both the intact and affected sides in patients without agnosia. In the hemispatial agnosia group, the peak latency of N140 following stimulation of the affected side was significantly longer than it was following stimulation of the intact side and when compared to that in patients without agnosia. In addition, abnormal N140 peak latencies were observed at the Cz and ipsilateral electrodes in patients with hemispatial agnosia following stimulation of the intact side. These findings suggest that somatosensory event-related potential N140 is independently generated in each hemisphere and may reflect cognitive attention.

  10. The functional and anatomical dissection of somatosensory subpopulations using mouse genetics

    Directory of Open Access Journals (Sweden)

    Claire E Le Pichon

    2014-04-01

    Full Text Available The word somatosensation comes from joining the Greek word for body (soma with a word for perception (sensation. Somatosensory neurons comprise the largest sensory system in mammals and have nerve endings coursing throughout the skin, viscera, muscle, and bone. Their cell bodies reside in a chain of ganglia adjacent to the dorsal spinal cord (the dorsal root ganglia and at the base of the skull (the trigeminal ganglia. While the neuronal cell bodies are intermingled within the ganglia, the somatosensory system is in reality composed of numerous sub-systems, each specialized to detect distinct stimuli, such as temperature and touch. Historically, somatosensory neurons have been classified using a diverse host of anatomical and physiological parameters, such as the size of the cell body, degree of myelination, histological labeling with markers, specialization of the nerve endings, projection patterns in the spinal cord and brainstem, receptive tuning, and conduction velocity of their action potentials. While useful, the picture that emerged was one of heterogeneity, with many markers at least partially overlapping. More recently, by capitalizing on advances in molecular techniques, researchers have identified specific ion channels and sensory receptors expressed in subsets of sensory neurons. These studies have proved invaluable as they allow genetic access to small subsets of neurons for further molecular dissection. Data being generated from transgenic mice favor the model whereby an array of dedicated neurons is responsible for selectively encoding different modalities. Here we review the current knowledge of the different sensory neuron subtypes in the mouse, the markers used to study them, and the neurogenetic strategies used to define their anatomical projections and functional roles.

  11. Paradigms for restoration of somatosensory feedback via stimulation of the peripheral nervous system.

    Science.gov (United States)

    Pasluosta, Cristian; Kiele, Patrick; Stieglitz, Thomas

    2018-04-01

    The somatosensory system contributes substantially to the integration of multiple sensor modalities into perception. Tactile sensations, proprioception and even temperature perception are integrated to perceive embodiment of our limbs. Damage of somatosensory networks can severely affect the execution of daily life activities. Peripheral injuries are optimally corrected via direct interfacing of the peripheral nerves. Recent advances in implantable devices, stimulation paradigms, and biomimetic sensors enabled the restoration of natural sensations after amputation of the limb. The refinement of stimulation patterns to deliver natural feedback that can be interpreted intuitively such to prescind from long-learning sessions is crucial to function restoration. For this review, we collected state-of-the-art knowledge on the evolution of stimulation paradigms from single fiber stimulation to the eliciting of multisensory sensations. Data from the literature are structured into six sections: (a) physiology of the somatosensory system; (b) stimulation of single fibers; (c) restoral of multisensory percepts; (d) closure of the control loop in hand prostheses; (e) sensory restoration and the sense of embodiment, and (f) methodologies to assess stimulation outcomes. Full functional recovery demands further research on multisensory integration and brain plasticity, which will bring new paradigms for intuitive sensory feedback in the next generation of limb prostheses. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  12. Effect of extradural morphine on somatosensory evoked potentials to dermatomal stimulation

    DEFF Research Database (Denmark)

    Lund, C; Selmar, P; Hansen, O B

    1987-01-01

    The effect of the extradural (L2-3) administration of morphine 6 mg on early (less than 0.5 s) somatosensory evoked cortical potentials (SEP) to electrical stimulation of the L1- and S1-dermatomes was examined in eight patients. Extradural morphine did not influence SEP amplitude. SEP latency did...

  13. Functional MRI activation of somatosensory and motor cortices in a hand-grafted patient with early clinical sensorimotor recovery

    International Nuclear Information System (INIS)

    Neugroschl, C.; Denolin, V.; Schuind, F.; Holder, C. van; David, P.; Baleriaux, D.; Metens, T.

    2005-01-01

    The aim of this study was to investigate somatosensory and motor cortical activity with functional MRI (fMRI) in a hand-grafted patient with early clinical recovery. The patient had motor fMRI examinations before transplantation, and motor and passive tactile stimulations after surgery. His normal hand and a normal group were studied for comparison. A patient with complete brachial plexus palsy was studied to assess the lack of a fMRI signal in somatosensory areas in the case of total axonal disconnection. Stimulating the grafted hand revealed significant activation in the contralateral somatosensory cortical areas in all fMRI examinations. The activation was seen as early as 10 days after surgery; this effect cannot be explained by the known physiological mechanisms of nerve regeneration. Although an imagination effect cannot be excluded, the objective clinical recovery of sensory function led us to formulate the hypothesis that a connection to the somatosensory cortex was rapidly established. Additional cases and fundamental studies are needed to assess this hypothesis, but several observations were compatible with this explanation. Before surgery, imaginary motion of the amputated hand produced less intense responses than executed movements of the intact hand, whereas the normal activation pattern for right-handed subjects was found after surgery, in agreement with the good clinical motor recovery. (orig.)

  14. Risk factors affecting somatosensory function after sagittal split osteotomy

    DEFF Research Database (Denmark)

    Thygesen, Torben Henrik; Jensen, Allan Bardow; Helleberg, M

    2008-01-01

    Purpose The aim of this study was to evaluate potential individual and intraoperative risk factors associated with bilateral sagittal split osteotomy (BSSO) and to correlate the findings with postoperative changes in somatosensory function. Patients and Methods A total of 18 men and 29 women (mean...... and free dissection of the inferior alveolar nerve during BSSO increased self-reported changes in lower lip sensation and lower lip tactile threshold after BSSO (P discrimination (P

  15. Effects of Ketamine on Neuronal Spontaneous Excitatory Postsynaptic Currents and Miniature Excitatory Postsynaptic Currents in the Somatosensory Cortex of Rats

    Directory of Open Access Journals (Sweden)

    Chengdong Yuan

    2016-07-01

    Full Text Available Background: Ketamine is a commonly used intravenous anesthetic which produces dissociation anesthesia, analgesia, and amnesia. The mechanism of ketamine-induced synaptic inhibition in high-level cortical areas is still unknown. We aimed to elucidate the effects of different concentrations of ketamine on the glutamatergic synaptic transmission of the neurons in the primary somatosensory cortex by using the whole-cell patch-clamp method. Methods: Sprague-Dawley rats (11–19 postnatal days, n=36 were used to obtain brain slices (300 μM. Spontaneous excitatory postsynaptic currents (data from 40 neurons were recorded at a command potential of -70 mV in the presence of bicuculline (a competitive antagonist of GABAA receptors, 30 μM and strychnine (glycine receptor antagonist, 30 μM. Miniature excitatory postsynaptic currents (data from 40 neurons were also recorded when 1 μM of tetrodotoxin was added into the artificial cerebrospinal fluid. We used GraphPad Prism5for statistical analysis. Significant differences in the mean amplitude and frequency were tested using the Student paired 2-tailed t test. Values of P<0.05 were considered significant. Results: Different concentrations of ketamine inhibited the frequency and amplitude of the spontaneous excitatory postsynaptic currents as well as the amplitude of the miniature excitatory postsynaptic currents in a concentration-dependent manner, but they exerted no significant effect on the frequency of the miniature excitatory postsynaptic currents. Conclusion: Ketamine inhibited the excitatory synaptic transmission of the neurons in the primary somatosensory cortex. The inhibition may have been mediated by a reduction in the sensitivity of the postsynaptic glutamatergic receptors.

  16. Laterodorsal nucleus of the thalamus: A processor of somatosensory inputs.

    Science.gov (United States)

    Bezdudnaya, Tatiana; Keller, Asaf

    2008-04-20

    The laterodorsal (LD) nucleus of the thalamus has been considered a "higher order" nucleus that provides inputs to limbic cortical areas. Although its functions are largely unknown, it is often considered to be involved in spatial learning and memory. Here we provide evidence that LD is part of a hitherto unknown pathway for processing somatosensory information. Juxtacellular and extracellular recordings from LD neurons reveal that they respond to vibrissa stimulation with short latency (median = 7 ms) and large magnitude responses (median = 1.2 spikes/stimulus). Most neurons (62%) had large receptive fields, responding to six and more individual vibrissae. Electrical stimulation of the trigeminal nucleus interpolaris (SpVi) evoked short latency responses (median = 3.8 ms) in vibrissa-responsive LD neurons. Labeling produced by anterograde and retrograde neuroanatomical tracers confirmed that LD neurons receive direct inputs from SpVi. Electrophysiological and neuroanatomical analyses revealed also that LD projects upon the cingulate and retrosplenial cortex, but has only sparse projections to the barrel cortex. These findings suggest that LD is part of a novel processing stream involved in spatial orientation and learning related to somatosensory cues. (c) 2008 Wiley-Liss, Inc.

  17. More than Skin Deep: Body Representation beyond Primary Somatosensory Cortex

    Science.gov (United States)

    Longo, Matthew R.; Azanon, Elena; Haggard, Patrick

    2010-01-01

    The neural circuits underlying initial sensory processing of somatic information are relatively well understood. In contrast, the processes that go beyond primary somatosensation to create more abstract representations related to the body are less clear. In this review, we focus on two classes of higher-order processing beyond Somatosensation.…

  18. The reactivation of somatosensory cortex and behavioral recovery after sensory loss in mature primates

    Directory of Open Access Journals (Sweden)

    Hui-Xin eQi

    2014-05-01

    Full Text Available In our experiments, we removed a major source of activation of somatosensory cortex in mature monkeys by unilaterally sectioning the sensory afferents in the dorsal columns of the spinal cord at a high cervical level. At this level, the ascending branches of tactile afferents from the hand are cut, while other branches of these afferents remain intact to terminate on neurons in the dorsal horn of the spinal cord. Immediately after such a lesion, the monkeys seem relatively unimpaired in locomotion and often use the forelimb, but further inspection reveals that they prefer to use the unaffected hand in reaching for food. In addition, systematic testing indicates that they make more errors in retrieving pieces of food, and start using visual inspection of the rotated hand to confirm the success of the grasping of the food. Such difficulties are not surprising as a complete dorsal column lesion totally deactivates the contralateral hand representation in primary somatosensory cortex (area 3b. However, hand use rapidly improves over the first post-lesion weeks, and much of the hand representational territory in contralateral area 3b is reactivated by inputs from the hand in roughly a normal somatotopic pattern. Quantitative measures of single neuron response properties reveal that reactivated neurons respond to tactile stimulation on the hand with high firing rates and only slightly longer latencies. We conclude that preserved dorsal column afferents after nearly complete lesions contribute to the reactivation of cortex and the recovery of the behavior, but second-order sensory pathways in the spinal cord may also play an important role. Our microelectrode recordings indicate that these preserved first-order, and second-order pathways are initially weak and largely ineffective in activating cortex, but they are potentiated during the recovery process. Therapies that would promote this potentiation could usefully enhance recovery after spinal cord

  19. "Lacking warmth": Alexithymia trait is related to warm-specific thermal somatosensory processing.

    Science.gov (United States)

    Borhani, Khatereh; Làdavas, Elisabetta; Fotopoulou, Aikaterini; Haggard, Patrick

    2017-09-01

    Alexithymia is a personality trait involving deficits in emotional processing. The personality construct has been extensively validated, but the underlying neural and physiological systems remain controversial. One theory suggests that low-level somatosensory mechanisms act as somatic markers of emotion, underpinning cognitive and affective impairments in alexithymia. In two separate samples (total N=100), we used an established Quantitative Sensory Testing (QST) battery to probe multiple neurophysiological submodalities of somatosensation, and investigated their associations with the widely-used Toronto Alexithymia Scale (TAS-20). Experiment one found reduced sensitivity to warmth in people with higher alexithymia scores, compared to individuals with lower scores, without deficits in other somatosensory submodalities. Experiment two replicated this result in a new group of participants using a full-sample correlation between threshold for warm detection and TAS-20 scores. We discuss the relations between low-level thermoceptive function and cognitive processing of emotion. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  20. Deep-brain electrical microstimulation is an effective tool to explore functional characteristics of somatosensory neurons in the rat brain.

    Directory of Open Access Journals (Sweden)

    Han-Jia Jiang

    Full Text Available In neurophysiology researches, peripheral stimulation is used along with recordings of neural activities to study the processing of somatosensory signals in the brain. However, limited precision of peripheral stimulation makes it difficult to activate the neuron with millisecond resolution and study its functional properties in this scale. Also, tissue/receptor damage that could occur in some experiments often limits the amount of responses that can be recorded and hence reduces data reproducibility. To overcome these limitations, electrical microstimulation (ES of the brain could be used to directly and more precisely evoke neural responses. For this purpose, a deep-brain ES protocol for rat somatosensory relay neurons was developed in this study. Three male Wistar rats were used in the experiment. The ES was applied to the thalamic region responsive to hindpaw tactile stimulation (TS via a theta glass microelectrode. The resulting ES-evoked cortical responses showed action potentials and thalamocortical relay latencies very similar to those evoked by TS. This result shows that the developed deep-brain ES protocol is an effective tool to bypass peripheral tissue for in vivo functional analysis of specific types of somatosensory neurons. This protocol could be readily applied in researches of nociception and other somatosensory systems to allow more extensive exploration of the neural functional networks.

  1. Differentiated effects of deep brain stimulation and medication on somatosensory processing in Parkinson's disease.

    Science.gov (United States)

    Sridharan, Kousik Sarathy; Højlund, Andreas; Johnsen, Erik Lisbjerg; Sunde, Niels Aagaard; Johansen, Lars Gottfried; Beniczky, Sándor; Østergaard, Karen

    2017-07-01

    Deep brain stimulation (DBS) and dopaminergic medication effectively alleviate the motor symptoms in Parkinson's disease (PD) patients, but their effects on the sensory symptoms of PD are still not well understood. To explore early somatosensory processing in PD, we recorded magnetoencephalography (MEG) from thirteen DBS-treated PD patients and ten healthy controls during median nerve stimulation. PD patients were measured during DBS-treated, untreated and dopaminergic-medicated states. We focused on early cortical somatosensory processing as indexed by N20m, induced gamma augmentation (31-45Hz and 55-100Hz) and induced beta suppression (13-30Hz). PD patients' motor symptoms were assessed by UPDRS-III. Using Bayesian statistics, we found positive evidence for differentiated effects of treatments on the induced gamma augmentation (31-45Hz) with highest gamma in the dopaminergic-medicated state and lowest in the DBS-treated and untreated states. In contrast, UPDRS-III scores showed beneficial effects of both DBS and dopaminergic medication on the patients' motor symptoms. Furthermore, treatments did not affect the amplitude of N20m. Our results suggest differentiated effects of DBS and dopaminergic medication on cortical somatosensory processing in PD patients despite consistent ameliorating effects of both treatments on PD motor symptoms. The differentiated effect suggests differences in the effect mechanisms of the two treatments. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  2. Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects

    International Nuclear Information System (INIS)

    Fox, P.T.; Raichle, M.E.

    1986-01-01

    Coupling between cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO 2 ) was studied using multiple sequential administrations of 15 O-labeled radiotracers and positron emission tomography. In the resting state an excellent correlation between CBF and CMRO 2 was found when paired measurements of CBF and CMRO 2 from multiple (30-48) brain regions were tested in each of 33 normal subjects. Regional uncoupling of CBF and CMRO 2 was found, however, during neuronal activation induced by somatosensory stimulation. Stimulus-induced focal augmentation of cerebral blood flow (29% mean) far exceeded the concomitant local increase in tissue metabolic rate (mean, 5%), when resting-state and stimulated-state measurements were obtained in each of 9 subjects. Stimulus duration had no significant effect on response magnitude or on the degree of CBF-CMRO 2 uncoupling observed. Dynamic, physiological regulation of CBF by a mechanism (neuronal or biochemical) dependent on neuronal firing per se, but independent of the cerebral metabolic rate of oxygen, is hypothesized

  3. Mechanosensor Channels in Mammalian Somatosensory Neurons

    Directory of Open Access Journals (Sweden)

    Patrick Delmas

    2007-09-01

    Full Text Available Mechanoreceptive sensory neurons innervating the skin, skeletal muscles andviscera signal both innocuous and noxious information necessary for proprioception, touchand pain. These neurons are responsible for the transduction of mechanical stimuli intoaction potentials that propagate to the central nervous system. The ability of these cells todetect mechanical stimuli impinging on them relies on the presence of mechanosensitivechannels that transduce the external mechanical forces into electrical and chemical signals.Although a great deal of information regarding the molecular and biophysical properties ofmechanosensitive channels in prokaryotes has been accumulated over the past two decades,less is known about the mechanosensitive channels necessary for proprioception and thesenses of touch and pain. This review summarizes the most pertinent data onmechanosensitive channels of mammalian somatosensory neurons, focusing on theirproperties, pharmacology and putative identity.

  4. Long-term stability of sensitivity to intracortical microstimulation of somatosensory cortex

    Science.gov (United States)

    Callier, Thierri; Schluter, Erik W.; Tabot, Gregg A.; Miller, Lee E.; Tenore, Francesco V.; Bensmaia, Sliman J.

    2015-10-01

    Objective. The dexterous manipulation of objects depends heavily on somatosensory signals from the limb. The development of anthropomorphic robotic arms and of algorithms to decode intended movements from neuronal signals has stimulated the need to restore somatosensation for use in upper-limb neuroprostheses. Without touch and proprioception, patients have difficulty controlling prosthetic limbs to a level that justifies the required invasive surgery. Intracortical microstimulation (ICMS) through chronically implanted electrode arrays has the potential to provide rich and intuitive sensory feedback. This approach to sensory restoration requires, however, that the evoked sensations remain stable over time. Approach. To investigate the stability of ICMS-evoked sensations, we measured the ability of non-human primates to detect ICMS over experimental sessions that spanned years. Main results. We found that the performance of the animals remained highly stable over time, even when they were tested with electrodes that had experienced extensive stimulation. Significance. Given the stability of the sensations that it evokes, ICMS may thus be a viable approach for sensory restoration.

  5. Alpha-Band Brain Oscillations Shape the Processing of Perceptible as well as Imperceptible Somatosensory Stimuli during Selective Attention.

    Science.gov (United States)

    Forschack, Norman; Nierhaus, Till; Müller, Matthias M; Villringer, Arno

    2017-07-19

    Attention filters and weights sensory information according to behavioral demands. Stimulus-related neural responses are increased for the attended stimulus. Does alpha-band activity mediate this effect and is it restricted to conscious sensory events (suprathreshold), or does it also extend to unconscious stimuli (subthreshold)? To address these questions, we recorded EEG in healthy male and female volunteers undergoing subthreshold and suprathreshold somatosensory electrical stimulation to the left or right index finger. The task was to detect stimulation at the randomly alternated cued index finger. Under attention, amplitudes of somatosensory evoked potentials increased 50-60 ms after stimulation (P1) for both suprathreshold and subthreshold events. Prestimulus amplitude of peri-Rolandic alpha, that is mu, showed an inverse relationship to P1 amplitude during attention compared to when the finger was unattended. Interestingly, intermediate and high amplitudes of mu rhythm were associated with the highest P1 amplitudes during attention and smallest P1 during lack of attention, that is, these levels of alpha rhythm seemed to optimally support the behavioral goal ("detect" stimuli at the cued finger while ignoring the other finger). Our results show that attention enhances neural processing for both suprathreshold and subthreshold stimuli and they highlight a rather complex interaction between attention, Rolandic alpha activity, and their effects on stimulus processing. SIGNIFICANCE STATEMENT Attention is crucial in prioritizing processing of relevant perceptible (suprathreshold) stimuli: it filters and weights sensory input. The present study investigates the controversially discussed question whether this attention effect extends to imperceptible (subthreshold) stimuli as well. We found noninvasive EEG signatures for attentional modulation of neural events following perceptible and imperceptible somatosensory stimulation in human participants. Specifically

  6. Acute Appendicitis, Somatosensory Disturbances ("Head Zones"), and the Differential Diagnosis of Anterior Cutaneous Nerve Entrapment Syndrome (ACNES).

    Science.gov (United States)

    Roumen, Rudi M H; Vening, Wouter; Wouda, Rosanne; Scheltinga, Marc M

    2017-06-01

    Anterior cutaneous nerve entrapment syndrome (ACNES) is a neuropathic abdominal wall pain syndrome typically characterized by locally altered skin sensations. On the other hand, visceral disease may also be associated with similar painful and altered skin sensations ("Head zones"). Aim of the study was to determine if patients with acute appendicitis demonstrated somatosensory disturbances in the corresponding right lower quadrant Head zone. The presence of somatosensory disturbances such as hyperalgesia, hypoesthesia, altered cool perception, or positive pinch test was determined in 100 patients before and after an appendectomy. Potential associations between altered skin sensations and various items including age, sex, history, body temperature, C-reactive protein (CRP), leukocyte count, and type of appendicopathy (normal, inflamed, necrotic, or perforated) were assessed. A total of 39 patients demonstrated at least one right lower abdominal quadrant skin somatosensory disturbance before the laparoscopic appendectomy. However, locoregional skin sensation normalized in all but 2 patients 2 weeks postoperatively. No differences were found concerning patient characteristics or type of appendicopathy between populations with or without altered lower abdominal skin sensations. A substantial portion of patients with acute appendicitis demonstrate right lower abdominal somatosensory disturbances that are similar as observed in acute ACNES. Both may be different sides of the same coin and are possibly expressions of segmental phenomena as described by Head. McBurney's point, a landmark area of maximum pain in acute appendicitis, is possibly a trigger point within a Head zone. Differentiating acute appendicitis from acute ACNES is extremely difficult, but imaging and observation may aid in the diagnostic process.

  7. Sensory adaptation to electrical stimulation of the somatosensory nerves.

    Science.gov (United States)

    Graczyk, Emily Lauren; Delhaye, Benoit; Schiefer, Matthew A; Bensmaia, Sliman J; Tyler, Dustin J

    2018-03-19

    Sensory systems adapt their sensitivity to ambient stimulation levels to improve their responsiveness to changes in stimulation. The sense of touch is also subject to adaptation, as evidenced by the desensitization produced by prolonged vibratory stimulation of the skin. Electrical stimulation of nerves elicits tactile sensations that can convey feedback for bionic limbs. In this study, we investigate whether artificial touch is also subject to adaptation, despite the fact that the peripheral mechanotransducers are bypassed. Approach: Using well-established psychophysical paradigms, we characterize the time course and magnitude of sensory adaptation caused by extended electrical stimulation of the residual somatosensory nerves in three human amputees implanted with cuff electrodes. Main results: We find that electrical stimulation of the nerve also induces perceptual adaptation that recovers after cessation of the stimulus. The time course and magnitude of electrically-induced adaptation are equivalent to their mechanically-induced counterparts. Significance: We conclude that, in natural touch, the process of mechanotransduction is not required for adaptation, and artificial touch naturally experiences adaptation-induced adjustments of the dynamic range of sensations. Further, as it does for native hands, adaptation confers to bionic hands enhanced sensitivity to changes in stimulation and thus a more natural sensory experience. . Creative Commons Attribution license.

  8. Impaired verbal memory in Parkinson disease: relationship to prefrontal dysfunction and somatosensory discrimination

    Directory of Open Access Journals (Sweden)

    Weniger Dorothea

    2009-12-01

    Full Text Available Abstract Objective To study the neurocognitive profile and its relationship to prefrontal dysfunction in non-demented Parkinson's disease (PD with deficient haptic perception. Methods Twelve right-handed patients with PD and 12 healthy control subjects underwent thorough neuropsychological testing including Rey complex figure, Rey auditory verbal and figural learning test, figural and verbal fluency, and Stroop test. Test scores reflecting significant differences between patients and healthy subjects were correlated with the individual expression coefficients of one principal component, obtained in a principal component analysis of an oxygen-15-labeled water PET study exploring somatosensory discrimination that differentiated between the two groups and involved prefrontal cortices. Results We found significantly decreased total scores for the verbal learning trials and verbal delayed free recall in PD patients compared with normal volunteers. Further analysis of these parameters using Spearman's ranking correlation showed a significantly negative correlation of deficient verbal recall with expression coefficients of the principal component whose image showed a subcortical-cortical network, including right dorsolateral-prefrontal cortex, in PD patients. Conclusion PD patients with disrupted right dorsolateral prefrontal cortex function and associated diminished somatosensory discrimination are impaired also in verbal memory functions. A negative correlation between delayed verbal free recall and PET activation in a network including the prefrontal cortices suggests that verbal cues and accordingly declarative memory processes may be operative in PD during activities that demand sustained attention such as somatosensory discrimination. Verbal cues may be compensatory in nature and help to non-specifically enhance focused attention in the presence of a functionally disrupted prefrontal cortex.

  9. An evaluation of the somatosensory profile of hemiparetic individuals

    Directory of Open Access Journals (Sweden)

    R.S. Mota

    2010-01-01

    Full Text Available The purpose of this study was to evaluate the somatosensory profile of 18 hemiparetic spastic victims of stroke with and without blocking vision. Maximal isometric contraction test was used for flexor and extensor muscles of the hip and knee, and flexor plantar muscles. The number of cycles per minute on stationary bike was also measured with eyes opened and closed. Significant differences were found suggesting the existence of miscommunication between sensory-motor neural mechanisms responsible for voluntary motor actions in these individuals.

  10. HANPP Collection: Human Appropriation of Net Primary Productivity as a Percentage of Net Primary Productivity

    Data.gov (United States)

    National Aeronautics and Space Administration — The Human Appropriation of Net Primary Productivity (HANPP) as a Percentage of Net Primary Product (NPP) portion of the HANPP Collection represents a map identifying...

  11. Primary ciliogenesis defects are associated with human astrocytoma/glioblastoma cells

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    Rattner Jerome B

    2009-12-01

    Full Text Available Abstract Background Primary cilia are non-motile sensory cytoplasmic organelles that have been implicated in signal transduction, cell to cell communication, left and right pattern embryonic development, sensation of fluid flow, regulation of calcium levels, mechanosensation, growth factor signaling and cell cycle progression. Defects in the formation and/or function of these structures underlie a variety of human diseases such as Alström, Bardet-Biedl, Joubert, Meckel-Gruber and oral-facial-digital type 1 syndromes. The expression and function of primary cilia in cancer cells has now become a focus of attention but has not been studied in astrocytomas/glioblastomas. To begin to address this issue, we compared the structure and expression of primary cilia in a normal human astrocyte cell line with five human astrocytoma/glioblastoma cell lines. Methods Cultured normal human astrocytes and five human astrocytoma/glioblastoma cell lines were examined for primary cilia expression and structure using indirect immunofluorescence and electron microscopy. Monospecific antibodies were used to detect primary cilia and map the relationship between the primary cilia region and sites of endocytosis. Results We show that expression of primary cilia in normal astrocytes is cell cycle related and the primary cilium extends through the cell within a unique structure which we show to be a site of endocytosis. Importantly, we document that in each of the five astrocytoma/glioblastoma cell lines fully formed primary cilia are either expressed at a very low level, are completely absent or have aberrant forms, due to incomplete ciliogenesis. Conclusions The recent discovery of the importance of primary cilia in a variety of cell functions raises the possibility that this structure may have a role in a variety of cancers. Our finding that the formation of the primary cilium is disrupted in cells derived from astrocytoma/glioblastoma tumors provides the first

  12. The Role of Attention in Somatosensory Processing: A Multi-Trait, Multi-Method Analysis

    Science.gov (United States)

    Wodka, Ericka L.; Puts, Nicolaas A. J.; Mahone, E. Mark; Edden, Richard A. E.; Tommerdahl, Mark; Mostofsky, Stewart H.

    2016-01-01

    Sensory processing abnormalities in autism have largely been described by parent report. This study used a multi-method (parent-report and measurement), multi-trait (tactile sensitivity and attention) design to evaluate somatosensory processing in ASD. Results showed multiple significant within-method (e.g., parent report of different…

  13. In vivo patch-clamp analysis of response properties of rat primary somatosensory cortical neurons responding to noxious stimulation of the facial skin

    Directory of Open Access Journals (Sweden)

    Nasu Masanori

    2010-05-01

    Full Text Available Abstract Background Although it has been widely accepted that the primary somatosensory (SI cortex plays an important role in pain perception, it still remains unclear how the nociceptive mechanisms of synaptic transmission occur at the single neuron level. The aim of the present study was to examine whether noxious stimulation applied to the orofacial area evokes the synaptic response of SI neurons in urethane-anesthetized rats using an in vivo patch-clamp technique. Results In vivo whole-cell current-clamp recordings were performed in rat SI neurons (layers III-IV. Twenty-seven out of 63 neurons were identified in the mechanical receptive field of the orofacial area (36 neurons showed no receptive field and they were classified as non-nociceptive (low-threshold mechanoreceptive; 6/27, 22% and nociceptive neurons. Nociceptive neurons were further divided into wide-dynamic range neurons (3/27, 11% and nociceptive-specific neurons (18/27, 67%. In the majority of these neurons, a proportion of the excitatory postsynaptic potentials (EPSPs reached the threshold, and then generated random discharges of action potentials. Noxious mechanical stimuli applied to the receptive field elicited a discharge of action potentials on the barrage of EPSPs. In the case of noxious chemical stimulation applied as mustard oil to the orofacial area, the membrane potential shifted depolarization and the rate of spontaneous discharges gradually increased as did the noxious pinch-evoked discharge rates, which were usually associated with potentiated EPSP amplitudes. Conclusions The present study provides evidence that SI neurons in deep layers III-V respond to the temporal summation of EPSPs due to noxious mechanical and chemical stimulation applied to the orofacial area and that these neurons may contribute to the processing of nociceptive information, including hyperalgesia.

  14. Inquiry-Based Learning in Teacher Education: A Primary Humanities Example

    Science.gov (United States)

    Preston, Lou; Harvie, Kate; Wallace, Heather

    2015-01-01

    Inquiry-based learning features strongly in the new Australian Humanities and Social Sciences curriculum and increasingly in primary school practice. Yet, there is little research into, and few exemplars of, inquiry approaches in the primary humanities context. In this article, we outline and explain the implementation of a place-based simulation…

  15. Age Effect on Automatic Inhibitory Function of the Somatosensory and Motor Cortex: An MEG Study

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    Chia-Hsiung Cheng

    2018-03-01

    Full Text Available Age-related deficiency in the top-down modulation of cognitive inhibition has been extensively documented, whereas the effects of age on a bottom-up or automatic operation of inhibitory function were less investigated. It is unknown that whether the older adults (OA’ reduced behavioral performance and neural responses are due to the insufficient bottom-up processes. Compared to behavioral assessments which have been widely used to examine the top-down control of response inhibition, electrophysiological recordings are more suitable to probe the early-stage processes of automatic inhibitory function. Sensory gating (SG, a phenomenon of attenuated neural response to the second identical stimulus in a paired-pulse paradigm, is an indicator to assess automatic inhibitory function of the sensory cortex. On the other hand, electricity-induced beta rebound oscillation in a single-pulse paradigm reflects cortical inhibition of the motor cortex. From the neurophysiological perspective, SG and beta rebound oscillation are replicable indicators to examine the automatic inhibitory function of human sensorimotor cortices. Thus, the present study aimed to use a whole-head magnetoencephalography (MEG to investigate the age-related alterations of SG function in the primary somatosensory cortex (SI and of beta rebound oscillation in the primary motor cortex (MI in 17 healthy younger and 15 older adults. The Stimulus 2/Stimulus 1 (S2/S1 amplitude ratio in response to the paired-pulse electrical stimulation to the left median nerve was used to evaluate the automatic inhibitory function of SI, and the beta rebound response in the single-pulse paradigm was used to evaluate the automatic inhibitory function of MI. Although there were no significant age-related differences found in the SI SG ratios, the MI beta rebound power was reduced and peak latency was prolonged in the OA. Furthermore, significant association between the SI SG ratio and the MI beta rebound

  16. Age Effect on Automatic Inhibitory Function of the Somatosensory and Motor Cortex: An MEG Study

    Science.gov (United States)

    Cheng, Chia-Hsiung; Lin, Mei-Yin; Yang, Shiou-Han

    2018-01-01

    Age-related deficiency in the top-down modulation of cognitive inhibition has been extensively documented, whereas the effects of age on a bottom-up or automatic operation of inhibitory function were less investigated. It is unknown that whether the older adults (OA)’ reduced behavioral performance and neural responses are due to the insufficient bottom-up processes. Compared to behavioral assessments which have been widely used to examine the top-down control of response inhibition, electrophysiological recordings are more suitable to probe the early-stage processes of automatic inhibitory function. Sensory gating (SG), a phenomenon of attenuated neural response to the second identical stimulus in a paired-pulse paradigm, is an indicator to assess automatic inhibitory function of the sensory cortex. On the other hand, electricity-induced beta rebound oscillation in a single-pulse paradigm reflects cortical inhibition of the motor cortex. From the neurophysiological perspective, SG and beta rebound oscillation are replicable indicators to examine the automatic inhibitory function of human sensorimotor cortices. Thus, the present study aimed to use a whole-head magnetoencephalography (MEG) to investigate the age-related alterations of SG function in the primary somatosensory cortex (SI) and of beta rebound oscillation in the primary motor cortex (MI) in 17 healthy younger and 15 older adults. The Stimulus 2/Stimulus 1 (S2/S1) amplitude ratio in response to the paired-pulse electrical stimulation to the left median nerve was used to evaluate the automatic inhibitory function of SI, and the beta rebound response in the single-pulse paradigm was used to evaluate the automatic inhibitory function of MI. Although there were no significant age-related differences found in the SI SG ratios, the MI beta rebound power was reduced and peak latency was prolonged in the OA. Furthermore, significant association between the SI SG ratio and the MI beta rebound power, which was

  17. Distinction between added-energy and phase-resetting mechanisms in non-invasively detected somatosensory evoked responses.

    Science.gov (United States)

    Fedele, T; Scheer, H-J; Burghoff, M; Waterstraat, G; Nikulin, V V; Curio, G

    2013-01-01

    Non-invasively recorded averaged event-related potentials (ERP) represent a convenient opportunity to investigate human brain perceptive and cognitive processes. Nevertheless, generative ERP mechanisms are still debated. Two previous approaches have been contested in the past: the added-energy model in which the response raises independently from the ongoing background activity, and the phase-reset model, based on stimulus-driven synchronization of oscillatory ongoing activity. Many criteria for the distinction of these two models have been proposed, but there is no definitive methodology to disentangle them, owing also to the limited information at the single trial level. Here, we propose a new approach combining low-noise EEG technology and multivariate decomposition techniques. We present theoretical analyses based on simulated data and identify in high-frequency somatosensory evoked responses an optimal target for the distinction between the two mechanisms.

  18. Effect of surgery on sensory threshold and somatosensory evoked potentials after skin stimulation

    DEFF Research Database (Denmark)

    Lund, C; Hansen, O B; Kehlet, H

    1990-01-01

    We have studied the effect of surgical injury on cutaneous sensitivity and somatosensory evoked potentials (SSEP) to dermatomal electrical stimulation in 10 patients undergoing hysterectomy. Forty-eight hours after surgery, sensory threshold increased from 2.2 (SEM 0.3) mA to 4.4 (1.1) mA (P less...

  19. Atypical visual and somatosensory adaptation in schizophrenia-spectrum disorders

    Science.gov (United States)

    Andrade, G N; Butler, J S; Peters, G A; Molholm, S; Foxe, J J

    2016-01-01

    Neurophysiological investigations in patients with schizophrenia consistently show early sensory processing deficits in the visual system. Importantly, comparable sensory deficits have also been established in healthy first-degree biological relatives of patients with schizophrenia and in first-episode drug-naive patients. The clear implication is that these measures are endophenotypic, related to the underlying genetic liability for schizophrenia. However, there is significant overlap between patient response distributions and those of healthy individuals without affected first-degree relatives. Here we sought to develop more sensitive measures of sensory dysfunction in this population, with an eye to establishing endophenotypic markers with better predictive capabilities. We used a sensory adaptation paradigm in which electrophysiological responses to basic visual and somatosensory stimuli presented at different rates (ranging from 250 to 2550 ms interstimulus intervals, in blocked presentations) were compared. Our main hypothesis was that adaptation would be substantially diminished in schizophrenia, and that this would be especially prevalent in the visual system. High-density event-related potential recordings showed amplitude reductions in sensory adaptation in patients with schizophrenia (N=15 Experiment 1, N=12 Experiment 2) compared with age-matched healthy controls (N=15 Experiment 1, N=12 Experiment 2), and this was seen for both sensory modalities. At the individual participant level, reduced adaptation was more robust for visual compared with somatosensory stimulation. These results point to significant impairments in short-term sensory plasticity across sensory modalities in schizophrenia. These simple-to-execute measures may prove valuable as candidate endophenotypes and will bear follow-up in future work. PMID:27163205

  20. Specific properties of the SI and SII somatosensory areas and their effects on motor control: a system neurophysiological study.

    Science.gov (United States)

    Friedrich, Julia; Mückschel, Moritz; Beste, Christian

    2018-03-01

    Sensorimotor integration is essential for successful motor control and the somatosensory modality has been shown to have strong effects on the execution of motor plans. The primary (SI) and the secondary somatosensory (SII) cortices are known to differ in their neuroanatomical connections to prefrontal areas, as well as in their involvement to encode cognitive aspects of tactile processing. Here, we ask whether the area-specific processing architecture or the structural neuroanatomical connections with prefrontal areas determine the efficacy of sensorimotor integration processes for motor control. In a system neurophysiological study including EEG signal decomposition (i.e., residue iteration decomposition, RIDE) and source localization, we investigated this question using vibrotactile stimuli optimized for SI or SII processing. The behavioral data show that when being triggered via the SI area, inhibitory control of motor processes is stronger as when being triggered via the SII area. On a neurophysiological level, these effects were reflected in the C-cluster as a result of a temporal decomposition of EEG data, indicating that the sensory processes affecting motor inhibition modulate the response selection level. These modulations were associated with a stronger activation of the right inferior frontal gyrus extending to the right middle frontal gyrus as parts of a network known to be involved in inhibitory motor control when response inhibition is triggered over SI. In addition, areas important for sensorimotor integration like the postcentral gyrus and superior parietal cortex showed activation differences. The data suggest that connection patterns are more important for sensorimotor integration and control than the more restricted area-specific processing architecture.

  1. Asymmetric multisensory interactions of visual and somatosensory responses in a region of the rat parietal cortex.

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    Michael T Lippert

    Full Text Available Perception greatly benefits from integrating multiple sensory cues into a unified percept. To study the neural mechanisms of sensory integration, model systems are required that allow the simultaneous assessment of activity and the use of techniques to affect individual neural processes in behaving animals. While rodents qualify for these requirements, little is known about multisensory integration and areas involved for this purpose in the rodent. Using optical imaging combined with laminar electrophysiological recordings, the rat parietal cortex was identified as an area where visual and somatosensory inputs converge and interact. Our results reveal similar response patterns to visual and somatosensory stimuli at the level of current source density (CSD responses and multi-unit responses within a strip in parietal cortex. Surprisingly, a selective asymmetry was observed in multisensory interactions: when the somatosensory response preceded the visual response, supra-linear summation of CSD was observed, but the reverse stimulus order resulted in sub-linear effects in the CSD. This asymmetry was not present in multi-unit activity however, which showed consistently sub-linear interactions. These interactions were restricted to a specific temporal window, and pharmacological tests revealed significant local intra-cortical contributions to this phenomenon. Our results highlight the rodent parietal cortex as a system to model the neural underpinnings of multisensory processing in behaving animals and at the cellular level.

  2. The influence of vibrissal somatosensory processing in rat superior colliculus on prey capture.

    Science.gov (United States)

    Favaro, P D N; Gouvêa, T S; de Oliveira, S R; Vautrelle, N; Redgrave, P; Comoli, E

    2011-03-10

    The lateral part of intermediate layer of superior colliculus (SCl) is a critical substrate for successful predation by rats. Hunting-evoked expression of the activity marker Fos is concentrated in SCl while prey capture in rats with NMDA lesions in SCl is impaired. Particularly affected are rapid orienting and stereotyped sequences of actions associated with predation of fast moving prey. Such deficits are consistent with the view that the deep layers of SC are important for sensory guidance of movement. Although much of the relevant evidence involves visual control of movement, less is known about movement guidance by somatosensory input from vibrissae. Indeed, our impression is that prey contact with whiskers is a likely stimulus to trigger predation. Moreover, SCl receives whisker and orofacial somatosensory information directly from trigeminal complex, and indirectly from zona incerta, parvicelular reticular formation and somatosensory barrel cortex. To better understand sensory guidance of predation by vibrissal information we investigated prey capture by rats after whisker removal and the role of superior colliculus (SC) by comparing Fos expression after hunting with and without whiskers. Rats were allowed to hunt cockroaches, after which their whiskers were removed. Two days later they were allowed to hunt cockroaches again. Without whiskers the rats were less able to retain the cockroaches after capture and less able to pursue them in the event of the cockroach escaping. The predatory behaviour of rats with re-grown whiskers returned to normal. In parallel, Fos expression in SCl induced by predation was significantly reduced in whiskerless animals. We conclude that whiskers contribute to the efficiency of rat prey capture and that the loss of vibrissal input to SCl, as reflected by reduced Fos expression, could play a critical role in predatory deficits of whiskerless rats. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. The biology of skin wetness perception and its implications in manual function and for reproducing complex somatosensory signals in neuroprosthetics

    Science.gov (United States)

    Ackerley, Rochelle

    2017-01-01

    Our perception of skin wetness is generated readily, yet humans have no known receptor (hygroreceptor) to signal this directly. It is easy to imagine the sensation of water running over our hands or the feel of rain on our skin. The synthetic sensation of wetness is thought to be produced from a combination of specific skin thermal and tactile inputs, registered through thermoreceptors and mechanoreceptors, respectively. The present review explores how thermal and tactile afference from the periphery can generate the percept of wetness centrally. We propose that the main signals include information about skin cooling, signaled primarily by thinly myelinated thermoreceptors, and rapid changes in touch, through fast-conducting, myelinated mechanoreceptors. Potential central sites for integration of these signals, and thus the perception of skin wetness, include the primary and secondary somatosensory cortices and the insula cortex. The interactions underlying these processes can also be modeled to aid in understanding and engineering the mechanisms. Furthermore, we discuss the role that sensing wetness could play in precision grip and the dexterous manipulation of objects. We expand on these lines of inquiry to the application of the knowledge in designing and creating skin sensory feedback in prosthetics. The addition of real-time, complex sensory signals would mark a significant advance in the use and incorporation of prosthetic body parts for amputees in everyday life. PMID:28123008

  4. Reconstituting development of pancreatic intraepithelial neoplasia from primary human pancreas duct cells

    OpenAIRE

    Lee, Jonghyeob; Snyder, Emily R.; Liu, Yinghua; Gu, Xueying; Wang, Jing; Flowers, Brittany M.; Kim, Yoo Jung; Park, Sangbin; Szot, Gregory L.; Hruban, Ralph H.; Longacre, Teri A.; Kim, Seung K.

    2017-01-01

    Development of systems that reconstitute hallmark features of human pancreatic intraepithelial neoplasia (PanINs), the precursor to pancreatic ductal adenocarcinoma, could generate new strategies for early diagnosis and intervention. However, human cell-based PanIN models with defined mutations are unavailable. Here, we report that genetic modification of primary human pancreatic cells leads to development of lesions resembling native human PanINs. Primary human pancreas duct cells harbouring...

  5. Forkhead Box C1 Regulates Human Primary Keratinocyte Terminal Differentiation.

    Directory of Open Access Journals (Sweden)

    Lianghua Bin

    Full Text Available The epidermis serves as a critical protective barrier between the internal and external environment of the human body. Its remarkable barrier function is established through the keratinocyte (KC terminal differentiation program. The transcription factors specifically regulating terminal differentiation remain largely unknown. Using a RNA-sequencing (RNA-seq profiling approach, we found that forkhead box c 1 (FOXC1 was significantly up-regulated in human normal primary KC during the course of differentiation. This observation was validated in human normal primary KC from several different donors and human skin biopsies. Silencing FOXC1 in human normal primary KC undergoing differentiation led to significant down-regulation of late terminal differentiation genes markers including epidermal differentiation complex genes, keratinization genes, sphingolipid/ceramide metabolic process genes and epidermal specific cell-cell adhesion genes. We further demonstrated that FOXC1 works down-stream of ZNF750 and KLF4, and upstream of GRHL3. Thus, this study defines FOXC1 as a regulator specific for KC terminal differentiation and establishes its potential position in the genetic regulatory network.

  6. Long-term culture and expansion of primary human hepatocytes

    NARCIS (Netherlands)

    Levy, G.; Bomze, D.; Heinz, S.; Ramachandran, S.D.; Noerenberg, A.; Cohen, M.; Shibolet, O.; Sklan, E.; Braspenning, J.C.; Nahmias, Y.

    2015-01-01

    Hepatocytes have a critical role in metabolism, but their study is limited by the inability to expand primary hepatocytes in vitro while maintaining proliferative capacity and metabolic function. Here we describe the oncostatin M (OSM)-dependent expansion of primary human hepatocytes by low

  7. Optogenetic conditioning of paradigm and pattern discrimination in the rat somatosensory system.

    Directory of Open Access Journals (Sweden)

    Kenta Abe

    Full Text Available The rodent whisker-barrel cortical system is a model for studying somatosensory discrimination at high spatiotemporal precision. Here, we applied optogenetics to produce somatosensory inputs in the whisker area using one of transgenic rat lines, W-TChR2V4, which expresses channelrhodopsin-2 (ChR2 in the mechanoreceptive nerve endings around whisker follicles. An awake W-TChR2V4 rat was head-fixed and irradiated by blue LED light on the whisker area with a paradigm conditioned with a reward. The Go task was designed so the rat is allowed to receive a reward, when it licked the nozzle within 5 s after photostimulation. The No-go task was designed so as the rat has to withhold licking for at least 5 s to obtain a reward after photostimulation. The Go-task conditioning was established within 1 hr of training with a reduction in the reaction time and increase of the success rate. To investigate the relationship between the spatiotemporal pattern of sensory inputs and the behavioral output, we designed a multi-optical fiber system that irradiates the whisker area at 9 spots in a 3×3 matrix. Although the Go-task conditioning was established using synchronous irradiation of 9 spots, the success rate was decreased with an increase of the reaction time for the asynchronous irradiation. After conditioning to the Go task, the rat responded to the blue LED flash irradiated on the barrel cortex, where many neurons also express ChR2, or photostimulation of the contralateral whisker area with a similar reaction time and success rate. Synchronous activation of the peripheral mechanoreceptive nerves is suggested to drive a neural circuit in the somatosensory cortex that efficiently couples with the decision. Our optogenetic system would enable the precise evaluation of the psychophysical values, such as the reaction time and success rate, to gain some insight into the brain mechanisms underlying conditioned behaviors.

  8. Control of Somatosensory Cortical Processing by Thalamic Posterior Medial Nucleus: A New Role of Thalamus in Cortical Function.

    Directory of Open Access Journals (Sweden)

    Carlos Castejon

    Full Text Available Current knowledge of thalamocortical interaction comes mainly from studying lemniscal thalamic systems. Less is known about paralemniscal thalamic nuclei function. In the vibrissae system, the posterior medial nucleus (POm is the corresponding paralemniscal nucleus. POm neurons project to L1 and L5A of the primary somatosensory cortex (S1 in the rat brain. It is known that L1 modifies sensory-evoked responses through control of intracortical excitability suggesting that L1 exerts an influence on whisker responses. Therefore, thalamocortical pathways targeting L1 could modulate cortical firing. Here, using a combination of electrophysiology and pharmacology in vivo, we have sought to determine how POm influences cortical processing. In our experiments, single unit recordings performed in urethane-anesthetized rats showed that POm imposes precise control on the magnitude and duration of supra- and infragranular barrel cortex whisker responses. Our findings demonstrated that L1 inputs from POm imposed a time and intensity dependent regulation on cortical sensory processing. Moreover, we found that blocking L1 GABAergic inhibition or blocking P/Q-type Ca2+ channels in L1 prevents POm adjustment of whisker responses in the barrel cortex. Additionally, we found that POm was also controlling the sensory processing in S2 and this regulation was modulated by corticofugal activity from L5 in S1. Taken together, our data demonstrate the determinant role exerted by the POm in the adjustment of somatosensory cortical processing and in the regulation of cortical processing between S1 and S2. We propose that this adjustment could be a thalamocortical gain regulation mechanism also present in the processing of information between cortical areas.

  9. Cytoarchitecture and cortical connections of the posterior cingulate and adjacent somatosensory fields in the rhesus monkey.

    Science.gov (United States)

    Morecraft, R J; Cipolloni, P B; Stilwell-Morecraft, K S; Gedney, M T; Pandya, D N

    2004-01-26

    The cytoarchitecture and connections of the caudal cingulate and medial somatosensory areas were investigated in the rhesus monkey. There is a stepwise laminar differentiation starting from retrosplenial area 30 towards the isocortical regions of the medial parietal cortex. This includes a gradational emphasis on supragranular laminar organization and general reduction of the infragranular neurons as one proceeds from area 30 toward the medial parietal regions, including areas 3, 1, 2, 5, 31, and the supplementary sensory area (SSA). This trend includes a progressive increase in layer IV neurons. Area 23c in the lower bank and transitional somatosensory area (TSA) in the upper bank of the cingulate sulcus appear as nodal points. From area 23c and TSA the architectonic progression can be traced in three directions: one culminates in areas 3a and 3b (core line), the second in areas 1, 2, and 5 (belt line), and the third in areas 31 and SSA (root line). These architectonic gradients are reflected in the connections of these regions. Thus, cingulate areas (30, 23a, and 23b) are connected with area 23c and TSA on the one hand and have widespread connections with parieto-temporal, frontal, and parahippocampal (limbic) regions on the other. Area 23c has connections with areas 30, 23a and b, and TSA as well as with medial somatosensory areas 3, 1, 2, 5, and SSA. Area 23c also has connections with parietotemporal, frontal, and limbic areas similar to areas 30, 23a, and 23b. Area TSA, like area 23c, has connections with areas 3, 1, 2, 5, and SSA. However, it has only limited connections with the parietotemporal and frontal regions and none with the parahippocampal gyrus. Medial area 3 is mainly connected to medial and dorsal sensory areas 3, 1, 2, 5, and SSA and to areas 4 and 6 as well as to supplementary (M2 or area 6m), rostral cingulate (M3 or areas 24c and d), and caudal cingulate (M4 or areas 23c and d) motor cortices. Thus, in parallel with the architectonic gradient

  10. Functional response of cerebral blood flow induced by somatosensory stimulation in rats with subarachnoid hemorrhage

    Science.gov (United States)

    Li, Zhiguo; Huang, Qin; Liu, Peng; Li, Pengcheng; Ma, Lianting; Lu, Jinling

    2015-09-01

    Subarachnoid hemorrhage (SAH) is often accompanied by cerebral vasospasm (CVS), which is the phenomenon of narrowing of large cerebral arteries, and then can produce delayed ischemic neurological deficit (DIND) such as lateralized sensory dysfunction. CVS was regarded as a major contributor to DIND in patients with SAH. However, therapy for preventing vasospasm after SAH to improve the outcomes may not work all the time. It is important to find answers to the relationship between CVS and DIND after SAH. How local cerebral blood flow (CBF) is regulated during functional activation after SAH still remains poorly understood, whereas, the regulation of CBF may play an important role in weakening the impact of CVS on cortex function. Therefore, it is worthwhile to evaluate the functional response of CBF in the activated cortex in an SAH animal model. Most evaluation of the effect of SAH is presently carried out by neurological behavioral scales. The functional imaging of cortical activation during sensory stimulation may help to reflect the function of the somatosensory cortex more locally than the behavioral scales do. We investigated the functional response of CBF in the somatosensory cortex induced by an electrical stimulation to contralateral forepaw via laser speckle imaging in a rat SAH model. Nineteen Sprague-Dawley rats from two groups (control group, n=10 and SAH group, n=9) were studied. SAH was induced in rats by double injection of autologous blood into the cisterna magna after CSF aspiration. The same surgical procedure was applied in the control group without CSF aspiration or blood injection. Significant CVS was found in the SAH group. Meanwhile, we observed a delayed peak of CBF response in rats with SAH compared with those in the control group, whereas no significant difference was found in magnitude, duration, and areas under curve of relative CBF changes between the two groups. The results suggest that the regulation function of local CBF during

  11. Diffuse optical tomography activation in the somatosensory cortex: specific activation by painful vs. non-painful thermal stimuli.

    Directory of Open Access Journals (Sweden)

    Lino Becerra

    2009-11-01

    Full Text Available Pain is difficult to assess due to the subjective nature of self-reporting. The lack of objective measures of pain has hampered the development of new treatments as well as the evaluation of current ones. Functional MRI studies of pain have begun to delineate potential brain response signatures that could be used as objective read-outs of pain. Using Diffuse Optical Tomography (DOT, we have shown in the past a distinct DOT signal over the somatosensory cortex to a noxious heat stimulus that could be distinguished from the signal elicited by innocuous mechanical stimuli. Here we further our findings by studying the response to thermal innocuous and noxious stimuli.Innocuous and noxious thermal stimuli were applied to the skin of the face of the first division (ophthalmic of the trigeminal nerve in healthy volunteers (N = 6. Stimuli temperatures were adjusted for each subject to evoke warm (equivalent to a 3/10 and painful hot (7/10 sensations in a verbal rating scale (0/10 = no/max pain. A set of 26 stimuli (5 sec each was applied for each temperature with inter-stimulus intervals varied between 8 and 15 sec using a Peltier thermode. A DOT system was used to capture cortical responses on both sides of the head over the primary somatosensory cortical region (S1. For the innocuous stimuli, group results indicated mainly activation on the contralateral side with a weak ipsilateral response. For the noxious stimuli, bilateral activation was observed with comparable amplitudes on both sides. Furthermore, noxious stimuli produced a temporal biphasic response while innocuous stimuli produced a monophasic response.These results are in accordance with fMRI and our other DOT studies of innocuous mechanical and noxious heat stimuli. The data indicate the differentiation of DOT cortical responses for pain vs. innocuous stimuli that may be useful in assessing objectively acute pain.

