Cortical Network Models of Firing Rates in the Resting and Active States Predict BOLD Responses.

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Maxwell R Bennett

Full Text Available Measurements of blood oxygenation level dependent (BOLD signals have produced some surprising observations. One is that their amplitude is proportional to the entire activity in a region of interest and not just the fluctuations in this activity. Another is that during sleep and anesthesia the average BOLD correlations between regions of interest decline as the activity declines. Mechanistic explanations of these phenomena are described here using a cortical network model consisting of modules with excitatory and inhibitory neurons, taken as regions of cortical interest, each receiving excitatory inputs from outside the network, taken as subcortical driving inputs in addition to extrinsic (intermodular connections, such as provided by associational fibers. The model shows that the standard deviation of the firing rate is proportional to the mean frequency of the firing when the extrinsic connections are decreased, so that the mean BOLD signal is proportional to both as is observed experimentally. The model also shows that if these extrinsic connections are decreased or the frequency of firing reaching the network from the subcortical driving inputs is decreased, or both decline, there is a decrease in the mean firing rate in the modules accompanied by decreases in the mean BOLD correlations between the modules, consistent with the observed changes during NREM sleep and under anesthesia. Finally, the model explains why a transient increase in the BOLD signal in a cortical area, due to a transient subcortical input, gives rises to responses throughout the cortex as observed, with these responses mediated by the extrinsic (intermodular connections.

Transfer function between EEG and BOLD signals of epileptic activity

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Marco eLeite

2013-01-01

Full Text Available Simultaneous EEG-fMRI recordings have seen growing application in the evaluation of epilepsy, namely in the characterization of brain networks related to epileptic activity. In EEG-correlated fMRI studies, epileptic events are usually described as boxcar signals based on the timing information retrieved from the EEG, and subsequently convolved with a heamodynamic response function to model the associated BOLD changes. Although more flexible approaches may allow a higher degree of complexity for the haemodynamics, the issue of how to model these dynamics based on the EEG remains an open question. In this work, a new methodology for the integration of simultaneous EEG-fMRI data in epilepsy is proposed, which incorporates a transfer function from the EEG to the BOLD signal. Independent component analysis (ICA of the EEG is performed, and a number of metrics expressing different models of the EEG-BOLD transfer function are extracted from the resulting time courses. These metrics are then used to predict the fMRI data and to identify brain areas associated with the EEG epileptic activity. The methodology was tested on both ictal and interictal EEG-fMRI recordings from one patient with a hypothalamic hamartoma. When compared to the conventional analysis approach, plausible, consistent and more significant activations were obtained. Importantly, frequency-weighted EEG metrics yielded superior results than those weighted solely on the EEG power, which comes in agreement with previous literature. Reproducibility, specificity and sensitivity should be addressed in an extended group of patients in order to further validate the proposed methodology and generalize the presented proof of concept.

Post-contractile BOLD contrast in skeletal muscle at 7 T reveals inter-individual heterogeneity in the physiological responses to muscle contraction.

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Towse, Theodore F; Elder, Christopher P; Bush, Emily C; Klockenkemper, Samuel W; Bullock, Jared T; Dortch, Richard D; Damon, Bruce M

2016-12-01

Muscle blood oxygenation-level dependent (BOLD) contrast is greater in magnitude and potentially more influenced by extravascular BOLD mechanisms at 7 T than it is at lower field strengths. Muscle BOLD imaging of muscle contractions at 7 T could, therefore, provide greater or different contrast than at 3 T. The purpose of this study was to evaluate the feasibility of using BOLD imaging at 7 T to assess the physiological responses to in vivo muscle contractions. Thirteen subjects (four females) performed a series of isometric contractions of the calf muscles while being scanned in a Philips Achieva 7 T human imager. Following 2 s maximal isometric plantarflexion contractions, BOLD signal transients ranging from 0.3 to 7.0% of the pre-contraction signal intensity were observed in the soleus muscle. We observed considerable inter-subject variability in both the magnitude and time course of the muscle BOLD signal. A subset of subjects (n = 7) repeated the contraction protocol at two different repetition times (T R : 1000 and 2500 ms) to determine the potential of T 1 -related inflow effects on the magnitude of the post-contractile BOLD response. Consistent with previous reports, there was no difference in the magnitude of the responses for the two T R values (3.8 ± 0.9 versus 4.0 ± 0.6% for T R  = 1000 and 2500 ms, respectively; mean ± standard error). These results demonstrate that studies of the muscle BOLD responses to contractions are feasible at 7 T. Compared with studies at lower field strengths, post-contractile 7 T muscle BOLD contrast may afford greater insight into microvascular function and dysfunction. Copyright © 2016 John Wiley & Sons, Ltd.

Effect of hypoxia on BOLD fMRI response and total cerebral blood flow in migraine with aura patients

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Arngrim, Nanna; Hougaard, Anders; Schytz, Henrik W

2018-01-01

was measured in the visual cortex ROIs V1-V5. Total cerebral blood flow (CBF) was calculated by measuring the blood velocity in the internal carotid arteries and the basilar artery using phase-contrast mapping (PCM) MRI. Hypoxia induced a greater decrease in BOLD response to visual stimulation in V1-V4 in MA......Experimentally induced hypoxia triggers migraine and aura attacks in patients suffering from migraine with aura (MA). We investigated the blood oxygenation level-dependent (BOLD) signal response to visual stimulation during hypoxia in MA patients and healthy volunteers. In a randomized double......-blind crossover study design, 15 MA patients were allocated to 180 min of normobaric poikilocapnic hypoxia (capillary oxygen saturation 70-75%) or sham (normoxia) on two separate days and 14 healthy volunteers were exposed to hypoxia. The BOLD functional MRI (fMRI) signal response to visual stimulation...

Abnormal Striatal BOLD Responses to Reward Anticipation and Reward Delivery in ADHD

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Furukawa, Emi; Bado, Patricia; Tripp, Gail; Mattos, Paulo; Wickens, Jeff R.; Bramati, Ivanei E.; Alsop, Brent; Ferreira, Fernanda Meireles; Lima, Debora; Tovar-Moll, Fernanda; Sergeant, Joseph A.; Moll, Jorge

2014-01-01

Altered reward processing has been proposed to contribute to the symptoms of attention deficit hyperactivity disorder (ADHD). The neurobiological mechanism underlying this alteration remains unclear. We hypothesize that the transfer of dopamine release from reward to reward-predicting cues, as normally observed in animal studies, may be deficient in ADHD. Functional magnetic resonance imaging (fMRI) was used to investigate striatal responses to reward-predicting cues and reward delivery in a classical conditioning paradigm. Data from 14 high-functioning and stimulant-naïve young adults with elevated lifetime symptoms of ADHD (8 males, 6 females) and 15 well-matched controls (8 males, 7 females) were included in the analyses. During reward anticipation, increased blood-oxygen-level-dependent (BOLD) responses in the right ventral and left dorsal striatum were observed in controls, but not in the ADHD group. The opposite pattern was observed in response to reward delivery; the ADHD group demonstrated significantly greater BOLD responses in the ventral striatum bilaterally and the left dorsal striatum relative to controls. In the ADHD group, the number of current hyperactivity/impulsivity symptoms was inversely related to ventral striatal responses during reward anticipation and positively associated with responses to reward. The BOLD response patterns observed in the striatum are consistent with impaired predictive dopamine signaling in ADHD, which may explain altered reward-contingent behaviors and symptoms of ADHD. PMID:24586543

BOLD fMRI of C-Fiber Mediated Nociceptive Processing in Mouse Brain in Response to Thermal Stimulation of the Forepaws.

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Simone C Bosshard

Full Text Available Functional magnetic resonance imaging (fMRI in rodents enables non-invasive studies of brain function in response to peripheral input or at rest. In this study we describe a thermal stimulation paradigm using infrared laser diodes to apply noxious heat to the forepaw of mice in order to study nociceptive processing. Stimulation at 45 and 46°C led to robust BOLD signal changes in various brain structures including the somatosensory cortices and the thalamus. The BOLD signal amplitude scaled with the temperature applied but not with the area irradiated by the laser beam. To demonstrate the specificity of the paradigm for assessing nociceptive signaling we administered the quaternary lidocaine derivative QX-314 to the forepaws, which due to its positive charge cannot readily cross biological membranes. However, upon activation of TRPV1 channels following the administration of capsaicin the BOLD signal was largely abolished, indicative of a selective block of the C-fiber nociceptors due to QX-314 having entered the cells via the now open TRPV1 channels. This demonstrates that the cerebral BOLD response to thermal noxious paw stimulation is specifically mediated by C-fibers.

BOLD repetition decreases in object-responsive ventral visual areas depend on spatial attention.

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Eger, E; Henson, R N A; Driver, J; Dolan, R J

2004-08-01

Functional imaging studies of priming-related repetition phenomena have become widely used to study neural object representation. Although blood oxygenation level-dependent (BOLD) repetition decreases can sometimes be observed without awareness of repetition, any role for spatial attention in BOLD repetition effects remains largely unknown. We used fMRI in 13 healthy subjects to test whether BOLD repetition decreases for repeated objects in ventral visual cortices depend on allocation of spatial attention to the prime. Subjects performed a size-judgment task on a probe object that had been attended or ignored in a preceding prime display of 2 lateralized objects. Reaction times showed faster responses when the probe was the same object as the attended prime, independent of the view tested (identical vs. mirror image). No behavioral effect was evident from unattended primes. BOLD repetition decreases for attended primes were found in lateral occipital and fusiform regions bilaterally, which generalized across identical and mirror-image repeats. No repetition decreases were observed for ignored primes. Our results suggest a critical role for attention in achieving visual representations of objects that lead to both BOLD signal decreases and behavioral priming on repeated presentation.

Decreased BOLD responses in audiovisual processing

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Wiersinga-Post, Esther; Tomaskovic, Sonja; Slabu, Lavinia; Renken, Remco; de Smit, Femke; Duifhuis, Hendrikus

2010-01-01

Audiovisual processing was studied in a functional magnetic resonance imaging study using the McGurk effect. Perceptual responses and the brain activity patterns were measured as a function of audiovisual delay. In several cortical and subcortical brain areas, BOLD responses correlated negatively

Placental baseline conditions modulate the hyperoxic BOLD-MRI response.

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Sinding, Marianne; Peters, David A; Poulsen, Sofie S; Frøkjær, Jens B; Christiansen, Ole B; Petersen, Astrid; Uldbjerg, Niels; Sørensen, Anne

2018-01-01

Human pregnancies complicated by placental dysfunction may be characterized by a high hyperoxic Blood oxygen level-dependent (BOLD) MRI response. The pathophysiology behind this phenomenon remains to be established. The aim of this study was to evaluate whether it is associated with altered placental baseline conditions, including a lower oxygenation and altered tissue morphology, as estimated by the placental transverse relaxation time (T2*). We included 49 normal pregnancies (controls) and 13 pregnancies complicated by placental dysfunction (cases), defined by a birth weight baseline BOLD)/baseline BOLD) from a dynamic single-echo gradient-recalled echo (GRE) MRI sequence and the absolute ΔT2* (hyperoxic T2*- baseline T2*) from breath-hold multi-echo GRE sequences. In the control group, the relative ΔBOLD response increased during gestation from 5% in gestational week 20 to 20% in week 40. In the case group, the relative ΔBOLD response was significantly higher (mean Z-score 4.94; 95% CI 2.41, 7.47). The absolute ΔT2*, however, did not differ between controls and cases (p = 0.37), whereas the baseline T2* was lower among cases (mean Z-score -3.13; 95% CI -3.94, -2.32). Furthermore, we demonstrated a strong negative linear correlation between the Log 10 ΔBOLD response and the baseline T2* (r = -0.88, p baseline conditions, as the absolute increase in placental oxygenation (ΔT2*) does not differ between groups. Copyright © 2017 Elsevier Ltd. All rights reserved.

Increased BOLD Signals Elicited by High Gamma Auditory Stimulation of the Left Auditory Cortex in Acute State Schizophrenia

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Hironori Kuga, M.D.

2016-10-01

We acquired BOLD responses elicited by click trains of 20, 30, 40 and 80-Hz frequencies from 15 patients with acute episode schizophrenia (AESZ, 14 symptom-severity-matched patients with non-acute episode schizophrenia (NASZ, and 24 healthy controls (HC, assessed via a standard general linear-model-based analysis. The AESZ group showed significantly increased ASSR-BOLD signals to 80-Hz stimuli in the left auditory cortex compared with the HC and NASZ groups. In addition, enhanced 80-Hz ASSR-BOLD signals were associated with more severe auditory hallucination experiences in AESZ participants. The present results indicate that neural over activation occurs during 80-Hz auditory stimulation of the left auditory cortex in individuals with acute state schizophrenia. Given the possible association between abnormal gamma activity and increased glutamate levels, our data may reflect glutamate toxicity in the auditory cortex in the acute state of schizophrenia, which might lead to progressive changes in the left transverse temporal gyrus.

Calibrating the BOLD signal during a motor task using an extended fusion model incorporating DOT, BOLD and ASL data

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Yücel, Meryem A.; Huppert, Theodore J.; Boas, David A.; Gagnon, Louis

2012-01-01

Multimodal imaging improves the accuracy of the localization and the quantification of brain activation when measuring different manifestations of the hemodynamic response associated with cerebral activity. In this study, we incorporated cerebral blood flow (CBF) changes measured with arterial spin labeling (ASL), Diffuse Optical Tomography (DOT) and blood oxygen level-dependent (BOLD) recordings to reconstruct changes in oxy- (ΔHbO2) and deoxyhemoglobin (ΔHbR). Using the Grubb relation between relative changes in CBF and cerebral blood volume (CBV), we incorporated the ASL measurement as a prior to the total hemoglobin concentration change (ΔHbT). We applied this ASL fusion model to both synthetic data and experimental multimodal recordings during a 2-sec finger-tapping task. Our results show that the new approach is very powerful in estimating ΔHbO2 and ΔHbR with high spatial and quantitative accuracy. Moreover, our approach allows the computation of baseline total hemoglobin concentration (HbT0) as well as of the BOLD calibration factor M on a single subject basis. We obtained an average HbT0 of 71 μM, an average M value of 0.18 and an average increase of 13 % in cerebral metabolic rate of oxygen (CMRO2), all of which are in agreement with values previously reported in the literature. Our method yields an independent measurement of M, which provides an alternative measurement to validate the hypercapnic calibration of the BOLD signal. PMID:22546318

Mapping transient hyperventilation induced alterations with estimates of the multi-scale dynamics of BOLD signal.

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Vesa J Kiviniemi

2009-07-01

Full Text Available Temporal blood oxygen level dependent (BOLD contrast signals in functional MRI during rest may be characterized by power spectral distribution (PSD trends of the form 1/f α. Trends with 1/f characteristics comprise fractal properties with repeating oscillation patterns in multiple time scales. Estimates of the fractal properties enable the quantification of phenomena that may otherwise be difficult to measure, such as transient, non-linear changes. In this study it was hypothesized that the fractal metrics of 1/f BOLD signal trends can map changes related to dynamic, multi-scale alterations in cerebral blood flow (CBF after a transient hyperventilation challenge. Twenty-three normal adults were imaged in a resting-state before and after hyperventilation. Different variables (1/f trend constant α, fractal dimension Df, and, Hurst exponent H characterizing the trends were measured from BOLD signals. The results show that fractal metrics of the BOLD signal follow the fractional Gaussian noise model, even during the dynamic CBF change that follows hyperventilation. The most dominant effect on the fractal metrics was detected in grey matter, in line with previous hyperventilation vaso-reactivity studies. The α was able to differentiate also blood vessels from grey matter changes. Df was most sensitive to grey matter. H correlated with default mode network areas before hyperventilation but this pattern vanished after hyperventilation due to a global increase in H. In the future, resting-state fMRI combined with fractal metrics of the BOLD signal may be used for analyzing multi-scale alterations of cerebral blood flow.

Mapping Transient Hyperventilation Induced Alterations with Estimates of the Multi-Scale Dynamics of BOLD Signal.

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Kiviniemi, Vesa; Remes, Jukka; Starck, Tuomo; Nikkinen, Juha; Haapea, Marianne; Silven, Olli; Tervonen, Osmo

2009-01-01

Temporal blood oxygen level dependent (BOLD) contrast signals in functional MRI during rest may be characterized by power spectral distribution (PSD) trends of the form 1/f(alpha). Trends with 1/f characteristics comprise fractal properties with repeating oscillation patterns in multiple time scales. Estimates of the fractal properties enable the quantification of phenomena that may otherwise be difficult to measure, such as transient, non-linear changes. In this study it was hypothesized that the fractal metrics of 1/f BOLD signal trends can map changes related to dynamic, multi-scale alterations in cerebral blood flow (CBF) after a transient hyperventilation challenge. Twenty-three normal adults were imaged in a resting-state before and after hyperventilation. Different variables (1/f trend constant alpha, fractal dimension D(f), and, Hurst exponent H) characterizing the trends were measured from BOLD signals. The results show that fractal metrics of the BOLD signal follow the fractional Gaussian noise model, even during the dynamic CBF change that follows hyperventilation. The most dominant effect on the fractal metrics was detected in grey matter, in line with previous hyperventilation vaso-reactivity studies. The alpha was able to differentiate also blood vessels from grey matter changes. D(f) was most sensitive to grey matter. H correlated with default mode network areas before hyperventilation but this pattern vanished after hyperventilation due to a global increase in H. In the future, resting-state fMRI combined with fractal metrics of the BOLD signal may be used for analyzing multi-scale alterations of cerebral blood flow.

Frequency-dependent tACS modulation of BOLD signal during rhythmic visual stimulation.

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Chai, Yuhui; Sheng, Jingwei; Bandettini, Peter A; Gao, Jia-Hong

2018-05-01

Transcranial alternating current stimulation (tACS) has emerged as a promising tool for modulating cortical oscillations. In previous electroencephalogram (EEG) studies, tACS has been found to modulate brain oscillatory activity in a frequency-specific manner. However, the spatial distribution and hemodynamic response for this modulation remains poorly understood. Functional magnetic resonance imaging (fMRI) has the advantage of measuring neuronal activity in regions not only below the tACS electrodes but also across the whole brain with high spatial resolution. Here, we measured fMRI signal while applying tACS to modulate rhythmic visual activity. During fMRI acquisition, tACS at different frequencies (4, 8, 16, and 32 Hz) was applied along with visual flicker stimulation at 8 and 16 Hz. We analyzed the blood-oxygen-level-dependent (BOLD) signal difference between tACS-ON vs tACS-OFF, and different frequency combinations (e.g., 4 Hz tACS, 8 Hz flicker vs 8 Hz tACS, 8 Hz flicker). We observed significant tACS modulation effects on BOLD responses when the tACS frequency matched the visual flicker frequency or the second harmonic frequency. The main effects were predominantly seen in regions that were activated by the visual task and targeted by the tACS current distribution. These findings bridge different scientific domains of tACS research and demonstrate that fMRI could localize the tACS effect on stimulus-induced brain rhythms, which could lead to a new approach for understanding the high-level cognitive process shaped by the ongoing oscillatory signal. © 2018 Wiley Periodicals, Inc.

Spatial attention related SEP amplitude modulations covary with BOLD signal in S1--a simultaneous EEG--fMRI study.

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Schubert, Ruth; Ritter, Petra; Wüstenberg, Torsten; Preuschhof, Claudia; Curio, Gabriel; Sommer, Werner; Villringer, Arno

2008-11-01

Recent studies investigating the influence of spatial-selective attention on primary somatosensory processing have produced inconsistent results. The aim of this study was to explore the influence of tactile spatial-selective attention on spatiotemporal aspects of evoked neuronal activity in the primary somatosensory cortex (S1). We employed simultaneous electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) in 14 right-handed subjects during bilateral index finger Braille stimulation to investigate the relationship between attentional effects on somatosensory evoked potential (SEP) components and the blood oxygenation level-dependent (BOLD) signal. The 1st reliable EEG response following left tactile stimulation (P50) was significantly enhanced by spatial-selective attention, which has not been reported before. FMRI analysis revealed increased activity in contralateral S1. Remarkably, the effect of attention on the P50 component as well as long-latency SEP components starting at 190 ms for left stimuli correlated with attentional effects on the BOLD signal in contralateral S1. The implications are 2-fold: First, the correlation between early and long-latency SEP components and the BOLD effect suggest that spatial-selective attention enhances processing in S1 at 2 time points: During an early passage of the signal and during a later passage, probably via re-entrant feedback from higher cortical areas. Second, attentional modulations of the fast electrophysiological signals and the slow hemodynamic response are linearly related in S1.

Comparison between subjects with long- and short-allele carriers in the BOLD signal within amygdala during emotional tasks

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Hadi, Shamil; Siadat, Mohamad R.; Babajani-Feremi, Abbas

2012-03-01

Emotional tasks may result in a strong blood oxygen level-dependent (BOLD) signal in the amygdala in 5- HTTLRP short-allele. Reduced anterior cingulate cortex (ACC)-amygdala connectivity in short-allele provides a potential mechanistic account for the observed increase in amygdala activity. In our study, fearful and threatening facial expressions were presented to two groups of 12 subjects with long- and short-allele carriers. The BOLD signals of the left amygdala of each group were averaged to increase the signal-to-noise ratio. A Bayesian approach was used to estimate the model parameters to elucidate the underlying hemodynamic mechanism. Our results showed a positive BOLD signal in the left amygdala for short-allele individuals, and a negative BOLD signal in the same region for long-allele individuals. This is due to the fact that short-allele is associated with lower availability of serotonin transporter (5-HTT) and this leads to an increase of serotonin (5-HT) concentration in the cACC-amygdala synapse.

In contrast to BOLD: signal enhancement by extravascular water protons as an alternative mechanism of endogenous fMRI signal change.

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Figley, Chase R; Leitch, Jordan K; Stroman, Patrick W

2010-10-01

Despite the popularity and widespread application of functional magnetic resonance imaging (fMRI) in recent years, the physiological bases of signal change are not yet fully understood. Blood oxygen level-dependant (BOLD) contrast - attributed to local changes in blood flow and oxygenation, and therefore magnetic susceptibility - has become the most prevalent means of functional neuroimaging. However, at short echo times, spin-echo sequences show considerable deviations from the BOLD model, implying a second, non-BOLD component of signal change. This has been dubbed "signal enhancement by extravascular water protons" (SEEP) and is proposed to result from proton-density changes associated with cellular swelling. Given that such changes are independent of magnetic susceptibility, SEEP may offer new and improved opportunities for carrying out fMRI in regions with close proximity to air-tissue and/or bone-tissue interfaces (e.g., the prefrontal cortex and spinal cord), as well as regions close to large blood vessels, which may not be ideally suited for BOLD imaging. However, because of the interdisciplinary nature of the literature, there has yet to be a thorough synthesis, tying together the various and sometimes disparate aspects of SEEP theory. As such, we aim to provide a concise yet comprehensive overview of SEEP, including recent and compelling evidence for its validity, its current applications and its future relevance to the rapidly expanding field of functional neuroimaging. Before presenting the evidence for a non-BOLD component of endogenous functional contrast, and to enable a more critical review for the nonexpert reader, we begin by reviewing the fundamental principles underlying BOLD theory. Copyright © 2010 Elsevier Inc. All rights reserved.

Neural Correlates of Facial Mimicry: Simultaneous Measurements of EMG and BOLD Responses during Perception of Dynamic Compared to Static Facial Expressions

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Rymarczyk, Krystyna; Żurawski, Łukasz; Jankowiak-Siuda, Kamila; Szatkowska, Iwona

2018-01-01

Facial mimicry (FM) is an automatic response to imitate the facial expressions of others. However, neural correlates of the phenomenon are as yet not well established. We investigated this issue using simultaneously recorded EMG and BOLD signals during perception of dynamic and static emotional facial expressions of happiness and anger. During display presentations, BOLD signals and zygomaticus major (ZM), corrugator supercilii (CS) and orbicularis oculi (OO) EMG responses were recorded simultaneously from 46 healthy individuals. Subjects reacted spontaneously to happy facial expressions with increased EMG activity in ZM and OO muscles and decreased CS activity, which was interpreted as FM. Facial muscle responses correlated with BOLD activity in regions associated with motor simulation of facial expressions [i.e., inferior frontal gyrus, a classical Mirror Neuron System (MNS)]. Further, we also found correlations for regions associated with emotional processing (i.e., insula, part of the extended MNS). It is concluded that FM involves both motor and emotional brain structures, especially during perception of natural emotional expressions. PMID:29467691

Moment-to-Moment BOLD Signal Variability Reflects Regional Changes in Neural Flexibility across the Lifespan.

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Nomi, Jason S; Bolt, Taylor S; Ezie, C E Chiemeka; Uddin, Lucina Q; Heller, Aaron S

2017-05-31

Variability of neuronal responses is thought to underlie flexible and optimal brain function. Because previous work investigating BOLD signal variability has been conducted within task-based fMRI contexts on adults and older individuals, very little is currently known regarding regional changes in spontaneous BOLD signal variability in the human brain across the lifespan. The current study used resting-state fMRI data from a large sample of male and female human participants covering a wide age range (6-85 years) across two different fMRI acquisition parameters (TR = 0.645 and 1.4 s). Variability in brain regions including a key node of the salience network (anterior insula) increased linearly across the lifespan across datasets. In contrast, variability in most other large-scale networks decreased linearly over the lifespan. These results demonstrate unique lifespan trajectories of BOLD variability related to specific regions of the brain and add to a growing literature demonstrating the importance of identifying normative trajectories of functional brain maturation. SIGNIFICANCE STATEMENT Although brain signal variability has traditionally been considered a source of unwanted noise, recent work demonstrates that variability in brain signals during task performance is related to brain maturation in old age as well as individual differences in behavioral performance. The current results demonstrate that intrinsic fluctuations in resting-state variability exhibit unique maturation trajectories in specific brain regions and systems, particularly those supporting salience detection. These results have implications for investigations of brain development and aging, as well as interpretations of brain function underlying behavioral changes across the lifespan. Copyright © 2017 the authors 0270-6474/17/375539-10$15.00/0.

Negative BOLD response and serotonin concentration within rostral subgenual portion of the anterior cingulate cortex for long-allele carriers during perceptual processing of emotional tasks

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Hadi, Shamil M.; Siadat, Mohamad R.; Babajani-Feremi, Abbas

2012-03-01

We investigated the effect of synaptic serotonin concentration on hemodynamic responses. The stimuli paradigm involved the presentation of fearful and threatening facial expressions to a set of 24 subjects who were either5HTTLPR long- or short-allele carriers (12 of each type in each group). The BOLD signals of the rACC from subjects of each group were averaged to increase the signal-to-noise ratio. We used a Bayesian approach to estimate the parameters of the underlying hemodynamic model. Our results, during this perceptual processing of emotional task, showed a negative BOLD signal in the rACC in the subjects with long-alleles. In contrast, the subjects with short-alleles showed positive BOLD signals in the rACC. These results suggest that high synaptic serotonin concentration in the rACC inhibits neuronal activity in a fashion similar to GABA, and a consequent negative BOLD signal ensues.

Effects of glyceryl trinitrate and calcitonin-gene-related peptide on BOLD signal and arterial diameter –methodological studies by fMRI and MRA

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Asghar, Mohammed Sohail; Ashina, Messoud

2013-01-01

Over the last decades MRI has proved to be very useful in the field of drug development and discovery. Pharmacological MRI (phMRI) explores the interaction between brain physiology, neuronal activity and drugs[1]. The BOLD-signal is an indirect method to investigate brain activity by way...... of measuring task-related hemodynamic changes. Pharmacological substances that induce hemodynamic changes can therefore potentially alter the BOLD-signal that in turn falsely can be interpreted as changes in neuronal activity. It is therefore important to characterize possible effects of a pharmacological...... substance on the BOLD-response per see before that substance can be used in an fMRI experiment. Furthermore MR-angiography is useful in determining the vascular site-of-action of vasoactive substances....

Interictal functional connectivity of human epileptic networks assessed by intracerebral EEG and BOLD signal fluctuations.

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Gaelle Bettus

Full Text Available In this study, we aimed to demonstrate whether spontaneous fluctuations in the blood oxygen level dependent (BOLD signal derived from resting state functional magnetic resonance imaging (fMRI reflect spontaneous neuronal activity in pathological brain regions as well as in regions spared by epileptiform discharges. This is a crucial issue as coherent fluctuations of fMRI signals between remote brain areas are now widely used to define functional connectivity in physiology and in pathophysiology. We quantified functional connectivity using non-linear measures of cross-correlation between signals obtained from intracerebral EEG (iEEG and resting-state functional MRI (fMRI in 5 patients suffering from intractable temporal lobe epilepsy (TLE. Functional connectivity was quantified with both modalities in areas exhibiting different electrophysiological states (epileptic and non affected regions during the interictal period. Functional connectivity as measured from the iEEG signal was higher in regions affected by electrical epileptiform abnormalities relative to non-affected areas, whereas an opposite pattern was found for functional connectivity measured from the BOLD signal. Significant negative correlations were found between the functional connectivities of iEEG and BOLD signal when considering all pairs of signals (theta, alpha, beta and broadband and when considering pairs of signals in regions spared by epileptiform discharges (in broadband signal. This suggests differential effects of epileptic phenomena on electrophysiological and hemodynamic signals and/or an alteration of the neurovascular coupling secondary to pathological plasticity in TLE even in regions spared by epileptiform discharges. In addition, indices of directionality calculated from both modalities were consistent showing that the epileptogenic regions exert a significant influence onto the non epileptic areas during the interictal period. This study shows that functional

One pair of hands is not like another: caudate BOLD response in dogs depends on signal source and canine temperament

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Peter F. Cook

2014-09-01

Full Text Available Having previously used functional MRI to map the response to a reward signal in the ventral caudate in awake unrestrained dogs, here we examined the importance of signal source to canine caudate activation. Hand signals representing either incipient reward or no reward were presented by a familiar human (each dog’s respective handler, an unfamiliar human, and via illustrated images of hands on a computer screen to 13 dogs undergoing voluntary fMRI. All dogs had received extensive training with the reward and no-reward signals from their handlers and with the computer images and had minimal exposure to the signals from strangers. All dogs showed differentially higher BOLD response in the ventral caudate to the reward versus no reward signals, and there was a robust effect at the group level. Further, differential response to the signal source had a highly significant interaction with a dog’s general aggressivity as measured by the C-BARQ canine personality assessment. Dogs with greater aggressivity showed a higher differential response to the reward signal versus no-reward signal presented by the unfamiliar human and computer, while dogs with lower aggressivity showed a higher differential response to the reward signal versus no-reward signal from their handler. This suggests that specific facets of canine temperament bear more strongly on the perceived reward value of relevant communication signals than does reinforcement history, as each of the dogs were reinforced similarly for each signal, regardless of the source (familiar human, unfamiliar human, or computer. A group-level psychophysiological interaction (PPI connectivity analysis showed increased functional coupling between the caudate and a region of cortex associated with visual discrimination and learning on reward versus no-reward trials. Our findings emphasize the sensitivity of the domestic dog to human social interaction, and may have other implications and applications

Correlation of BOLD Signal with Linear and Nonlinear Patterns of EEG in Resting State EEG-Informed fMRI

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Galina V. Portnova

2018-01-01

Full Text Available Concurrent EEG and fMRI acquisitions in resting state showed a correlation between EEG power in various bands and spontaneous BOLD fluctuations. However, there is a lack of data on how changes in the complexity of brain dynamics derived from EEG reflect variations in the BOLD signal. The purpose of our study was to correlate both spectral patterns, as linear features of EEG rhythms, and nonlinear EEG dynamic complexity with neuronal activity obtained by fMRI. We examined the relationships between EEG patterns and brain activation obtained by simultaneous EEG-fMRI during the resting state condition in 25 healthy right-handed adult volunteers. Using EEG-derived regressors, we demonstrated a substantial correlation of BOLD signal changes with linear and nonlinear features of EEG. We found the most significant positive correlation of fMRI signal with delta spectral power. Beta and alpha spectral features had no reliable effect on BOLD fluctuation. However, dynamic changes of alpha peak frequency exhibited a significant association with BOLD signal increase in right-hemisphere areas. Additionally, EEG dynamic complexity as measured by the HFD of the 2–20 Hz EEG frequency range significantly correlated with the activation of cortical and subcortical limbic system areas. Our results indicate that both spectral features of EEG frequency bands and nonlinear dynamic properties of spontaneous EEG are strongly associated with fluctuations of the BOLD signal during the resting state condition.

Brain functional BOLD perturbation modelling for forward fMRI and inverse mapping

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Robinson, Jennifer; Calhoun, Vince

2018-01-01

Purpose To computationally separate dynamic brain functional BOLD responses from static background in a brain functional activity for forward fMRI signal analysis and inverse mapping. Methods A brain functional activity is represented in terms of magnetic source by a perturbation model: χ = χ0 +δχ, with δχ for BOLD magnetic perturbations and χ0 for background. A brain fMRI experiment produces a timeseries of complex-valued images (T2* images), whereby we extract the BOLD phase signals (denoted by δP) by a complex division. By solving an inverse problem, we reconstruct the BOLD δχ dataset from the δP dataset, and the brain χ distribution from a (unwrapped) T2* phase image. Given a 4D dataset of task BOLD fMRI, we implement brain functional mapping by temporal correlation analysis. Results Through a high-field (7T) and high-resolution (0.5mm in plane) task fMRI experiment, we demonstrated in detail the BOLD perturbation model for fMRI phase signal separation (P + δP) and reconstructing intrinsic brain magnetic source (χ and δχ). We also provided to a low-field (3T) and low-resolution (2mm) task fMRI experiment in support of single-subject fMRI study. Our experiments show that the δχ-depicted functional map reveals bidirectional BOLD χ perturbations during the task performance. Conclusions The BOLD perturbation model allows us to separate fMRI phase signal (by complex division) and to perform inverse mapping for pure BOLD δχ reconstruction for intrinsic functional χ mapping. The full brain χ reconstruction (from unwrapped fMRI phase) provides a new brain tissue image that allows to scrutinize the brain tissue idiosyncrasy for the pure BOLD δχ response through an automatic function/structure co-localization. PMID:29351339

Brain functional BOLD perturbation modelling for forward fMRI and inverse mapping.

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Chen, Zikuan; Robinson, Jennifer; Calhoun, Vince

2018-01-01

To computationally separate dynamic brain functional BOLD responses from static background in a brain functional activity for forward fMRI signal analysis and inverse mapping. A brain functional activity is represented in terms of magnetic source by a perturbation model: χ = χ0 +δχ, with δχ for BOLD magnetic perturbations and χ0 for background. A brain fMRI experiment produces a timeseries of complex-valued images (T2* images), whereby we extract the BOLD phase signals (denoted by δP) by a complex division. By solving an inverse problem, we reconstruct the BOLD δχ dataset from the δP dataset, and the brain χ distribution from a (unwrapped) T2* phase image. Given a 4D dataset of task BOLD fMRI, we implement brain functional mapping by temporal correlation analysis. Through a high-field (7T) and high-resolution (0.5mm in plane) task fMRI experiment, we demonstrated in detail the BOLD perturbation model for fMRI phase signal separation (P + δP) and reconstructing intrinsic brain magnetic source (χ and δχ). We also provided to a low-field (3T) and low-resolution (2mm) task fMRI experiment in support of single-subject fMRI study. Our experiments show that the δχ-depicted functional map reveals bidirectional BOLD χ perturbations during the task performance. The BOLD perturbation model allows us to separate fMRI phase signal (by complex division) and to perform inverse mapping for pure BOLD δχ reconstruction for intrinsic functional χ mapping. The full brain χ reconstruction (from unwrapped fMRI phase) provides a new brain tissue image that allows to scrutinize the brain tissue idiosyncrasy for the pure BOLD δχ response through an automatic function/structure co-localization.

Electrophysiological correlates of the BOLD signal for EEG-informed fMRI

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Murta, Teresa; Leite, Marco; Carmichael, David W; Figueiredo, Patrícia; Lemieux, Louis

2015-01-01

Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are important tools in cognitive and clinical neuroscience. Combined EEG–fMRI has been shown to help to characterise brain networks involved in epileptic activity, as well as in different sensory, motor and cognitive functions. A good understanding of the electrophysiological correlates of the blood oxygen level-dependent (BOLD) signal is necessary to interpret fMRI maps, particularly when obtained in combination with EEG. We review the current understanding of electrophysiological–haemodynamic correlates, during different types of brain activity. We start by describing the basic mechanisms underlying EEG and BOLD signals and proceed by reviewing EEG-informed fMRI studies using fMRI to map specific EEG phenomena over the entire brain (EEG–fMRI mapping), or exploring a range of EEG-derived quantities to determine which best explain colocalised BOLD fluctuations (local EEG–fMRI coupling). While reviewing studies of different forms of brain activity (epileptic and nonepileptic spontaneous activity; cognitive, sensory and motor functions), a significant attention is given to epilepsy because the investigation of its haemodynamic correlates is the most common application of EEG-informed fMRI. Our review is focused on EEG-informed fMRI, an asymmetric approach of data integration. We give special attention to the invasiveness of electrophysiological measurements and the simultaneity of multimodal acquisitions because these methodological aspects determine the nature of the conclusions that can be drawn from EEG-informed fMRI studies. We emphasise the advantages of, and need for, simultaneous intracranial EEG–fMRI studies in humans, which recently became available and hold great potential to improve our understanding of the electrophysiological correlates of BOLD fluctuations. PMID:25277370

Caffeine reduces resting-state BOLD functional connectivity in the motor cortex.

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Rack-Gomer, Anna Leigh; Liau, Joy; Liu, Thomas T

2009-05-15

In resting-state functional magnetic resonance imaging (fMRI), correlations between spontaneous low-frequency fluctuations in the blood oxygenation level dependent (BOLD) signal are used to assess functional connectivity between different brain regions. Changes in resting-state BOLD connectivity measures are typically interpreted as changes in coherent neural activity across spatially distinct brain regions. However, this interpretation can be complicated by the complex dependence of the BOLD signal on both neural and vascular factors. For example, prior studies have shown that vasoactive agents that alter baseline cerebral blood flow, such as caffeine and carbon dioxide, can significantly alter the amplitude and dynamics of the task-related BOLD response. In this study, we examined the effect of caffeine (200 mg dose) on resting-state BOLD connectivity in the motor cortex across a sample of healthy young subjects (N=9). We found that caffeine significantly (pcaffeine. These results suggest that caffeine usage should be carefully considered in the design and interpretation of resting-state BOLD fMRI studies.

The BOLD cerebrovascular reactivity response to progressive hypercapnia in young and elderly

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Bhogal, Alex A.; De Vis, Jill B.; Siero, Jeroen C.W.

2016-01-01

to broaden our interpretation of the BOLD-CVR response. Significant age-related differences were observed. Grey matter CVR at 7 mm Hg above resting PetCO2 was lower amongst elderly (0.19 ± 0.06%ΔBOLD/mm Hg) as compared to young subjects (0.26 ± 0.07%ΔBOLD/mm Hg). White matter CVR at 7 mm Hg above baseline...

Accounting for the role of hematocrit in between-subject variations of MRI-derived baseline cerebral hemodynamic parameters and functional BOLD responses.

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Xu, Feng; Li, Wenbo; Liu, Peiying; Hua, Jun; Strouse, John J; Pekar, James J; Lu, Hanzhang; van Zijl, Peter C M; Qin, Qin

2018-01-01

Baseline hematocrit fraction (Hct) is a determinant for baseline cerebral blood flow (CBF) and between-subject variation of Hct thus causes variation in task-based BOLD fMRI signal changes. We first verified in healthy volunteers (n = 12) that Hct values can be derived reliably from venous blood T 1 values by comparison with the conventional lab test. Together with CBF measured using phase-contrast MRI, this noninvasive estimation of Hct, instead of using a population-averaged Hct value, enabled more individual determination of oxygen delivery (DO 2 ), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO 2 ). The inverse correlation of CBF and Hct explained about 80% of between-subject variation of CBF in this relatively uniform cohort of subjects, as expected based on the regulation of DO 2 to maintain constant CMRO 2 . Furthermore, we compared the relationships of visual task-evoked BOLD response with Hct and CBF. We showed that Hct and CBF contributed 22%-33% of variance in BOLD signal and removing the positive correlation with Hct and negative correlation with CBF allowed normalization of BOLD signal with 16%-22% lower variability. The results of this study suggest that adjustment for Hct effects is useful for studies of MRI perfusion and BOLD fMRI. Hum Brain Mapp 39:344-353, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

EEG-informed fMRI analysis during a hand grip task: estimating the relationship between EEG rhythms and the BOLD signal

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Roberta eSclocco

2014-04-01

Full Text Available In the last decade, an increasing interest has arisen in investigating the relationship between the electrophysiological and hemodynamic measurements of brain activity, such as EEG and (BOLD fMRI. In particular, changes in BOLD have been shown to be associated with changes in the spectral profile of neural activity, rather than with absolute power. Concurrently, recent findings showed that different EEG rhythms are independently related to changes in the BOLD signal: therefore, it would be important to distinguish between the contributions of the different EEG rhythms to BOLD fluctuations when modeling the relationship between the two signals. Here we propose a method to perform EEG-informed fMRI analysis, in which the EEG regressors take into account both the changes in the spectral profile and the rhythms distinction. We applied it to EEG-fMRI data during a hand grip task in healthy subjects, and compared the results with those obtained by two existing models found in literature. Our results showed that the proposed method better captures the correlations between BOLD signal and EEG rhythms modulations, identifying task-related, well localized activated volumes. Furthermore, we showed that including among the regressors also EEG rhythms not primarily involved in the task enhances the performance of the analysis, even when only correlations with BOLD signal and specific EEG rhythms are explored.

PARTICLE FILTERING WITH SEQUENTIAL PARAMETER LEARNING FOR NONLINEAR BOLD fMRI SIGNALS.

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Xia, Jing; Wang, Michelle Yongmei

Analyzing the blood oxygenation level dependent (BOLD) effect in the functional magnetic resonance imaging (fMRI) is typically based on recent ground-breaking time series analysis techniques. This work represents a significant improvement over existing approaches to system identification using nonlinear hemodynamic models. It is important for three reasons. First, instead of using linearized approximations of the dynamics, we present a nonlinear filtering based on the sequential Monte Carlo method to capture the inherent nonlinearities in the physiological system. Second, we simultaneously estimate the hidden physiological states and the system parameters through particle filtering with sequential parameter learning to fully take advantage of the dynamic information of the BOLD signals. Third, during the unknown static parameter learning, we employ the low-dimensional sufficient statistics for efficiency and avoiding potential degeneration of the parameters. The performance of the proposed method is validated using both the simulated data and real BOLD fMRI data.

The Relationship Between Dopamine Neurotransmitter Dynamics and the Blood-Oxygen-Level-Dependent (BOLD Signal: A Review of Pharmacological Functional Magnetic Resonance Imaging

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Tyler J. Bruinsma

2018-04-01

Full Text Available Functional magnetic resonance imaging (fMRI is widely used in investigations of normal cognition and brain disease and in various clinical applications. Pharmacological fMRI (pharma-fMRI is a relatively new application, which is being used to elucidate the effects and mechanisms of pharmacological modulation of brain activity. Characterizing the effects of neuropharmacological agents on regional brain activity using fMRI is challenging because drugs modulate neuronal function in a wide variety of ways, including through receptor agonist, antagonist, and neurotransmitter reuptake blocker events. Here we review current knowledge on neurotransmitter-mediated blood-oxygen-level dependent (BOLD fMRI mechanisms as well as recently updated methodologies aimed at more fully describing the effects of neuropharmacologic agents on the BOLD signal. We limit our discussion to dopaminergic signaling as a useful lens through which to analyze and interpret neurochemical-mediated changes in the hemodynamic BOLD response. We also discuss the need for future studies that use multi-modal approaches to expand the understanding and application of pharma-fMRI.

Nonlinear Bayesian Estimation of BOLD Signal under Non-Gaussian Noise

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Ali Fahim Khan

2015-01-01

Full Text Available Modeling the blood oxygenation level dependent (BOLD signal has been a subject of study for over a decade in the neuroimaging community. Inspired from fluid dynamics, the hemodynamic model provides a plausible yet convincing interpretation of the BOLD signal by amalgamating effects of dynamic physiological changes in blood oxygenation, cerebral blood flow and volume. The nonautonomous, nonlinear set of differential equations of the hemodynamic model constitutes the process model while the weighted nonlinear sum of the physiological variables forms the measurement model. Plagued by various noise sources, the time series fMRI measurement data is mostly assumed to be affected by additive Gaussian noise. Though more feasible, the assumption may cause the designed filter to perform poorly if made to work under non-Gaussian environment. In this paper, we present a data assimilation scheme that assumes additive non-Gaussian noise, namely, the e-mixture noise, affecting the measurements. The proposed filter MAGSF and the celebrated EKF are put to test by performing joint optimal Bayesian filtering to estimate both the states and parameters governing the hemodynamic model under non-Gaussian environment. Analyses using both the synthetic and real data reveal superior performance of the MAGSF as compared to EKF.

Patterns of cortical oscillations organize neural activity into whole-brain functional networks evident in the fMRI BOLD signal

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Jennifer C Whitman

2013-03-01

Full Text Available Recent findings from electrophysiology and multimodal neuroimaging have elucidated the relationship between patterns of cortical oscillations evident in EEG / MEG and the functional brain networks evident in the BOLD signal. Much of the existing literature emphasized how high-frequency cortical oscillations are thought to coordinate neural activity locally, while low-frequency oscillations play a role in coordinating activity between more distant brain regions. However, the assignment of different frequencies to different spatial scales is an oversimplification. A more informative approach is to explore the arrangements by which these low- and high-frequency oscillations work in concert, coordinating neural activity into whole-brain functional networks. When relating such networks to the BOLD signal, we must consider how the patterns of cortical oscillations change at the same speed as cognitive states, which often last less than a second. Consequently, the slower BOLD signal may often reflect the summed neural activity of several transient network configurations. This temporal mismatch can be circumvented if we use spatial maps to assess correspondence between oscillatory networks and BOLD networks.

Visual BOLD Response in Late Blind Subjects with Argus II Retinal Prosthesis.

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E Castaldi

2016-10-01

Full Text Available Retinal prosthesis technologies require that the visual system downstream of the retinal circuitry be capable of transmitting and elaborating visual signals. We studied the capability of plastic remodeling in late blind subjects implanted with the Argus II Retinal Prosthesis with psychophysics and functional MRI (fMRI. After surgery, six out of seven retinitis pigmentosa (RP blind subjects were able to detect high-contrast stimuli using the prosthetic implant. However, direction discrimination to contrast modulated stimuli remained at chance level in all of them. No subject showed any improvement of contrast sensitivity in either eye when not using the Argus II. Before the implant, the Blood Oxygenation Level Dependent (BOLD activity in V1 and the lateral geniculate nucleus (LGN was very weak or absent. Surprisingly, after prolonged use of Argus II, BOLD responses to visual input were enhanced. This is, to our knowledge, the first study tracking the neural changes of visual areas in patients after retinal implant, revealing a capacity to respond to restored visual input even after years of deprivation.

Differences in aggression, activity and boldness between native and introduced populations of an invasive crayfish

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Pintor, L.M.; Sih, A.; Bauer, M.L.

2008-01-01

Aggressiveness, along with foraging voracity and boldness, are key behavioral mechanisms underlying the competitive displacement and invasion success of exotic species. However, do aggressiveness, voracity and boldness of the invader depend on the presence of an ecologically similar native competitor in the invaded community? We conducted four behavioral assays to compare aggression, foraging voracity, threat response and boldness to forage under predation risk of multiple populations of exotic signal crayfish Pacifastacus leniusculus across its native and invaded range with and without a native congener, the Shasta crayfish P. fortis. We predicted that signal crayfish from the invaded range and sympatric with a native congener (IRS) should be more aggressive to outcompete a close competitor than populations from the native range (NR) or invaded range and allopatric to a native congener (IRA). Furthermore, we predicted that IRS populations of signal crayfish should be more voracious, but less bold to forage under predation risk since native predators and prey likely possess appropriate behavioral responses to the invader. Contrary to our predictions, results indicated that IRA signal crayfish were more aggressive towards conspecifics and more voracious and active foragers, yet also bolder to forage under predation risk in comparison to NR and IRS populations, which did not differ in behavior. Higher aggression/voracity/ boldness was positively correlated with prey consumption rates, and hence potential impacts on prey. We suggest that the positive correlations between aggression/voracity/boldness are the result of an overall aggression syndrome. Results of stream surveys indicated that IRA streams have significantly lower prey biomass than in IRS streams, which may drive invading signal crayfish to be more aggressive/voracious/bold to acquire resources to establish a population. ?? 2008 The Authors.

Analysis of Neural-BOLD Coupling through Four Models of the Neural Metabolic Demand

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Christopher W Tyler

2015-12-01

Full Text Available The coupling of the neuronal energetics to the blood-oxygen-level-dependent (BOLD response is still incompletely understood. To address this issue, we compared the fits of four plausible models of neurometabolic coupling dynamics to available data for simultaneous recordings of the local field potential (LFP and the local BOLD response recorded from monkey primary visual cortex over a wide range of stimulus durations. The four models of the metabolic demand driving the BOLD response were: direct coupling with the overall LFP; rectified coupling to the LFP; coupling with a slow adaptive component of the implied neural population response; and coupling with the non-adaptive intracellular input signal defined by the stimulus time course. Taking all stimulus durations into account, the results imply that the BOLD response is most closely coupled with metabolic demand derived from the intracellular input waveform, without significant influence from the adaptive transients and nonlinearities exhibited by the LFP waveform.

Identifying and characterizing systematic temporally-lagged BOLD artifacts.

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Byrge, Lisa; Kennedy, Daniel P

2018-05-01

Residual noise in the BOLD signal remains problematic for fMRI - particularly for techniques such as functional connectivity, where findings can be spuriously influenced by noise sources that can covary with individual differences. Many such potential noise sources - for instance, motion and respiration - can have a temporally lagged effect on the BOLD signal. Thus, here we present a tool for assessing residual lagged structure in the BOLD signal that is associated with nuisance signals, using a construction similar to a peri-event time histogram. Using this method, we find that framewise displacements - both large and very small - were followed by structured, prolonged, and global changes in the BOLD signal that depend on the magnitude of the preceding displacement and extend for tens of seconds. This residual lagged BOLD structure was consistent across datasets, and independently predicted considerable variance in the global cortical signal (as much as 30-40% in some subjects). Mean functional connectivity estimates varied similarly as a function of displacements occurring many seconds in the past, even after strict censoring. Similar patterns of residual lagged BOLD structure were apparent following respiratory fluctuations (which covaried with framewise displacements), implicating respiration as one likely mechanism underlying the displacement-linked structure observed. Global signal regression largely attenuates this artifactual structure. These findings suggest the need for caution in interpreting results of individual difference studies where noise sources might covary with the individual differences of interest, and highlight the need for further development of preprocessing techniques for mitigating such structure in a more nuanced and targeted manner. Copyright © 2018 Elsevier Inc. All rights reserved.

Anatomical and functional assemblies of brain BOLD oscillations

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Baria, Alexis T.; Baliki, Marwan N.; Parrish, Todd; Apkarian, A. Vania

2011-01-01

Brain oscillatory activity has long been thought to have spatial properties, the details of which are unresolved. Here we examine spatial organizational rules for the human brain oscillatory activity as measured by blood oxygen level-dependent (BOLD). Resting state BOLD signal was transformed into frequency space (Welch’s method), averaged across subjects, and its spatial distribution studied as a function of four frequency bands, spanning the full bandwidth of BOLD. The brain showed anatomically constrained distribution of power for each frequency band. This result was replicated on a repository dataset of 195 subjects. Next, we examined larger-scale organization by parceling the neocortex into regions approximating Brodmann Areas (BAs). This indicated that BAs of simple function/connectivity (unimodal), vs. complex properties (transmodal), are dominated by low frequency BOLD oscillations, and within the visual ventral stream we observe a graded shift of power to higher frequency bands for BAs further removed from the primary visual cortex (increased complexity), linking frequency properties of BOLD to hodology. Additionally, BOLD oscillation properties for the default mode network demonstrated that it is composed of distinct frequency dependent regions. When the same analysis was performed on a visual-motor task, frequency-dependent global and voxel-wise shifts in BOLD oscillations could be detected at brain sites mostly outside those identified with general linear modeling. Thus, analysis of BOLD oscillations in full bandwidth uncovers novel brain organizational rules, linking anatomical structures and functional networks to characteristic BOLD oscillations. The approach also identifies changes in brain intrinsic properties in relation to responses to external inputs. PMID:21613505

Spatial–temporal signature of resting-state BOLD signals in classic trigeminal neuralgia

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Wang Y

2017-12-01

Full Text Available Yanping Wang,1 Congying Xu,1 Liping Zhai,1 Xudong Lu,1 Xiaoqiang Wu,1 Yahui Yi,2 Ziyun Liu,1 Qiaobing Guan,1 Xiaoling Zhang1 1Department of Neurology, the Second Hospital of Jiaxing City, Jiaxing, Zhejiang, 2Department of Radiology, the Second Hospital of Jiaxing City, Jiaxing, Zhejiang, China Abstract: Resting-state functional magnetic resonance imaging (R-fMRI signals are spatiotemporally organized. R-fMRI studies in patients with classic trigeminal neuralgia (CTN have suggested alterations in functional connectivity. However, far less attention has been given to investigations of the local oscillations and their frequency-specific changes in these patients. The objective of this study was to address this issue in patients with CTN. R-fMRI data from 17 patients with CTN and 19 age- and gender-matched healthy controls (HCs were analyzed using amplitude of low-frequency fluctuation (ALFF. The ALFF was computed across different frequencies (slow-4: 0.027–0.073 Hz; slow-5: 0.01–0.027 Hz; and typical band: 0.01–0.08 Hz in patients with CTN compared to HCs. In the typical band, patients with CTN showed increases of ALFF in bilateral temporal, occipital, and left middle frontal regions and in the left middle cingulate gyrus, as well as decreases of ALFF in the right inferior temporal region and in regions (medial prefrontal regions of default mode network. These significant group differences were identified in different sub-bands, with greater brainstem findings in higher frequencies (slow-4 and extensive default mode network and right postparietal results in lower frequencies (slow-5. Furthermore, significant relationships were found between subjective pain ratings and both amplitudes of higher frequency (slow-4 blood oxygen level-dependent (BOLD signals in pain localization brain regions and lower frequencies (slow-5 in pain signaling/modulating brain regions in the patients, and decreased ALFF within the prefrontal regions was significantly

Evolution of boldness and life-history in response to selective harvesting

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Andersen, Ken Haste; Marty, Lise; Arlinghaus, Robert

2018-01-01

Whether intensive harvesting alters the behavioral repertoire of exploited fishes is currently unknown, but plausible. We extend a fish life-history model to account for boldness as a personality trait that affects foraging intensity, which affects energy intake and risk from predation and fishing...... gear. We systematically investigate life-history and behavioral trait evolution along the boldness–timidity axis in response to the full range of common selectivity and exploitation patterns in fisheries. In agreement with previous studies, we find that any type of harvesting selects for fast life...... histories and that merely elevated, yet unselective, fishing mortality favors boldness. We also find that timid-selective fishing (which can be expected in species targeted by active gear types) selects for increased boldness. By contrast, increased timidity is predicted when fishing targets bolder...

Correlations of noninvasive BOLD and TOLD MRI with pO2 and relevance to tumor radiation response.

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Hallac, Rami R; Zhou, Heling; Pidikiti, Rajesh; Song, Kwang; Stojadinovic, Strahinja; Zhao, Dawen; Solberg, Timothy; Peschke, Peter; Mason, Ralph P

2014-05-01

To examine the potential use of blood oxygenation level dependent (BOLD) and tissue oxygenation level dependent (TOLD) contrast MRI to assess tumor oxygenation and predict radiation response. BOLD and TOLD MRI were performed on Dunning R3327-AT1 rat prostate tumors during hyperoxic gas breathing challenge at 4.7 T. Animals were divided into two groups. In Group 1 (n = 9), subsequent (19) F MRI based on spin lattice relaxation of hexafluorobenzene reporter molecule provided quantitative oximetry for comparison. For Group 2 rats (n = 13) growth delay following a single dose of 30 Gy was compared with preirradiation BOLD and TOLD assessments. Oxygen (100%O2 ) and carbogen (95%O2 /5%CO2 ) challenge elicited similar BOLD, TOLD and pO2 responses. Strong correlations were observed between BOLD or R2* response and quantitative (19) F pO2 measurements. TOLD response showed a general trend with weaker correlation. Irradiation caused a significant tumor growth delay and tumors with larger changes in TOLD and R1 values upon oxygen breathing exhibited significantly increased tumor growth delay. These results provide further insight into the relationships between oxygen sensitive (BOLD/TOLD) MRI and tumor pO2 . Moreover, a larger increase in R1 response to hyperoxic gas challenge coincided with greater tumor growth delay following irradiation. Copyright © 2013 Wiley Periodicals, Inc.