  12. Metastatic behaviour of primary human tumours in a zebrafish xenotransplantation model

    International Nuclear Information System (INIS)

    Marques, Ines J; Bagowski, Christoph P; Weiss, Frank Ulrich; Vlecken, Danielle H; Nitsche, Claudia; Bakkers, Jeroen; Lagendijk, Anne K; Partecke, Lars Ivo; Heidecke, Claus-Dieter; Lerch, Markus M

    2009-01-01

    Aberrant regulation of cell migration drives progression of many diseases, including cancer cell invasion and metastasis formation. Analysis of tumour invasion and metastasis in living organisms to date is cumbersome and involves difficult and time consuming investigative techniques. For primary human tumours we establish here a simple, fast, sensitive and cost-effective in vivo model to analyse tumour invasion and metastatic behaviour. We fluorescently labelled small explants from gastrointestinal human tumours and investigated their metastatic behaviour after transplantation into zebrafish embryos and larvae. The transparency of the zebrafish embryos allows to follow invasion, migration and micrometastasis formation in real-time. High resolution imaging was achieved through laser scanning confocal microscopy of live zebrafish. In the transparent zebrafish embryos invasion, circulation of tumour cells in blood vessels, migration and micrometastasis formation can be followed in real-time. Xenografts of primary human tumours showed invasiveness and micrometastasis formation within 24 hours after transplantation, which was absent when non-tumour tissue was implanted. Furthermore, primary human tumour cells, when organotopically implanted in the zebrafish liver, demonstrated invasiveness and metastatic behaviour, whereas primary control cells remained in the liver. Pancreatic tumour cells showed no metastatic behaviour when injected into cloche mutant embryos, which lack a functional vasculature. Our results show that the zebrafish is a useful in vivo animal model for rapid analysis of invasion and metastatic behaviour of primary human tumour specimen

  13. Tibial nerve somatosensory evoked potentials in dogs with degenerative lumbosacral stenosis.

    Science.gov (United States)

    Meij, Björn P; Suwankong, Niyada; van den Brom, Walter E; Venker-van Haagen, Anjop J; Hazewinkel, Herman A W

    2006-02-01

    To determine somatosensory evoked potentials (SEPs) in dogs with degenerative lumbosacral stenosis (DLS) and in healthy dogs. Clinical and experimental study. Dogs with DLS (n = 21) and 11 clinically normal dogs, age, and weight matched. Under anesthesia, the tibial nerve was stimulated at the caudolateral aspect of the stifle, and lumbar SEP (LSEP) were recorded percutaneously from S1 to T13 at each interspinous space. Cortical SEP (CSEP) were recorded from the scalp. LSEP were identified as the N1-P1 (latency 3-6 ms) and N2-P2 (latency 7-13 ms) wave complexes in the recordings of dogs with DLS and control dogs. Latency of N1-P1 increased and that of N2-P2 decreased as the active recording electrode was moved cranially from S1 to T13. Compared with controls, latencies were significantly delayed in DLS dogs: .8 ms for N1-P1 and 1.7 ms for the N2-P2 complex. CSEP were not different between groups. Surface needle recording of tibial nerve SEP can be used to monitor somatosensory nerve function of pelvic limbs in dogs. In dogs with DLS, the latency of LSEP, but not of CSEP, is prolonged compared with normal dogs. In dogs with lumbosacral pain from DLS, the cauda equina compression is sufficient to affect LSEP at the lumbar level.

  14. Primary structure of the human M2 mitochondrial autoantigen of primary biliary cirrhosis: Dihydrolipoamide acetyltransferase

    International Nuclear Information System (INIS)

    Coppel, R.L.; McNeilage, L.J.; Surh, C.D.; Van De Water, J.; Spithill, T.W.; Whittingham, S.; Gershwin, M.E.

    1988-01-01

    Primary biliary cirrhosis is a chronic, destructive autoimmune liver disease of humans. Patient sera are characterized by a high frequency of autoantibodies to a M r 70,000 mitochondrial antigen a component of the M2 antigen complex. The authors have identified a human cDNA clone encoding the complete amino acid sequence of this autoantigen. The predicted structure has significant similarity with the dihydrolipoamide acetyltransferase of the Escherichia coli pyruvate dehydrogenase multienzyme complex. The human sequence preserves the Glu-Thr-Asp-Lys-Ala motif of the lipoyl-binding site and has two potential binding sites. Expressed fragments of the cDNA react strongly with sera from patients with primary biliary cirrhosis but not with sera from patients with autoimmune chronic active hepatitis or sera from healthy subjects

  15. Human Rights Texts: Converting Human Rights Primary Source Documents into Data.

    Science.gov (United States)

    Fariss, Christopher J; Linder, Fridolin J; Jones, Zachary M; Crabtree, Charles D; Biek, Megan A; Ross, Ana-Sophia M; Kaur, Taranamol; Tsai, Michael

    2015-01-01

    We introduce and make publicly available a large corpus of digitized primary source human rights documents which are published annually by monitoring agencies that include Amnesty International, Human Rights Watch, the Lawyers Committee for Human Rights, and the United States Department of State. In addition to the digitized text, we also make available and describe document-term matrices, which are datasets that systematically organize the word counts from each unique document by each unique term within the corpus of human rights documents. To contextualize the importance of this corpus, we describe the development of coding procedures in the human rights community and several existing categorical indicators that have been created by human coding of the human rights documents contained in the corpus. We then discuss how the new human rights corpus and the existing human rights datasets can be used with a variety of statistical analyses and machine learning algorithms to help scholars understand how human rights practices and reporting have evolved over time. We close with a discussion of our plans for dataset maintenance, updating, and availability.

  16. Exposure to Music and Noise During Pregnancy Influences Neurogenesis and Thickness in Motor and Somatosensory Cortex of Rat Pups

    Directory of Open Access Journals (Sweden)

    Chang-Hee Kim

    2013-09-01

    Full Text Available Purpose Prenatal environmental conditions affect the development of the fetus. In the present study, we investigated the effects of exposure to music and noise during pregnancy on neurogenesis and thickness in the motor and somatosensory cortex of rat pups. Methods The pregnant rats in the music-applied group were exposed to 65 dB of comfortable music for 1 hour, once per day, from the 15th day of pregnancy until delivery. The pregnant rats in the noise-applied group were exposed to 95 dB of sound from a supersonic sound machine for 1 hour, once per day, from the 15th day of pregnancy until delivery. After birth, the offspring were left undisturbed together with their mother. The rat pups were sacrificed at 21 days after birth. Results Exposure to music during pregnancy increased neurogenesis in the motor and somatosensory cortex of rat pups. In contrast, rat pups exposed to noise during pregnancy showed decreased neurogenesis and thickness in the motor and somatosensory cortex. Conclusions Our study suggests that music and noise during the developmental period are important factors influencing brain development and urogenital disorders.

  17. Presurgical motor, somatosensory and language fMRI: Technical feasibility and limitations in 491 patients over 13 years

    International Nuclear Information System (INIS)

    Tyndall, Anthony J.; Reinhardt, Julia; Stippich, Christoph; Tronnier, Volker; Mariani, Luigi

    2017-01-01

    To analyse the long-term feasibility and limitations of presurgical fMRI in a cohort of tumour and epilepsy patients with different MR-scanners at 1.5 and 3.0 T. Four hundred and ninety-one consecutive patients undergoing presurgical fMRI between 2000 and 2012 on five different MR-scanners using established paradigms and semi-automated data processing were included. Success rates of task performance and BOLD-activation were determined for motor and somatosensory somatotopic mapping and language localisation. Procedural success, failures and imaging artifacts were analysed. MR-field strengths were compared. Two thousand three hundred fifteen of 2348 (98.6 %) attempted paradigms (1033 motor, 1220 speech, 95 somatosensory) were successfully performed. 100 paradigms (4.3 %) were repetition runs. 23 speech, 6 motor and 2 sensory paradigms failed for non-compliance and technical issues. Most language paradigm failures were noted in overt sentence generation. Average significant BOLD-activation was higher for motor than language paradigms (95.8 vs. 81.6 %). Most language paradigms showed significantly higher activation rates at 3 T compared to 1.5 T, whereas no significant difference was found for motor paradigms. fMRI proved very robust for the presurgical localisation of the different motor and somatosensory body representations, as well as Broca's and Wernicke's language areas across different MR-scanners at 1.5 and 3.0 T over 13 years. (orig.)

  18. Presurgical motor, somatosensory and language fMRI: Technical feasibility and limitations in 491 patients over 13 years

    Energy Technology Data Exchange (ETDEWEB)

    Tyndall, Anthony J.; Reinhardt, Julia; Stippich, Christoph [University Hospital Basel, Division of Diagnostic and Interventional Neuroradiology, Basel (Switzerland); Tronnier, Volker [University Hospital Schleswig-Holstein, Luebeck Campus, Department of Neurosurgery, Luebeck (Germany); Mariani, Luigi [University Hospitals Basel, Department of Neurosurgery, Basel (Switzerland)

    2017-01-15

    To analyse the long-term feasibility and limitations of presurgical fMRI in a cohort of tumour and epilepsy patients with different MR-scanners at 1.5 and 3.0 T. Four hundred and ninety-one consecutive patients undergoing presurgical fMRI between 2000 and 2012 on five different MR-scanners using established paradigms and semi-automated data processing were included. Success rates of task performance and BOLD-activation were determined for motor and somatosensory somatotopic mapping and language localisation. Procedural success, failures and imaging artifacts were analysed. MR-field strengths were compared. Two thousand three hundred fifteen of 2348 (98.6 %) attempted paradigms (1033 motor, 1220 speech, 95 somatosensory) were successfully performed. 100 paradigms (4.3 %) were repetition runs. 23 speech, 6 motor and 2 sensory paradigms failed for non-compliance and technical issues. Most language paradigm failures were noted in overt sentence generation. Average significant BOLD-activation was higher for motor than language paradigms (95.8 vs. 81.6 %). Most language paradigms showed significantly higher activation rates at 3 T compared to 1.5 T, whereas no significant difference was found for motor paradigms. fMRI proved very robust for the presurgical localisation of the different motor and somatosensory body representations, as well as Broca's and Wernicke's language areas across different MR-scanners at 1.5 and 3.0 T over 13 years. (orig.)

  19. Immediate effects of somatosensory stimulation on hand function in patients with poststroke hemiparesis: a randomized cross-over trial.

    Science.gov (United States)

    Sim, Sun-Mi; Oh, Duck-Won; Chon, Seung-chul

    2015-12-01

    This study aimed to determine the immediate effects of somatosensory stimulation on hand function in patients with poststroke hemiparesis. Eleven patients with poststroke hemiparesis participated in this study. Four types (no stimulation, vibration, and light and rough touches) of somatosensory stimulation were performed randomly for 4 days applying only one type of somatosensory stimulation each day. The box and block test (BBT), the Jebsen-Taylor hand function test (JTHFT), hand grip strength (HGS), and movement distance and peak velocity of the wrist joint during a forward-reaching task were measured. The BBT and JTHFT scores for no stimulation [BBT: median (interquartile range), 0.00 (-1.00 to 1.00) and JTHFT: 2.57 (-0.47 to 4.92)] were significantly different from those for vibration [BBT: 3.00 (2.00-5.00) and JTHFT: -16.02 (-23.06 to -4.31)], light touch [BBT: 3.00 (1.00-4.00) and JTHFT: -5.00 (-21.20 to -0.94)], and rough touch [BBT: 2.00 (1.00-4.00) and JTHFT: -6.19 (-18.22 to -3.70)]. The JTHFT score was significantly higher for vibration than that for rough touch (Phemiparesis, with more favorable effects observed in vibration stimulation.

  20. Imaging the spatio-temporal dynamics of supragranular activity in the rat somatosensory cortex in response to stimulation of the paws.

    Directory of Open Access Journals (Sweden)

    M L Morales-Botello

    Full Text Available We employed voltage-sensitive dye (VSD imaging to investigate the spatio-temporal dynamics of the responses of the supragranular somatosensory cortex to stimulation of the four paws in urethane-anesthetized rats. We obtained the following main results. (1 Stimulation of the contralateral forepaw evoked VSD responses with greater amplitude and smaller latency than stimulation of the contralateral hindpaw, and ipsilateral VSD responses had a lower amplitude and greater latency than contralateral responses. (2 While the contralateral stimulation initially activated only one focus, the ipsilateral stimulation initially activated two foci: one focus was typically medial to the focus activated by contralateral stimulation and was stereotaxically localized in the motor cortex; the other focus was typically posterior to the focus activated by contralateral stimulation and was stereotaxically localized in the somatosensory cortex. (3 Forepaw and hindpaw somatosensory stimuli activated large areas of the sensorimotor cortex, well beyond the forepaw and hindpaw somatosensory areas of classical somatotopic maps, and forepaw stimuli activated larger cortical areas with greater activation velocity than hindpaw stimuli. (4 Stimulation of the forepaw and hindpaw evoked different cortical activation dynamics: forepaw responses displayed a clear medial directionality, whereas hindpaw responses were much more uniform in all directions. In conclusion, this work offers a complete spatio-temporal map of the supragranular VSD cortical activation in response to stimulation of the paws, showing important somatotopic differences between contralateral and ipsilateral maps as well as differences in the spatio-temporal activation dynamics in response to forepaw and hindpaw stimuli.

  1. Pheromones enhance somatosensory processing in newt brains through a vasotocin-dependent mechanism.

    Science.gov (United States)

    Thompson, R R; Dickinson, P S; Rose, J D; Dakin, K A; Civiello, G M; Segerdahl, A; Bartlett, R

    2008-07-22

    We tested whether the sex pheromones that stimulate courtship clasping in male roughskin newts do so, at least in part, by amplifying the somatosensory signals that directly trigger the motor pattern associated with clasping and, if so, whether that amplification is dependent on endogenous vasotocin (VT). Female olfactory stimuli increased the number of action potentials recorded in the medulla of males in response to tactile stimulation of the cloaca, which triggers the clasp motor reflex, as well as to tactile stimulation of the snout and hindlimb. That enhancement was blocked by exposing the medulla to a V1a receptor antagonist before pheromone exposure. However, the antagonist did not affect medullary responses to tactile stimuli in the absence of pheromone exposure, suggesting that pheromones amplify somatosensory signals by inducing endogenous VT release. The ability of VT to couple sensory systems together in response to social stimulation could allow this peptide to induce variable behavioural outcomes, depending on the immediate context of the social interaction and thus on the nature of the associated stimuli that are amplified. If widespread in vertebrates, this mechanism could account for some of the behavioural variability associated with this and related peptides both within and across species.

  2. Electrical somatosensory stimulation followed by motor training of the paretic upper limb in acute stroke

    DEFF Research Database (Denmark)

    Ghaziani, Emma; Couppé, Christian; Henkel, Cecilie

    2017-01-01

    functioning is most pronounced during the first 4 weeks post stroke, there are few studies investigating the effect of rehabilitation during this critical time window. The purpose of this trial is to determine the effect of electrical somatosensory stimulation (ESS) initiated in the acute stroke phase...

  3. The influence of visual perspective on the somatosensory steady-state response during pain observation

    Directory of Open Access Journals (Sweden)

    Dora Linsey Canizales

    2013-12-01

    Full Text Available The observation and evaluation of other's pain activate part of the neuronal network involved in the actual experience of pain, including those regions subserving the sensori-discriminative dimension of pain. This was largely interpreted as evidence showing that part of the painful experience can be shared vicariously. Here, we investigated the effect of the visual perspective from which other people’s pain is seen on the cortical response to continuous 25 Hz non-painful somatosensory stimulation (somatosensory steady-state response: SSSR. Based on the shared representation framework, we expected first-person visual perspective (1PP to yield more changes in cortical activity than third-person visual perspective (3PP during pain observation. Twenty healthy adults were instructed to rate a series of pseudo-dynamic pictures depicting hands in either painful or non-painful scenarios, presented either in 1PP (0°-45° angle or 3PP (180° angle, while changes in brain activity was measured with a 128-electode EEG system. The ratings demonstrated that the same scenarios were rated on average as more painful when observed from the 1PP than from the 3PP. As expected from previous works, the SSSR response was decreased after stimulus onset over the left caudal part of the parieto-central cortex, contralateral to the stimulation side. Moreover, the difference between the SSSR was of greater amplitude when the painful situations were presented from the 1PP compared to the 3PP. Together, these results suggest that a visuospatial congruence between the viewer and the observed scenarios is associated with both a higher subjective evaluation of pain and an increased modulation in the somatosensory representation of observed pain. These findings are discussed with regards to the potential role of visual perspective in pain communication and empathy.

  4. [Characterization of epithelial primary culture from human conjunctiva].

    Science.gov (United States)

    Rivas, L; Blázquez, A; Muñoz-Negrete, F J; López, S; Rebolleda, G; Domínguez, F; Pérez-Esteban, A

    2014-01-01

    To evaluate primary cultures from human conjunctiva supplemented with fetal bovine serum, autologous serum, and platelet-rich autologous serum, over human amniotic membrane and lens anterior capsules. One-hundred and forty-eight human conjunctiva explants were cultured in CnT50(®) supplemented with 1, 2.5, 5 and 10% fetal bovine serum, autologous serum and platelet-rich autologous serum. Conjunctival samples were incubated at 37°C, 5% CO2 and 95% HR, for 3 weeks. The typical phenotype corresponding to conjunctival epithelial cells was present in all primary cultures. Conjunctival cultures had MUC5AC-positive secretory cells, K19-positive conjunctival cells, and MUC4-positive non-secretory conjunctival cells, but were not corneal phenotype (cytokeratin K3-negative) and fibroblasts (CD90-negative). Conjunctiva epithelial progenitor cells were preserved in all cultures; thus, a cell culture in CnT50(®) supplemented with 1 to 5% autologous serum over human amniotic membrane can provide better information of epithelial cell differentiation for the conjunctival surface reconstruction. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  5. A 2.5-D Representation of the Human Hand

    Science.gov (United States)

    Longo, Matthew R.; Haggard, Patrick

    2012-01-01

    Primary somatosensory maps in the brain represent the body as a discontinuous, fragmented set of two-dimensional (2-D) skin regions. We nevertheless experience our body as a coherent three-dimensional (3-D) volumetric object. The links between these different aspects of body representation, however, remain poorly understood. Perceiving the body's…

  6. Motor and somatosensory conversion disorder: a functional unawareness syndrome?

    Science.gov (United States)

    Perez, David L; Barsky, Arthur J; Daffner, Kirk; Silbersweig, David A

    2012-01-01

    Although conversion disorder is closely connected to the origins of neurology and psychiatry, it remains poorly understood. In this article, the authors discuss neural and clinical parallels between lesional unawareness disorders and unilateral motor and somatosensory conversion disorder, emphasizing functional neuroimaging/disease correlates. Authors suggest that a functional-unawareness neurobiological framework, mediated by right hemisphere-lateralized, large-scale brain network dysfunction, may play a significant role in the neurobiology of conversion disorder. The perigenual anterior cingulate and the posterior parietal cortices are detailed as important in disease pathophysiology. Further investigations will refine the functional-unawareness concept, clarify the role of affective circuits, and delineate the process through which functional neurologic symptoms emerge.

  7. From acute to persistent low back pain: a longitudinal investigation of somatosensory changes using quantitative sensory testing—an exploratory study

    Science.gov (United States)

    Marcuzzi, Anna; Wrigley, Paul J.; Dean, Catherine M.; Graham, Petra L.; Hush, Julia M.

    2018-01-01

    Abstract Introduction: Chronic low back pain (LBP) is commonly associated with generalised pain hypersensitivity. It is suggested that such somatosensory alterations are important determinants for the transition to persistent pain from an acute episode of LBP. Although cross-sectional research investigating somatosensory function in the acute stage is developing, no longitudinal studies designed to evaluate temporal changes have been published. Objectives: This exploratory study aimed to investigate the temporal development of somatosensory changes from the acute stage of LBP to up to 4 months from onset. Methods: Twenty-five people with acute LBP (pain-free controls were prospectively assessed at baseline using quantitative sensory testing with the assessor blinded to group allocation, and again at 2 and 4 months. Psychological variables were concurrently assessed. People with acute LBP were classified based on their average pain severity over the previous week at 4 months as recovered (≤1/10 numeric rating scale) or persistent (≥2/10 numeric rating scale) LBP. Results: In the persistent LBP group, (1) there was a significant decrease in pressure pain threshold between 2 and 4 months (P pain threshold was significantly different from the recovered LBP group (P pain-free control reference value. Pain-related psychological variables were significantly higher in those with persistent LBP compared with the recovered LBP group at all time points (P pain sensitivity occurring in the subacute stage warrant further longitudinal evaluation to better understand the role of somatosensory changes in the development of persistent LBP. Pain-related cognitions at baseline distinguished persistent from the recovered LBP groups, emphasizing the importance of concurrent evaluation of psychological contributors in acute LBP. PMID:29756087

  8. From acute to persistent low back pain: a longitudinal investigation of somatosensory changes using quantitative sensory testing-an exploratory study.

    Science.gov (United States)

    Marcuzzi, Anna; Wrigley, Paul J; Dean, Catherine M; Graham, Petra L; Hush, Julia M

    2018-03-01

    Chronic low back pain (LBP) is commonly associated with generalised pain hypersensitivity. It is suggested that such somatosensory alterations are important determinants for the transition to persistent pain from an acute episode of LBP. Although cross-sectional research investigating somatosensory function in the acute stage is developing, no longitudinal studies designed to evaluate temporal changes have been published. This exploratory study aimed to investigate the temporal development of somatosensory changes from the acute stage of LBP to up to 4 months from onset. Twenty-five people with acute LBP (testing with the assessor blinded to group allocation, and again at 2 and 4 months. Psychological variables were concurrently assessed. People with acute LBP were classified based on their average pain severity over the previous week at 4 months as recovered (≤1/10 numeric rating scale) or persistent (≥2/10 numeric rating scale) LBP. In the persistent LBP group, (1) there was a significant decrease in pressure pain threshold between 2 and 4 months ( P psychological variables were significantly higher in those with persistent LBP compared with the recovered LBP group at all time points ( P importance of concurrent evaluation of psychological contributors in acute LBP.

  9. The biology of skin wetness perception and its implications in manual function and for reproducing complex somatosensory signals in neuroprosthetics.

    Science.gov (United States)

    Filingeri, Davide; Ackerley, Rochelle

    2017-04-01

    Our perception of skin wetness is generated readily, yet humans have no known receptor (hygroreceptor) to signal this directly. It is easy to imagine the sensation of water running over our hands or the feel of rain on our skin. The synthetic sensation of wetness is thought to be produced from a combination of specific skin thermal and tactile inputs, registered through thermoreceptors and mechanoreceptors, respectively. The present review explores how thermal and tactile afference from the periphery can generate the percept of wetness centrally. We propose that the main signals include information about skin cooling, signaled primarily by thinly myelinated thermoreceptors, and rapid changes in touch, through fast-conducting, myelinated mechanoreceptors. Potential central sites for integration of these signals, and thus the perception of skin wetness, include the primary and secondary somatosensory cortices and the insula cortex. The interactions underlying these processes can also be modeled to aid in understanding and engineering the mechanisms. Furthermore, we discuss the role that sensing wetness could play in precision grip and the dexterous manipulation of objects. We expand on these lines of inquiry to the application of the knowledge in designing and creating skin sensory feedback in prosthetics. The addition of real-time, complex sensory signals would mark a significant advance in the use and incorporation of prosthetic body parts for amputees in everyday life. NEW & NOTEWORTHY Little is known about the underlying mechanisms that generate the perception of skin wetness. Humans have no specific hygroreceptor, and thus temperature and touch information combine to produce wetness sensations. The present review covers the potential mechanisms leading to the perception of wetness, both peripherally and centrally, along with their implications for manual function. These insights are relevant to inform the design of neuroengineering interfaces, such as sensory

  10. fMRI assessment of somatotopy in human Brodmann area 3b by electrical finger stimulation.

    Science.gov (United States)

    Kurth, R; Villringer, K; Mackert, B M; Schwiemann, J; Braun, J; Curio, G; Villringer, A; Wolf, K J

    1998-01-26

    Functional magnetic resonance imaging (fMRI) is capable of detecting focal brain activation induced by electrical stimulation of single fingers in human subjects. In eight subjects somatotopic arrangement of the second and fifth finger was found in Brodmann area 3b of the primary somatosensory cortex. In four subjects the representation area of the second finger was located lateral and inferior to the fifth finger; in one subject the somatotopy was reversed. In three subjects representation areas of the two fingers in Brodmann area 3b were found overlapping. Additional activated areas were found on the crown of ipsilateral and contralateral postcentral gyrus (Brodmann areas 1 and 2) and posterior parietal cortex.

  11. Human primary visual cortex topography imaged via positron tomography

    International Nuclear Information System (INIS)

    Schwartz, E.L.; Christman, D.R.; Wolf, A.P.

    1984-01-01

    The visuotopic structure of primary visual cortex was studied in a group of 7 human volunteers using positron emission transaxial tomography (PETT) and 18 F-labeled 2-deoxy-2-fluoro-D-glucose ([ 18 F]DG). A computer animation was constructed with a spatial structure which was matched to estimates of human cortical magnification factor and to striate cortex stimulus preferences. A lateralized cortical 'checker-board' pattern of [ 18 F]DG was stimulated in primary visual cortex by having subjects view this computer animation following i.v. injection of [ 18 F]DG. The spatial structure of the stimulus was designed to produce an easily recognizable 'signature' in a series of 9 serial PETT scans obtained from each of a group of 7 volunteers. The predicted lateralized topographic 'signature' was observed in 6 of 7 subjects. Applications of this method for further PETT studies of human visual cortex are discussed. (Auth.)

  12. Central Somatosensory Networks Respond to a De Novo Innervated Penis: A Proof of Concept in Three Spina Bifida Patients.

    Science.gov (United States)

    Kortekaas, Rudie; Nanetti, Luca; Overgoor, Max L E; de Jong, Bauke M; Georgiadis, Janniko R

    2015-09-01

    Spina bifida (SB) causes low spinal lesions, and patients often have absent genital sensation and a highly impaired sex life. TOMAX (TO MAX-imize sensation, sexuality and quality of life) is a surgical procedure whereby the penis is newly innervated using a sensory nerve originally targeting the inguinal area. Most TOMAX-treated SB patients initially experience penile stimulation as inguinal sensation, but eventually, the perception shifts to penis sensation with erotic feelings. The brain mechanisms mediating this perceptual shift, which are completely unknown, could hold relevance for understanding the brain's role in sexual development. The aim of this study was to study how a newly perceived penis would be mapped onto the brain after a lifelong disconnection. Three TOMAX-treated SB patients participated in a functional magnetic resonance imagery experiment while glans penis, inguinal area, and index finger were stimulated with a paint brush. Brush stimulation-induced activation of the primary somatosensory cortex (SI) and functional connectivity between SI and remote cerebral regions. Stimulation of the re-innervated side of the glans penis and the intact contralateral inguinal area activated a very similar location on SI. Yet, connectivity analysis identified distinct SI functional networks. In all three subjects, the middle cingulate cortex (MCC) and the parietal operculum-insular cortex (OIC) were functionally connected to SI activity during glans penis stimulation, but not to SI activity induced by inguinal stimulation. Investigating central somatosensory network activity to a de novo innervated penis in SB patients is feasible and informative. The consistent involvement of MCC and OIC above and beyond the brain network expected on the basis of inguinal stimulation suggests that these areas mediate the novel penis sensation in these patients. The potential role of MCC and OIC in this process is discussed, along with recommendations for further research.

  13. Water-filled training tubes increase core muscle activation and somatosensory control of balance during squat.

    Science.gov (United States)

    Ditroilo, Massimiliano; O'Sullivan, Rory; Harnan, Brian; Crossey, Aislinn; Gillmor, Beth; Dardis, William; Grainger, Adam

    2018-09-01

    This study examined trunk muscle activation, balance and proprioception while squatting with a water-filled training tube (WT) and a traditional barbell (BB), with either closed (CE) or open eyes (OE). Eighteen male elite Gaelic footballers performed an isometric squat under the following conditions: BB-OE, BB-CE, WT-OE and WT-CE. The activity of rectus abdominis (RA), external oblique (EO) and multifidus (MF) was measured using electromyography, along with sway of the centre of pressure (CoP) using a force platform. Only the EO and the MF muscles exhibited an increased activity with WT (p velocity and range of the CoP increased significantly with WT (p velocity of the CoP was marginally reduced (d = 0.29). WT elicited a greater level core muscle activation and created a greater challenge to postural stability when compared to a BB. It appears that WT does not benefit from vision but emphasises the somatosensory control of balance. The use of WT may be beneficial in those sports requiring development of somatosensory/proprioceptive contribution to balance control.

  14. Somatosensory neuron types identified by high-coverage single-cell RNA-sequencing and functional heterogeneity

    Science.gov (United States)

    Li, Chang-Lin; Li, Kai-Cheng; Wu, Dan; Chen, Yan; Luo, Hao; Zhao, Jing-Rong; Wang, Sa-Shuang; Sun, Ming-Ming; Lu, Ying-Jin; Zhong, Yan-Qing; Hu, Xu-Ye; Hou, Rui; Zhou, Bei-Bei; Bao, Lan; Xiao, Hua-Sheng; Zhang, Xu

    2016-01-01

    Sensory neurons are distinguished by distinct signaling networks and receptive characteristics. Thus, sensory neuron types can be defined by linking transcriptome-based neuron typing with the sensory phenotypes. Here we classify somatosensory neurons of the mouse dorsal root ganglion (DRG) by high-coverage single-cell RNA-sequencing (10 950 ± 1 218 genes per neuron) and neuron size-based hierarchical clustering. Moreover, single DRG neurons responding to cutaneous stimuli are recorded using an in vivo whole-cell patch clamp technique and classified by neuron-type genetic markers. Small diameter DRG neurons are classified into one type of low-threshold mechanoreceptor and five types of mechanoheat nociceptors (MHNs). Each of the MHN types is further categorized into two subtypes. Large DRG neurons are categorized into four types, including neurexophilin 1-expressing MHNs and mechanical nociceptors (MNs) expressing BAI1-associated protein 2-like 1 (Baiap2l1). Mechanoreceptors expressing trafficking protein particle complex 3-like and Baiap2l1-marked MNs are subdivided into two subtypes each. These results provide a new system for cataloging somatosensory neurons and their transcriptome databases. PMID:26691752

  15. Transcriptional profiling at whole population and single cell levels reveals somatosensory neuron molecular diversity

    Science.gov (United States)

    Chiu, Isaac M; Barrett, Lee B; Williams, Erika K; Strochlic, David E; Lee, Seungkyu; Weyer, Andy D; Lou, Shan; Bryman, Gregory S; Roberson, David P; Ghasemlou, Nader; Piccoli, Cara; Ahat, Ezgi; Wang, Victor; Cobos, Enrique J; Stucky, Cheryl L; Ma, Qiufu; Liberles, Stephen D; Woolf, Clifford J

    2014-01-01

    The somatosensory nervous system is critical for the organism's ability to respond to mechanical, thermal, and nociceptive stimuli. Somatosensory neurons are functionally and anatomically diverse but their molecular profiles are not well-defined. Here, we used transcriptional profiling to analyze the detailed molecular signatures of dorsal root ganglion (DRG) sensory neurons. We used two mouse reporter lines and surface IB4 labeling to purify three major non-overlapping classes of neurons: 1) IB4+SNS-Cre/TdTomato+, 2) IB4−SNS-Cre/TdTomato+, and 3) Parv-Cre/TdTomato+ cells, encompassing the majority of nociceptive, pruriceptive, and proprioceptive neurons. These neurons displayed distinct expression patterns of ion channels, transcription factors, and GPCRs. Highly parallel qRT-PCR analysis of 334 single neurons selected by membership of the three populations demonstrated further diversity, with unbiased clustering analysis identifying six distinct subgroups. These data significantly increase our knowledge of the molecular identities of known DRG populations and uncover potentially novel subsets, revealing the complexity and diversity of those neurons underlying somatosensation. DOI: http://dx.doi.org/10.7554/eLife.04660.001 PMID:25525749

  16. Seeing touch in the somatosensory cortex: a TMS study of the visual perception of touch.

    Science.gov (United States)

    Bolognini, Nadia; Rossetti, Angela; Maravita, Angelo; Miniussi, Carlo

    2011-12-01

    Recent studies suggest the existence of a visuo-tactile mirror system, comprising the primary (SI) and secondary (SII) somatosensory cortices, which matches observed touch with felt touch. Here, repetitive transcranial magnetic stimulation (rTMS) was used to determine whether SI or SII play a functional role in the visual processing of tactile events. Healthy participants performed a visual discrimination task with tactile stimuli (a finger touching a hand) and a control task (a finger moving without touching). During both tasks, rTMS was applied over either SI or SII, and to the occipital cortex. rTMS over SI selectively reduced subject performance for interpreting whether a contralateral visual tactile stimulus contains a tactile event, whereas SII stimulation impaired visual processing regardless of the tactile component. These findings provide evidence for a multimodal sensory-motor system with mirror properties, where somatic and visual properties of action converge. SI, a cortical area traditionally viewed as modality-specific, is selectively implicated in the visual processing of touch. These results are in line with the existence of a sensory mirror system mediating the embodied simulation concept. Copyright © 2010 Wiley Periodicals, Inc.

  17. Evaluation of perfluoroalkyl acid activity using primary mouse and human hepatocytes

    International Nuclear Information System (INIS)

    Rosen, Mitchell B.; Das, Kaberi P.; Wood, Carmen R.; Wolf, Cynthia J.; Abbott, Barbara D.; Lau, Christopher

    2013-01-01

    While perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been studied at length, less is known about the biological activity of other perfluoroalkyl acids (PFAAs) detected in the environment. Using a transient transfection assay developed in COS-1 cells, our group has previously evaluated a variety of PFAAs for activity associated with activation of peroxisome proliferator-activated receptor alpha (PPARα). Here we use primary heptatocytes to further assess the biological activity of a similar group of PFAAs using custom designed Taqman Low Density Arrays. Primary mouse and human hepatoyctes were cultured for 48 h in the presence of varying concentrations of 12 different PFAAs or Wy14,643, a known activator of PPARα. Total RNA was collected and the expression of 48 mouse or human genes evaluated. Gene selection was based on either in-house liver microarray data (mouse) or published data using primary hepatocytes (human). Gene expression in primary mouse hepatocytes was more restricted than expected. Genes typically regulated in whole tissue by PPARα agonists were not altered in mouse cells including Acox1, Me1, Acaa1a, Hmgcs1, and Slc27a1. Cyp2b10, a gene regulated by the constitutive androstane receptor and a transcript normally up-regulated by in vivo exposure to PFAAs, was also unchanged in cultured mouse hepatocytes. Cyp4a14, Ehhadh, Pdk4, Cpt1b, and Fabp1 were regulated as expected in mouse cells. A larger group of genes were differentially expressed in human primary hepatocytes, however, little consistency was observed across compounds with respect to which genes produced a significant dose response making the determination of relative biological activity difficult. This likely reflects weaker activation of PPARα in human versus rodent cells as well as variation among individual cell donors. Unlike mouse cells, CYP2B6 was up-regulated in human hepatocytes by a number of PFAAs as was PPARδ. Rankings were conducted on the limited

  18. Decreased Somatosensory Activity to Non-threatening Touch in Combat Veterans with Posttraumatic Stress Disorder

    OpenAIRE

    Badura-Brack, Amy S.; Becker, Katherine M.; McDermott, Timothy J.; Ryan, Tara J.; Becker, Madelyn M.; Hearley, Allison R.; Heinrichs-Graham, Elizabeth; Wilson, Tony W.

    2015-01-01

    Posttraumatic stress disorder (PTSD) is a severe psychiatric disorder prevalent in combat veterans. Previous neuroimaging studies have demonstrated that patients with PTSD exhibit abnormal responses to non-threatening visual and auditory stimuli, but have not examined somatosensory processing. Thirty male combat veterans, 16 with PTSD and 14 without, completed a tactile stimulation task during a 306-sensor magnetoencephalography (MEG) recording. Significant oscillatory neural responses were i...

  19. An investigation of somatosensory profiles in work related upper limb disorders: a case-control observational study protocol.

    LENUS (Irish Health Repository)

    Moloney, Niamh

    2010-01-01

    BACKGROUND: Work related upper limb disorders constitute 45% of all occupational diseases and are a significant public health problem. A subgroup, non specific arm pain (NSAP), remains elusive in terms of understanding its pathophysiological mechanisms with its diagnosis based on the absence of specific clinical findings. One commonly proposed theory is that a neural tissue disorder is the primary dysfunction in NSAP and findings from previous studies lend some support to this theory. However, it is not clear if changes identified are simply a consequence of ongoing pain rather than due to specific neural changes. The presence of neuropathic pain has been investigated in several other musculoskeletal conditions but currently, there is no specific diagnostic tool or gold standard which permits an unequivocal diagnosis of neuropathic pain. The purpose of this study is to further describe the somatosensory profiles in patients with NSAP and to compare these profiles to a group of patients with MRI confirmed cervical radiculopathy who have been previously classified as having neuropathic pain. METHODS\\/DESIGN: Three groups of participants will be investigated: Groups 1 and 2 will be office workers with either NSAP or cervical radiculopathy and Group 3 will be a control group of non office workers without upper limb pain. Participants will undergo a clinical assessment, pain questionnaires (LANSS, Short Form McGill, DASH and TSK) and quantitative sensory testing comprising thermal detection and pain thresholds, vibration thresholds and pressure pain thresholds. DISCUSSION: The spectrum of clinically suspected neuropathic pain ranges from more obvious conditions such as trigeminal neuralgia to those with vague signs of nerve disorder such as NSAP. A thorough description of the somatosensory profiles of NSAP patients and a comparison with a more defined group of patients with evidence of neuropathic pain will help in the understanding of underlying neurophysiology in

  20. An investigation of somatosensory profiles in work related upper limb disorders: a case-control observational study protocol

    Directory of Open Access Journals (Sweden)

    Hall Toby

    2010-01-01

    Full Text Available Abstract Background Work related upper limb disorders constitute 45% of all occupational diseases and are a significant public health problem. A subgroup, non specific arm pain (NSAP, remains elusive in terms of understanding its pathophysiological mechanisms with its diagnosis based on the absence of specific clinical findings. One commonly proposed theory is that a neural tissue disorder is the primary dysfunction in NSAP and findings from previous studies lend some support to this theory. However, it is not clear if changes identified are simply a consequence of ongoing pain rather than due to specific neural changes. The presence of neuropathic pain has been investigated in several other musculoskeletal conditions but currently, there is no specific diagnostic tool or gold standard which permits an unequivocal diagnosis of neuropathic pain. The purpose of this study is to further describe the somatosensory profiles in patients with NSAP and to compare these profiles to a group of patients with MRI confirmed cervical radiculopathy who have been previously classified as having neuropathic pain. Methods/Design Three groups of participants will be investigated: Groups 1 and 2 will be office workers with either NSAP or cervical radiculopathy and Group 3 will be a control group of non office workers without upper limb pain. Participants will undergo a clinical assessment, pain questionnaires (LANSS, Short Form McGill, DASH and TSK and quantitative sensory testing comprising thermal detection and pain thresholds, vibration thresholds and pressure pain thresholds. Discussion The spectrum of clinically suspected neuropathic pain ranges from more obvious conditions such as trigeminal neuralgia to those with vague signs of nerve disorder such as NSAP. A thorough description of the somatosensory profiles of NSAP patients and a comparison with a more defined group of patients with evidence of neuropathic pain will help in the understanding of underlying

  1. Changes in the somatosensory evoked potentials and spontaneous electroencephalogram of hens during stunning in argon-induced anoxia.

    Science.gov (United States)

    Raj, A B; Gregory, N G; Wotton, S B

    1991-01-01

    This study examined the time to loss of consciousness in hens during stunning in argon-induced anoxia. Somatosensory evoked potentials (SEPs) and the spontaneous electroencephalogram (EEG) were recorded in 12 culled hens prior to and during stunning in less than 2% oxygen (air displaced by argon). An additional 20 hens were stunned with a similar concentration of oxygen and the time to loss of posture, eye closure, and the onset and duration of clonic and tonic convulsions were recorded. A further 10 hens were immersed in less than 2% oxygen for 15-17 s and their response to comb pinching was tested as soon as they had been transferred to atmospheric air. It is concluded that the birds had not lost the primary response in their SEPs by the time they started convulsing, but the reduction in the amplitude of the SEPs, changes in their spontaneous EEG and a negative response to comb pinch before the start of the convulsions indicated that the birds were unconscious when they convulsed.

  2. Vision first? The development of primary visual cortical networks is more rapid than the development of primary motor networks in humans.

    Directory of Open Access Journals (Sweden)

    Patricia Gervan

    Full Text Available The development of cortical functions and the capacity of the mature brain to learn are largely determined by the establishment and maintenance of neocortical networks. Here we address the human development of long-range connectivity in primary visual and motor cortices, using well-established behavioral measures--a Contour Integration test and a Finger-tapping task--that have been shown to be related to these specific primary areas, and the long-range neural connectivity within those. Possible confounding factors, such as different task requirements (complexity, cognitive load are eliminated by using these tasks in a learning paradigm. We find that there is a temporal lag between the developmental timing of primary sensory vs. motor areas with an advantage of visual development; we also confirm that human development is very slow in both cases, and that there is a retained capacity for practice induced plastic changes in adults. This pattern of results seems to point to human-specific development of the "canonical circuits" of primary sensory and motor cortices, probably reflecting the ecological requirements of human life.

  3. Cortical somatosensory-evoked potentials during spine surgery in patients with neuromuscular and idiopathic scoliosis under propofol-remifentanil anaesthesia

    NARCIS (Netherlands)

    Hermanns, H.; Lipfert, P.; Meier, S.; Jetzek-Zader, M.; Krauspe, R.; Stevens, M. F.

    2007-01-01

    BACKGROUND: Intraoperative monitoring of the spinal cord via cortical somatosensory-evoked potentials (SSEP) is a routine during spinal surgery. However, especially in neuromuscular scoliosis, the reliability of cortical SSEP has been questioned. Therefore, we compared the feasibility of cortical

  4. Cellular radiosensitivity and DNA damage in primary human fibroblasts

    International Nuclear Information System (INIS)

    Wurm, R.; Burnet, N.G.; Duggal, N.

    1994-01-01

    To evaluate the relationship between radiation-induced cell survival and DNA damage in primary human fibroblasts to decide whether the initial or residual DNA damage levels are more predictive of normal tissue cellular radiosensitivity. Five primary human nonsyndromic and two primary ataxia telangiectasia fibroblast strains grown in monolayer were studied. Cell survival was assessed by clonogenic assay. Irradiation was given at high dose rate (HDR) 1-2 Gy/min. DNA damage was measured in stationary phase cells and expressed as fraction released from the well by pulsed-field gel electrophoresis (PFGE). For initial damage, cells were embedded in agarose and irradiated at HDR on ice. Residual DNA damage was measured in monolayer by allowing a 4-h repair period after HDR irradiation. Following HDR irradiation, cell survival varied between SF 2 0.025 to 0.23. Measurement of initial DNA damage demonstrated linear induction up to 30 Gy, with small differences in the slope of the dose-response curve between strains. No correlation between cell survival and initial damage was found. Residual damage increased linearly up to 80 Gy with a variation in slope by a factor of 3.2. Cell survival correlated with the slope of the dose-response curves for residual damage of the different strains (p = 0.003). The relationship between radiation-induced cell survival and DNA damage in primary human fibroblasts of differing radiosensitivity is closest with the amount of DNA damage remaining after repair. If assays of DNA damage are to be used as predictors of normal tissue response to radiation, residual DNA damage provides the most likely correlation with cell survival. 52 refs., 5 figs., 2 tabs

  5. Probing region-specific microstructure of human cortical areas using high angular and spatial resolution diffusion MRI.

    Science.gov (United States)

    Aggarwal, Manisha; Nauen, David W; Troncoso, Juan C; Mori, Susumu

    2015-01-15

    Regional heterogeneity in cortical cyto- and myeloarchitecture forms the structural basis of mapping of cortical areas in the human brain. In this study, we investigate the potential of diffusion MRI to probe the microstructure of cortical gray matter and its region-specific heterogeneity across cortical areas in the fixed human brain. High angular resolution diffusion imaging (HARDI) data at an isotropic resolution of 92-μm and 30 diffusion-encoding directions were acquired using a 3D diffusion-weighted gradient-and-spin-echo sequence, from prefrontal (Brodmann area 9), primary motor (area 4), primary somatosensory (area 3b), and primary visual (area 17) cortical specimens (n=3 each) from three human subjects. Further, the diffusion MR findings in these cortical areas were compared with histological silver impregnation of the same specimens, in order to investigate the underlying architectonic features that constitute the microstructural basis of diffusion-driven contrasts in cortical gray matter. Our data reveal distinct and region-specific diffusion MR contrasts across the studied areas, allowing delineation of intracortical bands of tangential fibers in specific layers-layer I, layer VI, and the inner and outer bands of Baillarger. The findings of this work demonstrate unique sensitivity of diffusion MRI to differentiate region-specific cortical microstructure in the human brain, and will be useful for myeloarchitectonic mapping of cortical areas as well as to achieve an understanding of the basis of diffusion NMR contrasts in cortical gray matter. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Functional sex differences in human primary auditory cortex

    NARCIS (Netherlands)

    Ruytjens, Liesbet; Georgiadis, Janniko R.; Holstege, Gert; Wit, Hero P.; Albers, Frans W. J.; Willemsen, Antoon T. M.

    2007-01-01

    Background We used PET to study cortical activation during auditory stimulation and found sex differences in the human primary auditory cortex (PAC). Regional cerebral blood flow (rCBF) was measured in 10 male and 10 female volunteers while listening to sounds (music or white noise) and during a

  7. Telomerase-mediated life-span extension of human primary fibroblasts by human artificial chromosome (HAC) vector

    International Nuclear Information System (INIS)

    Shitara, Shingo; Kakeda, Minoru; Nagata, Keiko; Hiratsuka, Masaharu; Sano, Akiko; Osawa, Kanako; Okazaki, Akiyo; Katoh, Motonobu; Kazuki, Yasuhiro; Oshimura, Mitsuo; Tomizuka, Kazuma

    2008-01-01

    Telomerase-mediated life-span extension enables the expansion of normal cells without malignant transformation, and thus has been thought to be useful in cell therapies. Currently, integrating vectors including the retrovirus are used for human telomerase reverse transcriptase (hTERT)-mediated expansion of normal cells; however, the use of these vectors potentially causes unexpected insertional mutagenesis and/or activation of oncogenes. Here, we established normal human fibroblast (hPF) clones retaining non-integrating human artificial chromosome (HAC) vectors harboring the hTERT expression cassette. In hTERT-HAC/hPF clones, we observed the telomerase activity and the suppression of senescent-associated SA-β-galactosidase activity. Furthermore, the hTERT-HAC/hPF clones continued growing beyond 120 days after cloning, whereas the hPF clones retaining the silent hTERT-HAC senesced within 70 days. Thus, hTERT-HAC-mediated episomal expression of hTERT allows the extension of the life-span of human primary cells, implying that gene delivery by non-integrating HAC vectors can be used to control cellular proliferative capacity of primary cultured cells

  8. Predictive value of neurological examination for early cortical responses to somatosensory evoked potentials in patients with postanoxic coma

    NARCIS (Netherlands)

    Bouwes, Aline; Binnekade, Jan M.; Verbaan, Bart W.; Zandbergen, Eveline G. J.; Koelman, Johannes H. T. M.; Weinstein, Henry C.; Hijdra, Albert; Horn, Janneke

    2012-01-01

    Bilateral absence of cortical N20 responses of median nerve somatosensory evoked potentials (SEP) predicts poor neurological outcome in postanoxic coma after cardiopulmonary resuscitation (CPR). Although SEP is easy to perform and available in most hospitals, it is worthwhile to know how

  9. Neural cell adhesion molecule, NCAM, regulates thalamocortical axon pathfinding and the organization of the cortical somatosensory representation in mouse

    Science.gov (United States)

    Enriquez-Barreto, Lilian; Palazzetti, Cecilia; Brennaman, Leann H.; Maness, Patricia F.; Fairén, Alfonso

    2012-01-01

    To study the potential role of neural cell adhesion molecule (NCAM) in the development of thalamocortical (TC) axon topography, wild type, and NCAM null mutant mice were analyzed for NCAM expression, projection, and targeting of TC afferents within the somatosensory area of the neocortex. Here we report that NCAM and its α-2,8-linked polysialic acid (PSA) are expressed in developing TC axons during projection to the neocortex. Pathfinding of TC axons in wild type and null mutant mice was mapped using anterograde DiI labeling. At embryonic day E16.5, null mutant mice displayed misguided TC axons in the dorsal telencephalon, but not in the ventral telencephalon, an intermediate target that initially sorts TC axons toward correct neocortical areas. During the early postnatal period, rostrolateral TC axons within the internal capsule along the ventral telencephalon adopted distorted trajectories in the ventral telencephalon and failed to reach the neocortex in NCAM null mutant animals. NCAM null mutants showed abnormal segregation of layer IV barrels in a restricted portion of the somatosensory cortex. As shown by Nissl and cytochrome oxidase staining, barrels of the anterolateral barrel subfield (ALBSF) and the most distal barrels of the posteromedial barrel subfield (PMBSF) did not segregate properly in null mutant mice. These results indicate a novel role for NCAM in axonal pathfinding and topographic sorting of TC axons, which may be important for the function of specific territories of sensory representation in the somatosensory cortex. PMID:22723769

  10. Effects of distraction on magnetoencephalographic responses ascending through C-fibers in humans.

    Science.gov (United States)

    Qiu, Yunhai; Inui, Koji; Wang, Xiaohong; Nguyen, Binh Thi; Tran, Tuan Diep; Kakigi, Ryusuke

    2004-03-01

    Using magnetoencephalography (MEG), we evaluated the cerebral regions relating to second pain perception ascending through C-fibers and investigated the effect of distraction on each region. Thirteen normal subjects participated in this study. CO2 laser pulses were delivered to the dorsum of the left hand to selectively activate C-fibers. The MEG responses were analyzed using a multi-dipole model. (1) primary somatosensory cortex (SI), and (2) secondary somatosensory cortex (SII)--insula were the main generators for the primary component, 1M, whose mean peak latency was 744 ms. In addition to (1) and (2), (3) cingulate cortex and (4) medial temporal area (MT) were also activated for the subsequent component, 2M, whose mean peak latency was 947 ms. During a mental calculation task (Distraction), all 6 sources were significantly reduced in amplitude, but the SII-insula (P cognitive aspect of second pain perception. The SI, SII, cingulate and MT were activated during the C-fiber-related MEG response, and responses in these regions were significantly diminished during mental distraction.

  11. Lateralized delay period activity marks the focus of spatial attention in working memory: evidence from somatosensory event-related brain potentials.

    Science.gov (United States)

    Katus, Tobias; Eimer, Martin

    2015-04-29

    The short-term retention of sensory information in working memory (WM) is known to be associated with a sustained enhancement of neural activity. What remains controversial is whether this neural trace indicates the sustained storage of information or the allocation of attention. To evaluate the storage and attention accounts, we examined sustained tactile contralateral delay activity (tCDA component) of the event-related potential. The tCDA manifests over somatosensory cortex contralateral to task-relevant tactile information during stimulus retention. Two tactile sample sets (S1, S2) were presented sequentially, separated by 1.5 s. Each set comprised two stimuli, one per hand. Human participants memorized the location of one task-relevant stimulus per sample set and judged whether one of these locations was stimulated again at memory test. The two relevant pulses were unpredictably located on the same hand (stay trials) or on different hands (shift trials). Initially, tCDA components emerged contralateral to the relevant S1 pulse. Sequential loading of WM enhanced the tCDA after S2 was presented on stay trials. On shift trials, the tCDA's polarity reversed after S2 presentation, resulting in delay activity that was now contralateral to the task-relevant S2 pulse. The disappearance of a lateralized neural trace for the relevant S1 pulse did not impair memory accuracy for this stimulus on shift trials. These results contradict the storage account and suggest that delay period activity indicates the sustained engagement of an attention-based rehearsal mechanism. In conclusion, somatosensory delay period activity marks the current focus of attention in tactile WM. Copyright © 2015 the authors 0270-6474/15/356689-07$15.00/0.

  12. Illusory sensation of movement induced by repetitive transcranial magnetic stimulation

    DEFF Research Database (Denmark)

    Christensen, Mark Schram; Lundbye-Jensen, Jesper; Grey, Michael James

    2010-01-01

    Human movement sense relies on both somatosensory feedback and on knowledge of the motor commands used to produce the movement. We have induced a movement illusion using repetitive transcranial magnetic stimulation over primary motor cortex and dorsal premotor cortex in the absence of limb movement...... and its associated somatosensory feedback. Afferent and efferent neural signalling was abolished in the arm with ischemic nerve block, and in the leg with spinal nerve block. Movement sensation was assessed following trains of high-frequency repetitive transcranial magnetic stimulation applied over...... premotor cortex stimulation was less affected by sensory and motor deprivation than was primary motor cortex stimulation. We propose that repetitive transcranial magnetic stimulation over dorsal premotor cortex produces a corollary discharge that is perceived as movement....

  13. HANPP Collection: Global Patterns in Human Appropriation of Net Primary Productivity (HANPP)

    Data.gov (United States)

    National Aeronautics and Space Administration — The Global Patterns in Human Appropriation of Net Primary Productivity (HANPP) portion of the HANPP Collection represents a digital map of human appropriation of net...

  14. Transfection of Primary Human Skin Fibroblasts for Peroxisomal Studies

    NARCIS (Netherlands)

    Koster, Janet; Waterham, Hans R.

    2017-01-01

    Functional studies with primary human skin fibroblasts from patients with a peroxisomal disorder often require efficient transfection with plasmids to correct the genetic defect or to express heterologous reporter proteins. Here, we describe a protocol we commonly use for efficient nonviral

  15. Characterization of primary cilia and Hedgehog signaling during development of the human pancreas and in human pancreatic duct cancer cell lines

    DEFF Research Database (Denmark)

    Nielsen, Sonja K; Møllgård, Kjeld; Clement, Christian A

    2008-01-01

    Hedgehog (Hh) signaling controls pancreatic development and homeostasis; aberrant Hh signaling is associated with several pancreatic diseases. Here we investigated the link between Hh signaling and primary cilia in the human developing pancreatic ducts and in cultures of human pancreatic duct...... adenocarcinoma cell lines, PANC-1 and CFPAC-1. We show that the onset of Hh signaling from human embryogenesis to fetal development is associated with accumulation of Hh signaling components Smo and Gli2 in duct primary cilia and a reduction of Gli3 in the duct epithelium. Smo, Ptc, and Gli2 localized to primary...... cilia of PANC-1 and CFPAC-1 cells, which may maintain high levels of nonstimulated Hh pathway activity. These findings indicate that primary cilia are involved in pancreatic development and postnatal tissue homeostasis....

  16. Neurophysiological changes in the afferent somatosensory system indices in the case of vertebrogenic spine pathology in miners

    Directory of Open Access Journals (Sweden)

    Sharbanu Battakova

    2013-04-01

    Full Text Available Objectives: The aim of the paper was to prove that job conditions impact the state of the afferent part of the somatosensory system in miners. Materials and Methods: Data analysis of the electrophysiological examination of the syndrome in 148 patients, aged from 28 to 55 years, with a mild, moderate and severe degree of the pain syndrome was performed. The control group included 28 people without any pain symptoms. The method used was that of somatosensory stimulated potential (SSP with the potentials amplitude and latency main components taken into consideration. Results: It was proven that the true decrease of the somatosensory stimulated potential SSP N22 (p < 0.05 component amplitudes by 41%; N30 component amplitude tend to decrease by 26%. This proves that the true N22 (p < 0.01 component latency increase by 63.8% corresponds to afferent excitation wave conductibility under the pain syndrome of vertebral pathology through sensitivity pathways mainly in the posterior spinal cord columns and then, through the parts of the brain stem, involving the cerebral cortex, which is confirmed by the fact that the P38 and P46 components amplitudes tend to decrease. In addition to this, the proven N10–N13 (p < 0.05, N13–N20 (p < 0.05, N10–N20 (p < 0.05 intervals increases by 43.5–41.8–38.7%, respectively, correspond to the nervous impulse conductibility through the peripheral nervous system structures and allow to reveal the subclinical slowdown of impulse conductibility, which indicates that the conducting system is changed even under a mild pain syndrome. Conclusions: It was found that the data obtained allow for the better understanding of how the neuropathological pain syndrome under vertebral spine pathology is formed.

  17. Multimodal and widespread somatosensory abnormalities in persistent shoulder pain in the first 6 months efter stroke: An exploratory study

    NARCIS (Netherlands)

    Roosink, M.; van Dongen, Robert T.; Buitenweg, Jan R.; Renzenbrink, Gerbert J.; Geurts, Alexander C.; IJzerman, Maarten Joost

    2012-01-01

    Objective: To explore the role of multimodal and widespread somatosensory abnormalities in the development of persistent poststroke shoulder pain (pPSSP) in the first 6 months after stroke. Design: Prospective inception cohort study. Setting: Stroke units of 2 teaching hospitals. Participants: The

  18. Human factors and ergonomics for primary care.

    Science.gov (United States)

    Bowie, Paul; Jeffcott, Shelly

    2016-03-01

    In the second paper of this series, we provide a brief overview of the scientific discipline of human factors and ergonomics (HFE). Traditionally the HFE focus in healthcare has been in acute hospital settings which are perceived to exhibit characteristics more similar to other high-risk industries already applying related principles and methods. This paper argues that primary care is an area which could benefit extensively from an HFE approach, specifically in improving the performance and well-being of people and organisations. To this end, we define the purpose of HFE, outline its three specialist sub-domains (physical, cognitive and organisational HFE) and provide examples of guiding HFE principles and practices. Additionally, we describe HFE issues of significance to primary care education, improvement and research and outline early plans for building capacity and capability in this setting.

  19. Neurophysiological assessment of auditory, peripheral nerve, somatosensory, and visual system function after developmental exposure to gasoline, E15, and E85 vapors.

    Data.gov (United States)

    U.S. Environmental Protection Agency — Visual, auditory, somatosensory, and peripheral nerve evoked responses. This dataset is associated with the following publication: Herr , D., D. Freeborn , L. Degn ,...

  20. Ultrastructural characterization of primary cilia in pathologically characterized human glioblastoma multiforme (GBM) tumors.

    Science.gov (United States)

    Moser, Joanna J; Fritzler, Marvin J; Rattner, Jerome B

    2014-01-01

    Primary cilia are non-motile sensory cytoplasmic organelles that are involved in cell cycle progression. Ultrastructurally, the primary cilium region is complex, with normal ciliogenesis progressing through five distinct morphological stages in human astrocytes. Defects in early stages of ciliogenesis are key features of astrocytoma/glioblastoma cell lines and provided the impetus for the current study which describes the morphology of primary cilia in molecularly characterized human glioblastoma multiforme (GBM) tumors. Seven surgically resected human GBM tissue samples were molecularly characterized according to IDH1/2 mutation status, EGFR amplification status and MGMT promoter methylation status and were examined for primary cilia expression and structure using indirect immunofluorescence and electron microscopy. We report for the first time that primary cilia are disrupted in the early stages of ciliogenesis in human GBM tumors. We confirm that immature primary cilia and basal bodies/centrioles have aberrant ciliogenesis characteristics including absent paired vesicles, misshaped/swollen vesicular hats, abnormal configuration of distal appendages, and discontinuity of centriole microtubular blades. Additionally, the transition zone plate is able to form in the absence of paired vesicles on the distal end of the basal body and when a cilium progresses beyond the early stages of ciliogenesis, it has electron dense material clumped along the transition zone and a darkening of the microtubules at the proximal end of the cilium. Primary cilia play a role in a variety of human cancers. Previously primary cilia structure was perturbed in cultured cell lines derived from astrocytomas/glioblastomas; however there was always some question as to whether these findings were a cell culture phenomena. In this study we confirm that disruptions in ciliogenesis at early stages do occur in GBM tumors and that these ultrastructural findings bear resemblance to those previously

  1. Pathophysiology of somatosensory abnormalities in Parkinson disease.

    Science.gov (United States)

    Conte, Antonella; Khan, Nashaba; Defazio, Giovanni; Rothwell, John C; Berardelli, Alfredo

    2013-12-01

    Changes in sensory function that have been described in patients with Parkinson disease (PD) can be either 'pure' disorders of conscious perception such as elevations in sensory threshold, or disorders of sensorimotor integration, in which the interaction between sensory input and motor output is altered. In this article, we review the extensive evidence for disrupted tactile, nociceptive, thermal and proprioceptive sensations in PD, as well as the influences exerted on these sensations by dopaminergic therapy and deep brain stimulation. We argue that abnormal spatial and temporal processing of sensory information produces incorrect signals for the preparation and execution of voluntary movement. Sensory deficits are likely to be a consequence of the dopaminergic denervation of the basal ganglia that is the hallmark of PD. A possible mechanism to account for somatosensory deficits is one in which disease-related dopaminergic denervation leads to a loss of response specificity, resulting in transmission of noisier and less-differentiated information to cortical regions. Changes in pain perception might have a different explanation, possibly involving disease-related effects outside the basal ganglia, including involvement of peripheral pain receptors, as well as structures such as the periaqueductal grey matter and non-dopaminergic neurotransmitter systems.

  2. Corticospinal and Spinal Excitabilities Are Modulated during Motor Imagery Associated with Somatosensory Electrical Nerve Stimulation

    Directory of Open Access Journals (Sweden)

    E. Traverse

    2018-01-01

    Full Text Available Motor imagery (MI, the mental simulation of an action, influences the cortical, corticospinal, and spinal levels, despite the lack of somatosensory afferent feedbacks. The aim of this study was to analyze the effect of MI associated with somatosensory stimulation (SS on the corticospinal and spinal excitabilities. We used transcranial magnetic stimulation and peripheral nerve stimulation to induce motor-evoked potentials (MEP and H-reflexes, respectively, in soleus and medialis gastrocnemius (MG muscles of the right leg. Twelve participants performed three tasks: (1 MI of submaximal plantar flexion, (2 SS at 65 Hz on the posterior tibial nerve with an intensity below the motor threshold, and (3 MI + SS. MEP and H-reflex amplitudes were recorded before, during, and after the tasks. Our results confirmed that MI increased corticospinal excitability in a time-specific manner. We found that MI+SS tended to potentiate MEP amplitude of the MG muscle compared to MI alone. We confirmed that SS decreased spinal excitability, and this decrease was partially compensated when combined with MI, especially for the MG muscle. The increase of CSE could be explained by a modulation of the spinal inhibitions induced by SS, depending on the amount of afferent feedbacks.

  3. Effects of Improvement on Selective Attention: Developing Appropriate Somatosensory Video Game Interventions for Institutional-Dwelling Elderly with Disabilities

    Science.gov (United States)

    Chen, Shang-Ti; Chiang, I-Tsun; Liu, Eric Zhi-Feng; Chang, Maiga

    2012-01-01

    The purpose of this study was to develop appropriate somatosensory video game interventions on enhancing selective attention of institutional-dwelling elderly with disabilities. Fifty-eight participants aged 65[approximately]92 were recruited and divided into four groups, 4-week and 8-week experimental and two control groups, for evaluating the…

  4. Tactile interactions activate mirror system regions in the human brain.

    Science.gov (United States)

    McKyton, Ayelet

    2011-12-07

    Communicating with others is essential for the development of a society. Although types of communications, such as language and visual gestures, were thoroughly investigated in the past, little research has been done to investigate interactions through touch. To study this we used functional magnetic resonance imaging. Twelve participants were scanned with their eyes covered while stroking four kinds of items, representing different somatosensory stimuli: a human hand, a realistic rubber hand, an object, and a simple texture. Although the human and the rubber hands had the same overall shape, in three regions there was significantly more blood oxygen level dependent activation when touching the real hand: the anterior medial prefrontal cortex, the ventral premotor cortex, and the posterior superior temporal cortex. The last two regions are part of the mirror network and are known to be activated through visual interactions such as gestures. Interestingly, in this study, these areas were activated through a somatosensory interaction. A control experiment was performed to eliminate confounds of temperature, texture, and imagery, suggesting that the activation in these areas was correlated with the touch of a human hand. These results reveal the neuronal network working behind human tactile interactions, and highlight the participation of the mirror system in such functions.

  5. Vascular status in human primary and permanent teeth in health and disease.

    Science.gov (United States)

    Rodd, Helen D; Boissonade, Fiona M

    2005-04-01

    The present study sought to compare the vascular status of human primary teeth with that of human permanent teeth, and to determine whether caries or painful pulpitis was associated with changes in vascularity. Coronal pulps were removed from 62 primary and 62 permanent mandibular molars with a known pain history. Teeth were categorized as intact, moderately carious or grossly carious. Pulp sections were labelled with Ulex europaeus I lectin (UEIL), which is a marker of human vascular endothelium. Image analysis was then used to quantify the percentage area of UEIL-labelled tissue (vascularity) and the number of blood vessels present within three regions: the pulp horn, the subodontoblastic region, and the mid-coronal pulp. Only the mid-coronal region of the primary tooth pulp was found to be significantly more vascular than the corresponding area of the permanent tooth pulp. Both dentitions showed a significant increase in vascularity within the pulp horn region with caries progression, but this was not accompanied by an increase in vessel number. There was no correlation between vascularity and pain symptoms. These findings suggest that the primary tooth pulp is more vascular than its successor within the mid-coronal region. However, the functional and clinical significance of this finding remains speculative.

  6. On the use of information theory for the analysis of synchronous nociceptive withdrawal reflexes and somatosensory evoked potentials elicited by graded electrical stimulation.

    Science.gov (United States)

    Arguissain, Federico G; Biurrun Manresa, José A; Mørch, Carsten D; Andersen, Ole K

    2015-01-30

    To date, few studies have combined the simultaneous acquisition of nociceptive withdrawal reflexes (NWR) and somatosensory evoked potentials (SEPs). In fact, it is unknown whether the combination of these two signals acquired simultaneously could provide additional information on somatosensory processing at spinal and supraspinal level compared to individual NWR and SEP signals. By using the concept of mutual information (MI), it is possible to quantify the relation between electrical stimuli and simultaneous elicited electrophysiological responses in humans based on the estimated stimulus-response signal probability distributions. All selected features from NWR and SEPs were informative in regard to the stimulus when considered individually. Specifically, the information carried by NWR features was significantly higher than the information contained in the SEP features (pinformation carried by the combination of features showed an overall redundancy compared to the sum of the individual contributions. Comparison with existing methods MI can be used to quantify the information that single-trial NWR and SEP features convey, as well as the information carried jointly by NWR and SEPs. This is a model-free approach that considers linear and non-linear correlations at any order and is not constrained by parametric assumptions. The current study introduces a novel approach that allows the quantification of the individual and joint information content of single-trial NWR and SEP features. This methodology could be used to decode and interpret spinal and supraspinal interaction in studies modulating the responsiveness of the nociceptive system. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Apoptosis in the human periodontal membrane evaluated in primary and permanent teeth

    DEFF Research Database (Denmark)

    Bille, Marie-Louise Bastholm; Thomsen, Bjarke; Kjær, Inger

    2011-01-01

    that resorption is connected to apoptosis of the epithelial cells of Malassez. The purpose of this study is to localize cells undergoing apoptosis in the periodontal membrane of human primary and permanent teeth. Materials and methods. Human primary and permanent teeth were examined immunohistochemically...... for apoptosis and epithelial cells of Malassez in the periodontal membrane. All teeth examined were extracted in connection with treatment. Results. Apoptosis was seen in close proximity to the root surface and within the epithelial cells of Malassez. This pattern of apoptotis is similar in the periodontal...... membrane in primary and permanent teeth. Conclusions. The inter-relationship between apoptotis and root resorption cannot be concluded from the present study. Apoptosis seen in close proximity to the root surface presumably corresponds to the highly innervated layer of the periodontal membrane...

  8. Human embryonic stem cells in culture possess primary cilia with hedgehog signaling machinery

    DEFF Research Database (Denmark)

    Kiprilov, Enko N; Awan, Aashir; Desprat, Romain

    2008-01-01

    Human embryonic stem cells (hESCs) are potential therapeutic tools and models of human development. With a growing interest in primary cilia in signal transduction pathways that are crucial for embryological development and tissue differentiation and interest in mechanisms regulating human hESC d...

  9. The role of arginine vasopressin in electroacupuncture treatment of primary sciatica in human.

    Science.gov (United States)

    Zhao, Xue-Yan; Zhang, Qi-Shun; Yang, Jun; Sun, Fang-Jie; Wang, Da-Xin; Wang, Chang-Hong; He, Wei-Ya

    2015-08-01

    It has been implicated that electroacupuncture can relieve the symptoms of sciatica with the increase of pain threshold in human, and arginine vasopressin (AVP) in the brain rather than the spinal cord and blood circulation participates in antinociception. Our previous study has proven that AVP in the brain played a role in the process of electroacupuncture analgesia in rat. The goal of the present study was to investigate the role of AVP in electroacupuncture in treating primary sciatica in human. The results showed that (1) AVP concentration of cerebrospinal fluid (CSF) (7.5 ± 2.5 pg/ml), not plasma (13.2 ± 4.2 pg/ml) in primary sciatica patients was lower than that in health volunteers (16.1 ± 3.8 pg/ml and 12.3 ± 3.4 pg/ml), although the osmotic pressure in CSF and plasma did not change; (2) electroacupuncture of the bilateral "Zusanli" points (St. 36) for 60 min relieved the pain sensation in primary sciatica patients; (3) electroacupuncture increased the AVP level of CSF, not plasma in primary sciatica patients; and (4) there was the positive correlation between the effect of electroacupuncture relieving the pain and the AVP level of CSF in the primary sciatica patients. The data suggested that central AVP, not peripheral AVP might improve the effect of electroacupuncture treatment of primary sciatica in human, i.e., central AVP might take part in the electroacupuncture relieving the pain sensation in primary sciatica patients. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. HANPP Collection: Human Appropriation of Net Primary Productivity (HANPP) by Country and Product

    Data.gov (United States)

    National Aeronautics and Space Administration — The Global Patterns in Human Appropriation of Net Primary Productivity (HANPP) portion of the HANPP Collection represents a digital map of human appropriation of net...

  11. Visual cortical somatosensory and brainstem auditory evoked potentials following incidental irradiation of the rhombencephalon

    Energy Technology Data Exchange (ETDEWEB)

    Nightingale, S. (Royal Victoria Infirmary, Newcastle upon Tyne (UK)); Schofield, I.S.; Dawes, P.J.D.K. (Newcastle upon Tyne Univ. (UK). Newcastle General Hospital)

    1984-01-01

    Visual, cortical somatosensory and brainstem auditory evoked potentials were recorded before incidental irradiation of the rhombencephalon during radiotherapy in and around the middle ear, and at 11 weeks and eight months after completion of treatment. No patient experienced neurological symptoms during this period. No consistent changes in evoked potentials were found. The failure to demonstrate subclinical radiation-induced demyelination suggests either that the syndrome of early-delayed radiation rhombencephalopathy occurs in an idiosyncratic manner, or that any subclinical lesions are not detectable by serial evoked potential recordings.

  12. Cytotoxicity and accumulation of ergot alkaloids in human primary cells.

    Science.gov (United States)

    Mulac, Dennis; Humpf, Hans-Ulrich

    2011-04-11

    Ergot alkaloids are secondary metabolites produced by fungi of the species Claviceps. Toxic effects after consumption of contaminated grains are described since mediaeval times. Of the more than 40 known ergot alkaloids six are found predominantly. These are ergotamine, ergocornine, ergocryptine, ergocristine, ergosine and ergometrine, along with their corresponding isomeric forms (-inine-forms). Toxic effects are known to be induced by an interaction of the ergot alkaloids as neurotransmitters, like dopamine or serotonin. Nevertheless data concerning cytotoxic effects are missing and therefore a screening of the six main ergot alkaloids was performed in human primary cells in order to evaluate the toxic potential. As it is well known that ergot alkaloids isomerize easily the stability was tested in the cell medium. Based on these results factors were calculated to correct the used concentration values to the biologically active lysergic (-ine) form. These factors range from 1.4 for the most stable compound ergometrine to 5.0 for the most unstable ergot alkaloid ergocristine. With these factors, reflecting the instability, several controverse literature data concerning the toxicity could be explained. To evaluate the cytotoxic effects of ergot alkaloids, human cells in primary culture were used. These cells remain unchanged in contrast to cell lines and the data allow a better comparison to the in vivo situation than using immortalized cell lines. To characterize the effects on primary cells, renal proximal tubule epithelial cells (RPTEC) and normal human astrocytes (NHA) were used. The parameters necrosis (LDH-release) and apoptosis (caspase-3-activation, DNA condensation and fragmentation) were distinguished. The results show that depending on the individual structure of the peptide ergot alkaloids the toxic properties change. While ergometrine as a lysergic acid amide did not show any effect, the peptide ergot alkaloids revealed a different toxic potential. Of

  13. Retroviral-mediated gene transfer and expression of human phenylalanine hydroxylase in primary mouse hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Peng, H.; Armentano, D.; Mackenzie-Graham, L.; Shen, R.F.; Darlington, G.; Ledley, F.D.; Woo, S.L.C. (Baylor College of Medicine, Houston, TX (USA))

    1988-11-01

    Genetic therapy for phenylketonuria (severe phenylalanine hydroxylase deficiency) may require introduction of a normal phenylalanine hydroxylase gene into hepatic cells of patients. The authors report development of a recombinant retrovirus based on the N2 vector for gene transfer and expression of human phenylalanine hydroxylase cDNA in primary mouse hepatocytes. This construct contains an internal promoter of the human {alpha}{sub 1}-antitrypsin gene driving transcription of the phenylalanine hydroxylase cDNA. Primary mouse hepatocytes were isolated from newborn mice, infected with the recombinant virus, and selected for expression of the neomycin-resistance gene. Hepatocytes transformed with the recombinant virus contained high levels of human phenylalanine hydroxylase mRNA transcripts originating from the retroviral and internal promoters. These results demonstrate that the transcriptional regulatory elements of the {alpha}{sub 1} antitrypsin gene retain their tissue-specific function in the recombinant provirus and establish a method for efficient transfer and high-level expression of human phenylalanine hydroxylase in primary hepatocytes.

  14. Retroviral-mediated gene transfer and expression of human phenylalanine hydroxylase in primary mouse hepatocytes

    International Nuclear Information System (INIS)

    Peng, H.; Armentano, D.; Mackenzie-Graham, L.; Shen, R.F.; Darlington, G.; Ledley, F.D.; Woo, S.L.C.

    1988-01-01

    Genetic therapy for phenylketonuria (severe phenylalanine hydroxylase deficiency) may require introduction of a normal phenylalanine hydroxylase gene into hepatic cells of patients. The authors report development of a recombinant retrovirus based on the N2 vector for gene transfer and expression of human phenylalanine hydroxylase cDNA in primary mouse hepatocytes. This construct contains an internal promoter of the human α 1 -antitrypsin gene driving transcription of the phenylalanine hydroxylase cDNA. Primary mouse hepatocytes were isolated from newborn mice, infected with the recombinant virus, and selected for expression of the neomycin-resistance gene. Hepatocytes transformed with the recombinant virus contained high levels of human phenylalanine hydroxylase mRNA transcripts originating from the retroviral and internal promoters. These results demonstrate that the transcriptional regulatory elements of the α 1 antitrypsin gene retain their tissue-specific function in the recombinant provirus and establish a method for efficient transfer and high-level expression of human phenylalanine hydroxylase in primary hepatocytes

  15. Listening to another sense: somatosensory integration in the auditory system.

    Science.gov (United States)

    Wu, Calvin; Stefanescu, Roxana A; Martel, David T; Shore, Susan E

    2015-07-01

    Conventionally, sensory systems are viewed as separate entities, each with its own physiological process serving a different purpose. However, many functions require integrative inputs from multiple sensory systems and sensory intersection and convergence occur throughout the central nervous system. The neural processes for hearing perception undergo significant modulation by the two other major sensory systems, vision and somatosensation. This synthesis occurs at every level of the ascending auditory pathway: the cochlear nucleus, inferior colliculus, medial geniculate body and the auditory cortex. In this review, we explore the process of multisensory integration from (1) anatomical (inputs and connections), (2) physiological (cellular responses), (3) functional and (4) pathological aspects. We focus on the convergence between auditory and somatosensory inputs in each ascending auditory station. This review highlights the intricacy of sensory processing and offers a multisensory perspective regarding the understanding of sensory disorders.

  16. Critical Factors for Inducing Curved Somatosensory Saccades

    Directory of Open Access Journals (Sweden)

    Tamami Nakano

    2011-10-01

    Full Text Available We are able to make a saccade toward a tactile stimuli to one hand, but trajectories of many saccades curved markedly when the arms were crossed (Groh & Sparks, 2006. However, it remains unknown why some curved and others did not. We therefore examined critical factors for inducing the curved somatosensory saccades. Participants made a saccade as soon as possible from a central fixation point toward a tactile stimulus delivered to one of the two hands, and switched between arms-crossed and arms-uncrossed postures every 6 trials. Trajectories were generally straight when the arms were uncrossed, but all participants made curved saccades when the arms were crossed (12–64%. We found that the probability of curved saccades depended critically on the onset latency: the probability was less than 5% when the latency was larger than 250 ms, but the probability increased up to 70–80% when the onset latency was 160 ms. This relationship was shared across participants. The results suggest that a touch in the arms-crossed posture was always mapped to the wrong hand in the initial phase up to 160 ms, and then remapped to the correct hand during the next 100 ms by some fundamental neural mechanisms shared across participants.

  17. Visual cortical somatosensory and brainstem auditory evoked potentials following incidental irradiation of the rhombencephalon

    International Nuclear Information System (INIS)

    Nightingale, S.; Schofield, I.S.; Dawes, P.J.D.K.

    1984-01-01

    Visual, cortical somatosensory and brainstem auditory evoked potentials were recorded before incidental irradiation of the rhombencephalon during radiotherapy in and around the middle ear, and at 11 weeks and eight months after completion of treatment. No patient experienced neurological symptoms during this period. No consistent changes in evoked potentials were found. The failure to demonstrate subclinical radiation-induced demyelination suggests either that the syndrome of early-delayed radiation rhombencephalopathy occurs in an idiosyncratic manner, or that any subclinical lesions are not detectable by serial evoked potential recordings. (author)

  18. Somatosensory Tinnitus: Correlation between Cranio-Cervico-Mandibular Disorder History and Somatic Modulation.

    Science.gov (United States)

    Ralli, Massimo; Altissimi, Giancarlo; Turchetta, Rosaria; Mazzei, Filippo; Salviati, Massimo; Cianfrone, Francesca; Orlando, Maria Patrizia; Testugini, Valeria; Cianfrone, Giancarlo

    2016-01-01

    In a subpopulation of patients, tinnitus can be modulated by movements of the jaw or head and neck due to complex somatosensory-auditory interactions. In some of these subjects, tinnitus could be related to an underlying temporomandibular (TMJ) or craniocervical (NECK) dysfunction that, if correctly identified, could streamline treatment and increase chances of tinnitus improvement. However, it is still unclear whether somatic modulation of tinnitus could be used as a screening tool for identifying such patients. In this study, we included 310 tinnitus patients with normal hearing, no psychiatric comorbidities, and a positive history of TMJ and/or NECK dysfunction and/or a positive modulation of tinnitus to evaluate the characteristics of somatic modulation, investigate the relationship between positive history and positive modulation, and identify factors most strongly associated with somatic modulation. Tinnitus modulation was present in 79.67% of the patients. We found a significant association within the same subjects between a positive history and a positive tinnitus modulation for the same region, mainly for TMJ in unilateral tinnitus patients and for TMJ + NECK in bilateral tinnitus patients. A strong correlation between history and modulation in the same somatic region within the same subgroups of subjects was also identified. Most TMJ maneuvers resulted in an increased loudness, while NECK maneuvers showed an increase in tinnitus loudness in about 59% of cases. High-pitched tinnitus and male gender were associated with a higher prevalence of modulation; no differences were found for tinnitus onset, Tinnitus Handicap Inventory score, and age. In this paper, we report a strong association between history and modulation for the same regions within the same patients; such an association should always be investigated to improve chances of a correct diagnosis of somatosensory tinnitus. © 2017 S. Karger AG, Basel.

  19. Altered Cross-Modal Processing in the Primary Auditory Cortex of Congenitally Deaf Adults: A Visual-Somatosensory fMRI Study with a Double-Flash Illusion

    OpenAIRE

    Karns, Christina M.; Dow, Mark W.; Neville, Helen J.

    2012-01-01

    The developing brain responds to the environment by using statistical correlations in input to guide functional and structural changes—that is, the brain displays neuroplasticity. Experience shapes brain development throughout life, but neuroplasticity is variable from one brain system to another. How does the early loss of a sensory modality affect this complex process? We examined cross-modal neuroplasticity in anatomically defined subregions of Heschl's gyrus, the site of human primary aud...

  20. Tactile information processing in primate hand somatosensory cortex (S1) during passive arm movement.

    Science.gov (United States)

    Song, Weiguo; Francis, Joseph Thachil

    2013-11-01

    Motor output mostly depends on sensory input, which also can be affected by action. To further our understanding of how tactile information is processed in the primary somatosensory cortex (S1) in dynamic environments, we recorded neural responses to tactile stimulation of the hand in three awake monkeys under arm/hand passive movement and rest. We found that neurons generally responded to tactile stimulation under both conditions and were modulated by movement: with a higher baseline firing rate, a suppressed peak rate, and a smaller dynamic range during passive movement than during rest, while the area under the response curve was stable across these two states. By using an information theory-based method, the mutual information between tactile stimulation and neural responses was quantified with rate and spatial coding models under the two conditions. The two potential encoding models showed different contributions depending on behavioral contexts. Tactile information encoded with rate coding from individual units was lower than spatial coding of unit pairs, especially during movement; however, spatial coding had redundant information between unit pairs. Passive movement regulated the mutual information, and such regulation might play different roles depending on the encoding strategies used. The underlying mechanisms of our observation most likely come from a bottom-up strategy, where neurons in S1 were regulated through the activation of the peripheral tactile/proprioceptive receptors and the interactions between these different types of information.

  1. Respiratory compensation to a primary metabolic alkalosis in humans.

    Science.gov (United States)

    Feldman, Mark; Alvarez, Naiara M; Trevino, Michael; Weinstein, Gary L

    2012-11-01

    There is limited and disparate information about the extent of the respiratory compensation (hypoventilation) that occurs in response to a primary metabolic alkalosis in humans. Our aim was to examine the influence of the plasma bicarbonate concentration, the plasma base excess, and the arterial pH on the arterial carbon dioxide tension in 52 adult patients with primary metabolic alkalosis, mostly due to diuretic use or vomiting. Linear regression analysis was used to correlate degrees of alkalosis with arterial carbon dioxide tensions. In this alkalotic cohort, whose arterial plasma bicarbonate averaged 31.6 mEq/l, plasma base excess averaged 7.8 mEq/l, and pH averaged 7.48, both plasma bicarbonate and base excess correlated closely with arterial carbon dioxide tensions (r = 0.97 and 0.96, respectively; p respiratory compensation (hypoventilation) to primary metabolic alkalosis than has been reported in prior smaller studies.

  2. Differential effects of aging on fore- and hindpaw maps of rat somatosensory cortex.

    Directory of Open Access Journals (Sweden)

    Marianne David-Jürgens

    Full Text Available Getting older is associated with a decline of cognitive and sensorimotor abilities, but it remains elusive whether age-related changes are due to accumulating degenerational processes, rendering them largely irreversible, or whether they reflect plastic, adaptational and presumably compensatory changes. Using aged rats as a model we studied how aging affects neural processing in somatosensory cortex. By multi-unit recordings in the fore- and hindpaw cortical maps we compared the effects of aging on receptive field size and response latencies. While in aged animals response latencies of neurons of both cortical representations were lengthened by approximately the same amount, only RFs of hindpaw neurons showed severe expansion with only little changes of forepaw RFs. To obtain insight into parallel changes of walking behavior, we recorded footprints in young and old animals which revealed a general age-related impairment of walking. In addition we found evidence for a limb-specific deterioration of the hindlimbs that was not observed in the forelimbs. Our results show that age-related changes of somatosensory cortical neurons display a complex pattern of regional specificity and parameter-dependence indicating that aging acts rather selectively on cortical processing of sensory information. The fact that RFs of the fore- and hindpaws do not co-vary in aged animals argues against degenerational processes on a global scale. We therefore conclude that age-related alterations are composed of plastic-adaptive alterations in response to modified use and degenerational changes developing with age. As a consequence, age-related changes need not be irreversible but can be subject to amelioration through training and stimulation.

  3. Do patients with chronic unilateral orofacial pain due to a temporomandibular disorder show increased attending to somatosensory input at the painful side of the jaw?

    Science.gov (United States)

    Van Damme, Stefaan; Vanden Bulcke, Charlotte; Van Den Berghe, Linda; Poppe, Louise; Crombez, Geert

    2018-01-01

    Patients with chronic orofacial pain due to temporomandibular disorders (TMD) display alterations in somatosensory processing at the jaw, such as amplified perception of tactile stimuli, but the underlying mechanisms remain unclear. This study investigated one possible explanation, namely hypervigilance, and tested if TMD patients with unilateral pain showed increased attending to somatosensory input at the painful side of the jaw. TMD patients with chronic unilateral orofacial pain ( n  = 20) and matched healthy volunteers ( n  = 20) performed a temporal order judgment (TOJ) task indicated which one of two tactile stimuli, presented on each side of the jaw, they had perceived first. TOJ methodology allows examining spatial bias in somatosensory processing speed. Furthermore, after each block of trials, the participants rated the perceived intensity of tactile stimuli separately for both sides of the jaw. Finally, questionnaires assessing pain catastrophizing, fear-avoidance beliefs, and pain vigilance, were completed. TMD patients tended to perceive tactile stimuli at the painful jaw side as occurring earlier in time than stimuli at the non-painful side but this effect did not reach conventional levels of significance ( p  = .07). In the control group, tactile stimuli were perceived as occurring simultaneously. Secondary analyses indicated that the magnitude of spatial bias in the TMD group is positively associated with the extent of fear-avoidance beliefs. Overall, intensity ratings of tactile stimuli were significantly higher in the TMD group than in the control group, but there was no significant difference between the painful and non-painful jaw side in the TMD patients. The hypothesis that TMD patients with chronic unilateral orofacial pain preferentially attend to somatosensory information at the painful side of the jaw was not statistically supported, although lack of power could not be ruled out as a reason for this. The findings are discussed within

  4. Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Woolbright, Benjamin L.; Dorko, Kenneth [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Antoine, Daniel J.; Clarke, Joanna I. [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Gholami, Parviz [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Li, Feng [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Kumer, Sean C.; Schmitt, Timothy M.; Forster, Jameson [Department of Surgery, University of Kansas Medical Center, Kansas City, KS (United States); Fan, Fang [Department of Pathology, University of Kansas Medical Center, Kansas City, KS (United States); Jenkins, Rosalind E.; Park, B. Kevin [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Hagenbuch, Bruno [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Olyaee, Mojtaba [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States)

    2015-03-15

    Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation. To address this issue, this study assessed how pathophysiological concentrations of bile acids measured in cholestatic patients affected primary human hepatocytes. Individual bile acid levels were determined in serum and bile by UPLC/QTOFMS in patients with extrahepatic cholestasis with, or without, concurrent increases in serum transaminases. Bile acid levels increased in serum of patients with liver injury, while biliary levels decreased, implicating infarction of the biliary tracts. To assess bile acid-induced toxicity in man, primary human hepatocytes were treated with relevant concentrations, derived from patient data, of the model bile acid glycochenodeoxycholic acid (GCDC). Treatment with GCDC resulted in necrosis with no increase in apoptotic parameters. This was recapitulated by treatment with biliary bile acid concentrations, but not serum concentrations. Marked elevations in serum full-length cytokeratin-18, high mobility group box 1 protein (HMGB1), and acetylated HMGB1 confirmed inflammatory necrosis in injured patients; only modest elevations in caspase-cleaved cytokeratin-18 were observed. These data suggest human hepatocytes are more resistant to human-relevant bile acids than rodent hepatocytes, and die through necrosis when exposed to bile acids. These mechanisms of cholestasis in humans are fundamentally different to mechanisms observed in rodent models. - Highlights: • Cholestatic liver injury is due to cytoplasmic bile acid accumulation in hepatocytes. • Primary human hepatocytes are resistant to BA-induced injury

  5. Cited2 Regulates Neocortical Layer II/III Generation and Somatosensory Callosal Projection Neuron Development and Connectivity.

    Science.gov (United States)

    Fame, Ryann M; MacDonald, Jessica L; Dunwoodie, Sally L; Takahashi, Emi; Macklis, Jeffrey D

    2016-06-15

    The neocortex contains hundreds to thousands of distinct subtypes of precisely connected neurons, allowing it to perform remarkably complex tasks of high-level cognition. Callosal projection neurons (CPN) connect the cerebral hemispheres via the corpus callosum, integrating cortical information and playing key roles in associative cognition. CPN are a strikingly diverse set of neuronal subpopulations, and development of this diversity requires precise control by a complex, interactive set of molecular effectors. We have found that the transcriptional coregulator Cited2 regulates and refines two stages of CPN development. Cited2 is expressed broadly by progenitors in the embryonic day 15.5 subventricular zone, during the peak of superficial layer CPN birth, with a progressive postmitotic refinement in expression, becoming restricted to CPN of the somatosensory cortex postnatally. We generated progenitor-stage and postmitotic forebrain-specific Cited2 conditional knock-out mice, using the Emx1-Cre and NEX-Cre mouse lines, respectively. We demonstrate that Cited2 functions in progenitors, but is not necessary postmitotically, to regulate both (1) broad generation of layer II/III CPN and (2) acquisition of precise area-specific molecular identity and axonal/dendritic connectivity of somatosensory CPN. This novel CPN subtype-specific and area-specific control from progenitor action of Cited2 adds yet another layer of complexity to the multistage developmental regulation of neocortical development. This study identifies Cited2 as a novel subtype-specific and area-specific control over development of distinct subpopulations within the broad population of callosal projection neurons (CPN), whose axons connect the two cerebral hemispheres via the corpus callosum (CC). Currently, how the remarkable diversity of CPN subtypes is specified, and how they differentiate to form highly precise and specific circuits, are largely unknown. We found that Cited2 functions within

  6. [Normative aspects of somatosensory evoked P300 components].

    Science.gov (United States)

    Louzã Neto, M R; Maurer, K; Neuhauser, B

    1989-06-01

    Using a somatosensory version of the oddball-paradigma the influence of age and gender on the P300-component and the comparison of the potential after stimulation of the right and left median nerve was studied in 30 healthy right handed volunteers (age: 20-35 years). Latency, amplitude, area and duration of the P300-potential were analysed. No relationship between age, gender and the P300-parameters were observed. The amplitude and the area of the potential obtained from the F3 electrode were greater after stimulation of the right median nerve compared to the potential after stimulation of the left median nerve. All other results were not significantly different. Strong positive correlations between the results after stimulation of the right and left median nerve were observed. These results showed that by a young group of volunteers age and gender did not influence the P300-component. Although the P300-Parameters had a between-subject variability, their mean remained constant over the study, their correlation coefficients were strong positive and the side of stimulation did not influence them (except for the electrode F3).

  7. Effect of epidural 0.25% bupivacaine on somatosensory evoked potentials to dermatomal stimulation

    DEFF Research Database (Denmark)

    Lund, C; Hansen, O B; Kehlet, H

    1989-01-01

    The effect of lumbar epidural analgesia with similar volumes (about 25 ml) of 0.25% and 0.5% bupivacaine on early (less than 0.5 seconds) somatosensory evoked potentials (SEPs) to electrical stimulation of the S1, L1, and T10 dermatomes was examined in two groups of ten patients. Level of sensory...... analgesia to pinprick was T5.7 +/- 0.8 and T6.4 +/- 0.7 in the 0.25% and 0.5% bupivacaine group, respectively. Motor blockade was more pronounced in the 0.5% bupivacaine group (p less than 0.05). Despite similar analgesia to pinprick, SEPs were more reduced during 0.5% bupivacaine than during 0...

  8. Phosphoinositide-3-Kinase Signaling in Human Natural Killer Cells: New Insights from Primary Immunodeficiency

    Directory of Open Access Journals (Sweden)

    Emily M. Mace

    2018-03-01

    Full Text Available Human natural killer (NK cells play a critical role in the control of viral infections and malignancy. Their importance in human health and disease is illustrated by severe viral infections in patients with primary immunodeficiencies that affect NK cell function and/or development. The recent identification of patients with phosphoinositide-3-kinase (PI3K-signaling pathway mutations that can cause primary immunodeficiency provides valuable insight into the role that PI3K signaling plays in human NK cell maturation and lytic function. There is a rich literature that demonstrates a requirement for PI3K in multiple key aspects of NK cell biology, including development/maturation, homing, priming, and function. Here, I briefly review these previous studies and place them in context with recent findings from the study of primary immunodeficiency patients, particularly those with hyperactivating mutations in PI3Kδ signaling.

  9. Ebola virus glycoprotein-mediated anoikis of primary human cardiac microvascular endothelial cells

    International Nuclear Information System (INIS)

    Ray, Ratna B.; Basu, Arnab; Steele, Robert; Beyene, Aster; McHowat, Jane; Meyer, Keith; Ghosh, Asish K.; Ray, Ranjit

    2004-01-01

    Ebola virus glycoprotein (EGP) has been implicated for the induction of cytotoxicity and injury in vascular cells. On the other hand, EGP has also been suggested to induce massive cell rounding and detachment from the plastic surface by downregulating cell adhesion molecules without causing cytotoxicity. In this study, we have examined the cytotoxic role of EGP in primary endothelial cells by transduction with a replication-deficient recombinant adenovirus expressing EGP (Ad-EGP). Primary human cardiac microvascular endothelial cells (HCMECs) transduced with Ad-EGP displayed loss of cell adhesion from the plastic surface followed by cell death. Transfer of conditioned medium from EGP-transduced HCMEC into naive cells did not induce loss of adhesion or cell death, suggesting that EGP needs to be expressed intracellularly to exert its cytotoxic effect. Subsequent studies suggested that HCMEC death occurred through apoptosis. Results from this study shed light on the EGP-induced anoikis in primary human cardiac endothelial cells, which may have significant pathological consequences

  10. Symmetry of fMRI activation in the primary sensorimotor cortex during unilateral chewing.

    Science.gov (United States)

    Lotze, M; Domin, M; Kordass, B

    2017-05-01

    Functional magnetic resonance imaging (fMRI) is one of the most advanced techniques to analyze the cerebral effects on many behavior aspects of the oral system such as chewing and mastication. Studies on imaging of the cerebral representation of chewing demonstrated differential results with respect to cortical lateralization during unilateral chewing. The aim of our study is to clarify the effects of cerebral responses during unilateral chewing. We used fMRI to compare brain activities during occlusal function in centric occlusion on natural teeth and chewing on a gum located on the right or the left teeth in 15 healthy subjects. Group data were performed by Talairach normalization and in addition by an assignment of activation maxima to individual anatomical landmarks in order to avoid possible loss of spatial preciseness of activation sites by normalization procedures. Evaluation of group data by Talairach normalization revealed representation sites for occlusal movements in bilateral primary (S1) and secondary (S2) somatosensory cortices, primary motor (M1) and premotor cortices, supplementary motor area (SMA) and medial cingulate gyrus, bilateral anterior cerebellar hemispheres and vermis, insula, orbitofrontal cortex, thalamus, and left pallidum. Right-sided chewing showed no differential activation to left-sided chewing, and both showed activation in areas also involved in bilateral occlusion. Both techniques, the one based on group normalization and the one based on an individual evaluation method, revealed remarkable low differences in activation maximum location in the primary motor, the primary and secondary somatosensory cortices, and the anterior cerebellar lobe. All chewing movements tested involved bilateral sensorimotor activation without a significant lateralization of activation intensities. Overall, a general lateralization of occlusion movements to the dominant side could not be verified in the present study. Chewing on the left or on the right

  11. Associative learning in humans--conditioning of sensory-evoked brain activity.

    Science.gov (United States)

    Skrandies, W; Jedynak, A

    2000-01-01

    A classical conditioning paradigm was employed in two experiments performed on 35 human volunteers. In nine subjects, the presentation of Landolt rings (conditioned stimuli, CS + ) was paired with an electric stimulus (unconditioned stimuli, UCS) applied to the left median nerve. Neutral visual control stimuli were full circles (CS -) that were not paired with the UCS. The skin conductance response (SCR) was determined in a time interval of 5 s after onset of the visual stimuli, and it was measured in the acquisition and test phase. Associative learning was reflected by a SCR occurring selectively with CS +. The same experiment was repeated with another group of 26 adults while electroencephalogram (EEG) was recorded from 30 electrodes. For each subject, mean evoked potentials were computed. In 13 of the subjects, a conditioning paradigm was followed while the other subjects served as the control group (non-contingent stimulation). There were somatosensory and visual brain activity evoked by the stimuli. Conditioned components were identified by computing cross-correlation between evoked somatosensory components and the averaged EEG. In the visual evoked brain activity, three components with mean latencies of 105.4, 183.2, and 360.3 ms were analyzed. Somatosensory stimuli were followed by major components that occurred at mean latencies of 48.8, 132.5, 219.7, 294.8, and 374.2 ms latency after the shock. All components were analyzed in terms of latency, field strength, and topographic characteristics, and were compared between groups and experimental conditions. Both visual and somatosensory brain activity was significantly affected by classical conditioning. Our data illustrate how associative learning affects the topography of brain electrical activity elicited by presentation of conditioned visual stimuli.

  12. Pathophysiology of primary burning mouth syndrome with special focus on taste dysfunction: a review.

    Science.gov (United States)

    Kolkka-Palomaa, M; Jääskeläinen, S K; Laine, M A; Teerijoki-Oksa, T; Sandell, M; Forssell, H

    2015-11-01

    Primary burning mouth syndrome (BMS) is a chronic oral condition characterized by burning pain often accompanied with taste dysfunction and xerostomia. The most compelling evidence concerning BMS pathophysiology comes from studies on the somatosensory system using neurophysiologic or psychophysical methods such as blink reflex, thermal quantitative sensory testing, as well as functional brain imaging. They have provided convincing evidence for neuropathic involvement at several levels of the somatosensory system in BMS pain pathophysiology. The number of taste function studies trying to substantiate the subjective taste disturbances or studies on salivary factors in BMS is much more limited, and most of them suffer from definitional and methodological problems. This review aims to critically evaluate the existing literature on the pathophysiology of BMS, paying special attention to the correctness of case selection and the methodology used in published studies, and to summarize the current state of knowledge. Based on the recognition of several gaps in the current understanding of the pathophysiology of BMS especially as regards taste and pain system interactions, the review ends with future scenarios for research in this area. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Vibrotactile masking experiments reveal accelerated somatosensory processing in congenitally blind braille readers.

    Science.gov (United States)

    Bhattacharjee, Arindam; Ye, Amanda J; Lisak, Joy A; Vargas, Maria G; Goldreich, Daniel

    2010-10-27

    Braille reading is a demanding task that requires the identification of rapidly varying tactile patterns. During proficient reading, neighboring characters impact the fingertip at ∼100 ms intervals, and adjacent raised dots within a character at 50 ms intervals. Because the brain requires time to interpret afferent sensorineural activity, among other reasons, tactile stimuli separated by such short temporal intervals pose a challenge to perception. How, then, do proficient Braille readers successfully interpret inputs arising from their fingertips at such rapid rates? We hypothesized that somatosensory perceptual consolidation occurs more rapidly in proficient Braille readers. If so, Braille readers should outperform sighted participants on masking tasks, which demand rapid perceptual processing, but would not necessarily outperform the sighted on tests of simple vibrotactile sensitivity. To investigate, we conducted two-interval forced-choice vibrotactile detection, amplitude discrimination, and masking tasks on the index fingertips of 89 sighted and 57 profoundly blind humans. Sighted and blind participants had similar unmasked detection (25 ms target tap) and amplitude discrimination (compared with 100 μm reference tap) thresholds, but congenitally blind Braille readers, the fastest readers among the blind participants, exhibited significantly less masking than the sighted (masker, 50 Hz, 50 μm; target-masker delays, ±50 and ±100 ms). Indeed, Braille reading speed correlated significantly and specifically with masking task performance, and in particular with the backward masking decay time constant. We conclude that vibrotactile sensitivity is unchanged but that perceptual processing is accelerated in congenitally blind Braille readers.

  14. Golgi Analysis of Neuron Morphology in the Presumptive Somatosensory Cortex and Visual Cortex of the Florida Manatee (Trichechus manatus latirostris).

    Science.gov (United States)

    Reyes, Laura D; Harland, Tessa; Reep, Roger L; Sherwood, Chet C; Jacobs, Bob

    2016-01-01

    The current study investigates neuron morphology in presumptive primary somatosensory (S1) and primary visual (V1) cortices of the Florida manatee (Trichechus manatus latirostris) as revealed by Golgi impregnation. Sirenians, including manatees, have an aquatic lifestyle, a large body size, and a relatively large lissencephalic brain. The present study examines neuron morphology in 3 cortical areas: in S1, dorsolateral cortex area 1 (DL1) and cluster cortex area 2 (CL2) and in V1, dorsolateral cortex area 4 (DL4). Neurons exhibited a variety of morphological types, with pyramidal neurons being the most common. The large variety of neuron types present in the manatee cortex was comparable to that seen in other eutherian mammals, except for rodents and primates, where pyramid-shaped neurons predominate. A comparison between pyramidal neurons in S1 and V1 indicated relatively greater dendritic branching in S1. Across all 3 areas, the dendritic arborization pattern of pyramidal neurons was also similar to that observed previously in the afrotherian rock hyrax, cetartiodactyls, opossums, and echidnas but did not resemble the widely bifurcated dendrites seen in the large-brained African elephant. Despite adaptations for an aquatic environment, manatees did not share specific neuron types such as tritufted and star-like neurons that have been found in cetaceans. Manatees exhibit an evolutionarily primitive pattern of cortical neuron morphology shared with most other mammals and do not appear to have neuronal specializations for an aquatic niche. © 2016 S. Karger AG, Basel.

  15. RNA-Seq Analysis of Human Trigeminal and Dorsal Root Ganglia with a Focus on Chemoreceptors.

    Directory of Open Access Journals (Sweden)

    Caroline Flegel

    Full Text Available The chemosensory capacity of the somatosensory system relies on the appropriate expression of chemoreceptors, which detect chemical stimuli and transduce sensory information into cellular signals. Knowledge of the complete repertoire of the chemoreceptors expressed in human sensory ganglia is lacking. This study employed the next-generation sequencing technique (RNA-Seq to conduct the first expression analysis of human trigeminal ganglia (TG and dorsal root ganglia (DRG. We analyzed the data with a focus on G-protein coupled receptors (GPCRs and ion channels, which are (potentially involved in chemosensation by somatosensory neurons in the human TG and DRG. For years, transient receptor potential (TRP channels have been considered the main group of receptors for chemosensation in the trigeminal system. Interestingly, we could show that sensory ganglia also express a panel of different olfactory receptors (ORs with putative chemosensory function. To characterize OR expression in more detail, we performed microarray, semi-quantitative RT-PCR experiments, and immunohistochemical staining. Additionally, we analyzed the expression data to identify further known or putative classes of chemoreceptors in the human TG and DRG. Our results give an overview of the major classes of chemoreceptors expressed in the human TG and DRG and provide the basis for a broader understanding of the reception of chemical cues.

  16. Generation of iPSC lines from primary human chorionic villi cells

    Directory of Open Access Journals (Sweden)

    Björn Lichtner

    2015-11-01

    Full Text Available Primary human chorionic villi (CV cells were used to generate the iPSC line by retroviral transduction of the four Yamanaka-factors OCT4, SOX2, KLF4 and c-MYC. Pluripotency was confirmed both in vivo and in vitro. The transcriptomes of the CV-derived iPSC lines and the human embryonic stem cell lines—H1 and H9 have a Pearson correlation of 0.929 and 0.943 respectively.

  17. Posterior insular cortex - a site of vestibular-somatosensory interaction?

    Science.gov (United States)

    Baier, Bernhard; Zu Eulenburg, Peter; Best, Christoph; Geber, Christian; Müller-Forell, Wibke; Birklein, Frank; Dieterich, Marianne

    2013-09-01

    Background In previous imaging studies the insular cortex (IC) has been identified as an essential part of the processing of a wide spectrum of perception and sensorimotor integration. Yet, there are no systematic lesion studies in a sufficient number of patients examining whether processing of vestibular and the interaction of somatosensory and vestibular signals take place in the IC. Methods We investigated acute stroke patients with lesions affecting the IC in order to fill this gap. In detail, we explored signs of a vestibular tone imbalance such as the deviation of the subjective visual vertical (SVV). We applied voxel-lesion behaviour mapping analysis in 27 patients with acute unilateral stroke. Results Our data demonstrate that patients with lesions of the posterior IC have an abnormal tilt of SVV. Furthermore, re-analysing data of 20 patients from a previous study, we found a positive correlation between thermal perception contralateral to the stroke and the severity of the SVV tilt. Conclusions We conclude that the IC is a sensory brain region where different modalities might interact.

  18. PULPOTOMIES WITH PORTLAND CEMENT IN HUMAN PRIMARY MOLARS

    Science.gov (United States)

    Conti, Taísa Regina; Sakai, Vivien Thiemy; Fornetti, Ana Paula Camolese; Moretti, Ana Beatriz Silveira; Oliveira, Thais Marchini; Lourenço, Natalino; Machado, Maria Aparecida Andrade Moreira; Abdo, Ruy Cesar Camargo

    2009-01-01

    Two clinical cases in which Portland cement (PC) was applied as a medicament after pulpotomy of mandibular primary molars in children are presented. Pulpotomy using PC was carried out in two mandibular first molars and one mandibular second molar, which were further followed-up. At the 3, 6 and 12-month follow-up appointments, clinical and radiographic examinations of the pulpotomized teeth and their periradicular area revealed that the treatments were successful in maintaining the teeth asymptomatic and preserving pulpal vitality. Additionally, the formation of a dentin bridge immediately below the PC could be observed in the three molars treated. PC may be considered as an effective alternative for primary molar pulpotomies, at least in a short-term period. Randomized clinical trials with human teeth are required in order to determine the suitability of PC before unlimited clinical use can be recommended. PMID:19148409

  19. Primary Human Placental Trophoblasts are Permissive for Zika Virus (ZIKV) Replication.

    Science.gov (United States)

    Aagaard, Kjersti M; Lahon, Anismrita; Suter, Melissa A; Arya, Ravi P; Seferovic, Maxim D; Vogt, Megan B; Hu, Min; Stossi, Fabio; Mancini, Michael A; Harris, R Alan; Kahr, Maike; Eppes, Catherine; Rac, Martha; Belfort, Michael A; Park, Chun Shik; Lacorazza, Daniel; Rico-Hesse, Rebecca

    2017-01-27

    Zika virus (ZIKV) is an emerging mosquito-borne (Aedes genus) arbovirus of the Flaviviridae family. Although ZIKV has been predominately associated with a mild or asymptomatic dengue-like disease, its appearance in the Americas has been accompanied by a multi-fold increase in reported incidence of fetal microcephaly and brain malformations. The source and mode of vertical transmission from mother to fetus is presumptively transplacental, although a causal link explaining the interval delay between maternal symptoms and observed fetal malformations following infection has been missing. In this study, we show that primary human placental trophoblasts from non-exposed donors (n = 20) can be infected by primary passage ZIKV-FLR isolate, and uniquely allowed for ZIKV viral RNA replication when compared to dengue virus (DENV). Consistent with their being permissive for ZIKV infection, primary trophoblasts expressed multiple putative ZIKV cell entry receptors, and cellular function and differentiation were preserved. These findings suggest that ZIKV-FLR strain can replicate in human placental trophoblasts without host cell destruction, thereby serving as a likely permissive reservoir and portal of fetal transmission with risk of latent microcephaly and malformations.

  20. From acute to persistent low back pain: a longitudinal investigation of somatosensory changes using quantitative sensory testing—an exploratory study

    Directory of Open Access Journals (Sweden)

    Anna Marcuzzi

    2018-04-01

    Conclusion:. Changes in mechanical pain sensitivity occurring in the subacute stage warrant further longitudinal evaluation to better understand the role of somatosensory changes in the development of persistent LBP. Pain-related cognitions at baseline distinguished persistent from the recovered LBP groups, emphasizing the importance of concurrent evaluation of psychological contributors in acute LBP.

  1. Arctigenin from Arctium lappa inhibits interleukin-2 and interferon gene expression in primary human T lymphocytes.

    Science.gov (United States)

    Tsai, Wei-Jern; Chang, Chu-Ting; Wang, Guei-Jane; Lee, Tzong-Huei; Chang, Shwu-Fen; Lu, Shao-Chun; Kuo, Yuh-Chi

    2011-03-25

    Arctium lappa (Niubang), a Chinese herbal medicine, is used to treat tissue inflammation. This study investigates the effects of arctigenin (AC), isolated from A. lappa, on anti-CD3/CD28 Ab-stimulated cell proliferation and cytokine gene expression in primary human T lymphocytes. Cell proliferation was determined with enzyme immunoassays and the tritiated thymidine uptake method. Cytokine production and gene expression were analyzed with reverse transcription-polymerase chain reaction. AC inhibited primary human T lymphocytes proliferation activated by anti-CD3/CD28 Ab. Cell viability test indicated that the inhibitory effects of AC on primary human T lymphocyte proliferation were not due to direct cytotoxicity. AC suppressed interleukin-2 (IL-2) and interferon-γ (IFN-γ) production in a concentration-dependent manner. Furthermore, AC decreased the IL-2 and IFN-γ gene expression in primary human T lymphocytes induced by anti-CD3/CD28 Ab. Reporter gene analyses revealed that AC decreased NF-AT-mediated reporter gene expression. AC inhibited T lymphocyte proliferation and decreased the gene expression of IL-2, IFN-γ and NF-AT.

  2. Supramodal parametric working memory processing in humans.

    Science.gov (United States)

    Spitzer, Bernhard; Blankenburg, Felix

    2012-03-07

    Previous studies of delayed-match-to-sample (DMTS) frequency discrimination in animals and humans have succeeded in delineating the neural signature of frequency processing in somatosensory working memory (WM). During retention of vibrotactile frequencies, stimulus-dependent single-cell and population activity in prefrontal cortex was found to reflect the task-relevant memory content, whereas increases in occipital alpha activity signaled the disengagement of areas not relevant for the tactile task. Here, we recorded EEG from human participants to determine the extent to which these mechanisms can be generalized to frequency retention in the visual and auditory domains. Subjects performed analogous variants of a DMTS frequency discrimination task, with the frequency information presented either visually, auditorily, or by vibrotactile stimulation. Examining oscillatory EEG activity during frequency retention, we found characteristic topographical distributions of alpha power over visual, auditory, and somatosensory cortices, indicating systematic patterns of inhibition and engagement of early sensory areas, depending on stimulus modality. The task-relevant frequency information, in contrast, was found to be represented in right prefrontal cortex, independent of presentation mode. In each of the three modality conditions, parametric modulations of prefrontal upper beta activity (20-30 Hz) emerged, in a very similar manner as recently found in vibrotactile tasks. Together, the findings corroborate a view of parametric WM as supramodal internal scaling of abstract quantity information and suggest strong relevance of previous evidence from vibrotactile work for a more general framework of quantity processing in human working memory.

  3. A fast intracortical brain-machine interface with patterned optogenetic feedback.

    Science.gov (United States)

    Abbasi, Aamir; Goueytes, Dorian; Shulz, Daniel E; Ego-Stengel, Valerie; Estebanez, Luc

    2018-04-04

    The development of brain-machine interfaces (BMIs) brings a new perspective to patients with a loss of autonomy. By combining online recordings of brain activity with a decoding algorithm, patients can learn to control a robotic arm in order to perform simple actions. However, in contrast to the vast amounts of somatosensory information channeled by limbs to the brain, current BMIs are devoid of touch and force sensors. Patients must therefore rely solely on vision and audition, which are maladapted to the control of a prosthesis. In contrast, in a healthy limb, somatosensory inputs alone can efficiently guide the handling of a fragile object, or ensure a smooth trajectory. We have developed a BMI in the mouse that includes a rich artificial somatosensory-like cortical feedback. Our setup includes online recordings of the activity of multiple neurons in the whisker primary motor cortex (vM1), and delivers feedback simultaneously via a low-latency, high-refresh rate and spatially structured photo-stimulation of the whisker primary somatosensory cortex (vS1), based on a mapping obtained by intrinsic imaging. We demonstrate the operation of the loop and show that mice can detect the neuronal spiking in vS1 triggered by the photo-stimulations. Finally, we show that the mice can learn a behavioral task relying only on the artificial inputs and outputs of the closed-loop BMI. This is the first motor BMI that includes a short-latency, intracortical, somatosensory-like feedback. It will be a useful platform to discover efficient cortical feedback schemes towards future human BMI applications. Creative Commons Attribution license.