BOLD signal and functional connectivity associated with loving kindness meditation

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Garrison, Kathleen A; Scheinost, Dustin; Constable, R Todd; Brewer, Judson A

2014-01-01

Loving kindness is a form of meditation involving directed well-wishing, typically supported by the silent repetition of phrases such as “may all beings be happy,” to foster a feeling of selfless love. Here we used functional magnetic resonance imaging to assess the neural substrate of loving kindness meditation in experienced meditators and novices. We first assessed group differences in blood oxygen level-dependent (BOLD) signal during loving kindness meditation. We next used a relatively novel approach, the intrinsic connectivity distribution of functional connectivity, to identify regions that differ in intrinsic connectivity between groups, and then used a data-driven approach to seed-based connectivity analysis to identify which connections differ between groups. Our findings suggest group differences in brain regions involved in self-related processing and mind wandering, emotional processing, inner speech, and memory. Meditators showed overall reduced BOLD signal and intrinsic connectivity during loving kindness as compared to novices, more specifically in the posterior cingulate cortex/precuneus (PCC/PCu), a finding that is consistent with our prior work and other recent neuroimaging studies of meditation. Furthermore, meditators showed greater functional connectivity during loving kindness between the PCC/PCu and the left inferior frontal gyrus, whereas novices showed greater functional connectivity during loving kindness between the PCC/PCu and other cortical midline regions of the default mode network, the bilateral posterior insula lobe, and the bilateral parahippocampus/hippocampus. These novel findings suggest that loving kindness meditation involves a present-centered, selfless focus for meditators as compared to novices. PMID:24944863

Olfactory responses to natal stream water in sockeye salmon by BOLD fMRI.

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Hiroshi Bandoh

Full Text Available Many studies have shown that juvenile salmon imprint olfactory memory of natal stream odors during downstream migration, and adults recall this stream-specific odor information to discriminate their natal stream during upstream migration for spawning. The odor information processing of the natal stream in the salmon brain, however, has not been clarified. We applied blood oxygenation level-dependent (BOLD functional magnetic resonance imaging to investigate the odor information processing of the natal stream in the olfactory bulb and telencephalon of lacustrine sockeye salmon (Oncorhynchus nerka. The strong responses to the natal stream water were mainly observed in the lateral area of dorsal telencephalon (Dl, which are homologous to the medial pallium (hippocampus in terrestrial vertebrates. Although the concentration of L-serine (1 mM in the control water was 20,000-times higher than that of total amino acid in the natal stream water (47.5 nM, the BOLD signals resulting from the natal stream water were stronger than those by L-serine in the Dl. We concluded that sockeye salmon could process the odor information of the natal stream by integrating information in the Dl area of the telencephalon.

Spatiotopic coding of BOLD signal in human visual cortex depends on spatial attention.

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Sofia Crespi

Full Text Available The neural substrate of the phenomenological experience of a stable visual world remains obscure. One possible mechanism would be to construct spatiotopic neural maps where the response is selective to the position of the stimulus in external space, rather than to retinal eccentricities, but evidence for these maps has been inconsistent. Here we show, with fMRI, that when human subjects perform concomitantly a demanding attentive task on stimuli displayed at the fovea, BOLD responses evoked by moving stimuli irrelevant to the task were mostly tuned in retinotopic coordinates. However, under more unconstrained conditions, where subjects could attend easily to the motion stimuli, BOLD responses were tuned not in retinal but in external coordinates (spatiotopic selectivity in many visual areas, including MT, MST, LO and V6, agreeing with our previous fMRI study. These results indicate that spatial attention may play an important role in mediating spatiotopic selectivity.

Negative blood oxygen level dependent signals during speech comprehension.

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Rodriguez Moreno, Diana; Schiff, Nicholas D; Hirsch, Joy

2015-05-01

Speech comprehension studies have generally focused on the isolation and function of regions with positive blood oxygen level dependent (BOLD) signals with respect to a resting baseline. Although regions with negative BOLD signals in comparison to a resting baseline have been reported in language-related tasks, their relationship to regions of positive signals is not fully appreciated. Based on the emerging notion that the negative signals may represent an active function in language tasks, the authors test the hypothesis that negative BOLD signals during receptive language are more associated with comprehension than content-free versions of the same stimuli. Regions associated with comprehension of speech were isolated by comparing responses to passive listening to natural speech to two incomprehensible versions of the same speech: one that was digitally time reversed and one that was muffled by removal of high frequencies. The signal polarity was determined by comparing the BOLD signal during each speech condition to the BOLD signal during a resting baseline. As expected, stimulation-induced positive signals relative to resting baseline were observed in the canonical language areas with varying signal amplitudes for each condition. Negative BOLD responses relative to resting baseline were observed primarily in frontoparietal regions and were specific to the natural speech condition. However, the BOLD signal remained indistinguishable from baseline for the unintelligible speech conditions. Variations in connectivity between brain regions with positive and negative signals were also specifically related to the comprehension of natural speech. These observations of anticorrelated signals related to speech comprehension are consistent with emerging models of cooperative roles represented by BOLD signals of opposite polarity.

Searching for Conservation Laws in Brain Dynamics—BOLD Flux and Source Imaging

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Henning U. Voss

2014-07-01

Full Text Available Blood-oxygen-level-dependent (BOLD imaging is the most important noninvasive tool to map human brain function. It relies on local blood-flow changes controlled by neurovascular coupling effects, usually in response to some cognitive or perceptual task. In this contribution we ask if the spatiotemporal dynamics of the BOLD signal can be modeled by a conservation law. In analogy to the description of physical laws, which often can be derived from some underlying conservation law, identification of conservation laws in the brain could lead to new models for the functional organization of the brain. Our model is independent of the nature of the conservation law, but we discuss possible hints and motivations for conservation laws. For example, globally limited blood supply and local competition between brain regions for blood might restrict the large scale BOLD signal in certain ways that could be observable. One proposed selective pressure for the evolution of such conservation laws is the closed volume of the skull limiting the expansion of brain tissue by increases in blood volume. These ideas are demonstrated on a mental motor imagery fMRI experiment, in which functional brain activation was mapped in a group of volunteers imagining themselves swimming. In order to search for local conservation laws during this complex cognitive process, we derived maps of quantities resulting from spatial interaction of the BOLD amplitudes. Specifically, we mapped fluxes and sources of the BOLD signal, terms that would appear in a description by a continuity equation. Whereas we cannot present final answers with the particular analysis of this particular experiment, some results seem to be non-trivial. For example, we found that during task the group BOLD flux covered more widespread regions than identified by conventional BOLD mapping and was always increasing during task. It is our hope that these results motivate more work towards the search for conservation

Functional BOLD MRI: comparison of different field strengths in a motor task

International Nuclear Information System (INIS)

Meindl, T.; Born, C.; Britsch, S.; Reiser, M.; Schoenberg, S.

2008-01-01

The purpose was to evaluate the benefit of an increased field strength for functional magnetic resonance imaging in a motor task. Six right-handed volunteers were scanned at 1.5 T and 3.0 T using a motor task. Each experiment consisted of two runs with four activation blocks, each with right- and left-hand tapping. Analysis was done using BrainVoyagerQX registered . Differences between both field strengths concerning signal to noise (SNR), blood oxygen level-dependent (BOLD) signal change, functional sensitivity and BOLD contrast to noise (CNR) were tested using a paired t test. Delineation of activations and artifacts were graded by two independent readers. Results were further validated by means of a phantom study. The sensorimotor and premotor cortex, the supplementary motor area, subcortical and cerebellar structures were activated at each field strength. Additional activations of the right premotor cortex and right superior temporal gyrus were found at 3.0 T. Signal-to-noise, percentage of BOLD signal change, BOLD CNR and functional sensitivity improved at 3.0 T by a factor of up to 2.4. Functional imaging at 3.0 T results in detection of additional activated areas, increased SNR, BOLD signal change, functional sensitivity and BOLD CNR. (orig.)

Systematic protocol for assessment of the validity of BOLD MRI in a rabbit model of inflammatory arthritis at 1.5 tesla

Energy Technology Data Exchange (ETDEWEB)

Chan, Michael W.; Nathanael, George; Kis, Antonella; Amirabadi, Afsaneh; Zhong, Anguo; Rayner, Tammy; Weiss, Ruth; Detzler, Garry; Gahunia, Harpal [The Hospital for Sick Children, Department of Diagnostic Imaging, Toronto (Canada); Jong, Roland [Mount Sinai Hospital, Department of Pathology and Laboratory Medicine, Toronto (Canada); Moineddin, Rahim [Family and Community Medicine, Department of Public Health, Toronto (Canada); Crawley, Adrian [University of Toronto, Department of Medical Imaging, Toronto (Canada); Toronto Western Hospital, Department of Medical Imaging, Toronto (Canada); Doria, Andrea S. [The Hospital for Sick Children, Department of Diagnostic Imaging, Toronto (Canada); University of Toronto, Department of Medical Imaging, Toronto (Canada)

2014-05-15

Blood-oxygen-level-dependent (BOLD) MRI has the potential to identify regions of early hypoxic and vascular joint changes in inflammatory arthritis. There is no standard protocol for analysis of BOLD MRI measurements in musculoskeletal disorders. To optimize the following BOLD MRI reading parameters: (1) statistical threshold values (low, r > 0.01 versus high, r > 0.2); (2) summary measures of BOLD contrast (percentage of activated voxels [PT%] versus percentage signal difference between on-and-off signal intensities [diff{sub o}n{sub o}ff]); and (3) direction of BOLD response (positive, negative and positive + negative). Using BOLD MRI protocols at 1.5 T, arthritic (n = 21) and contralateral (n = 21) knees of 21 juvenile rabbits were imaged at baseline and on days 1, 14 and 28 after a unilateral intra-articular injection of carrageenan. Nine non-injected rabbits served as external control knees (n = 18). By comparing arthritic to contralateral knees, receiver operating characteristic curves were used to determine diagnostic accuracy. Using diff{sub o}n{sub o}ff and positive + negative responses, a threshold of r > 0.01 was more accurate than r > 0.2 (P = 0.03 at day 28). Comparison of summary measures yielded no statistically significant difference (P > 0.05). Although positive + negative (AUC = 0.86 at day 28) and negative responses (AUC = 0.90 at day 28) for PT% were the most diagnostically accurate, positive + negative responses for diff{sub o}n{sub o}ff (AUC = 0.78 at day 28) also had acceptable accuracy. The most clinically relevant reading parameters included a lower threshold of r > 0.01 and a positive + negative BOLD response. We propose that diff{sub o}n{sub o}ff is a more clinically relevant summary measure of BOLD MRI, while PT% can be used as an ancillary measure. (orig.)

Approaches to brain stress testing: BOLD magnetic resonance imaging with computer-controlled delivery of carbon dioxide.

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W Alan C Mutch

Full Text Available BACKGROUND: An impaired vascular response in the brain regionally may indicate reduced vascular reserve and vulnerability to ischemic injury. Changing the carbon dioxide (CO(2 tension in arterial blood is commonly used as a cerebral vasoactive stimulus to assess the cerebral vascular response, changing cerebral blood flow (CBF by up to 5-11 percent/mmHg in normal adults. Here we describe two approaches to generating the CO(2 challenge using a computer-controlled gas blender to administer: i a square wave change in CO(2 and, ii a ramp stimulus, consisting of a continuously graded change in CO(2 over a range. Responses were assessed regionally by blood oxygen level dependent (BOLD magnetic resonance imaging (MRI. METHODOLOGY/PRINCIPAL FINDINGS: We studied 8 patients with known cerebrovascular disease (carotid stenosis or occlusion and 2 healthy subjects. The square wave stimulus was used to study the dynamics of the vascular response, while the ramp stimulus assessed the steady-state response to CO(2. Cerebrovascular reactivity (CVR maps were registered by color coding and overlaid on the anatomical scans generated with 3 Tesla MRI to assess the corresponding BOLD signal change/mmHg change in CO(2, voxel-by-voxel. Using a fractal temporal approach, detrended fluctuation analysis (DFA maps of the processed raw BOLD signal per voxel over the same CO(2 range were generated. Regions of BOLD signal decrease with increased CO(2 (coded blue were seen in all of these high-risk patients, indicating regions of impaired CVR. All patients also demonstrated regions of altered signal structure on DFA maps (Hurst exponents less than 0.5; coded blue indicative of anti-persistent noise. While 'blue' CVR maps remained essentially stable over the time of analysis, 'blue' DFA maps improved. CONCLUSIONS/SIGNIFICANCE: This combined dual stimulus and dual analysis approach may be complementary in identifying vulnerable brain regions and thus constitute a regional as

Measurement of oxygen extraction fraction (OEF): An optimized BOLD signal model for use with hypercapnic and hyperoxic calibration.

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Merola, Alberto; Murphy, Kevin; Stone, Alan J; Germuska, Michael A; Griffeth, Valerie E M; Blockley, Nicholas P; Buxton, Richard B; Wise, Richard G

2016-04-01

Several techniques have been proposed to estimate relative changes in cerebral metabolic rate of oxygen consumption (CMRO2) by exploiting combined BOLD fMRI and cerebral blood flow data in conjunction with hypercapnic or hyperoxic respiratory challenges. More recently, methods based on respiratory challenges that include both hypercapnia and hyperoxia have been developed to assess absolute CMRO2, an important parameter for understanding brain energetics. In this paper, we empirically optimize a previously presented "original calibration model" relating BOLD and blood flow signals specifically for the estimation of oxygen extraction fraction (OEF) and absolute CMRO2. To do so, we have created a set of synthetic BOLD signals using a detailed BOLD signal model to reproduce experiments incorporating hypercapnic and hyperoxic respiratory challenges at 3T. A wide range of physiological conditions was simulated by varying input parameter values (baseline cerebral blood volume (CBV0), baseline cerebral blood flow (CBF0), baseline oxygen extraction fraction (OEF0) and hematocrit (Hct)). From the optimization of the calibration model for estimation of OEF and practical considerations of hypercapnic and hyperoxic respiratory challenges, a new "simplified calibration model" is established which reduces the complexity of the original calibration model by substituting the standard parameters α and β with a single parameter θ. The optimal value of θ is determined (θ=0.06) across a range of experimental respiratory challenges. The simplified calibration model gives estimates of OEF0 and absolute CMRO2 closer to the true values used to simulate the experimental data compared to those estimated using the original model incorporating literature values of α and β. Finally, an error propagation analysis demonstrates the susceptibility of the original and simplified calibration models to measurement errors and potential violations in the underlying assumptions of isometabolism

Detecting Activation in fMRI Data: An Approach Based on Sparse Representation of BOLD Signal

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Blanca Guillen

2018-01-01

Full Text Available This paper proposes a simple yet effective approach for detecting activated voxels in fMRI data by exploiting the inherent sparsity property of the BOLD signal in temporal and spatial domains. In the time domain, the approach combines the General Linear Model (GLM with a Least Absolute Deviation (LAD based regression method regularized by the pseudonorm l0 to promote sparsity in the parameter vector of the model. In the spatial domain, detection of activated regions is based on thresholding the spatial map of estimated parameters associated with a particular stimulus. The threshold is calculated by exploiting the sparseness of the BOLD signal in the spatial domain assuming a Laplacian distribution model. The proposed approach is validated using synthetic and real fMRI data. For synthetic data, results show that the proposed approach is able to detect most activated voxels without any false activation. For real data, the method is evaluated through comparison with the SPM software. Results indicate that this approach can effectively find activated regions that are similar to those found by SPM, but using a much simpler approach. This study may lead to the development of robust spatial approaches to further simplifying the complexity of classical schemes.

BOLD Granger causality reflects vascular anatomy.

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J Taylor Webb

Full Text Available A number of studies have tried to exploit subtle phase differences in BOLD time series to resolve the order of sequential activation of brain regions, or more generally the ability of signal in one region to predict subsequent signal in another region. More recently, such lag-based measures have been applied to investigate directed functional connectivity, although this application has been controversial. We attempted to use large publicly available datasets (FCON 1000, ADHD 200, Human Connectome Project to determine whether consistent spatial patterns of Granger Causality are observed in typical fMRI data. For BOLD datasets from 1,240 typically developing subjects ages 7-40, we measured Granger causality between time series for every pair of 7,266 spherical ROIs covering the gray matter and 264 seed ROIs at hubs of the brain's functional network architecture. Granger causality estimates were strongly reproducible for connections in a test and replication sample (n=620 subjects for each group, as well as in data from a single subject scanned repeatedly, both during resting and passive video viewing. The same effect was even stronger in high temporal resolution fMRI data from the Human Connectome Project, and was observed independently in data collected during performance of 7 task paradigms. The spatial distribution of Granger causality reflected vascular anatomy with a progression from Granger causality sources, in Circle of Willis arterial inflow distributions, to sinks, near large venous vascular structures such as dural venous sinuses and at the periphery of the brain. Attempts to resolve BOLD phase differences with Granger causality should consider the possibility of reproducible vascular confounds, a problem that is independent of the known regional variability of the hemodynamic response.

Hypercapnic normalization of BOLD fMRI: comparison across field strengths and pulse sequences

DEFF Research Database (Denmark)

Cohen, Eric R.; Rostrup, Egill; Sidaros, Karam

2004-01-01

to be more accurately localized and quantified based on changes in venous blood oxygenation alone. The normalized BOLD signal induced by the motor task was consistent across different magnetic fields and pulse sequences, and corresponded well with cerebral blood flow measurements. Our data suggest...... size, as well as experimental, such as pulse sequence and static magnetic field strength (B(0)). Thus, it is difficult to compare task-induced fMRI signals across subjects, field strengths, and pulse sequences. This problem can be overcome by normalizing the neural activity-induced BOLD fMRI response...... for global stimulation, subjects breathed a 5% CO(2) gas mixture. Under all conditions, voxels containing primarily large veins and those containing primarily active tissue (i.e., capillaries and small veins) showed distinguishable behavior after hypercapnic normalization. This allowed functional activity...

Hemodynamic modelling of BOLD fMRI - A machine learning approach

DEFF Research Database (Denmark)

Jacobsen, Danjal Jakup

2007-01-01

This Ph.D. thesis concerns the application of machine learning methods to hemodynamic models for BOLD fMRI data. Several such models have been proposed by different researchers, and they have in common a basis in physiological knowledge of the hemodynamic processes involved in the generation...... of the BOLD signal. The BOLD signal is modelled as a non-linear function of underlying, hidden (non-measurable) hemodynamic state variables. The focus of this thesis work has been to develop methods for learning the parameters of such models, both in their traditional formulation, and in a state space...... formulation. In the latter, noise enters at the level of the hidden states, as well as in the BOLD measurements themselves. A framework has been developed to allow approximate posterior distributions of model parameters to be learned from real fMRI data. This is accomplished with Markov chain Monte Carlo...

MEG and fMRI fusion for nonlinear estimation of neural and BOLD signal changes

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Sergey M Plis

2010-11-01

Full Text Available The combined analysis of MEG/EEG and functional MRI measurements can lead to improvement in the description of the dynamical and spatial properties of brain activity. In this paper we empirically demonstrate this improvement using simulated and recorded task related MEG and fMRI activity. Neural activity estimates were derived using a dynamic Bayesian network with continuous real valued parameters by means of a sequential Monte Carlo technique. In synthetic data, we show that MEG and fMRI fusion improves estimation of the indirectly observed neural activity and smooths tracking of the BOLD response. In recordings of task related neural activity the combination of MEG and fMRI produces a result with greater SNR, that confirms the expectation arising from the nature of the experiment. The highly nonlinear model of the BOLD response poses a difficult inference problem for neural activity estimation; computational requirements are also high due to the time and space complexity. We show that joint analysis of the data improves the system's behavior by stabilizing the differential equations system and by requiring fewer computational resources.

Quantifying the microvascular origin of BOLD-fMRI from first principles with two-photon microscopy and an oxygen-sensitive nanoprobe.

Science.gov (United States)

Gagnon, Louis; Sakadžić, Sava; Lesage, Frédéric; Musacchia, Joseph J; Lefebvre, Joël; Fang, Qianqian; Yücel, Meryem A; Evans, Karleyton C; Mandeville, Emiri T; Cohen-Adad, Jülien; Polimeni, Jonathan R; Yaseen, Mohammad A; Lo, Eng H; Greve, Douglas N; Buxton, Richard B; Dale, Anders M; Devor, Anna; Boas, David A

2015-02-25

The blood oxygenation level-dependent (BOLD) contrast is widely used in functional magnetic resonance imaging (fMRI) studies aimed at investigating neuronal activity. However, the BOLD signal reflects changes in blood volume and oxygenation rather than neuronal activity per se. Therefore, understanding the transformation of microscopic vascular behavior into macroscopic BOLD signals is at the foundation of physiologically informed noninvasive neuroimaging. Here, we use oxygen-sensitive two-photon microscopy to measure the BOLD-relevant microvascular physiology occurring within a typical rodent fMRI voxel and predict the BOLD signal from first principles using those measurements. The predictive power of the approach is illustrated by quantifying variations in the BOLD signal induced by the morphological folding of the human cortex. This framework is then used to quantify the contribution of individual vascular compartments and other factors to the BOLD signal for different magnet strengths and pulse sequences. Copyright © 2015 the authors 0270-6474/15/353663-13$15.00/0.

Volumetric BOLD fMRI simulation: from neurovascular coupling to multivoxel imaging

International Nuclear Information System (INIS)

Chen, Zikuan; Calhoun, Vince

2012-01-01

The blood oxygenation-level dependent (BOLD) functional magnetic resonance imaging (fMRI) modality has been numerically simulated by calculating single voxel signals. However, the observation on single voxel signals cannot provide information regarding the spatial distribution of the signals. Specifically, a single BOLD voxel signal simulation cannot answer the fundamental question: is the magnetic resonance (MR) image a replica of its underling magnetic susceptibility source? In this paper, we address this problem by proposing a multivoxel volumetric BOLD fMRI simulation model and a susceptibility expression formula for linear neurovascular coupling process, that allow us to examine the BOLD fMRI procedure from neurovascular coupling to MR image formation. Since MRI technology only senses the magnetism property, we represent a linear neurovascular-coupled BOLD state by a magnetic susceptibility expression formula, which accounts for the parameters of cortical vasculature, intravascular blood oxygenation level, and local neuroactivity. Upon the susceptibility expression of a BOLD state, we carry out volumetric BOLD fMRI simulation by calculating the fieldmap (established by susceptibility magnetization) and the complex multivoxel MR image (by intravoxel dephasing). Given the predefined susceptibility source and the calculated complex MR image, we compare the MR magnitude (phase, respectively) image with the predefined susceptibility source (the calculated fieldmap) by spatial correlation. The spatial correlation between the MR magnitude image and the magnetic susceptibility source is about 0.90 for the settings of T E = 30 ms, B 0 = 3 T, voxel size = 100 micron, vessel radius = 3 micron, and blood volume fraction = 2%. Using these parameters value, the spatial correlation between the MR phase image and the susceptibility-induced fieldmap is close to 1.00. Our simulation results show that the MR magnitude image is not an exact replica of the magnetic susceptibility

Distinct BOLD activation profiles following central and peripheral oxytocin administration in awake rats

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Craig F Ferris

2015-09-01

Full Text Available A growing body of literature has suggested that intranasal oxytocin (OT or other systemic routes of administration can alter prosocial behavior, presumably by directly activating OT sensitive neural circuits in the brain. Yet there is no clear evidence that OT given peripherally can cross the blood-brain-barrier at levels sufficient to engage the OT receptor. To address this issue we examined changes in blood oxygen level dependent (BOLD signal intensity in response to peripheral OT injections (0.1, 0.5 or 2.5 mg/kg during functional magnetic resonance (fMRI in awake rats imaged at 7.0 tesla. These data were compared to OT (1ug/5 µl given directly to the brain via the lateral cerebroventricle. Using a 3D annotated MRI atlas of the rat brain segmented into 171 brain areas and computational analysis we reconstructed the distributed integrated neural circuits identified with BOLD fMRI following central and peripheral OT. Both routes of administration caused significant changes in BOLD signal within the first 10 min of administration. As expected, central OT activated a majority of brain areas known to express a high density of OT receptors e.g., lateral septum, subiculum, shell of the accumbens, bed nucleus of the stria terminalis. This profile of activation was not matched by peripheral OT. The change in BOLD signal to peripheral OT did not show any discernible dose-response. Interestingly, peripheral OT affected all subdivisions of the olfactory bulb, in addition to the cerebellum and several brainstem areas relevant to the autonomic nervous system, including the solitary tract nucleus. The results from this imaging study do not support a direct central action of peripheral OT on the brain. Instead, the patterns of brain activity suggest that peripheral OT may interact at the level of the olfactory bulb and through sensory afferents from the autonomic nervous system to influence brain activity.

Distinct BOLD Activation Profiles Following Central and Peripheral Oxytocin Administration in Awake Rats.

Science.gov (United States)

Ferris, Craig F; Yee, Jason R; Kenkel, William M; Dumais, Kelly Marie; Moore, Kelsey; Veenema, Alexa H; Kulkarni, Praveen; Perkybile, Allison M; Carter, C Sue

2015-01-01

A growing body of literature has suggested that intranasal oxytocin (OT) or other systemic routes of administration can alter prosocial behavior, presumably by directly activating OT sensitive neural circuits in the brain. Yet there is no clear evidence that OT given peripherally can cross the blood-brain barrier at levels sufficient to engage the OT receptor. To address this issue we examined changes in blood oxygen level-dependent (BOLD) signal intensity in response to peripheral OT injections (0.1, 0.5, or 2.5 mg/kg) during functional magnetic resonance imaging (fMRI) in awake rats imaged at 7.0 T. These data were compared to OT (1 μg/5 μl) given directly to the brain via the lateral cerebroventricle. Using a 3D annotated MRI atlas of the rat brain segmented into 171 brain areas and computational analysis, we reconstructed the distributed integrated neural circuits identified with BOLD fMRI following central and peripheral OT. Both routes of administration caused significant changes in BOLD signal within the first 10 min of administration. As expected, central OT activated a majority of brain areas known to express a high density of OT receptors, e.g., lateral septum, subiculum, shell of the accumbens, bed nucleus of the stria terminalis. This profile of activation was not matched by peripheral OT. The change in BOLD signal to peripheral OT did not show any discernible dose-response. Interestingly, peripheral OT affected all subdivisions of the olfactory bulb, in addition to the cerebellum and several brainstem areas relevant to the autonomic nervous system, including the solitary tract nucleus. The results from this imaging study do not support a direct central action of peripheral OT on the brain. Instead, the patterns of brain activity suggest that peripheral OT may interact at the level of the olfactory bulb and through sensory afferents from the autonomic nervous system to influence brain activity.

Mapping glucose-mediated gut-to-brain signalling pathways in humans.

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Little, Tanya J; McKie, Shane; Jones, Richard B; D'Amato, Massimo; Smith, Craig; Kiss, Orsolya; Thompson, David G; McLaughlin, John T

2014-08-01

Previous fMRI studies have demonstrated that glucose decreases the hypothalamic BOLD response in humans. However, the mechanisms underlying the CNS response to glucose have not been defined. We recently demonstrated that the slowing of gastric emptying by glucose is dependent on activation of the gut peptide cholecystokinin (CCK1) receptor. Using physiological functional magnetic resonance imaging this study aimed to determine the whole brain response to glucose, and whether CCK plays a central role. Changes in blood oxygenation level-dependent (BOLD) signal were monitored using fMRI in 12 healthy subjects following intragastric infusion (250ml) of: 1M glucose+predosing with dexloxiglumide (CCK1 receptor antagonist), 1M glucose+placebo, or 0.9% saline (control)+placebo, in a single-blind, randomised fashion. Gallbladder volume, blood glucose, insulin, and GLP-1 and CCK concentrations were determined. Hunger, fullness and nausea scores were also recorded. Intragastric glucose elevated plasma glucose, insulin, and GLP-1, and reduced gall bladder volume (an in vivo assay for CCK secretion). Glucose decreased BOLD signal, relative to saline, in the brainstem and hypothalamus as well as the cerebellum, right occipital cortex, putamen and thalamus. The timing of the BOLD signal decrease was negatively correlated with the rise in blood glucose and insulin levels. The glucose+dex arm highlighted a CCK1-receptor dependent increase in BOLD signal only in the motor cortex. Glucose induces site-specific differences in BOLD response in the human brain; the brainstem and hypothalamus show a CCK1 receptor-independent reduction which is likely to be mediated by a circulatory effect of glucose and insulin, whereas the motor cortex shows an early dexloxiglumide-reversible increase in signal, suggesting a CCK1 receptor-dependent neural pathway. Copyright © 2014. Published by Elsevier Inc.

Mapping glucose-mediated gut-to-brain signalling pathways in humans☆

Science.gov (United States)

Little, Tanya J.; McKie, Shane; Jones, Richard B.; D'Amato, Massimo; Smith, Craig; Kiss, Orsolya; Thompson, David G.; McLaughlin, John T.

2014-01-01

Objectives Previous fMRI studies have demonstrated that glucose decreases the hypothalamic BOLD response in humans. However, the mechanisms underlying the CNS response to glucose have not been defined. We recently demonstrated that the slowing of gastric emptying by glucose is dependent on activation of the gut peptide cholecystokinin (CCK1) receptor. Using physiological functional magnetic resonance imaging this study aimed to determine the whole brain response to glucose, and whether CCK plays a central role. Experimental design Changes in blood oxygenation level-dependent (BOLD) signal were monitored using fMRI in 12 healthy subjects following intragastric infusion (250 ml) of: 1 M glucose + predosing with dexloxiglumide (CCK1 receptor antagonist), 1 M glucose + placebo, or 0.9% saline (control) + placebo, in a single-blind, randomised fashion. Gallbladder volume, blood glucose, insulin, and GLP-1 and CCK concentrations were determined. Hunger, fullness and nausea scores were also recorded. Principal observations Intragastric glucose elevated plasma glucose, insulin, and GLP-1, and reduced gall bladder volume (an in vivo assay for CCK secretion). Glucose decreased BOLD signal, relative to saline, in the brainstem and hypothalamus as well as the cerebellum, right occipital cortex, putamen and thalamus. The timing of the BOLD signal decrease was negatively correlated with the rise in blood glucose and insulin levels. The glucose + dex arm highlighted a CCK1-receptor dependent increase in BOLD signal only in the motor cortex. Conclusions Glucose induces site-specific differences in BOLD response in the human brain; the brainstem and hypothalamus show a CCK1 receptor-independent reduction which is likely to be mediated by a circulatory effect of glucose and insulin, whereas the motor cortex shows an early dexloxiglumide-reversible increase in signal, suggesting a CCK1 receptor-dependent neural pathway. PMID:24685436

Exploiting magnetic resonance angiography imaging improves model estimation of BOLD signal.

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Zhenghui Hu

Full Text Available The change of BOLD signal relies heavily upon the resting blood volume fraction ([Formula: see text] associated with regional vasculature. However, existing hemodynamic data assimilation studies pretermit such concern. They simply assign the value in a physiologically plausible range to get over ill-conditioning of the assimilation problem and fail to explore actual [Formula: see text]. Such performance might lead to unreliable model estimation. In this work, we present the first exploration of the influence of [Formula: see text] on fMRI data assimilation, where actual [Formula: see text] within a given cortical area was calibrated by an MR angiography experiment and then was augmented into the assimilation scheme. We have investigated the impact of [Formula: see text] on single-region data assimilation and multi-region data assimilation (dynamic cause modeling, DCM in a classical flashing checkerboard experiment. Results show that the employment of an assumed [Formula: see text] in fMRI data assimilation is only suitable for fMRI signal reconstruction and activation detection grounded on this signal, and not suitable for estimation of unobserved states and effective connectivity study. We thereby argue that introducing physically realistic [Formula: see text] in the assimilation process may provide more reliable estimation of physiological information, which contributes to a better understanding of the underlying hemodynamic processes. Such an effort is valuable and should be well appreciated.

Arm-in-Arm Response Regulator Dimers Promote Intermolecular Signal Transduction

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Baker, Anna W.; Satyshur, Kenneth A.; Morales, Neydis Moreno; Forest, Katrina T. (UW)

2016-02-01

Bacteriophytochrome photoreceptors (BphPs) and their cognate response regulators make up two-component signal transduction systems which direct bacteria to mount phenotypic responses to changes in environmental light quality. Most of these systems utilize single-domain response regulators to transduce signals through unknown pathways and mechanisms. Here we describe the photocycle and autophosphorylation kinetics of RtBphP1, a red light-regulated histidine kinase from the desert bacteriumRamlibacter tataouinensis. RtBphP1 undergoes red to far-red photoconversion with rapid thermal reversion to the dark state. RtBphP1 is autophosphorylated in the dark; this activity is inhibited under red light. The RtBphP1 cognate response regulator, theR. tataouinensisbacteriophytochrome response regulator (RtBRR), and a homolog, AtBRR fromAgrobacterium tumefaciens, crystallize unexpectedly as arm-in-arm dimers, reliant on a conserved hydrophobic motif, hFWAhL (where h is a hydrophobic M, V, L, or I residue). RtBRR and AtBRR dimerize distinctly from four structurally characterized phytochrome response regulators found in photosynthetic organisms and from all other receiver domain homodimers in the Protein Data Bank. A unique cacodylate-zinc-histidine tag metal organic framework yielded single-wavelength anomalous diffraction phases and may be of general interest. Examination of the effect of the BRR stoichiometry on signal transduction showed that phosphorylated RtBRR is accumulated more efficiently than the engineered monomeric RtBRR (RtBRR_mon) in phosphotransfer reactions. Thus, we conclude that arm-in-arm dimers are a relevant signaling intermediate in this class of two-component regulatory systems.

<bold>IMPORTANCE

BOLD Imaging in Awake Wild-Type and Mu-Opioid Receptor Knock-Out Mice Reveals On-Target Activation Maps in Response to Oxycodone

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Kelsey Moore

2016-11-01

Full Text Available Blood oxygen level dependent (BOLD imaging in awake mice was used to identify differences in brain activity between wild-type, and Mu (µ opioid receptor knock-outs (MuKO in response to oxycodone (OXY. Using a segmented, annotated MRI mouse atlas and computational analysis, patterns of integrated positive and negative BOLD activity were identified across 122 brain areas. The pattern of positive BOLD showed enhanced activation across the brain in WT mice within 15 min of intraperitoneal administration of 2.5 mg of OXY. BOLD activation was detected in 72 regions out of 122, and was most prominent in areas of high µ opioid receptor density (thalamus, ventral tegmental area, substantia nigra, caudate putamen, basal amygdala and hypothalamus, and focus on pain circuits indicated strong activation in major pain processing centers (central amygdala, solitary tract, parabrachial area, insular cortex, gigantocellularis area, ventral thalamus primary sensory cortex and prelimbic cortex. Importantly, the OXY-induced positive BOLD was eliminated in MuKO mice in most regions, with few exceptions (some cerebellar nuclei, CA3 of the hippocampus, medial amygdala and preoptic areas. This result indicates that most effects of OXY on positive BOLD are mediated by the µ opioid receptor (on-target effects. OXY also caused an increase in negative BOLD in WT mice in few regions (16 out of 122 and, unlike the positive BOLD response the negative BOLD was only partially eliminated in the MuKO mice (cerebellum, and in some case intensified (hippocampus. Negative BOLD analysis therefore shows activation and deactivation events in the absence of the µ receptor for some areas where receptor expression is normally extremely low or absent (off-target effects. Together, our approach permits establishing opioid-induced BOLD activation maps in awake mice. In addition, comparison of WT and MuKO mutant mice reveals both on-target and off-target activation events, and set an OXY

Larger Neural Responses Produce BOLD Signals That Begin Earlier in Time

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Serena eThompson

2014-06-01

Full Text Available Functional MRI analyses commonly rely on the assumption that the temporal dynamics of hemodynamic response functions (HRFs are independent of the amplitude of the neural signals that give rise to them. The validity of this assumption is particularly important for techniques that use fMRI to resolve sub-second timing distinctions between responses, in order to make inferences about the ordering of neural processes. Whether or not the detailed shape of the HRF is independent of neural response amplitude remains an open question, however. We performed experiments in which we measured responses in primary visual cortex (V1 to large, contrast-reversing checkerboards at a range of contrast levels, which should produce varying amounts of neural activity. Ten subjects (ages 22-52 were studied in each of two experiments using 3 Tesla scanners. We used rapid, 250 msec, temporal sampling (repetition time, or TR and both short and long inter-stimulus interval (ISI stimulus presentations. We tested for a systematic relationship between the onset of the HRF and its amplitude across conditions, and found a strong negative correlation between the two measures when stimuli were separated in time (long- and medium-ISI experiments, but not the short-ISI experiment. Thus, stimuli that produce larger neural responses, as indexed by HRF amplitude, also produced HRFs with shorter onsets. The relationship between amplitude and latency was strongest in voxels with lowest mean-normalized variance (i.e., parenchymal voxels. The onset differences observed in the longer-ISI experiments are likely attributable to mechanisms of neurovascular coupling, since they are substantially larger than reported differences in the onset of action potentials in V1 as a function of response amplitude.

Co-localization between the BOLD response and epileptiform discharges recorded by simultaneous intracranial EEG-fMRI at 3 T

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Yahya Aghakhani

2015-01-01

Conclusions: iEEG-fMRI is a feasible and low-risk method for assessment of hemodynamic changes of very focal IEDs that may not be recorded by scalp EEG. A high concordance rate between the location of the BOLD response and IEDs was seen for mesial temporal (6/7 IEDs. Significant BOLD activation was also seen in areas distant from the active electrode and these sites exhibited maximal BOLD activation in the majority of cases. This implies that iEEG-fMRI may further describe the areas involved in the generation of IEDs beyond the vicinity of the electrode(s.

Increased BOLD activation to predator stressor in subiculum and midbrain of amphetamine-sensitized maternal rats.

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Febo, Marcelo; Pira, Ashley S

2011-03-25

Amphetamine, which is known to cause sensitization, potentiates the hormonal and neurobiological signatures of stress and may also increase sensitivity to stress-inducing stimuli in limbic areas. Trimethylthiazoline (5μL TMT) is a chemical constituent of fox feces that evokes innate fear and activates the neuronal and hormonal signatures of stress in rats. We used blood oxygen level dependent (BOLD) MRI to test whether amphetamine sensitization (1mg/kg, i.p. ×3days) in female rats has a lasting effect on the neural response to a stress-evoking stimulus, the scent of a predator, during the postpartum period. The subiculum and dopamine-enriched midbrain VTA/SN of amphetamine-sensitized but not control mothers showed a greater BOLD signal response to predator odor than a control putrid scent. The greater responsiveness of these two brain regions following stimulant sensitization might impact neural processing in response to stressors in the maternal brain. Copyright © 2010 Elsevier B.V. All rights reserved.

Sustained negative BOLD response in human fMRI finger tapping task.

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Liu, Yadong; Shen, Hui; Zhou, Zongtan; Hu, Dewen

2011-01-01

In this work, we investigated the sustained negative blood oxygen level-dependent (BOLD) response (sNBR) using functional magnetic resonance imaging during a finger tapping task. We observed that the sNBR for this task was more extensive than has previously been reported. The cortical regions involved in sNBR are divided into the following three groups: frontal, somatosensory and occipital. By investigating the spatial structure, area, amplitude, and dynamics of the sNBR in comparison with those of its positive BOLD response (PBR) counterpart, we made the following observations. First, among the three groups, the somatosensory group contained the greatest number of activated voxels and the fewest deactivated voxels. In addition, the amplitude of the sNBR in this group was the smallest among the three groups. Second, the onset and peak time of the sNBR are both larger than those of the PBR, whereas the falling edge time of the sNBR is less than that of the PBR. Third, the long distance between most sNBR foci and their corresponding PBR foci makes it unlikely that they share the same blood supply artery. Fourth, the couplings between the sNBR and its PBR counterpart are distinct among different regions and thus should be investigated separately. These findings imply that the origin of most sNBR foci in the finger-tapping task is much more likely to be neuronal activity suppression rather than "blood steal."

Sustained negative BOLD response in human fMRI finger tapping task.

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Yadong Liu

Full Text Available In this work, we investigated the sustained negative blood oxygen level-dependent (BOLD response (sNBR using functional magnetic resonance imaging during a finger tapping task. We observed that the sNBR for this task was more extensive than has previously been reported. The cortical regions involved in sNBR are divided into the following three groups: frontal, somatosensory and occipital. By investigating the spatial structure, area, amplitude, and dynamics of the sNBR in comparison with those of its positive BOLD response (PBR counterpart, we made the following observations. First, among the three groups, the somatosensory group contained the greatest number of activated voxels and the fewest deactivated voxels. In addition, the amplitude of the sNBR in this group was the smallest among the three groups. Second, the onset and peak time of the sNBR are both larger than those of the PBR, whereas the falling edge time of the sNBR is less than that of the PBR. Third, the long distance between most sNBR foci and their corresponding PBR foci makes it unlikely that they share the same blood supply artery. Fourth, the couplings between the sNBR and its PBR counterpart are distinct among different regions and thus should be investigated separately. These findings imply that the origin of most sNBR foci in the finger-tapping task is much more likely to be neuronal activity suppression rather than "blood steal."

To be so bold: boldness is repeatable and related to within individual behavioural variability in North Island robins.

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He, Ruchuan; Pagani-Núñez, Emilio; Chevallier, Clément; Barnett, Craig R A

2017-07-01

Behavioural research traditionally focusses on the mean responses of a group of individuals rather than variation in behaviour around the mean or among individuals. However, examining the variation in behaviour among and within individuals may also yield important insights into the evolution and maintenance of behaviour. Repeatability is the most commonly used measure of variability among individuals in behavioural research. However, there are other forms of variation within populations that have received less attention. One such measure is intraindividual variation in behaviour (IIV), which is a short-term fluctuation of within-individual behaviour. Such variation in behaviour might be important during interactions because it could decrease the ability of conspecific and heterospecific individuals to predict the behaviour of the subject, thus increasing the cost of the interaction. In this experiment, we made repeated measures of the latency of North Island robins to attack a prey in a novel situation (a form of boldness) and examined (i) repeatability of boldness (the propensity to take a risk), (ii) IIV of boldness, and (iii) whether there was a significant relationship between these two traits (a behavioural syndrome). We found that boldness was highly repeatable, that there were high levels of IIV in boldness, and that there was a negative relationship between boldness and IIV in boldness. This suggests that despite high levels of repeatability for this behaviour, there were also still significant differences in IIV among different individuals within the population. Moreover, bolder individuals had significantly less IIV in their boldness, which suggests that they were forming routines (which reduces behavioural variability) compared to shyer individuals. Our results definitively demonstrate that IIV itself varies across individuals and is linked with key behavioural traits, and we argue for the importance of future studies aimed at understanding its causes

Serotonin 2A Receptor Signaling Underlies LSD-induced Alteration of the Neural Response to Dynamic Changes in Music.

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Barrett, Frederick S; Preller, Katrin H; Herdener, Marcus; Janata, Petr; Vollenweider, Franz X

2017-09-28

Classic psychedelic drugs (serotonin 2A, or 5HT2A, receptor agonists) have notable effects on music listening. In the current report, blood oxygen level-dependent (BOLD) signal was collected during music listening in 25 healthy adults after administration of placebo, lysergic acid diethylamide (LSD), and LSD pretreated with the 5HT2A antagonist ketanserin, to investigate the role of 5HT2A receptor signaling in the neural response to the time-varying tonal structure of music. Tonality-tracking analysis of BOLD data revealed that 5HT2A receptor signaling alters the neural response to music in brain regions supporting basic and higher-level musical and auditory processing, and areas involved in memory, emotion, and self-referential processing. This suggests a critical role of 5HT2A receptor signaling in supporting the neural tracking of dynamic tonal structure in music, as well as in supporting the associated increases in emotionality, connectedness, and meaningfulness in response to music that are commonly observed after the administration of LSD and other psychedelics. Together, these findings inform the neuropsychopharmacology of music perception and cognition, meaningful music listening experiences, and altered perception of music during psychedelic experiences. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Shy and bold great tits (Parus major): body temperature and breath rate in response to handling stress

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Carere, C.; Van Oers, K.

2004-01-01

A standard handling protocol was used to test the hypothesis that boldness predicts stress responsiveness in body temperature and breath rate. Great tit (Parus major) nestlings were taken from the field, hand reared until independence, and their response to a novel object was assessed. At the age of

Shy and bold great tits (Parus major) : body temperature and breath rate in response to handling stress

NARCIS (Netherlands)

Carere, C; van Oers, K

2004-01-01

A standard handling protocol was used to test the hypothesis that boldness predicts stress responsiveness in body temperature and breath rate. Great tit (Parus major) nestlings were taken from the field, hand reared until independence, and their response to a novel object was assessed. At the age of

Relationship between BOLD amplitude and pattern classification of orientation-selective activity in the human visual cortex

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Tong, Frank; Harrison, Stephenie A.; Dewey, John A.; Kamitani, Yukiyasu

2012-01-01

Orientation-selective responses can be decoded from fMRI activity patterns in the human visual cortex, using multivariate pattern analysis (MVPA). To what extent do these feature-selective activity patterns depend on the strength and quality of the sensory input, and might the reliability of these activity patterns be predicted by the gross amplitude of the stimulus-driven BOLD response? Observers viewed oriented gratings that varied in luminance contrast (4, 20 or 100%) or spatial frequency (0.25, 1.0 or 4.0 cpd). As predicted, activity patterns in early visual areas led to better discrimination of orientations presented at high than low contrast, with greater effects of contrast found in area V1 than in V3. A second experiment revealed generally better decoding of orientations at low or moderate as compared to high spatial frequencies. Interestingly however, V1 exhibited a relative advantage at discriminating high spatial frequency orientations, consistent with the finer scale of representation in the primary visual cortex. In both experiments, the reliability of these orientation-selective activity patterns was well predicted by the average BOLD amplitude in each region of interest, as indicated by correlation analyses, as well as decoding applied to a simple model of voxel responses to simulated orientation columns. Moreover, individual differences in decoding accuracy could be predicted by the signal-to-noise ratio of an individual's BOLD response. Our results indicate that decoding accuracy can be well predicted by incorporating the amplitude of the BOLD response into simple simulation models of cortical selectivity; such models could prove useful in future applications of fMRI pattern classification. PMID:22917989

Single-trial EEG-informed fMRI reveals spatial dependency of BOLD signal on early and late IC-ERP amplitudes during face recognition.

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Wirsich, Jonathan; Bénar, Christian; Ranjeva, Jean-Philippe; Descoins, Médéric; Soulier, Elisabeth; Le Troter, Arnaud; Confort-Gouny, Sylviane; Liégeois-Chauvel, Catherine; Guye, Maxime

2014-10-15

Simultaneous EEG-fMRI has opened up new avenues for improving the spatio-temporal resolution of functional brain studies. However, this method usually suffers from poor EEG quality, especially for evoked potentials (ERPs), due to specific artifacts. As such, the use of EEG-informed fMRI analysis in the context of cognitive studies has particularly focused on optimizing narrow ERP time windows of interest, which ignores the rich diverse temporal information of the EEG signal. Here, we propose to use simultaneous EEG-fMRI to investigate the neural cascade occurring during face recognition in 14 healthy volunteers by using the successive ERP peaks recorded during the cognitive part of this process. N170, N400 and P600 peaks, commonly associated with face recognition, were successfully and reproducibly identified for each trial and each subject by using a group independent component analysis (ICA). For the first time we use this group ICA to extract several independent components (IC) corresponding to the sequence of activation and used single-trial peaks as modulation parameters in a general linear model (GLM) of fMRI data. We obtained an occipital-temporal-frontal stream of BOLD signal modulation, in accordance with the three successive IC-ERPs providing an unprecedented spatio-temporal characterization of the whole cognitive process as defined by BOLD signal modulation. By using this approach, the pattern of EEG-informed BOLD modulation provided improved characterization of the network involved than the fMRI-only analysis or the source reconstruction of the three ERPs; the latter techniques showing only two regions in common localized in the occipital lobe. Copyright © 2014 Elsevier Inc. All rights reserved.

Acetazolamide-augmented dynamic BOLD (aczBOLD imaging for assessing cerebrovascular reactivity in chronic steno-occlusive disease of the anterior circulation: An initial experience

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Junjie Wu

2017-01-01

Full Text Available The purpose of this study was to measure cerebrovascular reactivity (CVR in chronic steno-occlusive disease using a novel approach that couples BOLD imaging with acetazolamide (ACZ vasoreactivity (aczBOLD, to evaluate dynamic effects of ACZ on BOLD and to establish the relationship between aczBOLD and dynamic susceptibility contrast (DSC perfusion MRI. Eighteen patients with unilateral chronic steno-occlusive disease of the anterior circulation underwent a 20-min aczBOLD imaging protocol, with ACZ infusion starting at 5 min of scan initiation. AczBOLD reactivity was calculated on a voxel-by-voxel basis to generate CVR maps for subsequent quantitative analyses. Reduced CVR was observed in the diseased vs. the normal hemisphere both by qualitative and quantitative assessment (gray matter (GM: 4.13% ± 1.16% vs. 4.90% ± 0.98%, P = 0.002; white matter (WM: 2.83% ± 1.23% vs. 3.50% ± 0.94%, P = 0.005. In all cases BOLD signal began increasing immediately following ACZ infusion, approaching a plateau at ~8.5 min after infusion, with the tissue volume of reduced augmentation increasing progressively with time, peaking at 2.60 min (time range above 95% of the maximum value: 0–4.43 min for the GM and 1.80 min (time range above 95% of the maximum value: 1.40–3.53 min for the WM. In the diseased hemisphere, aczBOLD CVR significantly correlated with baseline DSC time-to-maximum of the residue function (Tmax (P = 0.008 for the WM and normalized cerebral blood flow (P = 0.003 for the GM, and P = 0.001 for the WM. AczBOLD provides a novel, safe, easily implementable approach to CVR measurement in the routine clinical environments. Further studies can establish quantitative thresholds from aczBOLD towards identification of patients at heightened risk of recurrent ischemia and cognitive decline.

Comparison of fMRI BOLD response patterns by electrical stimulation of the ventroposterior complex and medial thalamus of the rat.

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Pai-Feng Yang

Full Text Available The objective of this study was to compare the functional connectivity of the lateral and medial thalamocortical pain pathways by investigating the blood oxygen level-dependent (BOLD activation patterns in the forebrain elicited by direct electrical stimulation of the ventroposterior (VP and medial (MT thalamus. An MRI-compatible stimulation electrode was implanted in the VP or MT of α-chloralose-anesthetized rats. Electrical stimulation was applied to the VP or MT at various intensities (50 µA to 300 µA and frequencies (1 Hz to 12 Hz. BOLD responses were analyzed in the ipsilateral forelimb region of the primary somatosensory cortex (iS1FL after VP stimulation and in the ipsilateral cingulate cortex (iCC after MT stimulation. When stimulating the VP, the strongest activation occurred at 3 Hz. The stimulation intensity threshold was 50 µA and the response rapidly peaked at 100 µA. When stimulating the MT, The optimal frequency for stimulation was 9 Hz or 12 Hz, the stimulation intensity threshold was 100 µA and we observed a graded increase in the BOLD response following the application of higher intensity stimuli. We also evaluated c-Fos expression following the application of a 200-µA stimulus. Ventroposterior thalamic stimulation elicited c-Fos-positivity in few cells in the iS1FL and caudate putamen (iCPu. Medial thalamic stimulation, however, produced numerous c-Fos-positive cells in the iCC and iCPu. The differential BOLD responses and c-Fos expressions elicited by VP and MT stimulation indicate differences in stimulus-response properties of the medial and lateral thalamic pain pathways.

Correcting for Blood Arrival Time in Global Mean Regression Enhances Functional Connectivity Analysis of Resting State fMRI-BOLD Signals.

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Erdoğan, Sinem B; Tong, Yunjie; Hocke, Lia M; Lindsey, Kimberly P; deB Frederick, Blaise

2016-01-01

Resting state functional connectivity analysis is a widely used method for mapping intrinsic functional organization of the brain. Global signal regression (GSR) is commonly employed for removing systemic global variance from resting state BOLD-fMRI data; however, recent studies have demonstrated that GSR may introduce spurious negative correlations within and between functional networks, calling into question the meaning of anticorrelations reported between some networks. In the present study, we propose that global signal from resting state fMRI is composed primarily of systemic low frequency oscillations (sLFOs) that propagate with cerebral blood circulation throughout the brain. We introduce a novel systemic noise removal strategy for resting state fMRI data, "dynamic global signal regression" (dGSR), which applies a voxel-specific optimal time delay to the global signal prior to regression from voxel-wise time series. We test our hypothesis on two functional systems that are suggested to be intrinsically organized into anticorrelated networks: the default mode network (DMN) and task positive network (TPN). We evaluate the efficacy of dGSR and compare its performance with the conventional "static" global regression (sGSR) method in terms of (i) explaining systemic variance in the data and (ii) enhancing specificity and sensitivity of functional connectivity measures. dGSR increases the amount of BOLD signal variance being modeled and removed relative to sGSR while reducing spurious negative correlations introduced in reference regions by sGSR, and attenuating inflated positive connectivity measures. We conclude that incorporating time delay information for sLFOs into global noise removal strategies is of crucial importance for optimal noise removal from resting state functional connectivity maps.

Mapping of the brain hemodynamic responses to sensorimotor stimulation in a rodent model: A BOLD fMRI study.

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Salem Boussida

Full Text Available Blood Oxygenation Level Dependent functional MRI (BOLD fMRI during electrical paw stimulation has been widely used in studies aimed at the understanding of the somatosensory network in rats. However, despite the well-established anatomical connections between cortical and subcortical structures of the sensorimotor system, most of these functional studies have been concentrated on the cortical effects of sensory electrical stimulation. BOLD fMRI study of the integration of a sensorimotor input across the sensorimotor network requires an appropriate methodology to elicit functional activation in cortical and subcortical areas owing to the regional differences in both neuronal and vascular architectures between these brain regions. Here, using a combination of low level anesthesia, long pulse duration of the electrical stimulation along with improved spatial and temporal signal to noise ratios, we provide a functional description of the main cortical and subcortical structures of the sensorimotor rat brain. With this calibrated fMRI protocol, unilateral non-noxious sensorimotor electrical hindpaw stimulation resulted in robust positive activations in the contralateral sensorimotor cortex and bilaterally in the sensorimotor thalamus nuclei, whereas negative activations were observed bilaterally in the dorsolateral caudate-putamen. These results demonstrate that, once the experimental setup allowing necessary spatial and temporal signal to noise ratios is reached, hemodynamic changes related to neuronal activity, as preserved by the combination of a soft anesthesia with a soft muscle relaxation, can be measured within the sensorimotor network. Moreover, the observed responses suggest that increasing pulse duration of the electrical stimulus adds a proprioceptive component to the sensory input that activates sensorimotor network in the brain, and that these activation patterns are similar to those induced by digits paw's movements. These findings may

Mapping and characterization of positive and negative BOLD responses to visual stimulation in multiple brain regions at 7T.

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Jorge, João; Figueiredo, Patrícia; Gruetter, Rolf; van der Zwaag, Wietske

2018-02-20

External stimuli and tasks often elicit negative BOLD responses in various brain regions, and growing experimental evidence supports that these phenomena are functionally meaningful. In this work, the high sensitivity available at 7T was explored to map and characterize both positive (PBRs) and negative BOLD responses (NBRs) to visual checkerboard stimulation, occurring in various brain regions within and beyond the visual cortex. Recently-proposed accelerated fMRI techniques were employed for data acquisition, and procedures for exclusion of large draining vein contributions, together with ICA-assisted denoising, were included in the analysis to improve response estimation. Besides the visual cortex, significant PBRs were found in the lateral geniculate nucleus and superior colliculus, as well as the pre-central sulcus; in these regions, response durations increased monotonically with stimulus duration, in tight covariation with the visual PBR duration. Significant NBRs were found in the visual cortex, auditory cortex, default-mode network (DMN) and superior parietal lobule; NBR durations also tended to increase with stimulus duration, but were significantly less sustained than the visual PBR, especially for the DMN and superior parietal lobule. Responses in visual and auditory cortex were further studied for checkerboard contrast dependence, and their amplitudes were found to increase monotonically with contrast, linearly correlated with the visual PBR amplitude. Overall, these findings suggest the presence of dynamic neuronal interactions across multiple brain regions, sensitive to stimulus intensity and duration, and demonstrate the richness of information obtainable when jointly mapping positive and negative BOLD responses at a whole-brain scale, with ultra-high field fMRI. © 2018 Wiley Periodicals, Inc.

Linear Discriminant Analysis achieves high classification accuracy for the BOLD fMRI response to naturalistic movie stimuli.

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Hendrik eMandelkow

2016-03-01

Full Text Available Naturalistic stimuli like movies evoke complex perceptual processes, which are of great interest in the study of human cognition by functional MRI (fMRI. However, conventional fMRI analysis based on statistical parametric mapping (SPM and the general linear model (GLM is hampered by a lack of accurate parametric models of the BOLD response to complex stimuli. In this situation, statistical machine-learning methods, a.k.a. multivariate pattern analysis (MVPA, have received growing attention for their ability to generate stimulus response models in a data-driven fashion. However, machine-learning methods typically require large amounts of training data as well as computational resources. In the past this has largely limited their application to fMRI experiments involving small sets of stimulus categories and small regions of interest in the brain. By contrast, the present study compares several classification algorithms known as Nearest Neighbour (NN, Gaussian Naïve Bayes (GNB, and (regularised Linear Discriminant Analysis (LDA in terms of their classification accuracy in discriminating the global fMRI response patterns evoked by a large number of naturalistic visual stimuli presented as a movie.Results show that LDA regularised by principal component analysis (PCA achieved high classification accuracies, above 90% on average for single fMRI volumes acquired 2s apart during a 300s movie (chance level 0.7% = 2s/300s. The largest source of classification errors were autocorrelations in the BOLD signal compounded by the similarity of consecutive stimuli. All classifiers performed best when given input features from a large region of interest comprising around 25% of the voxels that responded significantly to the visual stimulus. Consistent with this, the most informative principal components represented widespread distributions of co-activated brain regions that were similar between subjects and may represent functional networks. In light of these

Spatiotemporal dynamics of the brain at rest--exploring EEG microstates as electrophysiological signatures of BOLD resting state networks.

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Yuan, Han; Zotev, Vadim; Phillips, Raquel; Drevets, Wayne C; Bodurka, Jerzy

2012-05-01

Neuroimaging research suggests that the resting cerebral physiology is characterized by complex patterns of neuronal activity in widely distributed functional networks. As studied using functional magnetic resonance imaging (fMRI) of the blood-oxygenation-level dependent (BOLD) signal, the resting brain activity is associated with slowly fluctuating hemodynamic signals (~10s). More recently, multimodal functional imaging studies involving simultaneous acquisition of BOLD-fMRI and electroencephalography (EEG) data have suggested that the relatively slow hemodynamic fluctuations of some resting state networks (RSNs) evinced in the BOLD data are related to much faster (~100 ms) transient brain states reflected in EEG signals, that are referred to as "microstates". To further elucidate the relationship between microstates and RSNs, we developed a fully data-driven approach that combines information from simultaneously recorded, high-density EEG and BOLD-fMRI data. Using independent component analysis (ICA) of the combined EEG and fMRI data, we identified thirteen microstates and ten RSNs that are organized independently in their temporal and spatial characteristics, respectively. We hypothesized that the intrinsic brain networks that are active at rest would be reflected in both the EEG data and the fMRI data. To test this hypothesis, the rapid fluctuations associated with each microstate were correlated with the BOLD-fMRI signal associated with each RSN. We found that each RSN was characterized further by a specific electrophysiological signature involving from one to a combination of several microstates. Moreover, by comparing the time course of EEG microstates to that of the whole-brain BOLD signal, on a multi-subject group level, we unraveled for the first time a set of microstate-associated networks that correspond to a range of previously described RSNs, including visual, sensorimotor, auditory, attention, frontal, visceromotor and default mode networks. These

Distributed BOLD-response in association cortex vector state space predicts reaction time during selective attention.

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Musso, Francesco; Konrad, Andreas; Vucurevic, Goran; Schäffner, Cornelius; Friedrich, Britta; Frech, Peter; Stoeter, Peter; Winterer, Georg

2006-02-15

Human cortical information processing is thought to be dominated by distributed activity in vector state space (Churchland, P.S., Sejnowski, T.J., 1992. The Computational Brain. MIT Press, Cambridge.). In principle, it should be possible to quantify distributed brain activation with independent component analysis (ICA) through vector-based decomposition, i.e., through a separation of a mixture of sources. Using event-related functional magnetic resonance imaging (fMRI) during a selective attention-requiring task (visual oddball), we explored how the number of independent components within activated cortical areas is related to reaction time. Prior to ICA, the activated cortical areas were determined on the basis of a General linear model (GLM) voxel-by-voxel analysis of the target stimuli (checkerboard reversal). Two activated cortical areas (temporoparietal cortex, medial prefrontal cortex) were further investigated as these cortical regions are known to be the sites of simultaneously active electromagnetic generators which give rise to the compound event-related potential P300 during oddball task conditions. We found that the number of independent components more strongly predicted reaction time than the overall level of "activation" (GLM BOLD-response) in the left temporoparietal area whereas in the medial prefrontal cortex both ICA and GLM predicted reaction time equally well. Comparable correlations were not seen when principle components were used instead of independent components. These results indicate that the number of independently activated components, i.e., a high level of cortical activation complexity in cortical vector state space, may index particularly efficient information processing during selective attention-requiring tasks. To our best knowledge, this is the first report describing a potential relationship between neuronal generators of cognitive processes, the associated electrophysiological evidence for the existence of distributed networks

Differential Localization of Pain-Related and Pain-Unrelated Neural Responses for Acupuncture at BL60 Using BOLD fMRI

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Na-Hee Kim

2013-01-01

Full Text Available The objective of this study was to differentiate between pain-related and pain-unrelated neural responses of acupuncture at BL60 to investigate the specific effects of acupuncture. A total of 19 healthy volunteers were evaluated. fMRI was performed with sham or verum acupuncture stimulation at the left BL60 before and after local anesthesia. To investigate the relative BOLD signal effect for each session, a one-sample t-test was performed for individual contrast maps, and a paired t-test to investigate the differences between the pre- and post-anesthetic signal effects. Regarding verum acupuncture, areas that were more activated before local anesthesia included the superior, middle, and medial frontal gyri, inferior parietal lobule, superior temporal gyrus, thalamus, middle temporal gyrus, cingulate gyrus, culmen, and cerebellar tonsil. The postcentral gyrus was more deactivated before local anesthesia. After local anesthesia, the middle occipital gyrus, inferior temporal gyrus, postcentral gyrus, precuneus, superior parietal lobule, and declive were deactivated. Pre-anesthetic verum acupuncture at BL60 activated areas of vision and pain transmission. Post-anesthetic verum acupuncture deactivated brain areas of visual function, which is considered to be a pain-unrelated acupuncture response. It indicates that specific effects of acupoint BL60 are to control vision sense as used in the clinical setting.

Cholinergic enhancement reduces functional connectivity and BOLD variability in visual extrastriate cortex during selective attention.

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Ricciardi, Emiliano; Handjaras, Giacomo; Bernardi, Giulio; Pietrini, Pietro; Furey, Maura L

2013-01-01

Enhancing cholinergic function improves performance on various cognitive tasks and alters neural responses in task specific brain regions. We have hypothesized that the changes in neural activity observed during increased cholinergic function reflect an increase in neural efficiency that leads to improved task performance. The current study tested this hypothesis by assessing neural efficiency based on cholinergically-mediated effects on regional brain connectivity and BOLD signal variability. Nine subjects participated in a double-blind, placebo-controlled crossover fMRI study. Following an infusion of physostigmine (1 mg/h) or placebo, echo-planar imaging (EPI) was conducted as participants performed a selective attention task. During the task, two images comprised of superimposed pictures of faces and houses were presented. Subjects were instructed periodically to shift their attention from one stimulus component to the other and to perform a matching task using hand held response buttons. A control condition included phase-scrambled images of superimposed faces and houses that were presented in the same temporal and spatial manner as the attention task; participants were instructed to perform a matching task. Cholinergic enhancement improved performance during the selective attention task, with no change during the control task. Functional connectivity analyses showed that the strength of connectivity between ventral visual processing areas and task-related occipital, parietal and prefrontal regions reduced significantly during cholinergic enhancement, exclusively during the selective attention task. Physostigmine administration also reduced BOLD signal temporal variability relative to placebo throughout temporal and occipital visual processing areas, again during the selective attention task only. Together with the observed behavioral improvement, the decreases in connectivity strength throughout task-relevant regions and BOLD variability within stimulus

High spatial correspondence at a columnar level between activation and resting state fMRI signals and local field potentials.

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Shi, Zhaoyue; Wu, Ruiqi; Yang, Pai-Feng; Wang, Feng; Wu, Tung-Lin; Mishra, Arabinda; Chen, Li Min; Gore, John C

2017-05-16

Although blood oxygenation level-dependent (BOLD) fMRI has been widely used to map brain responses to external stimuli and to delineate functional circuits at rest, the extent to which BOLD signals correlate spatially with underlying neuronal activity, the spatial relationships between stimulus-evoked BOLD activations and local correlations of BOLD signals in a resting state, and whether these spatial relationships vary across functionally distinct cortical areas are not known. To address these critical questions, we directly compared the spatial extents of stimulated activations and the local profiles of intervoxel resting state correlations for both high-resolution BOLD at 9.4 T and local field potentials (LFPs), using 98-channel microelectrode arrays, in functionally distinct primary somatosensory areas 3b and 1 in nonhuman primates. Anatomic images of LFP and BOLD were coregistered within 0.10 mm accuracy. We found that the point spread functions (PSFs) of BOLD and LFP responses were comparable in the stimulus condition, and both estimates of activations were slightly more spatially constrained than local correlations at rest. The magnitudes of stimulus responses in area 3b were stronger than those in area 1 and extended in a medial to lateral direction. In addition, the reproducibility and stability of stimulus-evoked activation locations within and across both modalities were robust. Our work suggests that the intrinsic resolution of BOLD is not a limiting feature in practice and approaches the intrinsic precision achievable by multielectrode electrophysiology.

fMRI BOLD response to the eyes task in offspring from multiplex alcohol dependence families.

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Hill, Shirley Y; Kostelnik, Bryan; Holmes, Brian; Goradia, Dhruman; McDermott, Michael; Diwadkar, Vaibhav; Keshavan, Matcheri

2007-12-01

Increased susceptibility for developing alcohol dependence (AD) may be related to structural and functional differences in brain circuits that influence social cognition and more specifically, theory of mind (ToM). Alcohol dependent individuals have a greater likelihood of having deficits in social skills and greater social alienation. These characteristics may be related to inherited differences in the neuroanatomical network that comprises the social brain. Adolescent/young adult participants from multiplex AD families and controls (n = 16) were matched for gender, age, IQ, education, and handedness and administered the Eyes Task of Baron-Cohen during functional magnetic resonance imaging (fMRI). High-risk (HR) subjects showed significantly diminished blood oxygen level dependent (BOLD) response in comparison with low-risk control young adults in the right middle temporal gyrus (RMTG) and the left inferior frontal gyrus (LIFG), areas that have previously been implicated in ToM tasks. Offspring from multiplex families for AD may manifest one aspect of their genetic susceptibility by having a diminished BOLD response in brain regions associated with performance of ToM tasks. These results suggest that those at risk for developing AD may have reduced ability to empathize with others' state of mind, possibly resulting in diminished social skill.

Audiovisual synchrony enhances BOLD responses in a brain network including multisensory STS while also enhancing target-detection performance for both modalities

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Marchant, Jennifer L; Ruff, Christian C; Driver, Jon

2012-01-01

The brain seeks to combine related inputs from different senses (e.g., hearing and vision), via multisensory integration. Temporal information can indicate whether stimuli in different senses are related or not. A recent human fMRI study (Noesselt et al. [2007]: J Neurosci 27:11431–11441) used auditory and visual trains of beeps and flashes with erratic timing, manipulating whether auditory and visual trains were synchronous or unrelated in temporal pattern. A region of superior temporal sulcus (STS) showed higher BOLD signal for the synchronous condition. But this could not be related to performance, and it remained unclear if the erratic, unpredictable nature of the stimulus trains was important. Here we compared synchronous audiovisual trains to asynchronous trains, while using a behavioral task requiring detection of higher-intensity target events in either modality. We further varied whether the stimulus trains had predictable temporal pattern or not. Synchrony (versus lag) between auditory and visual trains enhanced behavioral sensitivity (d') to intensity targets in either modality, regardless of predictable versus unpredictable patterning. The analogous contrast in fMRI revealed BOLD increases in several brain areas, including the left STS region reported by Noesselt et al. [2007: J Neurosci 27:11431–11441]. The synchrony effect on BOLD here correlated with the subject-by-subject impact on performance. Predictability of temporal pattern did not affect target detection performance or STS activity, but did lead to an interaction with audiovisual synchrony for BOLD in inferior parietal cortex. PMID:21953980

Complex motor task associated with non-linear BOLD responses in cerebro-cortical areas and cerebellum.

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Alahmadi, Adnan A S; Samson, Rebecca S; Gasston, David; Pardini, Matteo; Friston, Karl J; D'Angelo, Egidio; Toosy, Ahmed T; Wheeler-Kingshott, Claudia A M

2016-06-01

Previous studies have used fMRI to address the relationship between grip force (GF) applied to an object and BOLD response. However, whilst the majority of these studies showed a linear relationship between GF and neural activity in the contralateral M1 and ipsilateral cerebellum, animal studies have suggested the presence of non-linear components in the GF-neural activity relationship. Here, we present a methodology for assessing non-linearities in the BOLD response to different GF levels, within primary motor as well as sensory and cognitive areas and the cerebellum. To be sensitive to complex forms, we designed a feasible grip task with five GF targets using an event-related visually guided paradigm and studied a cohort of 13 healthy volunteers. Polynomial functions of increasing order were fitted to the data. (1) activated motor areas irrespective of GF; (2) positive higher-order responses in and outside M1, involving premotor, sensory and visual areas and cerebellum; (3) negative correlations with GF, predominantly involving the visual domain. Overall, our results suggest that there are physiologically consistent behaviour patterns in cerebral and cerebellar cortices; for example, we observed the presence of a second-order effect in sensorimotor areas, consistent with an optimum metabolic response at intermediate GF levels, while higher-order behaviour was found in associative and cognitive areas. At higher GF levels, sensory-related cortical areas showed reduced activation, interpretable as a redistribution of the neural activity for more demanding tasks. These results have the potential of opening new avenues for investigating pathological mechanisms of neurological diseases.

Spatiotemporal alignment of in utero BOLD-MRI series.

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Turk, Esra Abaci; Luo, Jie; Gagoski, Borjan; Pascau, Javier; Bibbo, Carolina; Robinson, Julian N; Grant, P Ellen; Adalsteinsson, Elfar; Golland, Polina; Malpica, Norberto

2017-08-01

To present a method for spatiotemporal alignment of in-utero magnetic resonance imaging (MRI) time series acquired during maternal hyperoxia for enabling improved quantitative tracking of blood oxygen level-dependent (BOLD) signal changes that characterize oxygen transport through the placenta to fetal organs. The proposed pipeline for spatiotemporal alignment of images acquired with a single-shot gradient echo echo-planar imaging includes 1) signal nonuniformity correction, 2) intravolume motion correction based on nonrigid registration, 3) correction of motion and nonrigid deformations across volumes, and 4) detection of the outlier volumes to be discarded from subsequent analysis. BOLD MRI time series collected from 10 pregnant women during 3T scans were analyzed using this pipeline. To assess pipeline performance, signal fluctuations between consecutive timepoints were examined. In addition, volume overlap and distance between manual region of interest (ROI) delineations in a subset of frames and the delineations obtained through propagation of the ROIs from the reference frame were used to quantify alignment accuracy. A previously demonstrated rigid registration approach was used for comparison. The proposed pipeline improved anatomical alignment of placenta and fetal organs over the state-of-the-art rigid motion correction methods. In particular, unexpected temporal signal fluctuations during the first normoxia period were significantly decreased (P quantitative studies of placental function by improving spatiotemporal alignment across placenta and fetal organs. 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:403-412. © 2017 International Society for Magnetic Resonance in Medicine.

Mapping and characterization of positive and negative BOLD responses to visual stimulation in multiple brain regions at 7T

NARCIS (Netherlands)

Jorge, João; Figueiredo, Patrícia; Gruetter, Rolf; Van der Zwaag, W.

External stimuli and tasks often elicit negative BOLD responses in various brain regions, and growing experimental evidence supports that these phenomena are functionally meaningful. In this work, the high sensitivity available at 7T was explored to map and characterize both positive (PBRs) and

Altered auditory BOLD response to conspecific birdsong in zebra finches with stuttered syllables.

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Henning U Voss

2010-12-01

Full Text Available How well a songbird learns a song appears to depend on the formation of a robust auditory template of its tutor's song. Using functional magnetic resonance neuroimaging we examine auditory responses in two groups of zebra finches that differ in the type of song they sing after being tutored by birds producing stuttering-like syllable repetitions in their songs. We find that birds that learn to produce the stuttered syntax show attenuated blood oxygenation level-dependent (BOLD responses to tutor's song, and more pronounced responses to conspecific song primarily in the auditory area field L of the avian forebrain, when compared to birds that produce normal song. These findings are consistent with the presence of a sensory song template critical for song learning in auditory areas of the zebra finch forebrain. In addition, they suggest a relationship between an altered response related to familiarity and/or saliency of song stimuli and the production of variant songs with stuttered syllables.

Ultrafast bold fMRI using single-shot spin-echo echo planar imaging

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Boujraf Said

2009-01-01

Full Text Available The choice of imaging parameters for functional MRI can have an impact on the accuracy of functional localization by affecting the image quality and the degree of blood oxygenation-dependent (BOLD contrast achieved. By improving sampling efficiency, parallel acquisition techniques such as sensitivity encoding (SENSE have been used to shorten readout trains in single-shot (SS echo planar imaging (EPI. This has been applied to susceptibility artifact reduction and improving spatial resolution. SENSE together with single-shot spin-echo (SS-SE imaging may also reduce off-resonance artifacts. The goal of this work was to investigate the BOLD response of a SENSE-adapted SE-EPI on a three Tesla scanner. Whole-brain fMRI studies of seven healthy right hand-dominant volunteers were carried out in a three Tesla scanner. fMRI was performed using an SS-SE EPI sequence with SENSE. The data was processed using statistical parametric mapping. Both, group and individual subject data analyses were performed. Individual average percentage and maximal percentage signal changes attributed to the BOLD effect in M1 were calculated for all the subjects as a function of echo time. Corresponding activation maps and the sizes of the activated clusters were also calculated. Our results show that susceptibility artifacts were reduced with the use of SENSE; and the acquired BOLD images were free of the typical quadrature artifacts of SS-EPI. Such measures are crucial at high field strengths. SS SE-EPI with SENSE offers further benefits in this regard and is more specific for oxygenation changes in the microvasculature bed. Functional brain activity can be investigated with the help of single-shot spin echo EPI using SENSE at high magnetic fields.

The Not-So-Global Blood Oxygen Level-Dependent Signal.

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Billings, Jacob; Keilholz, Shella

2018-04-01

Global signal regression is a controversial processing step for resting-state functional magnetic resonance imaging, partly because the source of the global blood oxygen level-dependent (BOLD) signal remains unclear. On the one hand, nuisance factors such as motion can readily introduce coherent BOLD changes across the whole brain. On the other hand, the global signal has been linked to neural activity and vigilance levels, suggesting that it contains important neurophysiological information and should not be discarded. Any widespread pattern of coordinated activity is likely to contribute appreciably to the global signal. Such patterns may include large-scale quasiperiodic spatiotemporal patterns, known also to be tied to performance on vigilance tasks. This uncertainty surrounding the separability of the global BOLD signal from concurrent neurological processes motivated an examination of the global BOLD signal's spatial distribution. The results clarify that although the global signal collects information from all tissue classes, a diverse subset of the BOLD signal's independent components contribute the most to the global signal. Further, the timing of each network's contribution to the global signal is not consistent across volunteers, confirming the independence of a constituent process that comprises the global signal.

Wavelet entropy of BOLD time series : an application to Rolandic epilepsy

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Gupta, Lalit; Jansen, Jacobus F.A.; Hofman, Paul A.M.; Besseling, René M.H.; de Louw, Anton J.A.; Aldenkamp, Albert P.; Backes, Walter H.

2017-01-01

Purpose: To assess the wavelet entropy for the characterization of intrinsic aberrant temporal irregularities in the time series of resting-state blood-oxygen-level-dependent (BOLD) signal fluctuations. Further, to evaluate the temporal irregularities (disorder/order) on a voxel-by-voxel basis in

Background MR gradient noise and non-auditory BOLD activations: a data-driven perspective.

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Haller, Sven; Homola, György A; Scheffler, Klaus; Beckmann, Christian F; Bartsch, Andreas J

2009-07-28

The effect of echoplanar imaging (EPI) acoustic background noise on blood oxygenation level dependent (BOLD) activations was investigated. Two EPI pulse sequences were compared: (i) conventional EPI with a pulsating sound component of typically 8-10 Hz, which is a potent physiological stimulus, and (ii) the more recently developed continuous-sound EPI, which is perceived as less distractive despite equivalent peak sound pressure levels. Sixteen healthy subjects performed an established demanding visual n-back working memory task. Using an exploratory data analysis technique (tensorial probabilistic independent component analysis; tensor-PICA), we studied the inter-session/within-subject response variability introduced by continuous-sound versus conventional EPI acoustic background noise in addition to temporal and spatial signal characteristics. The analysis revealed a task-related component associated with the established higher-level working memory and motor feedback response network, which exhibited a significant 19% increase in its average effect size for the continuous-sound as opposed to conventional EPI. Stimulus-related lower-level activations, such as primary visual areas, were not modified. EPI acoustic background noise influences much more than the auditory system per se. This analysis provides additional evidence for an enhancement of task-related, extra-auditory BOLD activations by continuous-sound EPI due to less distractive acoustic background gradient noise.

Distinct BOLD fMRI Responses of Capsaicin-Induced Thermal Sensation Reveal Pain-Related Brain Activation in Nonhuman Primates.

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Abu Bakar Ali Asad

Full Text Available Approximately 20% of the adult population suffer from chronic pain that is not adequately treated by current therapies, highlighting a great need for improved treatment options. To develop effective analgesics, experimental human and animal models of pain are critical. Topically/intra-dermally applied capsaicin induces hyperalgesia and allodynia to thermal and tactile stimuli that mimics chronic pain and is a useful translation from preclinical research to clinical investigation. Many behavioral and self-report studies of pain have exploited the use of the capsaicin pain model, but objective biomarker correlates of the capsaicin augmented nociceptive response in nonhuman primates remains to be explored.Here we establish an aversive capsaicin-induced fMRI model using non-noxious heat stimuli in Cynomolgus monkeys (n = 8. BOLD fMRI data were collected during thermal challenge (ON:20 s/42°C; OFF:40 s/35°C, 4-cycle at baseline and 30 min post-capsaicin (0.1 mg, topical, forearm application. Tail withdrawal behavioral studies were also conducted in the same animals using 42°C or 48°C water bath pre- and post- capsaicin application (0.1 mg, subcutaneous, tail.Group comparisons between pre- and post-capsaicin application revealed significant BOLD signal increases in brain regions associated with the 'pain matrix', including somatosensory, frontal, and cingulate cortices, as well as the cerebellum (paired t-test, p<0.02, n = 8, while no significant change was found after the vehicle application. The tail withdrawal behavioral study demonstrated a significant main effect of temperature and a trend towards capsaicin induced reduction of latency at both temperatures.These findings provide insights into the specific brain regions involved with aversive, 'pain-like', responses in a nonhuman primate model. Future studies may employ both behavioral and fMRI measures as translational biomarkers to gain deeper understanding of pain processing and evaluate

Development of visual cortical function in infant macaques: A BOLD fMRI study.

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Tom J Van Grootel

Full Text Available Functional brain development is not well understood. In the visual system, neurophysiological studies in nonhuman primates show quite mature neuronal properties near birth although visual function is itself quite immature and continues to develop over many months or years after birth. Our goal was to assess the relative development of two main visual processing streams, dorsal and ventral, using BOLD fMRI in an attempt to understand the global mechanisms that support the maturation of visual behavior. Seven infant macaque monkeys (Macaca mulatta were repeatedly scanned, while anesthetized, over an age range of 102 to 1431 days. Large rotating checkerboard stimuli induced BOLD activation in visual cortices at early ages. Additionally we used static and dynamic Glass pattern stimuli to probe BOLD responses in primary visual cortex and two extrastriate areas: V4 and MT-V5. The resulting activations were analyzed with standard GLM and multivoxel pattern analysis (MVPA approaches. We analyzed three contrasts: Glass pattern present/absent, static/dynamic Glass pattern presentation, and structured/random Glass pattern form. For both GLM and MVPA approaches, robust coherent BOLD activation appeared relatively late in comparison to the maturation of known neuronal properties and the development of behavioral sensitivity to Glass patterns. Robust differential activity to Glass pattern present/absent and dynamic/static stimulus presentation appeared first in V1, followed by V4 and MT-V5 at older ages; there was no reliable distinction between the two extrastriate areas. A similar pattern of results was obtained with the two analysis methods, although MVPA analysis showed reliable differential responses emerging at later ages than GLM. Although BOLD responses to large visual stimuli are detectable, our results with more refined stimuli indicate that global BOLD activity changes as behavioral performance matures. This reflects an hierarchical development of

Interleaved quantitative BOLD: Combining extravascular R2' - and intravascular R2-measurements for estimation of deoxygenated blood volume and hemoglobin oxygen saturation.

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Lee, Hyunyeol; Englund, Erin K; Wehrli, Felix W

2018-03-23

Quantitative BOLD (qBOLD), a non-invasive MRI method for assessment of hemodynamic and metabolic properties of the brain in the baseline state, provides spatial maps of deoxygenated blood volume fraction (DBV) and hemoglobin oxygen saturation (HbO 2 ) by means of an analytical model for the temporal evolution of free-induction-decay signals in the extravascular compartment. However, mutual coupling between DBV and HbO 2 in the signal model results in considerable estimation uncertainty precluding achievement of a unique set of solutions. To address this problem, we developed an interleaved qBOLD method (iqBOLD) that combines extravascular R 2 ' and intravascular R 2 mapping techniques so as to obtain prior knowledge for the two unknown parameters. To achieve these goals, asymmetric spin echo and velocity-selective spin-labeling (VSSL) modules were interleaved in a single pulse sequence. Prior to VSSL, arterial blood and CSF signals were suppressed to produce reliable estimates for cerebral venous blood volume fraction (CBV v ) as well as venous blood R 2 (to yield HbO 2 ). Parameter maps derived from the VSSL module were employed to initialize DBV and HbO 2 in the qBOLD processing. Numerical simulations and in vivo experiments at 3 T were performed to evaluate the performance of iqBOLD in comparison to the parent qBOLD method. Data obtained in eight healthy subjects yielded plausible values averaging 60.1 ± 3.3% for HbO 2 and 3.1 ± 0.5 and 2.0 ± 0.4% for DBV in gray and white matter, respectively. Furthermore, the results show that prior estimates of CBV v and HbO 2 from the VSSL component enhance the solution stability in the qBOLD processing, and thus suggest the feasibility of iqBOLD as a promising alternative to the conventional technique for quantifying neurometabolic parameters. Copyright © 2018. Published by Elsevier Inc.

Computing moment to moment BOLD activation for real-time neurofeedback

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Hinds, Oliver; Ghosh, Satrajit; Thompson, Todd W.; Yoo, Julie J.; Whitfield-Gabrieli, Susan; Triantafyllou, Christina; Gabrieli, John D.E.

2013-01-01

Estimating moment to moment changes in blood oxygenation level dependent (BOLD) activation levels from functional magnetic resonance imaging (fMRI) data has applications for learned regulation of regional activation, brain state monitoring, and brain-machine interfaces. In each of these contexts, accurate estimation of the BOLD signal in as little time as possible is desired. This is a challenging problem due to the low signal-to-noise ratio of fMRI data. Previous methods for real-time fMRI analysis have either sacrificed the ability to compute moment to moment activation changes by averaging several acquisitions into a single activation estimate or have sacrificed accuracy by failing to account for prominent sources of noise in the fMRI signal. Here we present a new method for computing the amount of activation present in a single fMRI acquisition that separates moment to moment changes in the fMRI signal intensity attributable to neural sources from those due to noise, resulting in a feedback signal more reflective of neural activation. This method computes an incremental general linear model fit to the fMRI timeseries, which is used to calculate the expected signal intensity at each new acquisition. The difference between the measured intensity and the expected intensity is scaled by the variance of the estimator in order to transform this residual difference into a statistic. Both synthetic and real data were used to validate this method and compare it to the only other published real-time fMRI method. PMID:20682350

Development of BOLD signal hemodynamic responses in the human brain

NARCIS (Netherlands)

Arichi, T.; Varela, M.; Melendez-Calderon, A.; Allievi, A.; Merchant, N.; Tusor, N.; Counsell, S.J.; Burdet, E.; Beckmann, Christian; Edwards, A.D.

2012-01-01

In the rodent brain the hemodynamic response to a brief external stimulus changes significantly during development. Analogous changes in human infants would complicate the determination and use of the hemodynamic response function (HRF) for functional magnetic resonance imaging (fMRI) in developing

Implications of oxidative stress in the brain plasticity originated by fasting: a BOLD-fMRI study.

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Belaïch, Rachida; Boujraf, Saïd; Benzagmout, Mohammed; Magoul, Rabia; Maaroufi, Mustapha; Tizniti, Siham

2017-11-01

The goal of this study was assessing the intermittent fasting effect on brain plasticity and oxidative stress (OS) using blood-oxygenation-level dependent (BOLD)-functional magnetic resonance image (fMRI) approach. Evidences of physiological and molecular phenomena involved in this process are discussed and compared to reported literature. Six fully healthy male non-smokers volunteered in this study. All volunteers were right handed, and have an equilibrated, consistent and healthy daily nutritional habit, and a healthy lifestyle. Participants were allowed consuming food during evening and night time while fasting with self-prohibiting food and liquids during 14 hours/day from sunrise to sunset. All participants underwent identical brain BOLD-fMRI protocol. The images were acquired in the Department of Radiology and Clinical Imaging of the University Hospital of Fez, Fez, Morocco. The anatomical brain and BOLD-fMRIs were acquired using a 1.5-Tesla scanner (Signa, General Electric, Milwaukee, United States). BOLD-fMRI image acquisition was done using single-shot gradient echo echo-planer imaging sequence. BOLD-fMRI paradigm consisted of the motor task where volunteers were asked to perform finger taping of the right hand. Two BOLD-fMRI scan sessions were performed, the first one between the 5th and 10th days preceding the start of fasting and the second between days 25th and 28th of the fasting month. All sessions were performed between 3:30 PM and 5:30 PM. Although individual maps were originated from different individual participants, they cover the same anatomic area in each case. Image processing and statistical analysis were conducted with Statistical Parameter Mapping version 8 (2008, Welcome Department of Cognitive Neurology, London UK). The maximal BOLD signal changes were calculated for each subject in the motor area M1; Activation maps were calculated and overlaid on the anatomical images. Group analysis of the data was performed, and the average volume

Task-Related Modulations of BOLD Low-Frequency Fluctuations within the Default Mode Network

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Tommasin, Silvia; Mascali, Daniele; Gili, Tommaso; Assan, Ibrahim Eid; Moraschi, Marta; Fratini, Michela; Wise, Richard G.; Macaluso, Emiliano; Mangia, Silvia; Giove, Federico

2017-01-01

Spontaneous low-frequency Blood-Oxygenation Level-Dependent (BOLD) signals acquired during resting state are characterized by spatial patterns of synchronous fluctuations, ultimately leading to the identification of robust brain networks. The resting-state brain networks, including the Default Mode Network (DMN), are demonstrated to persist during sustained task execution, but the exact features of task-related changes of network properties are still not well characterized. In this work we sought to examine in a group of 20 healthy volunteers (age 33 ± 6 years, 8 F/12 M) the relationship between changes of spectral and spatiotemporal features of one prominent resting-state network, namely the DMN, during the continuous execution of a working memory n-back task. We found that task execution impacted on both functional connectivity and amplitude of BOLD fluctuations within large parts of the DMN, but these changes correlated between each other only in a small area of the posterior cingulate. We conclude that combined analysis of multiple parameters related to connectivity, and their changes during the transition from resting state to continuous task execution, can contribute to a better understanding of how brain networks rearrange themselves in response to a task. PMID:28845420

Task-Related Modulations of BOLD Low-Frequency Fluctuations within the Default Mode Network

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Silvia Tommasin

2017-07-01

Full Text Available Spontaneous low-frequency Blood-Oxygenation Level-Dependent (BOLD signals acquired during resting state are characterized by spatial patterns of synchronous fluctuations, ultimately leading to the identification of robust brain networks. The resting-state brain networks, including the Default Mode Network (DMN, are demonstrated to persist during sustained task execution, but the exact features of task-related changes of network properties are still not well characterized. In this work we sought to examine in a group of 20 healthy volunteers (age 33 ± 6 years, 8 F/12 M the relationship between changes of spectral and spatiotemporal features of one prominent resting-state network, namely the DMN, during the continuous execution of a working memory n-back task. We found that task execution impacted on both functional connectivity and amplitude of BOLD fluctuations within large parts of the DMN, but these changes correlated between each other only in a small area of the posterior cingulate. We conclude that combined analysis of multiple parameters related to connectivity, and their changes during the transition from resting state to continuous task execution, can contribute to a better understanding of how brain networks rearrange themselves in response to a task.

Development of a parallel zoomed EVI sequence for high temporal resolution analysis of the BOLD response

International Nuclear Information System (INIS)

Rabrait, C.

2006-01-01

The hemodynamic impulse response to any short stimulus typically lasts around 20 seconds. Thus, the detection of the Blood Oxygenation Level Dependent (BOLD) effect is usually performed using a 2D Echo Planar Imaging (EPI) sequence, with repetition times on the order of 1 or 2 seconds. This temporal resolution is generally enough for detection purposes. Nevertheless, when trying to accurately estimate the hemodynamic response functions (HRF), higher scanning rates represent a real advantage. Thus, in order to reach a temporal resolution around 200 ms, we developed a new acquisition method, based on Echo Volumar Imaging and 2D parallel acquisition (1). Echo Volumar Imaging (EVI) has been proposed in 1977 by Mansfield (2). EVI intrinsically possesses a lot of advantages for functional neuroimaging, as a 3 D single shot acquisition method. Nevertheless, to date, only a few applications have been reported (3, 4). Actually, very restricting hardware requirements make EVI difficult to perform in satisfactory experimental conditions, even today. The critical point in EVI is the echo train duration, which is longer than in EPI, due to 3D acquisition. Indeed, at equal field of view and spatial resolutions, EVI echo train duration must be approximately equal to EPI echo train duration multiplied by the number of slices acquired in EPI. Consequently, EVI is much more sensitive than EPI to geometric distortions, which are related to phase errors, and also to signal losses, which are due to long echo times (TE). Thus, a first improvement has been brought by 'zoomed' or 'localized' EVI (5), which allows to focus on a small volume of interest and thus limit echo train durations compared to full FOV acquisitions.To reduce echo train durations, we chose to apply parallel acquisition. Moreover, since EVI is a 3D acquisition method, we are able to perform parallel acquisition and SENSE reconstruction along the two phase directions (6). The R = 4 under-sampling consists in the

Vascular Steal Explains Early Paradoxical Blood Oxygen Level-Dependent Cerebrovascular Response in Brain Regions with Delayed Arterial Transit Times

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Julien Poublanc

2013-04-01

Full Text Available Introduction: Blood oxygen level-dependent (BOLD magnetic resonance imaging (MRI during manipulation of inhaled carbon dioxide (CO2 can be used to measure cerebrovascular reactivity (CVR and map regions of exhausted cerebrovascular reserve. These regions exhibit a reduced or negative BOLD response to inhaled CO2. In this study, we sought to clarify the mechanism behind the negative BOLD response by investigating its time delay (TD. Dynamic susceptibility contrast (DSC MRI with the injection of a contrast agent was used as the gold standard in order to provide measurement of the blood arrival time to which CVR TD could be compared. We hypothesize that if negative BOLD responses are the result of a steal phenomenon, they should be synchronized with positive BOLD responses from healthy brain tissue, even though the blood arrival time would be delayed. Methods: On a 3-tesla MRI system, BOLD CVR and DSC images were collected in a group of 19 patients with steno-occlusive cerebrovascular disease. For each patient, we generated a CVR magnitude map by regressing the BOLD signal with the end-tidal partial pressure of CO2 (PETCO2, and a CVR TD map by extracting the time of maximum cross-correlation between the BOLD signal and PETCO2. In addition, a blood arrival time map was generated by fitting the DSC signal with a gamma variate function. ROI masks corresponding to varying degrees of reactivity were constructed. Within these masks, the mean CVR magnitude, CVR TD and DSC blood arrival time were extracted and averaged over the 19 patients. CVR magnitude and CVR TD were then plotted against DSC blood arrival time. Results: The results show that CVR magnitude is highly correlated to DSC blood arrival time. As expected, the most compromised tissues with the longest blood arrival time have the lowest (most negative CVR magnitude. However, CVR TD shows a noncontinuous relationship with DSC blood arrival time. CVR TD is well correlated to DSC blood arrival time

Early Changes in Alpha Band Power and DMN BOLD Activity in Alzheimer’s Disease: A Simultaneous Resting State EEG-fMRI Study

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Katharina Brueggen

2017-10-01

Full Text Available Simultaneous resting state functional magnetic resonance imaging (rsfMRI–resting state electroencephalography (rsEEG studies in healthy adults showed robust positive associations of signal power in the alpha band with BOLD signal in the thalamus, and more heterogeneous associations in cortical default mode network (DMN regions. Negative associations were found in occipital regions. In Alzheimer’s disease (AD, rsfMRI studies revealed a disruption of the DMN, while rsEEG studies consistently reported a reduced power within the alpha band. The present study is the first to employ simultaneous rsfMRI-rsEEG in an AD sample, investigating the association of alpha band power and BOLD signal, compared to healthy controls (HC. We hypothesized to find reduced positive associations in DMN regions and reduced negative associations in occipital regions in the AD group. Simultaneous resting state fMRI–EEG was recorded in 14 patients with mild AD and 14 HC, matched for age and gender. Power within the EEG alpha band (8–12 Hz, 8–10 Hz, and 10–12 Hz was computed from occipital electrodes and served as regressor in voxel-wise linear regression analyses, to assess the association with the BOLD signal. Compared to HC, the AD group showed significantly decreased positive associations between BOLD signal and occipital alpha band power in clusters in the superior, middle and inferior frontal cortex, inferior temporal lobe and thalamus (p < 0.01, uncorr., cluster size ≥ 50 voxels. This group effect was more pronounced in the upper alpha sub-band, compared to the lower alpha sub-band. Notably, we observed a high inter-individual heterogeneity. Negative associations were only reduced in the lower alpha range in the hippocampus, putamen and cerebellum. The present study gives first insights into the relationship of resting-state EEG and fMRI characteristics in an AD sample. The results suggest that positive associations between alpha band power and BOLD

Changes in BOLD and ADC weighted imaging in acute hypoxia during sea-level and altitude adapted states

DEFF Research Database (Denmark)

Rostrup, Egill; Larsson, Henrik B.W.; Born, Alfred P.

2005-01-01

possible structural changes as measured by diffusion weighted imaging. Eleven healthy sea-level residents were studied after 5 weeks of adaptation to high altitude conditions at Chacaltaya, Bolivia (5260 m). The subjects were studied immediately after return to sea-level in hypoxic and normoxic conditions...... was slightly elevated in high altitude as compared to sea-level adaptation. It is concluded that hypoxia significantly diminishes the BOLD response, and the mechanisms underlying this finding are discussed. Furthermore, altitude adaptation may influence both the magnitude of the activation-related response......, and the examinations repeated 6 months later after re-adaptation to sea-level conditions. The BOLD response, measured at 1.5 T, was severely reduced during acute hypoxia both in the altitude and sea-level adapted states (50% reduction during an average S(a)O(2) of 75%). On average, the BOLD response magnitude was 23...

The dependencies of fronto-parietal BOLD responses evoked by covert visual search suggest eye-centred coding.

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Atabaki, A; Dicke, P W; Karnath, H-O; Thier, P

2013-04-01

Visual scenes explored covertly are initially represented in a retinal frame of reference (FOR). On the other hand, 'later' stages of the cortical network allocating spatial attention most probably use non-retinal or non-eye-centred representations as they may ease the integration of different sensory modalities for the formation of supramodal representations of space. We tested if the cortical areas involved in shifting covert attention are based on eye-centred or non-eye-centred coding by using functional magnetic resonance imaging. Subjects were scanned while detecting a target item (a regularly oriented 'L') amidst a set of distractors (rotated 'L's). The array was centred either 5° right or left of the fixation point, independent of eye-gaze orientation, the latter varied in three steps: straight relative to the head, 10° left or 10° right. A quantitative comparison of the blood-oxygen-level-dependent (BOLD) responses for the three eye-gaze orientations revealed stronger BOLD responses in the right intraparietal sulcus (IPS) and the right frontal eye field (FEF) for search in the contralateral (i.e. left) eye-centred space, independent of whether the array was located in the right or left head-centred hemispace. The left IPS showed the reverse pattern, i.e. an activation by search in the right eye-centred hemispace. In other words, the IPS and the right FEF, members of the cortical network underlying covert search, operate in an eye-centred FOR. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

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

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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.

Task-related modulations of BOLD low-frequency fluctuations within the default mode network

Science.gov (United States)

Tommasin, Silvia; Mascali, Daniele; Gili, Tommaso; Eid Assan, Ibrahim; Moraschi, Marta; Fratini, Michela; Wise, Richard G.; Macaluso, Emiliano; Mangia, Silvia; Giove, Federico

2017-07-01

Spontaneous low-frequency Blood-Oxygenation Level-Dependent (BOLD) signals acquired during resting state are characterized by spatial patterns of synchronous fluctuations, ultimately leading to the identification of robust brain networks. The resting-state brain networks, including the Default Mode Network (DMN), are demonstrated to persist during sustained task execution, but the exact features of task-related changes of network properties are still not well characterized. In this work we sought to examine in a group of 20 healthy volunteers (age 33±6 years, 8F/12M) the relationship between changes of spectral and spatiotemporal features of one prominent resting-state network, namely the DMN, during the steady-state execution of a sustained working memory n-back task. We found that the steady state execution of such a task impacted on both functional connectivity and amplitude of BOLD fluctuations within large parts of the DMN, but these changes correlated between each other only in a small area of the posterior cingulate. We conclude that combined analysis of multiple parameters related to connectivity, and their changes during the transition from resting state to steady-state task execution, can contribute to a better understanding of how brain networks rearrange themselves in response of a task.

Beware of Boldness

National Research Council Canada - National Science Library

Crane, Conrad C

2006-01-01

... to be?"1 Army Field Manual 7.0, Training the Force, states that the goals of operational deployments and major training opportunities are to enhance unit readiness and "produce bold, innovative leaders...

Effect of CGRP and sumatriptan on the BOLD response in visual cortex

DEFF Research Database (Denmark)

Asghar, Mohammed Sohail; Hansen, Adam E; Larsson, Henrik B W

2012-01-01

To test the hypothesis that calcitonin gene-related peptide (CGRP) modulates brain activity, we investigated the effect of intravenous CGRP on brain activity in response to a visual stimulus. In addition, we examined if possible alteration in brain activity was reversed by the anti-migraine drug......% of the participants reported headache after CGRP. We found no changes in brain activity after CGRP (P = 0.12) or after placebo (P = 0.41). Sumatriptan did not affect brain activity after CGRP (P = 0.71) or after placebo (P = 0.98). Systemic CGRP or sumatriptan has no direct effects on the BOLD activity in visual...... sumatriptan. Eighteen healthy volunteers were randomly allocated to receive CGRP infusion (1.5 µg/min for 20 min) or placebo. In vivo activity in the visual cortex was recorded before, during and after infusion and after 6 mg subcutaneous sumatriptan by functional magnetic resonance imaging (3 T). 77...

The time-course of cortico-limbic neural responses to air hunger.

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Binks, Andrew P; Evans, Karleyton C; Reed, Jeffrey D; Moosavi, Shakeeb H; Banzett, Robert B

2014-12-01

Several studies have mapped brain regions associated with acute dyspnea perception. However, the time-course of brain activity during sustained dyspnea is unknown. Our objective was to determine the time-course of neural activity when dyspnea is sustained. Eight healthy subjects underwent brain blood oxygen level dependent functional magnetic imaging (BOLD-fMRI) during mechanical ventilation with constant mild hypercapnia (∼ 45 mm Hg). Subjects rated dyspnea (air hunger) via visual analog scale (VAS). Tidal volume (V(T)) was alternated every 90 s between high VT (0.96 ± 0.23 L) that provided respiratory comfort (12 ± 6% full scale) and low V(T) (0.48 ± 0.08 L) which evoked air hunger (56 ± 11% full scale). BOLD signal was extracted from a priori brain regions and combined with VAS data to determine air hunger related neural time-course. Air hunger onset was associated with BOLD signal increases that followed two distinct temporal profiles within sub-regions of the anterior insula, anterior cingulate and prefrontal cortices (cortico-limbic circuitry): (1) fast, BOLD signal peak 40s. BOLD signal during air hunger offset followed fast and slow temporal profiles symmetrical, but inverse (signal decreases) to the time-courses of air hunger onset. We conclude that differential cortico-limbic circuit elements have unique contributions to dyspnea sensation over time. We suggest that previously unidentified sub-regions are responsible for either the acute awareness or maintenance of dyspnea. These data enhance interpretation of previous studies and inform hypotheses for future dyspnea research. Copyright © 2014 Elsevier B.V. All rights reserved.

"Extreme Bold" in the Faculty Ranks

Science.gov (United States)

Kuusisto, Stephen

2013-01-01

Boldness, defense, and the necessity of talking back remain as central to life with disability in one's time as in Francis Bacon's age. "Therefore all deformed persons are extreme bold," Bacon wrote, "first, as in their own defence, as being exposed to scorn, but in process of time, by a general habit." Perhaps no word carries…

Iterative analysis of cerebrovascular reactivity dynamic response by temporal decomposition.

Science.gov (United States)

van Niftrik, Christiaan Hendrik Bas; Piccirelli, Marco; Bozinov, Oliver; Pangalu, Athina; Fisher, Joseph A; Valavanis, Antonios; Luft, Andreas R; Weller, Michael; Regli, Luca; Fierstra, Jorn

2017-09-01

To improve quantitative cerebrovascular reactivity (CVR) measurements and CO 2 arrival times, we present an iterative analysis capable of decomposing different temporal components of the dynamic carbon dioxide- Blood Oxygen-Level Dependent (CO 2 -BOLD) relationship. Decomposition of the dynamic parameters included a redefinition of the voxel-wise CO 2 arrival time, and a separation from the vascular response to a stepwise increase in CO 2 (Delay to signal Plateau - DTP) and a decrease in CO 2 (Delay to signal Baseline -DTB). Twenty-five (normal) datasets, obtained from BOLD MRI combined with a standardized pseudo-square wave CO 2 change, were co-registered to generate reference atlases for the aforementioned dynamic processes to score the voxel-by-voxel deviation probability from normal range. This analysis is further illustrated in two subjects with unilateral carotid artery occlusion using these reference atlases. We have found that our redefined CO 2 arrival time resulted in the best data fit. Additionally, excluding both dynamic BOLD phases (DTP and DTB) resulted in a static CVR, that is maximal response, defined as CVR calculated only over a normocapnic and hypercapnic calibrated plateau. Decomposition and novel iterative modeling of different temporal components of the dynamic CO 2 -BOLD relationship improves quantitative CVR measurements.

Exploring BOLD changes during spatial attention in non-stimulated visual cortex.

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Linda Heinemann

Full Text Available Blood oxygen level-dependent (BOLD responses were measured in parts of primary visual cortex that represented unstimulated visual field regions at different distances from a stimulated central target location. The composition of the visual scene varied by the presence or absence of additional peripheral distracter stimuli. Bottom-up effects were assessed by comparing peripheral activity during central stimulation vs. no stimulation. Top-down effects were assessed by comparing active vs. passive conditions. In passive conditions subjects simply watched the central letter stimuli and in active conditions they had to report occurrence of pre-defined targets in a rapid serial letter stream. Onset of the central letter stream enhanced activity in V1 representations of the stimulated region. Within representations of the periphery activation decreased and finally turned into deactivation with increasing distance from the stimulated location. This pattern was most pronounced in the active conditions and during the presence of peripheral stimuli. Active search for a target did not lead to additional enhancement at areas representing the attentional focus but to a stronger deactivation in the vicinity. Suppressed neuronal activity was also found in the non distracter condition suggesting a top-down attention driven effect. Our observations suggest that BOLD signal decreases in primary visual cortex are modulated by bottom-up sensory-driven factors such as the presence of distracters in the visual field as well as by top-down attentional processes.

Blood oxygenation level dependent signal and neuronal adaptation to optogenetic and sensory stimulation in somatosensory cortex in awake animals.

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Aksenov, Daniil P; Li, Limin; Miller, Michael J; Wyrwicz, Alice M

2016-11-01

The adaptation of neuronal responses to stimulation, in which a peak transient response is followed by a sustained plateau, has been well-studied. The blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal has also been shown to exhibit adaptation on a longer time scale. However, some regions such as the visual and auditory cortices exhibit significant BOLD adaptation, whereas other such as the whisker barrel cortex may not adapt. In the sensory cortex a combination of thalamic inputs and intracortical activity drives hemodynamic changes, although the relative contributions of these components are not entirely understood. The aim of this study is to assess the role of thalamic inputs vs. intracortical processing in shaping BOLD adaptation during stimulation in the somatosensory cortex. Using simultaneous fMRI and electrophysiology in awake rabbits, we measured BOLD, local field potentials (LFPs), single- and multi-unit activity in the cortex during whisker and optogenetic stimulation. This design allowed us to compare BOLD and haemodynamic responses during activation of the normal thalamocortical sensory pathway (i.e., both inputs and intracortical activity) vs. the direct optical activation of intracortical circuitry alone. Our findings show that whereas LFP and multi-unit (MUA) responses adapted, neither optogenetic nor sensory stimulation produced significant BOLD adaptation. We observed for both paradigms a variety of excitatory and inhibitory single unit responses. We conclude that sensory feed-forward thalamic inputs are not primarily responsible for shaping BOLD adaptation to stimuli; but the single-unit results point to a role in this behaviour for specific excitatory and inhibitory neuronal sub-populations, which may not correlate with aggregate neuronal activity. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Wavelet entropy of BOLD time series: An application to Rolandic epilepsy.

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Gupta, Lalit; Jansen, Jacobus F A; Hofman, Paul A M; Besseling, René M H; de Louw, Anton J A; Aldenkamp, Albert P; Backes, Walter H

2017-12-01

To assess the wavelet entropy for the characterization of intrinsic aberrant temporal irregularities in the time series of resting-state blood-oxygen-level-dependent (BOLD) signal fluctuations. Further, to evaluate the temporal irregularities (disorder/order) on a voxel-by-voxel basis in the brains of children with Rolandic epilepsy. The BOLD time series was decomposed using the discrete wavelet transform and the wavelet entropy was calculated. Using a model time series consisting of multiple harmonics and nonstationary components, the wavelet entropy was compared with Shannon and spectral (Fourier-based) entropy. As an application, the wavelet entropy in 22 children with Rolandic epilepsy was compared to 22 age-matched healthy controls. The images were obtained by performing resting-state functional magnetic resonance imaging (fMRI) using a 3T system, an 8-element receive-only head coil, and an echo planar imaging pulse sequence ( T2*-weighted). The wavelet entropy was also compared to spectral entropy, regional homogeneity, and Shannon entropy. Wavelet entropy was found to identify the nonstationary components of the model time series. In Rolandic epilepsy patients, a significantly elevated wavelet entropy was observed relative to controls for the whole cerebrum (P = 0.03). Spectral entropy (P = 0.41), regional homogeneity (P = 0.52), and Shannon entropy (P = 0.32) did not reveal significant differences. The wavelet entropy measure appeared more sensitive to detect abnormalities in cerebral fluctuations represented by nonstationary effects in the BOLD time series than more conventional measures. This effect was observed in the model time series as well as in Rolandic epilepsy. These observations suggest that the brains of children with Rolandic epilepsy exhibit stronger nonstationary temporal signal fluctuations than controls. 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1728-1737. © 2017 International Society for Magnetic

Fitness Consequences of Boldness in Juvenile and Adult Largemouth Bass.

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Ballew, Nicholas G; Mittelbach, Gary G; Scribner, Kim T

2017-04-01

To date, most studies investigating the relationship between personality traits and fitness have focused on a single measure of fitness (such as survival) at a specific life stage. However, many personality traits likely have multiple effects on fitness, potentially operating across different functional contexts and stages of development. Here, we address the fitness consequences of boldness, under seminatural conditions, across life stages and functional contexts in largemouth bass (Micropterus salmoides). Specifically, we report the effect of boldness on (1) juvenile survivorship in an outdoor pond containing natural prey and predators and (2) adult reproductive success in three outdoor ponds across three reproductive seasons (years). Juvenile survival was negatively affected by boldness, with bolder juveniles having a lower probability of survival than shyer juveniles. In contrast, bolder adult male bass had greater reproductive success than their shyer male counterparts. Female reproductive success was not affected by boldness. These findings demonstrate that boldness can affect fitness differently across life stages. Further, boldness was highly consistent across years and significantly heritable, which suggests that boldness has a genetic component. Thus, our results support theory suggesting that fitness trade-offs across life stages may contribute to the maintenance of personality variation within populations.

Brain signal variability is modulated as a function of internal and external demand in younger and older adults.

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Grady, Cheryl L; Garrett, Douglas D

2018-04-01

Variability in the Blood Oxygen-Level Dependent (BOLD) signal from fMRI is often associated with better cognitive performance and younger age. It has been proposed that neural variability enables flexible responding to uncertainty in a changing environment. However, signal variability reflecting environmental uncertainty may reduce to the extent that a task depends on internally-directed attention and is supported by neural "solutions" that are schematic and relatively stable within each individual. Accordingly, we examined the hypothesis that BOLD variability will be low at rest, higher during internally-directed tasks, and higher still during externally-directed tasks, and that this effect will be reduced with aging. Modulation of BOLD variability across conditions was consistent with these hypotheses, and was associated with faster and more stable behavioral performance in both young and older adults. These data support the idea that brain signal variability may modulate in response to environmental uncertainty, which is presumed to be greater in the external environment than in the internal milieu. Reduced flexibility of signal variability with age may indicate less ability to switch between internal and external brain states. Copyright © 2017 Elsevier Inc. All rights reserved.

Augmentation of sensory-evoked hemodynamic response in an early Alzheimer's disease mouse model.