  4. Somatosensory Nerve Function, Measured by Vibration Thresholds in Asymptomatic Tennis Players: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Sarah Harrisson

    2015-06-01

    Full Text Available Tennis players are vulnerable to injury in their upper limbs due to the repetitive exposure to racket vibrations and torsional forces during play, leading to musculoskeletal adaptations in the dominant arm including some evidence of changes in nerve function (Colak et al., 2004. Vibration is a sensitive technique for diagnosing mild pathology in clinically asymptomatic participant groups. It has been used in participants with various musculoskeletal disorders (Laursen et al., 2006 (Tucker et al., 2007 showing widespread and bilateral increases in vibration threshold. Tests of somatosensory function by vibration will be abnormal prior to changes in nerve conduction velocity. Thus vibration testing in a sub-clinical group of participants may a more sensitive measure of nerve function compared to nerve conduction by electrodiagnostic testing. The aim of this pilot study was to conduct an exploratory investigation to establish whether tennis players have a reduction in their somatosensory nerve function compared to non- tennis playing controls. It also set out to compare the somatosensory nerve function of the dominant compared to the non-dominant upper limb in tennis players. Healthy tennis players (males, n = 8, females, n = 2, mean age 22 years and control non- tennis playing volunteers (males, n = 6, females, n = 4, mean age 22 years were recruited on an opportunistic basis from a tennis centre in London UK. Participants were excluded if they had any history of neurological impairment, serious injury or fracture or any arthritic condition affecting the upper limbs, cervical or thoracic spine. Control participants were excluded if it was deemed that they played a sport where there was exposure to repetitive use of the upper body. Ethical approval was obtained from the University College London Ethics Committee and all participants gave written informed consent. A preliminary clinical examination was carried out on all participants followed by

  5. Somatosensory evoked potentials in the assessment of peripheral neuropathies: Commented results of a survey among French-speaking practitioners and recommendations for practice.

    Science.gov (United States)

    Morizot-Koutlidis, R; André-Obadia, N; Antoine, J-C; Attarian, S; Ayache, S S; Azabou, E; Benaderette, S; Camdessanché, J-P; Cassereau, J; Convers, P; d'Anglejean, J; Delval, A; Durand, M-C; Etard, O; Fayet, G; Fournier, E; Franques, J; Gavaret, M; Guehl, D; Guerit, J-M; Krim, E; Kubis, N; Lacour, A; Lozeron, P; Mauguière, F; Merle, P-E; Mesrati, F; Mutschler, V; Nicolas, G; Nordine, T; Pautot, V; Péréon, Y; Petiot, P; Pouget, J; Praline, J; Salhi, H; Trébuchon, A; Tyvaert, L; Vial, C; Zola, J-M; Zyss, J; Lefaucheur, J-P

    2015-05-01

    Somatosensory evoked potentials (SSEPs) are increasingly performed for the assessment of peripheral neuropathies, but no practical guidelines have yet been established in this specific application. To determine the relevant indication criteria and optimal technical parameters for SSEP recording in peripheral neuropathy investigation. A survey was conducted among the French-speaking practitioners with experience of SSEP recording in the context of peripheral neuropathies. The results of the survey were analyzed and discussed to provide recommendations for practice. SSEPs appear to be a second-line test when electroneuromyographic investigation is not sufficiently conclusive, providing complementary and valuable information on central and proximal peripheral conduction in the somatosensory pathways. Guidelines for a standardized recording protocol, including the various parameters to be measured, are proposed. We hope that these proposals will help to recognize the value of this technique in peripheral neuropathy assessment in clinical practice. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  6. Enhancement of Median Nerve Regeneration by Mesenchymal Stem Cells Engraftment in an Absorbable Conduit: Improvement of Peripheral Nerve Morphology with Enlargement of Somatosensory Cortical Representation.

    Directory of Open Access Journals (Sweden)

    Julia Teixeira Oliveira

    2014-10-01

    Full Text Available We studied the morphology and the cortical representation of the median nerve (MN, 10 weeks after a transection immediately followed by treatment with tubulization using a polycaprolactone (PCL conduit with or without bone marrow-derived mesenchymal stem cell (MSC transplant. In order to characterize the cutaneous representation of MN inputs in primary somatosensory cortex (S1, electrophysiological cortical mapping of the somatosensory representation of the forepaw and adjacent body parts was performed after acute lesion of all brachial plexus nerves, except for the MN. This was performed in ten adult male Wistar rats randomly assigned in 3 groups: MN Intact (n=4, PCL-Only (n=3 and PCL+MSC (n=3. Ten weeks before mapping procedures in animals from PCL-Only and PCL+MSC groups, animal were subjected to MN transection with removal of a 4-mm-long segment, immediately followed by suturing a PCL conduit to the nerve stumps with (PCL+MSC group or without (PCL-Only group injection of MSC into the conduit. After mapping the representation of the MN in S1, animals had a segment of the regenerated nerve processed for light and transmission electron microscopy. For histomorphometric analysis of the nerve segment, sample size was increased to 5 animals per experimental group. The PCL+MSC group presented a higher number of myelinated fibers and a larger cortical representation of MN inputs in S1 (3,383±390 fibers; 2.3 mm2, respectively than the PCL-Only group (2,226±575 fibers; 1.6 mm2. In conclusion, MSC-based therapy associated with PCL conduits can improve MN regeneration. This treatment seems to rescue the nerve representation in S1, thus minimizing the stabilization of new representations of adjacent body parts in regions previously responsive to the MN.

  7. Primary pulmonary choriocarcinoma after human chorionic gonadotropin normalization following hydatidiform mole

    DEFF Research Database (Denmark)

    Maestá, Izildinha; Leite, Fábio Vicente; Michelin, Odair Carlito

    2010-01-01

    BACKGROUND: Primary pulmonary choriocarcinoma (PPC) is rare and frequently leads to death. CASES: Two young patients presented with previous molar pregnancy and spontaneous serum human chorionic gonadotropin (hCG) normalization. Patient 1 was referred to our center after partial response to chemo...

  8. Inducing homeostatic-like plasticity in human motor cortex through converging corticocortical inputs

    DEFF Research Database (Denmark)

    Pötter-Nerger, Monika; Fischer, Sarah; Mastroeni, Claudia

    2009-01-01

    Transcranial stimulation techniques have revealed homeostatic-like metaplasticity in the hand area of the human primary motor cortex (M1(HAND)) that controls stimulation-induced changes in corticospinal excitability. Here we combined two interventional protocols that induce long-term depression......TMS) of the left dorsal premotor cortex (PMD) was first applied to produce an LTP-like increase (5 Hz rTMS) or LTD-like decrease (1 Hz rTMS) in corticospinal excitability in left M1(HAND) via premotor-to-motor inputs. Following PMD rTMS, paired-associative stimulation (PAS) was applied to the right median nerve...... and left M1(HAND) to induce spike-time-dependent plasticity in sensory-to-motor inputs to left M1(HAND). We adjusted the interstimulus interval to the N20 latency of the median nerve somatosensory-evoked cortical potential to produce an LTP-like increase (PAS(N20+2ms)) or an LTD-like decrease (PAS(N20-5ms...

  9. Gating of the vertex somatosensory and auditory evoked potential P50 and the correlation to skin conductance orienting response in healthy men

    DEFF Research Database (Denmark)

    Arnfred, S M; Eder, D N; Hemmingsen, R P

    2001-01-01

    A defect in auditory evoked potential (AEP) P50 gating supports the theory of information-processing deficits in schizophrenia. The relationship between gating of the mid-latency evoked potentials (EP) in the somatosensory and the auditory modalities has not been studied together before. In schiz...

  10. Excessive body fat linked to blunted somatosensory cortex response to general reward in adolescents.

    Science.gov (United States)

    Navas, J F; Barrós-Loscertales, A; Costumero-Ramos, V; Verdejo-Román, J; Vilar-López, R; Verdejo-García, A

    2018-01-01

    The brain reward system is key to understanding adolescent obesity in the current obesogenic environment, rich in highly appetising stimuli, to which adolescents are particularly sensitive. We aimed to examine the association between body fat levels and brain reward system responsivity to general (monetary) rewards in male and female adolescents. Sixty-eight adolescents (34 females; mean age (s.d.)= 16.56 (1.35)) were measured for body fat levels with bioelectric impedance, and underwent a functional magnetic resonance imaging (fMRI) scan during the Monetary Incentive Delay (MID) task. The MID task reliably elicits brain activations associated with two fundamental aspects of reward processing: anticipation and feedback. We conducted regression analyses to examine the association between body fat and brain reward system responsivity during reward anticipation and feedback, while controlling for sex, age and socioeconomic status. We also analysed the moderating impact of sex on the relationship between fat levels and brain responsivity measures. Brain imaging analyses were corrected for multiple comparisons, with a cluster-defining threshold of Preward feedback after controlling for key sociodemographic variables. Although we did not find significant associations between body fat and brain activations during reward anticipation, S1/supramarginal gyrus activation during feedback was linked to increased negative prediction error, that is, less reward than expected, in illustrative post hoc analyses. Sex did not significantly moderate the association between body fat and brain activation in the MID task. In adolescents, higher adiposity is linked to hypo-responsivity of somatosensory regions during general (monetary) reward feedback. Findings suggest that adolescents with excess weight have blunted activation in somatosensory regions involved in reward feedback learning.

  11. Arctigenin from Arctium lappa inhibits interleukin-2 and interferon gene expression in primary human T lymphocytes

    Science.gov (United States)

    2011-01-01

    Background Arctium lappa (Niubang), a Chinese herbal medicine, is used to treat tissue inflammation. This study investigates the effects of arctigenin (AC), isolated from A. lappa, on anti-CD3/CD28 Ab-stimulated cell proliferation and cytokine gene expression in primary human T lymphocytes. Methods Cell proliferation was determined with enzyme immunoassays and the tritiated thymidine uptake method. Cytokine production and gene expression were analyzed with reverse transcription-polymerase chain reaction. Results AC inhibited primary human T lymphocytes proliferation activated by anti-CD3/CD28 Ab. Cell viability test indicated that the inhibitory effects of AC on primary human T lymphocyte proliferation were not due to direct cytotoxicity. AC suppressed interleukin-2 (IL-2) and interferon-γ (IFN-γ) production in a concentration-dependent manner. Furthermore, AC decreased the IL-2 and IFN-γ gene expression in primary human T lymphocytes induced by anti-CD3/CD28 Ab. Reporter gene analyses revealed that AC decreased NF-AT-mediated reporter gene expression. Conclusion AC inhibited T lymphocyte proliferation and decreased the gene expression of IL-2, IFN-γ and NF-AT. PMID:21435270

  12. Arctigenin from Arctium lappa inhibits interleukin-2 and interferon gene expression in primary human T lymphocytes

    Directory of Open Access Journals (Sweden)

    Chang Shwu-Fen

    2011-03-01

    Full Text Available Abstract Background Arctium lappa (Niubang, a Chinese herbal medicine, is used to treat tissue inflammation. This study investigates the effects of arctigenin (AC, isolated from A. lappa, on anti-CD3/CD28 Ab-stimulated cell proliferation and cytokine gene expression in primary human T lymphocytes. Methods Cell proliferation was determined with enzyme immunoassays and the tritiated thymidine uptake method. Cytokine production and gene expression were analyzed with reverse transcription-polymerase chain reaction. Results AC inhibited primary human T lymphocytes proliferation activated by anti-CD3/CD28 Ab. Cell viability test indicated that the inhibitory effects of AC on primary human T lymphocyte proliferation were not due to direct cytotoxicity. AC suppressed interleukin-2 (IL-2 and interferon-γ (IFN-γ production in a concentration-dependent manner. Furthermore, AC decreased the IL-2 and IFN-γ gene expression in primary human T lymphocytes induced by anti-CD3/CD28 Ab. Reporter gene analyses revealed that AC decreased NF-AT-mediated reporter gene expression. Conclusion AC inhibited T lymphocyte proliferation and decreased the gene expression of IL-2, IFN-γ and NF-AT.

  13. Heightened sensitivity to somatosensory stimuli in anorexia nervosa: an exploratory study with the SASTCA scale.

    Science.gov (United States)

    Calvo Sagardoy, Rosa; Gallego Morales, Luis T; Kassem García, Soledad; Codesal Julián, Rosana; Blanco Fernández, Ascensión; Solórzano Ostolaza, Gloria; Morales Martínez, Carmen

    2014-11-04

    To analyse the presence of heightened sensory sensitivity in patients with anorexia nervosa, which seems similar but not identical to that described in patients with unexplained somatic symptoms or body dysmorphic disorder. We developed a sensory sensitivity scale in eating disorders (SASTCA), which measures the intensity of the response to specific somatosensory stimuli. The scale was completed by 48 patients with anorexia and a control group of 31 participants matched in age, sex and social and educational level. The results were compared with those obtained with the Barsky Somatosensory Amplification Scale (SSAS). The reliability (Cronbach's/alpha, 0.946; Guttman/ split-half, 0.936) and validity (ROC, 0.933) of the SASTCA scale are indicative of its high sensitivity and specificity. The anorexia group had a significantly higher mean score on the SASTCA scale than the control group (pscales correlated positively (r=.634). These preliminary results suggest the presence in Anorexia of heightened sensory sensitivity which differs from the sensitivity of the control group. This sensitivity has a significant relationship with that described in patients with somatic complaints about health (SSD) or appearance (BDD). Could this heightened sensory sensitivity help us to explain the process of forming the distorted body self-concept (I'm fat, sick, ugly) in all these patients? Once its presence has been confirmed in other patients with anorexia, their relatives and other patients with somatic disorders this heightened sensitivity could constitute the somatic endophenotype of anorexia? Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  14. RANK and RANK ligand expression in primary human osteosarcoma

    Directory of Open Access Journals (Sweden)

    Daniel Branstetter

    2015-09-01

    Our results demonstrate RANKL expression was observed in the tumor element in 68% of human OS using IHC. However, the staining intensity was relatively low and only 37% (29/79 of samples exhibited≥10% RANKL positive tumor cells. RANK expression was not observed in OS tumor cells. In contrast, RANK expression was clearly observed in other cells within OS samples, including the myeloid osteoclast precursor compartment, osteoclasts and in giant osteoclast cells. The intensity and frequency of RANKL and RANK staining in OS samples were substantially less than that observed in GCTB samples. The observation that RANKL is expressed in OS cells themselves suggests that these tumors may mediate an osteoclastic response, and anti-RANKL therapy may potentially be protective against bone pathologies in OS. However, the absence of RANK expression in primary human OS cells suggests that any autocrine RANKL/RANK signaling in human OS tumor cells is not operative, and anti-RANKL therapy would not directly affect the tumor.

  15. Do patients with chronic unilateral orofacial pain due to a temporomandibular disorder show increased attending to somatosensory input at the painful side of the jaw?

    Directory of Open Access Journals (Sweden)

    Stefaan Van Damme

    2018-01-01

    Full Text Available Background Patients with chronic orofacial pain due to temporomandibular disorders (TMD display alterations in somatosensory processing at the jaw, such as amplified perception of tactile stimuli, but the underlying mechanisms remain unclear. This study investigated one possible explanation, namely hypervigilance, and tested if TMD patients with unilateral pain showed increased attending to somatosensory input at the painful side of the jaw. Methods TMD patients with chronic unilateral orofacial pain (n = 20 and matched healthy volunteers (n = 20 performed a temporal order judgment (TOJ task indicated which one of two tactile stimuli, presented on each side of the jaw, they had perceived first. TOJ methodology allows examining spatial bias in somatosensory processing speed. Furthermore, after each block of trials, the participants rated the perceived intensity of tactile stimuli separately for both sides of the jaw. Finally, questionnaires assessing pain catastrophizing, fear-avoidance beliefs, and pain vigilance, were completed. Results TMD patients tended to perceive tactile stimuli at the painful jaw side as occurring earlier in time than stimuli at the non-painful side but this effect did not reach conventional levels of significance (p = .07. In the control group, tactile stimuli were perceived as occurring simultaneously. Secondary analyses indicated that the magnitude of spatial bias in the TMD group is positively associated with the extent of fear-avoidance beliefs. Overall, intensity ratings of tactile stimuli were significantly higher in the TMD group than in the control group, but there was no significant difference between the painful and non-painful jaw side in the TMD patients. Discussion The hypothesis that TMD patients with chronic unilateral orofacial pain preferentially attend to somatosensory information at the painful side of the jaw was not statistically supported, although lack of power could not be ruled out as a

  16. On the presence of high-order interactions among somatosensory neurons and their effect on information transmission

    International Nuclear Information System (INIS)

    Ince, Robin A A; Montani, Fernando; Panzeri, Stefano; Arabzadeh, Ehsan; Diamond, Mathew E

    2009-01-01

    In order to understand how populations of neurons encode information about external correlates, it is important to develop minimal models of the probability of neural population responses which capture all the salient changes of neural responses with stimuli. In this context, it is particularly useful to determine whether interactions among neurons responding to stimuli can be described by a pairwise interaction model, or whether a higher order interaction model is needed. To address this question, we compared real neural population activity obtained from the rat somatosensory cortex to maximum-entropy models which take into account only interaction of up any given order. By performing these comparisons, we found that interactions of order two were sufficient to explain a large amount of observed stimulus-response distributions, but not all of them. Triple-wise interactions were necessary to fully explain the data. We then used Shannon information to compute the impact of high order correlations on the amount of somatosensory information transmitted by the neural population. We found that correlations of order two gave a good approximation of information carried by the neural population, within 4% of the true value. Third order correlations gave an even better approximation, within 2% of the true value. Taken together, these results suggest that higher order interactions exist and shape the dynamics of cortical networks, but play a quantitatively minor role in determining the information capacity of neural populations.

  17. On the presence of high-order interactions among somatosensory neurons and their effect on information transmission

    Energy Technology Data Exchange (ETDEWEB)

    Ince, Robin A A [Faculty of Life Science, University of Manchester, 3.431 Stopford Building, Oxford Road, Manchester M13 9PL (United Kingdom); Montani, Fernando; Panzeri, Stefano [Robotics, Brain, and Cognitive Sciences Department, Italian Institute of Technology, Via Morego 30, 16163 Genova (Italy); Arabzadeh, Ehsan [School of Psychology, University of New South Wales, Sydney, New South Wales (Australia); Diamond, Mathew E, E-mail: stefano.panzeri@iit.i [Cognitive Neuroscience Sector, International School for Advanced Studies, Trieste (Italy) and the SISSA Unit, Italian Institute of Technology, Trieste (Italy)

    2009-12-01

    In order to understand how populations of neurons encode information about external correlates, it is important to develop minimal models of the probability of neural population responses which capture all the salient changes of neural responses with stimuli. In this context, it is particularly useful to determine whether interactions among neurons responding to stimuli can be described by a pairwise interaction model, or whether a higher order interaction model is needed. To address this question, we compared real neural population activity obtained from the rat somatosensory cortex to maximum-entropy models which take into account only interaction of up any given order. By performing these comparisons, we found that interactions of order two were sufficient to explain a large amount of observed stimulus-response distributions, but not all of them. Triple-wise interactions were necessary to fully explain the data. We then used Shannon information to compute the impact of high order correlations on the amount of somatosensory information transmitted by the neural population. We found that correlations of order two gave a good approximation of information carried by the neural population, within 4% of the true value. Third order correlations gave an even better approximation, within 2% of the true value. Taken together, these results suggest that higher order interactions exist and shape the dynamics of cortical networks, but play a quantitatively minor role in determining the information capacity of neural populations.

  18. Natural HIV-1 NEF accelerates virus replication in primary human lymphocytes

    NARCIS (Netherlands)

    de Ronde, A.; Klaver, B.; Keulen, W.; Smit, L.; Goudsmit, J.

    1992-01-01

    HIV-1 NEF genes were isolated directly from peripheral blood lymphocyte DNA of two HIV-1-infected individuals and cloned into an HXB-2-infectious molecular clone. The effect of NEF on virus production in T-cell lines and primary human lymphocytes was studied. Naturally occurring NEF accelerates

  19. Humanized medium (h7H) allows long-term primary follicular thyroid cultures from human normal thyroid, benign neoplasm, and cancer.

    Science.gov (United States)

    Bravo, Susana B; Garcia-Rendueles, Maria E R; Garcia-Rendueles, Angela R; Rodrigues, Joana S; Perez-Romero, Sihara; Garcia-Lavandeira, Montserrat; Suarez-Fariña, Maria; Barreiro, Francisco; Czarnocka, Barbara; Senra, Ana; Lareu, Maria V; Rodriguez-Garcia, Javier; Cameselle-Teijeiro, Jose; Alvarez, Clara V

    2013-06-01

    Mechanisms of thyroid physiology and cancer are principally studied in follicular cell lines. However, human thyroid cancer lines were found to be heavily contaminated by other sources, and only one supposedly normal-thyroid cell line, immortalized with SV40 antigen, is available. In primary culture, human follicular cultures lose their phenotype after passage. We hypothesized that the loss of the thyroid phenotype could be related to culture conditions in which human cells are grown in medium optimized for rodent culture, including hormones with marked differences in its affinity for the relevant rodent/human receptor. The objective of the study was to define conditions that allow the proliferation of primary human follicular thyrocytes for many passages without losing phenotype. Concentrations of hormones, transferrin, iodine, oligoelements, antioxidants, metabolites, and ethanol were adjusted within normal homeostatic human serum ranges. Single cultures were identified by short tandem repeats. Human-rodent interspecies contamination was assessed. We defined an humanized 7 homeostatic additives medium enabling growth of human thyroid cultures for more than 20 passages maintaining thyrocyte phenotype. Thyrocytes proliferated and were grouped as follicle-like structures; expressed Na+/I- symporter, pendrin, cytokeratins, thyroglobulin, and thyroperoxidase showed iodine-uptake and secreted thyroglobulin and free T3. Using these conditions, we generated a bank of thyroid tumors in culture from normal thyroids, Grave's hyperplasias, benign neoplasms (goiter, adenomas), and carcinomas. Using appropriate culture conditions is essential for phenotype maintenance in human thyrocytes. The bank of thyroid tumors in culture generated under humanized humanized 7 homeostatic additives culture conditions will provide a much-needed tool to compare similarly growing cells from normal vs pathological origins and thus to elucidate the molecular basis of thyroid disease.

  20. HANPP Collection: Human Appropriation of Net Primary Productivity (HANPP) by Country and Product

    Data.gov (United States)

    National Aeronautics and Space Administration — The Human Appropriation of Net Primary Productivity (HANPP) by Country and Product portion of the HANPP Collection contains tabular data on carbon-equivalents of...

  1. Posterior insular cortex – a site of vestibular–somatosensory interaction?

    Science.gov (United States)

    Baier, Bernhard; zu Eulenburg, Peter; Best, Christoph; Geber, Christian; Müller-Forell, Wibke; Birklein, Frank; Dieterich, Marianne

    2013-01-01

    Background In previous imaging studies the insular cortex (IC) has been identified as an essential part of the processing of a wide spectrum of perception and sensorimotor integration. Yet, there are no systematic lesion studies in a sufficient number of patients examining whether processing of vestibular and the interaction of somatosensory and vestibular signals take place in the IC. Methods We investigated acute stroke patients with lesions affecting the IC in order to fill this gap. In detail, we explored signs of a vestibular tone imbalance such as the deviation of the subjective visual vertical (SVV). We applied voxel-lesion behaviour mapping analysis in 27 patients with acute unilateral stroke. Results Our data demonstrate that patients with lesions of the posterior IC have an abnormal tilt of SVV. Furthermore, re-analysing data of 20 patients from a previous study, we found a positive correlation between thermal perception contralateral to the stroke and the severity of the SVV tilt. Conclusions We conclude that the IC is a sensory brain region where different modalities might interact. PMID:24392273

  2. Cytoskeletal stability and metabolic alterations in primary human macrophages in long-term microgravity.

    Directory of Open Access Journals (Sweden)

    Svantje Tauber

    Full Text Available The immune system is one of the most affected systems of the human body during space flight. The cells of the immune system are exceptionally sensitive to microgravity. Thus, serious concerns arise, whether space flight associated weakening of the immune system ultimately precludes the expansion of human presence beyond the Earth's orbit. For human space flight, it is an urgent need to understand the cellular and molecular mechanisms by which altered gravity influences and changes the functions of immune cells. The CELLBOX-PRIME (= CellBox-Primary Human Macrophages in Microgravity Environment experiment investigated for the first time microgravity-associated long-term alterations in primary human macrophages, one of the most important effector cells of the immune system. The experiment was conducted in the U.S. National Laboratory on board of the International Space Station ISS using the NanoRacks laboratory and Biorack type I standard CELLBOX EUE type IV containers. Upload and download were performed with the SpaceX CRS-3 and the Dragon spaceship on April 18th, 2014 / May 18th, 2014. Surprisingly, primary human macrophages exhibited neither quantitative nor structural changes of the actin and vimentin cytoskeleton after 11 days in microgravity when compared to 1g controls. Neither CD18 or CD14 surface expression were altered in microgravity, however ICAM-1 expression was reduced. The analysis of 74 metabolites in the cell culture supernatant by GC-TOF-MS, revealed eight metabolites with significantly different quantities when compared to 1g controls. In particular, the significant increase of free fucose in the cell culture supernatant was associated with a significant decrease of cell surface-bound fucose. The reduced ICAM-1 expression and the loss of cell surface-bound fucose may contribute to functional impairments, e.g. the activation of T cells, migration and activation of the innate immune response. We assume that the surprisingly small

  3. Mechanisms of acetaminophen-induced cell death in primary human hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Yuchao; McGill, Mitchell R.; Dorko, Kenneth [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Kumer, Sean C.; Schmitt, Timothy M.; Forster, Jameson [Department of Surgery, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160 (United States)

    2014-09-15

    Acetaminophen (APAP) overdose is the most prevalent cause of drug-induced liver injury in western countries. Numerous studies have been conducted to investigate the mechanisms of injury after APAP overdose in various animal models; however, the importance of these mechanisms for humans remains unclear. Here we investigated APAP hepatotoxicity using freshly isolated primary human hepatocytes (PHH) from either donor livers or liver resections. PHH were exposed to 5 mM, 10 mM or 20 mM APAP over a period of 48 h and multiple parameters were assessed. APAP dose-dependently induced significant hepatocyte necrosis starting from 24 h, which correlated with the clinical onset of human liver injury after APAP overdose. Interestingly, cellular glutathione was depleted rapidly during the first 3 h. APAP also resulted in early formation of APAP-protein adducts (measured in whole cell lysate and in mitochondria) and mitochondrial dysfunction, indicated by the loss of mitochondrial membrane potential after 12 h. Furthermore, APAP time-dependently triggered c-Jun N-terminal kinase (JNK) activation in the cytosol and translocation of phospho-JNK to the mitochondria. Both co-treatment and post-treatment (3 h) with the JNK inhibitor SP600125 reduced JNK activation and significantly attenuated cell death at 24 h and 48 h after APAP. The clinical antidote N-acetylcysteine offered almost complete protection even if administered 6 h after APAP and a partial protection when given at 15 h. Conclusion: These data highlight important mechanistic events in APAP toxicity in PHH and indicate a critical role of JNK in the progression of injury after APAP in humans. The JNK pathway may represent a therapeutic target in the clinic. - Highlights: • APAP reproducibly causes cell death in freshly isolated primary human hepatocytes. • APAP induces adduct formation, JNK activation and mitochondrial dysfunction in PHH. • Mitochondrial adducts and JNK translocation are delayed in PHH compared to

  4. Managers' perspectives on recruitment and human resource development practices in primary health care.

    Science.gov (United States)

    Lammintakanen, Johanna; Kivinen, Tuula; Kinnunen, Juha

    2010-12-01

    The aim of this study is to describe primary health care managers' attitudes and views on recruitment and human resource development in general and to ascertain whether there are any differences in the views of managers in the southern and northern regions of Finland. A postal questionnaire was sent to 315 primary health care managers, of whom 55% responded. The data were analysed using descriptive statistics and cross-tabulation according to the location of the health centre. There were few differences in managers' attitudes and views on recruitment and human resource development. In the southern region, managers estimated that their organization would be less attractive to employees in the future and they were more positive about recruiting employees abroad. Furthermore, managers in the northern region were more positive regarding human resource development and its various practices. Although the results are preliminary in nature, it seems that managers in different regions have adopted different strategies in order to cope with the shrinking pool of new recruits. In the southern region, managers were looking abroad to find new employees, while in the northern region, managers put effort into retaining the employees in the organization with different human resource development practices.

  5. The primary motor and premotor areas of the human cerebral cortex.

    Science.gov (United States)

    Chouinard, Philippe A; Paus, Tomás

    2006-04-01

    Brodmann's cytoarchitectonic map of the human cortex designates area 4 as cortex in the anterior bank of the precentral sulcus and area 6 as cortex encompassing the precentral gyrus and the posterior portion of the superior frontal gyrus on both the lateral and medial surfaces of the brain. More than 70 years ago, Fulton proposed a functional distinction between these two areas, coining the terms primary motor area for cortex in Brodmann area 4 and premotor area for cortex in Brodmann area 6. The parcellation of the cortical motor system has subsequently become more complex. Several nonprimary motor areas have been identified in the brain of the macaque monkey, and associations between anatomy and function in the human brain are being tested continuously using brain mapping techniques. In the present review, the authors discuss the unique properties of the primary motor area (M1), the dorsal portion of the premotor cortex (PMd), and the ventral portion of the premotor cortex (PMv). They end this review by discussing how the premotor areas influence M1.

  6. Primary culture of human Schwann and schwannoma cells: improved and simplified protocol.

    Science.gov (United States)

    Dilwali, Sonam; Patel, Pratik B; Roberts, Daniel S; Basinsky, Gina M; Harris, Gordon J; Emerick, Kevin S; Stankovic, Konstantina M

    2014-09-01

    Primary culture of human Schwann cells (SCs) and vestibular schwannoma (VS) cells are invaluable tools to investigate SC physiology and VS pathobiology, and to devise effective pharmacotherapies against VS, which are sorely needed. However, existing culture protocols, in aiming to create robust, pure cultures, employ methods that can lead to loss of biological characteristics of the original cells, potentially resulting in misleading biological findings. We have developed a minimally manipulative method to culture primary human SC and VS cells, without the use of selective mitogens, toxins, or time-consuming and potentially transformative laboratory techniques. Schwann cell purity was quantified longitudinally using S100 staining in SC cultures derived from the great auricular nerve and VS cultures followed for 7 and 12 weeks, respectively. SC cultures retained approximately ≥85% purity for 2 weeks. VS cultures retained approximately ≥80% purity for the majority of the span of 12 weeks, with maximal purity of 87% at 2 weeks. The VS cultures showed high level of biological similarity (68% on average) to their respective parent tumors, as assessed using a protein array featuring 41 growth factors and receptors. Apoptosis rate in vitro negatively correlated with tumor volume. Our results, obtained using a faster, simplified culturing method than previously utilized, indicate that highly pure, primary human SC and VS cultures can be established with minimal manipulation, reaching maximal purity at 2 weeks of culture. The VS cultures recapitulate the parent tumors' biology to a great degree, making them relevant models to investigate VS pathobiology. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Mindfulness starts with the body: Somatosensory attention and top-down modulation of cortical alpha rhythms in mindfulness meditation

    Directory of Open Access Journals (Sweden)

    Catherine E Kerr

    2013-02-01

    Full Text Available Mindfulness Based Stress Reduction (MBSR and Mindfulness Based Cognitive Therapy (MBCT use a common set of exercises to reduce distress in chronic pain and decrease risk of depression relapse. These standardized mindfulness (ST-Mindfulness practices predominantly require attending to breath and body sensations. Here, we offer a novel view of ST-Mindfulness’s somatic focus as a form of training for optimizing attentional modulation of 7-14 Hz alpha rhythms that play a key role in filtering inputs to primary sensory neocortex and organizing the flow of sensory information. In support of the framework, we describe our previous finding (Kerr et al, 2011 that ST-Mindfulness enhanced attentional regulation of alpha in primary somatosensory cortex (SI. The framework allows us to make several predictions. In chronic pain, we predict somatic attention in ST-Mindfulness de-biases alpha in SI, freeing up pain-focused attentional resources. In depression relapse, we predict ST-Mindfulness’s somatic attention competes with internally focused rumination, as internally focused cognitive processes (e.g., working and short term memory rely on alpha filtering of sensory input. Our computational model (Jones et al, 2009 predicts ST-Mindfulness enhances top-down modulation of alpha by facilitating precise alterations in timing and efficacy of SI thalamocortical inputs. We conclude by considering how the proposed framework aligns with Buddhist teachings that mindfulness starts with mindfulness of the body. Translating this theory into neurophysiology, we hypothesize that with its somatic focus, mindfulness’ top-down alpha rhythm modulation in SI enhances gain control which, in turn, sensitizes practitioners to better detect and regulate when the mind wanders from its somatic focus. This enhanced regulation of somatic mind-wandering may be an early stage of mindfulness training, leading to cognitive regulation and metacognition.

  8. Immunotoxicity testing using human primary leukocytes: An adjunct approach for the evaluation of human risk.

    Science.gov (United States)

    Phadnis-Moghe, Ashwini S; Kaminski, Norbert E

    2017-04-01

    Historically, immunotoxicity testing for chemicals, pesticides and pharmaceuticals has relied heavily on animal models to identify effects on the immune system followed by extrapolation to humans. Substantial progress has been made in the past decade on understanding human immune cell regulation, adaptive and innate immune responses and its modulation. The human immune system is complex and there exists diversity within composition, localization, and activation of different immune cell types between individuals. The inherent variation in human populations owing to genetics and environment can have a significant influence on the response of the immune system to infectious agents, drugs, chemicals and other environmental factors. Several recent reports have highlighted that mouse models of sepsis and inflammation are poorly predictive of human disease physiology and pathology. Rodent and human immune cells differ in the expression of cell surface proteins and phenotypes expressed in disease models, which may significantly influence the mechanism of action of xenobiotics and susceptibility yielding a different profile of activity across animal species. In the light of these differences and recent trends toward precision medicine, personalized therapies and the 3Rs (reduce, replace and refine animal use) approaches, the importance of using 'all human' model systems cannot be overstated. Hence, this opinion piece aims to discuss new models used to assess the effects of environmental contaminants and immune modulators on the immune response in human cells, the advantages and challenges of using human primary cells in immunotoxicology research and the implication for the future of immunotoxicity testing.

  9. Pulpal status of human primary teeth with physiological root resorption.

    Science.gov (United States)

    Monteiro, Joana; Day, Peter; Duggal, Monty; Morgan, Claire; Rodd, Helen

    2009-01-01

    The overall aim of this study was to determine whether any changes occur in the pulpal structure of human primary teeth in association with physiological root resorption. The experimental material comprised 64 sound primary molars, obtained from children requiring routine dental extractions under general anaesthesia. Pulp sections were processed for indirect immunofluorescence using combinations of: (i) protein gene product 9.5 (a general neuronal marker); (ii) leucocyte common antigen CD45 (a general immune cell marker); and (iii) Ulex europaeus I lectin (a marker of vascular endothelium). Image analysis was then used to determine the percentage area of staining for each label within both the pulp horn and mid-coronal region. Following measurement of the greatest degree of root resorption in each sample, teeth were subdivided into three groups: those with physiological resorption involving less than one-third, one-third to two-thirds, and more than two-thirds of their root length. Wide variation was evident between different tooth samples with some resorbed teeth showing marked changes in pulpal histology. Decreased innervation density, increased immune cell accumulation, and increased vascularity were evident in some teeth with advanced root resorption. Analysis of pooled data, however, did not reveal any significant differences in mean percentage area of staining for any of these variables according to the three root resorption subgroups (P > 0.05, analysis of variance on transformed data). This investigation has revealed some changes in pulpal status of human primary teeth with physiological root resorption. These were not, however, as profound as one may have anticipated. It is therefore speculated that teeth could retain the potential for sensation, healing, and repair until advanced stages of root resorption.

  10. Different Chondrogenic Potential among Human Induced Pluripotent Stem Cells from Diverse Origin Primary Cells

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    Yeri Alice Rim

    2018-01-01

    Full Text Available Scientists have tried to reprogram various origins of primary cells into human induced pluripotent stem cells (hiPSCs. Every somatic cell can theoretically become a hiPSC and give rise to targeted cells of the human body. However, there have been debates on the controversy about the differentiation propensity according to the origin of primary cells. We reprogrammed hiPSCs from four different types of primary cells such as dermal fibroblasts (DF, n=3, peripheral blood mononuclear cells (PBMC, n=3, cord blood mononuclear cells (CBMC, n=3, and osteoarthritis fibroblast-like synoviocytes (OAFLS, n=3. Established hiPSCs were differentiated into chondrogenic pellets. All told, cartilage-specific markers tended to express more by the order of CBMC > DF > PBMC > FLS. Origin of primary cells may influence the reprogramming and differentiation thereafter. In the context of chondrogenic propensity, CBMC-derived hiPSCs can be a fairly good candidate cell source for cartilage regeneration. The differentiation of hiPSCs into chondrocytes may help develop “cartilage in a dish” in the future. Also, the ideal cell source of hiPSC for chondrogenesis may contribute to future application as well.

  11. Purification and primary structure determination of human lysosomal dipeptidase.

    Science.gov (United States)

    Dolenc, Iztok; Mihelic, Marko

    2003-02-01

    The lysosomal metallopeptidase is an enzyme that acts preferentially on dipeptides with unsubstituted N- and C-termini. Its activity is highest in slightly acidic pH. Here we describe the isolation and characterization of lysosomal dipeptidase from human kidney. The isolated enzyme has the amino-terminal sequence DVAKAIINLAVY and is a homodimer with a molecular mass of 100 kDa. So far no amino acid sequence has been determined for this metallopeptidase. The complete primary structure as deduced from the nucleotide sequence revealed that the isolated dipeptidase is similar to blood plasma glutamate carboxypeptidase.

  12. Uptake of gold nanoparticles in primary human endothelial cells

    DEFF Research Database (Denmark)

    Klingberg, Henrik; Oddershede, Lene B.; Löschner, Katrin

    2015-01-01

    Gold nanoparticles (AuNPs) are relevant in nanomedicine for drug delivery in the vascular system, where endothelial cells are the first point of contact. We investigated the uptake of 80 nm AuNPs in primary human umbilical vein endothelial cells (HUVECs) by flow cytometry, 3D confocal microscopy......–3 or more particles. Pre-treatment with chlorpromazine inhibited the AuNP-uptake in HUVECs, indicating that internalisation occurred mainly by clathrin-mediated endocytosis. Cell activation by exposure to tumour necrosis factor or lipopolysaccharide had a slight or no effect on the uptake of Au...

  13. A Primary Human Critical Success Factors Model for the ERP System Implementation

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    Jenko Aleksander

    2016-08-01

    Full Text Available Background and Purpose: Many researchers have investigated various Critical success factors (CSFs and the different causes of ERP implementation project failures. Despite a detailed literature preview, we were unable to find an appropriate research with a comprehensive overview of the true causes behind CSFs, observed from a human factors perspective. The objective of this research was therefore to develop and evaluate the Primary human factors (PHFs model and to confirm the significant impact of PHFs on traditional CSFs and on the project success.

  14. Screening for fecal carriage of MCR-producing Enterobacteriaceae in healthy humans and primary care patients

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    Katrin Zurfluh

    2017-03-01

    Full Text Available Abstract Background The extent of the occurrence of the plasmid-encoded colistin resistance genes mcr-1 and mcr-2 among humans is currently sparsely studied in Western Europe. Objectives To determine the occurrence of MCR-producing Enterobacteriaceae in fecal samples of healthy humans with high occupational exposure to food and primary care patients in Switzerland. Methods Stool samples from 1091 healthy individuals and fecal swabs from 53 primary care patients were screened for polymyxin-resistant Enterobacteriaceae using LB agar containing 4 mg/L colistin. Minimal inhibitory concentrations (MICs of colistin were determined for non-intrinsic colistin-resistant isolates. Isolates were screened by PCR for the presence of mcr-1 and mcr-2 genes. Results The fecal carriage rate of colistin resistant (MIC value >2 mg/l Enterobacteriaceae was 1.5% for healthy people and 3.8% for primary care patients. Isolates included Hafnia alvei (n = 9, Escherichia coli (n = 3, Enterobacter cloacae (n = 4, Klebsiella pneumoniae (n = 1 and Raoultella ornithinolytica (n = 1. None of the isolates harbored the mcr-1 or mcr-2 genes. Conclusions There is no evidence for the presence of MCR-producers in the fecal flora of healthy people or primary care patients. Therefore, the risk of transfer of mcr genes from animals, food or the environment to humans is likely to be low in Switzerland.

  15. Chemosensitivity of primary human fibroblasts with defective unhooking of DNA interstrand cross-links

    International Nuclear Information System (INIS)

    Clingen, Peter H.; Arlett, Colin F.; Hartley, John A.; Parris, Christopher N.

    2007-01-01

    Xeroderma pigmentosum (XP) is characterised by defects in nucleotide excision repair, ultraviolet (UV) radiation sensitivity and increased skin carcinoma. Compared to other complementation groups, XP-F patients show relatively mild cutaneous symptoms. DNA interstrand cross-linking agents are a highly cytotoxic class of DNA damage induced by common cancer chemotherapeutics such as cisplatin and nitrogen mustards. Although the XPF-ERCC1 structure-specific endonuclease is required for the repair of ICLs cellular sensitivity of primary human XP-F cells has not been established. In clonogenic survival assays, primary fibroblasts from XP-F patients were moderately sensitive to both UVC and HN2 compared to normal cells (2- to 3-fold and 3- to 5-fold, respectively). XP-A fibroblasts were considerably more sensitive to UVC (10- to 12-fold) but not sensitive to HN2. The sensitivity of XP-F fibroblasts to HN2 correlated with the defective incision or 'unhooking' step of ICL repair. Using the comet assay, XP-F cells exhibited only 20% residual unhooking activity over 24 h. Over the same time, normal and XP-A cells unhooked greater than 95% and 62% of ICLs, respectively. After HN2 treatment, ICL-associated DNA double-strand breaks (DSBs) are detected by pulse field gel electrophoresis in dividing cells. Induction and repair of DNA DSBs was normal in XP-F fibroblasts. These findings demonstrate that in primary human fibroblasts, XPF is required for the unhooking of ICLs and not for the induction or repair of ICL-associated DNA DSBs induced by HN2. In terms of cancer chemotherapy, people with mild DNA repair defects affecting ICL repair may be more prevalent in the general population than expected. Since cellular sensitivity of primary human fibroblasts usually reflects clinical sensitivity such patients with cancer would be at risk of increased toxicity

  16. Confirmatory factor analysis and sample invariance of the Chinese version of Somatosensory Amplification Scale (ChSAS) among Chinese adolescents

    OpenAIRE

    Tam, B. K.; Wong, W. S.

    2011-01-01

    Objective: This paper aimed to evaluate the factor structure of the Chinese version of Somatosensory Amplification Scale (ChSAS) in a sample of Chinese adolescents across different grade levels using confirmatory factor analysis (CFA). Methods: A total of 1991 Chinese adolescents completed the ChSAS. CFA assessed the fit of the one-factor model to the entire sample. Factorial invariance of the ChSAS was also examined across grade levels using multigroup CFA. Results: Results of CFA confirmed ...

  17. Isolation of primary human hepatocytes from normal and diseased liver tissue: a one hundred liver experience.

    Directory of Open Access Journals (Sweden)

    Ricky H Bhogal

    2011-03-01

    Full Text Available Successful and consistent isolation of primary human hepatocytes remains a challenge for both cell-based therapeutics/transplantation and laboratory research. Several centres around the world have extensive experience in the isolation of human hepatocytes from non-diseased livers obtained from donor liver surplus to surgical requirement or at hepatic resection for tumours. These livers are an important but limited source of cells for therapy or research. The capacity to isolate cells from diseased liver tissue removed at transplantation would substantially increase availability of cells for research. However no studies comparing the outcome of human hepatocytes isolation from diseased and non-diseased livers presently exist. Here we report our experience isolating human hepatocytes from organ donors, non-diseased resected liver and cirrhotic tissue. We report the cell yields and functional qualities of cells isolated from the different types of liver and demonstrate that a single rigorous protocol allows the routine harvest of good quality primary hepatocytes from the most commonly accessible human liver tissue samples.

  18. Transcriptome patterns from primary cutaneous Leishmania braziliensis infections associate with eventual development of mucosal disease in humans.

    Directory of Open Access Journals (Sweden)

    Ana Claudia Maretti-Mira

    Full Text Available INTRODUCTION: Localized Cutaneous Leishmaniasis (LCL and Mucosal Leishmaniasis (ML are two extreme clinical forms of American Tegumentary Leishmaniasis that usually begin as solitary primary cutaneous lesions. Host and parasite factors that influence the progression of LCL to ML are not completely understood. In this manuscript, we compare the gene expression profiles of primary cutaneous lesions from patients who eventually developed ML to those that did not. METHODS: Using RNA-seq, we analyzed both the human and Leishmania transcriptomes in primary cutaneous lesions. RESULTS: Limited number of reads mapping to Leishmania transcripts were obtained. For human transcripts, compared to ML patients, lesions from LCL patients displayed a general multi-polarization of the adaptive immune response and showed up-regulation of genes involved in chemoattraction of innate immune cells and in antigen presentation. We also identified a potential transcriptional signature in the primary lesions that may predict long-term disease outcome. CONCLUSIONS: We were able to simultaneously sequence both human and Leishmania mRNA transcripts in primary cutaneous leishmaniasis lesions. Our results suggest an intrinsic difference in the immune capacity of LCL and ML patients. The findings correlate the complete cure of L. braziliensis infection with a controlled inflammatory response and a balanced activation of innate and adaptive immunity.

  19. Tuning In to Sound: Frequency-Selective Attentional Filter in Human Primary Auditory Cortex

    Science.gov (United States)

    Da Costa, Sandra; van der Zwaag, Wietske; Miller, Lee M.; Clarke, Stephanie

    2013-01-01

    Cocktail parties, busy streets, and other noisy environments pose a difficult challenge to the auditory system: how to focus attention on selected sounds while ignoring others? Neurons of primary auditory cortex, many of which are sharply tuned to sound frequency, could help solve this problem by filtering selected sound information based on frequency-content. To investigate whether this occurs, we used high-resolution fMRI at 7 tesla to map the fine-scale frequency-tuning (1.5 mm isotropic resolution) of primary auditory areas A1 and R in six human participants. Then, in a selective attention experiment, participants heard low (250 Hz)- and high (4000 Hz)-frequency streams of tones presented at the same time (dual-stream) and were instructed to focus attention onto one stream versus the other, switching back and forth every 30 s. Attention to low-frequency tones enhanced neural responses within low-frequency-tuned voxels relative to high, and when attention switched the pattern quickly reversed. Thus, like a radio, human primary auditory cortex is able to tune into attended frequency channels and can switch channels on demand. PMID:23365225

  20. Infection of human and non-human cells by a highly fusogenic primary CD4-independent HIV-1 isolate with a truncated envelope cytoplasmic tail

    International Nuclear Information System (INIS)

    Saha, Kunal; Yan Hui; Nelson, Julie A.E.; Zerhouni-Layachi, Bouchra

    2005-01-01

    Truncation of the envelope cytoplasmic tail has enabled FIV, SIV, and some laboratory HIV-1 strains to acquire broader cellular tropism and enhanced fusogenicity. Here we have characterized a primary CD4-independent HIV-1 isolate (92UG046-T8) with a truncated cytoplasmic tail that was able to infect and induce syncytia in primary lymphocytes from human, chimpanzee, and monkey, as well as CD4-negative cell lines from human and monkey. Increased syncytia were also noticeable with 293 cells expressing the cloned envelope from the 92UG046-T8 isolate suggesting envelope-mediated cellular fusion. Except pooled serum from HIV-1-infected individuals, monoclonal anti-envelope antibodies or antibodies/antagonists against CD4, CXCR4, and CCR5 were not able to prevent infection by the 92UG046-T8 isolate. This is the first report showing a primary HIV-1 variant with truncated cytoplasmic tail which is highly fusogenic and can infect a broad range of cells from human and non-human origins. In vivo evolution of similar HIV-1 mutants may have important implications in AIDS pathogenesis

  1. A Cell Culture Platform to Maintain Long-term Phenotype of Primary Human Hepatocytes and Endothelial Cells.

    Science.gov (United States)

    Ware, Brenton R; Durham, Mitchell J; Monckton, Chase P; Khetani, Salman R

    2018-03-01

    Modeling interactions between primary human hepatocytes (PHHs) and primary human liver sinusoidal endothelial cells (LSECs) in vitro can help elucidate human-specific mechanisms underlying liver physiology/disease and drug responses; however, existing hepatocyte/endothelial coculture models are suboptimal because of their use of rodent cells, cancerous cell lines, and/or nonliver endothelial cells. Hence, we sought to develop a platform that could maintain the long-term phenotype of PHHs and primary human LSECs. Primary human LSECs or human umbilical vein endothelial cells as the nonliver control were cocultivated with micropatterned PHH colonies (to control homotypic interactions) followed by an assessment of PHH morphology and functions (albumin and urea secretion, and cytochrome P-450 2A6 and 3A4 enzyme activities) over 3 weeks. Endothelial phenotype was assessed via gene expression patterns and scanning electron microscopy to visualize fenestrations. Hepatic responses in PHH/endothelial cocultures were benchmarked against responses in previously developed PHH/3T3-J2 fibroblast cocultures. Finally, PHH/fibroblast/endothelial cell tricultures were created and characterized as described previously. LSECs, but not human umbilical vein endothelial cells, induced PHH albumin secretion for ∼11 days; however, neither endothelial cell type could maintain PHH morphology and functions to the same magnitude/longevity as the fibroblasts. In contrast, both PHHs and endothelial cells displayed stable phenotype for 3 weeks in PHH/fibroblast/endothelial cell tricultures; furthermore, layered tricultures in which PHHs and endothelial cells were separated by a protein gel to mimic the space of Disse displayed similar functional levels as the coplanar tricultures. PHH/fibroblast/endothelial tricultures constitute a robust platform to elucidate reciprocal interactions between PHHs and endothelial cells in physiology, disease, and after drug exposure.

  2. Concordant testing results between various Human Papillomavirus assays in primary cervical cancer screening

    DEFF Research Database (Denmark)

    de Thurah, Lena; Bonde, Jesper; Hoa Lam, Janni Uyen

    2018-01-01

    OBJECTIVES: Human Papillomavirus (HPV) assays are increasingly used for primary cervical screening and HPV vaccination effect monitoring. We undertook a systematic literature review to determine the concordance in positive test results (i.e., detection of HPV infections) between Hybrid Capture 2 ...

  3. Pudendal somatosensory evoked potentials in normal women

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    Geraldo A. Cavalcanti

    2007-12-01

    Full Text Available OBJECTIVE: Somatosensory evoked potential (SSEP is an electrophysiological test used to evaluate sensory innervations in peripheral and central neuropathies. Pudendal SSEP has been studied in dysfunctions related to the lower urinary tract and pelvic floor. Although some authors have already described technical details pertaining to the method, the standardization and the influence of physiological variables in normative values have not yet been established, especially for women. The aim of the study was to describe normal values of the pudendal SSEP and to compare technical details with those described by other authors. MATERIALS AND METHODS: The clitoral sensory threshold and pudendal SSEP latency was accomplished in 38 normal volunteers. The results obtained from stimulation performed on each side of the clitoris were compared to ages, body mass index (BMI and number of pregnancies. RESULTS: The values of clitoral sensory threshold and P1 latency with clitoral left stimulation were respectively, 3.64 ± 1.01 mA and 37.68 ± 2.60 ms. Results obtained with clitoral right stimulation were 3.84 ± 1.53 mA and 37.42 ± 3.12 ms, respectively. There were no correlations between clitoral sensory threshold and P1 latency with age, BMI or height of the volunteers. A significant difference was found in P1 latency between nulliparous women and volunteers who had been previously submitted to cesarean section. CONCLUSIONS: The SSEP latency represents an accessible and reproducible method to investigate the afferent pathways from the genitourinary tract. These results could be used as normative values in studies involving genitourinary neuropathies in order to better clarify voiding and sexual dysfunctions in females.

  4. Chemosensitivity testing of primary human renal cell carcinoma by a tetrazolium based microculture assay (MTT).

    Science.gov (United States)

    Mickisch, G; Fajta, S; Keilhauer, G; Schlick, E; Tschada, R; Alken, P

    1990-01-01

    MTT staining procedures have been used in chemosensitivity testing of established cell lines of human and other sources as well as of human leukaemias, but only limited information on its application in primary solid human tumors is presently available. We have evaluated MTT staining in primary human Renal Cell Carcinomas (RCCs), studied various factors interfering with the optimal use, and finally applied it in subsequent chemosensitivity testing. The method depends on the conversion of a water-soluble tetrazolium salt (MTT) to a purple colored formazan precipitate, a reaction effected by enzymes active only in living cells. Single cell suspensions of RCCs were obtained either by enzymatic dispersion or by mechanical dissagregation, filtered through gauze, and purified by Ficoll density centrifugation. Tests were carried out in 96-well microculture plates. 10(4) viable tumor cells per well at 4 h incubation time with 20 micrograms MTT/100 microliters total medium volume yielded best results. Formazan crystals were dissolved with DMSO, and the plates were immediately measured on a microculture plate reader at 540 nm. Under these criteria, linearity of the system could be demonstrated. For chemosensitivity testing, cells were continuously exposed to a number of drugs prior to the MTT staining procedure. Reproducibility of results was assessed and confirmed by culturing RCCs in flasks additionally, resubmitting them after 1, 2, and 4 weeks to the MTT assay. We conclude that the semiautomated MTT assay offers a valid, rapid, reliable and simple method to determine the degree of chemoresistance in primary human RCCs.

  5. Genome-wide binding and transcriptome analysis of human farnesoid X receptor in primary human hepatocytes.

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    Le Zhan

    Full Text Available Farnesoid X receptor (FXR, NR1H4 is a ligand-activated transcription factor, belonging to the nuclear receptor superfamily. FXR is highly expressed in the liver and is essential in regulating bile acid homeostasis. FXR deficiency is implicated in numerous liver diseases and mice with modulation of FXR have been used as animal models to study liver physiology and pathology. We have reported genome-wide binding of FXR in mice by chromatin immunoprecipitation - deep sequencing (ChIP-seq, with results indicating that FXR may be involved in regulating diverse pathways in liver. However, limited information exists for the functions of human FXR and the suitability of using murine models to study human FXR functions.In the current study, we performed ChIP-seq in primary human hepatocytes (PHHs treated with a synthetic FXR agonist, GW4064 or DMSO control. In parallel, RNA deep sequencing (RNA-seq and RNA microarray were performed for GW4064 or control treated PHHs and wild type mouse livers, respectively.ChIP-seq showed similar profiles of genome-wide FXR binding in humans and mice in terms of motif analysis and pathway prediction. However, RNA-seq and microarray showed more different transcriptome profiles between PHHs and mouse livers upon GW4064 treatment.In summary, we have established genome-wide human FXR binding and transcriptome profiles. These results will aid in determining the human FXR functions, as well as judging to what level the mouse models could be used to study human FXR functions.

  6. Efficient nanoparticle mediated sustained RNA interference in human primary endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Mukerjee, Anindita; Shankardas, Jwalitha; Ranjan, Amalendu P; Vishwanatha, Jamboor K, E-mail: Jamboor.vishwanatha@unthsc.edu [Department of Molecular Biology and Immunology and Institute for Cancer Research, Graduate School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX 76107 (United States)

    2011-11-04

    Endothelium forms an important target for drug and/or gene therapy since endothelial cells play critical roles in angiogenesis and vascular functions and are associated with various pathophysiological conditions. RNA mediated gene silencing presents a new therapeutic approach to overcome many such diseases, but the major challenge of such an approach is to ensure minimal toxicity and effective transfection efficiency of short hairpin RNA (shRNA) to primary endothelial cells. In the present study, we formulated shAnnexin A2 loaded poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles which produced intracellular small interfering RNA (siRNA) against Annexin A2 and brought about the downregulation of Annexin A2. The per cent encapsulation of the plasmid within the nanoparticle was found to be 57.65%. We compared our nanoparticle based transfections with Lipofectamine mediated transfection, and our studies show that nanoparticle based transfection efficiency is very high ({approx}97%) and is more sustained compared to conventional Lipofectamine mediated transfections in primary retinal microvascular endothelial cells and human cancer cell lines. Our findings also show that the shAnnexin A2 loaded PLGA nanoparticles had minimal toxicity with almost 95% of cells being viable 24 h post-transfection while Lipofectamine based transfections resulted in only 30% viable cells. Therefore, PLGA nanoparticle based transfection may be used for efficient siRNA transfection to human primary endothelial and cancer cells. This may serve as a potential adjuvant treatment option for diseases such as diabetic retinopathy, retinopathy of prematurity and age related macular degeneration besides various cancers.

  7. Efficient nanoparticle mediated sustained RNA interference in human primary endothelial cells

    Science.gov (United States)

    Mukerjee, Anindita; Shankardas, Jwalitha; Ranjan, Amalendu P.; Vishwanatha, Jamboor K.

    2011-11-01

    Endothelium forms an important target for drug and/or gene therapy since endothelial cells play critical roles in angiogenesis and vascular functions and are associated with various pathophysiological conditions. RNA mediated gene silencing presents a new therapeutic approach to overcome many such diseases, but the major challenge of such an approach is to ensure minimal toxicity and effective transfection efficiency of short hairpin RNA (shRNA) to primary endothelial cells. In the present study, we formulated shAnnexin A2 loaded poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles which produced intracellular small interfering RNA (siRNA) against Annexin A2 and brought about the downregulation of Annexin A2. The per cent encapsulation of the plasmid within the nanoparticle was found to be 57.65%. We compared our nanoparticle based transfections with Lipofectamine mediated transfection, and our studies show that nanoparticle based transfection efficiency is very high (~97%) and is more sustained compared to conventional Lipofectamine mediated transfections in primary retinal microvascular endothelial cells and human cancer cell lines. Our findings also show that the shAnnexin A2 loaded PLGA nanoparticles had minimal toxicity with almost 95% of cells being viable 24 h post-transfection while Lipofectamine based transfections resulted in only 30% viable cells. Therefore, PLGA nanoparticle based transfection may be used for efficient siRNA transfection to human primary endothelial and cancer cells. This may serve as a potential adjuvant treatment option for diseases such as diabetic retinopathy, retinopathy of prematurity and age related macular degeneration besides various cancers.

  8. Efficient nanoparticle mediated sustained RNA interference in human primary endothelial cells

    International Nuclear Information System (INIS)

    Mukerjee, Anindita; Shankardas, Jwalitha; Ranjan, Amalendu P; Vishwanatha, Jamboor K

    2011-01-01

    Endothelium forms an important target for drug and/or gene therapy since endothelial cells play critical roles in angiogenesis and vascular functions and are associated with various pathophysiological conditions. RNA mediated gene silencing presents a new therapeutic approach to overcome many such diseases, but the major challenge of such an approach is to ensure minimal toxicity and effective transfection efficiency of short hairpin RNA (shRNA) to primary endothelial cells. In the present study, we formulated shAnnexin A2 loaded poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles which produced intracellular small interfering RNA (siRNA) against Annexin A2 and brought about the downregulation of Annexin A2. The per cent encapsulation of the plasmid within the nanoparticle was found to be 57.65%. We compared our nanoparticle based transfections with Lipofectamine mediated transfection, and our studies show that nanoparticle based transfection efficiency is very high (∼97%) and is more sustained compared to conventional Lipofectamine mediated transfections in primary retinal microvascular endothelial cells and human cancer cell lines. Our findings also show that the shAnnexin A2 loaded PLGA nanoparticles had minimal toxicity with almost 95% of cells being viable 24 h post-transfection while Lipofectamine based transfections resulted in only 30% viable cells. Therefore, PLGA nanoparticle based transfection may be used for efficient siRNA transfection to human primary endothelial and cancer cells. This may serve as a potential adjuvant treatment option for diseases such as diabetic retinopathy, retinopathy of prematurity and age related macular degeneration besides various cancers.

  9. Strontium-Substituted Bioceramics Particles: A New Way to Modulate MCP-1 and Gro-α Production by Human Primary Osteoblastic Cells

    Directory of Open Access Journals (Sweden)

    Julien Braux

    2016-12-01

    Full Text Available Background: To avoid morbidity and limited availability associated with autografts, synthetic calcium phosphate (CaP ceramics were extensively developed and used as bone filling materials. Controlling their induced-inflammatory response nevertheless remained a major concern. Strontium-containing CaP ceramics were recently demonstrated for impacting cytokines’ secretion pattern of human primary monocytes. The present study focuses on the ability of strontium-containing CaP to control the human primary bone cell production of two major inflammatory and pro-osteoclastogenic mediators, namely MCP-1 and Gro-α, in response to ceramics particles. Methods: This in vitro study was performed using human primary osteoblasts in which their response to ceramics was evaluated by PCR arrays, antibody arrays were used for screening and real-time PCR and ELISA for more focused analyses. Results: Study of mRNA and protein expression highlights that human primary bone cells are able to produce these inflammatory mediators and reveal that the adjunction of CaP in the culture medium leads to their enhanced production. Importantly, the current work determines the down-regulating effect of strontium-substituted CaP on MCP-1 and Gro-α production. Conclusion: Our findings point out a new capability of strontium to modulate human primary bone cells’ communication with the immune system.

  10. Cytomegalovirus infection induces a stem cell phenotype in human primary glioblastoma cells

    DEFF Research Database (Denmark)

    Fornara, O; Bartek, J; Rahbar, A

    2016-01-01

    Glioblastoma (GBM) is associated with poor prognosis despite aggressive surgical resection, chemotherapy, and radiation therapy. Unfortunately, this standard therapy does not target glioma cancer stem cells (GCSCs), a subpopulation of GBM cells that can give rise to recurrent tumors. GBMs express...... human cytomegalovirus (HCMV) proteins, and previously we found that the level of expression of HCMV immediate-early (IE) protein in GBMs is a prognostic factor for poor patient survival. In this study, we investigated the relation between HCMV infection of GBM cells and the presence of GCSCs. Primary...... GBMs were characterized by their expression of HCMV-IE and GCSCs marker CD133 and by patient survival. The extent to which HCMV infection of primary GBM cells induced a GCSC phenotype was evaluated in vitro. In primary GBMs, a large fraction of CD133-positive cells expressed HCMV-IE, and higher co...

  11. Determination of fracture toughness of human permanent and primary enamel using an indentation microfracture method.

    Science.gov (United States)

    Hayashi-Sakai, Sachiko; Sakai, Jun; Sakamoto, Makoto; Endo, Hideaki

    2012-09-01

    The purpose of the present study was to examine the fracture toughness and Vickers microhardness number of permanent and primary human enamel using the indentation microfracture method. Crack resistance and a parameter indirectly related to fracture toughness were measured in 48 enamel specimens from 16 permanent teeth and 12 enamel specimens obtained from six primary teeth. The Vickers microhardness number of the middle portion was greater than the upper portion in primary enamel. The fracture toughness was highest in the middle portion of permanent enamel, because fracture toughness greatly depends upon microstructure. These findings suggest that primary teeth are not miniature permanent teeth but have specific and characteristic mechanical properties.

  12. Educational actions in human communication health: telehealth contributions in primary care

    Directory of Open Access Journals (Sweden)

    Gabriela Guedes de Sá Leitão

    Full Text Available ABSTRACT Objective: to characterize educational actions related to human communication health produced at the Tele-Health Center for health professionals in primary care. Methods: a cross-sectional study was conducted at the Tele-Health Center at the Federal University of Pernambuco Clinical Hospital. Educational actions produced by tele-consultants between 2008 and 2014 linked to the health of human communication were considered. Data collection was conducted in two phases. In the first phase, the data were explored and educational actions were selected based on the title and the relationship with human communication. In the second phase, each action was observed and evaluated for content. The data were analyzed using descriptive statistics. Results: a few educational actions related to human communication health were concentrated in 2014. Throughout the period analyzed, the actions were restricted to the field of language and concentrated on the education issue as well as the strategic area of child and adolescent health. The most frequent occupational category among the tele-consultants was nursing. Conclusion: a small number of educational actions addressing the health of human communication was produced and the participation of speech therapists remains incipient.

  13. Nutritional Ingredients Modulate Adipokine Secretion and Inflammation in Human Primary Adipocytes

    Science.gov (United States)

    Romacho, Tania; Glosse, Philipp; Richter, Isabel; Elsen, Manuela; Schoemaker, Marieke H.; van Tol, Eric A.; Eckel, Jürgen

    2015-01-01

    Nutritional factors such as casein hydrolysates and long chain polyunsaturated fatty acids have been proposed to exert beneficial metabolic effects. We aimed to investigate how a casein hydrolysate (eCH) and long chain polyunsaturated fatty acids could affect human primary adipocyte function in vitro. Incubation conditions with the different nutritional factors were validated by assessing cell vitality with lactate dehydrogenase (LDH) release and neutral red incorporation. Intracellular triglyceride content was assessed with Oil Red O staining. The effect of eCH, a non-peptidic amino acid mixture (AA), and long-chain polyunsaturated fatty acids (LC-PUFAs) on adiponectin and leptin secretion was determined by enzyme-linked immunosorbent assay (ELISA). Intracellular adiponectin expression and nuclear factor-κB (NF-κB) activation were analyzed by Western blot, while monocyte chemoattractant protein-1 (MCP-1) release was explored by ELISA. The eCH concentration dependently increased adiponectin secretion in human primary adipocytes through its intrinsic peptide bioactivity, since the non-peptidic mixture, AA, could not mimic eCH’s effects on adiponectin secretion. Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and DHA combined with arachidonic acid (ARA) upregulated adiponectin secretion. However, only DHA and DHA/ARA exerted a potentanti-inflammatory effect reflected by prevention of tumor necrosis factor-α (TNF-α) induced NF-κB activation and MCP-1 secretion in human adipocytes. eCH and DHA alone or in combination with ARA, may hold the key for nutritional programming through their anti-inflammatory action to prevent diseases with low-grade chronic inflammation such as obesity or diabetes. PMID:25629558

  14. Nutritional Ingredients Modulate Adipokine Secretion and Inflammation in Human Primary Adipocytes

    Directory of Open Access Journals (Sweden)

    Tania Romacho

    2015-01-01

    Full Text Available Nutritional factors such as casein hydrolysates and long chain polyunsaturated fatty acids have been proposed to exert beneficial metabolic effects. We aimed to investigate how a casein hydrolysate (eCH and long chain polyunsaturated fatty acids could affect human primary adipocyte function in vitro. Incubation conditions with the different nutritional factors were validated by assessing cell vitality with lactate dehydrogenase (LDH release and neutral red incorporation. Intracellular triglyceride content was assessed with Oil Red O staining. The effect of eCH, a non-peptidic amino acid mixture (AA, and long-chain polyunsaturated fatty acids (LC-PUFAs on adiponectin and leptin secretion was determined by enzyme-linked immunosorbent assay (ELISA. Intracellular adiponectin expression and nuclear factor-κB (NF-κB activation were analyzed by Western blot, while monocyte chemoattractant protein-1 (MCP-1 release was explored by ELISA. The eCH concentration dependently increased adiponectin secretion in human primary adipocytes through its intrinsic peptide bioactivity, since the non-peptidic mixture, AA, could not mimic eCH’s effects on adiponectin secretion. Eicosapentaenoic acid (EPA, docosahexaenoic acid (DHA, and DHA combined with arachidonic acid (ARA upregulated adiponectin secretion. However, only DHA and DHA/ARA exerted a potentanti-inflammatory effect reflected by prevention of tumor necrosis factor-α (TNF-α induced NF-κB activation and MCP-1 secretion in human adipocytes. eCH and DHA alone or in combination with ARA, may hold the key for nutritional programming through their anti-inflammatory action to prevent diseases with low-grade chronic inflammation such as obesity or diabetes.

  15. Momordica charantia (bitter melon inhibits primary human adipocyte differentiation by modulating adipogenic genes

    Directory of Open Access Journals (Sweden)

    Nerurkar Vivek R

    2010-06-01

    Full Text Available Abstract Background Escalating trends of obesity and associated type 2 diabetes (T2D has prompted an increase in the use of alternative and complementary functional foods. Momordica charantia or bitter melon (BM that is traditionally used to treat diabetes and complications has been demonstrated to alleviate hyperglycemia as well as reduce adiposity in rodents. However, its effects on human adipocytes remain unknown. The objective of our study was to investigate the effects of BM juice (BMJ on lipid accumulation and adipocyte differentiation transcription factors in primary human differentiating preadipocytes and adipocytes. Methods Commercially available cryopreserved primary human preadipocytes were treated with and without BMJ during and after differentiation. Cytotoxicity, lipid accumulation, and adipogenic genes mRNA expression was measured by commercial enzymatic assay kits and semi-quantitative RT-PCR (RT-PCR. Results Preadipocytes treated with varying concentrations of BMJ during differentiation demonstrated significant reduction in lipid content with a concomitant reduction in mRNA expression of adipocyte transcription factors such as, peroxisome proliferator-associated receptor γ (PPARγ and sterol regulatory element-binding protein 1c (SREBP-1c and adipocytokine, resistin. Similarly, adipocytes treated with BMJ for 48 h demonstrated reduced lipid content, perilipin mRNA expression, and increased lipolysis as measured by the release of glycerol. Conclusion Our data suggests that BMJ is a potent inhibitor of lipogenesis and stimulator of lipolysis activity in human adipocytes. BMJ may therefore prove to be an effective complementary or alternative therapy to reduce adipogenesis in humans.

  16. Differences in the Electrophysiological Properties of Mouse Somatosensory Layer 2/3 Neurons In Vivo and Slice Stem from Intrinsic Sources Rather than a Network-Generated High Conductance State

    Science.gov (United States)

    2018-01-01

    Abstract Synaptic activity in vivo can potentially alter the integration properties of neurons. Using recordings in awake mice, we targeted somatosensory layer 2/3 pyramidal neurons and compared neuronal properties with those from slices. Pyramidal cells in vivo had lower resistance and gain values, as well as broader spikes and increased spike frequency adaptation compared to the same cells in slices. Increasing conductance in neurons using dynamic clamp to levels observed in vivo, however, did not lessen the differences between in vivo and slice conditions. Further, local application of tetrodotoxin (TTX) in vivo blocked synaptic-mediated membrane voltage fluctuations but had little impact on pyramidal cell membrane input resistance and time constant values. Differences in electrophysiological properties of layer 2/3 neurons in mouse somatosensory cortex, therefore, stem from intrinsic sources separate from synaptic-mediated membrane voltage fluctuations. PMID:29662946

  17. Different Mode of Afferents Determines the Frequency Range of High Frequency Activities in the Human Brain: Direct Electrocorticographic Comparison between Peripheral Nerve and Direct Cortical Stimulation.

    Directory of Open Access Journals (Sweden)

    Katsuya Kobayashi

    Full Text Available Physiological high frequency activities (HFA are related to various brain functions. Factors, however, regulating its frequency have not been well elucidated in humans. To validate the hypothesis that different propagation modes (thalamo-cortical vs. cortico-coritcal projections, or different terminal layers (layer IV vs. layer II/III affect its frequency, we, in the primary somatosensory cortex (SI, compared HFAs induced by median nerve stimulation with those induced by electrical stimulation of the cortex connecting to SI. We employed 6 patients who underwent chronic subdural electrode implantation for presurgical evaluation. We evaluated the HFA power values in reference to the baseline overriding N20 (earliest cortical response and N80 (late response of somatosensory evoked potentials (HFA(SEP(N20 and HFA(SEP(N80 and compared those overriding N1 and N2 (first and second responses of cortico-cortical evoked potentials (HFA(CCEP(N1 and HFA(CCEP(N2. HFA(SEP(N20 showed the power peak in the frequency above 200 Hz, while HFA(CCEP(N1 had its power peak in the frequency below 200 Hz. Different propagation modes and/or different terminal layers seemed to determine HFA frequency. Since HFA(CCEP(N1 and HFA induced during various brain functions share a similar broadband profile of the power spectrum, cortico-coritcal horizontal propagation seems to represent common mode of neural transmission for processing these functions.

  18. RNAi mediated acute depletion of Retinoblastoma protein (pRb promotes aneuploidy in human primary cells via micronuclei formation

    Directory of Open Access Journals (Sweden)

    Iovino Flora

    2009-11-01

    Full Text Available Abstract Background Changes in chromosome number or structure as well as supernumerary centrosomes and multipolar mitoses are commonly observed in human tumors. Thus, centrosome amplification and mitotic checkpoint dysfunctions are believed possible causes of chromosomal instability. The Retinoblastoma tumor suppressor (RB participates in the regulation of synchrony between DNA synthesis and centrosome duplication and it is involved in transcription regulation of some mitotic genes. Primary human fibroblasts were transfected transiently with short interfering RNA (siRNA specific for human pRb to investigate the effects of pRb acute loss on chromosomal stability. Results Acutely pRb-depleted fibroblasts showed altered expression of genes necessary for cell cycle progression, centrosome homeostasis, kinetochore and mitotic checkpoint proteins. Despite altered expression of genes involved in the Spindle Assembly Checkpoint (SAC the checkpoint seemed to function properly in pRb-depleted fibroblasts. In particular AURORA-A and PLK1 overexpression suggested that these two genes might have a role in the observed genomic instability. However, when they were post-transcriptionally silenced in pRb-depleted fibroblasts we did not observe reduction in the number of aneuploid cells. This finding suggests that overexpression of these two genes did not contribute to genomic instability triggered by RB acute loss although it affected cell proliferation. Acutely pRb-depleted human fibroblasts showed the presence of micronuclei containing whole chromosomes besides the presence of supernumerary centrosomes and aneuploidy. Conclusion Here we show for the first time that RB acute loss triggers centrosome amplification and aneuploidy in human primary fibroblasts. Altogether, our results suggest that pRb-depleted primary human fibroblasts possess an intact spindle checkpoint and that micronuclei, likely caused by mis-attached kinetochores that in turn trigger

  19. [Intraoperative pain stimuli change somatosensory evoked potentials, but not auditory evoked potentials during isoflurane/nitrous oxide anesthesia].

    Science.gov (United States)

    Rundshagen, I; Kochs, E; Bischoff, P; Schulte am Esch, J

    1997-10-01

    Evoked potentials are used for intraoperative monitoring to assess changes of cerebral function. This prospective randomised study assesses the influence of surgical stimulation on midlatency components of somatosensory (SEPs) and auditory evoked potentials (AEPs) in anaesthetised patients. After approval of the Ethics Committee and written informed consent 36 orthopaedic patients (34 +/- 15 y, 73 +/- 14 kg. 1.71 +/- 0.07 m, ASA I-II) were randomly included in the study. Anaesthesia was induced with 1.5 micrograms/kg fentanyl, 0.3 mg/kg etomidate and 0.1 mg/kg vecuronium. The lungs were intubated and patients normoventilated in steady state anaesthesia with isoflurane (end-tidal 0.6%) and 66% nitrous oxide. 18 patients (group 1) were assigned to the SEP group: median nerve stimulation, recording at Erb, C 6 and the contralateral somatosensory cortex (N20, P25, N35) vs Fz. AEPs were recorded in group 2 (n = 18): binaural stimulation, recording at Cz versus linked mastoid (V, Na, Pa, Nb). Recordings were performed during 30 min before the start of surgery (baseline: BL), at skin incision (SURG1) and at the preparation of the periost (SURG2). Heart rate, mean arterial blood pressure, oxygen saturation, endtidal pCO2 and isoflurane (PetISO) concentrations were registered simultaneously. Data were analysed by one-way analysis of variance. Post hoc comparison were made by Mann-Whitney U-Wilcoxon Rank Sum Test with p beats/min) to SURG2 (76 +/- 12 beats/min). Increases of amplitudes of midlatency SEP amplitudes indicate increased nociceptive signal transmission which is not blunted by isoflurane-nitrous oxide anaesthesia. In contrast, unchanged AEPs indicate adequate levels of the hypnotic components of anaesthesia.

  20. Xenobiotic-Metabolizing Enzyme and Transporter Gene Expression in Primary Cultures of Human Hepatocytes Modulated by Toxcast Chemicals

    Science.gov (United States)

    Primary human hepatocyte cultures are useful in vitro model systems of human liver because when cultured under appropriate conditions the hepatocytes retain liver-like functionality such as metabolism, transport, and cell signaling. This model system was used to characterize the ...

  1. Electronic cigarette liquid increases inflammation and virus infection in primary human airway epithelial cells.

    Science.gov (United States)

    Wu, Qun; Jiang, Di; Minor, Maisha; Chu, Hong Wei

    2014-01-01

    The use of electronic cigarettes (e-cigarettes) is rapidly increasing in the United States, especially among young people since e-cigarettes have been perceived as a safer alternative to conventional tobacco cigarettes. However, the scientific evidence regarding the human health effects of e-cigarettes on the lung is extremely limited. The major goal of our current study is to determine if e-cigarette use alters human young subject airway epithelial functions such as inflammatory response and innate immune defense against respiratory viral (i.e., human rhinovirus, HRV) infection. We examined the effects of e-cigarette liquid (e-liquid) on pro-inflammatory cytokine (e.g., IL-6) production, HRV infection and host defense molecules (e.g., short palate, lung, and nasal epithelium clone 1, SPLUNC1) in primary human airway epithelial cells from young healthy non-smokers. Additionally, we examined the role of SPLUNC1 in lung defense against HRV infection using a SPLUNC1 knockout mouse model. We found that nicotine-free e-liquid promoted IL-6 production and HRV infection. Addition of nicotine into e-liquid further amplified the effects of nicotine-free e-liquid. Moreover, SPLUNC1 deficiency in mice significantly increased lung HRV loads. E-liquid inhibited SPLUNC1 expression in primary human airway epithelial cells. These findings strongly suggest the deleterious health effects of e-cigarettes in the airways of young people. Our data will guide future studies to evaluate the impact of e-cigarettes on lung health in human populations, and help inform the public about potential health risks of e-cigarettes.

  2. Electronic cigarette liquid increases inflammation and virus infection in primary human airway epithelial cells.

    Directory of Open Access Journals (Sweden)

    Qun Wu

    Full Text Available The use of electronic cigarettes (e-cigarettes is rapidly increasing in the United States, especially among young people since e-cigarettes have been perceived as a safer alternative to conventional tobacco cigarettes. However, the scientific evidence regarding the human health effects of e-cigarettes on the lung is extremely limited. The major goal of our current study is to determine if e-cigarette use alters human young subject airway epithelial functions such as inflammatory response and innate immune defense against respiratory viral (i.e., human rhinovirus, HRV infection.We examined the effects of e-cigarette liquid (e-liquid on pro-inflammatory cytokine (e.g., IL-6 production, HRV infection and host defense molecules (e.g., short palate, lung, and nasal epithelium clone 1, SPLUNC1 in primary human airway epithelial cells from young healthy non-smokers. Additionally, we examined the role of SPLUNC1 in lung defense against HRV infection using a SPLUNC1 knockout mouse model. We found that nicotine-free e-liquid promoted IL-6 production and HRV infection. Addition of nicotine into e-liquid further amplified the effects of nicotine-free e-liquid. Moreover, SPLUNC1 deficiency in mice significantly increased lung HRV loads. E-liquid inhibited SPLUNC1 expression in primary human airway epithelial cells. These findings strongly suggest the deleterious health effects of e-cigarettes in the airways of young people. Our data will guide future studies to evaluate the impact of e-cigarettes on lung health in human populations, and help inform the public about potential health risks of e-cigarettes.

  3. Early impairment of somatosensory evoked potentials in very young children with achondroplasia with foramen magnum stenosis.

    Science.gov (United States)

    Fornarino, Stefania; Rossi, Daniela Paola; Severino, Mariasavina; Pistorio, Angela; Allegri, Anna Elsa Maria; Martelli, Simona; Doria Lamba, Laura; Lanteri, Paola

    2017-02-01

    To evaluate the contribution of somatosensory evoked potentials after median nerve (MN-SEPs) and posterior tibial nerve (PTN-SEPs) stimulation in functional assessment of cervical and lumbar spinal stenosis in children with achondroplasia. We reviewed MN-SEPs, PTN-SEPs, and spinal magnetic resonance imaging (MRI) examinations performed in 58 patients with achondroplasia (25 males, 33 females; age range 21d-16y 10mo; mean age 4y 3mo [SD 4y 1mo]). Patients were subdivided into four age categories: achondroplasia, the cortical component of PTN-SEPs is more sensitive than the cortical component and central conduction time of MN-SEPs in detection of cervical spinal cord compression at early ages. © 2016 Mac Keith Press.

  4. Steroid synthesis by primary human keratinocytes; implications for skin disease

    Energy Technology Data Exchange (ETDEWEB)

    Hannen, Rosalind F., E-mail: r.f.hannen@qmul.ac.uk [Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT (United Kingdom); Michael, Anthony E. [Centre for Developmental and Endocrine Signalling, Academic Section of Obstetrics and Gynaecology, Division of Clinical Developmental Sciences, 3rd Floor, Lanesborough Wing, St. George' s, University of London, Cranmer Terrace, Tooting, London SW17 0RE (United Kingdom); Jaulim, Adil [Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT (United Kingdom); Bhogal, Ranjit [Life Science, Unilever R and D Colworth House, Sharnbrook, Bedfordshire MK44 1LQ (United Kingdom); Burrin, Jacky M. [Centre for Endocrinology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ (United Kingdom); Philpott, Michael P. [Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT (United Kingdom)

    2011-01-07

    Research highlights: {yields} Primary keratinocytes express the steroid enzymes required for cortisol synthesis. {yields} Normal primary human keratinocytes can synthesise cortisol. {yields} Steroidogenic regulators, StAR and MLN64, are expressed in normal epidermis. {yields} StAR expression is down regulated in eczema and psoriatic epidermis. -- Abstract: Cortisol-based therapy is one of the most potent anti-inflammatory treatments available for skin conditions including psoriasis and atopic dermatitis. Previous studies have investigated the steroidogenic capabilities of keratinocytes, though none have demonstrated that these skin cells, which form up to 90% of the epidermis are able to synthesise cortisol. Here we demonstrate that primary human keratinocytes (PHK) express all the elements required for cortisol steroidogenesis and metabolise pregnenolone through each intermediate steroid to cortisol. We show that normal epidermis and cultured PHK express each of the enzymes (CYP11A1, CYP17A1, 3{beta}HSD1, CYP21 and CYP11B1) that are required for cortisol synthesis. These enzymes were shown to be metabolically active for cortisol synthesis since radiometric conversion assays traced the metabolism of [7-{sup 3}H]-pregnenolone through each steroid intermediate to [7-{sup 3}H]-cortisol in cultured PHK. Trilostane (a 3{beta}HSD1 inhibitor) and ketoconazole (a CYP17A1 inhibitor) blocked the metabolism of both pregnenolone and progesterone. Finally, we show that normal skin expresses two cholesterol transporters, steroidogenic acute regulatory protein (StAR), regarded as the rate-determining protein for steroid synthesis, and metastatic lymph node 64 (MLN64) whose function has been linked to cholesterol transport in steroidogenesis. The expression of StAR and MLN64 was aberrant in two skin disorders, psoriasis and atopic dermatitis, that are commonly treated with cortisol, suggesting dysregulation of epidermal steroid synthesis in these patients. Collectively these data

  5. Steroid synthesis by primary human keratinocytes; implications for skin disease

    International Nuclear Information System (INIS)

    Hannen, Rosalind F.; Michael, Anthony E.; Jaulim, Adil; Bhogal, Ranjit; Burrin, Jacky M.; Philpott, Michael P.

    2011-01-01

    Research highlights: → Primary keratinocytes express the steroid enzymes required for cortisol synthesis. → Normal primary human keratinocytes can synthesise cortisol. → Steroidogenic regulators, StAR and MLN64, are expressed in normal epidermis. → StAR expression is down regulated in eczema and psoriatic epidermis. -- Abstract: Cortisol-based therapy is one of the most potent anti-inflammatory treatments available for skin conditions including psoriasis and atopic dermatitis. Previous studies have investigated the steroidogenic capabilities of keratinocytes, though none have demonstrated that these skin cells, which form up to 90% of the epidermis are able to synthesise cortisol. Here we demonstrate that primary human keratinocytes (PHK) express all the elements required for cortisol steroidogenesis and metabolise pregnenolone through each intermediate steroid to cortisol. We show that normal epidermis and cultured PHK express each of the enzymes (CYP11A1, CYP17A1, 3βHSD1, CYP21 and CYP11B1) that are required for cortisol synthesis. These enzymes were shown to be metabolically active for cortisol synthesis since radiometric conversion assays traced the metabolism of [7- 3 H]-pregnenolone through each steroid intermediate to [7- 3 H]-cortisol in cultured PHK. Trilostane (a 3βHSD1 inhibitor) and ketoconazole (a CYP17A1 inhibitor) blocked the metabolism of both pregnenolone and progesterone. Finally, we show that normal skin expresses two cholesterol transporters, steroidogenic acute regulatory protein (StAR), regarded as the rate-determining protein for steroid synthesis, and metastatic lymph node 64 (MLN64) whose function has been linked to cholesterol transport in steroidogenesis. The expression of StAR and MLN64 was aberrant in two skin disorders, psoriasis and atopic dermatitis, that are commonly treated with cortisol, suggesting dysregulation of epidermal steroid synthesis in these patients. Collectively these data show that PHK are capable of extra

  6. Trastorno Somatosensorial en niños con Trastornos por Déficit de Atención con Hiperactividad.

    OpenAIRE

    Romero Ayuso, Dulce María

    2016-01-01

    Introducción: El estudio de los trastornos por déficit de atención (ADHD) se ha centrado en la falta de control inhibitorio como déficit primario, aunque su fisiopatología también se ha relacionado con la corteza somatosensorial. El objetivo de este trabajo fue conocer si existe un trastorno para la discriminación sensorial táctil y praxis en los niños con ADHD y si éste es similar en los subtipos inatento (ADHD-I) y combinado (ADHD-C). Método: los participantes fueron 74 niños entre 7 y 11 a...

  7. Primary structure of human alpha 2-macroglobulin. V. The complete structure

    DEFF Research Database (Denmark)

    Sottrup-Jensen, Lars; Stepanik, Terrence M; Kristensen, Torsten

    1984-01-01

    The primary structure of the tetrameric plasma glycoprotein human alpha 2-macroglobulin has been determined. The identical subunits contain 1451 amino acid residues. Glucosamine-based oligosaccharide groups are attached to asparagine residues 32, 47, 224, 373, 387, 846, 968, and 1401. Eleven......-SH group of Cys-949 is thiol esterified to the gamma-carbonyl group of Glx-952, thus forming an activatable reactive site which can mediate covalent binding of nucleophiles. A putative transglutaminase cross-linking site is constituted by Gln-670 and Gln-671. The primary sites of proteolytic cleavage......-macroglobulin subunit is discussed. A comparison of stretches of sequences from alpha 2-macroglobulin with partial sequence data for complement components C3 and C4 indicates that these proteins are evolutionary related. The properties of alpha 2-macroglobulin are discussed within the context of proteolytically...

  8. Regulation of human renin expression in chorion cell primary cultures

    International Nuclear Information System (INIS)

    Duncan, K.G.; Haidar, M.A.; Baxter, J.D.; Reudelhuber, T.L.

    1990-01-01

    The human renin gene is expressed in the kidney, placenta, and several other sites. The release of renin or its precursor, prorenin, can be affected by several regulatory agents. In this study, primary cultures of human placental cells were used to examine the regulation of prorenin release and renin mRNA levels and of the transfected human renin promoter linked to chloramphenicol acetyltransferase reporter sequences. Treatment of the cultures with a calcium ionophore alone, calcium ionophore plus forskolin (that activates adenylate cyclase), or forskolin plus a phorbol ester increased prorenin release and renin mRNA levels 1.3 endash to 6 endash fold, but several classes of steroids did not affect prorenin secretion or renin RNA levels. These results suggest that (i) the first 584 base pairs of the renin gene 5'endash flanking DNA do not contain functional glucocorticoid or estrogen response elements, (ii) placental prorenin release and renin mRNA are regulated by calcium ion and by the combinations of cAMP with either C kinase or calcium ion, and (iii) the first 100 base pairs of the human renin 5'endash flanking DNA direct accurate initiation of transcription and can be regulated by cAMP. Thus, some control of renin release in the placenta (and by inference in other tissues) occurs via transcriptional influences on its promoter

  9. Immunocytochemical investigation of immune cells within human primary and permanent tooth pulp.

    Science.gov (United States)

    Rodd, H D; Boissonade, F M

    2006-01-01

    The aim of this study was to determine whether there are any differences in the number and distribution of immune cells within human primary and permanent tooth pulp, both in health and disease. The research took the form of a quantitative immunocytochemical study. One hundred and twenty-four mandibular first permanent molars and second primary molars were obtained from children requiring dental extractions under general anaesthesia. Following exodontia, 10-microm-thick frozen pulp sections were processed for indirect immunofluorescence. Triple-labelling regimes were employed using combinations of the following: (1) protein gene product 9.5, a general neuronal marker; (2) leucocyte common antigen (LCA); and (3) Ulex europaeus I lectin, a marker of vascular endothelium. Image analysis was then used to determine the percentage area of immunostaining for LCA. Leucocytes were significantly more abundant in the pulp horn and mid-coronal region of intact and carious primary teeth, as compared to permanent teeth (P < 0.05, anova). Both dentitions demonstrated the presence of well-localized inflammatory cell infiltrates and marked aborization of pulpal nerves in areas of dense leucocyte accumulation. Primary and permanent tooth pulps appear to have a similar potential to mount inflammatory responses to gross caries The management of the compromised primary tooth pulp needs to be reappraised in the light of these findings.

  10. Transient receptor potential channel polymorphisms are associated with the somatosensory function in neuropathic pain patients.

    Directory of Open Access Journals (Sweden)

    Andreas Binder

    Full Text Available Transient receptor potential channels are important mediators of thermal and mechanical stimuli and play an important role in neuropathic pain. The contribution of hereditary variants in the genes of transient receptor potential channels to neuropathic pain is unknown. We investigated the frequency of transient receptor potential ankyrin 1, transient receptor potential melastin 8 and transient receptor potential vanilloid 1 single nucleotide polymorphisms and their impact on somatosensory abnormalities in neuropathic pain patients. Within the German Research Network on Neuropathic Pain (Deutscher Forscbungsverbund Neuropathischer Schmerz 371 neuropathic pain patients were phenotypically characterized using standardized quantitative sensory testing. Pyrosequencing was employed to determine a total of eleven single nucleotide polymorphisms in transient receptor potential channel genes of the neuropathic pain patients and a cohort of 253 German healthy volunteers. Associations of quantitative sensory testing parameters and single nucleotide polymorphisms between and within groups and subgroups, based on sensory phenotypes, were analyzed. Single nucleotide polymorphisms frequencies did not differ between both the cohorts. However, in neuropathic pain patients transient receptor potential ankyrin 1 710G>A (rs920829, E179K was associated with the presence of paradoxical heat sensation (p = 0.03, and transient receptor potential vanilloid 1 1911A>G (rs8065080, I585V with cold hypoalgesia (p = 0.0035. Two main subgroups characterized by preserved (1 and impaired (2 sensory function were identified. In subgroup 1 transient receptor potential vanilloid 1 1911A>G led to significantly less heat hyperalgesia, pinprick hyperalgesia and mechanical hypaesthesia (p = 0.006, p = 0.005 and pG (rs222747, M315I to cold hypaesthesia (p = 0.002, but there was absence of associations in subgroup 2. In this study we found no evidence that genetic

  11. Abnormalities of somatosensory perception in patients with painful osteoarthritis normalize following successful treatment.

    Science.gov (United States)

    Kosek, E; Ordeberg, G

    2000-01-01

    To investigate the effect of chronic nociceptive pain on somatosensory perception, quantitative sensibility testing was performed in the most painful area and the homologous contralateral side in 14 patients with painful osteoarthritis of the hip. Twelve patients were reassessed in a painfree state 6-14 months following surgery. Von Frey filaments were used to test low-threshold mechanoreceptive function. Pressure pain sensitivity was assessed with a pressure algometer and thermal sensitivity with a Thermotest. Sex- and age-matched controls were examined in the corresponding areas at similar time intervals. There was no statistically significant difference between groups in the sensitivity to light touch and innocuous cold in either session. Compared to controls, patients had increased sensitivity to pressure pain in the most painful area (p pain (ppain (p = 0.054) before surgery. In the painful area, patients' sensitivity to pressure pain decreased (p pain. Copyright 2000 European Federation of Chapters of the International Association for the Study of Pain.

  12. Cytotoxic effects of denture adhesives on primary human oral keratinocytes, fibroblasts and permanent L929 cell lines.

    Science.gov (United States)

    Chen, Fengying; Wu, Tianfu; Cheng, Xiangrong

    2014-03-01

    To date, there have been very little data on the cytotoxic responses of different cell lines to denture adhesives. To determine the cytotoxicity of three denture adhesives on primary human oral keratinocytes (HOKs), fibroblasts (HOFs) and permanent mouse fibroblasts cell lines (L929). Three commercial denture adhesives (two creams and one powder) were prepared for indirect contact using the agar diffusion test, as well as extracts in MTT assay. The results of the MTT assay were statistically analysed by one-way anova and Tukey's test (p adhesives showed mild to moderate cytotoxicity to primary HOKs (p  0.05) in both assays. For primary HOFs cultures, slight cytotoxicity was observed for one of the products from the agar diffusion test and undiluted eluates of all tested adhesives with MTT assay (p adhesives are toxic to the primary HOKs and HOFs cultures, whereas non-toxic to L929 cells. The results suggest that primary human oral mucosal cells may provide more valuable information in toxicity screening of denture adhesives. © 2012 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd.

  13. 2,3,7,8-Tetrachlorodibenzo-p-dioxin-mediated disruption of the CD40 ligand-induced activation of primary human B cells

    International Nuclear Information System (INIS)

    Lu Haitian; Crawford, Robert B.; Kaplan, Barbara L.F.; Kaminski, Norbert E.

    2011-01-01

    Suppression of the primary antibody response is particularly sensitive to suppression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice; however, surprisingly little is known concerning the effects of TCDD on humoral immunity or B cell function in humans. Results from a limited number of previous studies, primarily employing in vitro activation models, suggested that human B cell effector function is suppressed by TCDD. The present study sought to extend these findings by investigating, in primary human B cells, the effects of TCDD on several critical stages leading to antibody secretion including activation and plasmacytic differentiation using an in vitro CD40 ligand activation model. These studies revealed important differences in the response of human and mouse B cells to TCDD, the most striking being altered expression of plasmacytic differentiation regulators, B lymphocyte-induced maturation protein 1 and paired box protein 5, in mouse but not human B cells. The activation of human B cells was profoundly impaired by TCDD, as evidenced by decreased expression of activation markers CD80, CD86, and CD69. The impaired activation correlated with decreased cell viability, which prevented the progression of human B cells toward plasmacytic differentiation. TCDD treatment also attenuated the early activation of mitogen-activated protein kinases (MAPK) and Akt signaling in human B cells. Collectively, the present study provided experimental evidence for novel mechanisms by which TCDD impairs the effector function of primary human B cells. - Highlights: → In this study primary human and mouse B cell toxicity to TCDD was compared. → TCDD altered the expression of Blimp-1 and Pax5 in mouse but not human B cells. → TCDD markedly suppressed human B cell activation as characterized by CD80, CD86 and CD69 expression. → TCDD inhibited ERK, p38, and Akt phosphorylation in human B cells.

  14. Dissection of the transformation of primary human hematopoietic cells by the oncogene NUP98-HOXA9.

    Directory of Open Access Journals (Sweden)

    Enas R Yassin

    2009-08-01

    Full Text Available NUP98-HOXA9 is the prototype of a group of oncoproteins associated with acute myeloid leukemia. It consists of an N-terminal portion of NUP98 fused to the homeodomain of HOXA9 and is believed to act as an aberrant transcription factor that binds DNA through the homeodomain. Here we show that NUP98-HOXA9 can regulate transcription without binding to DNA. In order to determine the relative contributions of the NUP98 and HOXA9 portions to the transforming ability of NUP98-HOXA9, the effects of NUP98-HOXA9 on primary human CD34+ cells were dissected and compared to those of wild-type HOXA9. In contrast to previous findings in mouse cells, HOXA9 had only mild effects on the differentiation and proliferation of primary human hematopoietic cells. The ability of NUP98-HOXA9 to disrupt the differentiation of primary human CD34+ cells was found to depend primarily on the NUP98 portion, whereas induction of long-term proliferation required both the NUP98 moiety and an intact homeodomain. Using oligonucleotide microarrays in primary human CD34+ cells, a group of genes was identified whose dysregulation by NUP98-HOXA9 is attributable primarily to the NUP98 portion. These include RAP1A, HEY1, and PTGS2 (COX-2. Their functions may reflect the contribution of the NUP98 moiety of NUP98-HOXA9 to leukemic transformation. Taken together, these results suggest that the effects of NUP98-HOXA9 on gene transcription and cell transformation are mediated by at least two distinct mechanisms: one that involves promoter binding through the homeodomain with direct transcriptional activation, and another that depends predominantly on the NUP98 moiety and does not involve direct DNA binding.

  15. Tinnitus in Temporomandibular Joint Disorders: Is it a Specific Somatosensory Tinnitus Subtype?

    Science.gov (United States)

    Algieri, Giuseppe Maria Antonio; Leonardi, Alessandra; Arangio, Paolo; Vellone, Valentino; Paolo, Carlo Di; Cascone, Piero

    2017-04-19

    The most significant otologic symptoms, consisting of ear pain, tinnitus, dizziness, hearing loss and auricolar "fullness", generally arise within the auditory system, often are associated with extra auricolar disorders, particularly disorder of the temporo-mandibular joint. In our study we examined a sample of 200 consecutive patients who had experienced severe disabling symptom. The patiens came to maxillofacial specialist assessment for temporomandibular disorder. Each patient was assessed by a detailed anamnestic and clinical temporomandibular joint examination and they are divided into five main groups according classification criteria established by Wilkes; tinnitus and subjective indicators of pain are evaluated. The results of this study provide a close correlation between the joint pathology and otologic symptoms, particularly regarding tinnitus and balance disorders, and that this relationship is greater the more advanced is the stage of joint pathology. Moreover, this study shows that TMD-related tinnitus principally affects a younger population (average fifth decade of life) and mainly women (more than 2/3 of the cases). Such evidence suggests the existence of a specific tinnitus subtype that may be defined as "TMD-related somatosensory tinnitus".

  16. Region and task-specific activation of Arc in primary motor cortex of rats following motor skill learning.

    Science.gov (United States)

    Hosp, J A; Mann, S; Wegenast-Braun, B M; Calhoun, M E; Luft, A R

    2013-10-10

    Motor learning requires protein synthesis within the primary motor cortex (M1). Here, we show that the immediate early gene Arc/Arg3.1 is specifically induced in M1 by learning a motor skill. Arc mRNA was quantified using a fluorescent in situ hybridization assay in adult Long-Evans rats learning a skilled reaching task (SRT), in rats performing reaching-like forelimb movement without learning (ACT) and in rats that were trained in the operant but not the motor elements of the task (controls). Apart from M1, Arc expression was assessed within the rostral motor area (RMA), primary somatosensory cortex (S1), striatum (ST) and cerebellum. In SRT animals, Arc mRNA levels in M1 contralateral to the trained limb were 31% higher than ipsilateral (pmotor skill learning in rats. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Estrogen decreases tight junction protein ZO-1 expression in human primary gut tissues.

    Science.gov (United States)

    Zhou, Zejun; Zhang, Lumin; Ding, Miao; Luo, Zhenwu; Yuan, Shao; Bansal, Meena B; Gilkeson, Gary; Lang, Ren; Jiang, Wei

    2017-10-01

    Females have a higher prevalence of most autoimmune diseases; however, the mechanism is unknown. In this study, we examined the expression of tight junction protein zonula occludens 1 (ZO-1) and estrogen receptor (ER)-α/β in human primary gut tissues by immunohistochemistry, immunofluorescence and qPCR. The expression of ZO-1 and ER-β but not ER-α was present in both male and female gut tissues. There was no sex difference in ER-β expression, but ZO-1 expression was decreased in females compared to males. In vitro, estrogen treatment decreased ZO-1 mRNA and protein expression, ZO-1 promoter activity, IL-6 production, and NF-κB activation in human primary gut tissues or the Caco-2 cells, but increased the ER-β expression in Caco-2 cells. Consistently, plasma IL-6 levels in females were reduced relative to males in vivo. Our finding indicates that estrogen may play a role in gut tight junction expression and permeability. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Functional magnetic resonance imaging of the human primary visual cortex during visual stimulation

    International Nuclear Information System (INIS)

    Miki, Atsushi; Abe, Haruki; Nakajima, Takashi; Fujita, Motoi; Watanabe, Hiroyuki; Kuwabara, Takeo; Naruse, Shoji; Takagi, Mineo.

    1995-01-01

    Signal changes in the human primary visual cortex during visual stimulation were evaluated using non-invasive functional magnetic resonance imaging (fMRI). The experiments were performed on 10 normal human volunteers and 2 patients with homonymous hemianopsia, including one who was recovering from the exacerbation of multiple sclerosis. The visual stimuli were provided by a pattern generator using the checkerboard pattern for determining the visual evoked potential of full-field and hemifield stimulation. In normal volunteers, a signal increase was observed on the bilateral primary visual cortex during the full-field stimulation and on the contra-lateral cortex during hemifield stimulation. In the patient with homonymous hemianopsia after cerebral infarction, the signal change was clearly decreased on the affected side. In the other patient, the one recovering from multiple sclerosis with an almost normal visual field, the fMRI was within normal limits. These results suggest that it is possible to visualize the activation of the visual cortex during visual stimulation, and that there is a possibility of using this test as an objective method of visual field examination. (author)

  19. Frequency-specific attentional modulation in human primary auditory cortex and midbrain.

    Science.gov (United States)

    Riecke, Lars; Peters, Judith C; Valente, Giancarlo; Poser, Benedikt A; Kemper, Valentin G; Formisano, Elia; Sorger, Bettina

    2018-07-01

    Paying selective attention to an audio frequency selectively enhances activity within primary auditory cortex (PAC) at the tonotopic site (frequency channel) representing that frequency. Animal PAC neurons achieve this 'frequency-specific attentional spotlight' by adapting their frequency tuning, yet comparable evidence in humans is scarce. Moreover, whether the spotlight operates in human midbrain is unknown. To address these issues, we studied the spectral tuning of frequency channels in human PAC and inferior colliculus (IC), using 7-T functional magnetic resonance imaging (FMRI) and frequency mapping, while participants focused on different frequency-specific sounds. We found that shifts in frequency-specific attention alter the response gain, but not tuning profile, of PAC frequency channels. The gain modulation was strongest in low-frequency channels and varied near-monotonically across the tonotopic axis, giving rise to the attentional spotlight. We observed less prominent, non-tonotopic spatial patterns of attentional modulation in IC. These results indicate that the frequency-specific attentional spotlight in human PAC as measured with FMRI arises primarily from tonotopic gain modulation, rather than adapted frequency tuning. Moreover, frequency-specific attentional modulation of afferent sound processing in human IC seems to be considerably weaker, suggesting that the spotlight diminishes toward this lower-order processing stage. Our study sheds light on how the human auditory pathway adapts to the different demands of selective hearing. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Gene-chip studies of adipogenesis-regulated microRNAs in mouse primary adipocytes and human obesity

    Directory of Open Access Journals (Sweden)

    Gallagher Iain J

    2011-03-01

    Full Text Available Abstract Background Adipose tissue abundance relies partly on the factors that regulate adipogenesis, i.e. proliferation and differentiation of adipocytes. While components of the transcriptional program that initiates adipogenesis is well-known, the importance of microRNAs in adipogenesis is less well studied. We thus set out to investigate whether miRNAs would be actively modulated during adipogenesis and obesity. Methods Several models exist to study adipogenesis in vitro, of which the cell line 3T3-L1 is the most well known, albeit not the most physiologically appropriate. Thus, as an alternative, we produced EXIQON microarray of brown and white primary murine adipocytes (prior to and following differentiation to yield global profiles of miRNAs. Results We found 65 miRNAs regulated during in vitro adipogenesis in primary adipocytes. We evaluated the similarity of our responses to those found in non-primary cell models, through literature data-mining. When comparing primary adipocyte profiles, with those of cell lines reported in the literature, we found a high degree of difference in 'adipogenesis' regulated miRNAs suggesting that the model systems may not be accurately representing adipogenesis. The expression of 10 adipogenesis-regulated miRNAs were studied using real-time qPCR and then we selected 5 miRNAs, that showed robust expression, were profiled in subcutaneous adipose tissue obtained from 20 humans with a range of body mass indices (BMI, range = 21-48, and all samples have U133+2 Affymetrix profiles provided. Of the miRNAs tested, mir-21 was robustly expressed in human adipose tissue and positively correlated with BMI (R2 = 0.49, p Conclusion In conclusion, we provide a preliminary analysis of miRNAs associated with primary cell in vitro adipogenesis and demonstrate that the inflammation-associated miRNA, mir-21 is up-regulated in subcutaneous adipose tissue in human obesity. Further, we provide a novel transcriptomics database of

  1. The awareness of primary caregivers in South Africa of the human rights of their children with intellectual disabilities.

    Science.gov (United States)

    Huus, K; Dada, S; Bornman, J; Lygnegård, F

    2016-11-01

    Besides the right to freedom, human rights can be seen as a basic requirement also for the maintenance of human dignity and the opportunity to thrive - particularly in the case of children with disabilities. It is imperative to explore primary caregivers' awareness of the human rights of their children with intellectual disabilities in view of the role they may play in either facilitating or restricting these rights. This paper explores the awareness of 219 primary caregivers of the human rights of their children with intellectual disabilities. A descriptive survey design was used with a custom-designed questionnaire that employed a deductive content analysis based on the articles of the United Nations Convention on the Rights of a Child. Comparisons were drawn between the awareness of primary caregivers from urban and those from rural areas. The majority (85.5%) of participants agreed that their child with intellectual disability had rights. Three broad kinds of right were mentioned (in descending order): provision rights, protection rights and participation rights. Participants from both urban and rural areas mentioned education (a provision right) most frequently. However, participants from urban areas were more aware of the different rights that existed than were their counterparts from rural areas. Primary caregivers in both rural and urban areas are aware of the rights of their children with disabilities, although there are significant differences between them. © 2016 John Wiley & Sons Ltd.

  2. High-throughput gene expression profiling of memory differentiation in primary human T cells

    Directory of Open Access Journals (Sweden)

    Russell Kate

    2008-08-01

    Full Text Available Abstract Background The differentiation of naive T and B cells into memory lymphocytes is essential for immunity to pathogens. Therapeutic manipulation of this cellular differentiation program could improve vaccine efficacy and the in vitro expansion of memory cells. However, chemical screens to identify compounds that induce memory differentiation have been limited by 1 the lack of reporter-gene or functional assays that can distinguish naive and memory-phenotype T cells at high throughput and 2 a suitable cell-line representative of naive T cells. Results Here, we describe a method for gene-expression based screening that allows primary naive and memory-phenotype lymphocytes to be discriminated based on complex genes signatures corresponding to these differentiation states. We used ligation-mediated amplification and a fluorescent, bead-based detection system to quantify simultaneously 55 transcripts representing naive and memory-phenotype signatures in purified populations of human T cells. The use of a multi-gene panel allowed better resolution than any constituent single gene. The method was precise, correlated well with Affymetrix microarray data, and could be easily scaled up for high-throughput. Conclusion This method provides a generic solution for high-throughput differentiation screens in primary human T cells where no single-gene or functional assay is available. This screening platform will allow the identification of small molecules, genes or soluble factors that direct memory differentiation in naive human lymphocytes.

  3. Human antibodies that neutralize primary human immunodeficiency virus type 1 in vitro do not provide protection in an in vivo model.

    NARCIS (Netherlands)

    M. Schutten (Martin); K. Tenner-Racz; P. Racz; D.W. van Bekkum (Dirk); A.D.M.E. Osterhaus (Albert)

    1996-01-01

    textabstractRecently, conflicting data have been published about the ability of antibodies which efficiently neutralize T cell-adapted human immunodeficiency virus type 1 (HIV-1) strains to neutralize primary HIV-1 strains in vitro and in vivo. Here we present data indicating that such antibodies

  4. Prevalence and factors associated with breast milk donation in banks that receive human milk in primary health care units,

    OpenAIRE

    Meneses, Tatiana Mota Xavier de; Oliveira, Maria Inês Couto de; Boccolini, Cristiano Siqueira

    2017-01-01

    Abstract Objective: To estimate the prevalence and to analyze factors associated with breast milk donation at primary health care units in order to increase the human milk bank reserves. Methods: Cross-sectional study carried out in 2013 in Rio de Janeiro, Brazil. A representative sample of 695 mothers of children younger than 1 year attended to at the nine primary health care units with human milk donation services were interviewed. A hierarchical approach was used to obtain adjusted preva...

  5. Prevalence and factors associated with breast milk donation in banks that receive human milk in primary health care units

    OpenAIRE

    Tatiana Mota Xavier de Meneses; Maria Inês Couto de Oliveira; Cristiano Siqueira Boccolini

    2017-01-01

    Abstract Objective: To estimate the prevalence and to analyze factors associated with breast milk donation at primary health care units in order to increase the human milk bank reserves. Methods: Cross-sectional study carried out in 2013 in Rio de Janeiro, Brazil. A representative sample of 695 mothers of children younger than 1 year attended to at the nine primary health care units with human milk donation services were interviewed. A hierarchical approach was used to obtain adjusted preva...

  6. Unimodal primary sensory cortices are directly connected by long-range horizontal projections in the rat sensory cortex

    Directory of Open Access Journals (Sweden)

    Jimmy eStehberg

    2014-09-01

    Full Text Available Research based on functional imaging and neuronal recordings in the barrel cortex subdivision of primary somatosensory cortex (SI of the adult rat has revealed novel aspects of structure-function relationships in this cortex. Specifically, it has demonstrated that single whisker stimulation evokes subthreshold neuronal activity that spreads symmetrically within gray matter from the appropriate barrel area, crosses cytoarchitectural borders of SI and reaches deeply into other unimodal primary cortices such as primary auditory (AI and primary visual (VI. It was further demonstrated that this spread is supported by a spatially matching underlying diffuse network of border-crossing, long-range projections that could also reach deeply into AI and VI. Here we seek to determine whether such a network of border-crossing, long-range projections is unique to barrel cortex or characterizes also other primary, unimodal sensory cortices and therefore could directly connect them. Using anterograde (BDA and retrograde (CTb tract-tracing techniques, we demonstrate that such diffuse horizontal networks directly and mutually connect VI, AI and SI. These findings suggest that diffuse, border-crossing axonal projections connecting directly primary cortices are an important organizational motif common to all major primary sensory cortices in the rat. Potential implications of these findings for topics including cortical structure-function relationships, multisensory integration, functional imaging and cortical parcellation are discussed.