Science.gov (United States)

Kim, Jinho; Jeong, Yong

2013-01-01

Based on enlarged blood oxygen level-dependent (BOLD) responses in cognitively normal subjects at risk for Alzheimer's disease (AD), compensatory neuronal hyperactivation has been proposed as an early marker for diagnosis of AD. The BOLD response results from neurovascular coupling, i.e., hemodynamic response induced by neuronal activity. However, there has been no evidence of task-induced increases in hemodynamic response in animal models of AD. Here, we observed an augmented hemodynamic response pattern in a transgenic AβPP(SWE)/PS1ΔE9 mouse model of AD using three in vivo imaging methods: intrinsic optical signal imaging, multi-photon laser scanning microscopy, and laser Doppler flowmetry. Sensory stimulation resulted in augmented and prolonged hemodynamic responses in transgenic mice evidenced by changes in total, oxygenated, and deoxygenated hemoglobin concentration. This difference between transgenic and wild-type mice was significant at 7 months of age when amyloid plaques and cerebral amyloid angiopathy had developed but not at younger or older ages. Correspondingly, sensory stimulation-induced pial arteriole diameter was also augmented and prolonged in transgenic mice at 7 months of age. Cerebral blood flow response in transgenic mice was augmented but not prolonged. These results are consistent with the existence of BOLD signal hyperactivation in non-demented AD-risk human subjects, supporting its potential use as an early diagnostic marker of AD.

Simultaneous Imaging of CBF Change and BOLD with Saturation-Recovery-T1 Method.

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Xiao Wang

Full Text Available A neuroimaging technique based on the saturation-recovery (SR-T1 MRI method was applied for simultaneously imaging blood oxygenation level dependence (BOLD contrast and cerebral blood flow change (ΔCBF, which is determined by CBF-sensitive T1 relaxation rate change (ΔR1CBF. This technique was validated by quantitatively examining the relationships among ΔR1CBF, ΔCBF, BOLD and relative CBF change (rCBF, which was simultaneously measured by laser Doppler flowmetry under global ischemia and hypercapnia conditions, respectively, in the rat brain. It was found that during ischemia, BOLD decreased 23.1±2.8% in the cortical area; ΔR1CBF decreased 0.020±0.004s-1 corresponding to a ΔCBF decrease of 1.07±0.24 ml/g/min and 89.5±1.8% CBF reduction (n=5, resulting in a baseline CBF value (=1.18 ml/g/min consistent with the literature reports. The CBF change quantification based on temperature corrected ΔR1CBF had a better accuracy than apparent R1 change (ΔR1app; nevertheless, ΔR1app without temperature correction still provides a good approximation for quantifying CBF change since perfusion dominates the evolution of the longitudinal relaxation rate (R1app. In contrast to the excellent consistency between ΔCBF and rCBF measured during and after ischemia, the BOLD change during the post-ischemia period was temporally disassociated with ΔCBF, indicating distinct CBF and BOLD responses. Similar results were also observed for the hypercapnia study. The overall results demonstrate that the SR-T1 MRI method is effective for noninvasive and quantitative imaging of both ΔCBF and BOLD associated with physiological and/or pathological changes.

Resting State BOLD Variability in Alzheimer’s Disease: A Marker of Cognitive Decline or Cerebrovascular Status?

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Vanessa Scarapicchia

2018-02-01

Full Text Available Background: Alzheimer’s disease (AD is a neurodegenerative disorder that may benefit from early diagnosis and intervention. Therefore, there is a need to identify early biomarkers of AD using non-invasive techniques such as functional magnetic resonance imaging (fMRI. Recently, novel approaches to the analysis of resting-state fMRI data have been developed that focus on the moment-to-moment variability in the blood oxygen level dependent (BOLD signal. The objective of the current study was to investigate BOLD variability as a novel early biomarker of AD and its associated psychophysiological correlates.Method: Data were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI 2 database from 19 participants with AD and 19 similarly aged controls. For each participant, a map of BOLD signal variability (SDBOLD was computed as the standard deviation of the BOLD timeseries at each voxel. Group comparisons were performed to examine global differences in resting state SDBOLD in AD versus healthy controls. Correlations were then examined between participant SDBOLD maps and (1 ADNI-derived composite scores of memory and executive function and (2 neuroimaging markers of cerebrovascular status.Results: Between-group comparisons revealed significant (p < 0.05 increases in SDBOLD in patients with AD relative to healthy controls in right-lateralized frontal regions. Lower memory scores and higher WMH burden were associated with greater SDBOLD in the healthy control group (p < 0.1, but not individuals with AD.Conclusion: The current study provides proof of concept of a novel resting state fMRI analysis technique that is non-invasive, easily accessible, and clinically compatible. To further explore the potential of SDBOLD as a biomarker of AD, additional studies in larger, longitudinal samples are needed to better understand the changes in SDBOLD that characterize earlier stages of disease progression and their underlying psychophysiological

Role of 3T multiparametric-MRI with BOLD hypoxia imaging for diagnosis and post therapy response evaluation of postoperative recurrent cervical cancers

Directory of Open Access Journals (Sweden)

Abhishek Mahajan

2016-01-01

Conclusion: Conventional-MR with MPMRI significantly increases the diagnostic accuracy for suspected vaginal vault/local recurrence. Post therapy serial MPMRI with hypoxia imaging follow-up objectively documents the response. MPMRI and BOLD hypoxia imaging provide information regarding tumor biology at the molecular, subcellular, cellular and tissue levels and this information may be used as an appropriate and reliable biologic target for radiation dose painting to optimize therapy in future.

Response of neural reward regions to food cues in autism spectrum disorders

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Cascio Carissa J

2012-05-01

Full Text Available Abstract Background One hypothesis for the social deficits that characterize autism spectrum disorders (ASD is diminished neural reward response to social interaction and attachment. Prior research using established monetary reward paradigms as a test of non-social reward to compare with social reward may involve confounds in the ability of individuals with ASD to utilize symbolic representation of money and the abstraction required to interpret monetary gains. Thus, a useful addition to our understanding of neural reward circuitry in ASD includes a characterization of the neural response to primary rewards. Method We asked 17 children with ASD and 18 children without ASD to abstain from eating for at least four hours before an MRI scan in which they viewed images of high-calorie foods. We assessed the neural reward network for increases in the blood oxygenation level dependent (BOLD signal in response to the food images Results We found very similar patterns of increased BOLD signal to these images in the two groups; both groups showed increased BOLD signal in the bilateral amygdala, as well as in the nucleus accumbens, orbitofrontal cortex, and insula. Direct group comparisons revealed that the ASD group showed a stronger response to food cues in bilateral insula along the anterior-posterior gradient and in the anterior cingulate cortex than the control group, whereas there were no neural reward regions that showed higher activation for controls than for ASD. Conclusion These results suggest that neural response to primary rewards is not diminished but in fact shows an aberrant enhancement in children with ASD.

Music reduces pain and increases resting state fMRI BOLD signal amplitude in the left angular gyrus in fibromyalgia patients

DEFF Research Database (Denmark)

Garza-Villarreal, Eduardo A; Jiang, Zhiguo; Vuust, Peter

2015-01-01

, correlated to the analgesia reports. The post-hoc seed-based functional connectivity analysis of the lAnG showed found higher connectivity after listening to music with right dorsolateral prefrontal cortex (rdlPFC), the left caudate (lCau), and decreased connectivity with right anterior cingulate cortex (r......Music reduces pain in fibromyalgia (FM), a chronic pain disease, but the functional neural correlates of music-induced analgesia (MIA) are still largely unknown. We recruited FM patients (n = 22) who listened to their preferred relaxing music and an auditory control (pink noise) for 5 min without...... external noise from fMRI image acquisition. Resting state fMRI was then acquired before and after the music and control conditions. A significant increase in the amplitude of low frequency fluctuations of the BOLD signal was evident in the left angular gyrus (lAnG) after listening to music, which in turn...

"Boldness" in the domestic dog differs among breeds and breed groups.

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Starling, Melissa J; Branson, Nicholas; Thomson, Peter C; McGreevy, Paul D

2013-07-01

"Boldness" in dogs is believed to be one end of the shy-bold axis, representing a super-trait. Several personality traits fall under the influence of this super-trait. Previous studies on boldness in dogs have found differences among breeds, but grouping breeds on the basis of behavioural similarities has been elusive. This study investigated differences in the expression of boldness among dog breeds, kennel club breed groups, and sub-groups of kennel club breed groups by way of a survey on dog personality circulated among Australian dog-training clubs and internet forums and lists. Breed had a significant effect on boldness (F=1.63, numDF=111, denDF=272, ppurpose. Retrievers were significantly bolder than flushing and pointing breeds (Reg. Coef.=2.148; S.E.=0.593; pdogs. Differences in boldness among groups and sub-groups suggest that behavioural tendencies may be influenced by historical purpose regardless of whether that purpose still factors in selective breeding. Copyright © 2013 Elsevier B.V. All rights reserved.

Variable reflectivity signal mirrors and signal response measurements

International Nuclear Information System (INIS)

Vine, Glenn de; Shaddock, Daniel A; McClelland, David E

2002-01-01

Future gravitational wave detectors will include some form of signal mirror in order to alter the signal response of the device. We introduce interferometer configurations which utilize a variable reflectivity signal mirror allowing a tunable peak frequency and variable signal bandwidth. A detector configured with a Fabry-Perot cavity as the signal mirror is compared theoretically with one using a Michelson interferometer for a signal mirror. A system for the measurement of the interferometer signal responses is introduced. This technique is applied to a power-recycled Michelson interferometer with resonant sideband extraction. We present broadband measurements of the benchtop prototype's signal response for a range of signal cavity detunings. This technique is also applicable to most other gravitational wave detector configurations

Variable reflectivity signal mirrors and signal response measurements

CERN Document Server

Vine, G D; McClelland, D E

2002-01-01

Future gravitational wave detectors will include some form of signal mirror in order to alter the signal response of the device. We introduce interferometer configurations which utilize a variable reflectivity signal mirror allowing a tunable peak frequency and variable signal bandwidth. A detector configured with a Fabry-Perot cavity as the signal mirror is compared theoretically with one using a Michelson interferometer for a signal mirror. A system for the measurement of the interferometer signal responses is introduced. This technique is applied to a power-recycled Michelson interferometer with resonant sideband extraction. We present broadband measurements of the benchtop prototype's signal response for a range of signal cavity detunings. This technique is also applicable to most other gravitational wave detector configurations.

Determination of relative CMRO2 from CBF and BOLD changes: significant increase of oxygen consumption rate during visual stimulation

DEFF Research Database (Denmark)

Kim, S.G.; Rostrup, Egill; Larsson, H.B.

1999-01-01

signal changes were measured simultaneously using the flow-sensitive alternating inversion recovery (FAIR) technique. During hypercapnia established by an end-tidal CO2 increase of 1.46 kPa, CBF in the visual cortex increased by 47.3 +/- 17.3% (mean +/- SD; n = 9), and deltaR2* was -0.478 +/- 0.147 sec......The blood oxygenation level-dependent (BOLD) effect in functional magnetic resonance imaging depends on at least partial uncoupling between cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) changes. By measuring CBF and BOLD simultaneously, the relative change in CMRO2 can...

Role of 3T multiparametric-MRI with BOLD hypoxia imaging for diagnosis and post therapy response evaluation of postoperative recurrent cervical cancers

International Nuclear Information System (INIS)

Mahajan, Abhishek; Engineer, Reena; Chopra, Supriya; Mahanshetty, Umesh; Juvekar, S.L.; Shrivastava, S.K.; Desekar, Naresh; Thakur, M.H.

2015-01-01

vaginal vault/local recurrence following primary surgery for cervical cancer. With institutional review board approval and written informed consent 30 women (median age: 45 years) from October 2009 to March 2010 with previous operated carcinoma cervix and suspected clinical vaginal vault/local recurrence were examined with 3.0T-MRI. MRI imaging included conventional and MPMRI sequences [dynamic contrast enhanced (DCE), diffusion weighted (DW), 1H-MR spectroscopy (1HMRS), blood oxygen level dependent hypoxia imaging (BOLD)]. Two radiologists, blinded to pathologic findings, independently assessed the pretherapy MRI findings and then correlated it with histopathology findings. Sensitivity, specificity, positive predictive value, negative predictive value and their confidence intervals were calculated. The pre and post therapy conventional and MPMRI parameters were analyzed and correlated with response to therapy. Of the 30 patients, there were 24 recurrent tumors and 6 benign lesions. The accuracy of diagnosing recurrent vault lesions was highest at combined MPMRI and conventional MRI (100%) than at conventional-MRI (70%) or MPMRI (96.7%) alone. Significant correlation was seen between percentage tumor regression and pre-treatment parameters such as negative enhancement integral (NEI) (p = 0.02), the maximum slope (p = 0.04), mADC value (p = 0.001) and amount of hypoxic fraction on the pretherapy MRI (p = 0.01). Conventional-MR with MPMRI significantly increases the diagnostic accuracy for suspected vaginal vault/local recurrence. Post therapy serial MPMRI with hypoxia imaging follow-up objectively documents the response. MPMRI and BOLD hypoxia imaging provide information regarding tumor biology at the molecular, subcellular, cellular and tissue levels and this information may be used as an appropriate and reliable biologic target for radiation dose painting to optimize therapy in future

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.

BOLD magnetic resonance imaging in nephrology

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Hall, Michael E; Jordan, Jennifer H; Juncos, Luis A; Hundley, W Gregory; Hall, John E

2018-01-01

Magnetic resonance (MR) imaging, a non-invasive modality that provides anatomic and physiologic information, is increasingly used for diagnosis of pathophysiologic conditions and for understanding renal physiology in humans. Although functional MR imaging methods were pioneered to investigate the brain, they also offer powerful techniques for investigation of other organ systems such as the kidneys. However, imaging the kidneys provides unique challenges due to potential complications from contrast agents. Therefore, development of non-contrast techniques to study kidney anatomy and physiology is important. Blood oxygen level-dependent (BOLD) MR is a non-contrast imaging technique that provides functional information related to renal tissue oxygenation in various pathophysiologic conditions. Here we discuss technical considerations, clinical uses and future directions for use of BOLD MR as well as complementary MR techniques to better understand renal pathophysiology. Our intent is to summarize kidney BOLD MR applications for the clinician rather than focusing on the complex physical challenges that functional MR imaging encompasses; however, we briefly discuss some of those issues. PMID:29559807

Blood oxygenation level dependent (BOLD). Renal imaging. Concepts and applications; Blood Oxygenation Level Dependent (BOLD). Bildgebung der Nieren. Konzepte und Anwendungen

Energy Technology Data Exchange (ETDEWEB)

Nissen, Johanna C.; Haneder, Stefan; Schoenberg, Stefan O.; Michaely, Henrik J. [Heidelberg Univ. Medizinische Fakultaet Mannheim (Germany). Inst. fuer Klinische Radiologie und Nuklearmedizin; Mie, Moritz B.; Zoellner, Frank G. [Heidelberg Univ. Medizinische Fakultaet Mannheim (DE). Inst. fuer Computerunterstuetzte Klinische Medizin (CKM)

2010-07-01

Many renal diseases as well as several pharmacons cause a change in renal blood flow and/or renal oxygenation. The blood oxygenation level dependent (BOLD) imaging takes advantage of local field inhomogeneities and is based on a T2{sup *}-weighted sequence. BOLD is a non-invasive method allowing an estimation of the renal, particularly the medullary oxygenation, and an indirect measurement of blood flow without administration of contrast agents. Thus, effects of different drugs on the kidney and various renal diseases can be controlled and observed. This work will provide an overview of the studies carried out so far and identify ways how BOLD can be used in clinical studies. (orig.)

Internal representations for face detection: an application of noise-based image classification to BOLD responses.

Science.gov (United States)

Nestor, Adrian; Vettel, Jean M; Tarr, Michael J

2013-11-01

What basic visual structures underlie human face detection and how can we extract such structures directly from the amplitude of neural responses elicited by face processing? Here, we address these issues by investigating an extension of noise-based image classification to BOLD responses recorded in high-level visual areas. First, we assess the applicability of this classification method to such data and, second, we explore its results in connection with the neural processing of faces. To this end, we construct luminance templates from white noise fields based on the response of face-selective areas in the human ventral cortex. Using behaviorally and neurally-derived classification images, our results reveal a family of simple but robust image structures subserving face representation and detection. Thus, we confirm the role played by classical face selective regions in face detection and we help clarify the representational basis of this perceptual function. From a theory standpoint, our findings support the idea of simple but highly diagnostic neurally-coded features for face detection. At the same time, from a methodological perspective, our work demonstrates the ability of noise-based image classification in conjunction with fMRI to help uncover the structure of high-level perceptual representations. Copyright © 2012 Wiley Periodicals, Inc.

Multi-regional investigation of the relationship between functional MRI blood oxygenation level dependent (BOLD activation and GABA concentration.

Directory of Open Access Journals (Sweden)

Ashley D Harris

Full Text Available Several recent studies have reported an inter-individual correlation between regional GABA concentration, as measured by MRS, and the amplitude of the functional blood oxygenation level dependent (BOLD response in the same region. In this study, we set out to investigate whether this coupling generalizes across cortex. In 18 healthy participants, we performed edited MRS measurements of GABA and BOLD-fMRI experiments using regionally related activation paradigms. Regions and tasks were the: occipital cortex with a visual grating stimulus; auditory cortex with a white noise stimulus; sensorimotor cortex with a finger-tapping task; frontal eye field with a saccade task; and dorsolateral prefrontal cortex with a working memory task. In contrast to the prior literature, no correlation between GABA concentration and BOLD activation was detected in any region. The origin of this discrepancy is not clear. Subtle differences in study design or insufficient power may cause differing results; these and other potential reasons for the discrepant results are discussed. This negative result, although it should be interpreted with caution, has a larger sample size than prior positive results, and suggests that the relationship between GABA and the BOLD response may be more complex than previously thought.

Global brain blood-oxygen level responses to autonomic challenges in obstructive sleep apnea.

Directory of Open Access Journals (Sweden)

Paul M Macey

Full Text Available Obstructive sleep apnea (OSA is accompanied by brain injury, perhaps resulting from apnea-related hypoxia or periods of impaired cerebral perfusion. Perfusion changes can be determined indirectly by evaluation of cerebral blood volume and oxygenation alterations, which can be measured rapidly and non-invasively with the global blood oxygen level dependent (BOLD signal, a magnetic resonance imaging procedure. We assessed acute BOLD responses in OSA subjects to pressor challenges that elicit cerebral blood flow changes, using a two-group comparative design with healthy subjects as a reference. We separately assessed female and male patterns, since OSA characteristics and brain injury differ between sexes. We studied 94 subjects, 37 with newly-diagnosed, untreated OSA (6 female (age mean ± std: 52.1±8.1 yrs; apnea/hypopnea index [AHI]: 27.7±15.6 events/hr and 31 male 54.3±8.4 yrs; AHI: 37.4±19.6 events/hr, and 20 female (age 50.5±8.1 yrs and 37 male (age 45.6±9.2 yrs healthy control subjects. We measured brain BOLD responses every 2 s while subjects underwent cold pressor, hand grip, and Valsalva maneuver challenges. The global BOLD signal rapidly changed after the first 2 s of each challenge, and differed in magnitude between groups to two challenges (cold pressor, hand grip, but not to the Valsalva maneuver (repeated measures ANOVA, p<0.05. OSA females showed greater differences from males in response magnitude and pattern, relative to healthy counterparts. Cold pressor BOLD signal increases (mean ± adjusted standard error at the 8 s peak were: OSA 0.14±0.08% vs. Control 0.31±0.06%, and hand grip at 6 s were: OSA 0.08±0.03% vs. Control at 0.30±0.02%. These findings, indicative of reduced cerebral blood flow changes to autonomic challenges in OSA, complement earlier reports of altered resting blood flow and reduced cerebral artery responsiveness. Females are more affected than males, an outcome which may contribute to the sex

Amphetamine modulates brain signal variability and working memory in younger and older adults.

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Garrett, Douglas D; Nagel, Irene E; Preuschhof, Claudia; Burzynska, Agnieszka Z; Marchner, Janina; Wiegert, Steffen; Jungehülsing, Gerhard J; Nyberg, Lars; Villringer, Arno; Li, Shu-Chen; Heekeren, Hauke R; Bäckman, Lars; Lindenberger, Ulman

2015-06-16

Better-performing younger adults typically express greater brain signal variability relative to older, poorer performers. Mechanisms for age and performance-graded differences in brain dynamics have, however, not yet been uncovered. Given the age-related decline of the dopamine (DA) system in normal cognitive aging, DA neuromodulation is one plausible mechanism. Hence, agents that boost systemic DA [such as d-amphetamine (AMPH)] may help to restore deficient signal variability levels. Furthermore, despite the standard practice of counterbalancing drug session order (AMPH first vs. placebo first), it remains understudied how AMPH may interact with practice effects, possibly influencing whether DA up-regulation is functional. We examined the effects of AMPH on functional-MRI-based blood oxygen level-dependent (BOLD) signal variability (SD(BOLD)) in younger and older adults during a working memory task (letter n-back). Older adults expressed lower brain signal variability at placebo, but met or exceeded young adult SD(BOLD) levels in the presence of AMPH. Drug session order greatly moderated change-change relations between AMPH-driven SD(BOLD) and reaction time means (RT(mean)) and SDs (RT(SD)). Older adults who received AMPH in the first session tended to improve in RT(mean) and RT(SD) when SD(BOLD) was boosted on AMPH, whereas younger and older adults who received AMPH in the second session showed either a performance improvement when SD(BOLD) decreased (for RT(mean)) or no effect at all (for RT(SD)). The present findings support the hypothesis that age differences in brain signal variability reflect aging-induced changes in dopaminergic neuromodulation. The observed interactions among AMPH, age, and session order highlight the state- and practice-dependent neurochemical basis of human brain dynamics.

SU-D-207A-03: Potential Role of BOLD MRI in Discrimination of Aggressive Tumor Habitat in Prostate Cancer

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Ford, J; Lopez, C; Tschudi, Y; Breto, A; Padgett, K; Pollack, A; Stoyanova, R [University of Miami Miller School of Medicine, Miami, FL (United States)

2016-06-15

Purpose: To determine whether blood oxygenation level dependent (BOLD) MRI signal measured in prostate cancer patients, in addition to quantitative diffusion and perfusion parameters from multiparametric (mp)MRI exams, can help discriminate aggressive and/or radioresistant lesions. Methods: Several ongoing clinical trials in our institution require mpMRI exam to determine eligibility (presence of identifiable tumor lesion on mpMRI) and prostate volumes for dose escalation. Upon consent, patients undergo fiducial markers placement and a T2*-weighted imaging at the time of CT sim to facilitate the fusion. In a retrospective analysis eleven clinical trial patients were identified who had undergone mpMRI on GE 3T magnet, followed by T2*-weighted imaging (time-period mean±SD = 48±20 days) using a consistent protocol (gradient echo, TR/TE=30/11.8ms, flip angle=12, matrix=256×256×75, voxel size=1.25×1.25×2.5mm). ROIs for prostate tumor lesions were automatically determined using ADC threshold ≤1200 µm2/s. Although the MR protocol was not intended for BOLD analysis, we utilized the T2*-weighted signal normalized to that in nearby muscle; likewise, T2-weighted lesion signal was normalized to muscle, following rigid registration of the T2 to T2* images. The ratio of these normalized signals, T2*/T2, is a measure of BOLD effect in the prostate tumors. Perfusion parameters (Ktrans, ve, kep) were also calculated. Results: T2*/T2 (mean±SE) was found to be substantially lower for Gleason score (GS) 8&9 (0.82±0.04) compared to GS 7 (1.08±0.07). A k-means cluster analysis of T2*/T2 versus kep = Ktrans/ve revealed two distinct clusters, one with higher T2*/T2 and lower kep, containing only GS 7 lesions, and another with lower T2*/T2 and higher kep, associated with tumor aggressiveness. This latter cluster contained all GS 8&9 lesions, as well as some GS 7. Conclusion: BOLD MRI, in addition to ADC and kep, may play a role (perhaps orthogonal to Gleason score) in

Insulin sensitivity affects corticolimbic brain responses to visual food cues in polycystic ovary syndrome patients.

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Alsaadi, Hanin M; Van Vugt, Dean A

2015-11-01

This study examined the effect of insulin sensitivity on the responsiveness of appetite regulatory brain regions to visual food cues. Nineteen participants diagnosed with polycystic ovary syndrome (PCOS) were divided into insulin-sensitive (n=8) and insulin-resistant (n=11) groups based on the homeostatic model assessment of insulin resistance (HOMA2-IR). Subjects underwent functional magnetic resonance imaging (fMRI) while viewing food pictures following water or dextrose consumption. The corticolimbic blood oxygen level dependent (BOLD) responses to high-calorie (HC) or low-calorie (LC) food pictures were compared within and between groups. BOLD responses to food pictures were reduced during a glucose challenge in numerous corticolimbic brain regions in insulin-sensitive but not insulin-resistant subjects. Furthermore, the degree of insulin resistance positively correlated with the corticolimbic BOLD response in the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), anterior cingulate and ventral tegmental area (VTA) in response to HC pictures, and in the dorsolateral prefrontal cortex (DLPFC), mPFC, anterior cingulate, and insula in response to LC pictures following a glucose challenge. BOLD signal in the OFC, midbrain, hippocampus, and amygdala following a glucose challenge correlated with HOMA2-IR in response to HC-LC pictures. We conclude that the normal inhibition of corticolimbic brain responses to food pictures during a glucose challenge is compromised in insulin-resistant subjects. The increase in brain responsiveness to food pictures during postprandial hyperinsulinemia may lead to greater non-homeostatic eating and perpetuate obesity in insulin-resistant subjects.

A NO way to BOLD?

DEFF Research Database (Denmark)

Aamand, Rasmus; Dalsgaard, Thomas; Ho, Yi Ching Lynn

2013-01-01

Neurovascular coupling links neuronal activity to vasodilation. Nitric oxide (NO) is a potent vasodilator, and in neurovascular coupling NO production from NO synthases plays an important role. However, another pathway for NO production also exists, namely the nitrate-nitrite-NO pathway. On this ......Neurovascular coupling links neuronal activity to vasodilation. Nitric oxide (NO) is a potent vasodilator, and in neurovascular coupling NO production from NO synthases plays an important role. However, another pathway for NO production also exists, namely the nitrate-nitrite-NO pathway...... to stimuli. A faster and smaller BOLD response, with less variation across local cortex, is consistent with an enhanced hemodynamic coupling during elevated nitrate intake. These findings suggest that dietary patterns, via the nitrate-nitrite-NO pathway, may be a potential way to affect key properties....... On this basis, we hypothesized that dietary nitrate (NO3-) could influence the brain's hemodynamic response to neuronal stimulation. In the present study, 20 healthy male participants were given either sodium nitrate (NaNO3) or sodium chloride (NaCl) (saline placebo) in a crossover study and were shown visual...

Cerebral Asymmetry of fMRI-BOLD Responses to Visual Stimulation.

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Anders Hougaard

Full Text Available Hemispheric asymmetry of a wide range of functions is a hallmark of the human brain. The visual system has traditionally been thought of as symmetrically distributed in the brain, but a growing body of evidence has challenged this view. Some highly specific visual tasks have been shown to depend on hemispheric specialization. However, the possible lateralization of cerebral responses to a simple checkerboard visual stimulation has not been a focus of previous studies. To investigate this, we performed two sessions of blood-oxygenation level dependent (BOLD functional magnetic resonance imaging (fMRI in 54 healthy subjects during stimulation with a black and white checkerboard visual stimulus. While carefully excluding possible non-physiological causes of left-to-right bias, we compared the activation of the left and the right cerebral hemispheres and related this to grey matter volume, handedness, age, gender, ocular dominance, interocular difference in visual acuity, as well as line-bisection performance. We found a general lateralization of cerebral activation towards the right hemisphere of early visual cortical areas and areas of higher-level visual processing, involved in visuospatial attention, especially in top-down (i.e., goal-oriented attentional processing. This right hemisphere lateralization was partly, but not completely, explained by an increased grey matter volume in the right hemisphere of the early visual areas. Difference in activation of the superior parietal lobule was correlated with subject age, suggesting a shift towards the left hemisphere with increasing age. Our findings suggest a right-hemispheric dominance of these areas, which could lend support to the generally observed leftward visual attentional bias and to the left hemifield advantage for some visual perception tasks.

SU-E-J-223: A BOLD Contrast Imaging Sequence to Evaluate Oxygenation Changes Due to Breath Holding for Breast Radiotherapy: A Pilot Study

International Nuclear Information System (INIS)

Adamson, J; Chang, Z; Cai, J; Palta, M; Horton, J; Yin, F; Blitzblau, R

2015-01-01

Purpose: To develop a robust MRI sequence to measure BOLD breath hold induced contrast in context of breast radiotherapy. Methods: Two sequences were selected from prior studies as candidates to measure BOLD contrast attributable to breath holding within the breast: (1) T2* based Gradient Echo EPI (TR/TE = 500/41ms, flip angle = 60°), and (2) T2 based Single Shot Fast Spin Echo (SSFSE) (TR/TE = 3000/60ms). We enrolled ten women post-lumpectomy for breast cancer who were undergoing treatment planning for whole breast radiotherapy. Each session utilized a 1.5T GE MRI and 4 channel breast coil with the subject immobilized prone on a custom board. For each sequence, 1–3 planes of the lumpectomy breast were imaged continuously during a background measurement (1min) and intermittent breath holds (20–40s per breath hold, 3–5 holds per sequence). BOLD contrast was quantified as correlation of changes in per-pixel intensity with the breath hold schedule convolved with a hemodynamic response function. Subtle motion was corrected using a deformable registration algorithm. Correlation with breath-holding was considered significant if p<0.001. Results: The percentage of the breast ROI with positive BOLD contrast measured by the two sequences were in agreement with a correlation coefficient of R=0.72 (p=0.02). While both sequences demonstrated areas with strong BOLD response, the response was more systematic throughout the breast for the SSFSE (T2) sequence (% breast with response in the same direction: 51.2%±0.7% for T2* vs. 68.1%±16% for T2). In addition, the T2 sequence was less prone to magnetic susceptibility artifacts, especially in presence of seroma, and provided a more robust image with little distortion or artifacts. Conclusion: A T2 SSFSE sequence shows promise for measuring BOLD contrast in the context of breast radiotherapy utilizing a breath hold technique. Further study in a larger patient cohort is warranted to better refine this novel technique

SU-E-J-223: A BOLD Contrast Imaging Sequence to Evaluate Oxygenation Changes Due to Breath Holding for Breast Radiotherapy: A Pilot Study

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Adamson, J; Chang, Z; Cai, J; Palta, M; Horton, J; Yin, F; Blitzblau, R [Duke University Medical Center, Durham, NC (United States)

2015-06-15

Purpose: To develop a robust MRI sequence to measure BOLD breath hold induced contrast in context of breast radiotherapy. Methods: Two sequences were selected from prior studies as candidates to measure BOLD contrast attributable to breath holding within the breast: (1) T2* based Gradient Echo EPI (TR/TE = 500/41ms, flip angle = 60°), and (2) T2 based Single Shot Fast Spin Echo (SSFSE) (TR/TE = 3000/60ms). We enrolled ten women post-lumpectomy for breast cancer who were undergoing treatment planning for whole breast radiotherapy. Each session utilized a 1.5T GE MRI and 4 channel breast coil with the subject immobilized prone on a custom board. For each sequence, 1–3 planes of the lumpectomy breast were imaged continuously during a background measurement (1min) and intermittent breath holds (20–40s per breath hold, 3–5 holds per sequence). BOLD contrast was quantified as correlation of changes in per-pixel intensity with the breath hold schedule convolved with a hemodynamic response function. Subtle motion was corrected using a deformable registration algorithm. Correlation with breath-holding was considered significant if p<0.001. Results: The percentage of the breast ROI with positive BOLD contrast measured by the two sequences were in agreement with a correlation coefficient of R=0.72 (p=0.02). While both sequences demonstrated areas with strong BOLD response, the response was more systematic throughout the breast for the SSFSE (T2) sequence (% breast with response in the same direction: 51.2%±0.7% for T2* vs. 68.1%±16% for T2). In addition, the T2 sequence was less prone to magnetic susceptibility artifacts, especially in presence of seroma, and provided a more robust image with little distortion or artifacts. Conclusion: A T2 SSFSE sequence shows promise for measuring BOLD contrast in the context of breast radiotherapy utilizing a breath hold technique. Further study in a larger patient cohort is warranted to better refine this novel technique.

Prospective MR image alignment between breath-holds: Application to renal BOLD MRI.

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Kalis, Inge M; Pilutti, David; Krafft, Axel J; Hennig, Jürgen; Bock, Michael

2017-04-01

To present an image registration method for renal blood oxygen level-dependent (BOLD) measurements that enables semiautomatic assessment of parenchymal and medullary R2* changes under a functional challenge. In a series of breath-hold acquisitions, three-dimensional data were acquired initially for prospective image registration of subsequent BOLD measurements. An algorithm for kidney alignment for BOLD renal imaging (KALIBRI) was implemented to detect the positions of the left and right kidney so that the kidneys were acquired in the subsequent BOLD measurement at consistent anatomical locations. Residual in-plane distortions were corrected retrospectively so that semiautomatic dynamic R2* measurements of the renal cortex and medulla become feasible. KALIBRI was tested in six healthy volunteers during a series of BOLD experiments, which included a 600- to 1000-mL water challenge. Prospective image registration and BOLD imaging of each kidney was achieved within a total measurement time of about 17 s, enabling its execution within a single breath-hold. KALIBRI improved the registration by up to 35% as found with mutual information measures. In four volunteers, a medullary R2* decrease of up to 40% was observed after water ingestion. KALIBRI improves the quality of two-dimensional time-resolved renal BOLD MRI by aligning local renal anatomy, which allows for consistent R2* measurements over many breath-holds. Magn Reson Med 77:1573-1582, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Blood oxygenation level dependent (BOLD). Renal imaging. Concepts and applications

International Nuclear Information System (INIS)

Nissen, Johanna C.; Haneder, Stefan; Schoenberg, Stefan O.; Michaely, Henrik J.

2010-01-01

Many renal diseases as well as several pharmacons cause a change in renal blood flow and/or renal oxygenation. The blood oxygenation level dependent (BOLD) imaging takes advantage of local field inhomogeneities and is based on a T2 * -weighted sequence. BOLD is a non-invasive method allowing an estimation of the renal, particularly the medullary oxygenation, and an indirect measurement of blood flow without administration of contrast agents. Thus, effects of different drugs on the kidney and various renal diseases can be controlled and observed. This work will provide an overview of the studies carried out so far and identify ways how BOLD can be used in clinical studies. (orig.)

Using BOLD imaging to measure renal oxygenation dynamics in rats injected with diuretics

International Nuclear Information System (INIS)

Kusakabe, Yoshinori; Matsushita, Taro; Honda, Saori; Okada, Sakie; Murase, Kenya

2010-01-01

We used blood oxygenation level-dependent magnetic resonance imaging (BOLD MRI) to measure renal oxygenation dynamics in rats injected with diuretics and evaluated diuretic effect on renal oxygenation. We performed BOLD MRI studies in 32 rats using a 1.5-tesla MR imaging system for animal experiments. We intravenously injected rats with saline (n=7), furosemide (n=7), acetazolamide (n=6), or mannitol (n=6). For controls, 6 rats were not injected with drugs. We estimated the apparent transverse relaxation rate (R 2 *) from the apparent transverse relaxation time (T 2 *)-weighted images and measured the time course of R 2 * at 4-min intervals over approximately 30 min. Compared with preadministration values, the R 2 * value did not change significantly in either the cortex or medulla in the control and mannitol groups but decreased significantly in the saline group; the R 2 * value significantly decreased in the medulla but did not change significantly in the cortex in the furosemide group; and the R 2 * value significantly increased in the medulla and significantly decreased in the cortex in the acetazolamide group. Our study results suggest that BOLD MRI is useful for evaluating the dynamics of renal oxygenation in response to various diuretics in the renal cortex and in the medulla. (author)

Heterogenous migraine aura symptoms correlate with visual cortex functional magnetic resonance imaging responses

DEFF Research Database (Denmark)

Arngrim, Nanna; Hougaard, Anders; Ahmadi, Khazar

2017-01-01

Objective: Migraine aura is sparsely studied due to the highly challenging task of capturing patients during aura. Cortical spreading depression (CSD) is likely the underlying phenomenon of aura. The possible correlation between the multifaceted phenomenology of aura symptoms and the effects of CSD...... on the brain has not been ascertained. Methods: Five migraine patients were studied during various forms of aura symptoms induced by hypoxia, sham hypoxia, or physical exercise with concurrent photostimulation. The blood oxygenation level–dependent (BOLD) functional magnetic resonance imaging (fMRI) signal...... response to visual stimulation was measured in retinotopic mapping–defined visual cortex areas V1 to V4. Results: We found reduced BOLD response in patients reporting scotoma and increased response in patients who only experienced positive symptoms. Furthermore, patients with bilateral visual symptoms had...

Modulation of cognitive control levels via manipulation of saccade trial-type probability assessed with event-related BOLD fMRI.

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Pierce, Jordan E; McDowell, Jennifer E

2016-02-01

Cognitive control supports flexible behavior adapted to meet current goals and can be modeled through investigation of saccade tasks with varying cognitive demands. Basic prosaccades (rapid glances toward a newly appearing stimulus) are supported by neural circuitry, including occipital and posterior parietal cortex, frontal and supplementary eye fields, and basal ganglia. These trials can be contrasted with complex antisaccades (glances toward the mirror image location of a stimulus), which are characterized by greater functional magnetic resonance imaging (MRI) blood oxygenation level-dependent (BOLD) signal in the aforementioned regions and recruitment of additional regions such as dorsolateral prefrontal cortex. The current study manipulated the cognitive demands of these saccade tasks by presenting three rapid event-related runs of mixed saccades with a varying probability of antisaccade vs. prosaccade trials (25, 50, or 75%). Behavioral results showed an effect of trial-type probability on reaction time, with slower responses in runs with a high antisaccade probability. Imaging results exhibited an effect of probability in bilateral pre- and postcentral gyrus, bilateral superior temporal gyrus, and medial frontal gyrus. Additionally, the interaction between saccade trial type and probability revealed a strong probability effect for prosaccade trials, showing a linear increase in activation parallel to antisaccade probability in bilateral temporal/occipital, posterior parietal, medial frontal, and lateral prefrontal cortex. In contrast, antisaccade trials showed elevated activation across all runs. Overall, this study demonstrated that improbable performance of a typically simple prosaccade task led to augmented BOLD signal to support changing cognitive control demands, resulting in activation levels similar to the more complex antisaccade task. Copyright © 2016 the American Physiological Society.

Linear increases in BOLD response associated with increasing proportion of incongruent trials across time in a colour Stroop task.

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Mitchell, Rachel L C

2010-05-01

Selective attention is popularly assessed with colour Stroop tasks in which participants name the ink colour of colour words, whilst resisting interference from the natural tendency to read the words. Prior studies hinted that the key brain regions (dorsolateral prefrontal (dlPFC) and anterior cingulate cortex (ACC)) may vary their degree of involvement, dependent on attentional demand. This study aimed to determine whether a parametrically varied increase in attentional demand resulted in linearly increased activity in these regions, and/or whether additional regions would be recruited during high attentional demand. Twenty-eight healthy young adults underwent fMRI whilst naming the font colour of colour words. Linear increases in BOLD response were assessed with increasing percentage incongruent trials per block (0, 20, 40, 60, 80, and 100%). Whilst ACC activation increased linearly according to incongruity level, dlPFC activity appeared constant. Together with behavioural evidence of reduced Stroop interference, these data support a load-dependent conflict-related response in ACC, but not dlPFC.

BOLD magnetic resonance imaging in nephrology

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Hall ME

2018-03-01

Full Text Available Michael E Hall,1,2 Jennifer H Jordan,3 Luis A Juncos,1,2 W Gregory Hundley,3 John E Hall2 1Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA; 2Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA; 3Department of Internal Medicine, Section on Cardiovascular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA Abstract: Magnetic resonance (MR imaging, a non-invasive modality that provides anatomic and physiologic information, is increasingly used for diagnosis of pathophysiologic conditions and for understanding renal physiology in humans. Although functional MR imaging methods were pioneered to investigate the brain, they also offer powerful techniques for investigation of other organ systems such as the kidneys. However, imaging the kidneys provides unique challenges due to potential complications from contrast agents. Therefore, development of non-contrast techniques to study kidney anatomy and physiology is important. Blood oxygen level-dependent (BOLD MR is a non-contrast imaging technique that provides functional information related to renal tissue oxygenation in various pathophysiologic conditions. Here we discuss technical considerations, clinical uses and future directions for use of BOLD MR as well as complementary MR techniques to better understand renal pathophysiology. Our intent is to summarize kidney BOLD MR applications for the clinician rather than focusing on the complex physical challenges that functional MR imaging encompasses; however, we briefly discuss some of those issues. Keywords: functional MRI, kidney, oxygenation, chronic kidney disease 

Ridding fMRI data of motion-related influences: Removal of signals with distinct spatial and physical bases in multiecho data.

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Power, Jonathan D; Plitt, Mark; Gotts, Stephen J; Kundu, Prantik; Voon, Valerie; Bandettini, Peter A; Martin, Alex

2018-02-27

"Functional connectivity" techniques are commonplace tools for studying brain organization. A critical element of these analyses is to distinguish variance due to neurobiological signals from variance due to nonneurobiological signals. Multiecho fMRI techniques are a promising means for making such distinctions based on signal decay properties. Here, we report that multiecho fMRI techniques enable excellent removal of certain kinds of artifactual variance, namely, spatially focal artifacts due to motion. By removing these artifacts, multiecho techniques reveal frequent, large-amplitude blood oxygen level-dependent (BOLD) signal changes present across all gray matter that are also linked to motion. These whole-brain BOLD signals could reflect widespread neural processes or other processes, such as alterations in blood partial pressure of carbon dioxide (pCO 2 ) due to ventilation changes. By acquiring multiecho data while monitoring breathing, we demonstrate that whole-brain BOLD signals in the resting state are often caused by changes in breathing that co-occur with head motion. These widespread respiratory fMRI signals cannot be isolated from neurobiological signals by multiecho techniques because they occur via the same BOLD mechanism. Respiratory signals must therefore be removed by some other technique to isolate neurobiological covariance in fMRI time series. Several methods for removing global artifacts are demonstrated and compared, and were found to yield fMRI time series essentially free of motion-related influences. These results identify two kinds of motion-associated fMRI variance, with different physical mechanisms and spatial profiles, each of which strongly and differentially influences functional connectivity patterns. Distance-dependent patterns in covariance are nearly entirely attributable to non-BOLD artifacts.

Music reduces pain and increases resting state fMRI BOLD signal amplitude in the left angular gyrus in fibromyalgia patients

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Eduardo A. Garza-Villarreal

2015-07-01

Full Text Available Music reduces pain in fibromyalgia (FM, a chronic pain disease, but the functional neural correlates of music-induced analgesia are still largely unknown. We recruited FM patients (n = 22 who listened to their preferred relaxing music and an auditory control (pink noise for 5 minutes without external noise from fMRI image acquisition. Resting state fMRI was then acquired before and after the music and control conditions. A significant increase in the amplitude of low frequency fluctuations of the BOLD signal was evident in the left angular gyrus after listening to music, which in turn, correlated to the analgesia reports. The post-hoc seed-based functional connectivity analysis of the left angular gyrus showed found higher connectivity after listening to music with right dorsolateral prefrontal cortex, the left caudate, and decreased connectivity with right anterior cingulate cortex, right supplementary motor area, precuneus and right precentral gyrus. Pain intensity analgesia was correlated (r = .61 to the connectivity of the left angular gyrus with the right precentral gyrus. Our results show that music-induced analgesia in FM is related to top-down regulation of the pain modulatory network by the default-mode network.

Boldness towards novelty and translocation success in captive-raised, orphaned Tasmanian devils.

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Sinn, David L; Cawthen, Lisa; Jones, Susan M; Pukk, Chrissy; Jones, Menna E

2014-01-01

Translocation of endangered animals is common, but success is often variable and/or poor. Despite its intuitive appeal, little is known with regards to how individual differences amongst translocated animals influence their post-release survival, growth, and reproduction. We measured consistent pre-release responses to novelty in a familiar environment (boldness; repeatability=0.55) and cortisol response in a group of captive-reared Tasmanian devils, currently listed as "Endangered" by the IUCN. The devils were then released at either a hard- or soft-release site within their mothers' population of origin, and individual growth, movement, reproduction (females only), and survival across 2-8 months post-release was measured. Sex, release method, cohort, behavior, and cortisol response did not affect post-release growth, nor did these factors influence the home range size of orphan devils. Final linear distances moved from the release site were impacted heavily by the release cohort, but translocated devils' movement overall was not different from that in the same-age wild devils. All orphan females of reproductive age were subsequently captured with offspring. Overall survival rates in translocated devils were moderate (∼42%), and were not affected by devil sex, release method, cohort, release weight, or pre-release cortisol response. Devils that survived during the study period were, however, 3.5 times more bold than those that did not (effect size r=0.76). Our results suggest that conservation managers may need to provide developmental conditions in captivity that promote a wide range of behaviors across individuals slated for wild release. © 2013 Wiley Periodicals, Inc.

BOLD cardiovascular magnetic resonance at 3.0 tesla in myocardial ischemia.

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Manka, Robert; Paetsch, Ingo; Schnackenburg, Bernhard; Gebker, Rolf; Fleck, Eckart; Jahnke, Cosima

2010-09-22

The purpose of this study was to determine the ability of blood oxygen level dependent (BOLD) cardiovascular magnetic resonance (CMR) to detect stress-inducible myocardial ischemic reactions in the presence of angiographically significant coronary artery disease (CAD). Forty-six patients (34 men; age 65 ± 9 years,) with suspected or known coronary artery disease underwent CMR at 3Tesla prior to clinically indicated invasive coronary angiography. BOLD CMR was performed in 3 short axis slices of the heart at rest and during adenosine stress (140 μg/kg/min) followed by late gadolinium enhancement (LGE) imaging. In all 16 standard myocardial segments, T2* values were derived at rest and under adenosine stress. Quantitative coronary angiography served as the standard of reference and defined normal myocardial segments (i.e. all 16 segments in patients without any CAD), ischemic segments (i.e. supplied by a coronary artery with ≥50% luminal narrowing) and non-ischemic segments (i.e. supplied by a non-significantly stenosed coronary artery in patients with significant CAD). Coronary angiography demonstrated significant CAD in 23 patients. BOLD CMR at rest revealed significantly lower T2* values for ischemic segments (26.7 ± 11.6 ms) compared to normal (31.9 ± 11.9 ms; p BOLD CMR at 3Tesla proved feasible and differentiated between ischemic, non-ischemic, and normal myocardial segments in a clinical patient population. BOLD CMR during vasodilator stress identified patients with significant CAD.

Non-invasive multiparametric qBOLD approach for robust mapping of the oxygen extraction fraction.

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Domsch, Sebastian; Mie, Moritz B; Wenz, Frederik; Schad, Lothar R

2014-09-01

The quantitative blood oxygenation level-dependent (qBOLD) method has not become clinically established yet because long acquisition times are necessary to achieve an acceptable certainty of the parameter estimates. In this work, a non-invasive multiparametric (nimp) qBOLD approach based on a simple analytical model is proposed to facilitate robust oxygen extraction fraction (OEF) mapping within clinically acceptable acquisition times by using separate measurements. The protocol consisted of a gradient-echo sampled spin-echo sequence (GESSE), a T2-weighted Carr-Purcell-Meiboom-Gill (CPMG) sequence, and a T2(*)-weighted multi-slice multi-echo gradient echo (MMGE) sequence. The GESSE acquisition time was less than 5 minutes and the extra measurement time for CPMG/MMGE was below 2 minutes each. The proposed nimp-qBOLD approach was validated in healthy subjects (N = 5) and one patient. The proposed nimp-qBOLD approach facilitated more robust OEF mapping with significantly reduced inter- and intra-subject variability compared to the standard qBOLD method. Thereby, an average OEF in all subjects of 27±2% in white matter (WM) and 29±2% in gray matter (GM) using the nimp-qBOLD method was more stable compared to 41±10% (WM) and 46±10% (GM) with standard qBOLD. Moreover, the spatial variance in the image slice (i.e. standard deviation divided by mean) was on average reduced from 35% to 25%. In addition, the preliminary results of the patient are encouraging. The proposed nimp-qBOLD technique provides a promising tool for robust OEF mapping within clinically acceptable acquisition times and could therefore provide an important contribution for analyzing tumors or monitoring the success of radio and chemo therapies. Copyright © 2014. Published by Elsevier GmbH.

Non-invasive multiparametric qBOLD approach for robust mapping of the oxygen extraction fraction

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Domsch, Sebastian; Mie, Moritz B.; Schad, Lothar R. [Heidelberg Univ., Medical Faculty Mannheim (Germany). Computer Assisted Clinical Medicine; Wenz, Frederik [Heidelberg Univ., Medical Faculty Mannheim (Germany). Dept. of Radiation Oncology

2014-10-01

Introduction: The quantitative blood oxygenation level-dependent (qBOLD) method has not become clinically established yet because long acquisition times are necessary to achieve an acceptable certainty of the parameter estimates. In this work, a non-invasive multiparametric (nimp) qBOLD approach based on a simple analytical model is proposed to facilitate robust oxygen extraction fraction (OEF) mapping within clinically acceptable acquisition times by using separate measurements. Methods: The protocol consisted of a gradient-echo sampled spin-echo sequence (GESSE), a T{sub 2}-weighted Carr-Purcell-Meiboom-Gill (CPMG) sequence, and a T{sub 2}{sup *}-weighted multi-slice multi-echo gradient echo (MMGE) sequence. The GESSE acquisition time was less than 5 minutes and the extra measurement time for CPMG / MMGE was below 2 minutes each. The proposed nimp-qBOLD approach was validated in healthy subjects (N = 5) and one patient. Results: The proposed nimp-qBOLD approach facilitated more robust OEF mapping with significantly reduced inter- and intra-subject variability compared to the standard qBOLD method. Thereby, an average OEF in all subjects of 27 ± 2 % in white matter (WM) and 29 ± 2 % in gray matter (GM) using the nimp-qBOLD method was more stable compared to 41 ± 10 % (WM) and 46 ± 10 % (GM) with standard qBOLD. Moreover, the spatial variance in the image slice (i.e. standard deviation divided by mean) was on average reduced from 35 % to 25 %. In addition, the preliminary results of the patient are encouraging. Conclusion: The proposed nimp-qBOLD technique provides a promising tool for robust OEF mapping within clinically acceptable acquisition times and could therefore provide an important contribution for analyzing tumors or monitoring the success of radio and chemo therapies. (orig.)

Separating neural and vascular effects of caffeine using simultaneous EEG–FMRI: Differential effects of caffeine on cognitive and sensorimotor brain responses

Science.gov (United States)

Diukova, Ana; Ware, Jennifer; Smith, Jessica E.; Evans, C. John; Murphy, Kevin; Rogers, Peter J.; Wise, Richard G.

2012-01-01

The effects of caffeine are mediated through its non-selective antagonistic effects on adenosine A1 and A2A adenosine receptors resulting in increased neuronal activity but also vasoconstriction in the brain. Caffeine, therefore, can modify BOLD FMRI signal responses through both its neural and its vascular effects depending on receptor distributions in different brain regions. In this study we aim to distinguish neural and vascular influences of a single dose of caffeine in measurements of task-related brain activity using simultaneous EEG–FMRI. We chose to compare low-level visual and motor (paced finger tapping) tasks with a cognitive (auditory oddball) task, with the expectation that caffeine would differentially affect brain responses in relation to these tasks. To avoid the influence of chronic caffeine intake, we examined the effect of 250 mg of oral caffeine on 14 non and infrequent caffeine consumers in a double-blind placebo-controlled cross-over study. Our results show that the task-related BOLD signal change in visual and primary motor cortex was significantly reduced by caffeine, while the amplitude and latency of visual evoked potentials over occipital cortex remained unaltered. However, during the auditory oddball task (target versus non-target stimuli) caffeine significantly increased the BOLD signal in frontal cortex. Correspondingly, there was also a significant effect of caffeine in reducing the target evoked response potential (P300) latency in the oddball task and this was associated with a positive potential over frontal cortex. Behavioural data showed that caffeine also improved performance in the oddball task with a significantly reduced number of missed responses. Our results are consistent with earlier studies demonstrating altered flow-metabolism coupling after caffeine administration in the context of our observation of a generalised caffeine-induced reduction in cerebral blood flow demonstrated by arterial spin labelling (19

BOLD cardiovascular magnetic resonance at 3.0 tesla in myocardial ischemia

Directory of Open Access Journals (Sweden)

Gebker Rolf

2010-09-01

Full Text Available Abstract Background The purpose of this study was to determine the ability of Blood Oxygen Level Dependent (BOLD cardiovascular magnetic resonance (CMR to detect stress-inducible myocardial ischemic reactions in the presence of angiographically significant coronary artery disease (CAD. Methods Forty-six patients (34 men; age 65 ± 9 years, with suspected or known coronary artery disease underwent CMR at 3Tesla prior to clinically indicated invasive coronary angiography. BOLD CMR was performed in 3 short axis slices of the heart at rest and during adenosine stress (140 μg/kg/min followed by late gadolinium enhancement (LGE imaging. In all 16 standard myocardial segments, T2* values were derived at rest and under adenosine stress. Quantitative coronary angiography served as the standard of reference and defined normal myocardial segments (i.e. all 16 segments in patients without any CAD, ischemic segments (i.e. supplied by a coronary artery with ≥50% luminal narrowing and non-ischemic segments (i.e. supplied by a non-significantly stenosed coronary artery in patients with significant CAD. Results Coronary angiography demonstrated significant CAD in 23 patients. BOLD CMR at rest revealed significantly lower T2* values for ischemic segments (26.7 ± 11.6 ms compared to normal (31.9 ± 11.9 ms; p Conclusions Rest and stress BOLD CMR at 3Tesla proved feasible and differentiated between ischemic, non-ischemic, and normal myocardial segments in a clinical patient population. BOLD CMR during vasodilator stress identified patients with significant CAD.

When the Brain Takes 'BOLD' Steps: Real-Time fMRI Neurofeedback Can Further Enhance the Ability to Gradually Self-regulate Regional Brain Activation.

Science.gov (United States)

Sorger, Bettina; Kamp, Tabea; Weiskopf, Nikolaus; Peters, Judith Caroline; Goebel, Rainer

2018-05-15

Brain-computer interfaces (BCIs) based on real-time functional magnetic resonance imaging (rtfMRI) are currently explored in the context of developing alternative (motor-independent) communication and control means for the severely disabled. In such BCI systems, the user encodes a particular intention (e.g., an answer to a question or an intended action) by evoking specific mental activity resulting in a distinct brain state that can be decoded from fMRI activation. One goal in this context is to increase the degrees of freedom in encoding different intentions, i.e., to allow the BCI user to choose from as many options as possible. Recently, the ability to voluntarily modulate spatial and/or temporal blood oxygenation level-dependent (BOLD)-signal features has been explored implementing different mental tasks and/or different encoding time intervals, respectively. Our two-session fMRI feasibility study systematically investigated for the first time the possibility of using magnitudinal BOLD-signal features for intention encoding. Particularly, in our novel paradigm, participants (n=10) were asked to alternately self-regulate their regional brain-activation level to 30%, 60% or 90% of their maximal capacity by applying a selected activation strategy (i.e., performing a mental task, e.g., inner speech) and modulation strategies (e.g., using different speech rates) suggested by the experimenters. In a second step, we tested the hypothesis that the additional availability of feedback information on the current BOLD-signal level within a region of interest improves the gradual-self regulation performance. Therefore, participants were provided with neurofeedback in one of the two fMRI sessions. Our results show that the majority of the participants were able to gradually self-regulate regional brain activation to at least two different target levels even in the absence of neurofeedback. When provided with continuous feedback on their current BOLD-signal level, most

Oxytocin modulates hemodynamic responses to monetary incentives in humans

Science.gov (United States)

Mickey, Brian J.; Heffernan, Joseph; Heisel, Curtis; Peciña, Marta; Hsu, David T.; Zubieta, Jon-Kar; Love, Tiffany M.