  7. Exploring Global Patterns in Human Appropriation of Net Primary Production Using Earth Observation Satellites and Statistical Data

    Science.gov (United States)

    Imhoff, M.; Bounoua, L.

    2004-12-01

    A unique combination of satellite and socio-economic data were used to explore the relationship between human consumption and the carbon cycle. Biophysical models were applied to consumption data to estimate the annual amount of Earth's terrestrial net primary production humans require for food, fiber and fuel using the same modeling architecture as satellite-supported NPP measurements. The amount of Earth's NPP required to support human activities is a powerful measure of the aggregate human impacts on the biosphere and indicator of societal vulnerability to climate change. Equations were developed estimating the amount of landscape-level NPP required to generate all the products consumed by 230 countries including; vegetal foods, meat, milk, eggs, wood, fuel-wood, paper and fiber. The amount of NPP required was calculated on a per capita basis and projected onto a global map of population to create a spatially explicit map of NPP-carbon demand in units of elemental carbon. NPP demand was compared to a map of Earth's average annual net primary production or supply created using 17 years (1982-1998) of AVHRR vegetation index to produce a geographically accurate balance sheet of terrestrial NPP-carbon supply and demand. Globally, humans consume 20 percent of Earth's total net primary production on land. Regionally the NPP-carbon balance percentage varies from 6 to over 70 percent and locally from near 0 to over 30,000 percent in major urban areas. The uneven distribution of NPP-carbon supply and demand, indicate the degree to which various human populations rely on NPP imports, are vulnerable to climate change and suggest policy options for slowing future growth in NPP demand.

  8. Transcranial focused ultrasound stimulation of human primary visual cortex

    Science.gov (United States)

    Lee, Wonhye; Kim, Hyun-Chul; Jung, Yujin; Chung, Yong An; Song, In-Uk; Lee, Jong-Hwan; Yoo, Seung-Schik

    2016-09-01

    Transcranial focused ultrasound (FUS) is making progress as a new non-invasive mode of regional brain stimulation. Current evidence of FUS-mediated neurostimulation for humans has been limited to the observation of subjective sensory manifestations and electrophysiological responses, thus warranting the identification of stimulated brain regions. Here, we report FUS sonication of the primary visual cortex (V1) in humans, resulting in elicited activation not only from the sonicated brain area, but also from the network of regions involved in visual and higher-order cognitive processes (as revealed by simultaneous acquisition of blood-oxygenation-level-dependent functional magnetic resonance imaging). Accompanying phosphene perception was also reported. The electroencephalo graphic (EEG) responses showed distinct peaks associated with the stimulation. None of the participants showed any adverse effects from the sonication based on neuroimaging and neurological examinations. Retrospective numerical simulation of the acoustic profile showed the presence of individual variability in terms of the location and intensity of the acoustic focus. With exquisite spatial selectivity and capability for depth penetration, FUS may confer a unique utility in providing non-invasive stimulation of region-specific brain circuits for neuroscientific and therapeutic applications.

  9. Attentional load modulates responses of human primary visual cortex to invisible stimuli.

    Science.gov (United States)

    Bahrami, Bahador; Lavie, Nilli; Rees, Geraint

    2007-03-20

    Visual neuroscience has long sought to determine the extent to which stimulus-evoked activity in visual cortex depends on attention and awareness. Some influential theories of consciousness maintain that the allocation of attention is restricted to conscious representations [1, 2]. However, in the load theory of attention [3], competition between task-relevant and task-irrelevant stimuli for limited-capacity attention does not depend on conscious perception of the irrelevant stimuli. The critical test is whether the level of attentional load in a relevant task would determine unconscious neural processing of invisible stimuli. Human participants were scanned with high-field fMRI while they performed a foveal task of low or high attentional load. Irrelevant, invisible monocular stimuli were simultaneously presented peripherally and were continuously suppressed by a flashing mask in the other eye [4]. Attentional load in the foveal task strongly modulated retinotopic activity evoked in primary visual cortex (V1) by the invisible stimuli. Contrary to traditional views [1, 2, 5, 6], we found that availability of attentional capacity determines neural representations related to unconscious processing of continuously suppressed stimuli in human primary visual cortex. Spillover of attention to cortical representations of invisible stimuli (under low load) cannot be a sufficient condition for their awareness.

  10. Effect of cell phone-like electromagnetic radiation on primary human thyroid cells.

    Science.gov (United States)

    Silva, Veronica; Hilly, Ohad; Strenov, Yulia; Tzabari, Cochava; Hauptman, Yirmi; Feinmesser, Raphael

    2016-01-01

    To evaluate the potential carcinogenic effects of radiofrequency energy (RFE) emitted by cell phones on human thyroid primary cells. Primary thyroid cell culture was prepared from normal thyroid tissue obtained from patients who underwent surgery at our department. Subconfluent thyroid cells were irradiated under different conditions inside a cell incubator using a device that simulates cell phone-RFE. Proliferation of control and irradiated cells was assessed by the immunohistochemical staining of antigen Kiel clone-67 (Ki-67) and tumor suppressor p53 (p53) expression. DNA ploidy and the stress biomarkers heat shock protein 70 (HSP70) and reactive oxygen species (ROS) was evaluated by fluorescence-activated cell sorting (FACS). Our cells highly expressed thyroglobulin (Tg) and sodium-iodide symporter (NIS) confirming the origin of the tissue. None of the irradiation conditions evaluated here had an effect neither on the proliferation marker Ki-67 nor on p53 expression. DNA ploidy was also not affected by RFE, as well as the expression of the biomarkers HSP70 and ROS. Our conditions of RFE exposure seem to have no potential carcinogenic effect on human thyroid cells. Moreover, common biomarkers usually associated to environmental stress also remained unchanged. We failed to find an association between cell phone-RFE and thyroid cancer. Additional studies are recommended.

  11. Dexamethasone-Mediated Upregulation of Calreticulin Inhibits Primary Human Glioblastoma Dispersal Ex Vivo

    Directory of Open Access Journals (Sweden)

    Mohan Nair

    2018-02-01

    Full Text Available Dispersal of Glioblastoma (GBM renders localized therapy ineffective and is a major cause of recurrence. Previous studies have demonstrated that Dexamethasone (Dex, a drug currently used to treat brain tumor–related edema, can also significantly reduce dispersal of human primary GBM cells from neurospheres. It does so by triggering α5 integrin activity, leading to restoration of fibronectin matrix assembly (FNMA, increased neurosphere cohesion, and reduction of neurosphere dispersal velocity (DV. How Dex specifically activates α5 integrin in these GBM lines is unknown. Several chaperone proteins are known to activate integrins, including calreticulin (CALR. We explore the role of CALR as a potential mediator of Dex-dependent induction of α5 integrin activity in primary human GBM cells. We use CALR knock-down and knock-in strategies to explore the effects on FNMA, aggregate compaction, and dispersal velocity in vitro, as well as dispersal ex vivo on extirpated mouse retina and brain slices. We show that Dex increases CALR expression and that siRNA knockdown suppresses Dex-mediated FNMA. Overexpression of CALR in GBM cells activates FNMA, increases compaction, and decreases DV in vitro and on explants of mouse retina and brain slices. Our results define a novel interaction between Dex, CALR, and FNMA as inhibitors of GBM dispersal.

  12. Isolation and Characterization of Current Human Coronavirus Strains in Primary Human Epithelial Cell Cultures Reveal Differences in Target Cell Tropism

    Science.gov (United States)

    Dijkman, Ronald; Jebbink, Maarten F.; Koekkoek, Sylvie M.; Deijs, Martin; Jónsdóttir, Hulda R.; Molenkamp, Richard; Ieven, Margareta; Goossens, Herman; Thiel, Volker

    2013-01-01

    The human airway epithelium (HAE) represents the entry port of many human respiratory viruses, including human coronaviruses (HCoVs). Nowadays, four HCoVs, HCoV-229E, HCoV-OC43, HCoV-HKU1, and HCoV-NL63, are known to be circulating worldwide, causing upper and lower respiratory tract infections in nonhospitalized and hospitalized children. Studies of the fundamental aspects of these HCoV infections at the primary entry port, such as cell tropism, are seriously hampered by the lack of a universal culture system or suitable animal models. To expand the knowledge on fundamental virus-host interactions for all four HCoVs at the site of primary infection, we used pseudostratified HAE cell cultures to isolate and characterize representative clinical HCoV strains directly from nasopharyngeal material. Ten contemporary isolates were obtained, representing HCoV-229E (n = 1), HCoV-NL63 (n = 1), HCoV-HKU1 (n = 4), and HCoV-OC43 (n = 4). For each strain, we analyzed the replication kinetics and progeny virus release on HAE cell cultures derived from different donors. Surprisingly, by visualizing HCoV infection by confocal microscopy, we observed that HCoV-229E employs a target cell tropism for nonciliated cells, whereas HCoV-OC43, HCoV-HKU1, and HCoV-NL63 all infect ciliated cells. Collectively, the data demonstrate that HAE cell cultures, which morphologically and functionally resemble human airways in vivo, represent a robust universal culture system for isolating and comparing all contemporary HCoV strains. PMID:23427150

  13. Neural mechanisms of transient neocortical beta rhythms: Converging evidence from humans, computational modeling, monkeys, and mice

    Science.gov (United States)

    Sherman, Maxwell A.; Lee, Shane; Law, Robert; Haegens, Saskia; Thorn, Catherine A.; Hämäläinen, Matti S.; Moore, Christopher I.; Jones, Stephanie R.

    2016-01-01

    Human neocortical 15–29-Hz beta oscillations are strong predictors of perceptual and motor performance. However, the mechanistic origin of beta in vivo is unknown, hindering understanding of its functional role. Combining human magnetoencephalography (MEG), computational modeling, and laminar recordings in animals, we present a new theory that accounts for the origin of spontaneous neocortical beta. In our MEG data, spontaneous beta activity from somatosensory and frontal cortex emerged as noncontinuous beta events typically lasting drive targeting proximal and distal dendrites of pyramidal neurons, where the defining feature of a beta event was a strong distal drive that lasted one beta period (∼50 ms). This beta mechanism rigorously accounted for the beta event profiles; several other mechanisms did not. The spatial location of synaptic drive in the model to supragranular and infragranular layers was critical to the emergence of beta events and led to the prediction that beta events should be associated with a specific laminar current profile. Laminar recordings in somatosensory neocortex from anesthetized mice and awake monkeys supported these predictions, suggesting this beta mechanism is conserved across species and recording modalities. These findings make several predictions about optimal states for perceptual and motor performance and guide causal interventions to modulate beta for optimal function. PMID:27469163

  14. Bisphenol A and Bisphenol S Induce Distinct Transcriptional Profiles in Differentiating Human Primary Preadipocytes.

    Directory of Open Access Journals (Sweden)

    Jonathan G Boucher

    Full Text Available Bisphenol S (BPS is increasingly used as a replacement plasticizer for bisphenol A (BPA but its effects on human health have not been thoroughly examined. Recent evidence indicates that both BPA and BPS induce adipogenesis, although the mechanisms leading to this effect are unclear. In an effort to identify common and distinct mechanisms of action in inducing adipogenesis, transcriptional profiles of differentiating human preadipocytes exposed to BPA or BPS were compared. Human subcutaneous primary preadipocytes were differentiated in the presence of either 25 μM BPA or BPS for 2 and 4 days. Poly-A RNA-sequencing was used to identify differentially expressed genes (DEGs. Functional analysis of DEGs was undertaken in Ingenuity Pathway Analysis. BPA-treatment resulted in 472 and 176 DEGs on days 2 and 4, respectively, affecting pathways such as liver X receptor (LXR/retinoid X receptor (RXR activation, hepatic fibrosis and cholestasis. BPS-treatment resulted in 195 and 51 DEGs on days 2 and 4, respectively, revealing enrichment of genes associated with adipogenesis and lipid metabolism including the adipogenesis pathway and cholesterol biosynthesis. Interestingly, the transcription repressor N-CoR was identified as a negative upstream regulator in both BPA- and BPS-treated cells. This study presents the first comparison of BPA- and BPS-induced transcriptional profiles in human differentiating preadipocytes. While we previously showed that BPA and BPS both induce adipogenesis, the results from this study show that BPS affects adipose specific transcriptional changes earlier than BPA, and alters the expression of genes specifically related to adipogenesis and lipid metabolism. The findings provide insight into potential BPS and BPA-mediated mechanisms of action in inducing adipogenesis in human primary preadipocytes.

  15. Primary mesenchymal stem cells in human transplanted lungs are CD90/CD105 perivascularly located tissue-resident cells

    DEFF Research Database (Denmark)

    Rolandsson, Sara; Andersson Sjöland, Annika; Brune, Jan C

    2014-01-01

    BACKGROUND: Mesenchymal stem cells (MSC) have not only been implicated in the development of lung diseases, but they have also been proposed as a future cell-based therapy for lung diseases. However, the cellular identity of the primary MSC in human lung tissues has not yet been reported. This st......BACKGROUND: Mesenchymal stem cells (MSC) have not only been implicated in the development of lung diseases, but they have also been proposed as a future cell-based therapy for lung diseases. However, the cellular identity of the primary MSC in human lung tissues has not yet been reported...

  16. Cortical Local Field Potential Power Is Associated with Behavioral Detection of Near-threshold Stimuli in the Rat Whisker System: Dissociation between Orbitofrontal and Somatosensory Cortices.

    Science.gov (United States)

    Rickard, Rachel E; Young, Andrew M J; Gerdjikov, Todor V

    2018-01-01

    There is growing evidence that ongoing brain oscillations may represent a key regulator of attentional processes and as such may contribute to behavioral performance in psychophysical tasks. OFC appears to be involved in the top-down modulation of sensory processing; however, the specific contribution of ongoing OFC oscillations to perception has not been characterized. Here we used the rat whiskers as a model system to further characterize the relationship between cortical state and tactile detection. Head-fixed rats were trained to report the presence of a vibrotactile stimulus (frequency = 60 Hz, duration = 2 sec, deflection amplitude = 0.01-0.5 mm) applied to a single vibrissa. We calculated power spectra of local field potentials preceding the onset of near-threshold stimuli from microelectrodes chronically implanted in OFC and somatosensory cortex. We found a dissociation between slow oscillation power in the two regions in relation to detection probability: Higher OFC but not somatosensory delta power was associated with increased detection probability. Furthermore, coherence between OFC and barrel cortex was reduced preceding successful detection. Consistent with the role of OFC in attention, our results identify a cortical network whose activity is differentially modulated before successful tactile detection.

  17. Induced Pluripotent Stem Cells: A novel frontier in the study of human primary immunodeficiencies

    Science.gov (United States)

    Pessach, Itai M.; Ordovas-Montanes, Jose; Zhang, Shen-Ying; Casanova, Jean-Laurent; Giliani, Silvia; Gennery, Andrew R.; Al-Herz, Waleed; Manos, Philip D.; Schlaeger, Thorsten M.; Park, In-Hyun; Rucci, Francesca; Agarwal, Suneet; Mostoslavsky, Gustavo; Daley, George Q.; Notarangelo, Luigi D.

    2010-01-01

    Background The novel ability to epigenetically reprogram somatic cells into induced pluripotent stem cells through the exogenous expression of transcription promises to revolutionize the study of human diseases. Objective Here we report on the generation of 25 induced pluripotent stem cell lines from 6 patients with various forms of Primary Immunodeficiencies, affecting adaptive and/or innate immunity. Methods Patients’ dermal fibroblasts were reprogrammed by expression of four transcription factors, OCT4, SOX2, KLF4, and c-MYC using a single excisable polycistronic lentiviral vector. Results Induced pluripotent stem cells derived from patients with primary immunodeficiencies show a stemness profile that is comparable to that observed in human embryonic stem cells. Following in vitro differentiation into embryoid bodies, pluripotency of the patient-derived indiced pluripotent stem cells lines was demonstrated by expression of genes characteristic of each of the three embryonic layers. We have confirmed the patient-specific origin of the induced pluripotent stem cell lines, and ascertained maintenance of karyotypic integrity. Conclusion By providing a limitless source of diseased stem cells that can be differentiated into various cell types in vitro, the repository of induced pluripotent stem cell lines from patients with primary immunodeficiencies represents a unique resource to investigate the pathophysiology of hematopoietic and extra-hematopoietic manifestations of these diseases, and may assist in the development of novel therapeutic approaches based on gene correction. PMID:21185069

  18. Human Primary Trophoblast Cell Culture Model to Study the Protective Effects of Melatonin Against Hypoxia/reoxygenation-induced Disruption.

    Science.gov (United States)

    Sagrillo-Fagundes, Lucas; Clabault, Hélène; Laurent, Laetitia; Hudon-Thibeault, Andrée-Anne; Salustiano, Eugênia Maria Assunção; Fortier, Marlène; Bienvenue-Pariseault, Josianne; Wong Yen, Philippe; Sanderson, J Thomas; Vaillancourt, Cathy

    2016-07-30

    This protocol describes how villous cytotrophoblast cells are isolated from placentas at term by successive enzymatic digestions, followed by density centrifugation, media gradient isolation and immunomagnetic purification. As observed in vivo, mononucleated villous cytotrophoblast cells in primary culture differentiate into multinucleated syncytiotrophoblast cells after 72 hr. Compared to normoxia (8% O2), villous cytotrophoblast cells that undergo hypoxia/reoxygenation (0.5% / 8% O2) undergo increased oxidative stress and intrinsic apoptosis, similar to that observed in vivo in pregnancy complications such as preeclampsia, preterm birth, and intrauterine growth restriction. In this context, primary villous trophoblasts cultured under hypoxia/reoxygenation conditions represent a unique experimental system to better understand the mechanisms and signalling pathways that are altered in human placenta and facilitate the search for effective drugs that protect against certain pregnancy disorders. Human villous trophoblasts produce melatonin and express its synthesizing enzymes and receptors. Melatonin has been suggested as a treatment for preeclampsia and intrauterine growth restriction because of its protective antioxidant effects. In the primary villous cytotrophoblast cell model described in this paper, melatonin has no effect on trophoblast cells in normoxic state but restores the redox balance of syncytiotrophoblast cells disrupted by hypoxia/reoxygenation. Thus, human villous trophoblast cells in primary culture are an excellent approach to study the mechanisms behind the protective effects of melatonin on placental function during hypoxia/reoxygenation.

  19. Delineation of somatosensory finger areas using vibrotactile stimulation, an ECoG study.

    Science.gov (United States)

    Wahnoun, Rémy; Benson, Michelle; Helms-Tillery, Stephen; Adelson, P David

    2015-10-01

    In surgical planning for epileptic focus resection, functional mapping of eloquent cortex is attained through direct electrical stimulation of the brain. This procedure is uncomfortable, can trigger seizures or nausea, and relies on subjective evaluation. We hypothesize that a method combining vibrotactile stimulation and statistical clustering may provide improved somatosensory mapping. Seven pediatric candidates for surgical resection underwent a task in which their fingers were independently stimulated using a custom designed finger pad, during electrocorticographic monitoring. A cluster-based statistical analysis was then performed to localize the elicited activity on the recording grids. Mid-Gamma clusters (65-115 Hz) arose in areas consistent with anatomical predictions as well as clinical findings, with five subjects presenting a somatotopic organization of the fingers. This process allowed us to delineate finger representation even in patients who were sleeping, with strong interictal activity, or when electrical stimulation did not successfully locate eloquent areas. We suggest that this scheme, relying on the endogenous neural response rather than exogenous electrical activation, could eventually be extended to map other sensory areas and provide a faster and more objective map to better anticipate outcomes of surgical resection.

  20. Phenotypic characterization of telomerase-immortalized primary non-malignant and malignant tumor-derived human prostate epithelial cell lines

    International Nuclear Information System (INIS)

    Gu Yongpeng; Li Hongzhen; Miki, Jun; Kim, Kee-Hong; Furusato, Bungo; Sesterhenn, Isabell A.; Chu, Wei-Sing; McLeod, David G.; Srivastava, Shiv; Ewing, Charles M.; Isaacs, William B.; Rhim, Johng S.

    2006-01-01

    In vitro human prostate cell culture models are critical for clarifying the mechanism of prostate cancer progression and for testing preventive and therapeutic agents. Cell lines ideal for the study of human primary prostate tumors would be those derived from spontaneously immortalized tumor cells; unfortunately, explanted primary prostate cells survive only short-term in culture, and rarely immortalize spontaneously. Therefore, we recently have generated five immortal human prostate epithelial cell cultures derived from both the benign and malignant tissues of prostate cancer patients with telomerase, a gene that prevents cellular senescence. Examination of these cell lines for their morphologies and proliferative capacities, their abilities to grow in low serum, to respond to androgen stimulation, to grow above the agar layer, to form tumors in SCID mice, suggests that they may serve as valid, useful tools for the elucidation of early events in prostate tumorigenesis. Furthermore, the chromosome alterations observed in these immortalized cell lines expressing aspects of the malignant phenotypes imply that these cell lines accurately recapitulate the genetic composition of primary tumors. These novel in vitro models may offer unique models for the study of prostate carcinogenesis and also provide the means for testing both chemopreventive and chemotherapeutic agents

  1. Primary Cilia Negatively Regulate Melanogenesis in Melanocytes and Pigmentation in a Human Skin Model.

    Science.gov (United States)

    Choi, Hyunjung; Shin, Ji Hyun; Kim, Eun Sung; Park, So Jung; Bae, Il-Hong; Jo, Yoon Kyung; Jeong, In Young; Kim, Hyoung-June; Lee, Youngjin; Park, Hea Chul; Jeon, Hong Bae; Kim, Ki Woo; Lee, Tae Ryong; Cho, Dong-Hyung

    2016-01-01

    The primary cilium is an organelle protruding from the cell body that senses external stimuli including chemical, mechanical, light, osmotic, fluid flow, and gravitational signals. Skin is always exposed to the external environment and responds to external stimuli. Therefore, it is possible that primary cilia have an important role in skin. Ciliogenesis was reported to be involved in developmental processes in skin, such as keratinocyte differentiation and hair formation. However, the relation between skin pigmentation and primary cilia is largely unknown. Here, we observed that increased melanogenesis in melanocytes treated with a melanogenic inducer was inhibited by a ciliogenesis inducer, cytochalasin D, and serum-free culture. However, these inhibitory effects disappeared in GLI2 knockdown cells. In addition, activation of sonic hedgehog (SHH)-smoothened (Smo) signaling pathway by a Smo agonist, SAG inhibited melanin synthesis in melanocytes and pigmentation in a human skin model. On the contrary, an inhibitor of primary cilium formation, ciliobrevin A1, activated melanogenesis in melanocytes. These results suggest that skin pigmentation may be regulated partly by the induction of ciliogenesis through Smo-GLI2 signaling.

  2. Primary Cilia Negatively Regulate Melanogenesis in Melanocytes and Pigmentation in a Human Skin Model.

    Directory of Open Access Journals (Sweden)

    Hyunjung Choi

    Full Text Available The primary cilium is an organelle protruding from the cell body that senses external stimuli including chemical, mechanical, light, osmotic, fluid flow, and gravitational signals. Skin is always exposed to the external environment and responds to external stimuli. Therefore, it is possible that primary cilia have an important role in skin. Ciliogenesis was reported to be involved in developmental processes in skin, such as keratinocyte differentiation and hair formation. However, the relation between skin pigmentation and primary cilia is largely unknown. Here, we observed that increased melanogenesis in melanocytes treated with a melanogenic inducer was inhibited by a ciliogenesis inducer, cytochalasin D, and serum-free culture. However, these inhibitory effects disappeared in GLI2 knockdown cells. In addition, activation of sonic hedgehog (SHH-smoothened (Smo signaling pathway by a Smo agonist, SAG inhibited melanin synthesis in melanocytes and pigmentation in a human skin model. On the contrary, an inhibitor of primary cilium formation, ciliobrevin A1, activated melanogenesis in melanocytes. These results suggest that skin pigmentation may be regulated partly by the induction of ciliogenesis through Smo-GLI2 signaling.

  3. The pattern and time course of somatosensory changes in the human UVB sunburn model reveal the presence of peripheral and central sensitization.

    Science.gov (United States)

    Gustorff, Burkhard; Sycha, Thomas; Lieba-Samal, Doris; Rolke, Roman; Treede, Rolf-Detlef; Magerl, Walter

    2013-04-01

    The ultraviolet B (UVB) sunburn model was characterized with a comprehensive battery of quantitative sensory testing (QST). Primary hyperalgesia in UVB-irradiated skin and secondary hyperalgesia in adjacent nonirradiated skin were studied in 22 healthy subjects 24h after irradiation with UVB at 3-fold minimal erythema dose of a skin area 5 cm in diameter at the thigh and compared to mirror-image contralateral control areas. The time course of hyperalgesia over 96 h was studied in a subgroup of 12 subjects. Within the sunburn area, cold hyperesthesia (P=.01), profound generalized hyperalgesia to heat (Psunburn was surrounded by large areas of pinprick hyperalgesia (mean±SEM, 218±32 cm(2)) and a small rim of dynamic mechanical allodynia but no other sensory changes. Although of smaller magnitude, secondary hyperalgesia and dynamic mechanical allodynia adjacent to the UVB-irradiated area were statistically highly significant. Primary and secondary hyperalgesia developed in parallel within hours, peaked after 24-32 h, and lasted for more than 96 h. These data reveal that the UVB sunburn model activates a broad spectrum of peripheral and central sensitization mechanisms and hence is a useful human surrogate model to be used as a screening tool for target engagement in phases 1 and 2a of drug development. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  4. Prevalence and factors associated with breast milk donation in banks that receive human milk in primary health care units.

    Science.gov (United States)

    Meneses, Tatiana Mota Xavier de; Oliveira, Maria Inês Couto de; Boccolini, Cristiano Siqueira

    To estimate the prevalence and to analyze factors associated with breast milk donation at primary health care units in order to increase the human milk bank reserves. Cross-sectional study carried out in 2013 in Rio de Janeiro, Brazil. A representative sample of 695 mothers of children younger than 1 year attended to at the nine primary health care units with human milk donation services were interviewed. A hierarchical approach was used to obtain adjusted prevalence ratios (APR) by Poisson regression with robust variance. The final model included the variables associated with breast milk donation (p≤0.05). 7.3% of the mothers had donated breast milk. Having been encouraged to donate breast milk by healthcare professionals, relatives, or friends (APR=7.06), receiving information on breast milk expression by the primary health care unit (APR=3.65), and receiving help from the unit professionals to breastfeed (APR=2.24) were associated with a higher prevalence of donation. Admission of the newborn to the neonatal unit was associated with a lower prevalence of donation (APR=0.09). Encouragement to breast milk donation, and information and help provided by primary health care unit professionals to breastfeeding were shown to be important for the practice of human milk donation. Copyright © 2017. Published by Elsevier Editora Ltda.

  5. [The role of the cervical spine and the craniomandibular system in the pathogenesis of tinnitus. Somatosensory tinnitus].

    Science.gov (United States)

    Biesinger, E; Reisshauer, A; Mazurek, B

    2008-07-01

    The causes of tinnitus, vertigo, and hearing disturbances may be pathological processes in the cervical spine and temporomaxillary joint. In these cases, tinnitus is called somatosensory tinnitus (SST). For afferences of the cervical spine, projections of neuronal connections in the cochlear nucleus were found. A reflex-like impact of the cervical spine on the cochlear nucleus can be assumed. The tinnitus treatment concept of the Charité University Hospital in Berlin involves the cooperation of ENT specialists with many other disciplines in an outpatient clinic. A standardized examination protocol has been established, and physical therapy has been integrated into the interdisciplinary tinnitus treatment. For tinnitus-modulating therapy of muscular trigger points, local anesthetics as well as self-massage or treatment by a physiotherapist or osteopath are useful.

  6. c-Fos expression during temporal order judgment in mice.

    Directory of Open Access Journals (Sweden)

    Makoto Wada

    Full Text Available The neuronal mechanisms for ordering sensory signals in time still need to be clarified despite a long history of research. To address this issue, we recently developed a behavioral task of temporal order judgment in mice. In the present study, we examined the expression of c-Fos, a marker of neural activation, in mice just after they carried out the temporal order judgment task. The expression of c-Fos was examined in C57BL/6N mice (male, n = 5 that were trained to judge the order of two air-puff stimuli delivered bilaterally to the right and left whiskers with stimulation intervals of 50-750 ms. The mice were rewarded with a food pellet when they responded by orienting their head toward the first stimulus (n = 2 or toward the second stimulus (n = 3 after a visual "go" signal. c-Fos-stained cell densities of these mice (test group were compared with those of two control groups in coronal brain sections prepared at bregma -2, -1, 0, +1, and +2 mm by applying statistical parametric mapping to the c-Fos immuno-stained sections. The expression of c-Fos was significantly higher in the test group than in the other groups in the bilateral barrel fields of the primary somatosensory cortex, the left secondary somatosensory cortex, the dorsal part of the right secondary auditory cortex. Laminar analyses in the primary somatosensory cortex revealed that c-Fos expression in the test group was most evident in layers II and III, where callosal fibers project. The results suggest that temporal order judgment involves processing bilateral somatosensory signals through the supragranular layers of the primary sensory cortex and in the multimodal sensory areas, including marginal zone between the primary somatosensory cortex and the secondary sensory cortex.

  7. How Does Chronic Cigarette Smoke Exposure Affect Human Skin? A Global Proteomics Study in Primary Human Keratinocytes.

    Science.gov (United States)

    Rajagopalan, Pavithra; Nanjappa, Vishalakshi; Raja, Remya; Jain, Ankit P; Mangalaparthi, Kiran K; Sathe, Gajanan J; Babu, Niraj; Patel, Krishna; Cavusoglu, Nükhet; Soeur, Jeremie; Pandey, Akhilesh; Roy, Nita; Breton, Lionel; Chatterjee, Aditi; Misra, Namita; Gowda, Harsha

    2016-11-01

    Cigarette smoking has been associated with multiple negative effects on human skin. Long-term physiological effects of cigarette smoke are through chronic and not acute exposure. Molecular alterations due to chronic exposure to cigarette smoke remain unclear. Primary human skin keratinocytes chronically exposed to cigarette smoke condensate (CSC) showed a decreased wound-healing capacity with an increased expression of NRF2 and MMP9. Using quantitative proteomics, we identified 4728 proteins, of which 105 proteins were overexpressed (≥2-fold) and 41 proteins were downregulated (≤2-fold) in primary skin keratinocytes chronically exposed to CSC. We observed an alteration in the expression of several proteins involved in maintenance of epithelial barrier integrity, including keratin 80 (5.3 fold, p value 2.5 × 10 -7 ), cystatin A (3.6-fold, p value 3.2 × 10 -3 ), and periplakin (2.4-fold, p value 1.2 × 10 -8 ). Increased expression of proteins associated with skin hydration, including caspase 14 (2.2-fold, p value 4.7 × 10 -2 ) and filaggrin (3.6-fold, p value 5.4 × 10 -7 ), was also observed. In addition, we report differential expression of several proteins, including adipogenesis regulatory factor (2.5-fold, p value 1.3 × 10 -3 ) and histone H1.0 (2.5-fold, p value 6.3 × 10 -3 ) that have not been reported earlier. Bioinformatics analyses demonstrated that proteins differentially expressed in response to CSC are largely related to oxidative stress, maintenance of skin integrity, and anti-inflammatory responses. Importantly, treatment with vitamin E, a widely used antioxidant, could partially rescue adverse effects of CSC exposure in primary skin keratinocytes. The utility of antioxidant-based new dermatological formulations in delaying or preventing skin aging and oxidative damages caused by chronic cigarette smoke exposure warrants further clinical investigations and multi-omics research.

  8. Comparative Analysis of Human and Rodent Brain Primary Neuronal Culture Spontaneous Activity Using Micro-Electrode Array Technology.

    Science.gov (United States)

    Napoli, Alessandro; Obeid, Iyad

    2016-03-01

    Electrical activity in embryonic brain tissue has typically been studied using Micro Electrode Array (MEA) technology to make dozens of simultaneous recordings from dissociated neuronal cultures, brain stem cell progenitors, or brain slices from fetal rodents. Although these rodent neuronal primary culture electrical properties are mostly investigated, it has not been yet established to what extent the electrical characteristics of rodent brain neuronal cultures can be generalized to those of humans. A direct comparison of spontaneous spiking activity between rodent and human primary neurons grown under the same in vitro conditions using MEA technology has never been carried out before and will be described in the present study. Human and rodent dissociated fetal brain neuronal cultures were established in-vitro by culturing on a glass grid of 60 planar microelectrodes neurons under identical conditions. Three different cultures of human neurons were produced from tissue sourced from a single aborted fetus (at 16-18 gestational weeks) and these were compared with seven different cultures of embryonic rat neurons (at 18 gestational days) originally isolated from a single rat. The results show that the human and rodent cultures behaved significantly differently. Whereas the rodent cultures demonstrated robust spontaneous activation and network activity after only 10 days, the human cultures required nearly 40 days to achieve a substantially weaker level of electrical function. These results suggest that rat neuron preparations may yield inferences that do not necessarily transfer to humans. © 2015 Wiley Periodicals, Inc.

  9. The Antimicrobial Peptide Human Beta-Defensin-3 Is Induced by Platelet-Released Growth Factors in Primary Keratinocytes

    Directory of Open Access Journals (Sweden)

    Andreas Bayer

    2017-01-01

    Full Text Available Platelet-released growth factors (PRGF and its related clinically used formulations (e.g., Vivostat Platelet-Rich Fibrin (PRF® contain a variety of chemokines, cytokines, and growth factors and are therefore used to support healing of chronic, hard-to-heal, or infected wounds. Human beta-defensin-3 (hBD-3 is an antimicrobial peptide inducibly expressed in human keratinocytes especially upon wounding. The potent antimicrobial activity of hBD-3 together with its wound closure-promoting activities suggests that hBD-3 may play a crucial role in wound healing. Therefore, we analyzed the influence of PRGF on hBD-3 expression in human primary keratinocytes in vitro. In addition, we investigated the influence of Vivostat PRF on hBD-3 expression in artificially generated human skin wounds in vivo. PRGF treatment of primary keratinocytes induced a significant, concentration- and time-dependent increase in hBD-3 gene expression which was partially mediated by the epidermal growth factor receptor (EGFR. In line with these cell culture data, in vivo experiments revealed an enhanced hBD-3 expression in experimentally produced human wounds after the treatment with Vivostat PRF. Thus, the induction of hBD-3 may contribute to the beneficial effects of thrombocyte concentrate lysates in the treatment of chronic or infected wounds.

  10. The Antimicrobial Peptide Human Beta-Defensin-3 Is Induced by Platelet-Released Growth Factors in Primary Keratinocytes

    Science.gov (United States)

    Lammel, Justus; Tohidnezhad, Mersedeh; Lippross, Sebastian; Behrendt, Peter; Klüter, Tim; Pufe, Thomas; Cremer, Jochen; Jahr, Holger; Rademacher, Franziska; Gläser, Regine; Harder, Jürgen

    2017-01-01

    Platelet-released growth factors (PRGF) and its related clinically used formulations (e.g., Vivostat Platelet-Rich Fibrin (PRF®)) contain a variety of chemokines, cytokines, and growth factors and are therefore used to support healing of chronic, hard-to-heal, or infected wounds. Human beta-defensin-3 (hBD-3) is an antimicrobial peptide inducibly expressed in human keratinocytes especially upon wounding. The potent antimicrobial activity of hBD-3 together with its wound closure-promoting activities suggests that hBD-3 may play a crucial role in wound healing. Therefore, we analyzed the influence of PRGF on hBD-3 expression in human primary keratinocytes in vitro. In addition, we investigated the influence of Vivostat PRF on hBD-3 expression in artificially generated human skin wounds in vivo. PRGF treatment of primary keratinocytes induced a significant, concentration- and time-dependent increase in hBD-3 gene expression which was partially mediated by the epidermal growth factor receptor (EGFR). In line with these cell culture data, in vivo experiments revealed an enhanced hBD-3 expression in experimentally produced human wounds after the treatment with Vivostat PRF. Thus, the induction of hBD-3 may contribute to the beneficial effects of thrombocyte concentrate lysates in the treatment of chronic or infected wounds. PMID:28811680

  11. Rearrangement of a common cellular DNA domain on chromosome 4 in human primary liver tumors

    International Nuclear Information System (INIS)

    Pasquinelli, C.; Garreau, F.; Bougueleret, L.; Cariani, E.; Thiers, V.; Croissant, O.; Hadchouel, M.; Tiollais, P.; Brechot, C.; Grzeschik, K.H.

    1988-01-01

    Hepatitis B virus (HBV) DNA integration has been shown to occur frequently in human hepatocellular carcinomas. The authors have investigated whether common cellular DNA domains might be rearranged, possibly by HBV integration, in human primary liver tumors. Unique cellular DNA sequences adjacent to an HBV integration site were isolated from a patient with hepatitis B surface antigen-positive hepatocellular carcinoma. These probes detected rearrangement of this cellular region of chromosomal DNA in 3 of 50 additional primary liver tumors studied. Of these three tumor samples, two contained HBV DNA, without an apparent link between the viral DNA and the rearranged allele; HBV DNA sequences were not detected in the third tumor sample. By use of a panel of somatic cell hybrids, these unique cellular DNA sequences were shown to be located on chromosome 4. Therefore, this region of chromosomal DNA might be implicated in the formation of different tumors at one step of liver cell transformation, possible related to HBV integration

  12. Neuroprotective effects of rosmarinic acid on ciguatoxin in primary human neurons.

    Science.gov (United States)

    Braidy, N; Matin, A; Rossi, F; Chinain, M; Laurent, D; Guillemin, G J

    2014-02-01

    Ciguatoxin (CTX), is a toxic compound produced by microalgae (dinoflagellate) Gambierdiscus spp., and is bio-accumulated and bio-transformed through the marine food chain causing neurological deficits. To determine the mechanism of CTX-mediated cytotoxicity in human neurons, we measured extracellular lactate dehydrogenase (LDH) activity, intracellular levels of nicotinamide adenine dinucleotide (NAD(+)) and H2AX phosphorylation at serine 139 as a measure for DNA damage in primary cultures of human neurons treated with Pacific (P)-CTX-1B and P-CTX-3C. We found these marine toxins can induce a time and dose-dependent increase in extracellular LDH activity, with a concomitant decline in intracellular NAD(+) levels and increased DNA damage at the concentration range of 5-200 nM. We also showed that pre- and post-treatment with rosmarinic acid (RA), the active constituent of the Heliotropium foertherianum (Boraginaceae) can attenuate CTX-mediated neurotoxicity. These results further highlight the potential of RA in the treatment of CTX-induced neurological deficits.

  13. Predictivity of dog co-culture model, primary human hepatocytes and HepG2 cells for the detection of hepatotoxic drugs in humans

    International Nuclear Information System (INIS)

    Atienzar, Franck A.; Novik, Eric I.; Gerets, Helga H.; Parekh, Amit; Delatour, Claude; Cardenas, Alvaro; MacDonald, James; Yarmush, Martin L.; Dhalluin, Stéphane

    2014-01-01

    Drug Induced Liver Injury (DILI) is a major cause of attrition during early and late stage drug development. Consequently, there is a need to develop better in vitro primary hepatocyte models from different species for predicting hepatotoxicity in both animals and humans early in drug development. Dog is often chosen as the non-rodent species for toxicology studies. Unfortunately, dog in vitro models allowing long term cultures are not available. The objective of the present manuscript is to describe the development of a co-culture dog model for predicting hepatotoxic drugs in humans and to compare the predictivity of the canine model along with primary human hepatocytes and HepG2 cells. After rigorous optimization, the dog co-culture model displayed metabolic capacities that were maintained up to 2 weeks which indicates that such model could be also used for long term metabolism studies. Most of the human hepatotoxic drugs were detected with a sensitivity of approximately 80% (n = 40) for the three cellular models. Nevertheless, the specificity was low approximately 40% for the HepG2 cells and hepatocytes compared to 72.7% for the canine model (n = 11). Furthermore, the dog co-culture model showed a higher superiority for the classification of 5 pairs of close structural analogs with different DILI concerns in comparison to both human cellular models. Finally, the reproducibility of the canine system was also satisfactory with a coefficient of correlation of 75.2% (n = 14). Overall, the present manuscript indicates that the dog co-culture model may represent a relevant tool to perform chronic hepatotoxicity and metabolism studies. - Highlights: • Importance of species differences in drug development. • Relevance of dog co-culture model for metabolism and toxicology studies. • Hepatotoxicity: higher predictivity of dog co-culture vs HepG2 and human hepatocytes

  14. Predictivity of dog co-culture model, primary human hepatocytes and HepG2 cells for the detection of hepatotoxic drugs in humans

    Energy Technology Data Exchange (ETDEWEB)

    Atienzar, Franck A., E-mail: franck.atienzar@ucb.com [UCB Pharma SA, Non-Clinical Development, Chemin du Foriest, 1420 Braine-l' Alleud (Belgium); Novik, Eric I. [H mu rel Corporation, 675 U.S. Highway 1, North Brunswick, NJ 08902 (United States); Gerets, Helga H. [UCB Pharma SA, Non-Clinical Development, Chemin du Foriest, 1420 Braine-l' Alleud (Belgium); Parekh, Amit [H mu rel Corporation, 675 U.S. Highway 1, North Brunswick, NJ 08902 (United States); Delatour, Claude; Cardenas, Alvaro [UCB Pharma SA, Non-Clinical Development, Chemin du Foriest, 1420 Braine-l' Alleud (Belgium); MacDonald, James [Chrysalis Pharma Consulting, LLC, 385 Route 24, Suite 1G, Chester, NJ 07930 (United States); Yarmush, Martin L. [Department of Biomedical Engineering, Rutgers University, Piscataway, NJ 08854 (United States); Dhalluin, Stéphane [UCB Pharma SA, Non-Clinical Development, Chemin du Foriest, 1420 Braine-l' Alleud (Belgium)

    2014-02-15

    Drug Induced Liver Injury (DILI) is a major cause of attrition during early and late stage drug development. Consequently, there is a need to develop better in vitro primary hepatocyte models from different species for predicting hepatotoxicity in both animals and humans early in drug development. Dog is often chosen as the non-rodent species for toxicology studies. Unfortunately, dog in vitro models allowing long term cultures are not available. The objective of the present manuscript is to describe the development of a co-culture dog model for predicting hepatotoxic drugs in humans and to compare the predictivity of the canine model along with primary human hepatocytes and HepG2 cells. After rigorous optimization, the dog co-culture model displayed metabolic capacities that were maintained up to 2 weeks which indicates that such model could be also used for long term metabolism studies. Most of the human hepatotoxic drugs were detected with a sensitivity of approximately 80% (n = 40) for the three cellular models. Nevertheless, the specificity was low approximately 40% for the HepG2 cells and hepatocytes compared to 72.7% for the canine model (n = 11). Furthermore, the dog co-culture model showed a higher superiority for the classification of 5 pairs of close structural analogs with different DILI concerns in comparison to both human cellular models. Finally, the reproducibility of the canine system was also satisfactory with a coefficient of correlation of 75.2% (n = 14). Overall, the present manuscript indicates that the dog co-culture model may represent a relevant tool to perform chronic hepatotoxicity and metabolism studies. - Highlights: • Importance of species differences in drug development. • Relevance of dog co-culture model for metabolism and toxicology studies. • Hepatotoxicity: higher predictivity of dog co-culture vs HepG2 and human hepatocytes.

  15. Human herpesvirus 6A induces apoptosis of primary human fetal astrocytes via both caspase-dependent and -independent pathways

    Directory of Open Access Journals (Sweden)

    Gu Bin

    2011-12-01

    Full Text Available Abstract Background Human herpesvirus 6 (HHV-6 is a T-lymphtropic and neurotropic virus that can infect various types of cells. Sequential studies reported that apoptosis of glia and neurons induced by HHV-6 might act a potential trigger for some central nervous system (CNS diseases. HHV-6 is involved in the pathogenesis of encephalitis, multiple sclerosis (MS and fatigue syndrome. However, the mechanisms responsible for the apoptosis of infected CNS cells induced by HHV-6 are poorly understood. In this study, we investigated the cell death processes of primary human fetal astrocytes (PHFAs during productive HHV-6A infection and the underlying mechanisms. Results HHV-6A can cause productive infection in primary human fetal astrocytes. Annexin V-PI staining and electron microscopic analysis indicated that HHV-6A was an inducer of apoptosis. The cell death was associated with activation of caspase-3 and cleavage of poly (ADP-ribose polymerase (PARP, which is known to be an important substrate for activated caspase-3. Caspase-8 and -9 were also significantly activated in HHV-6A-infected cells. Moreover, HHV-6A infection led to Bax up-regulation and Bcl-2 down-regulation. HHV-6A infection increased the release of Smac/Diablo, AIF and cytochrome c from mitochondria to cytosol, which induced apoptosis via the caspase-dependent and -independent pathways. In addition, we also found that anti-apoptotic factors such as IAPs and NF-κB decreased in HHV-6A infected PHFAs. Conclusion This is the first demonstration of caspase-dependent and -independent apoptosis in HHV-6A-infected glial cells. These findings would be helpful in understanding the mechanisms of CNS diseases caused by HHV-6.

  16. Rhythm generation through period concatenation in rat somatosensory cortex.

    Directory of Open Access Journals (Sweden)

    Mark A Kramer

    2008-09-01

    Full Text Available Rhythmic voltage oscillations resulting from the summed activity of neuronal populations occur in many nervous systems. Contemporary observations suggest that coexistent oscillations interact and, in time, may switch in dominance. We recently reported an example of these interactions recorded from in vitro preparations of rat somatosensory cortex. We found that following an initial interval of coexistent gamma ( approximately 25 ms period and beta2 ( approximately 40 ms period rhythms in the superficial and deep cortical layers, respectively, a transition to a synchronous beta1 ( approximately 65 ms period rhythm in all cortical layers occurred. We proposed that the switch to beta1 activity resulted from the novel mechanism of period concatenation of the faster rhythms: gamma period (25 ms+beta2 period (40 ms = beta1 period (65 ms. In this article, we investigate in greater detail the fundamental mechanisms of the beta1 rhythm. To do so we describe additional in vitro experiments that constrain a biologically realistic, yet simplified, computational model of the activity. We use the model to suggest that the dynamic building blocks (or motifs of the gamma and beta2 rhythms combine to produce a beta1 oscillation that exhibits cross-frequency interactions. Through the combined approach of in vitro experiments and mathematical modeling we isolate the specific components that promote or destroy each rhythm. We propose that mechanisms vital to establishing the beta1 oscillation include strengthened connections between a population of deep layer intrinsically bursting cells and a transition from antidromic to orthodromic spike generation in these cells. We conclude that neural activity in the superficial and deep cortical layers may temporally combine to generate a slower oscillation.

  17. Data on gene and protein expression changes induced by apabetalone (RVX-208 in ex vivo treated human whole blood and primary hepatocytes

    Directory of Open Access Journals (Sweden)

    Sylwia Wasiak

    2016-09-01

    Full Text Available Apabetalone (RVX-208 inhibits the interaction between epigenetic regulators known as bromodomain and extraterminal (BET proteins and acetyl-lysine marks on histone tails. Data presented here supports the manuscript published in Atherosclerosis “RVX-208, a BET-inhibitor for Treating Atherosclerotic Cardiovascular Disease, Raises ApoA-I/HDL and Represses Pathways that Contribute to Cardiovascular Disease” (Gilham et al., 2016 [1]. It shows that RVX-208 and a comparator BET inhibitor (BETi JQ1 increase mRNA expression and production of apolipoprotein A-I (ApoA-I, the main protein component of high density lipoproteins, in primary human and African green monkey hepatocytes. In addition, reported here are gene expression changes from a microarray-based analysis of human whole blood and of primary human hepatocytes treated with RVX-208. Keywords: Bromodomain, BET proteins, BET inhibitor, RVX-208, JQ1, Vascular inflammation, ApoA-I, Apolipoprotein A-I, African green monkey, Primary human hepatocytes, Gene expression, Microarrays

  18. Mutation induction in γ-irradiated primary human bronchial epithelial cells and molecular analysis of the HPRT- mutants

    International Nuclear Information System (INIS)

    Suzuki, Keiji; Hei, Tom K.

    1996-01-01

    We have examined various radiobiological parameters using commercially-available primary normal human bronchial epithelial (NHBE) cells, which can be subcultured more than 20 population doublings, and have established the mutation system in order to characterize the molecular changes in γ-irradiated primary cells. The survival curve, obtained after irradiation of cells with 137 Cs γ-rays, indicates that the D 0 , D q , and n values are 1.34 Gy, 1.12 Gy, and 2.3, respectively. The induction of HPRT - mutation was dose-dependent and the mutant fraction increased in a non-linear fashion. Since the doubling number of NHBE cells is limited, DNA was extracted directly from the single mutant colonies and alteration in the HPRT gene locus was analyzed using multiplex PCR technique. Among spontaneous mutants, the proportion with total and partial deletions of the gene was 10.0% (2/20) and 60.0% (12/20), respectively, while 30.0% (6/20) did not have any detectable changes in the nine exons examined. On the other hand, the fraction of total deletion increased by more than 2-fold among mutants induced by γ-rays in that 26.3% (10/38) of them showed the total gene deletions. Twenty-five out of 38 γ-induced mutants (65.8%) had partial deletions and 3 mutants (7.9%) had no detectable alteration. The present results showed that γ-irradiation efficiently induced HPRT gene mutation in primary human epithelial cells and that most of the induced mutants suffered larger deletions compared to that observed in spontaneous mutants. This system provides a useful tool for determination of mutagenicity and understanding the molecular mechanisms of environmental carcinogens in primary human bronchial cells

  19. Prevalence and factors associated with breast milk donation in banks that receive human milk in primary health care units,

    Directory of Open Access Journals (Sweden)

    Tatiana Mota Xavier de Meneses

    Full Text Available Abstract Objective: To estimate the prevalence and to analyze factors associated with breast milk donation at primary health care units in order to increase the human milk bank reserves. Methods: Cross-sectional study carried out in 2013 in Rio de Janeiro, Brazil. A representative sample of 695 mothers of children younger than 1 year attended to at the nine primary health care units with human milk donation services were interviewed. A hierarchical approach was used to obtain adjusted prevalence ratios (APR by Poisson regression with robust variance. The final model included the variables associated with breast milk donation (p ≤ 0.05. Results: 7.3% of the mothers had donated breast milk. Having been encouraged to donate breast milk by healthcare professionals, relatives, or friends (APR = 7.06, receiving information on breast milk expression by the primary health care unit (APR = 3.65, and receiving help from the unit professionals to breastfeed (APR = 2.24 were associated with a higher prevalence of donation. Admission of the newborn to the neonatal unit was associated with a lower prevalence of donation (APR = 0.09. Conclusions: Encouragement to breast milk donation, and information and help provided by primary health care unit professionals to breastfeeding were shown to be important for the practice of human milk donation.

  20. Humans rather than climate the primary cause of Pleistocene megafaunal extinction in Australia

    Science.gov (United States)

    van der Kaars, Sander; Miller, Gifford H.; Turney, Chris S. M.; Cook, Ellyn J.; Nürnberg, Dirk; Schönfeld, Joachim; Kershaw, A. Peter; Lehman, Scott J.

    2017-01-01

    Environmental histories that span the last full glacial cycle and are representative of regional change in Australia are scarce, hampering assessment of environmental change preceding and concurrent with human dispersal on the continent ca. 47,000 years ago. Here we present a continuous 150,000-year record offshore south-western Australia and identify the timing of two critical late Pleistocene events: wide-scale ecosystem change and regional megafaunal population collapse. We establish that substantial changes in vegetation and fire regime occurred ∼70,000 years ago under a climate much drier than today. We record high levels of the dung fungus Sporormiella, a proxy for herbivore biomass, from 150,000 to 45,000 years ago, then a marked decline indicating megafaunal population collapse, from 45,000 to 43,100 years ago, placing the extinctions within 4,000 years of human dispersal across Australia. These findings rule out climate change, and implicate humans, as the primary extinction cause. PMID:28106043

  1. Dedifferentiation of Human Primary Thyrocytes into Multilineage Progenitor Cells without Gene Introduction

    Science.gov (United States)

    Saenko, Vladimir; Suzuki, Masatoshi; Matsuse, Michiko; Ohtsuru, Akira; Kumagai, Atsushi; Uga, Tatsuya; Yano, Hiroshi; Nagayama, Yuji; Yamashita, Shunichi

    2011-01-01

    While identification and isolation of adult stem cells have potentially important implications, recent reports regarding dedifferentiation/reprogramming from differentiated cells have provided another clue to gain insight into source of tissue stem/progenitor cells. In this study, we developed a novel culture system to obtain dedifferentiated progenitor cells from normal human thyroid tissues. After enzymatic digestion, primary thyrocytes, expressing thyroglobulin, vimentin and cytokeratin-18, were cultured in a serum-free medium called SAGM. Although the vast majority of cells died, a small proportion (∼0.5%) survived and proliferated. During initial cell expansion, thyroglobulin/cytokeratin-18 expression was gradually declined in the proliferating cells. Moreover, sorted cells expressing thyroid peroxidase gave rise to proliferating clones in SAGM. These data suggest that those cells are derived from thyroid follicular cells or at least thyroid-committed cells. The SAGM-grown cells did not express any thyroid-specific genes. However, after four-week incubation with FBS and TSH, cytokeratin-18, thyroglobulin, TSH receptor, PAX8 and TTF1 expressions re-emerged. Moreover, surprisingly, the cells were capable of differentiating into neuronal or adipogenic lineage depending on differentiating conditions. In summary, we have developed a novel system to generate multilineage progenitor cells from normal human thyroid tissues. This seems to be achieved by dedifferentiation of thyroid follicular cells. The presently described culture system may be useful for regenerative medicine, but the primary importance will be as a tool to elucidate the mechanisms of thyroid diseases. PMID:21556376

  2. Standardized 3D Bioprinting of Soft Tissue Models with Human Primary Cells.

    Science.gov (United States)

    Rimann, Markus; Bono, Epifania; Annaheim, Helene; Bleisch, Matthias; Graf-Hausner, Ursula

    2016-08-01

    Cells grown in 3D are more physiologically relevant than cells cultured in 2D. To use 3D models in substance testing and regenerative medicine, reproducibility and standardization are important. Bioprinting offers not only automated standardizable processes but also the production of complex tissue-like structures in an additive manner. We developed an all-in-one bioprinting solution to produce soft tissue models. The holistic approach included (1) a bioprinter in a sterile environment, (2) a light-induced bioink polymerization unit, (3) a user-friendly software, (4) the capability to print in standard labware for high-throughput screening, (5) cell-compatible inkjet-based printheads, (6) a cell-compatible ready-to-use BioInk, and (7) standard operating procedures. In a proof-of-concept study, skin as a reference soft tissue model was printed. To produce dermal equivalents, primary human dermal fibroblasts were printed in alternating layers with BioInk and cultured for up to 7 weeks. During long-term cultures, the models were remodeled and fully populated with viable and spreaded fibroblasts. Primary human dermal keratinocytes were seeded on top of dermal equivalents, and epidermis-like structures were formed as verified with hematoxylin and eosin staining and immunostaining. However, a fully stratified epidermis was not achieved. Nevertheless, this is one of the first reports of an integrative bioprinting strategy for industrial routine application. © 2015 Society for Laboratory Automation and Screening.

  3. TGF-β signaling is an effective target to impair survival and induce apoptosis of human cholangiocarcinoma cells: A study on human primary cell cultures.

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    Anna Maria Lustri

    Full Text Available Cholangiocarcinoma (CCA and its subtypes (mucin- and mixed-CCA arise from the neoplastic transformation of cholangiocytes, the epithelial cells lining the biliary tree. CCA has a high mortality rate owing to its aggressiveness, late diagnosis and high resistance to radiotherapy and chemotherapeutics. We have demonstrated that CCA is enriched for cancer stem cells which express epithelial to mesenchymal transition (EMT traits, with these features being associated with aggressiveness and drug resistance. TGF-β signaling is upregulated in CCA and involved in EMT. We have recently established primary cell cultures from human mucin- and mixed-intrahepatic CCA. In human CCA primary cultures with different levels of EMT trait expression, we evaluated the anticancer effects of: (i CX-4945, a casein kinase-2 (CK2 inhibitor that blocks TGF-β1-induced EMT; and (ii LY2157299, a TGF-β receptor I kinase inhibitor. We tested primary cell lines expressing EMT trait markers (vimentin, N-cadherin and nuclear catenin but negative for epithelial markers, and cell lines expressing epithelial markers (CK19-positive in association with EMT traits. Cell viability was evaluated by MTS assays, apoptosis by Annexin V FITC and cell migration by wound-healing assay.at a dose of 10 μM, CX4945 significantly decreased cell viability of primary human cell cultures from both mucin and mixed CCA, whereas in CK19-positive cell cultures, the effect of CX4945 on cell viability required higher concentrations (>30μM. At the same concentrations, CX4945 also induced apoptosis (3- fold increase vs controls which correlated with the expression level of CK2 in the different CCA cell lines (mucin- and mixed-CCA. Indeed, no apoptotic effects were observed in CK19-positive cells expressing lower CK2 levels. The effects of CX4945 on viability and apoptosis were associated with an increased number of γ-H2ax (biomarker for DNA double-strand breaks foci, suggesting the active role of CK2 as

  4. Brain regions with mirror properties: a meta-analysis of 125 human fMRI studies.

    Science.gov (United States)

    Molenberghs, Pascal; Cunnington, Ross; Mattingley, Jason B

    2012-01-01

    Mirror neurons in macaque area F5 fire when an animal performs an action, such as a mouth or limb movement, and also when the animal passively observes an identical or similar action performed by another individual. Brain-imaging studies in humans conducted over the last 20 years have repeatedly attempted to reveal analogous brain regions with mirror properties in humans, with broad and often speculative claims about their functional significance across a range of cognitive domains, from language to social cognition. Despite such concerted efforts, the likely neural substrates of these mirror regions have remained controversial, and indeed the very existence of a distinct subcategory of human neurons with mirroring properties has been questioned. Here we used activation likelihood estimation (ALE), to provide a quantitative index of the consistency of patterns of fMRI activity measured in human studies of action observation and action execution. From an initial sample of more than 300 published works, data from 125 papers met our strict inclusion and exclusion criteria. The analysis revealed 14 separate clusters in which activation has been consistently attributed to brain regions with mirror properties, encompassing 9 different Brodmann areas. These clusters were located in areas purported to show mirroring properties in the macaque, such as the inferior parietal lobule, inferior frontal gyrus and the adjacent ventral premotor cortex, but surprisingly also in regions such as the primary visual cortex, cerebellum and parts of the limbic system. Our findings suggest a core network of human brain regions that possess mirror properties associated with action observation and execution, with additional areas recruited during tasks that engage non-motor functions, such as auditory, somatosensory and affective components. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

  5. Emotional modulation of pain: is it the sensation or what we recall?

    Science.gov (United States)

    Godinho, Fabio; Magnin, Michel; Frot, Maud; Perchet, Caroline; Garcia-Larrea, Luis

    2006-11-01

    Emotions modulate pain perception, although the mechanisms underlying this phenomenon remain unclear. In this study, we show that intensity reports significantly increased when painful stimuli were concomitant to images showing human pain, whereas pictures with identical emotional values but without somatic content failed to modulate pain. Early somatosensory responses (emotions. Conversely, late responses showed a significant enhancement associated with increased pain ratings, localized to the right prefrontal, right temporo-occipital junction, and right temporal pole. In contrast to selective attention, which enhances pain ratings by increasing sensory gain, emotions triggered by seeing other people's pain did not alter processing in SI-SII (primary and second somatosensory areas), but may have biased the transfer to, and the representation of pain in short-term memory buffers (prefrontal), as well as the affective assignment to this representation (temporal pole). Memory encoding and recall, rather than sensory processing, appear to be modulated by empathy with others' physical suffering.

  6. Development of Functional Microfold (M Cells from Intestinal Stem Cells in Primary Human Enteroids.

    Directory of Open Access Journals (Sweden)

    Joshua D Rouch

    Full Text Available Intestinal microfold (M cells are specialized epithelial cells that act as gatekeepers of luminal antigens in the intestinal tract. They play a critical role in the intestinal mucosal immune response through transport of viruses, bacteria and other particles and antigens across the epithelium to immune cells within Peyer's patch regions and other mucosal sites. Recent studies in mice have demonstrated that M cells are generated from Lgr5+ intestinal stem cells (ISCs, and that infection with Salmonella enterica serovar Typhimurium increases M cell formation. However, it is not known whether and how these findings apply to primary human small intestinal epithelium propagated in an in vitro setting.Human intestinal crypts were grown as monolayers with growth factors and treated with recombinant RANKL, and assessed for mRNA transcripts, immunofluorescence and uptake of microparticles and S. Typhimurium.Functional M cells were generated by short-term culture of freshly isolated human intestinal crypts in a dose- and time-dependent fashion. RANKL stimulation of the monolayer cultures caused dramatic induction of the M cell-specific markers, SPIB, and Glycoprotein-2 (GP2 in a process primed by canonical WNT signaling. Confocal microscopy demonstrated a pseudopod phenotype of GP2-positive M cells that preferentially take up microparticles. Furthermore, infection of the M cell-enriched cultures with the M cell-tropic enteric pathogen, S. Typhimurium, led to preferential association of the bacteria with M cells, particularly at lower inoculum sizes. Larger inocula caused rapid induction of M cells.Human intestinal crypts containing ISCs can be cultured and differentiate into an epithelial layer with functional M cells with characteristic morphological and functional properties. This study is the first to demonstrate that M cells can be induced to form from primary human intestinal epithelium, and that S. Typhimurium preferentially infect these cells in an

  7. Effectiveness of temporary deafferentation of the arm on somatosensory and motor functions following stroke: a systematic review.

    Science.gov (United States)

    Opsommer, Emmanuelle; Zwissig, Camille; Korogod, Natalya; Weiss, Thomas

    2016-12-01

    After stroke, regaining functional use of the upper limb can be challenging. Temporary deafferentation (TD) is a novel approach used in neurorehabilitation to voluntarily reduce the somatosensory input in a body part by temporary anesthesia; which has been shown to improve sensorimotor functions in the affected limb. The primary objective of this systematic review was to present the best available evidence related to the effects of TD of the affected arm on the recovery of motor function and activity of the upper limb (arm and hand) following stroke. Further, this review aimed to assess the effects of TD on sensory function, activities of daily living (ADL) and quality of life following stroke, the acceptability and safety of the intervention as well as adverse events. Adult patients (18 years and older) with a clinical diagnosis of stroke, either hemorrhagic or ischemic. Reports of rehabilitation that included the use of a pneumatic tourniquet, regional anesthesia or nerve block to achieve TD of an arm, or the use of TD as a stand-alone intervention. Primary outcomes were motor function and activity of the upper limb using assessment scales, motor tests and global motor functions.Secondary outcomes included measures of sensory function, ADL, impact of stroke and quality of life and pain.Additional outcomes were neurophysiological changes as studied with functional magnetic resonance imaging, magnetoencephalography and/or transcranial magnetic stimulation.Acceptability and safety of the intervention as well as adverse events were also included. We included any experimental and epidemiological studies. There were no randomized controlled trials. We included non-randomized controlled trials, quasi-experimental, before and after studies and case-control studies. We searched for both published and unpublished studies in major databases and all reference lists of relevant articles in English, German or French languages. We included studies published from January 1980 to

  8. Dipolar sources of the early scalp somatosensory evoked potentials to upper limb stimulation. Effect of increasing stimulus rates.

    Science.gov (United States)

    Valeriani, M; Restuccia, D; Di Lazzaro, V; Le Pera, D; Barba, C; Tonali, P; Mauguiere, F

    1998-06-01

    Brain electrical source analysis (BESA) of the scalp electroencephalographic activity is well adapted to distinguish neighbouring cerebral generators precisely. Therefore, we performed dipolar source modelling in scalp medium nerve somatosensory evoked potentials (SEPs) recorded at 1.5-Hz stimulation rate, where all the early components should be identifiable. We built a four-dipole model, which was issued from the grand average, and applied it also to recordings from single individuals. Our model included a dipole at the base of the skull and three other perirolandic dipoles. The first of the latter dipoles was tangentially oriented and was active at the same latencies as the N20/P20 potential and, with opposite polarity, the P24/N24 response. The second perirolandic dipole showed an initial peak of activity slightly earlier than that of the N20/P20 dipolar source and, later, it was active at the same latency as the central P22 potential. Lastly, the third perirolandic dipole explaining the fronto-central N30 potential scalp distribution was constantly more posterior than the first one. In order to evaluate the effect of an increasing repetition frequency on the activity of SEP dipolar sources, we applied the model built from 1.5-Hz SEPs to traces recorded at 3-Hz and 10-Hz repetition rates. We found that the 10-Hz stimulus frequency reduced selectively the later of the two activity phases of the first perirolandic dipole. The decrement in strength of this dipolar source can be explained if we assume that: (a) the later activity of the first perirolandic dipole can represent the inhibitory phase of a "primary response"; (b) two different clusters of cells generate the opposite activities of the tangential perirolandic dipole. An additional finding in our model was that two different perirolandic dipoles contribute to the centro-parietal N20 potential generation.

  9. The gap in human resources to deliver the guaranteed package of prevention and health promotion services at urban and rural primary care facilities in Mexico.

    Science.gov (United States)

    Alcalde-Rabanal, Jacqueline Elizabeth; Nigenda, Gustavo; Bärnighausen, Till; Velasco-Mondragón, Héctor Eduardo; Darney, Blair Grant

    2017-08-03

    The purpose of this study was to estimate the gap between the available and the ideal supply of human resources (physicians, nurses, and health promoters) to deliver the guaranteed package of prevention and health promotion services at urban and rural primary care facilities in Mexico. We conducted a cross-sectional observational study using a convenience sample. We selected 20 primary health facilities in urban and rural areas in 10 states of Mexico. We calculated the available and the ideal supply of human resources in these facilities using estimates of time available, used, and required to deliver health prevention and promotion services. We performed descriptive statistics and bivariate hypothesis testing using Wilcoxon and Friedman tests. Finally, we conducted a sensitivity analysis to test whether the non-normal distribution of our time variables biased estimation of available and ideal supply of human resources. The comparison between available and ideal supply for urban and rural primary health care facilities reveals a low supply of physicians. On average, primary health care facilities are lacking five physicians when they were estimated with time used and nine if they were estimated with time required (P human resources in primary health facilities.

  10. Vestibular and Somatosensory Covergence in Postural Equilibrium Control: Insights from Spaceflight and Bed Rest Studies

    Science.gov (United States)

    Mulavara, A. P.; Batson, C. D.; Buxton, R. E.; Feiveson, A. H.; Kofman, I. S.; Lee, S. M. C.; Miller, C. A.; Peters, B. T.; Phillips, T.; Platts, S. H.; hide

    2014-01-01

    The goal of the Functional Task Test study is to determine the effects of space flight on functional tests that are representative of high priority exploration mission tasks and to identify the key underlying physiological factors that contribute to decrements in performance. We are currently conducting studies on both International Space Station (ISS) astronauts experiencing up to 6 months of microgravity and subjects experiencing 70 days of 6??head-down bed-rest as an analog for space flight. Bed-rest provides the opportunity for us to investigate the role of prolonged axial body unloading in isolation from the other physiological effects produced by exposure to the microgravity environment of space flight. This allows us to parse out the contribution of the body unloading somatosensory component on functional performance. Both ISS crewmembers and bed-rest subjects were tested using a protocol that evaluated functional performance along with tests of postural and locomotor control before and after space flight and bed-rest, respectively. Functional tests included ladder climbing, hatch opening, jump down, manual manipulation of objects and tool use, seat egress and obstacle avoidance, recovery from a fall, and object translation tasks. Astronauts were tested three times before flight, and on 1, 6, and 30 days after landing. Bed-rest subjects were tested three times before bed-rest and immediately after getting up from bed-rest as well as 1, 6, and 12 days after re-ambulation. A comparison of bed-rest and space flight data showed a significant concordance in performance changes across all functional tests. Tasks requiring a greater demand for dynamic control of postural equilibrium (i.e. fall recovery, seat egress/obstacle avoidance during walking, object translation, jump down) showed the greatest decrement in performance. Functional tests with reduced requirements for postural stability showed less reduction in performance. Results indicate that body unloading

  11. Sequential immunization with V3 peptides from primary human immunodeficiency virus type 1 produces cross-neutralizing antibodies against primary isolates with a matching narrow-neutralization sequence motif.

    Science.gov (United States)

    Eda, Yasuyuki; Takizawa, Mari; Murakami, Toshio; Maeda, Hiroaki; Kimachi, Kazuhiko; Yonemura, Hiroshi; Koyanagi, Satoshi; Shiosaki, Kouichi; Higuchi, Hirofumi; Makizumi, Keiichi; Nakashima, Toshihiro; Osatomi, Kiyoshi; Tokiyoshi, Sachio; Matsushita, Shuzo; Yamamoto, Naoki; Honda, Mitsuo

    2006-06-01

    An antibody response capable of neutralizing not only homologous but also heterologous forms of the CXCR4-tropic human immunodeficiency virus type 1 (HIV-1) MNp and CCR5-tropic primary isolate HIV-1 JR-CSF was achieved through sequential immunization with a combination of synthetic peptides representing HIV-1 Env V3 sequences from field and laboratory HIV-1 clade B isolates. In contrast, repeated immunization with a single V3 peptide generated antibodies that neutralized only type-specific laboratory-adapted homologous viruses. To determine whether the cross-neutralization response could be attributed to a cross-reactive antibody in the immunized animals, we isolated a monoclonal antibody, C25, which neutralized the heterologous primary viruses of HIV-1 clade B. Furthermore, we generated a humanized monoclonal antibody, KD-247, by transferring the genes of the complementary determining region of C25 into genes of the human V region of the antibody. KD-247 bound with high affinity to the "PGR" motif within the HIV-1 Env V3 tip region, and, among the established reference antibodies, it most effectively neutralized primary HIV-1 field isolates possessing the matching neutralization sequence motif, suggesting its promise for clinical applications involving passive immunizations. These results demonstrate that sequential immunization with B-cell epitope peptides may contribute to a humoral immune-based HIV vaccine strategy. Indeed, they help lay the groundwork for the development of HIV-1 vaccine strategies that use sequential immunization with biologically relevant peptides to overcome difficulties associated with otherwise poorly immunogenic epitopes.

  12. Dopamine Receptor Activation Increases HIV Entry into Primary Human Macrophages

    Science.gov (United States)

    Gaskill, Peter J.; Yano, Hideaki H.; Kalpana, Ganjam V.; Javitch, Jonathan A.; Berman, Joan W.

    2014-01-01

    Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers. PMID:25268786

  13. UVA and UVB Irradiation Differentially Regulate microRNA Expression in Human Primary Keratinocytes

    Science.gov (United States)

    Kraemer, Anne; Chen, I-Peng; Henning, Stefan; Faust, Alexandra; Volkmer, Beate; Atkinson, Michael J.; Moertl, Simone; Greinert, Ruediger

    2013-01-01

    MicroRNA (miRNA)-mediated regulation of the cellular transcriptome is an important epigenetic mechanism for fine-tuning regulatory pathways. These include processes related to skin cancer development, progression and metastasis. However, little is known about the role of microRNA as an intermediary in the carcinogenic processes following exposure to UV-radiation. We now show that UV irradiation of human primary keratinocytes modulates the expression of several cellular miRNAs. A common set of miRNAs was influenced by exposure to both UVA and UVB. However, each wavelength band also activated a distinct subset of miRNAs. Common sets of UVA- and UVB-regulated miRNAs harbor the regulatory elements GLYCA-nTRE, GATA-1-undefined-site-13 or Hox-2.3-undefined-site-2 in their promoters. In silico analysis indicates that the differentially expressed miRNAs responding to UV have potential functions in the cellular pathways of cell growth and proliferation. Interestingly, the expression of miR-23b, which is a differentiation marker of human keratinocytes, is remarkably up-regulated after UVA irradiation. Studying the interaction between miR-23b and its putative skin-relevant targets using a Luciferase reporter assay revealed that RRAS2 (related RAS viral oncogene homolog 2), which is strongly expressed in highly aggressive malignant skin cancer, to be a direct target of miR-23b. This study demonstrates for the first time a differential miRNA response to UVA and UVB in human primary keratinocytes. This suggests that selective regulation of signaling pathways occurs in response to different UV energies. This may shed new light on miRNA-regulated carcinogenic processes involved in UV-induced skin carcinogenesis. PMID:24391759

  14. UVA and UVB irradiation differentially regulate microRNA expression in human primary keratinocytes.

    Directory of Open Access Journals (Sweden)

    Anne Kraemer

    Full Text Available MicroRNA (miRNA-mediated regulation of the cellular transcriptome is an important epigenetic mechanism for fine-tuning regulatory pathways. These include processes related to skin cancer development, progression and metastasis. However, little is known about the role of microRNA as an intermediary in the carcinogenic processes following exposure to UV-radiation. We now show that UV irradiation of human primary keratinocytes modulates the expression of several cellular miRNAs. A common set of miRNAs was influenced by exposure to both UVA and UVB. However, each wavelength band also activated a distinct subset of miRNAs. Common sets of UVA- and UVB-regulated miRNAs harbor the regulatory elements GLYCA-nTRE, GATA-1-undefined-site-13 or Hox-2.3-undefined-site-2 in their promoters. In silico analysis indicates that the differentially expressed miRNAs responding to UV have potential functions in the cellular pathways of cell growth and proliferation. Interestingly, the expression of miR-23b, which is a differentiation marker of human keratinocytes, is remarkably up-regulated after UVA irradiation. Studying the interaction between miR-23b and its putative skin-relevant targets using a Luciferase reporter assay revealed that RRAS2 (related RAS viral oncogene homolog 2, which is strongly expressed in highly aggressive malignant skin cancer, to be a direct target of miR-23b. This study demonstrates for the first time a differential miRNA response to UVA and UVB in human primary keratinocytes. This suggests that selective regulation of signaling pathways occurs in response to different UV energies. This may shed new light on miRNA-regulated carcinogenic processes involved in UV-induced skin carcinogenesis.

  15. Automatic analysis of the micronucleus test in primary human lymphocytes using image analysis.

    Science.gov (United States)

    Frieauff, W; Martus, H J; Suter, W; Elhajouji, A

    2013-01-01

    The in vitro micronucleus test (MNT) is a well-established test for early screening of new chemical entities in industrial toxicology. For assessing the clastogenic or aneugenic potential of a test compound, micronucleus induction in cells has been shown repeatedly to be a sensitive and a specific parameter. Various automated systems to replace the tedious and time-consuming visual slide analysis procedure as well as flow cytometric approaches have been discussed. The ROBIAS (Robotic Image Analysis System) for both automatic cytotoxicity assessment and micronucleus detection in human lymphocytes was developed at Novartis where the assay has been used to validate positive results obtained in the MNT in TK6 cells, which serves as the primary screening system for genotoxicity profiling in early drug development. In addition, the in vitro MNT has become an accepted alternative to support clinical studies and will be used for regulatory purposes as well. The comparison of visual with automatic analysis results showed a high degree of concordance for 25 independent experiments conducted for the profiling of 12 compounds. For concentration series of cyclophosphamide and carbendazim, a very good correlation between automatic and visual analysis by two examiners could be established, both for the relative division index used as cytotoxicity parameter, as well as for micronuclei scoring in mono- and binucleated cells. Generally, false-positive micronucleus decisions could be controlled by fast and simple relocation of the automatically detected patterns. The possibility to analyse 24 slides within 65h by automatic analysis over the weekend and the high reproducibility of the results make automatic image processing a powerful tool for the micronucleus analysis in primary human lymphocytes. The automated slide analysis for the MNT in human lymphocytes complements the portfolio of image analysis applications on ROBIAS which is supporting various assays at Novartis.

  16. Brain Regions Associated to a Kinesthetic Illusion Evoked by Watching a Video of One's Own Moving Hand.

    Science.gov (United States)

    Kaneko, Fuminari; Blanchard, Caroline; Lebar, Nicolas; Nazarian, Bruno; Kavounoudias, Anne; Romaiguère, Patricia

    2015-01-01

    It is well known that kinesthetic illusions can be induced by stimulation of several sensory systems (proprioception, touch, vision…). In this study we investigated the cerebral network underlying a kinesthetic illusion induced by visual stimulation by using functional magnetic resonance imaging (fMRI) in humans. Participants were instructed to keep their hand still while watching the video of their own moving hand (Self Hand) or that of someone else's moving hand (Other Hand). In the Self Hand condition they experienced an illusory sensation that their hand was moving whereas the Other Hand condition did not induce any kinesthetic illusion. The contrast between the Self Hand and Other Hand conditions showed significant activation in the left dorsal and ventral premotor cortices, in the left Superior and Inferior Parietal lobules, at the right Occipito-Temporal junction as well as in bilateral Insula and Putamen. Most strikingly, there was no activation in the primary motor and somatosensory cortices, whilst previous studies have reported significant activation in these regions for vibration-induced kinesthetic illusions. To our knowledge, this is the first study that indicates that humans can experience kinesthetic perception without activation in the primary motor and somatosensory areas. We conclude that under some conditions watching a video of one's own moving hand could lead to activation of a network that is usually involved in processing copies of efference, thus leading to the illusory perception that the real hand is indeed moving.

  17. Brain Regions Associated to a Kinesthetic Illusion Evoked by Watching a Video of One's Own Moving Hand.

    Directory of Open Access Journals (Sweden)

    Fuminari Kaneko

    Full Text Available It is well known that kinesthetic illusions can be induced by stimulation of several sensory systems (proprioception, touch, vision…. In this study we investigated the cerebral network underlying a kinesthetic illusion induced by visual stimulation by using functional magnetic resonance imaging (fMRI in humans. Participants were instructed to keep their hand still while watching the video of their own moving hand (Self Hand or that of someone else's moving hand (Other Hand. In the Self Hand condition they experienced an illusory sensation that their hand was moving whereas the Other Hand condition did not induce any kinesthetic illusion. The contrast between the Self Hand and Other Hand conditions showed significant activation in the left dorsal and ventral premotor cortices, in the left Superior and Inferior Parietal lobules, at the right Occipito-Temporal junction as well as in bilateral Insula and Putamen. Most strikingly, there was no activation in the primary motor and somatosensory cortices, whilst previous studies have reported significant activation in these regions for vibration-induced kinesthetic illusions. To our knowledge, this is the first study that indicates that humans can experience kinesthetic perception without activation in the primary motor and somatosensory areas. We conclude that under some conditions watching a video of one's own moving hand could lead to activation of a network that is usually involved in processing copies of efference, thus leading to the illusory perception that the real hand is indeed moving.

  18. Mitochondrial protein adducts formation and mitochondrial dysfunction during N-acetyl-m-aminophenol (AMAP)-induced hepatotoxicity in primary human hepatocytes

    International Nuclear Information System (INIS)

    Xie, Yuchao; McGill, Mitchell R.; Du, Kuo; Dorko, Kenneth; Kumer, Sean C.; Schmitt, Timothy M.; Ding, Wen-Xing; Jaeschke, Hartmut

    2015-01-01

    3′-Hydroxyacetanilide or N-acetyl-meta-aminophenol (AMAP) is generally regarded as a non-hepatotoxic analog of acetaminophen (APAP). Previous studies demonstrated the absence of toxicity after AMAP in mice, hamsters, primary mouse hepatocytes and several cell lines. In contrast, experiments with liver slices suggested that it may be toxic to human hepatocytes; however, the mechanism of toxicity is unclear. To explore this, we treated primary human hepatocytes (PHH) with AMAP or APAP for up to 48 h and measured several parameters to assess metabolism and injury. Although less toxic than APAP, AMAP dose-dependently triggered cell death in PHH as indicated by alanine aminotransferase (ALT) release and propidium iodide (PI) staining. Similar to APAP, AMAP also significantly depleted glutathione (GSH) in PHH and caused mitochondrial damage as indicated by glutamate dehydrogenase (GDH) release and the JC-1 assay. However, unlike APAP, AMAP treatment did not cause relevant c-jun-N-terminal kinase (JNK) activation in the cytosol or phospho-JNK translocation to mitochondria. To compare, AMAP toxicity was assessed in primary mouse hepatocytes (PMH). No cytotoxicity was observed as indicated by the lack of lactate dehydrogenase release and no PI staining. Furthermore, there was no GSH depletion or mitochondrial dysfunction after AMAP treatment in PMH. Immunoblotting for arylated proteins suggested that AMAP treatment caused extensive mitochondrial protein adduct formation in PHH but not in PMH. In conclusion, AMAP is hepatotoxic in PHH and the mechanism involves the formation of mitochondrial protein adducts and mitochondrial dysfunction. - Highlights: • AMAP induces cell death in primary human hepatocytes (PHH). • AMAP does not cause cell death in primary mouse hepatocytes (PMH). • AMAP leads to mitochondria dysfunction in PHH but not PMH. • Protein adduct formation and dysfunction in mitochondria correlate with toxicity.

  19. Mitochondrial protein adducts formation and mitochondrial dysfunction during N-acetyl-m-aminophenol (AMAP)-induced hepatotoxicity in primary human hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Yuchao; McGill, Mitchell R.; Du, Kuo; Dorko, Kenneth [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Kumer, Sean C.; Schmitt, Timothy M. [Department of Surgery, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Ding, Wen-Xing [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160 (United States)

    2015-12-01

    3′-Hydroxyacetanilide or N-acetyl-meta-aminophenol (AMAP) is generally regarded as a non-hepatotoxic analog of acetaminophen (APAP). Previous studies demonstrated the absence of toxicity after AMAP in mice, hamsters, primary mouse hepatocytes and several cell lines. In contrast, experiments with liver slices suggested that it may be toxic to human hepatocytes; however, the mechanism of toxicity is unclear. To explore this, we treated primary human hepatocytes (PHH) with AMAP or APAP for up to 48 h and measured several parameters to assess metabolism and injury. Although less toxic than APAP, AMAP dose-dependently triggered cell death in PHH as indicated by alanine aminotransferase (ALT) release and propidium iodide (PI) staining. Similar to APAP, AMAP also significantly depleted glutathione (GSH) in PHH and caused mitochondrial damage as indicated by glutamate dehydrogenase (GDH) release and the JC-1 assay. However, unlike APAP, AMAP treatment did not cause relevant c-jun-N-terminal kinase (JNK) activation in the cytosol or phospho-JNK translocation to mitochondria. To compare, AMAP toxicity was assessed in primary mouse hepatocytes (PMH). No cytotoxicity was observed as indicated by the lack of lactate dehydrogenase release and no PI staining. Furthermore, there was no GSH depletion or mitochondrial dysfunction after AMAP treatment in PMH. Immunoblotting for arylated proteins suggested that AMAP treatment caused extensive mitochondrial protein adduct formation in PHH but not in PMH. In conclusion, AMAP is hepatotoxic in PHH and the mechanism involves the formation of mitochondrial protein adducts and mitochondrial dysfunction. - Highlights: • AMAP induces cell death in primary human hepatocytes (PHH). • AMAP does not cause cell death in primary mouse hepatocytes (PMH). • AMAP leads to mitochondria dysfunction in PHH but not PMH. • Protein adduct formation and dysfunction in mitochondria correlate with toxicity.

  20. Characteristics of human infant primary fibroblast cultures from Achilles tendons removed post-mortem

    DEFF Research Database (Denmark)

    Rohde, Marianne Cathrine; Corydon, Thomas Juhl; Hansen, Jakob

    2014-01-01

    Primary cell cultures were investigated as a tool for molecular diagnostics in a forensic setting. Fibroblast cultures had been established from human Achilles tendon resected at autopsies, from cases of sudden infant death syndrome and control infants who died in traumatic events (n=41). After...... established from post-mortem tissue are renewable sources of biological material; they can be the foundation for genetic, metabolic and other functional studies and thus constitute a valuable tool for molecular and pathophysiological investigations in biomedical and forensic sciences....

  1. Non-primary motor areas in the human frontal lobe are connected directly to hand muscles.

    Science.gov (United States)

    Teitti, S; Määttä, S; Säisänen, L; Könönen, M; Vanninen, R; Hannula, H; Mervaala, E; Karhu, J

    2008-04-15

    Structural studies in primates have shown that, in addition to the primary motor cortex (M1), premotor areas are a source of corticospinal tracts. The function of these putative corticospinal neuronal tracts in humans is still unclear. We found frontal non-primary motor areas (NPMAs), which react to targeted non-invasive magnetic pulses and activate peripheral muscles as fast as or even faster than those in M1. Hand muscle movements were observed in all our subjects about 20 ms after transcranial stimulation of the superior frontal gyrus (Brodmann areas 6 and 8). Stimulation of NPMA could activate both proximal and distal upper limb muscles with the same delay as a stimulation of the M1, indicating converging motor representations with direct functional connections to the hand. We suggest that these non-primary cortical motor representations provide additional capacity for the fast execution of movements. Such a capacity may play a role in motor learning and in recovery from motor deficits.

  2. The human papillomavirus vaccine: A powerful tool for the primary prevention of cervical cancer.

    OpenAIRE

    Nubia Muñoz; Julio César Reina; Gloria Inés Sánchez

    2009-01-01

    Prophylactic human papillomavirus (HPV) vaccine is the most promissory public health tool for primary prevention of cervical cancer. Immunization of females before the acquisition of HPV infection has the greatest impact in preventing pre-neoplasic lesions and cervical cancer. Current HPV vaccines do not eliminate cervical cancer risk, therefore, screening should continue covering vaccinated as well as women that do not get the vaccine. The strategies that include combination of high-coverage...

  3. Resveratrol Differentially Regulates NAMPT and SIRT1 in Hepatocarcinoma Cells and Primary Human Hepatocytes

    Science.gov (United States)

    Schuster, Susanne; Penke, Melanie; Gorski, Theresa; Petzold-Quinque, Stefanie; Damm, Georg; Gebhardt, Rolf; Kiess, Wieland; Garten, Antje

    2014-01-01

    Resveratrol is reported to possess chemotherapeutic properties in several cancers. In this study, we wanted to investigate the molecular mechanisms of resveratrol-induced cell cycle arrest and apoptosis as well as the impact of resveratrol on NAMPT and SIRT1 protein function and asked whether there are differences in hepatocarcinoma cells (HepG2, Hep3B cells) and non-cancerous primary human hepatocytes. We found a lower basal NAMPT mRNA and protein expression in hepatocarcinoma cells compared to primary hepatocytes. In contrast, SIRT1 was significantly higher expressed in hepatocarcinoma cells than in primary hepatocytes. Resveratrol induced cell cycle arrest in the S- and G2/M- phase and apoptosis was mediated by activation of p53 and caspase-3 in HepG2 cells. In contrast to primary hepatocytes, resveratrol treated HepG2 cells showed a reduction of NAMPT enzymatic activity and increased p53 acetylation (K382). Resveratrol induced NAMPT release from HepG2 cells which was associated with increased NAMPT mRNA expression. This effect was absent in primary hepatocytes where resveratrol was shown to function as NAMPT and SIRT1 activator. SIRT1 inhibition by EX527 resembled resveratrol effects on HepG2 cells. Furthermore, a SIRT1 overexpression significantly decreased both p53 hyperacetylation and resveratrol-induced NAMPT release as well as S-phase arrest in HepG2 cells. We could show that NAMPT and SIRT1 are differentially regulated by resveratrol in hepatocarcinoma cells and primary hepatocytes and that resveratrol did not act as a SIRT1 activator in hepatocarcinoma cells. PMID:24603648

  4. Resveratrol differentially regulates NAMPT and SIRT1 in Hepatocarcinoma cells and primary human hepatocytes.

    Directory of Open Access Journals (Sweden)

    Susanne Schuster

    Full Text Available Resveratrol is reported to possess chemotherapeutic properties in several cancers. In this study, we wanted to investigate the molecular mechanisms of resveratrol-induced cell cycle arrest and apoptosis as well as the impact of resveratrol on NAMPT and SIRT1 protein function and asked whether there are differences in hepatocarcinoma cells (HepG2, Hep3B cells and non-cancerous primary human hepatocytes. We found a lower basal NAMPT mRNA and protein expression in hepatocarcinoma cells compared to primary hepatocytes. In contrast, SIRT1 was significantly higher expressed in hepatocarcinoma cells than in primary hepatocytes. Resveratrol induced cell cycle arrest in the S- and G2/M- phase and apoptosis was mediated by activation of p53 and caspase-3 in HepG2 cells. In contrast to primary hepatocytes, resveratrol treated HepG2 cells showed a reduction of NAMPT enzymatic activity and increased p53 acetylation (K382. Resveratrol induced NAMPT release from HepG2 cells which was associated with increased NAMPT mRNA expression. This effect was absent in primary hepatocytes where resveratrol was shown to function as NAMPT and SIRT1 activator. SIRT1 inhibition by EX527 resembled resveratrol effects on HepG2 cells. Furthermore, a SIRT1 overexpression significantly decreased both p53 hyperacetylation and resveratrol-induced NAMPT release as well as S-phase arrest in HepG2 cells. We could show that NAMPT and SIRT1 are differentially regulated by resveratrol in hepatocarcinoma cells and primary hepatocytes and that resveratrol did not act as a SIRT1 activator in hepatocarcinoma cells.

  5. Primary cilia: the chemical antenna regulating human adipose-derived stem cell osteogenesis.

    Directory of Open Access Journals (Sweden)

    Josephine C Bodle

    Full Text Available Adipose-derived stem cells (ASC are multipotent stem cells that show great potential as a cell source for osteogenic tissue replacements and it is critical to understand the underlying mechanisms of lineage specification. Here we explore the role of primary cilia in human ASC (hASC differentiation. This study focuses on the chemosensitivity of the primary cilium and the action of its associated proteins: polycystin-1 (PC1, polycystin-2 (PC2 and intraflagellar transport protein-88 (IFT88, in hASC osteogenesis. To elucidate cilia-mediated mechanisms of hASC differentiation, siRNA knockdown of PC1, PC2 and IFT88 was performed to disrupt cilia-associated protein function. Immunostaining of the primary cilium structure indicated phenotypic-dependent changes in cilia morphology. hASC cultured in osteogenic differentiation media yielded cilia of a more elongated conformation than those cultured in expansion media, indicating cilia-sensitivity to the chemical environment and a relationship between the cilium structure and phenotypic determination. Abrogation of PC1, PC2 and IFT88 effected changes in both hASC proliferation and differentiation activity, as measured through proliferative activity, expression of osteogenic gene markers, calcium accretion and endogenous alkaline phosphatase activity. Results indicated that IFT88 may be an early mediator of the hASC differentiation process with its knockdown increasing hASC proliferation and decreasing Runx2, alkaline phosphatase and BMP-2 mRNA expression. PC1 and PC2 knockdown affected later osteogenic gene and end-product expression. PC1 knockdown resulted in downregulation of alkaline phosphatase and osteocalcin gene expression, diminished calcium accretion and reduced alkaline phosphatase enzymatic activity. Taken together our results indicate that the structure of the primary cilium is intimately associated with the process of hASC osteogenic differentiation and that its associated proteins are critical

  6. Effect of thoracic epidural etidocaine 1.5% on somatosensory evoked potentials, cortisol and glucose during cholecystectomy

    DEFF Research Database (Denmark)

    Dahl, J B; Rosenberg, J; Kehlet, H

    1992-01-01

    The effect of thoracic (T7-8) epidural etidocaine 1.5%, 9 ml, and continuous per- and postoperative epidural infusion of etidocaine 1.5%, 4 ml/h, on early (less than 500 ms) somatosensory evoked potentials (SEPs), and cortisol and glucose in plasma during cholecystectomy, was examined in ten...... stimulation at the L1, T10 or T6 dermatomal level (P greater than 0.09). SEPs were abolished in only two patients at T6, and no patient had SEPs abolished at T10 or L1. The plasma concentrations of cortisol and glucose were significantly increased 20 min after surgical incision and remained increased...... throughout the study. No correlation was found between the block-induced decrease in the peak-to-peak amplitude at T6 or T10 and increase in plasma cortisol, except for a negative correlation at T10 and the initial increase in cortisol (Rs = 0.72, P = 0.03). In conclusion, thoracic epidural administration...

  7. Whisker Deprivation Drives Two Phases of Inhibitory Synapse Weakening in Layer 4 of Rat Somatosensory Cortex.

    Directory of Open Access Journals (Sweden)

    Melanie A Gainey

    Full Text Available Inhibitory synapse development in sensory neocortex is experience-dependent, with sustained sensory deprivation yielding fewer and weaker inhibitory synapses. Whether this represents arrest of synapse maturation, or a more complex set of processes, is unclear. To test this, we measured the dynamics of inhibitory synapse development in layer 4 of rat somatosensory cortex (S1 during continuous whisker deprivation from postnatal day 7, and in age-matched controls. In deprived columns, spontaneous miniature inhibitory postsynaptic currents (mIPSCs and evoked IPSCs developed normally until P15, when IPSC amplitude transiently decreased, recovering by P16 despite ongoing deprivation. IPSCs remained normal until P22, when a second, sustained phase of weakening began. Delaying deprivation onset by 5 days prevented the P15 weakening. Both early and late phase weakening involved measurable reduction in IPSC amplitude relative to prior time points. Thus, deprivation appears to drive two distinct phases of active IPSC weakening, rather than simple arrest of synapse maturation.

  8. Processing of primary and secondary rewards: a quantitative meta-analysis and review of human functional neuroimaging studies

    NARCIS (Netherlands)

    Sescousse, G.T.; Caldu, X.; Segura, B.; Dreher, J.C.

    2013-01-01

    One fundamental question concerning brain reward mechanisms is to determine how reward-related activity is influenced by the nature of rewards. Here, we review the neuroimaging literature and explicitly assess to what extent the representations of primary and secondary rewards overlap in the human

  9. Electrotransfection and lipofection show comparable efficiency for in vitro gene delivery of primary human myoblasts.

    Science.gov (United States)

    Mars, Tomaz; Strazisar, Marusa; Mis, Katarina; Kotnik, Nejc; Pegan, Katarina; Lojk, Jasna; Grubic, Zoran; Pavlin, Mojca

    2015-04-01

    Transfection of primary human myoblasts offers the possibility to study mechanisms that are important for muscle regeneration and gene therapy of muscle disease. Cultured human myoblasts were selected here because muscle cells still proliferate at this developmental stage, which might have several advantages in gene therapy. Gene therapy is one of the most sought-after tools in modern medicine. Its progress is, however, limited due to the lack of suitable gene transfer techniques. To obtain better insight into the transfection potential of the presently used techniques, two non-viral transfection methods--lipofection and electroporation--were compared. The parameters that can influence transfection efficiency and cell viability were systematically approached and compared. Cultured myoblasts were transfected with the pEGFP-N1 plasmid either using Lipofectamine 2000 or with electroporation. Various combinations for the preparation of the lipoplexes and the electroporation media, and for the pulsing protocols, were tested and compared. Transfection efficiency and cell viability were inversely proportional for both approaches. The appropriate ratio of Lipofectamine and plasmid DNA provides optimal conditions for lipofection, while for electroporation, RPMI medium and a pulsing protocol using eight pulses of 2 ms at E = 0.8 kV/cm proved to be the optimal combination. The transfection efficiencies for the optimal lipofection and optimal electrotransfection protocols were similar (32 vs. 32.5%, respectively). Both of these methods are effective for transfection of primary human myoblasts; however, electroporation might be advantageous for in vivo application to skeletal muscle.

  10. Using constellation pharmacology to define comprehensively a somatosensory neuronal subclass

    Science.gov (United States)

    Teichert, Russell W.; Memon, Tosifa; Aman, Joseph W.; Olivera, Baldomero M.

    2014-01-01

    Change is intrinsic to nervous systems; change is required for learning and conditioning and occurs with disease progression, normal development, and aging. To better understand mammalian nervous systems and effectively treat nervous-system disorders, it is essential to track changes in relevant individual neurons. A critical challenge is to identify and characterize the specific cell types involved and the molecular-level changes that occur in each. Using an experimental strategy called constellation pharmacology, we demonstrate that we can define a specific somatosensory neuronal subclass, cold thermosensors, across different species and track changes in these neurons as a function of development. Cold thermosensors are uniformly responsive to menthol and innocuous cool temperature (17 °C), indicating that they express TRPM8 channels. A subset of cold thermosensors expressed α7 nicotinic acetylcholine receptors (nAChRs) but not other nAChR subtypes. Differences in temperature threshold of cold thermosensors correlated with functional expression of voltage-gated K channels Kv1.1/1.2: Relatively higher expression of KV1.1/1.2 channels resulted in a higher threshold response to cold temperature. Other signaling components varied during development and between species. In cold thermosensors of neonatal mice and rats, ATP receptors were functionally expressed, but the expression disappeared with development. This developmental change occurred earlier in low-threshold than high-threshold cold thermosensors. Most rat cold thermosensors expressed TRPA1 channels, whereas mouse cold thermosensors did not. The broad implications of this study are that it is now feasible to track changes in receptor and ion-channel expression in individual neuronal subclasses as a function of development, learning, disease, or aging. PMID:24469798

  11. Sex differences in sensorimotor mu rhythms during selective attentional processing.

    Science.gov (United States)

    Popovich, C; Dockstader, C; Cheyne, D; Tannock, R

    2010-12-01

    We used magnetoencephalography to investigate the effect of directed attention on sensorimotor mu (8-12 Hz) response (mu reactivity) to non-painful electrical stimulation of the median nerve in healthy adults. Mu desynchronization in the 10-12 Hz bandwidth is typically observed during higher-order cognitive functions including selective attentional processing of sensorimotor information (Pfurtscheller, Neuper, & Krauz, 2000). We found attention-related sex differences in mu reactivity, with females showing (i) prolonged mu desynchrony when attending to somatosensory stimuli, (ii) attentional modulation of the mu response based on whether attention was directed towards or away from somatosensory stimuli, which was absent in males, and (iii) a trend for greater neuronal excitability of the primary somatosensory region suggesting greater physiological responsiveness to sensory stimulation overall. Our findings suggest sex differences in attentional control strategies when processing somatosensory stimuli, whose salience may be greater for females. These sex differences in attention to somatosensory stimuli may help elucidate the well-documented sex biases in pain processing wherein females typically report greater sensitivity to experimental and clinical pain. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. CCL2 binding is CCR2 independent in primary adult human astrocytes.

    Science.gov (United States)

    Fouillet, A; Mawson, J; Suliman, O; Sharrack, B; Romero, I A; Woodroofe, M N

    2012-02-09

    Chemokines are low relative molecular mass proteins, which have chemoattractant actions on many cell types. The chemokine, CCL2, has been shown to play a major role in the recruitment of monocytes in central nervous system (CNS) lesions in multiple sclerosis (MS). Since resident astrocytes constitute a major source of chemokine synthesis including CCL2, we were interested to assess the regulation of CCL2 by astrocytes. We showed that CCL2 bound to the cell surface of astrocytes and binding was not modulated by inflammatory conditions. However, CCR2 protein was not detected nor was activation of the classical CCR2 downstream signaling pathways. Recent studies have shown that non-signaling decoy chemokine receptors bind and modulate the expression of chemokines at site of inflammation. Here, we show that the D6 chemokine decoy receptor is constitutively expressed by primary human adult astrocytes at both mRNA and protein level. In addition, CCL3, which binds to D6, but not CCL19, which does not bind to D6, displaced CCL2 binding to astrocytes; indicating that CCL2 may bind to this cell type via the D6 receptor. Our results suggest that CCL2 binding to primary adult human astrocytes is CCR2-independent and is likely to be mediated via the D6 decoy chemokine receptor. Therefore we propose that astrocytes are implicated in both the establishment of chemokine gradients for the migration of leukocytes into and within the CNS and in the regulation of CCL2 levels at inflammatory sites in the CNS. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Glucosamine exposure reduces proteoglycan synthesis in primary human endothelial cells in vitro

    Directory of Open Access Journals (Sweden)

    Trine M. Reine

    2016-09-01

    Full Text Available Purpose: Glucosamine (GlcN supplements are promoted for medical reasons, for example, for patients with arthritis and other joint-related diseases. Oral intake of GlcN is followed by uptake in the intestine, transport in the circulation and thereafter delivery to chondrocytes. Here, it is postulated to have an effect on synthesis and turnover of extracellular matrix constituents expressed by these cells. Following uptake in the intestine, serum levels are transiently increased, and the endothelium is exposed to increased levels of GlcN. We investigated the possible effects of GlcN on synthesis of proteoglycans (PGs, an important matrix component, in primary human endothelial cells. Methods: Primary human endothelial cells were cultured in vitro in medium with 5 mM glucose and 0–10 mM GlcN. PGs were recovered and analysed by western blotting, or by SDS-PAGE, gel chromatography or ion-exchange chromatography of 35S-PGs after 35S-sulphate labelling of the cells. Results: The synthesis and secretion of 35S-PGs from cultured endothelial cells were reduced in a dose- and time-dependent manner after exposure to GlcN. PGs are substituted with sulphated glycosaminoglycan (GAG chains, vital for PG function. The reduction in 35S-PGs was not related to an effect on GAG chain length, number or sulphation, but rather to the total expression of PGs. Conclusion: Exposure of endothelial cells to GlcN leads to a general decrease in 35S-PG synthesis. These results suggest that exposure to high levels of GlcN can lead to decreased matrix synthesis, contrary to what has been claimed by supporters of such supplements.

  14. Primary Human Blood Dendritic Cells for Cancer Immunotherapy—Tailoring the Immune Response by Dendritic Cell Maturation

    Directory of Open Access Journals (Sweden)

    Simone P. Sittig

    2015-12-01

    Full Text Available Dendritic cell (DC-based cancer vaccines hold the great promise of tipping the balance from tolerance of the tumor to rejection. In the last two decades, we have gained tremendous knowledge about DC-based cancer vaccines. The maturation of DCs has proven indispensable to induce immunogenic T cell responses. We review the insights gained from the development of maturation cocktails in monocyte derived DC-based trials. More recently, we have also gained insights into the functional specialization of primary human blood DC subsets. In peripheral human blood, we can distinguish at least three primary DC subsets, namely CD1c+ and CD141+ myeloid DCs and plasmacytoid DCs. We reflect the current knowledge on maturation and T helper polarization by these blood DC subsets in the context of DC-based cancer vaccines. The maturation stimulus in combination with the DC subset will determine the type of T cell response that is induced. First trials with these natural DCs underline their excellent in vivo functioning and mark them as promising tools for future vaccination strategies.

  15. Enhanced uptake of multiple sclerosis-derived myelin by THP-1 macrophages and primary human microglia.

    Science.gov (United States)

    Hendrickx, Debbie A E; Schuurman, Karianne G; van Draanen, Michael; Hamann, Jörg; Huitinga, Inge

    2014-03-31

    The pathological hallmark of multiple sclerosis (MS) is myelin phagocytosis. It remains unclear why microglia and macrophages demyelinate axons in MS, but previously found or yet-unknown changes in the myelin of MS patients could contribute to this process. We therefore studied whether myelin from normal-appearing white matter (NAWM) of MS donors is phagocytosed more efficiently than myelin from control donors. Myelin was isolated from 11 MS and 12 control brain donors and labeled with the pH-sensitive fluorescent dye pHrodo to quantify uptake in lysosomes. Phagocytosis by differentiated THP-1 macrophages and by primary human microglia was quantified with flow cytometry. Whereas myelin uptake by THP-1 macrophages reached a plateau after approximately 24 hours, uptake by primary human microglia showed an almost linear increase over a 72-hour period. Data were statistically analyzed with the Mann-Whitney U test. MS-derived myelin was phagocytosed more efficiently by THP-1 macrophages after 6-hour incubation (P = 0.001 for the percentage of myelin-phagocytosing cells and P = 0.0005 for total myelin uptake) and after 24-hour incubation (P = 0.0006 and P = 0.0001, respectively), and by microglia after 24-hour incubation (P = 0.0106 for total myelin uptake). This enhanced uptake was not due to differences in the oxidation status of the myelin. Interestingly, myelin phagocytosis correlated negatively with the age of myelin donors, whereas the age of microglia donors showed a positive trend with myelin phagocytosis. Myelin isolated from normal-appearing white matter of MS donors was phagocytosed more efficiently than was myelin isolated from control brain donors by both THP-1 macrophages and primary human microglia. These data indicate that changes in MS myelin might precede phagocyte activation and subsequent demyelination in MS. Identifying these myelin changes responsible for enhancing phagocytic ability could be an interesting therapeutic target to

  16. Prevalence and factors associated with breast milk donation in banks that receive human milk in primary health care units

    Directory of Open Access Journals (Sweden)

    Tatiana Mota Xavier de Meneses

    2017-07-01

    Conclusions: Encouragement to breast milk donation, and information and help provided by primary health care unit professionals to breastfeeding were shown to be important for the practice of human milk donation.

  17. Characteristics of primary infection of a European human immunodeficiency virus type 1 clade B isolate in chimpanzees

    NARCIS (Netherlands)

    Bogers, W. M.; Koornstra, W. H.; Dubbes, R. H.; ten Haaft, P. J.; Verstrepen, B. E.; Jhagjhoorsingh, S. S.; Haaksma, A. G.; Niphuis, H.; Laman, J. D.; Norley, S.; Schuitemaker, H.; Goudsmit, J.; Hunsmann, G.; Heeney, J. L.; Wigzell, H.

    1998-01-01

    The aim of the study was to select, from a panel of candidate European human immunodeficiency virus type 1 (HIV-1) clade B primary virus isolates, one isolate based on replication properties in chimpanzee peripheral blood mononuclear cells (PBMC). Secondly, to evaluate the in vivo kinetics of

  18. Dopamine receptor activation increases HIV entry into primary human macrophages.

    Directory of Open Access Journals (Sweden)

    Peter J Gaskill

    Full Text Available Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers.

  19. Bimodal stimulus timing-dependent plasticity in primary auditory cortex is altered after noise exposure with and without tinnitus.

    Science.gov (United States)

    Basura, Gregory J; Koehler, Seth D; Shore, Susan E

    2015-12-01

    Central auditory circuits are influenced by the somatosensory system, a relationship that may underlie tinnitus generation. In the guinea pig dorsal cochlear nucleus (DCN), pairing spinal trigeminal nucleus (Sp5) stimulation with tones at specific intervals and orders facilitated or suppressed subsequent tone-evoked neural responses, reflecting spike timing-dependent plasticity (STDP). Furthermore, after noise-induced tinnitus, bimodal responses in DCN were shifted from Hebbian to anti-Hebbian timing rules with less discrete temporal windows, suggesting a role for bimodal plasticity in tinnitus. Here, we aimed to determine if multisensory STDP principles like those in DCN also exist in primary auditory cortex (A1), and whether they change following noise-induced tinnitus. Tone-evoked and spontaneous neural responses were recorded before and 15 min after bimodal stimulation in which the intervals and orders of auditory-somatosensory stimuli were randomized. Tone-evoked and spontaneous firing rates were influenced by the interval and order of the bimodal stimuli, and in sham-controls Hebbian-like timing rules predominated as was seen in DCN. In noise-exposed animals with and without tinnitus, timing rules shifted away from those found in sham-controls to more anti-Hebbian rules. Only those animals with evidence of tinnitus showed increased spontaneous firing rates, a purported neurophysiological correlate of tinnitus in A1. Together, these findings suggest that bimodal plasticity is also evident in A1 following noise damage and may have implications for tinnitus generation and therapeutic intervention across the central auditory circuit. Copyright © 2015 the American Physiological Society.

  20. Decreased somatosensory activity to non-threatening touch in combat veterans with posttraumatic stress disorder.

    Science.gov (United States)

    Badura-Brack, Amy S; Becker, Katherine M; McDermott, Timothy J; Ryan, Tara J; Becker, Madelyn M; Hearley, Allison R; Heinrichs-Graham, Elizabeth; Wilson, Tony W

    2015-08-30

    Posttraumatic stress disorder (PTSD) is a severe psychiatric disorder prevalent in combat veterans. Previous neuroimaging studies have demonstrated that patients with PTSD exhibit abnormal responses to non-threatening visual and auditory stimuli, but have not examined somatosensory processing. Thirty male combat veterans, 16 with PTSD and 14 without, completed a tactile stimulation task during a 306-sensor magnetoencephalography (MEG) recording. Significant oscillatory neural responses were imaged using a beamforming approach. Participants also completed clinical assessments of PTSD, combat exposure, and depression. We found that veterans with PTSD exhibited significantly reduced activity during early (0-125 ms) tactile processing compared with combat controls. Specifically, veterans with PTSD had weaker activity in the left postcentral gyrus, left superior parietal area, and right prefrontal cortex in response to nonthreatening tactile stimulation relative to veterans without PTSD. The magnitude of activity in these brain regions was inversely correlated with symptom severity, indicating that those with the most severe PTSD had the most abnormal neural responses. Our findings are consistent with a resource allocation view of perceptual processing in PTSD, which directs attention away from nonthreatening sensory information. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Being watched: the effect of social self-focus on interoceptive and exteroceptive somatosensory perception.

    Science.gov (United States)

    Durlik, Caroline; Cardini, Flavia; Tsakiris, Manos

    2014-04-01

    We become aware of our bodies interoceptively, by processing signals arising from within the body, and exteroceptively, by processing signals arising on or outside the body. Recent research highlights the importance of the interaction of exteroceptive and interoceptive signals in modulating bodily self-consciousness. The current study investigated the effect of social self-focus, manipulated via a video camera that was facing the participants and that was either switched on or off, on interoceptive sensitivity (using a heartbeat perception task) and on tactile perception (using the Somatic Signal Detection Task (SSDT)). The results indicated a significant effect of self-focus on SSDT performance, but not on interoception. SSDT performance was not moderated by interoceptive sensitivity, although interoceptive sensitivity scores were positively correlated with false alarms, independently of self-focus. Together with previous research, our results suggest that self-focus may exert different effects on body perception depending on its mode (private versus social). While interoception has been previously shown to be enhanced by private self-focus, the current study failed to find an effect of social self-focus on interoceptive sensitivity, instead demonstrating that social self-focus improves exteroceptive somatosensory processing. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. The organisational and human resource challenges facing primary care trusts: protocol of a multiple case study

    Directory of Open Access Journals (Sweden)

    Tim Scott J

    2001-11-01

    Full Text Available Abstract Background The study is designed to assess the organisational and human resource challenges faced by Primary Care Trusts (PCTs. Its objectives are to: specify the organisational and human resources challenges faced by PCTs in fulfilling the roles envisaged in government and local policy; examine how PCTs are addressing these challenges, in particular, to describe the organisational forms they have adopted, and the OD/HR strategies and initiatives they have planned or in place; assess how effective these structures, strategies and initiatives have been in enabling the PCTs to meet the organisational and human resources challenges they face; identify the factors, both internal to the PCT and in the wider health community, which have contributed to the success or failure of different structures, strategies and initiatives. Methods The study will be undertaken in three stages. In Stage 1 the key literature on public sector and NHS organisational development and human resources management will be reviewed, and discussions will be held with key researchers and policy makers working in this area. Stage 2 will focus on detailed case studies in six PCTs designed to examine the organisational and human resources challenges they face. Data will be collected using semi-structured interviews, group discussion, site visits, observation of key meetings and examination of local documentation. The findings from the case study PCTs will be cross checked with a Reference Group of up to 20 other PCG/Ts, and key officers working in organisational development or primary care at local, regional and national level. In Stage 3 analysis of findings from the preparatory work, the case studies and the feedback from the Reference Group will be used to identify practical lessons for PCTs, key messages for policy makers, and contributions to further theoretical development.