2016-01-01

Oxytocin is a neuropeptide widely recognized for its role in regulating social and reproductive behavior. Increasing evidence from animal models suggests that oxytocin also modulates reward circuitry in non-social contexts, but evidence in humans is lacking. Here we examined the effects of oxytocin administration on reward circuit function in 18 healthy men as they performed a monetary incentive task. The blood oxygenation level dependent (BOLD) signal was measured using functional magnetic resonance imaging in the context of a randomized, double-blind, placebo-controlled, crossover trial of intranasal oxytocin. We found that oxytocin increases the BOLD signal in the midbrain (substantia nigra and ventral tegmental area) during the late phase of the hemodynamic response to incentive stimuli. Oxytocin’s effects on midbrain responses correlated positively with its effects on positive emotional state. We did not detect an effect of oxytocin on responses in the nucleus accumbens. Whole-brain analyses revealed that oxytocin attenuated medial prefrontal cortical deactivation specifically during anticipation of loss. Our findings demonstrate that intranasal administration of oxytocin modulates human midbrain and medial prefrontal function during motivated behavior. These findings suggest that endogenous oxytocin is a neurochemical mediator of reward behaviors in humans – even in a non-social context – and that the oxytocinergic system is a potential target of pharmacotherapy for psychiatric disorders that involve dysfunction of reward circuitry. PMID:27614896

Oxytocin modulates hemodynamic responses to monetary incentives in humans.

Science.gov (United States)

Mickey, Brian J; Heffernan, Joseph; Heisel, Curtis; Peciña, Marta; Hsu, David T; Zubieta, Jon-Kar; Love, Tiffany M

2016-12-01

Oxytocin is a neuropeptide widely recognized for its role in regulating social and reproductive behavior. Increasing evidence from animal models suggests that oxytocin also modulates reward circuitry in non-social contexts, but evidence in humans is lacking. We examined the effects of oxytocin administration on reward circuit function in 18 healthy men as they performed a monetary incentive task. The blood oxygenation level-dependent (BOLD) signal was measured using functional magnetic resonance imaging in the context of a randomized, double-blind, placebo-controlled, crossover trial of intranasal oxytocin. We found that oxytocin increases the BOLD signal in the midbrain (substantia nigra and ventral tegmental area) during the late phase of the hemodynamic response to incentive stimuli. Oxytocin's effects on midbrain responses correlated positively with its effects on positive emotional state. We did not detect an effect of oxytocin on responses in the nucleus accumbens. Whole-brain analyses revealed that oxytocin attenuated medial prefrontal cortical deactivation specifically during anticipation of loss. Our findings demonstrate that intranasal administration of oxytocin modulates human midbrain and medial prefrontal function during motivated behavior. These findings suggest that endogenous oxytocin is a neurochemical mediator of reward behaviors in humans-even in a non-social context-and that the oxytocinergic system is a potential target of pharmacotherapy for psychiatric disorders that involve dysfunction of reward circuitry.

BOLD cardiovascular magnetic resonance at 3.0 tesla in myocardial ischemia.

OpenAIRE

Manka, R; Paetsch, I; Schnackenburg, B; Gebker, R; Fleck, E; Jahnke, C

2010-01-01

Abstract Background The purpose of this study was to determine the ability of Blood Oxygen Level Dependent (BOLD) cardiovascular magnetic resonance (CMR) to detect stress-inducible myocardial ischemic reactions in the presence of angiographically significant coronary artery disease (CAD). Methods Forty-six patients (34 men; age 65 ± 9 years,) with suspected or known coronary artery disease underwent CMR at 3Tesla prior to clinically indicated invasive coronary angiography. BOLD CMR was perfor...

Effect of hypnotherapy and educational intervention on brain response to visceral stimulus in the irritable bowel syndrome.

Science.gov (United States)

Lowén, M B O; Mayer, E A; Sjöberg, M; Tillisch, K; Naliboff, B; Labus, J; Lundberg, P; Ström, M; Engström, M; Walter, S A

2013-06-01

Gut-directed hypnotherapy can reduce IBS symptoms, but the mechanisms underlying this therapeutic effect remain unknown. To determine the effect of hypnotherapy and educational intervention on brain responses to cued rectal distensions in IBS patients. Forty-four women with moderate-to-severe IBS and 20 healthy controls (HCs) were included. Blood oxygen level dependent (BOLD) signals were measured by functional Magnetic Resonance Imaging (fMRI) during expectation and delivery of high- (45 mmHg) and low-intensity (15 mmHg) rectal distensions. Twenty-five patients were assigned to hypnotherapy (HYP) and 16 to educational intervention (EDU). Thirty-one patients completed treatments and posttreatment fMRI. Similar symptom reduction was achieved in both groups. Clinically successful treatment (all responders) was associated with significant BOLD attenuation during high-intensity distension in the dorsal and ventral anterior insula (cluster size 142, P = 0.006, and cluster size 101, P = 0.005 respectively). Moreover HYP responders demonstrated a pre-post treatment BOLD attenuation in posterior insula (cluster sizes 59, P = 0.05) while EDU responders had a BOLD attenuation in prefrontal cortex (cluster size 60, P = 0.05). Pre-post differences for expectation conditions were almost exclusively seen in the HYP group. Following treatment, the brain response to distension was similar to that observed in HCs, suggesting that the treatment had a normalising effect on the central processing abnormality of visceral signals in IBS. The abnormal processing and enhanced perception of visceral stimuli in IBS can be normalised by psychological interventions. Symptom improvement in the treatment groups may be mediated by different brain mechanisms. NCT01815164. © 2013 John Wiley & Sons Ltd.

Brain activation by short-term nicotine exposure in anesthetized wild-type and beta2-nicotinic receptors knockout mice: a BOLD fMRI study

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Suarez, S.V.; Changeux, J.P.; Granon, S. [Unite de Neurobiologie Integrative du Systeme Cholinergique, URA CNRS 2182, Institut Pasteur, Departement de Neuroscience, 25 rue du Dr Roux, 75015 Paris (France); Amadon, A.; Giacomini, E.; Le Bihan, D. [Service Hospitalier Frederic Joliot, 4 place du general Leclerc, 91400 Orsay (France); Wiklund, A. [Section of Anaesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm (Sweden)

2009-07-01

Rationale: The behavioral effects of nicotine and the role of the beta2-containing nicotinic receptors in these behaviors are well documented. However, the behaviors altered by nicotine rely on the functioning on multiple brain circuits where the high-affinity {beta}2-containing nicotinic receptors ({beta}2*nAChRs) are located. Objectives We intend to see which brain circuits are activated when nicotine is given in animals naive for nicotine and whether the {beta}2*nAChRs are needed for its activation of the blood oxygen level dependent (BOLD) signal in all brain areas. Materials and methods: We used functional magnetic resonance imaging (fMRI) to measure the brain activation evoked by nicotine (1 mg/kg delivered at a slow rate for 45 min) in anesthetized C57BL/6J mice and {beta}2 knockout (KO) mice. Results: Acute nicotine injection results in a significant increased activation in anterior frontal, motor, and somatosensory cortices and in the ventral tegmental area and the substantia nigra. Anesthetized mice receiving no nicotine injection exhibited a major decreased activation in all cortical and subcortical structures, likely due to prolonged anesthesia. At a global level, {beta}2 KO mice were not rescued from the globally declining BOLD signal. However, nicotine still activated regions of a meso-cortico-limbic circuit likely via {alpha}7 nicotinic receptors. Conclusions: Acute nicotine exposure compensates for the drop in brain activation due to anesthesia through the meso-cortico-limbic network via the action of nicotine on {beta}2*nAChRs. The developed fMRI method is suitable for comparing responses in wild-type and mutant mice. (authors)

Brain activation by short-term nicotine exposure in anesthetized wild-type and beta2-nicotinic receptors knockout mice: a BOLD fMRI study

International Nuclear Information System (INIS)

Suarez, S.V.; Changeux, J.P.; Granon, S.; Amadon, A.; Giacomini, E.; Le Bihan, D.; Wiklund, A.

2009-01-01

Rationale: The behavioral effects of nicotine and the role of the beta2-containing nicotinic receptors in these behaviors are well documented. However, the behaviors altered by nicotine rely on the functioning on multiple brain circuits where the high-affinity β2-containing nicotinic receptors (β2*nAChRs) are located. Objectives We intend to see which brain circuits are activated when nicotine is given in animals naive for nicotine and whether the β2*nAChRs are needed for its activation of the blood oxygen level dependent (BOLD) signal in all brain areas. Materials and methods: We used functional magnetic resonance imaging (fMRI) to measure the brain activation evoked by nicotine (1 mg/kg delivered at a slow rate for 45 min) in anesthetized C57BL/6J mice and β2 knockout (KO) mice. Results: Acute nicotine injection results in a significant increased activation in anterior frontal, motor, and somatosensory cortices and in the ventral tegmental area and the substantia nigra. Anesthetized mice receiving no nicotine injection exhibited a major decreased activation in all cortical and subcortical structures, likely due to prolonged anesthesia. At a global level, β2 KO mice were not rescued from the globally declining BOLD signal. However, nicotine still activated regions of a meso-cortico-limbic circuit likely via α7 nicotinic receptors. Conclusions: Acute nicotine exposure compensates for the drop in brain activation due to anesthesia through the meso-cortico-limbic network via the action of nicotine on β2*nAChRs. The developed fMRI method is suitable for comparing responses in wild-type and mutant mice. (authors)

Study of asymmetry in motor areas related to handedness using the fMRI BOLD response Gaussian convolution model

Energy Technology Data Exchange (ETDEWEB)

Gao Qing [School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054 (China); School of Applied Mathematics, University of Electronic Science and Technology of China, Chengdu 610054 (China); Chen Huafu [School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054 (China); School of Applied Mathematics, University of Electronic Science and Technology of China, Chengdu 610054 (China)], E-mail: Chenhf@uestc.edu.cn; Gong Qiyong [Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu 610041 (China)

2009-10-30

Brain asymmetry is a phenomenon well known for handedness, and has been studied in the motor cortex. However, few studies have quantitatively assessed the asymmetrical cortical activities for handedness in motor areas. In the present study, we systematically and quantitatively investigated asymmetry in the left and right primary motor cortices during sequential finger movements using the Gaussian convolution model approach based on the functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) response. Six right-handed and six left-handed subjects were recruited to perform three types of hand movement tasks. The results for the expected value of the Gaussian convolution model showed that it took the dominant hand a longer average interval of response delay regardless of the handedness and bi- or uni-manual performance. The results for the standard deviation of the Gaussian model suggested that in the mass neurons, these intervals of the dominant hand were much more variable than those of the non-dominant hand. When comparing bi-manual movement conditions with uni-manual movement conditions in the primary motor cortex (PMC), both the expected value and standard deviation in the Gaussian function were significantly smaller (p < 0.05) in the bi-manual conditions, showing that the movement of the non-dominant hand influenced that of the dominant hand.

Study of asymmetry in motor areas related to handedness using the fMRI BOLD response Gaussian convolution model

International Nuclear Information System (INIS)

Gao Qing; Chen Huafu; Gong Qiyong

2009-01-01

Brain asymmetry is a phenomenon well known for handedness, and has been studied in the motor cortex. However, few studies have quantitatively assessed the asymmetrical cortical activities for handedness in motor areas. In the present study, we systematically and quantitatively investigated asymmetry in the left and right primary motor cortices during sequential finger movements using the Gaussian convolution model approach based on the functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) response. Six right-handed and six left-handed subjects were recruited to perform three types of hand movement tasks. The results for the expected value of the Gaussian convolution model showed that it took the dominant hand a longer average interval of response delay regardless of the handedness and bi- or uni-manual performance. The results for the standard deviation of the Gaussian model suggested that in the mass neurons, these intervals of the dominant hand were much more variable than those of the non-dominant hand. When comparing bi-manual movement conditions with uni-manual movement conditions in the primary motor cortex (PMC), both the expected value and standard deviation in the Gaussian function were significantly smaller (p < 0.05) in the bi-manual conditions, showing that the movement of the non-dominant hand influenced that of the dominant hand.

Zolpidem reduces the blood oxygen level-dependent signal during visual system stimulation.

Science.gov (United States)

Licata, Stephanie C; Lowen, Steven B; Trksak, George H; Maclean, Robert R; Lukas, Scott E

2011-08-15

Zolpidem is a short-acting imidazopyridine hypnotic that binds at the benzodiazepine binding site on specific GABA(A) receptors to enhance fast inhibitory neurotransmission. The behavioral and receptor pharmacology of zolpidem has been studied extensively, but little is known about its neuronal substrates in vivo. In the present within-subject, double-blind, and placebo-controlled study, blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) at 3 Tesla was used to assess the effects of zolpidem within the brain. Healthy participants (n=12) were scanned 60 min after acute oral administration of zolpidem (0, 5, 10, or 20mg), and changes in BOLD signal were measured in the visual cortex during presentation of a flashing checkerboard. Heart rate and oxygen saturation were monitored continuously throughout the session. Zolpidem (10 and 20mg) reduced the robust visual system activation produced by presentation of this stimulus, but had no effects on physiological activity during the fMRI scan. Zolpidem's modulation of the BOLD signal within the visual cortex is consistent with the abundant distribution of GABA(A) receptors localized in this region, as well as previous studies showing a relationship between increased GABA-mediated neuronal inhibition and a reduction in BOLD activation. Copyright © 2011 Elsevier Inc. All rights reserved.

Zolpidem reduces the blood oxygen level-dependent signal during visual system stimulation

Science.gov (United States)

Licata, Stephanie C.; Lowen, Steven B.; Trksak, George H.; MacLean, Robert R.; Lukas, Scott E.

2011-01-01

Zolpidem is a short-acting imidazopyridine hypnotic that binds at the benzodiazepine binding site on specific GABAA receptors to enhance fast inhibitory neurotransmission. The behavioral and receptor pharmacology of zolpidem has been studied extensively, but little is known about its neuronal substrates in vivo. In the present within-subject, double-blind, and placebo-controlled study, blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) at 3 Tesla was used to assess the effects of zolpidem within the brain. Healthy participants (n=12) were scanned 60 minutes after acute oral administration of zolpidem (0, 5, 10, or 20 mg), and changes in BOLD signal were measured in the visual cortex during presentation of a flashing checkerboard. Heart rate and oxygen saturation were monitored continuously throughout the session. Zolpidem (10 and 20 mg) reduced the robust visual system activation produced by presentation of this stimulus, but had no effects on physiological activity during the fMRI scan. Zolpidem’s modulation of the BOLD signal within the visual cortex is consistent with the abundant distribution of GABAA receptors localized in this region, as well as previous studies showing a relationship between increased GABA-mediated neuronal inhibition and a reduction in BOLD activation. PMID:21640782

D2 receptor genotype and striatal dopamine signaling predict motor cortical activity and behavior in humans.

Science.gov (United States)

Fazio, Leonardo; Blasi, Giuseppe; Taurisano, Paolo; Papazacharias, Apostolos; Romano, Raffaella; Gelao, Barbara; Ursini, Gianluca; Quarto, Tiziana; Lo Bianco, Luciana; Di Giorgio, Annabella; Mancini, Marina; Popolizio, Teresa; Rubini, Giuseppe; Bertolino, Alessandro

2011-02-14

Pre-synaptic D2 receptors regulate striatal dopamine release and DAT activity, key factors for modulation of motor pathways. A functional SNP of DRD2 (rs1076560 G>T) is associated with alternative splicing such that the relative expression of D2S (mainly pre-synaptic) vs. D2L (mainly post-synaptic) receptor isoforms is decreased in subjects with the T allele with a putative increase of striatal dopamine levels. To evaluate how DRD2 genotype and striatal dopamine signaling predict motor cortical activity and behavior in humans, we have investigated the association of rs1076560 with BOLD fMRI activity during a motor task. To further evaluate the relationship of this circuitry with dopamine signaling, we also explored the correlation between genotype based differences in motor brain activity and pre-synaptic striatal DAT binding measured with [(123)I] FP-CIT SPECT. Fifty healthy subjects, genotyped for DRD2 rs1076560 were studied with BOLD-fMRI at 3T while performing a visually paced motor task with their right hand; eleven of these subjects also underwent [(123)I]FP-CIT SPECT. SPM5 random-effects models were used for statistical analyses. Subjects carrying the T allele had greater BOLD responses in left basal ganglia, thalamus, supplementary motor area, and primary motor cortex, whose activity was also negatively correlated with reaction time at the task. Moreover, left striatal DAT binding and activity of left supplementary motor area were negatively correlated. The present results suggest that DRD2 genetic variation was associated with focusing of responses in the whole motor network, in which activity of predictable nodes was correlated with reaction time and with striatal pre-synaptic dopamine signaling. Our results in humans may help shed light on genetic risk for neurobiological mechanisms involved in the pathophysiology of disorders with dysregulation of striatal dopamine like Parkinson's disease. Copyright © 2010 Elsevier Inc. All rights reserved.

Research progress of BOLD-fMRI in minimal hepatic encephalopathy

International Nuclear Information System (INIS)

Zhou Zhiming; Zhao Jiannong

2013-01-01

The minimal hepatic encephalopathy is the early stage of hepatic encephalopathy. It has few apparent clinical symptoms and specific manifestations, and is difficult to diagnose. In the recent years, BOLD-fMRI has been used to study hepatic encephalopathy gradually. Through detection of the brain neuron activities in different states, it can not only locate the abnormal activity of brain functional areas, but also can find the changes of brain functional connectivity. BOLD- fMRI combining with other MR technologies can explore the pathology and pathogenesis of minimal hepatic encephalopathy from micro to macro and from structure to function. (authors)

Correlative BOLD MR imaging of stages of synovitis in a rabbit model of antigen-induced arthritis

International Nuclear Information System (INIS)

Doria, Andrea S.; Crawley, Adrian; Gahunia, Harpal; Rayner, Tammy; Tassos, Vivian; Zhong, Anguo; Moineddin, Rahim; Pritzker, Kenneth; Mendes, Maria; Jong, Roland; Salter, Robert B.

2012-01-01

Because of the ability of blood-oxygen-level-dependent (BOLD) MRI to assess blood oxygenation changes within the microvasculature, this technique holds potential for evaluating early perisynovial changes in inflammatory arthritis. To evaluate the feasibility of BOLD MRI to detect interval perisynovial changes in knees of rabbits with inflammatory arthritis. Rabbit knees were injected with albumin (n=9) or saline (n=6) intra-articularly, or were not injected (control knees, n=9). Except for two rabbits (albumin-injected, n=2 knees; saline-injected, n=2 knees) that unexpectedly died on days 7 and 21 of the experiment, respectively, all other animals were scanned with BOLD MRI on days 0, 1, 7, 14, 21 and 28 after induction of arthritis. T2*-weighted gradient-echo MRI was performed during alternate 30 s of normoxia/hyperoxia. BOLD MRI measurements were compared with clinical, laboratory and histological markers. Percentage of activated voxels was significantly greater in albumin-injected knees than in contralateral saline-injected knees (P=0.04). For albumin-injected knees (P < 0.05) and among different categories of knees (P=0.009), the percentage of activated BOLD voxels varied over time. A quadratic curve for on-and-off BOLD difference was delineated for albumin- and saline-injected knees over time (albumin-injected, P=0.047; saline-injected, P=0.009). A trend toward a significant difference in synovial histological scores between albumin-injected and saline-injected knees was noted only for acute scores (P=0.07). As a proof of concept, BOLD MRI can depict perisynovial changes during progression of experimental arthritis. (orig.)

Correlative BOLD MR imaging of stages of synovitis in a rabbit model of antigen-induced arthritis

Energy Technology Data Exchange (ETDEWEB)

Doria, Andrea S. [Hospital for Sick Children, Department of Diagnostic Imaging, Toronto (Canada); University of Toronto, Department of Medical Imaging, Toronto (Canada); Crawley, Adrian [University of Toronto, Department of Medical Imaging, Toronto (Canada); Toronto Western Hospital, Department of Medical Imaging, Toronto (Canada); Gahunia, Harpal; Rayner, Tammy; Tassos, Vivian; Zhong, Anguo [Hospital for Sick Children, Department of Diagnostic Imaging, Toronto (Canada); Moineddin, Rahim [Family and Community Medicine, Department of Public Health, Toronto (Canada); Pritzker, Kenneth; Mendes, Maria; Jong, Roland [Mount Sinai Hospital, Department of Pathology and Laboratory Medicine, Toronto (Canada); Salter, Robert B. [Hospital for Sick Children, Department of Orthopedic Surgery, Toronto (Canada)

2012-01-15

Because of the ability of blood-oxygen-level-dependent (BOLD) MRI to assess blood oxygenation changes within the microvasculature, this technique holds potential for evaluating early perisynovial changes in inflammatory arthritis. To evaluate the feasibility of BOLD MRI to detect interval perisynovial changes in knees of rabbits with inflammatory arthritis. Rabbit knees were injected with albumin (n=9) or saline (n=6) intra-articularly, or were not injected (control knees, n=9). Except for two rabbits (albumin-injected, n=2 knees; saline-injected, n=2 knees) that unexpectedly died on days 7 and 21 of the experiment, respectively, all other animals were scanned with BOLD MRI on days 0, 1, 7, 14, 21 and 28 after induction of arthritis. T2*-weighted gradient-echo MRI was performed during alternate 30 s of normoxia/hyperoxia. BOLD MRI measurements were compared with clinical, laboratory and histological markers. Percentage of activated voxels was significantly greater in albumin-injected knees than in contralateral saline-injected knees (P=0.04). For albumin-injected knees (P < 0.05) and among different categories of knees (P=0.009), the percentage of activated BOLD voxels varied over time. A quadratic curve for on-and-off BOLD difference was delineated for albumin- and saline-injected knees over time (albumin-injected, P=0.047; saline-injected, P=0.009). A trend toward a significant difference in synovial histological scores between albumin-injected and saline-injected knees was noted only for acute scores (P=0.07). As a proof of concept, BOLD MRI can depict perisynovial changes during progression of experimental arthritis. (orig.)

Variability of the hemodynamic response as a function of age and frequency of epileptic discharge in children with epilepsy.

Science.gov (United States)

Jacobs, Julia; Hawco, Colin; Kobayashi, Eliane; Boor, Rainer; LeVan, Pierre; Stephani, Ulrich; Siniatchkin, Michael; Gotman, Jean

2008-04-01

EEG-fMRI is a non-invasive tool to investigate epileptogenic networks in patients with epilepsy. Different patterns of BOLD responses have been observed in children as compared to adults. A high intra- and intersubject variability of the hemodynamic response function (HRF) to epileptic discharges has been observed in adults. The actual HRF to epileptic discharges in children and its dependence on age are unknown. We analyzed 64 EEG-fMRI event types in 37 children (3 months to 18 years), 92% showing a significant BOLD response. HRFs were calculated for each BOLD cluster using a Fourier basis set. After excluding HRFs with a low signal-to-noise ratio, 126 positive and 98 negative HRFs were analyzed. We evaluated age-dependent changes as well as the effect of increasing numbers of spikes. Peak time, amplitude and signal-to-noise ratio of the HRF and the t-statistic score of the cluster were used as dependent variables. We observed significantly longer peak times of the HRF in the youngest children (0 to 2 years), suggesting that the use of multiple HRFs might be important in this group. A different coupling between neuronal activity and metabolism or blood flow in young children may cause this phenomenon. Even if the t-value increased with frequent spikes, the amplitude of the HRF decreased significantly with spike frequency. This reflects a violation of the assumptions of the General Linear Model and therefore the use of alternative analysis techniques may be more appropriate with high spiking rates, a common situation in children.

Origins of intersubject variability of blood oxygenation level dependent and arterial spin labeling fMRI: implications for quantification of brain activity.

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Gaxiola-Valdez, Ismael; Goodyear, Bradley G

2012-12-01

Accurate localization of brain activity using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has been challenged because of the large BOLD signal within distal veins. Arterial spin labeling (ASL) techniques offer greater sensitivity to the microvasculature but possess low temporal resolution and limited brain coverage. In this study, we show that the physiological origins of BOLD and ASL depend on whether percent change or statistical significance is being considered. For BOLD and ASL fMRI data collected during a simple unilateral hand movement task, we found that in the area of the contralateral motor cortex the centre of gravity (CoG) of the intersubject coefficient of variation (CV) of BOLD fMRI was near the brain surface for percent change in signal, whereas the CoG of the intersubject CV for Z-score was in close proximity of sites of brain activity for both BOLD and ASL. These findings suggest that intersubject variability of BOLD percent change is vascular in origin, whereas the origin of inter-subject variability of Z-score is neuronal for both BOLD and ASL. For longer duration tasks (12 s or greater), however, there was a significant correlation between BOLD and ASL percent change, which was not evident for short duration tasks (6 s). These findings suggest that analyses directly comparing percent change in BOLD signal between pre-defined regions of interest using short duration stimuli, as for example in event-related designs, may be heavily weighted by large-vessel responses rather than neuronal responses. Copyright © 2012 Elsevier Inc. All rights reserved.

Continuous EEG-fMRI in Pre-Surgical Evaluation of a Patient with Symptomatic Seizures: Bold Activation Linked to Interictal Epileptic Discharges Caused by Cavernoma.

Science.gov (United States)

Avesani, M; Formaggio, E; Milanese, F; Baraldo, A; Gasparini, A; Cerini, R; Bongiovanni, L G; Pozzi Mucelli, R; Fiaschi, A; Manganotti, P

2008-04-07

We used continuous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) to identify the linkage between the "epileptogenic" and the "irritative" area in a patient with symptomatic epilepsy (cavernoma, previously diagnosed and surgically treated), i.e. a patient with a well known "epileptogenic area", and to increase the possibility of a non invasive pre-surgical evaluation of drug-resistant epilepsies. A compatible MRI system was used (EEG with 29 scalp electrodes and two electrodes for ECG and EMG) and signals were recorded with a 1.5 Tesla MRI scanner. After the recording session and MRI artifact removal, EEG data were analyzed offline and used as paradigms in fMRI study. Activation (EEG sequences with interictal slow-spiked-wave activity) and rest (sequences of normal EEG) conditions were compared to identify the potential resulting focal increase in BOLD signal and to consider if this is spatially linked to the interictal focus used as a paradigm and to the lesion. We noted an increase in the BOLD signal in the left neocortical temporal region, laterally and posteriorly to the poro-encephalic cavity (residual of cavernoma previously removed), that is around the "epileptogenic area". In our study "epileptogenic" and "irritative" areas were connected with each other. Combined EEG-fMRI may become routine in clinical practice for a better identification of an irritative and lesional focus in patients with symptomatic drug-resistant epilepsy.

Gamma rays induced bold seeded high yielding mutant in chickpea

International Nuclear Information System (INIS)

Wani, A.A.; Anis, M.

2001-01-01

In pulses especially in chickpea (Cicer arietinum L.), genetic variability has been exhausted due to natural selection and hence conventional breeding methods are not very fruitful. Mutation techniques are the best methods to enlarge the genetically conditioned variability of a species within a short time and have played a significant role in the development of many crop varieties. Investigations on the effects of ionizing radiations and chemical mutagens in induction of macro-mutations have received much attention owing to their utmost importance in plant breeding. The present study reports a bold seeded mutant in chickpea, the most dominating pulse crop on the Indian subcontinent. Fresh seeds of chickpea variety 'Pusa-212' were procured from IARI, New Delhi and treated with different doses/concentrations of gamma rays ( 60 Co source at NBRI, Lucknow) and ethyl methanesulphonate (EMS), individually as well as in combination, to raise the M1 generation. Seeds of M 1 plants were sown to raise M2 plant progenies. A bold seeded mutant was isolated from 400 Gy gamma ray treatments. The mutant was confirmed as true bred, all the mutant seeds gave rise to morphologically similar plants in M 3 , which were quite distinct from the control. The bold seeded mutant showed 'gigas' characteristics and vigorous growth. The plant remained initially straight but later on attained a trailing habit due to heavy secondary branching. The leaves, petioles, flowers, pods and seeds were almost double that of the parent variety, in size. The flowering occurred 10 days later than the parent and maturity was also delayed accordingly. Observations were recorded on various quantitative traits. Plant height and number of primary branches showed a significant improvement over the parent. It is interesting to note that the number of pods and number of seeds per pod significantly decreased. However, the hundred seed weight (31.73±0.59g) in the mutant plants was more than double in the parent

Exploration of changes in the brain response to sleep-related pictures after cognitive–behavioral therapy for psychophysiological insomnia

OpenAIRE

Kim, Seog Ju; Lee, Yu Jin; Kim, Nambeom; Kim, Soohyun; Choi, Jae-Won; Park, Juhyun; Gwak, Ah Reum; Kang, Chang-Ki; Kang, Seung-Gul; Jeong, Do-Un

2017-01-01

Psychophysiological insomnia (PI) includes arousal to sleep-related stimuli (SS), which can be treated by cognitive behavioral therapy for insomnia (CBT-I). The present study was an exploratory, prospective intervention study that aimed to explore brain response to visual SS in PI before and after CBT-I. Blood oxygen level dependent (BOLD) signal differences in response to SS and neutral stimuli (NS) were compared between 14 drug-free PI patients and 18 good sleepers (GS) using functional mag...

Cocaine-associated odor cue re-exposure increases blood oxygenation level dependent signal in memory and reward regions of the maternal rat brain.

Science.gov (United States)

Caffrey, Martha K; Febo, Marcelo

2014-01-01

Cue triggered relapse during the postpartum period can negatively impact maternal care. Given the high reward value of pups in maternal rats, we designed an fMRI experiment to test whether offspring presence reduces the neural response to a cocaine associated olfactory cue. Cocaine conditioned place preference was carried out before pregnancy in the presence of two distinct odors that were paired with cocaine or saline (+Cue and -Cue). The BOLD response to +Cue and -Cue was measured in dams on postpartum days 2-4. Odor cues were delivered to dams in the absence and then the presence of pups. Our data indicate that several limbic and cognitive regions of the maternal rat brain show a greater BOLD signal response to a +Cue versus -Cue. These include dorsal striatum, prelimbic cortex, parietal cortex, habenula, bed nucleus of stria terminalis, lateral septum and the mediodorsal and the anterior thalamic nucleus. Of the aforementioned brain regions, only the parietal cortex of cocaine treated dams showed a significant modulatory effect of pup presence. In this area of the cortex, cocaine exposed maternal rats showed a greater BOLD activation in response to the +Cue in the presence than in the absence of pups. Specific regions of the cocaine exposed maternal rat brain are strongly reactive to drug associated cues. The regions implicated in cue reactivity have been previously reported in clinical imaging work, and previous work supports their role in various motivational and cognitive functions. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

COCAINE-ASSOCIATED ODOR CUE RE-EXPOSURE INCREASES BLOOD OXYGENATION LEVEL DEPENDENT SIGNAL IN MEMORY AND REWARD REGIONS OF THE MATERNAL RAT BRAIN*

Science.gov (United States)

Caffrey, Martha K.; Febo, Marcelo

2013-01-01

BACKGROUND Cue triggered relapse during the postpartum period can negatively impact maternal care. Given the high reward value of pups in maternal rats, we designed an fMRI experiment to test whether offspring presence reduces the neural response to a cocaine associated olfactory cue. METHODS Cocaine conditioned place preference was carried out before pregnancy in the presence of two distinct odors that were paired with cocaine or saline (+Cue and −Cue). The BOLD response to +Cue and −Cue was measured in dams on postpartum days 2–4. Odor cues were delivered to dams in the absence and then the presence of pups. RESULTS Our data indicate that several limbic and cognitive regions of the maternal rat brain show a greater BOLD signal response to a +Cue versus −Cue. These include dorsal striatum, prelimbic cortex, parietal cortex, habenula, bed nucleus of stria terminalis, lateral septum and the mediodorsal and the anterior thalamic nucleus. Of the aforementioned brain regions, only the parietal cortex of cocaine treated dams showed a significant modulatory effect of pup presence. In this area of the cortex, cocaine exposed maternal rats showed a greater BOLD activation in response to the +Cue in the presence than in the absence of pups. CONCLUSIONS Specific regions of the cocaine exposed maternal rat brain are strongly reactive to drug associated cues. The regions implicated in cue reactivity have been previously reported in clinical imaging work, and previous work supports their role in various motivational and cognitive functions. PMID:24183499

Optogenetic activation of CA1 pyramidal neurons at the dorsal and ventral hippocampus evokes distinct brain-wide responses revealed by mouse fMRI.

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Norio Takata

Full Text Available The dorsal and ventral hippocampal regions (dHP and vHP are proposed to have distinct functions. Electrophysiological studies have revealed intra-hippocampal variances along the dorsoventral axis. Nevertheless, the extra-hippocampal influences of dHP and vHP activities remain unclear. In this study, we compared the spatial distribution of brain-wide responses upon dHP or vHP activation and further estimate connection strengths between the dHP and the vHP with corresponding extra-hippocampal areas. To achieve this, we first investigated responses of local field potential (LFP and multi unit activities (MUA upon light stimulation in the hippocampus of an anesthetized transgenic mouse, whose CA1 pyramidal neurons expressed a step-function opsin variant of channelrhodopsin-2 (ChR2. Optogenetic stimulation increased hippocampal LFP power at theta, gamma, and ultra-fast frequency bands, and augmented MUA, indicating light-induced activation of CA1 pyramidal neurons. Brain-wide responses examined using fMRI revealed that optogenetic activation at the dHP or vHP caused blood oxygenation level-dependent (BOLD fMRI signals in situ. Although activation at the dHP induced BOLD responses at the vHP, the opposite was not observed. Outside the hippocampal formation, activation at the dHP, but not the vHP, evoked BOLD responses at the retrosplenial cortex (RSP, which is in line with anatomical evidence. In contrast, BOLD responses at the lateral septum (LS were induced only upon vHP activation, even though both dHP and vHP send axonal fibers to the LS. Our findings suggest that the primary targets of dHP and vHP activation are distinct, which concurs with attributed functions of the dHP and RSP in spatial memory, as well as of the vHP and LS in emotional responses.

ABA signaling in stress-response and seed development.

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Nakashima, Kazuo; Yamaguchi-Shinozaki, Kazuko

2013-07-01

KEY MESSAGE : We review the recent progress on ABA signaling, especially ABA signaling for ABA-dependent gene expression, including the AREB/ABF regulon, SnRK2 protein kinase, 2C-type protein phosphatases and ABA receptors. Drought negatively impacts plant growth and the productivity of crops. Drought causes osmotic stress to organisms, and the osmotic stress causes dehydration in plant cells. Abscisic acid (ABA) is produced under osmotic stress conditions, and it plays an important role in the stress response and tolerance of plants. ABA regulates many genes under osmotic stress conditions. It also regulates gene expression during seed development and germination. The ABA-responsive element (ABRE) is the major cis-element for ABA-responsive gene expression. ABRE-binding protein (AREB)/ABRE-binding factor (ABF) transcription factors (TFs) regulate ABRE-dependent gene expression. Other TFs are also involved in ABA-responsive gene expression. SNF1-related protein kinases 2 are the key regulators of ABA signaling including the AREB/ABF regulon. Recently, ABA receptors and group A 2C-type protein phosphatases were shown to govern the ABA signaling pathway. Moreover, recent studies have suggested that there are interactions between the major ABA signaling pathway and other signaling factors in stress-response and seed development. The control of the expression of ABA signaling factors may improve tolerance to environmental stresses.

Factors related to the magnitude of T2* MR signal changes during functional imaging

International Nuclear Information System (INIS)

Krings, T.; Reinges, M.H.T.; Gilsbach, J.M.; Willmes, K.; Nuerk, H.C.; Meister, I.G.; Thron, A.

2002-01-01

Our aim was to determine whether age, sex, the degree of weakness, anticonvulsants, the histology of the underlying lesion(s), the presence of oedema or the distance of the lesion from the motor region have an impact on the blood oxygenation level-dependent (BOLD) signal strength and therefore on the validity of functional MRI (fMRI). We studied 98 patients with masses near the central region imaged for surgical planning at 1.5 tesla, employing a BOLD sequence during a motor task. We calculated percentage signal change in the primary motor cortex between rest and activation and carried out multiple linear regression to examine the impact of the above factors on signal strength. Using a stepwise analysis strategy, the distance of the lesion from the motor region had the strongest influence (r=0.653, P 0.20). Disturbances of cerebral blood flow and metabolism induced by the tumour were presumed to be the causes of a decrease in signal in the adjacent cortex. (orig.)

Adolescent heavy drinkers' amplified brain responses to alcohol cues decrease over one month of abstinence.

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Brumback, Ty; Squeglia, Lindsay M; Jacobus, Joanna; Pulido, Carmen; Tapert, Susan F; Brown, Sandra A

2015-07-01

Heavy drinking during adolescence is associated with increased reactivity to alcohol related stimuli and to differential neural development. Alcohol cue reactivity has been widely studied among adults with alcohol use disorders, but little is known about the neural substrates of cue reactivity in adolescent drinkers. The current study aimed to identify changes in blood-oxygen level dependent (BOLD) signal during a cue reactivity task pre- and post-monitored abstinence from alcohol. Demographically matched adolescents (16.0-18.9 years, 54% female) with histories of heavy episodic drinking (HD; n=22) and light or non-drinking control teens (CON; n=16) were recruited to participate in a month-long study. All participants completed a functional Magnetic Resonance Imaging (fMRI) scan with an alcohol cue reactivity task and substance use assessments at baseline and after 28 days of monitored abstinence from alcohol and drugs (i.e., urine toxicology testing every 48-72 h). Repeated-measure analysis of variance (ANOVA) examined main effects of group, time, and group×time interactions on BOLD signal response in regions of interest defined by functional differences at baseline. The HD group exhibited greater (pbrain regions, differences in BOLD response were no longer apparent following a month of abstinence, suggesting a decrease in alcohol cue reactivity among adolescent non-dependent heavy drinkers as a consequence of abstaining from alcohol. These results highlight the malleability of adolescent brain function despite no formal intervention targeting cue reactivity. Increased understanding of the neural underpinnings of cue reactivity could have implications for prevention and intervention strategies in adolescent heavy alcohol users. Copyright © 2015 Elsevier Ltd. All rights reserved.

A comparison of measures of boldness and their relationships to survival in young fish.

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James R White

Full Text Available Boldness is the propensity of an animal to engage in risky behavior. Many variations of novel-object or novel-environment tests have been used to quantify the boldness of animals, although the relationship between test outcomes has rarely been investigated. Furthermore, the relationship of outcomes to any ecological aspect of fitness is generally assumed, rather than measured directly. Our study is the first to compare how the outcomes of the same test of boldness differ among observers and how different tests of boldness relate to the survival of individuals in the field. Newly-metamorphosed lemon damselfish, Pomacentrus moluccensis, were placed onto replicate patches of natural habitat. Individual behavior was quantified using four tests (composed of a total of 12 different measures of behavior: latency to enter a novel environment, activity in a novel environment, and reactions to threatening and benign novel objects. After behavior was quantified, survival was monitored for two days during which time fish were exposed to natural predators. Variation among observers was low for most of the 12 measures, except distance moved and the threat test (reaction to probe thrust, which displayed unacceptable amounts of inter-observer variation. Overall, the results of the behavioral tests suggested that novel environment and novel object tests quantified similar behaviors, yet these behavioral measures were not interchangeable. Multiple measures of behavior within the context of novel environment or object tests were the most robust way to assess boldness and these measures have a complex relationship with survivorship of young fish in the field. Body size and distance ventured from shelter were the only variables that had a direct and positive relationship with survival.

Visual cortex reactivity in sedated children examined with perfusion MRI (FAIR)

DEFF Research Database (Denmark)

Born, A.P.; Rostrup, Egill; Miranda Gimenez-Ricco, Maria Jo

2002-01-01

Sleeping and sedated children can respond to visual stimulation with a decrease in blood oxygenation level dependent (BOLD) functional MRI signal response. The contribution of metabolic and hemodynamic parameters to this inverse signal response is incompletely understood. It has been hypothesized...... that it is caused by a relatively greater increase of oxygen consumption compared to rCBF (regional cerebral blood flow) increase. We studied the rCBF changes during visual stimulation in four sedated children, aged 4-71 months, and four alert adults, with an arterial water spin labeling technique (FAIR) and BOLD f.......99-2.93), respectively. Thus, in the children, an rCBF increase could not be detected by perfusion MRI, but indications of a FAIR signal decrease were found. An rCBF decrease in the primary visual cortex during stimulation has not been reported previously, but it is a possible explanation for the negative BOLD response...

Pretreatment Differences in BOLD Response to Emotional Faces Correlate with Antidepressant Response to Scopolamine.

Science.gov (United States)

Furey, Maura L; Drevets, Wayne C; Szczepanik, Joanna; Khanna, Ashish; Nugent, Allison; Zarate, Carlos A

2015-03-28

Faster acting antidepressants and biomarkers that predict treatment response are needed to facilitate the development of more effective treatments for patients with major depressive disorders. Here, we evaluate implicitly and explicitly processed emotional faces using neuroimaging to identify potential biomarkers of treatment response to the antimuscarinic, scopolamine. Healthy participants (n=15) and unmedicated-depressed major depressive disorder patients (n=16) participated in a double-blind, placebo-controlled crossover infusion study using scopolamine (4 μg/kg). Before and following scopolamine, blood oxygen-level dependent signal was measured using functional MRI during a selective attention task. Two stimuli comprised of superimposed pictures of faces and houses were presented. Participants attended to one stimulus component and performed a matching task. Face emotion was modulated (happy/sad) creating implicit (attend-houses) and explicit (attend-faces) emotion processing conditions. The pretreatment difference in blood oxygen-level dependent response to happy and sad faces under implicit and explicit conditions (emotion processing biases) within a-priori regions of interest was correlated with subsequent treatment response in major depressive disorder. Correlations were observed exclusively during implicit emotion processing in the regions of interest, which included the subgenual anterior cingulate (Pemotional faces prior to treatment reflect the potential to respond to scopolamine. These findings replicate earlier results, highlighting the potential for pretreatment neural activity in the middle occipital cortices and subgenual anterior cingulate to inform us about the potential to respond clinically to scopolamine. Published by Oxford University Press on behalf of CINP 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Blood Flow and Brain Function: Investigations of neurovascular coupling using BOLD fMRI at 7 tesla

NARCIS (Netherlands)

Siero, J.C.W.

2013-01-01

The advent of ultra high field (7 tesla) MRI systems has opened the possibility to probe biological processes of the human body in great detail. Especially for studying brain function using BOLD fMRI there is a large benefit from the increased magnetic field strength. BOLD fMRI is the working horse

Distinction between Neural and Vascular BOLD Oscillations and Intertwined Heart Rate Oscillations at 0.1 Hz in the Resting State and during Movement.

Directory of Open Access Journals (Sweden)

Gert Pfurtscheller

Full Text Available In the resting state, blood oxygen level-dependent (BOLD oscillations with a frequency of about 0.1 Hz are conspicuous. Whether their origin is neural or vascular is not yet fully understood. Furthermore, it is not clear whether these BOLD oscillations interact with slow oscillations in heart rate (HR. To address these two questions, we estimated phase-locking (PL values between precentral gyrus (PCG and insula in 25 scanner-naïve individuals during rest and stimulus-paced finger movements in both hemispheres. PL was quantified in terms of time delay and duration in the frequency band 0.07 to 0.13 Hz. Results revealed both positive and negative time delays. Positive time delays characterize neural BOLD oscillations leading in the PCG, whereas negative time delays represent vascular BOLD oscillations leading in the insula. About 50% of the participants revealed positive time delays distinctive for neural BOLD oscillations, either with short or long unilateral or bilateral phase-locking episodes. An expected preponderance of neural BOLD oscillations was found in the left hemisphere during right-handed movement and unexpectedly in the right hemisphere during rest. Only neural BOLD oscillations were significantly associated with heart rate variability (HRV in the 0.1-Hz range in the first resting state. It is well known that participating in magnetic resonance imaging (MRI studies may be frightening and cause anxiety. In this respect it is important to note that the most significant hemispheric asymmetry (p<0.002 with a right-sided dominance of neural BOLD and a left-sided dominance of vascular BOLD oscillations was found in the first resting session in the scanner-naïve individuals. Whether the enhanced left-sided perfusion (dominance of vascular BOLD or the right-sided dominance of neural BOLD is related to the increased level of anxiety, attention or stress needs further research.

Socially bold personality in the real communication and Internet communication: the analysis of representations of people of the different age

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Pogodina A. V.

2017-03-01

Full Text Available The article is concerned with the results of the study, subject of which is the submis- sion of the respondents of the different age groups about the social and bold personality. Required property of the respondents was the presence in the Internet environment and participation in various social networks. They assessed social and bold personal- ity in such contexts of communication, as real communication and Internet communication. Analyses were undertaken to determine the structural and content features of emotional and semantic representations of the phenomenon of the social and bold personality, depending on the context of communication, but also the detection of age-sensitive representations of the young respondents (19—35 years, middle-aged respondents (36-55 years and older respondents (from 56 to 70 years. The concept of the “social and bold personality in real communion” is shown to have a high semantic relevance, strongly marked positive emotional coloration and a similar factor structure for respondents of all age groups. The concept of the “social and bold personality in online communication” with a high semantic significance in the perception of the young respondents moves into a zone of moderate and semantic importance in representations of the middle-aged and older respondents. In representations of the respondents of all age groups, the attractiveness of the "social and bold personality in Internet communication" is less than in comparison with the "social and bold personality in the real communication". The age-specific of the social representations about social and bold personality in the real and virtual communication has been analysed in detail.

Sex Differences in Stress Response Circuitry Activation Dependent on Female Hormonal Cycle

Science.gov (United States)

Goldstein, Jill M.; Jerram, Matthew; Abbs, Brandon; Whitfield-Gabrieli, Susan; Makris, Nikos

2010-01-01

Understanding sex differences in stress regulation has important implications for understanding basic physiological differences in the male and female brain and their impact on vulnerability to sex differences in chronic medical disorders associated with stress response circuitry. In this fMRI study, we demonstrated that significant sex differences in brain activity in stress response circuitry were dependent on women's menstrual cycle phase. Twelve healthy Caucasian premenopausal women were compared to a group of healthy men from the same population, based on age, ethnicity, education, and right-handedness. Subjects were scanned using negative valence/high arousal versus neutral visual stimuli that we demonstrated activated stress response circuitry (amygdala, hypothalamus, hippocampus, brainstem, orbitofrontal and medial prefrontal cortices (OFC and mPFC), and anterior cingulate gyrus (ACG). Women were scanned twice based on normal variation in menstrual cycle hormones (i.e., early follicular (EF) compared with late follicular-midcycle menstrual phases (LF/MC)). Using SPM8b, there were few significant differences in BOLD signal changes in men compared to EF women, except ventromedial (VMN) and lateral (LHA) hypothalamus, left amygdala, and ACG. In contrast, men exhibited significantly greater BOLD signal changes compared to LF/MC women on bilateral ACG and OFC, mPFC, LHA, VMN, hippocampus, and periaqueductal gray, with largest effect sizes in mPFC and OFC. Findings suggest that sex differences in stress response circuitry are hormonally regulated via the impact of subcortical brain activity on the cortical control of arousal, and demonstrate that females have been endowed with a natural hormonal capacity to regulate the stress response that differs from males. PMID:20071507

Detection of Acute Tubular Necrosis Using Blood Oxygenation Level-Dependent (BOLD MRI

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Frederic Bauer

2017-12-01

Full Text Available Background/Aims: To date, there is no imaging technique to assess tubular function in vivo. Blood oxygen level-dependent magnetic resonance imaging (BOLD MRI measures tissue oxygenation based on the transverse relaxation rate (R2*. The present study investigates whether BOLD MRI can assess tubular function using a tubule-specific pharmacological maneuver. Methods: Cross sectional study with 28 participants including 9 subjects with ATN-induced acute kidney injury (AKI, 9 healthy controls, and 10 subjects with nephron sparing tumor resection (NSS with clamping of the renal artery serving as a model of ischemia/reperfusion (I/R-induced subclinical ATN (median clamping time 15 min, no significant decrease of eGFR, p=0.14. BOLD MRI was performed before and 5, 7, and 10 min after intravenous administration of 40 mg furosemide. Results: Urinary neutrophil gelatinase-associated lipocalin was significantly higher in ATN-induced AKI and NSS subjects than in healthy controls (p=0.03 and p=0.01, respectively. Before administration of furosemide, absolute medullary R2*, cortical R2*, and medullary/cortical R2* ratio did not significantly differ between ATN-induced AKI vs. healthy controls and between NSS-I/R vs. contralateral healthy kidneys (p>0.05 each. Furosemide led to a significant decrease in the medullary and cortical R2* of healthy subjects and NSS contralateral kidneys (p<0.05 each, whereas there was no significant change of R2* in ATN-induced AKI and the NSS-I/R kidneys (p>0.05 each. Conclusion: BOLD-MRI is able to detect even mild tubular injury but necessitates a tubule-specific pharmacological maneuver, e.g. blocking the Na+-K+-2Cl- transporter by furosemide.

Orientation-specific contextual modulation of the fMRI BOLD response to luminance and chromatic gratings in human visual cortex.

Science.gov (United States)

McDonald, J Scott; Seymour, Kiley J; Schira, Mark M; Spehar, Branka; Clifford, Colin W G

2009-05-01

The responses of orientation-selective neurons in primate visual cortex can be profoundly affected by the presence and orientation of stimuli falling outside the classical receptive field. Our perception of the orientation of a line or grating also depends upon the context in which it is presented. For example, the perceived orientation of a grating embedded in a surround tends to be repelled from the predominant orientation of the surround. Here, we used fMRI to investigate the basis of orientation-specific surround effects in five functionally-defined regions of visual cortex: V1, V2, V3, V3A/LO1 and hV4. Test stimuli were luminance-modulated and isoluminant gratings that produced responses similar in magnitude. Less BOLD activation was evident in response to gratings with parallel versus orthogonal surrounds across all the regions of visual cortex investigated. When an isoluminant test grating was surrounded by a luminance-modulated inducer, the degree of orientation-specific contextual modulation was no larger for extrastriate areas than for V1, suggesting that the observed effects might originate entirely in V1. However, more orientation-specific modulation was evident in extrastriate cortex when both test and inducer were luminance-modulated gratings than when the test was isoluminant; this difference was significant in area V3. We suggest that the pattern of results in extrastriate cortex may reflect a refinement of the orientation-selectivity of surround suppression specific to the colour of the surround or, alternatively, processes underlying the segmentation of test and inducer by spatial phase or orientation when no colour cue is available.

Boldness in a deep sea hermit crab to simulated tactile predator attacks is unaffected by ocean acidification

Science.gov (United States)

Kim, Tae Won; Barry, James P.

2016-09-01

Despite rapidly growing interest in the effects of ocean acidification on marine animals, the ability of deep-sea animals to acclimate or adapt to reduced pH conditions has received little attention. Deep-sea species are generally thought to be less tolerant of environmental variation than shallow-living species because they inhabit relatively stable conditions for nearly all environmental parameters. To explore whether deep-sea hermit crabs ( Pagurus tanneri) can acclimate to ocean acidification over several weeks, we compared behavioral "boldness," measured as time taken to re-emerge from shells after a simulated predatory attack by a toy octopus, under ambient (pH ˜7.6) and expected future (pH ˜7.1) conditions. The boldness measure for crab behavioral responses did not differ between different pH treatments, suggesting that future deep-sea acidification would not influence anti-predatory behavior. However, we did not examine the effects of olfactory cues released by predators that may affect hermit crab behavior and could be influenced by changes in the ocean carbonate system driven by increasing CO2 levels.

BOLD data representing activation and connectivity for rare no-go versus frequent go cues

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Harma Meffert

2016-06-01

Full Text Available The neural circuitry underlying response control is often studied using go/no-go tasks, in which participants are required to respond as fast as possible to go cues and withhold from responding to no-go stimuli. In the current task, response control was studied using a fully counterbalanced design in which blocks with a low frequency of no-go cues (75% go, 25% no-go were alternated with blocks with a low frequency of go cues (25% go, 75% no-go; see also “Segregating attention from response control when performing a motor inhibition task: Segregating attention from response control” [1]. We applied a whole brain corrected, paired t-test to the data assessing for regions differentially activated by low frequency no-go cues relative to high frequency go cues. In addition, we conducted a generalized psychophysiological interaction analysis on the data using a right inferior frontal gyrus seed region. This region was identified through the BOLD response t-test and was chosen because right inferior gyrus is highly implicated in response inhibition.

Physiological denoising of BOLD fMRI data using Regressor Interpolation at Progressive Time Delays (RIPTiDe) processing of concurrent fMRI and near-infrared spectroscopy (NIRS).

Science.gov (United States)

Frederick, Blaise deB; Nickerson, Lisa D; Tong, Yunjie

2012-04-15

Confounding noise in BOLD fMRI data arises primarily from fluctuations in blood flow and oxygenation due to cardiac and respiratory effects, spontaneous low frequency oscillations (LFO) in arterial pressure, and non-task related neural activity. Cardiac noise is particularly problematic, as the low sampling frequency of BOLD fMRI ensures that these effects are aliased in recorded data. Various methods have been proposed to estimate the noise signal through measurement and transformation of the cardiac and respiratory waveforms (e.g. RETROICOR and respiration volume per time (RVT)) and model-free estimation of noise variance through examination of spatial and temporal patterns. We have previously demonstrated that by applying a voxel-specific time delay to concurrently acquired near infrared spectroscopy (NIRS) data, we can generate regressors that reflect systemic blood flow and oxygenation fluctuations effects. Here, we apply this method to the task of removing physiological noise from BOLD data. We compare the efficacy of noise removal using various sets of noise regressors generated from NIRS data, and also compare the noise removal to RETROICOR+RVT. We compare the results of resting state analyses using the original and noise filtered data, and we evaluate the bias for the different noise filtration methods by computing null distributions from the resting data and comparing them with the expected theoretical distributions. Using the best set of processing choices, six NIRS-generated regressors with voxel-specific time delays explain a median of 10.5% of the variance throughout the brain, with the highest reductions being seen in gray matter. By comparison, the nine RETROICOR+RVT regressors together explain a median of 6.8% of the variance in the BOLD data. Detection of resting state networks was enhanced with NIRS denoising, and there were no appreciable differences in the bias of the different techniques. Physiological noise regressors generated using

Amnestic mild cognitive impairment: functional MR imaging study of response in posterior cingulate cortex and adjacent precuneus during problem-solving tasks.

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Jin, Guangwei; Li, Kuncheng; Hu, Yingying; Qin, Yulin; Wang, Xiangqing; Xiang, Jie; Yang, Yanhui; Lu, Jie; Zhong, Ning

2011-11-01

To compare the blood oxygen level-dependent (BOLD) response, measured with functional magnetic resonance (MR) imaging, in the posterior cingulate cortex (PCC) and adjacent precuneus regions between healthy control subjects and patients with amnestic mild cognitive impairment (MCI) during problem-solving tasks. This study was approved by the institutional review board. Each subject provided written informed consent. Thirteen patients with amnestic MCI and 13 age- and sex-matched healthy control subjects participated in the study. The functional magnetic resonance (MR) imaging tasks were simplified 4 × 4-grid number placement puzzles that were divided into a simple task (using the row rule or the column rule to solve the puzzle) and a complex task (using both the row and column rules to solve the puzzle). Behavioral results and functional imaging results between the healthy control group and the amnestic MCI group were analyzed. The accuracy for the complex task in the healthy control group was significantly higher than that in the amnestic MCI group (P < .05). The healthy control group exhibited a deactivated BOLD signal intensity (SI) change in the bilateral PCC and adjacent precuneus regions during the complex task, whereas the amnestic MCI group showed activation. The positive linear correlations between the BOLD SI change in bilateral PCC and adjacent precuneus regions and in bilateral hippocampi in the amnestic MCI group were significant (P < .001), while in the healthy control group, they were not (P ≥ .23). These findings suggest that an altered BOLD response in amnestic MCI patients during complex tasks might be related to a decline in problem-solving ability and to memory impairment and, thus, may indicate a compensatory response to memory impairment. RSNA, 2011

Corticostriatal and Dopaminergic Response to Beer Flavor with Both fMRI and [(11) C]raclopride Positron Emission Tomography.