  3. Primary human polarized small intestinal epithelial barriers respond differently to a hazardous and an innocuous protein.

    Science.gov (United States)

    Eaton, A D; Zimmermann, C; Delaney, B; Hurley, B P

    2017-08-01

    An experimental platform employing human derived intestinal epithelial cell (IEC) line monolayers grown on permeable Transwell ® filters was previously investigated to differentiate between hazardous and innocuous proteins. This approach was effective at distinguishing these types of proteins and perturbation of monolayer integrity, particularly transepithelial electrical resistance (TEER), was the most sensitive indicator. In the current report, in vitro indicators of monolayer integrity, cytotoxicity, and inflammation were evaluated using primary (non-transformed) human polarized small intestinal epithelial barriers cultured on Transwell ® filters to compare effects of a hazardous protein (Clostridium difficile Toxin A [ToxA]) and an innocuous protein (bovine serum albumin [BSA]). ToxA exerted a reproducible decrease on barrier integrity at doses comparable to those producing effects observed from cell line-derived IEC monolayers, with TEER being the most sensitive indicator. In contrast, BSA, tested at concentrations substantially higher than ToxA, did not cause changes in any of the tested variables. These results demonstrate a similarity in response to certain proteins between cell line-derived polarized IEC models and a primary human polarized small intestinal epithelial barrier model, thereby reinforcing the potential usefulness of cell line-derived polarized IECs as a valid experimental platform to differentiate between hazardous and non-hazardous proteins. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Human norovirus in untreated sewage and effluents from primary, secondary and tertiary treatment processes.

    Science.gov (United States)

    Campos, Carlos J A; Avant, Justin; Lowther, James; Till, Dale; Lees, David N

    2016-10-15

    Wastewater treatments are considered important means to control the environmental transmission of human norovirus (NoV). Information about NoV concentrations in untreated and treated effluents, their seasonality and typical removal rates achieved by different treatment processes is required to assess the effectiveness of sewage treatment processes in reducing human exposure to NoV. This paper reports on a characterisation of concentrations of NoV (genogroups I and II) in untreated sewage (screened influent) and treated effluents from five full scale wastewater treatment works (WwTW) in England. Results are shown for effluent samples characteristic of primary- (primary settlement, storm tank overflows), secondary- (activated sludge, trickling filters, humus tanks) and tertiary (UV disinfection) treatments. NoV occurrence in untreated sewage varied between years. This variation was consistent with the annual variation of the virus in the community as indicated by outbreak laboratory reports. Significant differences were found between mean NoV concentrations in effluents subject to different levels of treatment. Primary settlement achieved approximately 1 log10 removal for both genogroups. Concentrations of NoV and Escherichia coli in untreated sewage were of the same order of magnitude of those in storm tank overflows. Of the secondary treatments studied, activated sludge was the most effective in removing NoV with mean log10 removals of 3.11 and 2.34 for GI and GII, respectively. The results of this study provide evidence that monitoring of NoV in raw sewage or treated effluents could provide early warning of an elevated risk for NoV and potentially help prevent outbreaks through environmental exposure. They also provide evidence that elimination of stormwater discharges and improvement of the efficiency of activated sludge for NoV removal would be effective for reducing the risk of environmental transmission. Crown Copyright © 2016. Published by Elsevier Ltd. All

  5. SORBS2 and TLR3 induce premature senescence in primary human fibroblasts and keratinocytes

    International Nuclear Information System (INIS)

    Liesenfeld, Melanie; Mosig, Sandy; Funke, Harald; Jansen, Lars; Runnebaum, Ingo B; Dürst, Matthias; Backsch, Claudia

    2013-01-01

    Genetic aberrations are required for the progression of HPV-induced cervical precancers. A prerequisite for clonal expansion of cancer cells is unlimited proliferative capacity. In a cell culture model for cervical carcinogenesis loss of genes located on chromosome 4q35→qter and chromosome 10p14-p15 were found to be associated with escape from senescence. Moreover, by LOH and I-FISH analyses a higher frequency of allele loss of these regions was also observed in cervical carcinomas as compared to CIN3. The aim of this study was to identify candidate senescence-related genes located on chromosome 4q35→qter and chromosome 10p14-p15 which may contribute to clonal expansion at the transition of CIN3 to cancer. Microarray expression analyses were used to identify candidate genes down-regulated in cervical carcinomas as compared to CIN3. In order to relate these genes with the process of senescence their respective cDNAs were overexpressed in HPV16-immortalized keratinocytes as well as in primary human fibroblasts and keratinocytes using lentivirus mediated gene transduction. Overall fifteen genes located on chromosome 4q35→qter and chromosome 10p14-p15 were identified. Ten of these genes could be validated in biopsies by RT-PCR. Of interest is the novel finding that SORBS2 and TLR3 can induce senescence in primary human fibroblasts and keratinocytes but not in HPV-immortalized cell lines. Intriguingly, the endogenous expression of both genes increases during finite passaging of primary keratinocytes in vitro. The relevance of the genes SORBS2 and TLR3 in the process of cellular senescence warrants further investigation. In ongoing experiments we are investigating whether this increase in gene expression is also characteristic of replicative senescence

  6. Predictors of human immunodeficiency virus (HIV) infection in primary care: a systematic review protocol.

    Science.gov (United States)

    Rumbwere Dube, Benhildah N; Marshall, Tom P; Ryan, Ronan P

    2016-09-20

    Antiretroviral therapies for human immunodeficiency virus are more effective if infected individuals are diagnosed early, before they have irreversible immunologic damage. A large proportion of patients that are diagnosed with HIV, in United Kingdom, would have seen a general practitioner (GP) within the previous year. Determining the demographic and clinical characteristics of HIV-infected patients prior to diagnosis of HIV may be useful in identifying patients likely to be HIV positive in primary care. This could help inform a strategy of early HIV testing in primary care. This systematic review aims to identify characteristics of HIV-infected adults prior to diagnosis that could be used in a prediction model for early detection of HIV in primary care. The systematic review will search for literature, mainly observational (cohort and case-control) studies, with human participants aged 18 years and over. The exposures are demographic, socio-economic or clinical risk factors or characteristics associated with HIV infection. The comparison group will be patients with no risk factors or no comparison group. The outcome is laboratory-confirmed HIV/AIDS infection. Evidence will be identified from electronic searches of online databases of EMBASE, MEDLINE, The Cochrane Library and grey literature search engines of Open Grey, Web of Science Conference Proceedings Citation Index and examination of reference lists from selected studies (reference searching). Two reviewers will be involved in quality assessment and data extraction of the review. A data extraction form will be developed to collate data from selected studies. A checklist for quality assessment will be adapted from the Scottish Intercollegiate Guidelines Network (SIGN). This systematic review will identify and consolidate existing scientific evidence on characteristics of HIV infected individuals that could be used to inform decision-making in prognostic model development. PROSPERO CRD42016042427.

  7. Multiplicity of nuclear receptor activation by PFOA and PFOS in primary human and rodent hepatocytes

    International Nuclear Information System (INIS)

    Bjork, J.A.; Butenhoff, J.L.; Wallace, K.B.

    2011-01-01

    Perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) are surface active fluorochemicals that, due to their exceptional stability to degradation, are persistent in the environment. Both PFOA and PFOS are eliminated slowly in humans, with geometric mean serum elimination half-lives estimated at 3.5 and 4.8 years, respectively. The biological activity of PFOA and PFOS in rodents is attributed primarily to transactivation of the nuclear receptor peroxisome proliferator activated receptor alpha (PPARA), which is an important regulator of lipid and carbohydrate metabolism. However, there are significant species-specific differences in the response to PFOA and PFOS exposure; non-rodent species, including humans, are refractory to several but not all of these effects. Many of the metabolic effects have been attributed to the activation of PPARA; however, recent studies using PPARα knockout mice demonstrate residual PPARA-independent effects, some of which may involve the activation of alternate nuclear receptors, including NR1I2 (PXR), NR1I3 (CAR), NR1H3 (LXRA), and NR1H4 (FXR). The objective of this investigation was to characterize the activation of multiple nuclear receptors and modulation of metabolic pathways associated with exposure to PFOA and PFOS, and to compare and contrast the effects between rat and human primary liver cells using quantitative reverse transcription PCR (RT-qPCR). Our results demonstrate that multiple nuclear receptors participate in the metabolic response to PFOA and PFOS exposure resulting in a substantial shift from carbohydrate metabolism to fatty acid oxidation and hepatic triglyceride accumulation in rat liver cells. This shift in intermediary metabolism was more pronounced for PFOA than PFOS. Furthermore, while there is some similarity in the activation of metabolic pathways between rat and humans, particularly in PPARA regulated responses; the changes in primary human cells were more subtle and possibly reflect an adaptive

  8. Gravity Cues Embedded in the Kinematics of Human Motion Are Detected in Form-from-Motion Areas of the Visual System and in Motor-Related Areas.

    Science.gov (United States)

    Cignetti, Fabien; Chabeauti, Pierre-Yves; Menant, Jasmine; Anton, Jean-Luc J J; Schmitz, Christina; Vaugoyeau, Marianne; Assaiante, Christine

    2017-01-01

    The present study investigated the cortical areas engaged in the perception of graviceptive information embedded in biological motion (BM). To this end, functional magnetic resonance imaging was used to assess the cortical areas active during the observation of human movements performed under normogravity and microgravity (parabolic flight). Movements were defined by motion cues alone using point-light displays. We found that gravity modulated the activation of a restricted set of regions of the network subtending BM perception, including form-from-motion areas of the visual system (kinetic occipital region, lingual gyrus, cuneus) and motor-related areas (primary motor and somatosensory cortices). These findings suggest that compliance of observed movements with normal gravity was carried out by mapping them onto the observer's motor system and by extracting their overall form from local motion of the moving light points. We propose that judgment on graviceptive information embedded in BM can be established based on motor resonance and visual familiarity mechanisms and not necessarily by accessing the internal model of gravitational motion stored in the vestibular cortex.

  9. Image-Based Phenotypic Screening with Human Primary T Cells Using One-Dimensional Imaging Cytometry with Self-Tuning Statistical-Gating Algorithms.

    Science.gov (United States)

    Wang, Steve S; Ehrlich, Daniel J

    2017-09-01

    The parallel microfluidic cytometer (PMC) is an imaging flow cytometer that operates on statistical analysis of low-pixel-count, one-dimensional (1D) line scans. It is highly efficient in data collection and operates on suspension cells. In this article, we present a supervised automated pipeline for the PMC that minimizes operator intervention by incorporating multivariate logistic regression for data scoring. We test the self-tuning statistical algorithms in a human primary T-cell activation assay in flow using nuclear factor of activated T cells (NFAT) translocation as a readout and readily achieve an average Z' of 0.55 and strictly standardized mean difference of 13 with standard phorbol myristate acetate/ionomycin induction. To implement the tests, we routinely load 4 µL samples and can readout 3000 to 9000 independent conditions from 15 mL of primary human blood (buffy coat fraction). We conclude that the new technology will support primary-cell protein-localization assays and "on-the-fly" data scoring at a sample throughput of more than 100,000 wells per day and that it is, in principle, consistent with a primary pharmaceutical screen.

  10. Neuromagnetic detection of the laryngeal area: Sensory-evoked fields to air-puff stimulation.

    Science.gov (United States)

    Miyaji, Hideaki; Hironaga, Naruhito; Umezaki, Toshiro; Hagiwara, Koichi; Shigeto, Hiroshi; Sawatsubashi, Motohiro; Tobimatsu, Shozo; Komune, Shizuo

    2014-03-01

    The sensory projections from the oral cavity, pharynx, and larynx are crucial in assuring safe deglutition, coughing, breathing, and voice production/speaking. Although several studies using neuroimaging techniques have demonstrated cortical activation related to pharyngeal and laryngeal functions, little is known regarding sensory projections from the laryngeal area to the somatosensory cortex. The purpose of this study was to establish the cortical activity evoked by somatic air-puff stimulation at the laryngeal mucosa using magnetoencephalography. Twelve healthy volunteers were trained to inhibit swallowing in response to air stimuli delivered to the larynx. Minimum norm estimates was performed on the laryngeal somatosensory evoked fields (LSEFs) to best differentiate the target activations from non-task-related activations. Evoked magnetic fields were recorded with acceptable reproducibility in the left hemisphere, with a peak latency of approximately 100ms in 10 subjects. Peak activation was estimated at the caudolateral region of the primary somatosensory area (S1). These results establish the ability to detect LSEFs with an acceptable reproducibility within a single subject and among subjects. These results also suggest the existence of laryngeal somatic afferent input to the caudolateral region of S1 in human. Our findings indicate that further investigation in this area is needed, and should focus on laryngeal lateralization, swallowing, and speech processing. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Effects of somatosensory electrical stimulation on motor function and cortical oscillations.

    Science.gov (United States)

    Tu-Chan, Adelyn P; Natraj, Nikhilesh; Godlove, Jason; Abrams, Gary; Ganguly, Karunesh

    2017-11-13

    Few patients recover full hand dexterity after an acquired brain injury such as stroke. Repetitive somatosensory electrical stimulation (SES) is a promising method to promote recovery of hand function. However, studies using SES have largely focused on gross motor function; it remains unclear if it can modulate distal hand functions such as finger individuation. The specific goal of this study was to monitor the effects of SES on individuation as well as on cortical oscillations measured using EEG, with the additional goal of identifying neurophysiological biomarkers. Eight participants with a history of acquired brain injury and distal upper limb motor impairments received a single two-hour session of SES using transcutaneous electrical nerve stimulation. Pre- and post-intervention assessments consisted of the Action Research Arm Test (ARAT), finger fractionation, pinch force, and the modified Ashworth scale (MAS), along with resting-state EEG monitoring. SES was associated with significant improvements in ARAT, MAS and finger fractionation. Moreover, SES was associated with a decrease in low frequency (0.9-4 Hz delta) ipsilesional parietomotor EEG power. Interestingly, changes in ipsilesional motor theta (4.8-7.9 Hz) and alpha (8.8-11.7 Hz) power were significantly correlated with finger fractionation improvements when using a multivariate model. We show the positive effects of SES on finger individuation and identify cortical oscillations that may be important electrophysiological biomarkers of individual responsiveness to SES. These biomarkers can be potential targets when customizing SES parameters to individuals with hand dexterity deficits. NCT03176550; retrospectively registered.

  12. Characterization of primary human mammary epithelial cells isolated and propagated by conditional reprogrammed cell culture.

    Science.gov (United States)

    Jin, Liting; Qu, Ying; Gomez, Liliana J; Chung, Stacey; Han, Bingchen; Gao, Bowen; Yue, Yong; Gong, Yiping; Liu, Xuefeng; Amersi, Farin; Dang, Catherine; Giuliano, Armando E; Cui, Xiaojiang

    2018-02-20

    Conditional reprogramming methods allow for the inexhaustible in vitro proliferation of primary epithelial cells from human tissue specimens. This methodology has the potential to enhance the utility of primary cell culture as a model for mammary gland research. However, few studies have systematically characterized this method in generating in vitro normal human mammary epithelial cell models. We show that cells derived from fresh normal breast tissues can be propagated and exhibit heterogeneous morphologic features. The cultures are composed of CK18, desmoglein 3, and CK19-positive luminal cells and vimentin, p63, and CK14-positive myoepithelial cells, suggesting the maintenance of in vivo heterogeneity. In addition, the cultures contain subpopulations with different CD49f and EpCAM expression profiles. When grown in 3D conditions, cells self-organize into distinct structures that express either luminal or basal cell markers. Among these structures, CK8-positive cells enclosing a lumen are capable of differentiation into milk-producing cells in the presence of lactogenic stimulus. Furthermore, our short-term cultures retain the expression of ERα, as well as its ability to respond to estrogen stimulation. We have investigated conditionally reprogrammed normal epithelial cells in terms of cell type heterogeneity, cellular marker expression, and structural arrangement in two-dimensional (2D) and three-dimensional (3D) systems. The conditional reprogramming methodology allows generation of a heterogeneous culture from normal human mammary tissue in vitro . We believe that this cell culture model will provide a valuable tool to study mammary cell function and malignant transformation.

  13. Characterization of cellular immune response and innate immune signaling in human and nonhuman primate primary mononuclear cells exposed to Burkholderia mallei.

    Science.gov (United States)

    Alam, Shahabuddin; Amemiya, Kei; Bernhards, Robert C; Ulrich, Robert G; Waag, David M; Saikh, Kamal U

    2015-01-01

    Burkholderia pseudomallei infection causes melioidosis and is often characterized by severe sepsis. Although rare in humans, Burkholderia mallei has caused infections in laboratory workers, and the early innate cellular response to B. mallei in human and nonhuman primates has not been characterized. In this study, we examined the primary cellular immune response to B. mallei in PBMC cultures of non-human primates (NHPs), Chlorocebus aethiops (African Green Monkeys), Macaca fascicularis (Cynomolgus macaque), and Macaca mulatta (Rhesus macaque) and humans. Our results demonstrated that B. mallei elicited strong primary pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1β, and IL-6) equivalent to the levels of B. pseudomallei in primary PBMC cultures of NHPs and humans. When we examined IL-1β and other cytokine responses by comparison to Escherichia coli LPS, African Green Monkeys appears to be most responsive to B. mallei than Cynomolgus or Rhesus. Characterization of the immune signaling mechanism for cellular response was conducted by using a ligand induced cell-based reporter assay, and our results demonstrated that MyD88 mediated signaling contributed to the B. mallei and B. pseudomallei induced pro-inflammatory responses. Notably, the induced reporter activity with B. mallei, B. pseudomallei, or purified LPS from these pathogens was inhibited and cytokine production was attenuated by a MyD88 inhibitor. Together, these results show that in the scenario of severe hyper-inflammatory responses to B. mallei infection, MyD88 targeted therapeutic intervention may be a successful strategy for therapy. Published by Elsevier Ltd.

  14. The provision of Primary Health Care in two rural districts of the Eastern Cape Province with particular reference to human resources and accessibility

    Directory of Open Access Journals (Sweden)

    M. Thipanyana

    1998-09-01

    Full Text Available The provision of Primary Health Care Services (PHC is still a problem in developing countries like South Africa. In other countries, one finds enough human resources whilst in other countries there may be enough material resources. A both qualitative and quantitative research was conducted at Mqanduli and part of the Eastern Elliotdale districts in the Eastern Cape Province with the aim of investigating the provision of Primary health Care Services, reference was made to the availability of human resources and accessibility of PHC services.

  15. Sensory disturbance, CT, and somatosensory evoked potentials in thalamic hemorrhages

    International Nuclear Information System (INIS)

    Koga, Hisanobu; Miyazaki, Takayoshi; Miyazaki, Hisaya

    1985-01-01

    Thalamic hemorrhages often lead to sensory disturbances. However, no effective method for the evaluation of their prognoses has yet been clinically utilized. The somatosensory evoked potential (SEP) has been reported as an effective method, but it remains controversial. A CT scan is eminently suitable for determining the size and position of the hemorrhage. However, the correlation between the localization of the hematoma on the CT scan and the sensory distrubance has not been investigated fully. The authors selected 20 cases with the chronic stage of a thalamic hemorrhage. Each one was clinically evaluated as to sensory disturbance; they were then classified into the following five groups: Group 1: no sensory deficit (3 cases); Group 2: complete recovery from initial deficit (2 cases); Group 3: mild hypesthesia (5 cases); Group 4: severe hypesthesia (5 cases), and Group 5: paresthesia or dysesthesia (5 cases). Also, the CT scan was investigated with regard to the localization of the hematoma and the SEP. We could thus find a characteristic pattern in each group. The results may be summarized as follows. 1. The correlation between the degree of the sensory disturbance and the size and expansion of the hematoma was clearly detected. Especially, the most severe sensory disturbance was found in the hematoma extending to the lateral nuclear and ventral nuclear regions. 2. In Group 1 and 2, each SEP component (N 1 N 2 N 3 ) was shown to be normal. In Group 3, SEP components could be detected, but not completely. In Group 4, no components at all could be found. 3. In Group 5, all cases were small hematoma localized in the lateral nuclear region of the thalamus, while the N 3 components were prolonged on the SEP findings. The authors demonstrate the results and discuss the correlation between the sensory disturbance and the CT or SEP findings. (author)

  16. Characterization of connective tissue growth factor expression in primary cultures of human tubular epithelial cells: modulation by hypoxia

    NARCIS (Netherlands)

    Kroening, Sven; Neubauer, Emily; Wullich, Bernd; Aten, Jan; Goppelt-Struebe, Margarete

    2010-01-01

    Kroening S, Neubauer E, Wullich B, Aten J, Goppelt-Struebe M. Characterization of connective tissue growth factor expression in primary cultures of human tubular epithelial cells: modulation by hypoxia. Am J Physiol Renal Physiol 298:F796-F806, 2010. First published December 23, 2009;

  17. RTTN Mutations Cause Primary Microcephaly and Primordial Dwarfism in Humans.

    Science.gov (United States)

    Shamseldin, Hanan; Alazami, Anas M; Manning, Melanie; Hashem, Amal; Caluseiu, Oana; Tabarki, Brahim; Esplin, Edward; Schelley, Susan; Innes, A Micheil; Parboosingh, Jillian S; Lamont, Ryan; Majewski, Jacek; Bernier, Francois P; Alkuraya, Fowzan S

    2015-12-03

    Primary microcephaly is a developmental brain anomaly that results from defective proliferation of neuroprogenitors in the germinal periventricular zone. More than a dozen genes are known to be mutated in autosomal-recessive primary microcephaly in isolation or in association with a more generalized growth deficiency (microcephalic primordial dwarfism), but the genetic heterogeneity is probably more extensive. In a research protocol involving autozygome mapping and exome sequencing, we recruited a multiplex consanguineous family who is affected by severe microcephalic primordial dwarfism and tested negative on clinical exome sequencing. Two candidate autozygous intervals were identified, and the second round of exome sequencing revealed a single intronic variant therein (c.2885+8A>G [p.Ser963(∗)] in RTTN exon 23). RT-PCR confirmed that this change creates a cryptic splice donor and thus causes retention of the intervening 7 bp of the intron and leads to premature truncation. On the basis of this finding, we reanalyzed the exome file of a second consanguineous family affected by a similar phenotype and identified another homozygous change in RTTN as the likely causal mutation. Combined linkage analysis of the two families confirmed that RTTN maps to the only significant linkage peak. Finally, through international collaboration, a Canadian multiplex family affected by microcephalic primordial dwarfism and biallelic mutation of RTTN was identified. Our results expand the phenotype of RTTN-related disorders, hitherto limited to polymicrogyria, to include microcephalic primordial dwarfism with a complex brain phenotype involving simplified gyration. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  18. Biomimetic rehabilitation engineering: the importance of somatosensory feedback for brain-machine interfaces

    Science.gov (United States)

    Perruchoud, David; Pisotta, Iolanda; Carda, Stefano; Murray, Micah M.; Ionta, Silvio

    2016-08-01

    Objective. Brain-machine interfaces (BMIs) re-establish communication channels between the nervous system and an external device. The use of BMI technology has generated significant developments in rehabilitative medicine, promising new ways to restore lost sensory-motor functions. However and despite high-caliber basic research, only a few prototypes have successfully left the laboratory and are currently home-deployed. Approach. The failure of this laboratory-to-user transfer likely relates to the absence of BMI solutions for providing naturalistic feedback about the consequences of the BMI’s actions. To overcome this limitation, nowadays cutting-edge BMI advances are guided by the principle of biomimicry; i.e. the artificial reproduction of normal neural mechanisms. Main results. Here, we focus on the importance of somatosensory feedback in BMIs devoted to reproducing movements with the goal of serving as a reference framework for future research on innovative rehabilitation procedures. First, we address the correspondence between users’ needs and BMI solutions. Then, we describe the main features of invasive and non-invasive BMIs, including their degree of biomimicry and respective advantages and drawbacks. Furthermore, we explore the prevalent approaches for providing quasi-natural sensory feedback in BMI settings. Finally, we cover special situations that can promote biomimicry and we present the future directions in basic research and clinical applications. Significance. The continued incorporation of biomimetic features into the design of BMIs will surely serve to further ameliorate the realism of BMIs, as well as tremendously improve their actuation, acceptance, and use.

  19. Human resources for primary health care in sub-Saharan Africa: progress or stagnation?

    Science.gov (United States)

    Willcox, Merlin L; Peersman, Wim; Daou, Pierre; Diakité, Chiaka; Bajunirwe, Francis; Mubangizi, Vincent; Mahmoud, Eman Hassan; Moosa, Shabir; Phaladze, Nthabiseng; Nkomazana, Oathokwa; Khogali, Mustafa; Diallo, Drissa; De Maeseneer, Jan; Mant, David

    2015-09-10

    The World Health Organization defines a "critical shortage" of health workers as being fewer than 2.28 health workers per 1000 population and failing to attain 80% coverage for deliveries by skilled birth attendants. We aimed to quantify the number of health workers in five African countries and the proportion of these currently working in primary health care facilities, to compare this to estimates of numbers needed and to assess how the situation has changed in recent years. This study is a review of published and unpublished "grey" literature on human resources for health in five disparate countries: Mali, Sudan, Uganda, Botswana and South Africa. Health worker density has increased steadily since 2000 in South Africa and Botswana which already meet WHO targets but has not significantly increased since 2004 in Sudan, Mali and Uganda which have a critical shortage of health workers. In all five countries, a minority of doctors, nurses and midwives are working in primary health care, and shortages of qualified staff are greatest in rural areas. In Uganda, shortages are greater in primary health care settings than at higher levels. In Mali, few community health centres have a midwife or a doctor. Even South Africa has a shortage of doctors in primary health care in poorer districts. Although most countries recognize village health workers, traditional healers and traditional birth attendants, there are insufficient data on their numbers. There is an "inverse primary health care law" in the countries studied: staffing is inversely related to poverty and level of need, and health worker density is not increasing in the lowest income countries. Unless there is money to recruit and retain staff in these areas, training programmes will not improve health worker density because the trained staff will simply leave to work elsewhere. Information systems need to be improved in a way that informs policy on the health workforce. It may be possible to use existing resources

  20. Recognition memory for vibrotactile rhythms: an fMRI study in blind and sighted individuals.

    Science.gov (United States)

    Sinclair, Robert J; Dixit, Sachin; Burton, Harold

    2011-01-01

    Calcarine sulcal cortex possibly contributes to semantic recognition memory in early blind (EB). We assessed a recognition memory role using vibrotactile rhythms and a retrieval success paradigm involving learned "old" and "new" rhythms in EB and sighted. EB showed no activation differences in occipital cortex indicating retrieval success but replicated findings of somatosensory processing. Both groups showed retrieval success in primary somatosensory, precuneus, and orbitofrontal cortex. The S1 activity might indicate generic sensory memory processes.

  1. Temporal summation of heat pain in humans: Evidence supporting thalamocortical modulation.

    Science.gov (United States)

    Tran, Tuan D; Wang, Heng; Tandon, Animesh; Hernandez-Garcia, Luis; Casey, Kenneth L

    2010-07-01

    Noxious cutaneous contact heat stimuli (48 degrees C) are perceived as increasingly painful when the stimulus duration is extended from 5 to 10s, reflecting the temporal summation of central neuronal activity mediating heat pain. However, the sensation of increasing heat pain disappears, reaching a plateau as stimulus duration increases from 10 to 20s. We used functional magnetic resonance imaging (fMRI) in 10 healthy subjects to determine if active central mechanisms could contribute to this psychophysical plateau. During heat pain durations ranging from 5 to 20s, activation intensities in the bilateral orbitofrontal cortices and the activation volume in the left primary (S1) somatosensory cortex correlated only with perceived stimulus intensity and not with stimulus duration. Activation volumes increased with both stimulus duration and perceived intensity in the left lateral thalamus, posterior insula, inferior parietal cortex, and hippocampus. In contrast, during the psychophysical plateau, both the intensity and volume of thalamic and cortical activations in the right medial thalamus, right posterior insula, and left secondary (S2) somatosensory cortex continued to increase with stimulus duration but not with perceived stimulus intensity. Activation volumes in the left medial and right lateral thalamus, and the bilateral mid-anterior cingulate, left orbitofrontal, and right S2 cortices also increased only with stimulus duration. The increased activity of specific thalamic and cortical structures as stimulus duration, but not perceived intensity, increases is consistent with the recruitment of a thalamocortical mechanism that participates in the modulation of pain-related cortical responses and the temporal summation of heat pain. Published by Elsevier B.V.

  2. Susceptibility and response of human blood monocyte subsets to primary dengue virus infection.

    Directory of Open Access Journals (Sweden)

    Kok Loon Wong

    Full Text Available Human blood monocytes play a central role in dengue infections and form the majority of virus infected cells in the blood. Human blood monocytes are heterogeneous and divided into CD16(- and CD16(+ subsets. Monocyte subsets play distinct roles during disease, but it is not currently known if monocyte subsets differentially contribute to dengue protection and pathogenesis. Here, we compared the susceptibility and response of the human CD16(- and CD16(+ blood monocyte subsets to primary dengue virus in vitro. We found that both monocyte subsets were equally susceptible to dengue virus (DENV2 NGC, and capable of supporting the initial production of new infective virus particles. Both monocyte subsets produced anti-viral factors, including IFN-α, CXCL10 and TRAIL. However, CD16(+ monocytes were the major producers of inflammatory cytokines and chemokines in response to dengue virus, including IL-1β, TNF-α, IL-6, CCL2, 3 and 4. The susceptibility of both monocyte subsets to infection was increased after IL-4 treatment, but this increase was more profound for the CD16(+ monocyte subset, particularly at early time points after virus exposure. These findings reveal the differential role that monocyte subsets might play during dengue disease.

  3. Hand grips strength effect on motor function in human brain using fMRI: a pilot study

    International Nuclear Information System (INIS)

    Ismail, S S; Mohamad, M; Syazarina, S O; Nafisah, W Y

    2014-01-01

    Several methods of motor tasks for fMRI scanning have been evolving from simple to more complex tasks. Motor tasks on upper extremity were applied in order to excite the increscent of motor activation on contralesional and ipsilateral hemispheres in brain. The main objective of this study is to study the different conditions for motor tasks on upper extremity that affected the brain activation. Ten healthy right handed with normal vision (3 male and 7 female, age range=20-30 years, mean=24.6 years, SD=2.21) participated in this study. Prior to the scanning, participants were trained on hand grip tasks using rubber ball and pressure gauge tool outside the scanner. During fMRI session, a block design with 30-s task blocks and alternating 30-s rest periods was employed while participants viewed a computer screen via a back projection-mirror system and instructed to follow the instruction by gripping their hand with normal and strong grips using a rubber ball. Statistical Parametric mapping (SPM8) software was used to determine the brain activation. Both tasks activated the primary motor (M1), supplementary motor area (SMA), dorsal and ventral of premotor cortex area (PMA) in left hemisphere while in right hemisphere the area of primary motor (M1) somatosensory was activated. However, the comparison between both tasks revealed that the strong hand grip showed the higher activation at M1, PMA and SMA on left hemisphere and also the area of SMA on right hemisphere. Both conditions of motor tasks could provide insights the functional organization on human brain

  4. Hand grips strength effect on motor function in human brain using fMRI: a pilot study

    Science.gov (United States)

    Ismail, S. S.; Mohamad, M.; Syazarina, S. O.; Nafisah, W. Y.

    2014-11-01

    Several methods of motor tasks for fMRI scanning have been evolving from simple to more complex tasks. Motor tasks on upper extremity were applied in order to excite the increscent of motor activation on contralesional and ipsilateral hemispheres in brain. The main objective of this study is to study the different conditions for motor tasks on upper extremity that affected the brain activation. Ten healthy right handed with normal vision (3 male and 7 female, age range=20-30 years, mean=24.6 years, SD=2.21) participated in this study. Prior to the scanning, participants were trained on hand grip tasks using rubber ball and pressure gauge tool outside the scanner. During fMRI session, a block design with 30-s task blocks and alternating 30-s rest periods was employed while participants viewed a computer screen via a back projection-mirror system and instructed to follow the instruction by gripping their hand with normal and strong grips using a rubber ball. Statistical Parametric mapping (SPM8) software was used to determine the brain activation. Both tasks activated the primary motor (M1), supplementary motor area (SMA), dorsal and ventral of premotor cortex area (PMA) in left hemisphere while in right hemisphere the area of primary motor (M1) somatosensory was activated. However, the comparison between both tasks revealed that the strong hand grip showed the higher activation at M1, PMA and SMA on left hemisphere and also the area of SMA on right hemisphere. Both conditions of motor tasks could provide insights the functional organization on human brain.

  5. DIFFERENCES IN PROPIONATE-INDUCED INHIBITION OF CHOLESTEROL AND TRIACYLGLYCEROL SYNTHESIS BETWEEN HUMAN AND RAT HEPATOCYTES IN PRIMARY CULTURE

    NARCIS (Netherlands)

    LIN, YG; VONK, RJ; SLOOFF, MJH; KUIPERS, F; SMIT, MJ

    Propionate is a short-chain fatty acid formed in the colon and supposedly involved in the cholesterol-lowering effect of soluble fibre. To explore the underlying mechanism(s) of this fibre action, we have used human hepatocytes in primary culture to study the effects of propionate on hepatic lipid

  6. Overexpression of octamer transcription factors 1 or 2 alone has no effect on HIV-1 transcription in primary human CD4 T cells

    International Nuclear Information System (INIS)

    Zhang Mingce; Genin, Anna; Cron, Randy Q.

    2004-01-01

    We explored the binding of octamer (Oct) transcription factors to the HIV-1 long terminal repeat (LTR) by gel shift assays and showed none of the previously identified four potential Oct binding sites bound Oct-1 or Oct-2. Overexpression of Oct-1 or Oct-2 had no effect on HIV-1 LTR activity in transiently transfected primary human CD4 T cells. Next, primary human CD4 T cells were co-transfected with a green fluorescent protein (GFP)-expression vector and an Oct-1 or Oct-2 expression plasmid. The transfected cells were stimulated for 2 days and then infected with the NL4-3 strain of HIV-1. After 3 days of infection, there were no differences in HIV-1 p24 supernatant levels. Apoptosis of infected or bystander cells overexpressing Oct-1 or Oct-2 compared to control was also unaffected. Our studies demonstrate that Oct-1 and Oct-2 fail to bind to the HIV-1 LTR and have no effect on HIV-1 transcription in primary human CD4 T cells

  7. Human primary erythroid cells as a more sensitive alternative in vitro hematological model for nanotoxicity studies: Toxicological effects of silver nanoparticles.

    Science.gov (United States)

    Rujanapun, Narawadee; Aueviriyavit, Sasitorn; Boonrungsiman, Suwimon; Rosena, Apiwan; Phummiratch, Duangkamol; Riolueang, Suchada; Chalaow, Nipon; Viprakasit, Vip; Maniratanachote, Rawiwan

    2015-12-01

    Although immortalized cells established from cancerous cells have been widely used for studies in nanotoxicology studies, the reliability of the results derived from immortalized cells has been questioned because of their different characteristics from normal cells. In the present study, human primary erythroid cells in liquid culture were used as an in vitro hematological cell model for investigation of the nanotoxicity of silver nanoparticles (AgNPs) and comparing the results to the immortalized hematological cell lines HL60 and K562. The AgNPs caused significant cytotoxic effects in the primary erythroid cells, as shown by the decreased cell viability and induction of intracellular ROS generation and apoptosis, whereas they showed much lower cytotoxic and apoptotic effects in HL60 and K562 cells and did not induced ROS generation in these cell lines. Scanning electron microcopy revealed an interaction of AgNPs to the cell membrane in both primary erythroid and immortalized cells. In addition, AgNPs induced hemolysis in the primary erythroid cells in a dose-dependent manner, and transmission electron microcopy analysis revealed that AgNPs damaged the erythroid cell membrane. Taken together, these results suggest that human primary erythroid cells in liquid culture are a more sensitive alternative in vitro hematological model for nanotoxicology studies. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Inhibition of primary human T cell proliferation by Helicobacter pylori vacuolating toxin (VacA) is independent of VacA effects on IL-2 secretion

    OpenAIRE

    Sundrud, Mark S.; Torres, Victor J.; Unutmaz, Derya; Cover, Timothy L.

    2004-01-01

    Recent evidence indicates that the secreted Helicobacter pylori vacuolating toxin (VacA) inhibits the activation of T cells. VacA blocks IL-2 secretion in transformed T cell lines by suppressing the activation of nuclear factor of activated T cells (NFAT). In this study, we investigated the effects of VacA on primary human CD4+ T cells. VacA inhibited the proliferation of primary human T cells activated through the T cell receptor (TCR) and CD28. VacA-treated Jurkat T cells secreted markedly ...

  9. Flow cytometry of human primary epidermal and follicular keratinocytes.

    Science.gov (United States)

    Gragnani, Alfredo; Ipolito, Michelle Zampieri; Sobral, Christiane S; Brunialti, Milena Karina Coló; Salomão, Reinaldo; Ferreira, Lydia Masako

    2008-02-19

    The aim of this study was to characterize using flow cytometry cultured human primary keratinocytes isolated from the epidermis and hair follicles by different methods. Human keratinocytes derived from discarded fragments of total skin and scalp hair follicles from patients who underwent plastic surgery in the Plastic Surgery Division at UNIFESP were used. The epidermal keratinocytes were isolated by using 3 different methods: the standard method, upon exposure to trypsin for 30 minutes; the second, by treatment with dispase for 18 hours and with trypsin for 10 minutes; and the third, by treatment with dispase for 18 hours and with trypsin for 30 minutes. Follicular keratinocytes were isolated using the standard method. On comparing the group treated with dispase for 18 hours and with trypsin for 10 minutes with the group treated with dispase for 18 hours and with trypsin for 30 minutes, it was observed that the first group presented the largest number of viable cells, the smallest number of cells in late apoptosis and necrosis with statistical significance, and no difference in apoptosis. When we compared the group treated with dispase for 18 hours and with trypsin for 10 minutes with the group treated with trypsin, the first group presented the largest number of viable cells, the smallest number of cells in apoptosis with statistical significance, and no difference in late apoptosis and necrosis. When we compared the results of the group treated with dispase for 18 hours and with trypsin for 10 minutes with the results for follical isolation, there was a statistical difference in apoptosis and viable cells. The isolation method of treatment with dispase for 18 hours and with trypsin for 10 minutes produced the largest number of viable cells and the smallest number of cells in apoptosis/necrosis.

  10. Participation of primary motor cortex area 4a in complex sensory processing: 3.0-T fMRI study.

    Science.gov (United States)

    Terumitsu, Makoto; Ikeda, Kotaro; Kwee, Ingrid L; Nakada, Tsutomu

    2009-05-06

    The precise movement of human fingers requires continuous and reciprocal interaction between motor and sensory systems. Similar to other primates, there is double representation of the digits and wrists within the human primary motor cortex (M1), which are generally referred to as area 4 anterior (M1-4a) and area 4 posterior (M1-4p). In this high-field (3.0 T) functional magnetic resonance imaging (fMRI) study, we hypothesized that M1-4p is more important for initiation of motion, whereas M1-4a is important for execution of a given motion involving more complex sensoriomotor interaction. We investigated M1-4a and M1-4p activation associated with two representative motor tasks, namely, finger tapping (voluntary motion, VM) and passive finger movement accomplished by continuous pressure (passive motor, PM), and two representative sensory stimulations, namely, simple stimulation of flutter vibration (simple sensory, SS), and complex stimulation by a row of pins moving either vertically or horizontally (complex sensory, CS). Both M1-4a and M1-4p were activated in both motor tasks, VM and PM. M1-4p was not activated by either of the two sensory tasks, whereas M1-4a was activated by CS but not by SS. Analysis of the center of gravities (COG) of the activated areas showed that VM and PM moved COG towards M1-4p and 3a. SS moved COG towards somatosensory cortex Brodmann areas 1, 2, and 3b, whereas CS towards M1-4a. The result clearly showed that M1-4a represents the area of secondary motor execution, which actively participates in CS processing.

  11. Unsaponifiable fraction isolated from grape (Vitis vinifera L.) seed oil attenuates oxidative and inflammatory responses in human primary monocytes.

    Science.gov (United States)

    Millan-Linares, Maria C; Bermudez, Beatriz; Martin, Maria E; Muñoz, Ernesto; Abia, Rocio; Millan, Francisco; Muriana, Francisco J G; Montserrat-de la Paz, Sergio

    2018-04-25

    Grape (Vitis vinifera L.) seed has well-known potential for production of oil as a byproduct of winemaking and is a rich source of bioactive compounds. Herein, we report that the unsaponifiable fraction (UF) isolated from grape seed oil (GSO) possesses anti-oxidative and anti-inflammatory properties towards human primary monocytes. The UF isolated from GSO was phytochemically characterized by GC-MS and HPLC. Freshly obtained human monocytes were used to analyse the effects of GSOUF (10-100 μg mL-1) on oxidative and inflammatory responses using FACS analysis, RT-qPCR, and ELISA procedures. GSOUF skewed the monocyte plasticity towards the anti-inflammatory non-classical CD14+CD16++ monocytes and reduced the inflammatory competence of LPS-treated human primary monocytes diminishing TNF-α, IL-1β, and IL-6 gene expression and secretion. In addition, GSOUF showed a strong reactive oxygen species (ROS)-scavenging activity, reducing significantly nitrite levels with a significant decrease in Nos2 gene expression. Our results suggest that the UF isolated from GSO has significant potential for the management of inflammatory and oxidative conditions and offer novel benefits derived from the consumption of GSO in the prevention of inflammation-related diseases.

  12. Structure of receptive fields in a computational model of area 3b of primary sensory cortex.

    Science.gov (United States)

    Detorakis, Georgios Is; Rougier, Nicolas P

    2014-01-01

    In a previous work, we introduced a computational model of area 3b which is built upon the neural field theory and receives input from a simplified model of the index distal finger pad populated by a random set of touch receptors (Merkell cells). This model has been shown to be able to self-organize following the random stimulation of the finger pad model and to cope, to some extent, with cortical or skin lesions. The main hypothesis of the model is that learning of skin representations occurs at the thalamo-cortical level while cortico-cortical connections serve a stereotyped competition mechanism that shapes the receptive fields. To further assess this hypothesis and the validity of the model, we reproduced in this article the exact experimental protocol of DiCarlo et al. that has been used to examine the structure of receptive fields in area 3b of the primary somatosensory cortex. Using the same analysis toolset, the model yields consistent results, having most of the receptive fields to contain a single region of excitation and one to several regions of inhibition. We further proceeded our study using a dynamic competition that deeply influences the formation of the receptive fields. We hypothesized this dynamic competition to correspond to some form of somatosensory attention that may help to precisely shape the receptive fields. To test this hypothesis, we designed a protocol where an arbitrary region of interest is delineated on the index distal finger pad and we either (1) instructed explicitly the model to attend to this region (simulating an attentional signal) (2) preferentially trained the model on this region or (3) combined the two aforementioned protocols simultaneously. Results tend to confirm that dynamic competition leads to shrunken receptive fields and its joint interaction with intensive training promotes a massive receptive fields migration and shrinkage.

  13. Structure of Receptive Fields in a Computational Model of Area 3b of Primary Sensory Cortex

    Directory of Open Access Journals (Sweden)

    Georgios eDetorakis

    2014-07-01

    Full Text Available In a previous work, we introduced a computational model of area 3b which is built upon the neural field theory and receives input from a simplified model of the index distal finger pad populated by a random set of touch receptors(Merkell cells. This model has been shown to be able to self-organize following the random stimulation of the finger pad model and to cope, to some extent, with cortical or skin lesions. The main hypothesis of the model is that learning of skin representations occurs at the thalamo-cortical level while cortico-cortical connections serve a stereotyped competition mechanism that shapes the receptive fields. To further assess this hypothesis and the validity of the model, we reproduced in this article the exact experimental protocol of DiCarlo et al. that has been used to examine the structure of receptive fields in area 3b of the primary somatosensory cortex. Using the same analysis toolset, the model yields consistent results, having most of the receptive fields to contain a single region of excitation and one to severalregions of inhibition. We further proceeded our study using a dynamic competition that deeply influences the formation of the receptive fields. We hypothesized this dynamic competition to correspond to some form of somatosensory attention that may help to precisely shape the receptive fields. To test this hypothesis, we designed a protocol where an arbitrary region of interest is delineated on the index distal finger pad and we either (1 instructed explicitly the model to attend to this region (simulating an attentional signal (2 preferentially trained the model on this region or (3combined the two aforementioned protocols simultaneously. Results tend to confirm that dynamic competition leads to shrunken receptive fields and its joint interaction with intensive training promotes a massive receptive fields migration and shrinkage.

  14. Attention Determines Contextual Enhancement versus Suppression in Human Primary Visual Cortex.

    Science.gov (United States)

    Flevaris, Anastasia V; Murray, Scott O

    2015-09-02

    Neural responses in primary visual cortex (V1) depend on stimulus context in seemingly complex ways. For example, responses to an oriented stimulus can be suppressed when it is flanked by iso-oriented versus orthogonally oriented stimuli but can also be enhanced when attention is directed to iso-oriented versus orthogonal flanking stimuli. Thus the exact same contextual stimulus arrangement can have completely opposite effects on neural responses-in some cases leading to orientation-tuned suppression and in other cases leading to orientation-tuned enhancement. Here we show that stimulus-based suppression and enhancement of fMRI responses in humans depends on small changes in the focus of attention and can be explained by a model that combines feature-based attention with response normalization. Neurons in the primary visual cortex (V1) respond to stimuli within a restricted portion of the visual field, termed their "receptive field." However, neuronal responses can also be influenced by stimuli that surround a receptive field, although the nature of these contextual interactions and underlying neural mechanisms are debated. Here we show that the response in V1 to a stimulus in the same context can either be suppressed or enhanced depending on the focus of attention. We are able to explain the results using a simple computational model that combines two well established properties of visual cortical responses: response normalization and feature-based enhancement. Copyright © 2015 the authors 0270-6474/15/3512273-08$15.00/0.

  15. The effect of spaceflight and microgravity on the human brain.

    Science.gov (United States)

    Van Ombergen, Angelique; Demertzi, Athena; Tomilovskaya, Elena; Jeurissen, Ben; Sijbers, Jan; Kozlovskaya, Inessa B; Parizel, Paul M; Van de Heyning, Paul H; Sunaert, Stefan; Laureys, Steven; Wuyts, Floris L

    2017-10-01

    Microgravity, confinement, isolation, and immobilization are just some of the features astronauts have to cope with during space missions. Consequently, long-duration space travel can have detrimental effects on human physiology. Although research has focused on the cardiovascular and musculoskeletal system in particular, the exact impact of spaceflight on the human central nervous system remains to be determined. Previous studies have reported psychological problems, cephalic fluid shifts, neurovestibular problems, and cognitive alterations, but there is paucity in the knowledge of the underlying neural substrates. Previous space analogue studies and preliminary spaceflight studies have shown an involvement of the cerebellum, cortical sensorimotor, and somatosensory areas and the vestibular pathways. Extending this knowledge is crucial, especially in view of long-duration interplanetary missions (e.g., Mars missions) and space tourism. In addition, the acquired insight could be relevant for vestibular patients, patients with neurodegenerative disorders, as well as the elderly population, coping with multisensory deficit syndromes, immobilization, and inactivity.

  16. Primary afferent terminal sprouting after a cervical dorsal rootlet section in the macaque monkey.

    Science.gov (United States)

    Darian-Smith, Corinna

    2004-03-01

    We examined the role of primary afferent neurons in the somatosensory cortical "reactivation" that occurs after a localized cervical dorsal root lesion (Darian-Smith and Brown [2000] Nat. Neurosci. 3:476-481). After section of the dorsal rootlets that enervate the macaque's thumb and index finger (segments C6-C8), the cortical representation of these digits was initially silenced but then re-emerged for these same digits over 2-4 postlesion months. Cortical reactivation was accompanied by the emergence of physiologically detectable input from these same digits within dorsal rootlets bordering the lesion site. We investigated whether central axonal sprouting of primary afferents spared by the rhizotomy could mediate this cortical reactivation. The cortical representation of the hand was mapped electrophysiologically 15-25 weeks after the dorsal rootlet section to define this reactivation. Cholera toxin subunit B conjugated to horseradish peroxidase was then injected into the thumb and index finger pads bilaterally to label the central terminals of any neurons that innervated these digits. Primary afferent terminal proliferation was assessed in the spinal dorsal horn and cuneate nucleus at 7 days and 15-25 postlesion weeks. Labeled terminal bouton distributions were reconstructed and the "lesion" and control sides compared within each monkey. Distributions were significantly larger on the side of the lesion in the dorsal horn and cuneate nucleus at 15-25 weeks after the dorsal rootlet section, than those mapped only 7 days postlesion. Our results provide direct evidence for localized sprouting of spared (uninjured) primary afferent terminals in the dorsal horn and cuneate nucleus after a restricted dorsal root injury. Copyright 2004 Wiley-Liss, Inc.

  17. CTCF and CohesinSA-1 Mark Active Promoters and Boundaries of Repressive Chromatin Domains in Primary Human Erythroid Cells.

    Directory of Open Access Journals (Sweden)

    Laurie A Steiner

    Full Text Available CTCF and cohesinSA-1 are regulatory proteins involved in a number of critical cellular processes including transcription, maintenance of chromatin domain architecture, and insulator function. To assess changes in the CTCF and cohesinSA-1 interactomes during erythropoiesis, chromatin immunoprecipitation coupled with high throughput sequencing and mRNA transcriptome analyses via RNA-seq were performed in primary human hematopoietic stem and progenitor cells (HSPC and primary human erythroid cells from single donors.Sites of CTCF and cohesinSA-1 co-occupancy were enriched in gene promoters in HSPC and erythroid cells compared to single CTCF or cohesin sites. Cell type-specific CTCF sites in erythroid cells were linked to highly expressed genes, with the opposite pattern observed in HSPCs. Chromatin domains were identified by ChIP-seq with antibodies against trimethylated lysine 27 histone H3, a modification associated with repressive chromatin. Repressive chromatin domains increased in both number and size during hematopoiesis, with many more repressive domains in erythroid cells than HSPCs. CTCF and cohesinSA-1 marked the boundaries of these repressive chromatin domains in a cell-type specific manner.These genome wide data, changes in sites of protein occupancy, chromatin architecture, and related gene expression, support the hypothesis that CTCF and cohesinSA-1 have multiple roles in the regulation of gene expression during erythropoiesis including transcriptional regulation at gene promoters and maintenance of chromatin architecture. These data from primary human erythroid cells provide a resource for studies of normal and perturbed erythropoiesis.

  18. Inhibition of aromatase activity by methyl sulfonyl PCB metabolites in primary culture of human mammary fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Berg, M. van den; Heneweer, M.; Geest, M. de; Sanderson, T. [Inst. for Risk Assessment Sciences and Utrecht Univ. (Netherlands); Jong, P. de [St. Antonius Hospital, Nieuwegein (Netherlands); Bergman, A. [Stockholm Univ., Stockholm (Sweden)

    2004-09-15

    Methyl sulfonyl PCB metabolites (MeSO2-PCBs) are persistent contaminants and are ubiquitously present in humans and the environment. Lipophilicity of MeSO2- PCB metabolites is similar to the parent compounds and they have been detected in human milk, adipose, liver and lung tissue. 4- MeSO2-PCB-149 is the most abundant PCB metabolite in human adipose tissue and milk at a level of 1.5 ng/g lipids. Human blood concentration of 4-MeSO2-PCB-149 is approximately 0.03 nM. 3- MeSO2-PCB-101 is the predominant PCB metabolite in muscle and blubber in wildlife, such as otter, mink and grey seal. In the environment, they have been linked to chronic and reproductive toxicity in exposed mink. Additionaly, some MeSO{sub 2}-PCBs have been shown to be glucocorticoid receptor (GR) antagonists. Since approximately 60% of all breast tumors are estrogen responsive, exposure to compounds that are able to alter estrogen synthesis through interference with the aromatase enzyme, can lead to changes in estrogen levels and possibly to accelerated or inhibit breast tumor growth. Therefore, it is important to identify exogenous compounds that can alter aromatase activity in addition to those compounds which have direct interaction with the estrogen receptor (ER). Aromatase (CYP19) comprises the ubiquitous flavoprotein, NADPH-cytochrome P450 reductase, and a unique cytochrome P450 that is exclusively expressed in estrogen producing cells. Previous studies have revealed that expression of the aromatase gene is regulated in a species- and tissue specific manner. In healthy breast tissue, the predominantly active aromatase promoter region I.4 is regulated by glucocorticoids and class I cytokines. Therefore, it is important to investigate possible aromatase inhibiting properties of MeSO{sub 2}-PCBs (as anti glucocorticoids?) in relevant human tissues. We used primary human mammary fibroblasts because of their role in breast cancer development. We compared the results in primary fibroblasts with

  19. Vessel co-option in primary human tumors and metastases: an obstacle to effective anti-angiogenic treatment?

    Science.gov (United States)

    Donnem, Tom; Hu, Jiangting; Ferguson, Mary; Adighibe, Omanma; Snell, Cameron; Harris, Adrian L; Gatter, Kevin C; Pezzella, Francesco

    2013-08-01

    Angiogenesis has been regarded as essential for tumor growth and progression. Studies of many human tumors, however, suggest that their microcirculation may be provided by nonsprouting vessels and that a variety of tumors can grow and metastasize without angiogenesis. Vessel co-option, where tumor cells migrate along the preexisting vessels of the host organ, is regarded as an alternative tumor blood supply. Vessel co-option may occur in many malignancies, but so far mostly reported in highly vascularized tissues such as brain, lung, and liver. In primary and metastatic lung cancer and liver metastasis from different primary origins, as much as 10-30% of the tumors are reported to use this alternative blood supply. In addition, vessel co-option is introduced as a potential explanation of antiangiogenic drug resistance, although the impact of vessel co-option in this clinical setting is still to be further explored. In this review we discuss tumor vessel co-option with specific examples of vessel co-option in primary and secondary tumors and a consideration of the clinical implications of this alternative tumor blood supply.

  20. High serotonin levels during brain development alter the structural input-output connectivity of neural networks in the rat somatosensory layer IV

    Directory of Open Access Journals (Sweden)

    Stéphanie eMiceli

    2013-06-01

    Full Text Available Homeostatic regulation of serotonin (5-HT concentration is critical for normal topographical organization and development of thalamocortical (TC afferent circuits. Down-regulation of the serotonin transporter (SERT and the consequent impaired reuptake of 5-HT at the synapse, results in a reduced terminal branching of developing TC afferents within the primary somatosensory cortex (S1. Despite the presence of multiple genetic models, the effect of high extracellular 5-HT levels on the structure and function of developing intracortical neural networks is far from being understood. Here, using juvenile SERT knockout (SERT-/- rats we investigated, in vitro, the effect of increased 5-HT levels on the structural organization of (i the thalamocortical projections of the ventroposteromedial thalamic nucleus towards S1, (ii the general barrel-field pattern and (iii the electrophysiological and morphological properties of the excitatory cell population in layer IV of S1 (spiny stellate and pyramidal cells. Our results confirmed previous findings that high levels of 5-HT during development lead to a reduction of the topographical precision of TCA projections towards the barrel cortex. Also, the barrel pattern was altered but not abolished in SERT-/- rats. In layer IV, both excitatory spiny stellate and pyramidal cells showed a significantly reduced intracolumnar organization of their axonal projections. In addition, the layer IV spiny stellate cells gave rise to a prominent projection towards the infragranular layer Vb. Our findings point to a structural and functional reorganization, of TCAs, as well as early stage intracortical microcircuitry, following the disruption of 5-HT reuptake during critical developmental periods. The increased projection pattern of the layer IV neurons suggests that the intracortical network changes are not limited to the main entry layer IV but may also affect the subsequent stages of the canonical circuits of the barrel