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Oberlin, Brandon G; Dzemidzic, Mario; Harezlak, Jaroslaw; Kudela, Maria A; Tran, Stella M; Soeurt, Christina M; Yoder, Karmen K; Kareken, David A

2016-09-01

Cue-evoked drug-seeking behavior likely depends on interactions between frontal activity and ventral striatal (VST) dopamine (DA) transmission. Using [(11) C]raclopride (RAC) positron emission tomography (PET), we previously demonstrated that beer flavor (absent intoxication) elicited VST DA release in beer drinkers, inferred by RAC displacement. Here, a subset of subjects from this previous RAC-PET study underwent a similar paradigm during functional magnetic resonance imaging (fMRI) to test how orbitofrontal cortex (OFC) and VST blood oxygenation level-dependent (BOLD) responses to beer flavor are related to VST DA release and motivation to drink. Male beer drinkers (n = 28, age = 24 ± 2, drinks/wk = 16 ± 10) from our previous PET study participated in a similar fMRI paradigm wherein subjects tasted their most frequently consumed brand of beer and Gatorade(®) (appetitive control). We tested for correlations between BOLD activation in fMRI and VST DA responses in PET, and drinking-related variables. Compared to Gatorade, beer flavor increased wanting and desire to drink, and induced BOLD responses in bilateral OFC and right VST. Wanting and desire to drink correlated with both right VST and medial OFC BOLD activation to beer flavor. Like the BOLD findings, beer flavor (relative to Gatorade) again induced right VST DA release in this fMRI subject subset, but there was no correlation between DA release and the magnitude of BOLD responses in frontal regions of interest. Both imaging modalities showed a right-lateralized VST response (BOLD and DA release) to a drug-paired conditioned stimulus, whereas fMRI BOLD responses in the VST and medial OFC also reflected wanting and desire to drink. The data suggest the possibility that responses to drug-paired cues may be rightward biased in the VST (at least in right-handed males) and that VST and OFC responses in this gustatory paradigm reflect stimulus wanting. Copyright © 2016 by the Research Society on

A functional MRI study of happy and sad affective states induced by classical music.

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Mitterschiffthaler, Martina T; Fu, Cynthia H Y; Dalton, Jeffrey A; Andrew, Christopher M; Williams, Steven C R

2007-11-01

The present study investigated the functional neuroanatomy of transient mood changes in response to Western classical music. In a pilot experiment, 53 healthy volunteers (mean age: 32.0; SD = 9.6) evaluated their emotional responses to 60 classical musical pieces using a visual analogue scale (VAS) ranging from 0 (sad) through 50 (neutral) to 100 (happy). Twenty pieces were found to accurately induce the intended emotional states with good reliability, consisting of 5 happy, 5 sad, and 10 emotionally unevocative, neutral musical pieces. In a subsequent functional magnetic resonance imaging (fMRI) study, the blood oxygenation level dependent (BOLD) signal contrast was measured in response to the mood state induced by each musical stimulus in a separate group of 16 healthy participants (mean age: 29.5; SD = 5.5). Mood state ratings during scanning were made by a VAS, which confirmed the emotional valence of the selected stimuli. Increased BOLD signal contrast during presentation of happy music was found in the ventral and dorsal striatum, anterior cingulate, parahippocampal gyrus, and auditory association areas. With sad music, increased BOLD signal responses were noted in the hippocampus/amygdala and auditory association areas. Presentation of neutral music was associated with increased BOLD signal responses in the insula and auditory association areas. Our findings suggest that an emotion processing network in response to music integrates the ventral and dorsal striatum, areas involved in reward experience and movement; the anterior cingulate, which is important for targeting attention; and medial temporal areas, traditionally found in the appraisal and processing of emotions. Copyright 2006 Wiley-Liss, Inc.

Crossing the implementation chasm: a proposal for bold action.

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Lorenzi, Nancy M; Novak, Laurie L; Weiss, Jacob B; Gadd, Cynthia S; Unertl, Kim M

2008-01-01

As health care organizations dramatically increase investment in information technology (IT) and the scope of their IT projects, implementation failures become critical events. Implementation failures cause stress on clinical units, increase risk to patients, and result in massive costs that are often not recoverable. At an estimated 28% success rate, the current level of investment defies management logic. This paper asserts that there are "chasms" in IT implementations that represent risky stages in the process. Contributors to the chasms are classified into four categories: design, management, organization, and assessment. The American College of Medical Informatics symposium participants recommend bold action to better understand problems and challenges in implementation and to improve the ability of organizations to bridge these implementation chasms. The bold action includes the creation of a Team Science for Implementation strategy that allows for participation from multiple institutions to address the long standing and costly implementation issues. The outcomes of this endeavor will include a new focus on interdisciplinary research and an inter-organizational knowledge base of strategies and methods to optimize implementations and subsequent achievement of organizational objectives.

Food cues do not modulate the neuroendocrine response to a prolonged fast in healthy men.

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Snel, Marieke; Wijngaarden, Marjolein A; Bizino, Maurice B; van der Grond, Jeroen; Teeuwisse, Wouter M; van Buchem, Mark A; Jazet, Ingrid M; Pijl, Hanno

2012-01-01

Dietary restriction benefits health and increases lifespan in several species. Food odorants restrain the beneficial effects of dietary restriction in Drosophila melanogaster. We hypothesized that the presence of visual and odorous food stimuli during a prolonged fast modifies the neuroendocrine and metabolic response to fasting in humans. In this randomized, crossover intervention study, healthy young men (n = 12) fasted twice for 60 h; once in the presence and once in the absence of food-related visual and odorous stimuli. At baseline and on the last morning of each intervention, an oral glucose tolerance test (OGTT) was performed. During the OGTT, blood was sampled and a functional MRI scan was made. The main effects of prolonged fasting were: (1) decreased plasma thyroid stimulating hormone and triiodothyronine levels; (2) downregulation of the pituitary-gonadal axis; (3) reduced plasma glucose and insulin concentrations, but increased glucose and insulin responses to glucose ingestion; (4) altered hypothalamic blood oxygenation level-dependent (BOLD) signal in response to the glucose load (particularly during the first 20 min after ingestion); (5) increased resting energy expenditure. Exposure to food cues did not affect these parameters. This study shows that 60 h of fasting in young men (1) decreases the hypothalamic BOLD signal in response to glucose ingestion; (2) induces glucose intolerance; (3) increases resting energy expenditure, and (4) downregulates the pituitary-thyroid and pituitary-gonadal axes. Exposure to visual and odorous food cues did not alter these metabolic and neuroendocrine adaptations to nutrient deprivation. Copyright © 2012 S. Karger AG, Basel.

Visual cortex and auditory cortex activation in early binocularly blind macaques: A BOLD-fMRI study using auditory stimuli.

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Wang, Rong; Wu, Lingjie; Tang, Zuohua; Sun, Xinghuai; Feng, Xiaoyuan; Tang, Weijun; Qian, Wen; Wang, Jie; Jin, Lixin; Zhong, Yufeng; Xiao, Zebin

2017-04-15

Cross-modal plasticity within the visual and auditory cortices of early binocularly blind macaques is not well studied. In this study, four healthy neonatal macaques were assigned to group A (control group) or group B (binocularly blind group). Sixteen months later, blood oxygenation level-dependent functional imaging (BOLD-fMRI) was conducted to examine the activation in the visual and auditory cortices of each macaque while being tested using pure tones as auditory stimuli. The changes in the BOLD response in the visual and auditory cortices of all macaques were compared with immunofluorescence staining findings. Compared with group A, greater BOLD activity was observed in the bilateral visual cortices of group B, and this effect was particularly obvious in the right visual cortex. In addition, more activated volumes were found in the bilateral auditory cortices of group B than of group A, especially in the right auditory cortex. These findings were consistent with the fact that there were more c-Fos-positive cells in the bilateral visual and auditory cortices of group B compared with group A (p visual cortices of binocularly blind macaques can be reorganized to process auditory stimuli after visual deprivation, and this effect is more obvious in the right than the left visual cortex. These results indicate the establishment of cross-modal plasticity within the visual and auditory cortices. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Evaluating the impact of spatio-temporal smoothness constraints on the BOLD hemodynamic response function estimation: an analysis based on Tikhonov regularization

International Nuclear Information System (INIS)

Casanova, R; Yang, L; Hairston, W D; Laurienti, P J; Maldjian, J A

2009-01-01

Recently we have proposed the use of Tikhonov regularization with temporal smoothness constraints to estimate the BOLD fMRI hemodynamic response function (HRF). The temporal smoothness constraint was imposed on the estimates by using second derivative information while the regularization parameter was selected based on the generalized cross-validation function (GCV). Using one-dimensional simulations, we previously found this method to produce reliable estimates of the HRF time course, especially its time to peak (TTP), being at the same time fast and robust to over-sampling in the HRF estimation. Here, we extend the method to include simultaneous temporal and spatial smoothness constraints. This method does not need Gaussian smoothing as a pre-processing step as usually done in fMRI data analysis. We carried out two-dimensional simulations to compare the two methods: Tikhonov regularization with temporal (Tik-GCV-T) and spatio-temporal (Tik-GCV-ST) smoothness constraints on the estimated HRF. We focus our attention on quantifying the influence of the Gaussian data smoothing and the presence of edges on the performance of these techniques. Our results suggest that the spatial smoothing introduced by regularization is less severe than that produced by Gaussian smoothing. This allows more accurate estimates of the response amplitudes while producing similar estimates of the TTP. We illustrate these ideas using real data. (note)

Associations of resting-state fMRI functional connectivity with flow-BOLD coupling and regional vasculature.

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Tak, Sungho; Polimeni, Jonathan R; Wang, Danny J J; Yan, Lirong; Chen, J Jean

2015-04-01

There has been tremendous interest in applying functional magnetic resonance imaging-based resting-state functional connectivity (rs-fcMRI) measurements to the study of brain function. However, a lack of understanding of the physiological mechanisms of rs-fcMRI limits their ability to interpret rs-fcMRI findings. In this work, the authors examine the regional associations between rs-fcMRI estimates and dynamic coupling between the blood oxygenation level-dependent (BOLD) and cerebral blood flow (CBF), as well as resting macrovascular volume. Resting-state BOLD and CBF data were simultaneously acquired using a dual-echo pseudocontinuous arterial spin labeling (pCASL) technique, whereas macrovascular volume fraction was estimated using time-of-flight MR angiography. Functional connectivity within well-known functional networks—including the default mode, frontoparietal, and primary sensory-motor networks—was calculated using a conventional seed-based correlation approach. They found the functional connectivity strength to be significantly correlated with the regional increase in CBF-BOLD coupling strength and inversely proportional to macrovascular volume fraction. These relationships were consistently observed within all functional networks considered. Their findings suggest that highly connected networks observed using rs-fcMRI are not likely to be mediated by common vascular drainage linking distal cortical areas. Instead, high BOLD functional connectivity is more likely to reflect tighter neurovascular connections, attributable to neuronal pathways.

Towards a mechanistic understanding of vulnerability to hook-and-line fishing: Boldness as the basic target of angling-induced selection

DEFF Research Database (Denmark)

Klefoth, Thomas; Skov, Christian; Kuparinen, Anna

2017-01-01

by juvenile growth rate, while morphological traits were only weakly related to angling vulnerability. In addition, we found juvenile growth rate to be moderately correlated with boldness. Hence, direct selection on boldness will also induce indirect selection on juvenile growth and vice versa, but given......In passively operated fishing gear, boldness-related behaviors should fundamentally affect the vulnerability of individual fish and thus be under fisheries selection. To test this hypothesis, we used juvenile common-garden reared carp (Cyprinus carpio) within a narrow size range to investigate...... the mechanistic basis of behavioral selection caused by angling. We focused on one key personality trait (i.e., boldness), measured in groups within ponds, two morphological traits (body shape and head shape), and one life-history trait (juvenile growth capacity) and studied mean standardized selection gradients...

Modelling cardiac signal as a confound in EEG-fMRI and its application in focal epilepsy studies

DEFF Research Database (Denmark)

Liston, A. D.; Ellegaard Lund, Torben; Salek-Haddadi, A

2006-01-01

effects to be modelled, as effects of no interest. Our model is based on an over-complete basis set covering a linear relationship between cardiac-related MR signal and the phase of the cardiac cycle or time after pulse (TAP). This method showed that, on average, 24.6 +/- 10.9% of grey matter voxels......Cardiac noise has been shown to reduce the sensitivity of functional Magnetic Resonance Imaging (fMRI) to an experimental effect due to its confounding presence in the blood oxygenation level-dependent (BOLD) signal. Its effect is most severe in particular regions of the brain and a method is yet...... to take it into account in routine fMRI analysis. This paper reports the development of a general and robust technique to improve the reliability of EEG-fMRI studies to BOLD signal correlated with interictal epileptiform discharges (IEDs). In these studies, ECG is routinely recorded, enabling cardiac...

The effect of sleep deprivation on BOLD activity elicited by a divided attention task.

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Jackson, Melinda L; Hughes, Matthew E; Croft, Rodney J; Howard, Mark E; Crewther, David; Kennedy, Gerard A; Owens, Katherine; Pierce, Rob J; O'Donoghue, Fergal J; Johnston, Patrick

2011-06-01

Sleep loss, widespread in today's society and associated with a number of clinical conditions, has a detrimental effect on a variety of cognitive domains including attention. This study examined the sequelae of sleep deprivation upon BOLD fMRI activation during divided attention. Twelve healthy males completed two randomized sessions; one after 27 h of sleep deprivation and one after a normal night of sleep. During each session, BOLD fMRI was measured while subjects completed a cross-modal divided attention task (visual and auditory). After normal sleep, increased BOLD activation was observed bilaterally in the superior frontal gyrus and the inferior parietal lobe during divided attention performance. Subjects reported feeling significantly more sleepy in the sleep deprivation session, and there was a trend towards poorer divided attention task performance. Sleep deprivation led to a down regulation of activation in the left superior frontal gyrus, possibly reflecting an attenuation of top-down control mechanisms on the attentional system. These findings have implications for understanding the neural correlates of divided attention and the neurofunctional changes that occur in individuals who are sleep deprived.

Interneuronal systems of the cervical spinal cord assessed with BOLD imaging at 1.5 T

International Nuclear Information System (INIS)

Stracke, C.P.; Schoth, F.; Moeller-Hartmann, W.; Krings, T.; Pettersson, L.G.

2005-01-01

The purpose of this study was to investigate if functional activity with spinal cord somatosensory stimulation can be visualized using BOLD fMRI. We investigated nine healthy volunteers using a somatosensory stimulus generator. The stimuli were applied in three different runs at the first, third, and fifth finger tip of the right hand, respectively, corresponding to dermatomes c6, c7, and c8. The stimuli gave an increase of BOLD signal (activation) in three different locations of the spinal cord and brain stem. First, activations could be seen in the spinal segment corresponding to the stimulated dermatome in seven out of nine volunteers for c6 stimulation, two out of eight for c7, and three out of eight for c8. These activations were located close to the posterior margin of the spinal cord, presumably reflecting synaptic transmission to dorsal horn interneurons. Second, activation in the medulla oblongata was evident in four subjects, most likely corresponding to the location of the nucleus cuneatus. The third location of activation, which was the strongest and most reliable observed was inside the spinal cord in the c3 and c4 segments. Activation at these spinal levels was almost invariably observed independently of the dermatome stimulated (9/9 for c6, 8/8 for c7, and 7/8 for c8 stimulation). These activations may pertain to an interneuronal system at this spinal level. The results are discussed in relation to neurophysiological studies on cervical spinal interneuronal pathways in animals and humans. (orig.)

Investigations into the bystander effect: signal versus response

International Nuclear Information System (INIS)

Vines, A.M.; Seymour, C.B.; Mothersill, C.E.

2003-01-01

The bystander effect is the general term used to describe the effects seen in cells or tissue that have never been directly irradiated, but display similar symptoms to those that have. Some of these symptoms include reduced cell survival, chromosomal aberrations, and increased apoptosis. This investigation aims to explore the signal produced by certain cell and tissue types, and the relationship this has with the subsequent response. The goal is to elucidate whether the reduction in cell survival frequently seen in response to the bystander effect is determined by the signal produced or the response of the cell type. Firstly, a matrix design experiment was set up using 3 cell lines. Each cell line was irradiated to produce ICCM (Irradiated Cell Conditioned Medium), which was in turn used to treat all cell lines in the study. Medium transfer is carried out within cell lines, (ICCM from CHO onto CHO cells) and between cell lines (ICCM from CHO onto HPV-G cells). In the second set of experiments, tissue samples from male Wister rats were used to generate ITCM (Irradiated Tissue Conditioned Medium). This medium was then tested on a cell line with an established response to the bystander effect. As an extension to these two experimental protocols, both ICCM and ITCM were used to investigate if there is calcium flux in the cells as a response to the bystander medium. This has recently been shown to be an early response to the bystander signal. Results indicate that it is the signal produced by the irradiated cells that determine the overall effect of the bystander signal, and not the response of the cells expose to it. CHO-K1 cells treated with autologous ICCM show a 16.2% drop in cell survival. However, when this cell line is treated with HPV-G ICCM, it shows a 36.5% drop in survival. HPV-G cells treated with autologous medium display a similar response to this, with a 41.1% drop in survival, though when treated with CHO-K1 ICCM, the drop in survival is 22.9%. This

Agrobacterium tumefaciens responses to plant-derived signaling molecules

Science.gov (United States)

Subramoni, Sujatha; Nathoo, Naeem; Klimov, Eugene; Yuan, Ze-Chun

2014-01-01

As a special phytopathogen, Agrobacterium tumefaciens infects a wide range of plant hosts and causes plant tumors also known as crown galls. The complexity of Agrobacterium–plant interaction has been studied for several decades. Agrobacterium pathogenicity is largely attributed to its evolved capabilities of precise recognition and response to plant-derived chemical signals. Agrobacterium perceives plant-derived signals to activate its virulence genes, which are responsible for transferring and integrating its Transferred DNA (T-DNA) from its Tumor-inducing (Ti) plasmid into the plant nucleus. The expression of T-DNA in plant hosts leads to the production of a large amount of indole-3-acetic acid (IAA), cytokinin (CK), and opines. IAA and CK stimulate plant growth, resulting in tumor formation. Agrobacterium utilizes opines as nutrient sources as well as signals in order to activate its quorum sensing (QS) to further promote virulence and opine metabolism. Intriguingly, Agrobacterium also recognizes plant-derived signals including γ-amino butyric acid and salicylic acid (SA) to activate quorum quenching that reduces the level of QS signals, thereby avoiding the elicitation of plant defense and preserving energy. In addition, Agrobacterium hijacks plant-derived signals including SA, IAA, and ethylene to down-regulate its virulence genes located on the Ti plasmid. Moreover, certain metabolites from corn (Zea mays) also inhibit the expression of Agrobacterium virulence genes. Here we outline the responses of Agrobacterium to major plant-derived signals that impact Agrobacterium–plant interactions. PMID:25071805

Agrobacterium tumefaciens responses to plant-derived signaling molecules

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Sujatha eSubramoni

2014-07-01

Full Text Available As a special phytopathogen, Agrobacterium tumefaciens infects a wide range of plant hosts and causes plant tumors also known as crown galls. The complexity of Agrobacterium-plant interaction has been studied for several decades. Agrobacterium pathogenicity is largely attributed to its evolved capabilities of precise recognition and response to plant-derived chemical signals. Agrobacterium perceives plant-derived signals to activate its virulence genes, which are responsible for transferring and integrating its T-DNA (Transferred DNA from its Tumour-inducing (Ti plasmid into the plant nucleus. The expression of T-DNA in plant hosts leads to the production of a large amount of indole-3-acetic acid (IAA, cytokinin (CK and opines. IAA and CK stimulate plant growth, resulting in tumor formation. Agrobacterium utilizes opines as nutrient sources as well as signals in order to activate its quorum sensing (QS to further promote virulence and opine metabolism. Intriguingly, Agrobacterium also recognizes plant-derived signals including -amino butyric acid (GABA and salicylic acid (SA to activate quorum quenching that reduces the level of QS signals, thereby avoiding the elicitation of plant defense and preserving energy. In addition, Agrobacterium hijacks plant-derived signals including SA, IAA, and ethylene (ET to down-regulate its virulence genes located on the Ti plasmid. Moreover, certain metabolites from corn (Zea mays also inhibit the expression of Agrobacterium virulence genes. Here we outline the responses of Agrobacterium to major plant-derived signals that impact Agrobacterium-plant interactions.

Negative BOLD in sensory cortices during verbal memory: a component in generating internal representations?

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Azulay, Haim; Striem, Ella; Amedi, Amir

2009-05-01

People tend to close their eyes when trying to retrieve an event or a visual image from memory. However the brain mechanisms behind this phenomenon remain poorly understood. Recently, we showed that during visual mental imagery, auditory areas show a much more robust deactivation than during visual perception. Here we ask whether this is a special case of a more general phenomenon involving retrieval of intrinsic, internally stored information, which would result in crossmodal deactivations in other sensory cortices which are irrelevant to the task at hand. To test this hypothesis, a group of 9 sighted individuals were scanned while performing a memory retrieval task for highly abstract words (i.e., with low imaginability scores). We also scanned a group of 10 congenitally blind, which by definition do not have any visual imagery per se. In sighted subjects, both auditory and visual areas were robustly deactivated during memory retrieval, whereas in the blind the auditory cortex was deactivated while visual areas, shown previously to be relevant for this task, presented a positive BOLD signal. These results suggest that deactivation may be most prominent in task-irrelevant sensory cortices whenever there is a need for retrieval or manipulation of internally stored representations. Thus, there is a task-dependent balance of activation and deactivation that might allow maximization of resources and filtering out of non relevant information to enable allocation of attention to the required task. Furthermore, these results suggest that the balance between positive and negative BOLD might be crucial to our understanding of a large variety of intrinsic and extrinsic tasks including high-level cognitive functions, sensory processing and multisensory integration.

Higher frequency network activity flow predicts lower frequency node activity in intrinsic low-frequency BOLD fluctuations.

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Bajaj, Sahil; Adhikari, Bhim Mani; Dhamala, Mukesh

2013-01-01

The brain remains electrically and metabolically active during resting conditions. The low-frequency oscillations (LFO) of the blood oxygen level-dependent (BOLD) signal of functional magnetic resonance imaging (fMRI) coherent across distributed brain regions are known to exhibit features of this activity. However, these intrinsic oscillations may undergo dynamic changes in time scales of seconds to minutes during resting conditions. Here, using wavelet-transform based time-frequency analysis techniques, we investigated the dynamic nature of default-mode networks from intrinsic BOLD signals recorded from participants maintaining visual fixation during resting conditions. We focused on the default-mode network consisting of the posterior cingulate cortex (PCC), the medial prefrontal cortex (mPFC), left middle temporal cortex (LMTC) and left angular gyrus (LAG). The analysis of the spectral power and causal flow patterns revealed that the intrinsic LFO undergo significant dynamic changes over time. Dividing the frequency interval 0 to 0.25 Hz of LFO into four intervals slow-5 (0.01-0.027 Hz), slow-4 (0.027-0.073 Hz), slow-3 (0.073-0.198 Hz) and slow-2 (0.198-0.25 Hz), we further observed significant positive linear relationships of slow-4 in-out flow of network activity with slow-5 node activity, and slow-3 in-out flow of network activity with slow-4 node activity. The network activity associated with respiratory related frequency (slow-2) was found to have no relationship with the node activity in any of the frequency intervals. We found that the net causal flow towards a node in slow-3 band was correlated with the number of fibers, obtained from diffusion tensor imaging (DTI) data, from the other nodes connecting to that node. These findings imply that so-called resting state is not 'entirely' at rest, the higher frequency network activity flow can predict the lower frequency node activity, and the network activity flow can reflect underlying structural

Brain Signal Variability Differentially Affects Cognitive Flexibility and Cognitive Stability.

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Armbruster-Genç, Diana J N; Ueltzhöffer, Kai; Fiebach, Christian J

2016-04-06

Recent research yielded the intriguing conclusion that, in healthy adults, higher levels of variability in neuronal processes are beneficial for cognitive functioning. Beneficial effects of variability in neuronal processing can also be inferred from neurocomputational theories of working memory, albeit this holds only for tasks requiring cognitive flexibility. However, cognitive stability, i.e., the ability to maintain a task goal in the face of irrelevant distractors, should suffer under high levels of brain signal variability. To directly test this prediction, we studied both behavioral and brain signal variability during cognitive flexibility (i.e., task switching) and cognitive stability (i.e., distractor inhibition) in a sample of healthy human subjects and developed an efficient and easy-to-implement analysis approach to assess BOLD-signal variability in event-related fMRI task paradigms. Results show a general positive effect of neural variability on task performance as assessed by accuracy measures. However, higher levels of BOLD-signal variability in the left inferior frontal junction area result in reduced error rate costs during task switching and thus facilitate cognitive flexibility. In contrast, variability in the same area has a detrimental effect on cognitive stability, as shown in a negative effect of variability on response time costs during distractor inhibition. This pattern was mirrored at the behavioral level, with higher behavioral variability predicting better task switching but worse distractor inhibition performance. Our data extend previous results on brain signal variability by showing a differential effect of brain signal variability that depends on task context, in line with predictions from computational theories. Recent neuroscientific research showed that the human brain signal is intrinsically variable and suggested that this variability improves performance. Computational models of prefrontal neural networks predict differential

Real-time fMRI neurofeedback of the mediodorsal and anterior thalamus enhances correlation between thalamic BOLD activity and alpha EEG rhythm.

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Zotev, Vadim; Misaki, Masaya; Phillips, Raquel; Wong, Chung Ki; Bodurka, Jerzy

2018-02-01

Real-time fMRI neurofeedback (rtfMRI-nf) with simultaneous EEG allows volitional modulation of BOLD activity of target brain regions and investigation of related electrophysiological activity. We applied this approach to study correlations between thalamic BOLD activity and alpha EEG rhythm. Healthy volunteers in the experimental group (EG, n = 15) learned to upregulate BOLD activity of the target region consisting of the mediodorsal (MD) and anterior (AN) thalamic nuclei using rtfMRI-nf during retrieval of happy autobiographical memories. Healthy subjects in the control group (CG, n = 14) were provided with a sham feedback. The EG participants were able to significantly increase BOLD activities of the MD and AN. Functional connectivity between the MD and the inferior precuneus was significantly enhanced during the rtfMRI-nf task. Average individual changes in the occipital alpha EEG power significantly correlated with the average MD BOLD activity levels for the EG. Temporal correlations between the occipital alpha EEG power and BOLD activities of the MD and AN were significantly enhanced, during the rtfMRI-nf task, for the EG compared to the CG. Temporal correlations with the alpha power were also significantly enhanced for the posterior nodes of the default mode network, including the precuneus/posterior cingulate, and for the dorsal striatum. Our findings suggest that the temporal correlation between the MD BOLD activity and posterior alpha EEG power is modulated by the interaction between the MD and the inferior precuneus, reflected in their functional connectivity. Our results demonstrate the potential of the rtfMRI-nf with simultaneous EEG for noninvasive neuromodulation studies of human brain function. © 2017 Wiley Periodicals, Inc.

Factors related to the magnitude of T2* MR signal changes during functional imaging

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Krings, T. [Department of Neuroradiology, University Hospital of the Technical University Aachen (Germany); Department of Neurosurgery, University Hospital of the Technical University Aachen (Germany); Interdisciplinary Centre for Clinical Research - Central Nervous System, University Hospital of the Technical University Aachen, Pauwelsstrasse 30, 52057 Aachen (Germany); Reinges, M.H.T.; Gilsbach, J.M. [Department of Neurosurgery, University Hospital of the Technical University Aachen (Germany); Willmes, K.; Nuerk, H.C. [Section of Neuropsychology, Department of Neurology, University Hospital of the Technical University Aachen (Germany); Meister, I.G. [Department of Neurology, University Hospital of the Technical University Aachen (Germany); Thron, A. [Department of Neuroradiology, University Hospital of the Technical University Aachen (Germany)

2002-06-01

Our aim was to determine whether age, sex, the degree of weakness, anticonvulsants, the histology of the underlying lesion(s), the presence of oedema or the distance of the lesion from the motor region have an impact on the blood oxygenation level-dependent (BOLD) signal strength and therefore on the validity of functional MRI (fMRI). We studied 98 patients with masses near the central region imaged for surgical planning at 1.5 tesla, employing a BOLD sequence during a motor task. We calculated percentage signal change in the primary motor cortex between rest and activation and carried out multiple linear regression to examine the impact of the above factors on signal strength. Using a stepwise analysis strategy, the distance of the lesion from the motor region had the strongest influence (r=0.653, P<0.001). The factor with largest uncorrelated additional impact on signal change was the presence of oedema. Both predictors together formed a highly significant multiple r=0.739 (P<0.001). No other predictive factor was identified (all P>0.20). Disturbances of cerebral blood flow and metabolism induced by the tumour were presumed to be the causes of a decrease in signal in the adjacent cortex. (orig.)

Physiologic characterization of inflammatory arthritis in a rabbit model with BOLD and DCE MRI at 1.5 Tesla

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Nasui, Otilia C.; Chan, Michael W.; Nathanael, George; Rayner, Tammy; Weiss, Ruth; Detzler, Garry; Zhong, Anguo [The Hospital for Sick Children, Department of Diagnostic Imaging, Toronto, ON (Canada); Crawley, Adrian [University of Toronto, Department of Medical Imaging, Toronto, ON (Canada); Toronto Western Hospital, Department of Medical Imaging, Toronto, ON (Canada); Miller, Elka [Children' s Hospital of Eastern Ontario (CHEO), Department of Diagnostic Imaging, Ottawa, ON (Canada); Belik, Jaques [The Hospital for Sick Children, Department of Neonatology, Toronto, ON (Canada); Cheng, Hai-Ling; Kassner, Andrea; Doria, Andrea S. [The Hospital for Sick Children, Department of Diagnostic Imaging, Toronto, ON (Canada); University of Toronto, Department of Medical Imaging, Toronto, ON (Canada); Moineddin, Rahim [Department of Public Health, Family and Community Medicine, Toronto, ON (Canada); Jong, Roland; Rogers, Marianne [Mount Sinai Hospital, Department of Pathology, Toronto, ON (Canada)

2014-11-15

Our aim was to test the feasibility of blood oxygen level dependent magnetic resonance imaging (BOLD MRI) and dynamic contrast-enhanced (DCE) MRI to monitor periarticular hypoxic/inflammatory changes over time in a juvenile rabbit model of arthritis. We examined arthritic and contralateral nonarthritic knees of 21 juvenile rabbits at baseline and days 1,14, and 28 after induction of arthritis by unilateral intra-articular injection of carrageenin with BOLD and DCE MRI at 1.5 Tesla (T). Nine noninjected rabbits served as controls. Associations between BOLD and DCE-MRI and corresponding intra-articular oxygen pressure (PO{sub 2}) and blood flow [blood perfusion units (BPU)] (polarographic probes, reference standards) or clinical-histological data were measured by correlation coefficients. Percentage BOLD MRI change obtained in contralateral knees correlated moderately with BPU on day 0 (r = -0.51, p = 0.02) and excellently on day 28 (r = -0.84, p = 0.03). A moderate correlation was observed between peak enhancement DCE MRI (day 1) and BPU measurements in arthritic knees (r = 0.49, p = 0.04). In acute arthritis, BOLD and DCE MRI highly correlated (r = 0.89, p = 0.04; r = 1.0, p < 0.0001) with histological scores in arthritic knees. The proposed techniques are feasible to perform at 1.5 T, and they hold potential as surrogate measures to monitor hypoxic and inflammatory changes over time in arthritis at higher-strength MRI fields. (orig.)

Graph Theoretical Analysis of BOLD Functional Connectivity during Human Sleep without EEG Monitoring.

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Jun Lv

Full Text Available Functional brain networks of human have been revealed to have small-world properties by both analyzing electroencephalogram (EEG and functional magnetic resonance imaging (fMRI time series.In our study, by using graph theoretical analysis, we attempted to investigate the changes of paralimbic-limbic cortex between wake and sleep states. Ten healthy young people were recruited to our experiment. Data from 2 subjects were excluded for the reason that they had not fallen asleep during the experiment. For each subject, blood oxygen level dependency (BOLD images were acquired to analyze brain network, and peripheral pulse signals were obtained continuously to identify if the subject was in sleep periods. Results of fMRI showed that brain networks exhibited stronger small-world characteristics during sleep state as compared to wake state, which was in consistent with previous studies using EEG synchronization. Moreover, we observed that compared with wake state, paralimbic-limbic cortex had less connectivity with neocortical system and centrencephalic structure in sleep.In conclusion, this is the first study, to our knowledge, has observed that small-world properties of brain functional networks altered when human sleeps without EEG synchronization. Moreover, we speculate that paralimbic-limbic cortex organization owns an efficient defense mechanism responsible for suppressing the external environment interference when humans sleep, which is consistent with the hypothesis that the paralimbic-limbic cortex may be functionally disconnected from brain regions which directly mediate their interactions with the external environment. Our findings also provide a reasonable explanation why stable sleep exhibits homeostasis which is far less susceptible to outside world.

Ionic signaling in plant responses to gravity and touch

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Fasano, Jeremiah M.; Massa, Gioia D.; Gilroy, Simon

2002-01-01

Touch and gravity are two of the many stimuli that plants must integrate to generate an appropriate growth response. Due to the mechanical nature of both of these signals, shared signal transduction elements could well form the basis of the cross-talk between these two sensory systems. However, touch stimulation must elicit signaling events across the plasma membrane whereas gravity sensing is thought to represent transformation of an internal force, amyloplast sedimentation, to signal transduction events. In addition, factors such as turgor pressure and presence of the cell wall may also place unique constraints on these plant mechanosensory systems. Even so, the candidate signal transduction elements in both plant touch and gravity sensing, changes in Ca2+, pH and membrane potential, do mirror the known ionic basis of signaling in animal mechanosensory cells. Distinct spatial and temporal signatures of Ca2+ ions may encode information about the different mechanosignaling stimuli. Signals such as Ca2+ waves or action potentials may also rapidly transfer information perceived in one cell throughout a tissue or organ leading to the systemic reactions characteristic of plant touch and gravity responses. Longer-term growth responses are likely sustained via changes in gene expression and asymmetries in compounds such as inositol-1,4,5-triphosphate (IP3) and calmodulin. Thus, it seems likely that plant mechanoperception involves both spatial and temporal encoding of information at all levels, from the cell to the whole plant. Defining this patterning will be a critical step towards understanding how plants integrate information from multiple mechanical stimuli to an appropriate growth response.

Cerebral Metabolic Rate of Oxygen (CMRO2 ) Mapping by Combining Quantitative Susceptibility Mapping (QSM) and Quantitative Blood Oxygenation Level-Dependent Imaging (qBOLD).

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Cho, Junghun; Kee, Youngwook; Spincemaille, Pascal; Nguyen, Thanh D; Zhang, Jingwei; Gupta, Ajay; Zhang, Shun; Wang, Yi

2018-03-07

To map the cerebral metabolic rate of oxygen (CMRO 2 ) by estimating the oxygen extraction fraction (OEF) from gradient echo imaging (GRE) using phase and magnitude of the GRE data. 3D multi-echo gradient echo imaging and perfusion imaging with arterial spin labeling were performed in 11 healthy subjects. CMRO 2 and OEF maps were reconstructed by joint quantitative susceptibility mapping (QSM) to process GRE phases and quantitative blood oxygen level-dependent (qBOLD) modeling to process GRE magnitudes. Comparisons with QSM and qBOLD alone were performed using ROI analysis, paired t-tests, and Bland-Altman plot. The average CMRO 2 value in cortical gray matter across subjects were 140.4 ± 14.9, 134.1 ± 12.5, and 184.6 ± 17.9 μmol/100 g/min, with corresponding OEFs of 30.9 ± 3.4%, 30.0 ± 1.8%, and 40.9 ± 2.4% for methods based on QSM, qBOLD, and QSM+qBOLD, respectively. QSM+qBOLD provided the highest CMRO 2 contrast between gray and white matter, more uniform OEF than QSM, and less noisy OEF than qBOLD. Quantitative CMRO 2 mapping that fits the entire complex GRE data is feasible by combining QSM analysis of phase and qBOLD analysis of magnitude. © 2018 International Society for Magnetic Resonance in Medicine.

Non-invasive pre-clinical MR imaging of prostate tumor hypoxia for radiation therapy prognosis

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Derek White

2014-03-01

Full Text Available Purpose: To investigate the usefulness of Oxygen-Enhanced Magnetic Resonance Imaging (OE-MRI changes in signal intensity related to oxygen challenge for predicting tumor response to radiation therapy.Methods: Dynamic MR signal changes were acquired using Varian 4.7T small animal MR scanner prior to image-guided radiation therapy (IGRT of small (n = 6 and large subcutaneous (n = 5 prostate tumors in adult male rats. An interleaved blood-oxygen level dependent (BOLD and tissue-oxygen level dependent (TOLD data acquisition or (IBT was performed using a baseline of medical air as positive control and using medical oxygen as a breathing challenge. BOLD used a 2-D multi-slice spoiled gradient-echo with multi-echo sequence. TOLD used a 2-D multi-slice spoiled gradient-echo sequence. Voxel changes in signal intensity were determined by a correlation coefficient mapping technique. Irradiation technique planned consisted of 1F × 15 Gy AP/PA or 2F × 7.5 Gy AP/PA to the gross tumor volume (GTV. Tumor growth measurements were recorded over time to assess the response to IGRT.Results: BOLD and TOLD signals variously illustrated positive or negative impulse responses in the tumor ROI due to inhaling medical oxygen. Correlation coefficient mapping demonstrated heterogeneity in tumors after inhaling medical oxygen. BOLD and TOLD signals exhibited increased changes in signal intensities after the first fraction of dose. Multi-fractionation had minimum effect until the second fraction of dose was applied. Tumor growth delays were observed when inhaling medical oxygen during IGRT.Conclusion: OE-MRI is a non-invasive imaging modality that can provide insight to the oxygen status of tumors. Observed increase percent changes in BOLD and TOLD signal intensities after the first fraction of dose suggest tumors experienced reoxygenation. OE-MRI could be used for predicting tumor response to IGRT when using medical oxygen for increasing GTV radiosensitivity, suggesting

Fourier power, subjective distance, and object categories all provide plausible models of BOLD responses in scene-selective visual areas

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Lescroart, Mark D.; Stansbury, Dustin E.; Gallant, Jack L.

2015-01-01

Perception of natural visual scenes activates several functional areas in the human brain, including the Parahippocampal Place Area (PPA), Retrosplenial Complex (RSC), and the Occipital Place Area (OPA). It is currently unclear what specific scene-related features are represented in these areas. Previous studies have suggested that PPA, RSC, and/or OPA might represent at least three qualitatively different classes of features: (1) 2D features related to Fourier power; (2) 3D spatial features such as the distance to objects in a scene; or (3) abstract features such as the categories of objects in a scene. To determine which of these hypotheses best describes the visual representation in scene-selective areas, we applied voxel-wise modeling (VM) to BOLD fMRI responses elicited by a set of 1386 images of natural scenes. VM provides an efficient method for testing competing hypotheses by comparing predictions of brain activity based on encoding models that instantiate each hypothesis. Here we evaluated three different encoding models that instantiate each of the three hypotheses listed above. We used linear regression to fit each encoding model to the fMRI data recorded from each voxel, and we evaluated each fit model by estimating the amount of variance it predicted in a withheld portion of the data set. We found that voxel-wise models based on Fourier power or the subjective distance to objects in each scene predicted much of the variance predicted by a model based on object categories. Furthermore, the response variance explained by these three models is largely shared, and the individual models explain little unique variance in responses. Based on an evaluation of previous studies and the data we present here, we conclude that there is currently no good basis to favor any one of the three alternative hypotheses about visual representation in scene-selective areas. We offer suggestions for further studies that may help resolve this issue. PMID:26594164

Spectral responses of gravel beaches to tidal signals

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Geng, Xiaolong; Boufadel, Michel C.

2017-01-01

Tides have been recognized as a major driving forcing affecting coastal aquifer system, and deterministic modeling has been very effective in elucidating mechanisms caused by tides. However, such modeling does not lend itself to capture embedded information in the signal, and rather focuses on the primary processes. Here, using yearlong data sets measured at beaches in Alaska Prince William Sound, we performed spectral and correlation analyses to identify temporal behavior of pore-water pressure, temperature and salinity. We found that the response of the beach system was characterized by fluctuations of embedded diurnal, semidiurnal, terdiurnal and quarterdiurnal tidal components. Hydrodynamic dispersion of salinity and temperature, and the thermal conductivity greatly affected pore water signals. Spectral analyses revealed a faster dissipation of the semi-diurnal component with respect to the diurnal components. Correlation functions showed that salinity had a relatively short memory of the tidal signal when inland freshwater recharge was large. In contrast, the signature of the tidal signal on pore-water temperature persisted for longer times, up to a week. We also found that heterogeneity greatly affected beach response. The response varied from a simple linear mapping in the frequency domain to complete modulation and masking of the input frequencies.

Glucose-induced inhibition of the appetitive brain response to visual food cues in polycystic ovary syndrome patients.

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Van Vugt, Dean A; Krzemien, Alicja; Alsaadi, Hanin; Frank, Tamar C; Reid, Robert L

2014-04-16

We postulate that insulin regulation of food intake is compromised when insulin resistance is present. In order to investigate the effect of insulin sensitivity on appetitive brain responses, we conducted functional magnetic resonance imaging studies in a group of women diagnosed with polycystic ovary syndrome (PCOS) in which insulin sensitivity ranged from normal to resistant. Subjects (n=19) were imaged while viewing pictures of high calorie (HC) foods and low calorie (LC) foods after ingesting either 75 g glucose or an equivalent volume of water. The insulin sensitive group showed reduced blood oxygen level dependent (BOLD) signal in response to food pictures following glucose ingestion in numerous corticolimbic brain regions, whereas the insulin resistant group did not. There was a significant interaction between insulin sensitivity (sensitive vs resistant) and condition (water vs glucose). The largest clusters identified included the left insula, bilateral limbic/parahippocampal gyrus/culmen/midbrain, bilateral limbic lobe/precuneus, and left superior/mid temporal gyrus/parietal for HC and LC stimuli combined, the left parahippocampal gyrus/fusiform/pulvinar/midbrain for HC pictures, and the left superior/mid temporal gyrus/parietal and middle/inferior frontal gyrus/orbitofrontal cortex for LC pictures. Furthermore, BOLD signal in the anterior cingulate, medial frontal gyrus, posterior cingulate/precuneus, and parietal cortex during a glucose challenge correlated negatively with insulin sensitivity. We conclude the PCOS women with insulin resistance have an impaired brain response to a glucose challenge. The inability of postprandial hyperinsulinemia to inhibit brain responsiveness to food cues in insulin resistant subjects may lead to greater non-homeostatic eating. Copyright © 2014 Elsevier B.V. All rights reserved.

Functional magnetic resonance imaging in awake transgenic fragile X rats: evidence of dysregulation in reward processing in the mesolimbic/habenular neural circuit.

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Kenkel, W M; Yee, J R; Moore, K; Madularu, D; Kulkarni, P; Gamber, K; Nedelman, M; Ferris, C F

2016-03-22

Anxiety and social deficits, often involving communication impairment, are fundamental clinical features of fragile X syndrome. There is growing evidence that dysregulation in reward processing is a contributing factor to the social deficits observed in many psychiatric disorders. Hence, we hypothesized that transgenic fragile X mental retardation 1 gene (fmr1) KO (FX) rats would display alterations in reward processing. To this end, awake control and FX rats were imaged for changes in blood oxygen level dependent (BOLD) signal intensity in response to the odor of almond, a stimulus to elicit the innate reward response. Subjects were 'odor naive' to this evolutionarily conserved stimulus. The resulting changes in brain activity were registered to a three-dimensional segmented, annotated rat atlas delineating 171 brain regions. Both wild-type (WT) and FX rats showed robust brain activation to a rewarding almond odor, though FX rats showed an altered temporal pattern and tended to have a higher number of voxels with negative BOLD signal change from baseline. This pattern of greater negative BOLD was especially apparent in the Papez circuit, critical to emotional processing and the mesolimbic/habenular reward circuit. WT rats showed greater positive BOLD response in the supramammillary area, whereas FX rats showed greater positive BOLD response in the dorsal lateral striatum, and greater negative BOLD response in the retrosplenial cortices, the core of the accumbens and the lateral preoptic area. When tested in a freely behaving odor-investigation paradigm, FX rats failed to show the preference for almond odor which typifies WT rats. However, FX rats showed investigation profiles similar to WT when presented with social odors. These data speak to an altered processing of this highly salient novel odor in the FX phenotype and lend further support to the notion that altered reward systems in the brain may contribute to fragile X syndrome symptomology.

Danger Signals Activating the Immune Response after Trauma

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Stefanie Hirsiger

2012-01-01

Full Text Available Sterile injury can cause a systemic inflammatory response syndrome (SIRS that resembles the host response during sepsis. The inflammatory response following trauma comprises various systems of the human body which are cross-linked with each other within a highly complex network of inflammation. Endogenous danger signals (danger-associated molecular patterns; DAMPs; alarmins as well as exogenous pathogen-associated molecular patterns (PAMPs play a crucial role in the initiation of the immune response. With popularization of the “danger theory,” numerous DAMPs and PAMPs and their corresponding pathogen-recognition receptors have been identified. In this paper, we highlight the role of the DAMPs high-mobility group box protein 1 (HMGB1, interleukin-1α (IL-1α, and interleukin-33 (IL-33 as unique dual-function mediators as well as mitochondrial danger signals released upon cellular trauma and necrosis.

Preliminary evidence for genetic overlap between body mass index and striatal reward response.

Science.gov (United States)

Lancaster, T M; Ihssen, I; Brindley, L M; Linden, D E

2018-01-10

The reward-processing network is implicated in the aetiology of obesity. Several lines of evidence suggest obesity-linked genetic risk loci (such as DRD2 and FTO) may influence individual variation in body mass index (BMI) through neuropsychological processes reflected in alterations in activation of the striatum during reward processing. However, no study has tested the broader hypotheses that (a) the relationship between BMI and reward-related brain activation (measured through the blood oxygenation-dependent (BOLD) signal) may be observed in a large population study and (b) the overall genetic architecture of these phenotypes overlap, an assumption critical for the progression of imaging genetic studies in obesity research. Using data from the Human Connectome Project (N = 1055 healthy, young individuals: average BMI = 26.4), we first establish a phenotypic relationship between BMI and ventral striatal (VS) BOLD during the processing of rewarding (monetary) stimuli (β = 0.44, P = 0.013), accounting for potential confounds. BMI and VS BOLD were both significantly influenced by additive genetic factors (H2r = 0.57; 0.12, respectively). Further decomposition of this variance suggested that the relationship was driven by shared genetic (ρ g  = 0.47, P = 0.011), but not environmental (ρ E  = -0.07, P = 0.29) factors. To validate the assumption of genetic pleiotropy between BMI and VS BOLD, we further show that polygenic risk for higher BMI is also associated with increased VS BOLD response to appetitive stimuli (calorically high food images), in an independent sample (N = 81; P FWE-ROI  < 0.005). Together, these observations suggest that the genetic factors link risk to obesity to alterations within key nodes of the brain's reward circuity. These observations provide a basis for future work exploring the mechanistic role of genetic loci that confer risk for obesity using the imaging genetics approach.

Functional dissociation of transient and sustained fMRI BOLD components in human auditory cortex revealed with a streaming paradigm based on interaural time differences.

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Schadwinkel, Stefan; Gutschalk, Alexander

2010-12-01

A number of physiological studies suggest that feature-selective adaptation is relevant to the pre-processing for auditory streaming, the perceptual separation of overlapping sound sources. Most of these studies are focused on spectral differences between streams, which are considered most important for streaming. However, spatial cues also support streaming, alone or in combination with spectral cues, but physiological studies of spatial cues for streaming remain scarce. Here, we investigate whether the tuning of selective adaptation for interaural time differences (ITD) coincides with the range where streaming perception is observed. FMRI activation that has been shown to adapt depending on the repetition rate was studied with a streaming paradigm where two tones were differently lateralized by ITD. Listeners were presented with five different ΔITD conditions (62.5, 125, 187.5, 343.75, or 687.5 μs) out of an active baseline with no ΔITD during fMRI. The results showed reduced adaptation for conditions with ΔITD ≥ 125 μs, reflected by enhanced sustained BOLD activity. The percentage of streaming perception for these stimuli increased from approximately 20% for ΔITD = 62.5 μs to > 60% for ΔITD = 125 μs. No further sustained BOLD enhancement was observed when the ΔITD was increased beyond ΔITD = 125 μs, whereas the streaming probability continued to increase up to 90% for ΔITD = 687.5 μs. Conversely, the transient BOLD response, at the transition from baseline to ΔITD blocks, increased most prominently as ΔITD was increased from 187.5 to 343.75 μs. These results demonstrate a clear dissociation of transient and sustained components of the BOLD activity in auditory cortex. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Regional differences in the CBF and BOLD responses to hypercapnia: a combined PET and fMRI study

DEFF Research Database (Denmark)

Rostrup, Egill; Law, I; Blinkenberg, M

2000-01-01

Previous fMRI studies of the cerebrovascular response to hypercapnia have shown signal change in cerebral gray matter, but not in white matter. Therefore, the objective of the present study was to compare (15)O PET and T *(2)-weighted MRI during a hypercapnic challenge. The measurements were perf...

Boldness and intermittent locomotion in the bluegill sunfish, Lepomis macrochirus

OpenAIRE

Alexander D.M. Wilson; Jean-Guy J. Godin

2009-01-01

Intermittent locomotion, characterized by moves interspersed with pauses, is a common pattern of locomotion in animals, but its ecological and evolutionary significance relative to continuous locomotion remains poorly understood. Although many studies have examined individual differences in both intermittent locomotion and boldness separately, to our knowledge, no study to date has investigated the relationship between these 2 traits. Characterizing and understanding this relationship is impo...

Signalling network construction for modelling plant defence response.

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Dragana Miljkovic

Full Text Available Plant defence signalling response against various pathogens, including viruses, is a complex phenomenon. In resistant interaction a plant cell perceives the pathogen signal, transduces it within the cell and performs a reprogramming of the cell metabolism leading to the pathogen replication arrest. This work focuses on signalling pathways crucial for the plant defence response, i.e., the salicylic acid, jasmonic acid and ethylene signal transduction pathways, in the Arabidopsis thaliana model plant. The initial signalling network topology was constructed manually by defining the representation formalism, encoding the information from public databases and literature, and composing a pathway diagram. The manually constructed network structure consists of 175 components and 387 reactions. In order to complement the network topology with possibly missing relations, a new approach to automated information extraction from biological literature was developed. This approach, named Bio3graph, allows for automated extraction of biological relations from the literature, resulting in a set of (component1, reaction, component2 triplets and composing a graph structure which can be visualised, compared to the manually constructed topology and examined by the experts. Using a plant defence response vocabulary of components and reaction types, Bio3graph was applied to a set of 9,586 relevant full text articles, resulting in 137 newly detected reactions between the components. Finally, the manually constructed topology and the new reactions were merged to form a network structure consisting of 175 components and 524 reactions. The resulting pathway diagram of plant defence signalling represents a valuable source for further computational modelling and interpretation of omics data. The developed Bio3graph approach, implemented as an executable language processing and graph visualisation workflow, is publically available at http://ropot.ijs.si/bio3graph/and can be

Greater BOLD variability in older compared with younger adults during audiovisual speech perception.

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Sarah H Baum

Full Text Available Older adults exhibit decreased performance and increased trial-to-trial variability on a range of cognitive tasks, including speech perception. We used blood oxygen level dependent functional magnetic resonance imaging (BOLD fMRI to search for neural correlates of these behavioral phenomena. We compared brain responses to simple speech stimuli (audiovisual syllables in 24 healthy older adults (53 to 70 years old and 14 younger adults (23 to 39 years old using two independent analysis strategies: region-of-interest (ROI and voxel-wise whole-brain analysis. While mean response amplitudes were moderately greater in younger adults, older adults had much greater within-subject variability. The greatly increased variability in older adults was observed for both individual voxels in the whole-brain analysis and for ROIs in the left superior temporal sulcus, the left auditory cortex, and the left visual cortex. Increased variability in older adults could not be attributed to differences in head movements between the groups. Increased neural variability may be related to the performance declines and increased behavioral variability that occur with aging.

A Big Five facet analysis of sub-clinical narcissism: understanding boldness in terms of well-known personality traits.

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Furnham, Adrian; Crump, John

2014-08-01

This study aimed to examine a Big Five 'bright-side' analysis of a sub-clinical personality disorder, i.e. narcissism. A total of 6957 British adults completed the NEO-PI-R, which measures the Big Five Personality factors at the domain and the facet level, as well as the Hogan Development Survey (HDS), which has a measure of Narcissism called Bold as one of its dysfunctional interpersonal tendencies. Correlation and regression results confirmed many of the associations between the Big Five domains and facets (NEO-PI-R) and sub-clinical narcissism. The Bold (Narcissism) scale from the HDS was the criterion variable in all analyses. Bold individuals are disagreeable extraverts with very low scores on facet Modesty but moderately high scores on Assertiveness, Competence and Achievement Striving. The study confirmed work using different population groups and different measures. Copyright © 2014 John Wiley & Sons, Ltd.

Working memory in volunteers and schizophrenics using BOLD fMRI; Das Arbeitsgedaechtnis bei Gesunden und bei Schizophrenen: Untersuchungen mit BOLD-fMRT

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Giesel, F.L. [Deutsches Krebsforschungszentrum (DKFZ) Heidelberg, Abteilung Radiologie (Germany); Deutsches Krebsforschungszentrum (DKFZ), Abteilung Radiologie, Heidelberg (Germany); Hohmann, N. [Deutsches Krebsforschungszentrum (DKFZ) Heidelberg, Abteilung Radiologie (Germany); Psychiatrische Universitaetsklinik Heidelberg, Sektion Gerontopsychiatrie (Germany); Seidl, U.; Kress, K.R.; Schoenknecht, P.; Schroeder, J. [Psychiatrische Universitaetsklinik Heidelberg, Sektion Gerontopsychiatrie (Germany); Kauczor, H.-U.; Essig, M. [Deutsches Krebsforschungszentrum (DKFZ) Heidelberg, Abteilung Radiologie (Germany)

2005-02-01

Functional magnetic resonance imaging uses the blood oxygen level-dependent effect (BOLD MRI) for noninvasive display of cerebral correlatives of cognitive function. The importance for the understanding of physiological and pathological processes is demonstrated by investigations of working memory in schizophrenics and healthy controls. Working memory is involved in processing rather than storage of information and therefore is linked to complex processes such as learning and problem solving. In schizophrenic psychosis, these functions are clearly restricted. Training effects in the working memory task follow an inverse U-shape function, suggesting that cerebral activation reaches a peak before economics of the brain find a more efficient method and activation decreases. (orig.) [German] Die funktionelle Magnetresonanztomographie (fMRT) nutzt den ''blood oxygen level dependent effect'' (BOLD-Effekt) zur nichtinvasiven Darstellung zerebraler Korrelate kognitiver Funktionen. Die Bedeutung dieses Verfahrens fuer das Verstaendnis physiologischer und pathologischer Prozesse wird anhand von Untersuchungen zum Arbeitsgedaechtnis bei Schizophrenen und gesunden Kontrollpersonen verdeutlicht. Das Arbeitsgedaechtnis dient weniger der Speicherung, sondern vielmehr der Verarbeitung von Informationen und ist deshalb in komplexe Prozesse wie Lernen und Problemloesen eingebunden. Im Rahmen schizophrener Psychosen kommt es zu einer deutlichen Einschraenkung dieser Funktionen. Erwartungsgemaess zeigen sich unter Durchfuehrung eines Arbeitsgedaechtnisparadigmas Unterschiede in der zerebralen Aktivitaet, die jedoch bei den Erkrankten unter Therapie prinzipiell reversibel sind. Von Interesse sind auch Trainingseffekte bei Gesunden, wobei eine verminderte Aktivierung nach Training auf eine ''Oekonomisierung'' schliessen laesst. (orig.)

Inter-donor variation in cell subset specific immune signaling responses in healthy individuals.

Science.gov (United States)

Longo, Diane M; Louie, Brent; Wang, Ena; Pos, Zoltan; Marincola, Francesco M; Hawtin, Rachael E; Cesano, Alessandra

2012-01-01

Single cell network profiling (SCNP) is a multi-parameter flow cytometry based approach that allows for the simultaneous interrogation of intracellular signaling pathways in multiple cell subpopulations within heterogeneous tissues, without the need for individual cell subset isolation. Thus, the technology is extremely well-suited for characterizing the multitude of interconnected signaling pathways and immune cell subpopulations that regulate the function of the immune system. Recently, SCNP was applied to generate a functional map of the healthy human immune cell signaling network by profiling immune signaling pathways downstream of 12 immunomodulators in 7 distinct immune cell subsets within peripheral blood mononuclear cells (PBMCs) from 60 healthy donors. In the study reported here, the degree of inter-donor variation in the magnitude of the immune signaling responses was analyzed. The highest inter-donor differences in immune signaling pathway activity occurred following perturbation of the immune signaling network, rather than in basal signaling. When examining the full panel of immune signaling responses, as one may expect, the overall degree of inter-donor variation was positively correlated (r = 0.727) with the magnitude of node response (i.e. a larger median signaling response was associated with greater inter-donor variation). However, when examining the degree of heterogeneity across cell subpopulations for individual signaling nodes, cell subset specificity in the degree of inter-donor variation was observed for several nodes. For such nodes, relatively weak correlations between inter-donor variation and the magnitude of the response were observed. Further, within the phenotypically distinct subpopulations, a fraction of the immune signaling responses had bimodal response profiles in which (a) only a portion of the cells had elevated phospho-protein levels following modulation and (b) the proportion of responsive cells varied by donor. These data

A novel Bayesian approach to accounting for uncertainty in fMRI-derived estimates of cerebral oxygen metabolism fluctuations.

Science.gov (United States)

Simon, Aaron B; Dubowitz, David J; Blockley, Nicholas P; Buxton, Richard B

2016-04-01

Calibrated blood oxygenation level dependent (BOLD) imaging is a multimodal functional MRI technique designed to estimate changes in cerebral oxygen metabolism from measured changes in cerebral blood flow and the BOLD signal. This technique addresses fundamental ambiguities associated with quantitative BOLD signal analysis; however, its dependence on biophysical modeling creates uncertainty in the resulting oxygen metabolism estimates. In this work, we developed a Bayesian approach to estimating the oxygen metabolism response to a neural stimulus and used it to examine the uncertainty that arises in calibrated BOLD estimation due to the presence of unmeasured model parameters. We applied our approach to estimate the CMRO2 response to a visual task using the traditional hypercapnia calibration experiment as well as to estimate the metabolic response to both a visual task and hypercapnia using the measurement of baseline apparent R2' as a calibration technique. Further, in order to examine the effects of cerebral spinal fluid (CSF) signal contamination on the measurement of apparent R2', we examined the effects of measuring this parameter with and without CSF-nulling. We found that the two calibration techniques provided consistent estimates of the metabolic response on average, with a median R2'-based estimate of the metabolic response to CO2 of 1.4%, and R2'- and hypercapnia-calibrated estimates of the visual response of 27% and 24%, respectively. However, these estimates were sensitive to different sources of estimation uncertainty. The R2'-calibrated estimate was highly sensitive to CSF contamination and to uncertainty in unmeasured model parameters describing flow-volume coupling, capillary bed characteristics, and the iso-susceptibility saturation of blood. The hypercapnia-calibrated estimate was relatively insensitive to these parameters but highly sensitive to the assumed metabolic response to CO2. Copyright © 2016 Elsevier Inc. All rights reserved.

A novel Bayesian approach to accounting for uncertainty in fMRI-derived estimates of cerebral oxygen metabolism fluctuations

Science.gov (United States)

Simon, Aaron B.; Dubowitz, David J.; Blockley, Nicholas P.; Buxton, Richard B.

2016-01-01

Calibrated blood oxygenation level dependent (BOLD) imaging is a multimodal functional MRI technique designed to estimate changes in cerebral oxygen metabolism from measured changes in cerebral blood flow and the BOLD signal. This technique addresses fundamental ambiguities associated with quantitative BOLD signal analysis; however, its dependence on biophysical modeling creates uncertainty in the resulting oxygen metabolism estimates. In this work, we developed a Bayesian approach to estimating the oxygen metabolism response to a neural stimulus and used it to examine the uncertainty that arises in calibrated BOLD estimation due to the presence of unmeasured model parameters. We applied our approach to estimate the CMRO2 response to a visual task using the traditional hypercapnia calibration experiment as well as to estimate the metabolic response to both a visual task and hypercapnia using the measurement of baseline apparent R2′ as a calibration technique. Further, in order to examine the effects of cerebral spinal fluid (CSF) signal contamination on the measurement of apparent R2′, we examined the effects of measuring this parameter with and without CSF-nulling. We found that the two calibration techniques provided consistent estimates of the metabolic response on average, with a median R2′-based estimate of the metabolic response to CO2 of 1.4%, and R2′- and hypercapnia-calibrated estimates of the visual response of 27% and 24%, respectively. However, these estimates were sensitive to different sources of estimation uncertainty. The R2′-calibrated estimate was highly sensitive to CSF contamination and to uncertainty in unmeasured model parameters describing flow-volume coupling, capillary bed characteristics, and the iso-susceptibility saturation of blood. The hypercapnia-calibrated estimate was relatively insensitive to these parameters but highly sensitive to the assumed metabolic response to CO2. PMID:26790354

A simple solution for model comparison in bold imaging: the special case of reward prediction error and reward outcomes.

Science.gov (United States)

Erdeniz, Burak; Rohe, Tim; Done, John; Seidler, Rachael D

2013-01-01

Conventional neuroimaging techniques provide information about condition-related changes of the BOLD (blood-oxygen-level dependent) signal, indicating only where and when the underlying cognitive processes occur. Recently, with the help of a new approach called "model-based" functional neuroimaging (fMRI), researchers are able to visualize changes in the internal variables of a time varying learning process, such as the reward prediction error or the predicted reward value of a conditional stimulus. However, despite being extremely beneficial to the imaging community in understanding the neural correlates of decision variables, a model-based approach to brain imaging data is also methodologically challenging due to the multicollinearity problem in statistical analysis. There are multiple sources of multicollinearity in functional neuroimaging including investigations of closely related variables and/or experimental designs that do not account for this. The source of multicollinearity discussed in this paper occurs due to correlation between different subjective variables that are calculated very close in time. Here, we review methodological approaches to analyzing such data by discussing the special case of separating the reward prediction error signal from reward outcomes.

Modelling Cardiac Signal as a Confound in EEG-fMRI and its Application in Focal Epilepsy

DEFF Research Database (Denmark)

Liston, Adam David; Salek-Haddadi, Afraim; Hamandi, Khalid

2005-01-01

Cardiac noise has been shown to reduce the sensitivity of functional Magnetic Resonance Imaging (fMRI) to an experimental effect due to its confounding presence in the blood oxygenation level-dependent (BOLD) signal. Its effect is most severe in particular regions of the brain and a method is yet...

The role of ecological context and predation risk-stimuli in revealing the true picture about the genetic basis of boldness evolution in fish

DEFF Research Database (Denmark)

Klefoth, Thomas; Skov, Christian; Krause, Jens

2011-01-01

To showcase the importance of genotype × environment interactions and the presence of predation risk in the experimental assessment of boldness in fish, we investigated boldness in terms of feeding behavior and refuge use in two genetically different populations of juvenile carp (Cyprinus carpio)...

BOLD quantified renal pO2 is sensitive to pharmacological challenges in rats.

Science.gov (United States)

Thacker, Jon; Zhang, Jeff L; Franklin, Tammy; Prasad, Pottumarthi

2017-07-01

Blood oxygen level-dependent (BOLD) MRI has been effectively used to monitor changes in renal oxygenation. However, R2* (or T2*) is not specific to blood oxygenation and is dependent on other factors. This study investigates the use of a statistical model that takes these factors into account and maps BOLD MRI measurements to blood pO2. Spin echo and gradient echo images were obtained in six Sprague-Dawley rats and R2 and R2* maps were computed. Measurements were made at baseline, post-nitric oxide synthase inhibitor (L-NAME), and post-furosemide administration. A simulation of each region was performed to map R2' (computed as R2*-R2) to blood pO2. At baseline, blood pO2 in the outer medulla was 30.5 ± 1.2 mmHg and 51.9 ± 5.2 mmHg in the cortex, in agreement with previous invasive studies. Blood pO2 was found to decrease within the outer medulla following L-NAME (P pO2 in the cortex increased following furosemide (P pO2 is sensitive to pharmacological challenges, and baseline pO2 is comparable to literature values. Reporting pO2 instead of R2* could lead to a greater clinical impact of renal BOLD MRI and facilitate the identification of hypoxic regions. Magn Reson Med 78:297-302, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

"To Boldly Go" versus "Last, Best Hope" : The Future of Human Civilization as Depicted in American Science Fiction

OpenAIRE

Glasø, Alexander

2012-01-01

"'To Boldly Go" versus "Last, Best Hope'" examines a total of four American television series from the Star Trek and Babylon 5 franchises, and the portrayal of human civilization in the future. The thesis traces how Star Trek set out "to boldly go" and how Babylon 5 was the "last, best hope" in depicting a coherent, futuristic vision for humanity. The initial chapter focuses on the background of the series and also the ways they differed from one another, while chapter 2 is devoted to the por...

Personality in the cockroach Diploptera punctata: Evidence for stability across developmental stages despite age effects on boldness.

Science.gov (United States)

Stanley, Christina R; Mettke-Hofmann, Claudia; Preziosi, Richard F

2017-01-01

Despite a recent surge in the popularity of animal personality studies and their wide-ranging associations with various aspects of behavioural ecology, our understanding of the development of personality over ontogeny remains poorly understood. Stability over time is a central tenet of personality; ecological pressures experienced by an individual at different life stages may, however, vary considerably, which may have a significant effect on behavioural traits. Invertebrates often go through numerous discrete developmental stages and therefore provide a useful model for such research. Here we test for both differential consistency and age effects upon behavioural traits in the gregarious cockroach Diploptera punctata by testing the same behavioural traits in both juveniles and adults. In our sample, we find consistency in boldness, exploration and sociality within adults whilst only boldness was consistent in juveniles. Both boldness and exploration measures, representative of risk-taking behaviour, show significant consistency across discrete juvenile and adult stages. Age effects are, however, apparent in our data; juveniles are significantly bolder than adults, most likely due to differences in the ecological requirements of these life stages. Size also affects risk-taking behaviour since smaller adults are both bolder and more highly explorative. Whilst a behavioural syndrome linking boldness and exploration is evident in nymphs, this disappears by the adult stage, where links between other behavioural traits become apparent. Our results therefore indicate that differential consistency in personality can be maintained across life stages despite age effects on its magnitude, with links between some personality traits changing over ontogeny, demonstrating plasticity in behavioural syndromes.

Personality in the cockroach Diploptera punctata: Evidence for stability across developmental stages despite age effects on boldness

Science.gov (United States)

Mettke-Hofmann, Claudia; Preziosi, Richard F.

2017-01-01

Despite a recent surge in the popularity of animal personality studies and their wide-ranging associations with various aspects of behavioural ecology, our understanding of the development of personality over ontogeny remains poorly understood. Stability over time is a central tenet of personality; ecological pressures experienced by an individual at different life stages may, however, vary considerably, which may have a significant effect on behavioural traits. Invertebrates often go through numerous discrete developmental stages and therefore provide a useful model for such research. Here we test for both differential consistency and age effects upon behavioural traits in the gregarious cockroach Diploptera punctata by testing the same behavioural traits in both juveniles and adults. In our sample, we find consistency in boldness, exploration and sociality within adults whilst only boldness was consistent in juveniles. Both boldness and exploration measures, representative of risk-taking behaviour, show significant consistency across discrete juvenile and adult stages. Age effects are, however, apparent in our data; juveniles are significantly bolder than adults, most likely due to differences in the ecological requirements of these life stages. Size also affects risk-taking behaviour since smaller adults are both bolder and more highly explorative. Whilst a behavioural syndrome linking boldness and exploration is evident in nymphs, this disappears by the adult stage, where links between other behavioural traits become apparent. Our results therefore indicate that differential consistency in personality can be maintained across life stages despite age effects on its magnitude, with links between some personality traits changing over ontogeny, demonstrating plasticity in behavioural syndromes. PMID:28489864

Early disrupted neurovascular coupling and changed event level hemodynamic response function in type 2 diabetes: an fMRI study.

Science.gov (United States)

Duarte, João V; Pereira, João M S; Quendera, Bruno; Raimundo, Miguel; Moreno, Carolina; Gomes, Leonor; Carrilho, Francisco; Castelo-Branco, Miguel

2015-10-01

Type 2 diabetes (T2DM) patients develop vascular complications and have increased risk for neurophysiological impairment. Vascular pathophysiology may alter the blood flow regulation in cerebral microvasculature, affecting neurovascular coupling. Reduced fMRI signal can result from decreased neuronal activation or disrupted neurovascular coupling. The uncertainty about pathophysiological mechanisms (neurodegenerative, vascular, or both) underlying brain function impairments remains. In this cross-sectional study, we investigated if the hemodynamic response function (HRF) in lesion-free brains of patients is altered by measuring BOLD (Blood Oxygenation Level-Dependent) response to visual motion stimuli. We used a standard block design to examine the BOLD response and an event-related deconvolution approach. Importantly, the latter allowed for the first time to directly extract the true shape of HRF without any assumption and probe neurovascular coupling, using performance-matched stimuli. We discovered a change in HRF in early stages of diabetes. T2DM patients show significantly different fMRI response profiles. Our visual paradigm therefore demonstrated impaired neurovascular coupling in intact brain tissue. This implies that functional studies in T2DM require the definition of HRF, only achievable with deconvolution in event-related experiments. Further investigation of the mechanisms underlying impaired neurovascular coupling is needed to understand and potentially prevent the progression of brain function decrements in diabetes.

P300 amplitude variation is related to ventral striatum BOLD response during gain and loss anticipation: an EEG and fMRI experiment.

Science.gov (United States)

Pfabigan, Daniela M; Seidel, Eva-Maria; Sladky, Ronald; Hahn, Andreas; Paul, Katharina; Grahl, Arvina; Küblböck, Martin; Kraus, Christoph; Hummer, Allan; Kranz, Georg S; Windischberger, Christian; Lanzenberger, Rupert; Lamm, Claus

2014-08-01

The anticipation of favourable or unfavourable events is a key component in our daily life. However, the temporal dynamics of anticipation processes in relation to brain activation are still not fully understood. A modified version of the monetary incentive delay task was administered during separate functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG) sessions in the same 25 participants to assess anticipatory processes with a multi-modal neuroimaging set-up. During fMRI, gain and loss anticipation were both associated with heightened activation in ventral striatum and reward-related areas. EEG revealed most pronounced P300 amplitudes for gain anticipation, whereas CNV amplitudes distinguished neutral from gain and loss anticipation. Importantly, P300, but not CNV amplitudes, were correlated to neural activation in the ventral striatum for both gain and loss anticipation. Larger P300 amplitudes indicated higher ventral striatum blood oxygen level dependent (BOLD) response. Early stimulus evaluation processes indexed by EEG seem to be positively related to higher activation levels in the ventral striatum, indexed by fMRI, which are usually associated with reward processing. The current results, however, point towards a more general motivational mechanism processing salient stimuli during anticipation. Copyright © 2014. Published by Elsevier Inc.

Response of resonant gravitational wave detectors to damped sinusoid signals

International Nuclear Information System (INIS)

Pai, A; Celsi, C; Pallottino, G V; D'Antonio, S; Astone, P

2007-01-01

Till date, the search for burst signals with resonant gravitational wave (GW) detectors has been done using the δ-function approximation for the signal, which was reasonable due to the very small bandwidth of these detectors. However, now with increased bandwidth (of the order of 10 or more Hz) and with the possibility of comparing results with interferometric GW detectors (broad-band), it is very important to exploit the resonant detectors' capability to detect also signals with specific wave shapes. As a first step, we present a study of the response of resonant GW detectors to damped sinusoids with given frequency and decay time and report on the development of a filter matched to these signals. This study is a preliminary step towards the comprehension of the detector response and of the filtering for signals such as the excitation of stellar quasi-normal modes

An fMRI study on cortical responses during active self-touch and passive touch from others

Directory of Open Access Journals (Sweden)

Rochelle eAckerley

2012-08-01

Full Text Available Active, self-touch and the passive touch from an external source engage comparable afferent mechanoreceptors on the touched skin site. However, touch directed to glabrous skin compared to hairy skin will activate different types of afferent mechanoreceptors. Despite perceptual similarities between touch to different body sites, it is likely that the touch information is processed differently. In the present study, we used functional magnetic resonance imaging (fMRI to elucidate the cortical differences in the neural signal of touch representations during active, self-touch and passive touch from another, to both glabrous (palm and hairy (arm skin, where a soft brush was used as the stimulus. There were two active touch conditions, where the participant used the brush in their right hand to stroke either their left palm or arm. There were two similar passive, touch conditions where the experimenter used an identical brush to stroke the same palm and arm areas on the participant. Touch on the left palm elicited a large, significant, positive blood-oxygenation level dependence (BOLD signal in right sensorimotor areas. Less extensive activity was found for touch to the arm. Separate somatotopical palm and arm representations were found in Brodmann area 3 of the right primary somatosensory cortex (SI and in both these areas, active stroking gave significantly higher signals than passive stroking. Active, self-touch elicited a positive BOLD signal in a network of sensorimotor cortical areas in the left hemisphere, compared to the resting baseline. In contrast, during passive touch, a significant negative BOLD signal was found in the left SI. Thus, each of the four conditions had a unique cortical signature despite similarities in afferent signalling or evoked perception. It is hypothesized that attentional mechanisms play a role in the modulation of the touch signal in the right SI, accounting for the differences found between active and passive touch.

Resting bold fMRI differentiates dementia with Lewy bodies vs Alzheimer disease

Science.gov (United States)

Price, J.L.; Yan, Z.; Morris, J.C.; Sheline, Y.I.

2011-01-01

Objective: Clinicopathologic phenotypes of dementia with Lewy bodies (DLB) and Alzheimer disease (AD) often overlap, making discrimination difficult. We performed resting state blood oxygen level–dependent (BOLD) functional connectivity MRI (fcMRI) to determine whether there were differences between AD and DLB. Methods: Participants (n = 88) enrolled in a longitudinal study of memory and aging underwent 3-T fcMRI. Clinical diagnoses of probable DLB (n = 15) were made according to published criteria. Cognitively normal control participants (n = 38) were selected for the absence of cerebral amyloid burden as imaged with Pittsburgh compound B (PiB). Probable AD cases (n = 35) met published criteria and had appreciable amyloid deposits with PiB imaging. Functional images were collected using a gradient spin-echo sequence sensitive to BOLD contrast (T2* weighting). Correlation maps selected a seed region in the combined bilateral precuneus. Results: Participants with DLB had a functional connectivity pattern for the precuneus seed region that was distinct from AD; both the DLB and AD groups had functional connectivity patterns that differed from the cognitively normal group. In the DLB group, we found increased connectivity between the precuneus and regions in the dorsal attention network and the putamen. In contrast, we found decreased connectivity between the precuneus and other task-negative default regions and visual cortices. There was also a reversal of connectivity in the right hippocampus. Conclusions: Changes in functional connectivity in DLB indicate patterns of activation that are distinct from those seen in AD and may improve discrimination of DLB from AD and cognitively normal individuals. Since patterns of connectivity differ between AD and DLB groups, measurements of BOLD functional connectivity can shed further light on neuroanatomic connections that distinguish DLB from AD. PMID:21525427

Intraindividual variability of boldness is repeatable across contexts in a wild lizard.

Directory of Open Access Journals (Sweden)

Laura Highcock

Full Text Available Animals do not behave in exactly the same way when repeatedly tested in the same context or situation, even once systematic variation, such as habituation, has been controlled for. This unpredictability is called intraindividual variability (IIV and has been little studied in animals. Here we investigated how IIV in boldness (estimated by flight initiation distances changed across two seasons--the dry, non-breeding season and the wet, breeding season--in a wild population of the Namibian rock agama, Agama planiceps. We found significant differences in IIV both between individuals and seasons, and IIV was higher in the wet season, suggesting plasticity in IIV. Further, IIV was highly repeatable (r = 0.61 between seasons and we found strong negative correlations between consistent individual differences in flight initiation distances, i.e. their boldness, and individuals' IIVs. We suggest that to understand personality in animals, researchers should generate a personality 'profile' that includes not only the relative level of a trait (i.e. its personality, but also its plasticity and variability under natural conditions.

DC response of dust to low frequency AC signals

Science.gov (United States)

McKinlay, Michael; Konopka, Uwe; Thomas, Edward

2017-10-01

Macroscopic changes in the shape and equilibrium position of clouds of charged microparticles suspended in a plasma have been observed in response to low frequency AC signals. In these experiments, dusty plasmas consisting of 2-micron diameter silica microspheres suspended between an anode and cathode in an argon, DC glow discharge plasma are produced in a grounded, 6-way cross vacuum chamber. An AC signal, produced by a function generator and amplified by a bipolar op-amp, is superimposed onto the potential from the cathode. The frequencies of the applied AC signals, ranging from tens to hundreds of kHz, are comparable to the ion-neutral collision frequency; well below the ion/electron plasma frequencies, but also considerably higher than the dust plasma frequency. This presentation will detail the experimental setup, present documentation and categorization of observations of the dust response, and present an initial model of the response. This work is supported by funding from the US Dept. of Energy, Grant Number DE-SC0016330, and by the National Science Foundation, Grant Number PHY-1613087.

Area-specific modulation of neural activation comparing escitalopram and citalopram revealed by pharmaco-fMRI: a randomized cross-over study.

Science.gov (United States)

Windischberger, Christian; Lanzenberger, Rupert; Holik, Alexander; Spindelegger, Christoph; Stein, Patrycja; Moser, Ulrike; Gerstl, Florian; Fink, Martin; Moser, Ewald; Kasper, Siegfried

2010-01-15

Area-specific and stimulation-dependent changes of human brain activation by selective serotonin reuptake inhibitors (SSRI) are an important issue for improved understanding of treatment mechanisms, given the frequent prescription of these drugs in depression and anxiety disorders. The aim of this neuroimaging study was to investigate differences in BOLD-signal caused by administration of the SSRIs escitalopram and citalopram using pharmacological functional magnetic resonance imaging (pharmaco-fMRI). Eighteen healthy subjects participated in a placebo-controlled, randomized, double-blind study in cross-over repeated measures design. Each volunteer performed facial emotional discrimination and a sensorimotor control paradigm during three scanning sessions. Citalopram (20 mg/d), escitalopram (10 mg/d) and placebo were administered for 10 days each with a drug-free period of at least 21 days. Significant pharmacological effects on BOLD-signal were found in the amygdala, medial frontal gyrus, parahippocampal, fusiform and middle temporal gyri. Post-hoc t-tests revealed decreased BOLD-signal in the right amygdala and left parahippocampal gyrus in both pharmacological conditions, compared to placebo. Escitalopram, compared to citalopram, induced a decrease of BOLD-signal in the medial frontal gyrus and an increase in the right fusiform and left parahippocampal gyri. Drug effects were concentrated in brain regions with dense serotonergic projections. Both escitalopram and citalopram attenuated BOLD-signal in the amygdala and parahippocampal cortex to emotionally significant stimuli compared to control stimuli. We believe that reduced reactivity in the medial frontal gyrus found for escitalopram compared to citalopram administration might explain the response differences between study drugs as demonstrated in previous clinical trials.

Assessment of cerebral blood flow reserve using blood oxygen level-dependent echo planar imaging after acetazolamide administration in patients post-STA-MCA anastomosis surgery

International Nuclear Information System (INIS)

Zenke, Kiichiro; Kusunoki, Katsusuke; Saito, Masahiro; Sadamoto, Kazuhiko; Ohta, Shinsuke; Kumon, Yoshiaki; Sakaki, Saburo; Nagasawa, Kiyoshi

1998-01-01

Recently, blood oxygen level-dependent (BOLD) echo planar imaging (EPI) has been used to estimate blood flow changes. Theoretically, a relative decrement of deoxyhemoglobin in cerebral blood supply induces a MR signal change after neuronal stimulation. In the present study, we have attempted to evaluate CBF reserve capacity by the BOLD EPI in patients who had undergone STA-MCA anastomosis surgery. Then, we compared with the signal intensity changes obtained by this procedure with the CBF changes by Xe-SPECT after acetazolamide administration. Six patients, post-STA-MCA anastomosis surgery, were studied. Pre-operatively, MR signal intensity and CBF, by Xe-SPECT, were increased in the intact side after acetazolamide administration in all patients, and MR signal intensities were decreased in low flow regions after acetazolamide administration in all four patients in whom so-called steal phenomenon was demonstrated by Xe-SPECT study. Post-operatively, poor response was shown after acetazolamide administration with both Xe-SPECT and BOLD EPI in the two patients who had unsuccessful anastomoses. In the successfully anastomosed patients, improved vascular reactivity was demonstrated on BOLD EPI after acetazolamide administration in 3 of 4 patients in whom an improvement of vascular reactivity was demonstrated on Xe-SPECT. In one patient, MRI studies were considered to have technical artifacts, because the MR signal intensity did not increase, even in the intact side after acetazolamide administration. In conclusion, BOLD EPI after acetazolamide administration is an useful procedure for the pre- and post-operative of vascular reserve in patients with ischemic stroke. (author)

Hypoxia in Prostate Cancer: Correlation of BOLD-MRI With Pimonidazole Immunohistochemistry-Initial Observations

International Nuclear Information System (INIS)

Hoskin, Peter J.; Carnell, Dawn M.; Taylor, N. Jane; Smith, Rowena E.; Stirling, J. James; Daley, Frances M.; Saunders, Michele I.; Bentzen, Soren M.; Collins, David J.; D'Arcy, James A.; Padhani, Anwar P.

2007-01-01

Purpose: To investigate the ability of blood oxygen level-dependent (BOLD) MRI to depict clinically significant prostate tumor hypoxia. Methods and Materials: Thirty-three patients with prostate carcinoma undergoing radical prostatectomy were studied preoperatively, using gradient echo sequences without and with contrast medium enhancement, to map relative tissue oxygenation according to relaxivity rates and relative blood volume (rBV). Pimonidazole was administered preoperatively, and whole-mount sections of selected tumor-bearing slices were stained for pimonidazole fixation and tumor and nontumor localization. Histologic and imaging parameters were independently mapped onto patient prostate outlines. Using 5-mm grids, 861 nontumor grid locations were compared with 237 tumor grids (with >50% tumor per location) using contingency table analysis with respect to the ability of imaging to predict pimonidazole staining. Results: Twenty patients completed the imaging and histologic protocols. Pimonidazole staining was found in 33% of nontumor and in 70% of tumor grids. The sensitivity of the MR relaxivity parameter R 2 * in depicting tumor hypoxia was high (88%), improving with the addition of low rBV information (95%) without changing specificity (36% and 29%, respectively). High R 2 * increased the positive predictive value for hypoxia by 6% (70% to 76%); conversely, low R 2 * decreased the likelihood of hypoxia being present by 26% (70% to 44%) and by 41% (71% to 30%) when combined with rBV information. Conclusion: R 2 * maps from BOLD-MRI have high sensitivity but low specificity for defining intraprostatic tumor hypoxia. This together with the negative predictive value of 70% when combined with blood volume information makes BOLD-MRI a potential noninvasive technique for mapping prostatic tumor hypoxia

Dictionary-driven Ischemia Detection from Cardiac Phase-Resolved Myocardial BOLD MRI at Rest

Science.gov (United States)

Bevilacqua, Marco; Dharmakumar, Rohan; Tsaftaris, Sotirios A.

2016-01-01

Cardiac Phase-resolved Blood-Oxygen-Level Dependent (CP–BOLD) MRI provides a unique opportunity to image an ongoing ischemia at rest. However, it requires post-processing to evaluate the extent of ischemia. To address this, here we propose an unsupervised ischemia detection (UID) method which relies on the inherent spatio-temporal correlation between oxygenation and wall motion to formalize a joint learning and detection problem based on dictionary decomposition. Considering input data of a single subject, it treats ischemia as an anomaly and iteratively learns dictionaries to represent only normal observations (corresponding to myocardial territories remote to ischemia). Anomaly detection is based on a modified version of One-class Support Vector Machines (OCSVM) to regulate directly the margins by incorporating the dictionary-based representation errors. A measure of ischemic extent (IE) is estimated, reflecting the relative portion of the myocardium affected by ischemia. For visualization purposes an ischemia likelihood map is created by estimating posterior probabilities from the OCSVM outputs, thus obtaining how likely the classification is correct. UID is evaluated on synthetic data and in a 2D CP–BOLD data set from a canine experimental model emulating acute coronary syndromes. Comparing early ischemic territories identified with UID against infarct territories (after several hours of ischemia), we find that IE, as measured by UID, is highly correlated (Pearson’s r = 0.84) w.r.t. infarct size. When advances in automated registration and segmentation of CP–BOLD images and full coverage 3D acquisitions become available, we hope that this method can enable pixel-level assessment of ischemia with this truly non-invasive imaging technique. PMID:26292338

Yeast signaling pathways in the oxidative stress response

Energy Technology Data Exchange (ETDEWEB)

Ikner, Aminah [Section of Microbiology, Division of Biological Sciences, University of California, Davis, CA 95616 (United States); Shiozaki, Kazuhiro [Section of Microbiology, Division of Biological Sciences, University of California, Davis, CA 95616 (United States)]. E-mail: kshiozaki@ucdavis.edu

2005-01-06

Oxidative stress that generates the reactive oxygen species (ROS) is one of the major causes of DNA damage and mutations. The 'DNA damage checkpoint' that arrests cell cycle and repairs damaged DNA has been a focus of recent studies, and the genetically amenable model systems provided by yeasts have been playing a leading role in the eukaryotic checkpoint research. However, means to eliminate ROS are likely to be as important as the DNA repair mechanisms in order to suppress mutations in the chromosomal DNA, and yeasts also serve as excellent models to understand how eukaryotes combat oxidative stress. In this article, we present an overview of the signaling pathways that sense oxidative stress and induce expression of various anti-oxidant genes in the budding yeast Saccharomyces cerevisiae, the fission yeast Schizosaccharomyces pombe and the pathogenic yeast Candida albicans. Three conserved signaling modules have been identified in the oxidative stress response of these diverse yeast species: the stress-responsive MAP kinase cascade, the multistep phosphorelay and the AP-1-like transcription factor. The structure and function of these signaling modules are discussed.

Yeast signaling pathways in the oxidative stress response

International Nuclear Information System (INIS)

Ikner, Aminah; Shiozaki, Kazuhiro

2005-01-01

Oxidative stress that generates the reactive oxygen species (ROS) is one of the major causes of DNA damage and mutations. The 'DNA damage checkpoint' that arrests cell cycle and repairs damaged DNA has been a focus of recent studies, and the genetically amenable model systems provided by yeasts have been playing a leading role in the eukaryotic checkpoint research. However, means to eliminate ROS are likely to be as important as the DNA repair mechanisms in order to suppress mutations in the chromosomal DNA, and yeasts also serve as excellent models to understand how eukaryotes combat oxidative stress. In this article, we present an overview of the signaling pathways that sense oxidative stress and induce expression of various anti-oxidant genes in the budding yeast Saccharomyces cerevisiae, the fission yeast Schizosaccharomyces pombe and the pathogenic yeast Candida albicans. Three conserved signaling modules have been identified in the oxidative stress response of these diverse yeast species: the stress-responsive MAP kinase cascade, the multistep phosphorelay and the AP-1-like transcription factor. The structure and function of these signaling modules are discussed

Driving innovation through big open linked data (BOLD) : Exploring antecedents using interpretive structural modelling

NARCIS (Netherlands)

Dwivedi, Yogesh K.; Janssen, M.F.W.H.A.; Slade, Emma L.; Rana, Nripendra P.; Weerakkody, Vishanth; Millard, Jeremy; Hidders, Jan; Snijders, D.

2016-01-01

Innovation is vital to find new solutions to problems, increase quality, and improve profitability. Big open linked data (BOLD) is a fledgling and rapidly evolving field that creates new opportunities for innovation. However, none of the existing literature has yet considered the

Male responses to conspecific advertisement signals in the field cricket Gryllus rubens (Orthoptera: Gryllidae).

Science.gov (United States)

Jang, Yikweon

2011-01-20

In many species males aggregate and produce long-range advertisement signals to attract conspecific females. The majority of the receivers of these signals are probably other males most of the time, and male responses to competitors' signals can structure the spatial and temporal organization of the breeding aggregation and affect male mating tactics. I quantified male responses to a conspecific advertisement stimulus repeatedly over three age classes in Gryllus rubens (Orthoptera: Gryllidae) in order to estimate the type and frequency of male responses to the broadcast stimulus and to determine the factors affecting them. Factors tested included body size, wing dimorphism, age, and intensity of the broadcast stimulus. Overall, males employed acoustic response more often than positive phonotactic response. As males aged, the frequency of positive phonotactic response decreased but that of the acoustic response increased. That is, males may use positive phonotaxis in the early stages of their adult lives, possibly to find suitable calling sites or parasitize calling males, and then later in life switch to acoustic responses in response to conspecific advertisement signals. Males with smaller body size more frequently exhibited acoustic responses. This study suggests that individual variation, more than any factors measured, is critical for age-dependent male responses to conspecific advertisement signals.

Convergence of human brain mapping tools: neuronavigated TMS parameters and fMRI activity in the hand motor area.

Science.gov (United States)

Sarfeld, Anna-Sophia; Diekhoff, Svenja; Wang, Ling E; Liuzzi, Gianpiero; Uludağ, Kamil; Eickhoff, Simon B; Fink, Gereon R; Grefkes, Christian

2012-05-01

Functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) are well-established tools for investigating the human motor system in-vivo. We here studied the relationship between movement-related fMRI signal changes in the primary motor cortex (M1) and electrophysiological properties of the hand motor area assessed with neuronavigated TMS in 17 healthy subjects. The voxel showing the highest task-related BOLD response in the left hand motor area during right hand movements was identified for each individual subject. This fMRI peak voxel in M1 served as spatial target for coil positioning during neuronavigated TMS. We performed correlation analyses between TMS parameters, BOLD signal estimates and effective connectivity parameters of M1 assessed with dynamic causal modeling (DCM). The results showed a negative correlation between the movement-related BOLD signal in left M1 and resting as well as active motor threshold (MT) obtained for left M1. The DCM analysis revealed that higher excitability of left M1 was associated with a stronger coupling between left supplementary motor area (SMA) and M1. Furthermore, BOLD activity in left M1 correlated with ipsilateral silent period (ISP), i.e. the stronger the task-related BOLD response in left M1, the higher interhemispheric inhibition effects targeting right M1. DCM analyses revealed a positive correlation between the coupling of left SMA with left M1 and the duration of ISP. The data show that TMS parameters assessed for the hand area of M1 do not only reflect the intrinsic properties at the stimulation site but also interactions with remote areas in the human motor system. Copyright © 2011 Wiley-Liss, Inc.

The effect of renal denervation on kidney oxygenation as determined by BOLD MRI in patients with hypertension

Energy Technology Data Exchange (ETDEWEB)

Vink, E.E.; Boer, A.; Blankestijn, P.J. [University Medical Center Utrecht, Department of Nephrology, P.O. Box 85500, GA, Utrecht (Netherlands); Verloop, W.L.; Voskuil, M. [University Medical Center Utrecht, Department of Cardiology, Utrecht (Netherlands); Spiering, W.; Leiner, T. [University Medical Center Utrecht, Department of Vascular Medicine, Utrecht (Netherlands); Vonken, E.; Hoogduin, J.M. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Bots, M.L. [University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht (Netherlands)

2015-07-15

Renal denervation (RDN) is a promising therapy for resistant hypertension. RDN is assumed to decrease sympathetic activity. Consequently, RDN can potentially increase renal oxygenation. Blood oxygen level-dependent MRI (BOLD-MRI) provides a non-invasive tool to determine renal oxygenation in humans. The aim of the current study was to investigate the effect of RDN on renal oxygenation as determined by BOLD-MRI. Patients with resistant hypertension or the inability to follow a stable drug regimen due to unacceptable side effects were included. BOLD-MRI was performed before and 12 months after RDN. Twenty-seven patients were imaged on 3 T and 19 on 1.5 T clinical MRI systems. Fifty-four patients were included, 46 patients (23 men, mean age 57 years) completed the study. Mean 24-h BP changed from 163(±20)/98(±14) mmHg to 154(±22)/92(±13) mmHg (p = 0.001 and p < 0.001). eGFR did not change after RDN [77(±18) vs. 79(±20) mL/min/1.73 m{sup 2}; p = 0.13]. RDN did not affect renal oxygenation [1.5 T: cortical R2*: 12.5(±0.9) vs. 12.5(±0.9), p = 0.94; medullary R2*: 19.6(±1.7) vs. 19.3(1.4), p = 0.40; 3 T: cortical R2*: 18.1(±0.8) vs. 17.8(±1.2), p = 0.47; medullary R2*: 27.4(±1.9) vs. 26.7(±1.8), p = 0.19]. The current study shows that RDN does not lead to changes in renal oxygenation 1 year after RDN as determined by BOLD-MRI. (orig.)

Perceptual learning of motion direction discrimination with suppressed and unsuppressed MT in humans: an fMRI study.

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Benjamin Thompson

Full Text Available The middle temporal area of the extrastriate visual cortex (area MT is integral to motion perception and is thought to play a key role in the perceptual learning of motion tasks. We have previously found, however, that perceptual learning of a motion discrimination task is possible even when the training stimulus contains locally balanced, motion opponent signals that putatively suppress the response of MT. Assuming at least partial suppression of MT, possible explanations for this learning are that 1 training made MT more responsive by reducing motion opponency, 2 MT remained suppressed and alternative visual areas such as V1 enabled learning and/or 3 suppression of MT increased with training, possibly to reduce noise. Here we used fMRI to test these possibilities. We first confirmed that the motion opponent stimulus did indeed suppress the BOLD response within hMT+ compared to an almost identical stimulus without locally balanced motion signals. We then trained participants on motion opponent or non-opponent stimuli. Training with the motion opponent stimulus reduced the BOLD response within hMT+ and greater reductions in BOLD response were correlated with greater amounts of learning. The opposite relationship between BOLD and behaviour was found at V1 for the group trained on the motion-opponent stimulus and at both V1 and hMT+ for the group trained on the non-opponent motion stimulus. As the average response of many cells within MT to motion opponent stimuli is the same as their response to non-directional flickering noise, the reduced activation of hMT+ after training may reflect noise reduction.

Infraslow Electroencephalographic and Dynamic Resting State Network Activity.

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Grooms, Joshua K; Thompson, Garth J; Pan, Wen-Ju; Billings, Jacob; Schumacher, Eric H; Epstein, Charles M; Keilholz, Shella D

2017-06-01

A number of studies have linked the blood oxygenation level dependent (BOLD) signal to electroencephalographic (EEG) signals in traditional frequency bands (δ, θ, α, β, and γ), but the relationship between BOLD and its direct frequency correlates in the infraslow band (resting state magnetic resonance imaging data were acquired simultaneously. The DC EEG signals were correlated with the BOLD signal in patterns that resembled resting state networks. Subsequent dynamic analysis showed that the correlation between DC EEG and the BOLD signal varied substantially over time, even within individual subjects. The variation in DC EEG appears to reflect the time-varying contribution of different resting state networks. Furthermore, some of the patterns of DC EEG and BOLD correlation are consistent with previous work demonstrating quasiperiodic spatiotemporal patterns of large-scale network activity in resting state. These findings demonstrate that infraslow electrical activity is linked to BOLD fluctuations in humans and that it may provide a basis for large-scale organization comparable to that observed in animal studies.

Visual, Auditory, and Cross Modal Sensory Processing in Adults with Autism: An EEG Power and BOLD fMRI Investigation

Science.gov (United States)

Hames, Elizabeth’ C.; Murphy, Brandi; Rajmohan, Ravi; Anderson, Ronald C.; Baker, Mary; Zupancic, Stephen; O’Boyle, Michael; Richman, David

2016-01-01

Electroencephalography (EEG) and blood oxygen level dependent functional magnetic resonance imagining (BOLD fMRI) assessed the neurocorrelates of sensory processing of visual and auditory stimuli in 11 adults with autism (ASD) and 10 neurotypical (NT) controls between the ages of 20–28. We hypothesized that ASD performance on combined audiovisual trials would be less accurate with observable decreased EEG power across frontal, temporal, and occipital channels and decreased BOLD fMRI activity in these same regions; reflecting deficits in key sensory processing areas. Analysis focused on EEG power, BOLD fMRI, and accuracy. Lower EEG beta power and lower left auditory cortex fMRI activity were seen in ASD compared to NT when they were presented with auditory stimuli as demonstrated by contrasting the activity from the second presentation of an auditory stimulus in an all auditory block vs. the second presentation of a visual stimulus in an all visual block (AA2-VV2).We conclude that in ASD, combined audiovisual processing is more similar than unimodal processing to NTs. PMID:27148020

Visual, Auditory, and Cross Modal Sensory Processing in Adults with Autism:An EEG Power and BOLD fMRI Investigation

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Elizabeth C Hames

2016-04-01

Full Text Available Electroencephalography (EEG and Blood Oxygen Level Dependent Functional Magnetic Resonance Imagining (BOLD fMRI assessed the neurocorrelates of sensory processing of visual and auditory stimuli in 11 adults with autism (ASD and 10 neurotypical (NT controls between the ages of 20-28. We hypothesized that ASD performance on combined audiovisual trials would be less accurate with observable decreased EEG power across frontal, temporal, and occipital channels and decreased BOLD fMRI activity in these same regions; reflecting deficits in key sensory processing areas. Analysis focused on EEG power, BOLD fMRI, and accuracy. Lower EEG beta power and lower left auditory cortex fMRI activity were seen in ASD compared to NT when they were presented with auditory stimuli as demonstrated by contrasting the activity from the second presentation of an auditory stimulus in an all auditory block versus the second presentation of a visual stimulus in an all visual block (AA2­VV2. We conclude that in ASD, combined audiovisual processing is more similar than unimodal processing to NTs.

Reduced error signalling in medication-naive children with ADHD

DEFF Research Database (Denmark)

Plessen, Kerstin J; Allen, Elena A; Eichele, Heike

2016-01-01

reduced in children with ADHD. This adaptation was inversely related to activation of the right-lateralized ventral attention network (VAN) on error trials and to task-driven connectivity between the cingulo-opercular system and the VAN. LIMITATIONS: Our study was limited by the modest sample size......BACKGROUND: We examined the blood-oxygen level-dependent (BOLD) activation in brain regions that signal errors and their association with intraindividual behavioural variability and adaptation to errors in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: We acquired...

Association Between Brain Activation and Functional Connectivity.

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Tomasi, Dardo; Volkow, Nora D

2018-04-13

The origin of the "resting-state" brain activity recorded with functional magnetic resonance imaging (fMRI) is still uncertain. Here we provide evidence for the neurovascular origins of the amplitude of the low-frequency fluctuations (ALFF) and the local functional connectivity density (lFCD) by comparing them with task-induced blood-oxygen level dependent (BOLD) responses, which are considered a proxy for neuronal activation. Using fMRI data for 2 different tasks (Relational and Social) collected by the Human Connectome Project in 426 healthy adults, we show that ALFF and lFCD have linear associations with the BOLD response. This association was significantly attenuated by a novel task signal regression (TSR) procedure, indicating that task performance enhances lFCD and ALFF in activated regions. We also show that lFCD predicts BOLD activation patterns, as was recently shown for other functional connectivity metrics, which corroborates that resting functional connectivity architecture impacts brain activation responses. Thus, our findings indicate a common source for BOLD responses, ALFF and lFCD, which is consistent with the neurovascular origin of local hemodynamic synchrony presumably reflecting coordinated fluctuations in neuronal activity. This study also supports the development of task-evoked functional connectivity density mapping.

Non-linear Relationship between BOLD Activation and Amplitude of Beta Oscillations in the Supplementary Motor Area during Rhythmic Finger Tapping and Internal Timing

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Gompf, Florian; Pflug, Anja; Laufs, Helmut; Kell, Christian A.

2017-01-01

Functional imaging studies using BOLD contrasts have consistently reported activation of the supplementary motor area (SMA) both during motor and internal timing tasks. Opposing findings, however, have been shown for the modulation of beta oscillations in the SMA. While movement suppresses beta oscillations in the SMA, motor and non-motor tasks that rely on internal timing increase the amplitude of beta oscillations in the SMA. These independent observations suggest that the relationship between beta oscillations and BOLD activation is more complex than previously thought. Here we set out to investigate this rapport by examining beta oscillations in the SMA during movement with varying degrees of internal timing demands. In a simultaneous EEG-fMRI experiment, 20 healthy right-handed subjects performed an auditory-paced finger-tapping task. Internal timing was operationalized by including conditions with taps on every fourth auditory beat, which necessitates generation of a slow internal rhythm, while tapping to every auditory beat reflected simple auditory-motor synchronization. In the SMA, BOLD activity increased and power in both the low and the high beta band decreased expectedly during each condition compared to baseline. Internal timing was associated with a reduced desynchronization of low beta oscillations compared to conditions without internal timing demands. In parallel with this relative beta power increase, internal timing activated the SMA more strongly in terms of BOLD. This documents a task-dependent non-linear relationship between BOLD and beta-oscillations in the SMA. We discuss different roles of beta synchronization and desynchronization in active processing within the same cortical region. PMID:29249950

Non-linear Relationship between BOLD Activation and Amplitude of Beta Oscillations in the Supplementary Motor Area during Rhythmic Finger Tapping and Internal Timing.

Science.gov (United States)

Gompf, Florian; Pflug, Anja; Laufs, Helmut; Kell, Christian A

2017-01-01

Functional imaging studies using BOLD contrasts have consistently reported activation of the supplementary motor area (SMA) both during motor and internal timing tasks. Opposing findings, however, have been shown for the modulation of beta oscillations in the SMA. While movement suppresses beta oscillations in the SMA, motor and non-motor tasks that rely on internal timing increase the amplitude of beta oscillations in the SMA. These independent observations suggest that the relationship between beta oscillations and BOLD activation is more complex than previously thought. Here we set out to investigate this rapport by examining beta oscillations in the SMA during movement with varying degrees of internal timing demands. In a simultaneous EEG-fMRI experiment, 20 healthy right-handed subjects performed an auditory-paced finger-tapping task. Internal timing was operationalized by including conditions with taps on every fourth auditory beat, which necessitates generation of a slow internal rhythm, while tapping to every auditory beat reflected simple auditory-motor synchronization. In the SMA, BOLD activity increased and power in both the low and the high beta band decreased expectedly during each condition compared to baseline. Internal timing was associated with a reduced desynchronization of low beta oscillations compared to conditions without internal timing demands. In parallel with this relative beta power increase, internal timing activated the SMA more strongly in terms of BOLD. This documents a task-dependent non-linear relationship between BOLD and beta-oscillations in the SMA. We discuss different roles of beta synchronization and desynchronization in active processing within the same cortical region.

Differential Recruitment of Brain Regions During Response Inhibition in Children Prenatally Exposed to Alcohol.

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Kodali, Vikas N; Jacobson, Joseph L; Lindinger, Nadine M; Dodge, Neil C; Molteno, Christopher D; Meintjes, Ernesta M; Jacobson, Sandra W

2017-02-01

Response inhibition is a distinct aspect of executive function that is frequently impaired in children with fetal alcohol spectrum disorders (FASD). We used a Go/NoGo (GNG) task in a functional MRI protocol to investigate differential activation of brain regions in the response inhibition network in children diagnosed with full or partial fetal alcohol syndrome (FAS/PFAS), compared with healthy controls. A rapid, event-related task with 120 Go and 60 NoGo trials was used to study children aged 8 to 12 years-8 with FAS/PFAS, 17 controls. Letters were projected sequentially, with Go and NoGo trials randomly interspersed across the task. BOLD signal in the whole brain was contrasted for the correct NoGo minus correct Go trials between the FAS/PFAS and control groups. Compared to the FAS/PFAS group, controls showed greater activation of the inferior frontal and anterior cingulate network linked to response inhibition in typically developing children. By contrast, the FAS/PFAS group showed greater BOLD response in dorsolateral prefrontal cortex and other middle prefrontal regions, suggesting compensation for inefficient function of pathways that normally mediate inhibitory processing. All group differences were significant after control for potential confounding variables. None of the effects of prenatal alcohol exposure on activation of the regions associated with response inhibition were attributable to the effects of this exposure on IQ. This is the first FASD GNG study in which all participants in the exposed group met criteria for a diagnosis of full FAS or PFAS. Although FASD is frequently comorbid with attention deficit hyperactivity disorder, the pattern of brain activation seen in these disorders differs, suggesting that different neural pathways mediate response inhibition in FASD and that different interventions for FASD are, therefore, warranted. Copyright © 2017 by the Research Society on Alcoholism.

Sphingosine-1-Phosphate Signaling Regulates Myogenic Responsiveness in Human Resistance Arteries.

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Sonya Hui

Full Text Available We recently identified sphingosine-1-phosphate (S1P signaling and the cystic fibrosis transmembrane conductance regulator (CFTR as prominent regulators of myogenic responsiveness in rodent resistance arteries. However, since rodent models frequently exhibit limitations with respect to human applicability, translation is necessary to validate the relevance of this signaling network for clinical application. We therefore investigated the significance of these regulatory elements in human mesenteric and skeletal muscle resistance arteries. Mesenteric and skeletal muscle resistance arteries were isolated from patient tissue specimens collected during colonic or cardiac bypass surgery. Pressure myography assessments confirmed endothelial integrity, as well as stable phenylephrine and myogenic responses. Both human mesenteric and skeletal muscle resistance arteries (i express critical S1P signaling elements, (ii constrict in response to S1P and (iii lose myogenic responsiveness following S1P receptor antagonism (JTE013. However, while human mesenteric arteries express CFTR, human skeletal muscle resistance arteries do not express detectable levels of CFTR protein. Consequently, modulating CFTR activity enhances myogenic responsiveness only in human mesenteric resistance arteries. We conclude that human mesenteric and skeletal muscle resistance arteries are a reliable and consistent model for translational studies. We demonstrate that the core elements of an S1P-dependent signaling network translate to human mesenteric resistance arteries. Clear species and vascular bed variations are evident, reinforcing the critical need for further translational study.

Interaction Dynamics Determine Signaling and Output Pathway Responses

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Klement Stojanovski

2017-04-01

Full Text Available The understanding of interaction dynamics in signaling pathways can shed light on pathway architecture and provide insights into targets for intervention. Here, we explored the relevance of kinetic rate constants of a key upstream osmosensor in the yeast high-osmolarity glycerol-mitogen-activated protein kinase (HOG-MAPK pathway to signaling output responses. We created mutant pairs of the Sln1-Ypd1 complex interface that caused major compensating changes in the association (kon and dissociation (koff rate constants (kinetic perturbations but only moderate changes in the overall complex affinity (Kd. Yeast cells carrying a Sln1-Ypd1 mutant pair with moderate increases in kon and koff displayed a lower threshold of HOG pathway activation than wild-type cells. Mutants with higher kon and koff rates gave rise to higher basal signaling and gene expression but impaired osmoadaptation. Thus, the kon and koff rates of the components in the Sln1 osmosensor determine proper signaling dynamics and osmoadaptation.

DMPD: Innate immune responses: crosstalk of signaling and regulation of genetranscription. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 16753195 Innate immune responses: crosstalk of signaling and regulation of genetran...l) (.csml) Show Innate immune responses: crosstalk of signaling and regulation of genetranscription. PubmedI...D 16753195 Title Innate immune responses: crosstalk of signaling and regulation o

Oral glucose intake inhibits hypothalamic neuronal activity more effectively than glucose infusion

NARCIS (Netherlands)

Smeets, P.A.M.; Vidarsdottir, S.; Graaf, C. de; Stafleu, A.; Osch, M.J.P. van; Viergever, M.A.; Pijl, H.; Grond, J. van der

2007-01-01

We previously showed that hypothalamic neuronal activity, as measured by the blood oxygen level-dependent (BOLD) functional MRI signal, declines in response to oral glucose intake. To further explore the mechanism driving changes in hypothalamic neuronal activity in response to an oral glucose load,

Reproducibility and signal response linearity of Alanine gel dosimeter

International Nuclear Information System (INIS)

Silva, Cleber Feijo Silva; Campos, Leticia Lucente

2008-01-01

Gel Dosimetry has been studied mainly for medical applications, because it presents signal response in the dose range used in radiotherapy treatments and it can be applied for three dimensional dosimetry. Alanine gel dosimeter is a new gel material developed at IPEN that presents significant improvement on previous alanine systems developed by Costa (1994). The DL-Alanine (C 3 H 7 NO 2 ) is an amino acid tissue equivalent that improves the production of ferric ions in the solution. These ferric ions concentration can be measured by spectrophotometry technique. This work aims to study the reproducibility of the alanine gel solutions and the signal response as a function of gamma radiation dose, considering that these two properties are very important for characterizing and standardizing any dosimeter. (author)

WRKY proteins: signaling and regulation of expression during abiotic stress responses.

Science.gov (United States)

Banerjee, Aditya; Roychoudhury, Aryadeep

2015-01-01

WRKY proteins are emerging players in plant signaling and have been thoroughly reported to play important roles in plants under biotic stress like pathogen attack. However, recent advances in this field do reveal the enormous significance of these proteins in eliciting responses induced by abiotic stresses. WRKY proteins act as major transcription factors, either as positive or negative regulators. Specific WRKY factors which help in the expression of a cluster of stress-responsive genes are being targeted and genetically modified to induce improved abiotic stress tolerance in plants. The knowledge regarding the signaling cascade leading to the activation of the WRKY proteins, their interaction with other proteins of the signaling pathway, and the downstream genes activated by them are altogether vital for justified targeting of the WRKY genes. WRKY proteins have also been considered to generate tolerance against multiple abiotic stresses with possible roles in mediating a cross talk between abiotic and biotic stress responses. In this review, we have reckoned the diverse signaling pattern and biological functions of WRKY proteins throughout the plant kingdom along with the growing prospects in this field of research.

Dynamics of response-conflict monitoring and individual differences in response control and behavioral control: an electrophysiological investigation using a stop-signal task.

Science.gov (United States)

Stahl, Jutta; Gibbons, Henning

2007-03-01

The aim of the present study was to investigate the functional significance of error (related) negativity Ne/ERN and individual differences in human action monitoring. A response-conflict model of Ne/ERN should be tested applying a stop-signal paradigm. After a few modifications of Ne/ERN response-conflict theory (Yeung N, Botvinick MM, Cohen JD. The neural basis of error detection: conflict monitoring and the error-related negativity. Psychological Review 2004:111(4);931-959), strength and time course of response conflict could be modeled as a function of stop-signal delay. In Experiment 1, 35 participants performed a visual two-choice response-time task but tried to withhold the response if an auditory stop signal was presented. Probability of stopping errors was held at 50% using variable delays between visual and auditory stimuli. Experiment 2 (n=10) employed both auditory go and stop signals and confirmed that Ne/ERN effects are due to conflict induced by the auditory stop signal, and not the mere presence or absence of an additional stimulus. As predicted, amplitudes of both the stimulus-locked and response-locked Ne/ERN were largest for non-stopped responses, followed by successfully stopped and go responses. However, independently of response type Ne/ERN also increased with increasing stop-signal delay. Since longer delay invokes stronger response conflict, results specifically support the notion of Ne/ERN reflecting response-conflict monitoring. Furthermore, individual differences related to measures of response control and behavioral control were observed. Both low response control estimated from stop-task performance and high psychometric impulsivity were accompanied by smaller Ne/ERN amplitude on stop trials, suggesting reduced response-conflict monitoring. The present study supported the response-conflict view of Ne/ERN. Furthermore, the observed relationship between impulsivity and Ne/ERN amplitude suggested that individuals with low behavioral

The ap?ritif effect: alcohol's effects on the brain's response to food aromas in women

OpenAIRE

Eiler, William J.A.; D?emid?i?, Mario; Case, K. Rose; Soeurt, Christina M.; Armstrong, Cheryl L.H.; Mattes, Richard D.; O'Connor, Sean J.; Harezlak, Jaroslaw; Acton, Anthony J.; Considine, Robert V.; Kareken, David A.

2015-01-01

Objective Consuming alcohol prior to a meal (an ap?ritif) increases food consumption. This greater food consumption may result from increased activity in brain regions that mediate reward and regulate feeding behavior. Using functional magnetic resonance imaging, we evaluated the blood oxygenation level dependent (BOLD) response to the food aromas of either roast beef or Italian meat sauce following pharmacokinetically controlled intravenous infusion of alcohol. Methods BOLD activation to foo...

Differential Cellular Responses to Hedgehog Signalling in Vertebrates—What is the Role of Competence?

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Kiecker, Clemens; Graham, Anthony; Logan, Malcolm

2016-01-01

A surprisingly small number of signalling pathways generate a plethora of cellular responses ranging from the acquisition of multiple cell fates to proliferation, differentiation, morphogenesis and cell death. These diverse responses may be due to the dose-dependent activities of signalling factors, or to intrinsic differences in the response of cells to a given signal—a phenomenon called differential cellular competence. In this review, we focus on temporal and spatial differences in competence for Hedgehog (HH) signalling, a signalling pathway that is reiteratively employed in embryos and adult organisms. We discuss the upstream signals and mechanisms that may establish differential competence for HHs in a range of different tissues. We argue that the changing competence for HH signalling provides a four-dimensional framework for the interpretation of the signal that is essential for the emergence of functional anatomy. A number of diseases—including several types of cancer—are caused by malfunctions of the HH pathway. A better understanding of what provides differential competence for this signal may reveal HH-related disease mechanisms and equip us with more specific tools to manipulate HH signalling in the clinic. PMID:29615599

Differential Cellular Responses to Hedgehog Signalling in Vertebrates—What is the Role of Competence?

Directory of Open Access Journals (Sweden)

Clemens Kiecker

2016-12-01

Full Text Available A surprisingly small number of signalling pathways generate a plethora of cellular responses ranging from the acquisition of multiple cell fates to proliferation, differentiation, morphogenesis and cell death. These diverse responses may be due to the dose-dependent activities of signalling factors, or to intrinsic differences in the response of cells to a given signal—a phenomenon called differential cellular competence. In this review, we focus on temporal and spatial differences in competence for Hedgehog (HH signalling, a signalling pathway that is reiteratively employed in embryos and adult organisms. We discuss the upstream signals and mechanisms that may establish differential competence for HHs in a range of different tissues. We argue that the changing competence for HH signalling provides a four-dimensional framework for the interpretation of the signal that is essential for the emergence of functional anatomy. A number of diseases—including several types of cancer—are caused by malfunctions of the HH pathway. A better understanding of what provides differential competence for this signal may reveal HH-related disease mechanisms and equip us with more specific tools to manipulate HH signalling in the clinic.

Stimulus-Responsive Plasmonic Chiral Signals of Gold Nanorods Organized on DNA Origami.

Science.gov (United States)

Jiang, Qiao; Liu, Qing; Shi, Yuefeng; Wang, Zhen-Gang; Zhan, Pengfei; Liu, Jianbing; Liu, Chao; Wang, Hui; Shi, Xinghua; Zhang, Li; Sun, Jiashu; Ding, Baoquan; Liu, Minghua

2017-11-08

In response to environmental variations, living cells need to arrange the conformational changes of macromolecules to achieve the specific biofunctions. Inspired by natural molecular machines, artificial macromolecular assemblies with controllable nanostructures and environmentally responsive functions can be designed. By assembling macromolecular nanostructures with noble metal nanoparticles, environmental information could be significantly amplified and modulated. However, manufacturing dynamic plasmonic nanostructures that are efficiently responsive to different stimuli is still a challenging task. Here we demonstrate a stimulus-responsive plasmonic nanosystem based on DNA origami-organized gold nanorods (GNRs). L-shaped GNR dimers were assembled on rhombus-shaped DNA origami templates. The geometry and chiral signals of the GNR nanoarchitectures respond to multiple stimuli, including glutathione reduction, restriction enzyme action, pH change, or photoirradiation. While the glutathione reduction or restriction enzyme caused irreversible changes in the plasmonic circular dichroism (CD) signals, both pH and light irradiation triggered reversible changes in the plasmonic CD. Our system transduces external stimuli into conformational changes and circular dichroism responses in near-infrared (NIR) wavelengths. By this approach, programmable optical reporters for essential biological signals can be fabricated.

Fish Oil Supplementation Increases Event-Related Posterior Cingulate Activation in Older Adults with Subjective Memory Impairment.

Science.gov (United States)

Boespflug, E L; McNamara, R K; Eliassen, J C; Schidler, M D; Krikorian, R

2016-02-01

To determine the effects of long-chain omega-3 (LCn-3) fatty acids found in fish oil, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on cortical blood oxygen level-dependent (BOLD) activity during a working memory task in older adults with subjective memory impairment. Randomized, double-blind, placebo-controlled study. Academic medical center. Healthy older adults (62-80 years) with subjective memory impairment, but not meeting criteria for mild cognitive impairment or dementia. Fish oil (EPA+DHA: 2.4 g/d, n=11) or placebo (corn oil, n=10) for 24 weeks. Cortical BOLD response patterns during performance of a sequential letter n-back working memory task were determined at baseline and week 24 by functional magnetic resonance imaging (fMRI). At 24 weeks erythrocyte membrane EPA+DHA composition increased significantly from baseline in participants receiving fish oil (+31%, p ≤ 0.0001) but not placebo (-17%, p=0.06). Multivariate modeling of fMRI data identified a significant interaction among treatment, visit, and memory loading in the right cingulate (BA 23/24), and in the right sensorimotor area (BA 3/4). In the fish oil group, BOLD increases at 24 weeks were observed in the right posterior cingulate and left superior frontal regions during memory loading. A region-of-interest analysis indicated that the baseline to endpoint change in posterior cingulate cortex BOLD activity signal was significantly greater in the fish oil group compared with the placebo group during the 1-back (p=0.0003) and 2-back (p=0.0005) conditions. Among all participants, the change in erythrocyte EPA+DHA during the intervention was associated with performance in the 2-back working memory task (p = 0.01), and with cingulate BOLD signal during the 1-back (p = 0.005) with a trend during the 2-back (p = 0.09). Further, cingulate BOLD activity was related to performance in the 2-back condition. Dietary fish oil supplementation increases red blood cell omega-3 content

Response inhibition signals and miscoding of direction in dorsomedial striatum

Directory of Open Access Journals (Sweden)

Daniel W Bryden

2012-09-01

Full Text Available The ability to inhibit action is critical for everyday behavior and is affected by a variety of disorders. Behavioral control and response inhibition is thought to depend on a neural circuit that includes the dorsal striatum, yet the neural signals that lead to response inhibition and its failure are unclear. To address this issue, we recorded from neurons in rat dorsomedial striatum (mDS in a novel task in which rats responded to a spatial cue that signaled that reward would be delivered either to the left or to the right. On 80% of trials rats were instructed to respond in the direction cued by the light (GO. On 20% of trials a second light illuminated instructing the rat to refrain from making the cued movement and move in the opposite direction (STOP. Many neurons in mDS encoded direction, firing more or less strongly for GO movements made ipsilateral or contralateral to the recording electrode. Neurons that fired more strongly for contralateral GO responses were more active when rats were faster, showed reduced activity on STOP trials, and miscoded direction on errors, suggesting that when these neurons were overly active, response inhibition failed. Neurons that decreased firing for contralateral movement were excited during trials in which the rat was required to stop the ipsilateral movement. For these neurons activity was reduced when errors were made and was negatively correlated with movement time suggesting that when these neurons were less active on STOP trials, response inhibition failed. Finally, the activity of a significant number of neurons represented a global inhibitory signal, firing more strongly during response inhibition regardless of response direction. Breakdown by cell type suggests that putative medium spiny neurons tended to fire more strongly under STOP trials, whereas putative interneurons exhibited both activity patterns. 

Using CO5BOLD models to predict the effects of granulation on colours .

Science.gov (United States)

Bonifacio, P.; Caffau, E.; Ludwig, H.-G.; Steffen, M.; Castelli, F.; Gallagher, A. J.; Prakapavičius, D.; Kučinskas, A.; Cayrel, R.; Freytag, B.; Plez, B.; Homeier, D.

In order to investigate the effects of granulation on fluxes and colours, we computed the emerging fluxes from the models in the CO5BOLD grid with metallicities [M/H]=0.0,-1.0,-2.0 and -3.0. These fluxes have been used to compute colours in different photometric systems. We explain here how our computations have been performed and provide some results.

Investigating the Neural Bases for Intra-Subject Cognitive Efficiency Using Functional Magnetic Resonance Imaging

Directory of Open Access Journals (Sweden)

Neena K. Rao

2014-10-01

Full Text Available Several fMRI studies have examined brain regions mediating inter-subject variability in cognitive efficiency, but none have examined regions mediating intra-subject variability in efficiency. Thus, the present study was designed to identify brain regions involved in intra-subject variability in cognitive efficiency via participant-level correlations between trial-level reaction time (RT and trial-level fMRI BOLD percent signal change on a processing speed task. On each trial, participants indicated whether a digit-symbol probe-pair was present or absent in an array of nine digit-symbol probe-pairs while fMRI data were collected. Deconvolution analyses, using RT time-series models (derived from the proportional scaling of an event-related hemodynamic response function model by trial-level RT, were used to evaluate relationships between trial-level RTs and BOLD percent signal change. Although task-related patterns of activation and deactivation were observed in regions including bilateral occipital, bilateral parietal, portions of the medial wall such as the precuneus, default mode network regions including anterior cingulate, posterior cingulate, bilateral temporal, right cerebellum, and right cuneus, RT-BOLD correlations were observed in a more circumscribed set of regions. Positive RT-related patterns, or RT-BOLD correlations where fast RTs were associated with lower BOLD percent signal change, were observed in regions including bilateral occipital, bilateral parietal, and the precuneus. RT-BOLD correlations were not observed in the default mode network indicating a smaller set of regions associated with intra-subject variability in cognitive efficiency. The results are discussed in terms of a distributed area of regions that mediate variability in the cognitive efficiency that might underlie processing speed differences between individuals.

Overweight adolescents' brain response to sweetened beverages mirrors addiction pathways.

Science.gov (United States)

Feldstein Ewing, Sarah W; Claus, Eric D; Hudson, Karen A; Filbey, Francesca M; Yakes Jimenez, Elizabeth; Lisdahl, Krista M; Kong, Alberta S

2017-08-01

Many adolescents struggle with overweight/obesity, which exponentially increases in the transition to adulthood. Overweight/obesity places youth at risk for serious health conditions, including type 2 diabetes. In adults, neural substrates implicated in addiction (e.g., orbitofrontal cortex (OFC), striatum, amygdala, and ventral tegmental area) have been found to be relevant to risk for overweight/obesity. In this study, we examined three hypotheses to disentangle the potential overlap between addiction and overweight/obesity processing by examining (1) brain response to high vs. low calorie beverages, (2) the strength of correspondence between biometrics, including body mass index (BMI) and insulin resistance, and brain response and (3) the relationship between a measure of food addiction and brain response using an established fMRI gustatory cue exposure task with a sample of overweight/obese youth (M age = 16.46; M BMI = 33.1). Greater BOLD response was observed across the OFC, inferior frontal gyrus (IFG), nucleus accumbens, right amygdala, and additional frontoparietal and temporal regions in neural processing of high vs. low calorie beverages. Further, BMI scores positively correlated with BOLD activation in the high calorie > low calorie contrast in the right postcentral gyrus and central operculum. Insulin resistance positively correlated with BOLD activation across the bilateral middle/superior temporal gyrus, left OFC, and superior parietal lobe. No relationships were observed between measures of food addiction and brain response. These findings support the activation of parallel addiction-related neural pathways in adolescents' high calorie processing, while also suggesting the importance of refining conceptual and neurocognitive models to fit this developmental period.

Model-based synthesis of locally contingent responses to global market signals

Science.gov (United States)

Magliocca, N. R.

2015-12-01

Rural livelihoods and the land systems on which they depend are increasingly influenced by distant markets through economic globalization. Place-based analyses of land and livelihood system sustainability must then consider both proximate and distant influences on local decision-making. Thus, advancing land change theory in the context of economic globalization calls for a systematic understanding of the general processes as well as local contingencies shaping local responses to global signals. Synthesis of insights from place-based case studies of land and livelihood change is a path forward for developing such systematic knowledge. This paper introduces a model-based synthesis approach to investigating the influence of local socio-environmental and agent-level factors in mediating land-use and livelihood responses to changing global market signals. A generalized agent-based modeling framework is applied to six case-study sites that differ in environmental conditions, market access and influence, and livelihood settings. The largest modeled land conversions and livelihood transitions to market-oriented production occurred in sties with relatively productive agricultural land and/or with limited livelihood options. Experimental shifts in the distributions of agents' risk tolerances generally acted to attenuate or amplify responses to changes in global market signals. Importantly, however, responses of agents at different points in the risk tolerance distribution varied widely, with the wealth gap growing wider between agents with higher or lower risk tolerance. These results demonstrate model-based synthesis is a promising approach to overcome many of the challenges of current synthesis methods in land change science, and to identify generalized as well as locally contingent responses to global market signals.

Towards prognostic biomarkers from BOLD fluctuations to differentiate a first epileptic seizure from new-onset epilepsy.

Science.gov (United States)

Gupta, Lalit; Janssens, Rick; Vlooswijk, Mariëlle C G; Rouhl, Rob P W; de Louw, Anton; Aldenkamp, Albert P; Ulman, Shrutin; Besseling, René M H; Hofman, Paul A M; van Kranen-Mastenbroek, Vivianne H; Hilkman, Danny M; Jansen, Jacobus F A; Backes, Walter H

2017-03-01

The diagnosis of epilepsy cannot be reliably made prior to a patient's second seizure in most cases. Therefore, adequate diagnostic tools are needed to differentiate subjects with a first seizure from those with a seizure preceding the onset of epilepsy. The objective was to explore spontaneous blood oxygen level-dependent (BOLD) fluctuations in subjects with a first-ever seizure and patients with new-onset epilepsy (NOE), and to find characteristic biomarkers for seizure recurrence after the first seizure. We examined 17 first-seizure subjects, 19 patients with new-onset epilepsy (NOE), and 18 healthy controls. All subjects underwent clinical investigation and received electroencephalography and resting-state functional magnetic resonance imaging (MRI). The BOLD time series were analyzed in terms of regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFFs). We found significantly stronger amplitudes (higher fALFFs) in patients with NOE relative to first-seizure subjects and healthy controls. The frequency range of 73-198 mHz (slow-3 subband) appeared most useful for discriminating patients with NOE from first-seizure subjects. The ReHo measure did not show any significant differences. The fALFF appears to be a noninvasive measure that characterizes spontaneous BOLD fluctuations and shows stronger amplitudes in the slow-3 subband of patients with NOE relative first-seizure subjects and healthy controls. A larger study population with follow-up is required to determine whether fALFF holds promise as a potential biomarker for identifying subjects at increased risk to develop epilepsy. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

BOLD VENTURE COMPUTATION SYSTEM for nuclear reactor core analysis, Version III

International Nuclear Information System (INIS)

Vondy, D.R.; Fowler, T.B.; Cunningham, G.W. III.

1981-06-01

This report is a condensed documentation for VERSION III of the BOLD VENTURE COMPUTATION SYSTEM for nuclear reactor core analysis. An experienced analyst should be able to use this system routinely for solving problems by referring to this document. Individual reports must be referenced for details. This report covers basic input instructions and describes recent extensions to the modules as well as to the interface data file specifications. Some application considerations are discussed and an elaborate sample problem is used as an instruction aid. Instructions for creating the system on IBM computers are also given

BOLD VENTURE COMPUTATION SYSTEM for nuclear reactor core analysis, Version III

Energy Technology Data Exchange (ETDEWEB)

Vondy, D.R.; Fowler, T.B.; Cunningham, G.W. III.

1981-06-01

This report is a condensed documentation for VERSION III of the BOLD VENTURE COMPUTATION SYSTEM for nuclear reactor core analysis. An experienced analyst should be able to use this system routinely for solving problems by referring to this document. Individual reports must be referenced for details. This report covers basic input instructions and describes recent extensions to the modules as well as to the interface data file specifications. Some application considerations are discussed and an elaborate sample problem is used as an instruction aid. Instructions for creating the system on IBM computers are also given.

The UVR8 UV-B Photoreceptor: Perception, Signaling and Response

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Tilbrook, Kimberley; Arongaus, Adriana B.; Binkert, Melanie; Heijde, Marc; Yin, Ruohe; Ulm, Roman

2013-01-01

Ultraviolet-B radiation (UV-B) is an intrinsic part of sunlight that is accompanied by significant biological effects. Plants are able to perceive UV-B using the UV-B photoreceptor UVR8 which is linked to a specific molecular signaling pathway and leads to UV-B acclimation. Herein we review the biological process in plants from initial UV-B perception and signal transduction through to the known UV-B responses that promote survival in sunlight. The UVR8 UV-B photoreceptor exists as a homodimer that instantly monomerises upon UV-B absorption via specific intrinsic tryptophans which act as UV-B chromophores. The UVR8 monomer interacts with COP1, an E3 ubiquitin ligase, initiating a molecular signaling pathway that leads to gene expression changes. This signaling output leads to UVR8-dependent responses including UV-B-induced photomorphogenesis and the accumulation of UV-B-absorbing flavonols. Negative feedback regulation of the pathway is provided by the WD40-repeat proteins RUP1 and RUP2, which facilitate UVR8 redimerization, disrupting the UVR8-COP1 interaction. Despite rapid advancements in the field of recent years, further components of UVR8 UV-B signaling are constantly emerging, and the precise interplay of these and the established players UVR8, COP1, RUP1, RUP2 and HY5 needs to be defined. UVR8 UV-B signaling represents our further understanding of how plants are able to sense their light environment and adjust their growth accordingly. PMID:23864838

Brain response to images of food varying in energy density is associated with body composition in 7- to 10-year-old children: Results of an exploratory study.

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Fearnbach, S Nicole; English, Laural K; Lasschuijt, Marlou; Wilson, Stephen J; Savage, Jennifer S; Fisher, Jennifer O; Rolls, Barbara J; Keller, Kathleen L

2016-08-01

Energy balance is regulated by a multifaceted system of physiological signals that influence energy intake and expenditure. Therefore, variability in the brain's response to food may be partially explained by differences in levels of metabolically active tissues throughout the body, including fat-free mass (FFM) and fat mass (FM). The purpose of this study was to test the hypothesis that children's body composition would be related to their brain response to food images varying in energy density (ED), a measure of energy content per weight of food. Functional magnetic resonance imaging (fMRI) was used to measure brain response to High (>1.5kcal/g) and Low (vs. Low ED) in a priori defined brain regions of interest previously implicated in energy homeostasis and reward processing. Pearson's correlations were then calculated between activation in these regions for various contrasts (High ED-Low ED, High ED-Control, Low ED-Control) and child body composition (FFM index, FM index, % body fat). Relative to Low ED foods, High ED foods elicited greater BOLD activation in the left thalamus. In the right substantia nigra, BOLD activation for the contrast of High ED-Low ED foods was positively associated with child FFM. There were no significant results for the High ED-Control or Low ED-Control contrasts. Our findings support literature on FFM as an appetitive driver, such that greater amounts of lean mass were associated with greater activation for High ED foods in an area of the brain associated with dopamine signaling and reward (substantia nigra). These results confirm our hypothesis that brain response to foods varying in energy content is related to measures of child body composition. Copyright © 2016 Elsevier Inc. All rights reserved.

Cerebral responses and role of the prefrontal cortex in conditioned pain modulation: an fMRI study in healthy subjects

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Bogdanov, Volodymyr B.; Viganò, Alessandro; Noirhomme, Quentin; Bogdanova, Olena V.; Guy, Nathalie; Laureys, Steven; Renshaw, Perry F.; Dallel, Radhouane; Phillips, Christophe; Schoenen, Jean

2017-01-01

The mechanisms underlying conditioned pain modulation (CPM) are multifaceted. We searched for a link between individual differences in prefrontal cortex activity during multi-trial heterotopic noxious cold conditioning and modulation of the cerebral response to phasic heat pain. In 24 healthy female subjects, we conditioned laser heat stimuli to the left hand by applying alternatively ice-cold or lukewarm compresses to the right foot. We compared pain ratings with cerebral fMRI BOLD responses. We also analyzed the relation between CPM and BOLD changes produced by the heterotopic cold conditioning itself, as well as the impact of anxiety and habituation of cold-pain ratings. Specific cerebral activation was identified in precuneus and left posterior insula/SII, respectively, during early and sustained phases of cold application. During cold conditioning, laser pain decreased (n = 7), increased (n = 10) or stayed unchanged (n = 7). At the individual level, the psychophysical effect was directly proportional to the cold-induced modulation of the laser-induced BOLD response in left posterior insula/SII. The latter correlated with the BOLD response recorded 80 s earlier during the initial 10-s phase of cold application in anterior cingulate, orbitofrontal and lateral prefrontal cortices. High anxiety and habituation of cold pain were associated with greater laser heat-induced pain during heterotopic cold stimulation. The habituation was also linked to the early cold-induced orbitofrontal responses. We conclude that individual differences in conditioned pain modulation are related to different levels of prefrontal cortical activation by the early part of the conditioning stimulus, possibly due to different levels in trait anxiety. PMID:25461267

Working memory in volunteers and schizophrenics using BOLD fMRI

International Nuclear Information System (INIS)

Giesel, F.L.; Hohmann, N.; Seidl, U.; Kress, K.R.; Schoenknecht, P.; Schroeder, J.; Kauczor, H.-U.; Essig, M.

2005-01-01

Functional magnetic resonance imaging uses the blood oxygen level-dependent effect (BOLD MRI) for noninvasive display of cerebral correlatives of cognitive function. The importance for the understanding of physiological and pathological processes is demonstrated by investigations of working memory in schizophrenics and healthy controls. Working memory is involved in processing rather than storage of information and therefore is linked to complex processes such as learning and problem solving. In schizophrenic psychosis, these functions are clearly restricted. Training effects in the working memory task follow an inverse U-shape function, suggesting that cerebral activation reaches a peak before economics of the brain find a more efficient method and activation decreases. (orig.) [de

Developmental Changes in Sensory-Evoked Optical Intrinsic Signals in the Rat Barrel Cortex

Directory of Open Access Journals (Sweden)

Mikhail Sintsov

2017-12-01

Full Text Available Optical Intrinsic Signal imaging (OISi is a powerful technique for optical brain studies. OIS mainly reflects the hemodynamic response (HR and metabolism, but it may also involve changes in tissue light scattering (LS caused by transient cellular swelling in the active tissue. Here, we explored the developmental features of sensory-evoked OIS in the rat barrel cortex during the first 3 months after birth. Multispectral OISi revealed that two temporally distinct components contribute to the neonatal OIS: an early phase of LS followed by a late phase of HR. The contribution of LS to the early response was also evidenced by an increase in light transmission through the active barrel. The early OIS phase correlated in time and amplitude with the sensory-evoked electrophysiological response. Application of the Modified Beer-Lambert Law (MBLL to the OIS data revealed that HR during the early phase involved only a slight decrease in blood oxygenation without any change in blood volume. In contrast, HR during the late phase manifested an adult-like increase in blood volume and oxygenation. During development, the peak time of the delayed HR progressively shortened with age, nearly reaching the stimulus onset and overlapping with the early LS phase by the fourth postnatal week. Thus, LS contributes to the sensory-evoked OIS in the barrel cortex of rats at all ages, and it dominates the early OIS phase in neonatal rats due to delayed HR. Our results are also consistent with the delayed blood oxygen level dependent (BOLD signal in human preterm infants.

A signal detection-item response theory model for evaluating neuropsychological measures.

Science.gov (United States)

Thomas, Michael L; Brown, Gregory G; Gur, Ruben C; Moore, Tyler M; Patt, Virginie M; Risbrough, Victoria B; Baker, Dewleen G

2018-02-05

Models from signal detection theory are commonly used to score neuropsychological test data, especially tests of recognition memory. Here we show that certain item response theory models can be formulated as signal detection theory models, thus linking two complementary but distinct methodologies. We then use the approach to evaluate the validity (construct representation) of commonly used research measures, demonstrate the impact of conditional error on neuropsychological outcomes, and evaluate measurement bias. Signal detection-item response theory (SD-IRT) models were fitted to recognition memory data for words, faces, and objects. The sample consisted of U.S. Infantry Marines and Navy Corpsmen participating in the Marine Resiliency Study. Data comprised item responses to the Penn Face Memory Test (PFMT; N = 1,338), Penn Word Memory Test (PWMT; N = 1,331), and Visual Object Learning Test (VOLT; N = 1,249), and self-report of past head injury with loss of consciousness. SD-IRT models adequately fitted recognition memory item data across all modalities. Error varied systematically with ability estimates, and distributions of residuals from the regression of memory discrimination onto self-report of past head injury were positively skewed towards regions of larger measurement error. Analyses of differential item functioning revealed little evidence of systematic bias by level of education. SD-IRT models benefit from the measurement rigor of item response theory-which permits the modeling of item difficulty and examinee ability-and from signal detection theory-which provides an interpretive framework encompassing the experimentally validated constructs of memory discrimination and response bias. We used this approach to validate the construct representation of commonly used research measures and to demonstrate how nonoptimized item parameters can lead to erroneous conclusions when interpreting neuropsychological test data. Future work might include the

Personality and the collective: bold homing pigeons occupy higher leadership ranks in flocks.

Science.gov (United States)

Sasaki, Takao; Mann, Richard P; Warren, Katherine N; Herbert, Tristian; Wilson, Tara; Biro, Dora

2018-05-19

While collective movement is ecologically widespread and conveys numerous benefits on individuals, it also poses a coordination problem: who controls the group's movements? The role that animal 'personalities' play in this question has recently become a focus of research interest. Although many animal groups have distributed leadership (i.e. multiple individuals influence collective decisions), studies linking personality and leadership have focused predominantly on the group's single most influential individual. In this study, we investigate the relationship between personality and the influence of multiple leaders on collective movement using homing pigeons, Columba livia , a species known to display complex multilevel leadership hierarchies during flock flights. Our results show that more exploratory (i.e. 'bold') birds are more likely to occupy higher ranks in the leadership hierarchy and thus have more influence on the direction of collective movement than less exploratory (i.e. 'shy') birds during both free flights around their lofts and homing flights from a distant site. Our data also show that bold pigeons fly faster than shy birds during solo flights. We discuss our results in light of theories about the evolution of personality, with specific reference to the adaptive value of heterogeneity in animal groups.This article is part of the theme issue 'Collective movement ecology'. © 2018 The Author(s).

Signalling through C-type lectin receptors: shaping immune responses

NARCIS (Netherlands)

Geijtenbeek, Teunis B. H.; Gringhuis, Sonja I.

2009-01-01

C-type lectin receptors (CLRs) expressed by dendritic cells are crucial for tailoring immune responses to pathogens. Following pathogen binding, CLRs trigger distinct signalling pathways that induce the expression of specific cytokines which determine T cell polarization fates. Some CLRs can induce

Neural responses to multimodal ostensive signals in 5-month-old infants.

Directory of Open Access Journals (Sweden)

Eugenio Parise

Full Text Available Infants' sensitivity to ostensive signals, such as direct eye contact and infant-directed speech, is well documented in the literature. We investigated how infants interpret such signals by assessing common processing mechanisms devoted to them and by measuring neural responses to their compounds. In Experiment 1, we found that ostensive signals from different modalities display overlapping electrophysiological activity in 5-month-old infants, suggesting that these signals share neural processing mechanisms independently of their modality. In Experiment 2, we found that the activation to ostensive signals from different modalities is not additive to each other, but rather reflects the presence of ostension in either stimulus stream. These data support the thesis that ostensive signals obligatorily indicate to young infants that communication is directed to them.

Mechanisms Underlying the Antidepressant Response of Acupuncture via PKA/CREB Signaling Pathway.

Science.gov (United States)

Jiang, Huili; Zhang, Xuhui; Wang, Yu; Zhang, Huimin; Li, Jing; Yang, Xinjing; Zhao, Bingcong; Zhang, Chuntao; Yu, Miao; Xu, Mingmin; Yu, Qiuyun; Liang, Xingchen; Li, Xiang; Shi, Peng; Bao, Tuya

2017-01-01

Protein kinase A (PKA)/cAMP response element-binding (CREB) protein signaling pathway, contributing to impaired neurogenesis parallel to depressive-like behaviors, has been identified as the crucial factor involved in the antidepressant response of acupuncture. However, the molecular mechanisms associated with antidepressant response of acupuncture, neurogenesis, and depressive-like behaviors ameliorating remain unexplored. The objective was to identify the mechanisms underlying the antidepressant response of acupuncture through PKA signaling pathway in depression rats by employing the PKA signaling pathway inhibitor H89 in in vivo experiments. Our results indicated that the expression of hippocampal PKA- α and p-CREB was significantly downregulated by chronic unpredicted mild stress (CUMS) procedures. Importantly, acupuncture reversed the downregulation of PKA- α and p-CREB. The expression of PKA- α was upregulated by fluoxetine, but not p-CREB. No significant difference was found between Acu and FLX groups on the expression of PKA- α and p-CREB. Interestingly, H89 inhibited the effects of acupuncture or fluoxetine on upregulating the expression of p-CREB, but not PKA- α . There was no significant difference in expression of CREB among the groups. Conclusively, our findings further support the hypothesis that acupuncture could ameliorate depressive-like behaviors by regulating PKA/CREB signaling pathway, which might be mainly mediated by regulating the phosphorylation level of CREB.

Artificial Neural Network-Based Early-Age Concrete Strength Monitoring Using Dynamic Response Signals.

Science.gov (United States)

Kim, Junkyeong; Lee, Chaggil; Park, Seunghee

2017-06-07

Concrete is one of the most common materials used to construct a variety of civil infrastructures. However, since concrete might be susceptible to brittle fracture, it is essential to confirm the strength of concrete at the early-age stage of the curing process to prevent unexpected collapse. To address this issue, this study proposes a novel method to estimate the early-age strength of concrete, by integrating an artificial neural network algorithm with a dynamic response measurement of the concrete material. The dynamic response signals of the concrete, including both electromechanical impedances and guided ultrasonic waves, are obtained from an embedded piezoelectric sensor module. The cross-correlation coefficient of the electromechanical impedance signals and the amplitude of the guided ultrasonic wave signals are selected to quantify the variation in dynamic responses according to the strength of the concrete. Furthermore, an artificial neural network algorithm is used to verify a relationship between the variation in dynamic response signals and concrete strength. The results of an experimental study confirm that the proposed approach can be effectively applied to estimate the strength of concrete material from the early-age stage of the curing process.

Synthetic generation of myocardial blood-oxygen-level-dependent MRI time series via structural sparse decomposition modeling.

Science.gov (United States)

Rusu, Cristian; Morisi, Rita; Boschetto, Davide; Dharmakumar, Rohan; Tsaftaris, Sotirios A

2014-07-01

This paper aims to identify approaches that generate appropriate synthetic data (computer generated) for cardiac phase-resolved blood-oxygen-level-dependent (CP-BOLD) MRI. CP-BOLD MRI is a new contrast agent- and stress-free approach for examining changes in myocardial oxygenation in response to coronary artery disease. However, since signal intensity changes are subtle, rapid visualization is not possible with the naked eye. Quantifying and visualizing the extent of disease relies on myocardial segmentation and registration to isolate the myocardium and establish temporal correspondences and ischemia detection algorithms to identify temporal differences in BOLD signal intensity patterns. If transmurality of the defect is of interest pixel-level analysis is necessary and thus a higher precision in registration is required. Such precision is currently not available affecting the design and performance of the ischemia detection algorithms. In this work, to enable algorithmic developments of ischemia detection irrespective to registration accuracy, we propose an approach that generates synthetic pixel-level myocardial time series. We do this by 1) modeling the temporal changes in BOLD signal intensity based on sparse multi-component dictionary learning, whereby segmentally derived myocardial time series are extracted from canine experimental data to learn the model; and 2) demonstrating the resemblance between real and synthetic time series for validation purposes. We envision that the proposed approach has the capacity to accelerate development of tools for ischemia detection while markedly reducing experimental costs so that cardiac BOLD MRI can be rapidly translated into the clinical arena for the noninvasive assessment of ischemic heart disease.

Differential Cellular Responses to Hedgehog Signalling in Vertebrates—What is the Role of Competence?

OpenAIRE

Clemens Kiecker; Anthony Graham; Malcolm Logan

2016-01-01

A surprisingly small number of signalling pathways generate a plethora of cellular responses ranging from the acquisition of multiple cell fates to proliferation, differentiation, morphogenesis and cell death. These diverse responses may be due to the dose-dependent activities of signalling factors, or to intrinsic differences in the response of cells to a given signal—a phenomenon called differential cellular competence. In this review, we focus on temporal and spatial differences in compete...

Effects of Tasks on BOLD Signal Responses to Sentence Contrasts: Review and Commentary

Science.gov (United States)

Caplan, David; Gow, David

2012-01-01

Functional neuroimaging studies of syntactic processing have been interpreted as identifying the neural locations of parsing and interpretive operations. However, current behavioral studies of sentence processing indicate that many operations occur simultaneously with parsing and interpretation. In this review, we point to issues that arise in…

Volatile-Mediated within-Plant Signaling in Hybrid Aspen: Required for Systemic Responses.

Science.gov (United States)

Li, Tao; Blande, James D

2017-04-01

Plant volatiles play crucial roles in signaling between plants and their associated community members, but their role in within-plant signaling remains largely unexplored, particularly under field conditions. Using a system comprising the hybrid aspen (Populus tremula x tremuloides) and the specialized herbivorous leaf beetle (Phratora laticollis) and, combining field, greenhouse and laboratory experiments, we examined whether local damage triggered systemic responses in undamaged branches that lack vascular connection to the damaged branches, and to what extent this was caused by airborne volatile signals versus internal signals. An experiment tracing dye through the vasculature of saplings revealed no downward movement of the dye from upper to lower branches, suggesting a lack of vascular connectivity among branches. However, we found under both field and laboratory conditions that herbivore feeding on upper branches elicited volatile emissions by undamaged lower branches. Greenhouse experiments manipulating air contact between damaged and undamaged branches showed that systemic induction of volatiles was almost eliminated when air contact was interrupted. Our findings clearly demonstrate that herbivore-induced volatiles overcome vascular constraints and mediate within-plant signaling. Further, we found that volatile signaling led to induction of different classes of volatiles under field and environment controlled conditions, with a weaker response observed in the field. This difference not only reflects the dose- and time-dependent nature of volatile signaling, but also points out that future studies should focus more on field observations to better understand the ecological role of volatile-mediated within-plant signaling.

[Response of arbuscular mycorrhizal fungal lipid metabolism to symbiotic signals in mycorrhiza].

Science.gov (United States)

Tian, Lei; Li, Yuanjing; Tian, Chunjie

2016-01-04

Arbuscular mycorrhizal (AM) fungi play an important role in energy flow and nutrient cycling, besides their wide distribution in the cosystem. With a long co-evolution, AM fungi and host plant have formed a symbiotic relationship, and fungal lipid metabolism may be the key point to find the symbiotic mechanism in arbusculart mycorrhiza. Here, we reviewed the most recent progress on the interaction between AM fungal lipid metabolism and symbiotic signaling networks, especially the response of AM fungal lipid metabolism to symbiotic signals. Furthermore, we discussed the response of AM fungal lipid storage and release to symbiotic or non-symbiotic status, and the correlation between fungal lipid metabolism and nutrient transfer in mycorrhiza. In addition, we explored the feedback of the lipolysis process to molecular signals during the establishment of symbiosis, and the corresponding material conversion and energy metabolism besides the crosstalk of fungal lipid metabolism and signaling networks. This review will help understand symbiotic mechanism of arbuscular mycorrhiza fungi and further application in ecosystem.

Target of Rapamycin (TOR) Regulates Growth in Response to Nutritional Signals.

Science.gov (United States)

Weisman, Ronit

2016-10-01

All organisms can respond to the availability of nutrients by regulating their metabolism, growth, and cell division. Central to the regulation of growth in response to nutrient availability is the target of rapamycin (TOR) signaling that is composed of two structurally distinct complexes: TOR complex 1 (TORC1) and TOR complex 2 (TORC2). The TOR genes were first identified in yeast as target of rapamycin, a natural product of a soil bacterium, which proved beneficial as an immunosuppressive and anticancer drug and is currently being tested for a handful of other pathological conditions including diabetes, neurodegeneration, and age-related diseases. Studies of the TOR pathway unraveled a complex growth-regulating network. TOR regulates nutrient uptake, transcription, protein synthesis and degradation, as well as metabolic pathways, in a coordinated manner that ensures that cells grow or cease growth in response to nutrient availability. The identification of specific signals and mechanisms that stimulate TOR signaling is an active and exciting field of research that has already identified nitrogen and amino acids as key regulators of TORC1 activity. The signals, as well as the cellular functions of TORC2, are far less well understood. Additional open questions in the field concern the relationships between TORC1 and TORC2, as well as the links with other nutrient-responsive pathways. Here I review the main features of TORC1 and TORC2, with a particular focus on yeasts as model organisms.

Affective neural response to restricted interests in autism spectrum disorders.

Science.gov (United States)

Cascio, Carissa J; Foss-Feig, Jennifer H; Heacock, Jessica; Schauder, Kimberly B; Loring, Whitney A; Rogers, Baxter P; Pryweller, Jennifer R; Newsom, Cassandra R; Cockhren, Jurnell; Cao, Aize; Bolton, Scott

2014-01-01

Restricted interests are a class of repetitive behavior in autism spectrum disorders (ASD) whose intensity and narrow focus often contribute to significant interference with daily functioning. While numerous neuroimaging studies have investigated executive circuits as putative neural substrates of repetitive behavior, recent work implicates affective neural circuits in restricted interests. We sought to explore the role of affective neural circuits and determine how restricted interests are distinguished from hobbies or interests in typical development. We compared a group of children with ASD to a typically developing (TD) group of children with strong interests or hobbies, employing parent report, an operant behavioral task, and functional imaging with personalized stimuli based on individual interests. While performance on the operant task was similar between the two groups, parent report of intensity and interference of interests was significantly higher in the ASD group. Both the ASD and TD groups showed increased BOLD response in widespread affective neural regions to the pictures of their own interest. When viewing pictures of other children's interests, the TD group showed a similar pattern, whereas BOLD response in the ASD group was much more limited. Increased BOLD response in the insula and anterior cingulate cortex distinguished the ASD from the TD group, and parent report of the intensity and interference with daily life of the child's restricted interest predicted insula response. While affective neural network response and operant behavior are comparable in typical and restricted interests, the narrowness of focus that clinically distinguishes restricted interests in ASD is reflected in more interference in daily life and aberrantly enhanced insula and anterior cingulate response to individuals' own interests in the ASD group. These results further support the involvement of affective neural networks in repetitive behaviors in ASD. © 2013 The

Assessing denoising strategies to increase signal to noise ratio in spinal cord and in brain cortical and subcortical regions

Science.gov (United States)

Maugeri, L.; Moraschi, M.; Summers, P.; Favilla, S.; Mascali, D.; Cedola, A.; Porro, C. A.; Giove, F.; Fratini, M.

2018-02-01

Functional Magnetic Resonance Imaging (fMRI) based on Blood Oxygenation Level Dependent (BOLD) contrast has become one of the most powerful tools in neuroscience research. On the other hand, fMRI approaches have seen limited use in the study of spinal cord and subcortical brain regions (such as the brainstem and portions of the diencephalon). Indeed obtaining good BOLD signal in these areas still represents a technical and scientific challenge, due to poor control of physiological noise and to a limited overall quality of the functional series. A solution can be found in the combination of optimized experimental procedures at acquisition stage, and well-adapted artifact mitigation procedures in the data processing. In this framework, we studied two different data processing strategies to reduce physiological noise in cortical and subcortical brain regions and in the spinal cord, based on the aCompCor and RETROICOR denoising tools respectively. The study, performed in healthy subjects, was carried out using an ad hoc isometric motor task. We observed an increased signal to noise ratio in the denoised functional time series in the spinal cord and in the subcortical brain region.

Short repetition time multiband echo-planar imaging with simultaneous pulse recording allows dynamic imaging of the cardiac pulsation signal.

Science.gov (United States)

Tong, Yunjie; Hocke, Lia M; Frederick, Blaise deB

2014-11-01

Recently developed simultaneous multislice echo-planar imaging (EPI) sequences permit imaging of the whole brain at short repetition time (TR), allowing the cardiac fluctuations to be fully sampled in blood-oxygen-level dependent functional MRI (BOLD fMRI). A novel low computational analytical method was developed to dynamically map the passage of the pulsation signal through the brain and visualize the whole cerebral vasculature affected by the pulse signal. This algorithm is based on a simple combination of fast BOLD fMRI and the scanner's own built-in pulse oximeter. Multiple, temporally shifted copies of the pulse oximeter data (with 0.08 s shifting step and coverage of a 1-s span) were downsampled and used as cardiac pulsation regressors in a general linear model based analyses (FSL) of the fMRI data. The resulting concatenated z-statistics maps show the voxels that are affected as the cardiac signal travels through the brain. Many voxels were highly correlated with the pulsation regressor or its temporally shifted version. The dynamic and static cardiac pulsation maps obtained from both the task and resting state scans, resembled cerebral vasculature. The results demonstrated: (i) cardiac pulsation significantly affects most voxels in the brain; (ii) combining fast fMRI and this analytical method can reveal additional clinical information to functional studies. Copyright © 2013 Wiley Periodicals, Inc.

Equivalent dose determination in foraminifera: analytical description of the CO2--signal dose-response curve

International Nuclear Information System (INIS)

Hoffmann, D.; Woda, C.; Mangini, A.

2003-01-01

The dose-response of the CO 2 - signal (g=2.0006) in foraminifera with ages between 19 and 300 ka is investigated. The sum of two exponential saturation functions is an adequate function to describe the dose-response curve up to an additional dose of 8000 Gy. It yields excellent dating results but requires an artificial doses of at least 5000 Gy. For small additional doses of about 500 Gy the single exponential saturation function can be used to calculate a reliable equivalent dose D E , although it does not describ the dose-response for higher doses. The CO 2 - -signal dose-response indicates that the signal has two components of which one is less stable than the other

Ethylene signaling renders the jasmonate response of Arabidopsis insensitive to future suppression by salicylic Acid.

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Leon-Reyes, Antonio; Du, Yujuan; Koornneef, Annemart; Proietti, Silvia; Körbes, Ana P; Memelink, Johan; Pieterse, Corné M J; Ritsema, Tita

2010-02-01

Cross-talk between jasmonate (JA), ethylene (ET), and Salicylic acid (SA) signaling is thought to operate as a mechanism to fine-tune induced defenses that are activated in response to multiple attackers. Here, 43 Arabidopsis genotypes impaired in hormone signaling or defense-related processes were screened for their ability to express SA-mediated suppression of JA-responsive gene expression. Mutant cev1, which displays constitutive expression of JA and ET responses, appeared to be insensitive to SA-mediated suppression of the JA-responsive marker genes PDF1.2 and VSP2. Accordingly, strong activation of JA and ET responses by the necrotrophic pathogens Botrytis cinerea and Alternaria brassicicola prior to SA treatment counteracted the ability of SA to suppress the JA response. Pharmacological assays, mutant analysis, and studies with the ET-signaling inhibitor 1-methylcyclopropene revealed that ET signaling renders the JA response insensitive to subsequent suppression by SA. The APETALA2/ETHYLENE RESPONSE FACTOR transcription factor ORA59, which regulates JA/ET-responsive genes such as PDF1.2, emerged as a potential mediator in this process. Collectively, our results point to a model in which simultaneous induction of the JA and ET pathway renders the plant insensitive to future SA-mediated suppression of JA-dependent defenses, which may prioritize the JA/ET pathway over the SA pathway during multi-attacker interactions.

The Yeast Retrograde Response as a Model of Intracellular Signaling of Mitochondrial Dysfunction

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S. Michal eJazwinski

2012-05-01

Full Text Available Mitochondrial dysfunction activates intracellular signaling pathways that impact yeast longevity, and the best known of these pathways is the retrograde response. More recently, similar responses have been discerned in other systems, from invertebrates to human cells. However, the identity of the signal transducers is either unknown or apparently diverse, contrasting with the well-established signaling module of the yeast retrograde response. On the other hand, it has become equally clear that several other pathways and processes interact with the retrograde response, embedding it in a network responsive to a variety of cellular states. An examination of this network supports the notion that the master regulator NFkB aggregated a variety of mitochondria-related cellular responses at some point in evolution and has become the retrograde transcription factor. This has significant consequences for how we view some of the deficits associated with aging, such as inflammation. The support for NFkB as the retrograde response transcription factor is not only based on functional analyses. It is bolstered by the fact that NFkB can regulate Myc-Max, which is activated in human cells with dysfunctional mitochondria and impacts cellular metabolism. Myc-Max is homologous to the yeast retrograde response transcription factor Rtg1-Rtg3. Further research will be needed to disentangle the pro-aging from the anti-aging effects of NFkB. Interestingly, this is also a challenge for the complete understanding of the yeast retrograde response.

Stat5 signaling specifies basal versus stress erythropoietic responses through distinct binary and graded dynamic modalities.

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Ermelinda Porpiglia

2012-08-01

Full Text Available Erythropoietin (Epo-induced Stat5 phosphorylation (p-Stat5 is essential for both basal erythropoiesis and for its acceleration during hypoxic stress. A key challenge lies in understanding how Stat5 signaling elicits distinct functions during basal and stress erythropoiesis. Here we asked whether these distinct functions might be specified by the dynamic behavior of the Stat5 signal. We used flow cytometry to analyze Stat5 phosphorylation dynamics in primary erythropoietic tissue in vivo and in vitro, identifying two signaling modalities. In later (basophilic erythroblasts, Epo stimulation triggers a low intensity but decisive, binary (digital p-Stat5 signal. In early erythroblasts the binary signal is superseded by a high-intensity graded (analog p-Stat5 response. We elucidated the biological functions of binary and graded Stat5 signaling using the EpoR-HM mice, which express a "knocked-in" EpoR mutant lacking cytoplasmic phosphotyrosines. Strikingly, EpoR-HM mice are restricted to the binary signaling mode, which rescues these mice from fatal perinatal anemia by promoting binary survival decisions in erythroblasts. However, the absence of the graded p-Stat5 response in the EpoR-HM mice prevents them from accelerating red cell production in response to stress, including a failure to upregulate the transferrin receptor, which we show is a novel stress target. We found that Stat5 protein levels decline with erythroblast differentiation, governing the transition from high-intensity graded signaling in early erythroblasts to low-intensity binary signaling in later erythroblasts. Thus, using exogenous Stat5, we converted later erythroblasts into high-intensity graded signal transducers capable of eliciting a downstream stress response. Unlike the Stat5 protein, EpoR expression in erythroblasts does not limit the Stat5 signaling response, a non-Michaelian paradigm with therapeutic implications in myeloproliferative disease. Our findings show how the

Macrophage CGI-58 Attenuates Inflammatory Responsiveness via Promotion of PPARγ Signaling

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Dan Yang

2016-02-01

Full Text Available Background/Aims: Comparative gene identification-58 (CGI-58, an adipose triglyceride lipase (ATGL coactivator, strongly promotes ATGL-mediated triglyceride (TG catabolism. Beyond its function in promoting lipolysis, other features of CGI-58 have been proposed. Here, we investigated the role of CGI-58 in the regulation of inflammatory responsiveness in macrophages. Methods: Macrophage-specific GCI-58 transgenic mice (TG and wild type mice (WT were fed a high fat diet (HFD, and RAW264.7 cells were treated with lipopolysaccharide (LPS. The peroxisome proliferator-activated receptor (PPAR signaling was detected. The inflammatory responsiveness and mitochondrial function were examined. Results: TG mice showed lower serum levels of proinflammatory cytokines and better mitochondrial function in macrophages compared with WT control. Knockdown of CGI-58 in RAW264.7 cells aggravated LPS-induced inflammation and mitochondrial dysfunction. CGI-58 overexpression and silencing in macrophages induced and inhibited PPARγ expression and activity, respectively. Most importantly, the PPARγ-specific agonist rosiglitazone significantly suppressed inflammation and mitochondrial dysfunction induced by CGI-58 deficiency. Furthermore, knockdown of PPARγ in macrophages significantly dampened the role of CGI-58 in suppression of inflammation and mitochondrial dysfunction. Interestingly, CGI-58 inhibited histone deacetylation and the recruitment of histone deacetylase (HDAC to the PPARγ promoter. Finally, ATGL deficiency did not affect inflammatory responsiveness and PPARγ signaling in macrophages. Conclusion: These results demonstrate that macrophage CGI-58 enhances PPARγ signaling and thus suppresses inflammatory responsiveness and mitochondrial dysfunction.

Responses to olfactory signals reflect network structure of flower-visitor interactions.

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Junker, Robert R; Höcherl, Nicole; Blüthgen, Nico

2010-07-01

1. Network analyses provide insights into the diversity and complexity of ecological interactions and have motivated conclusions about community stability and co-evolution. However, biological traits and mechanisms such as chemical signals regulating the interactions between individual species--the microstructure of a network--are poorly understood. 2. We linked the responses of receivers (flower visitors) towards signals (flower scent) to the structure of a highly diverse natural flower-insect network. For each interaction, we define link temperature--a newly developed metric--as the deviation of the observed interaction strength from neutrality, assuming that animals randomly interact with flowers. 3. Link temperature was positively correlated to the specific visitors' responses to floral scents, experimentally examined in a mobile olfactometer. Thus, communication between plants and consumers via phytochemical signals reflects a significant part of the microstructure in a complex network. Negative as well as positive responses towards floral scents contributed to these results, where individual experience was important apart from innate behaviour. 4. Our results indicate that: (1) biological mechanisms have a profound impact on the microstructure of complex networks that underlies the outcome of aggregate statistics, and (2) floral scents act as a filter, promoting the visitation of some flower visitors, but also inhibiting the visitation of others.

Consistency in boldness, activity and exploration at different stages of life

Science.gov (United States)

2013-01-01

Background Animals show consistent individual behavioural patterns over time and over situations. This phenomenon has been referred to as animal personality or behavioural syndromes. Little is known about consistency of animal personalities over entire life times. We investigated the repeatability of behaviour in common voles (Microtus arvalis) at different life stages, with different time intervals, and in different situations. Animals were tested using four behavioural tests in three experimental groups: 1. before and after maturation over three months, 2. twice as adults during one week, and 3. twice as adult animals over three months, which resembles a substantial part of their entire adult life span of several months. Results Different behaviours were correlated within and between tests and a cluster analysis showed three possible behavioural syndrome-axes, which we name boldness, exploration and activity. Activity and exploration behaviour in all tests was highly repeatable in adult animals tested over one week. In animals tested over maturation, exploration behaviour was consistent whereas activity was not. Voles that were tested as adults with a three-month interval showed the opposite pattern with stable activity but unstable exploration behaviour. Conclusions The consistency in behaviour over time suggests that common voles do express stable personality over short time. Over longer periods however, behaviour is more flexible and depending on life stage (i.e. tested before/after maturation or as adults) of the tested individual. Level of boldness or activity does not differ between tested groups and maintenance of variation in behavioural traits can therefore not be explained by expected future assets as reported in other studies. PMID:24314274

Dissociation between unconscious motor response facilitation and conflict in medial frontal areas.

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D'Ostilio, Kevin; Garraux, Gaëtan

2012-01-01

Masked prime tasks have shown that sensory information that has not been consciously perceived can nevertheless modulate behavior. The neuronal correlates of behavioral manifestations of visuomotor priming remain debated, particularly with respect to the distribution and direction (i.e. increase or decrease) of activity changes in medial frontal areas. Here, we predicted that these discrepant results could be accounted for by two automatic and unconscious processes embedded in this task: response conflict and facilitation. We used event-related functional magnetic resonance imaging (fMRI), as 24 healthy participants had to respond, as fast as possible, to a target arrow presented immediately after a subliminal masked prime arrow. There were three experimental conditions defined by the prime-target relationship: compatible, incompatible, and neutral. The classical visuomotor priming effect was reproduced, with relatively longer reaction times (RTs) in incompatible trials. Longer RTs in incompatible than in neutral trials were specifically associated with stronger blood oxygen level-dependent (BOLD) activity in a conflict-related network comprising the anterior cingulate cortex and right frontal associative areas. Motor response facilitation as shown by shorter RTs in compatible than in neutral trials was associated with reduced activation in a motor preparation network including the medial and lateral premotor cortices, as a result of the repetition suppression of the fMRI BOLD signal. The present results provide new insights into automatic and unconscious visuomotor priming processes, suggesting an involvement of either a cognitive or motor network, depending on the prime-target relationship. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Estrogen signalling and the DNA damage response in hormone dependent breast cancers

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C Elizabeth Caldon

2014-05-01

Full Text Available Estrogen is necessary for the normal growth and development of breast tissue, but high levels of estrogen are a major risk factor for breast cancer. One mechanism by which estrogen could contribute to breast cancer is via the induction of DNA damage. This perspective discusses the mechanisms by which estrogen alters the DNA damage response (DDR and DNA repair through the regulation of key effector proteins including ATM, ATR, CHK1, BRCA1 and p53 and the feedback on estrogen receptor signalling from these proteins. We put forward the hypothesis that estrogen receptor signalling converges to suppress effective DNA repair and apoptosis in favour of proliferation. This is important in hormone-dependent breast cancer as it will affect processing of estrogen-induced DNA damage, as well as other genotoxic insults. DDR and DNA repair proteins are frequently mutated or altered in estrogen responsive breast cancer which will further change the processing of DNA damage. Finally the action of estrogen signalling on DNA damage is also relevant to the therapeutic setting as the suppression of a DNA damage response by estrogen has the potential to alter the response of cancers to anti-hormone treatment or chemotherapy that induces DNA damage.

Amphetamine sensitization alters reward processing in the human striatum and amygdala.

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Owen G O'Daly

Full Text Available Dysregulation of mesolimbic dopamine transmission is implicated in a number of psychiatric illnesses characterised by disruption of reward processing and goal-directed behaviour, including schizophrenia, drug addiction and impulse control disorders associated with chronic use of dopamine agonists. Amphetamine sensitization (AS has been proposed to model the development of this aberrant dopamine signalling and the subsequent dysregulation of incentive motivational processes. However, in humans the effects of AS on the dopamine-sensitive neural circuitry associated with reward processing remains unclear. Here we describe the effects of acute amphetamine administration, following a sensitising dosage regime, on blood oxygen level dependent (BOLD signal in dopaminoceptive brain regions during a rewarded gambling task performed by healthy volunteers. Using a randomised, double-blind, parallel-groups design, we found clear evidence for sensitization to the subjective effects of the drug, while rewarded reaction times were unchanged. Repeated amphetamine exposure was associated with reduced dorsal striatal BOLD signal during decision making, but enhanced ventromedial caudate activity during reward anticipation. The amygdala BOLD response to reward outcomes was blunted following repeated amphetamine exposure. Positive correlations between subjective sensitization and changes in anticipation- and outcome-related BOLD signal were seen for the caudate nucleus and amygdala, respectively. These data show for the first time in humans that AS changes the functional impact of acute stimulant exposure on the processing of reward-related information within dopaminoceptive regions. Our findings accord with pathophysiological models which implicate aberrant dopaminergic modulation of striatal and amygdala activity in psychosis and drug-related compulsive disorders.

Effect of luminance contrast on BOLD-fMRI response in deaf and normal occipital visual cortex

International Nuclear Information System (INIS)

Xue Yanping; Zhai Renyou; Jiang Tao; Cui Yong; Zhou Tiangang; Rao Hengyi; Zhuo Yan

2002-01-01

Objective: To examine the effect of luminance contrast stimulus by using blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) within deaf occipital visual cortex, and to compare the distribution, extent, and intensity of activated areas between deaf subjects and normal hearing subjects. Methods: Twelve deaf subjects (average age 16.5) and 15 normal hearing subjects (average age 23.7) were stimulated by 4 kinds of luminance contrast (0.7, 2.2, 50.0, 180.0 lm). The fMRI data were collected on GE 1.5 T Signa Horizon LX MRI system and analyzed by AFNI to generate the activation map. Results: Responding to all 4 kinds of stimulus luminance contrast, all deaf and normal subjects showed significant activations in occipital visual cortex. For both deaf and normal subjects, the number of activated pixels increased significantly with increasing luminance contrast (F normal = 4.27, P deaf = 6.41, P 0.05). The local mean activation level for all activated pixels remained constant with increasing luminance contrast. However, there was an increase in the mean activation level for those activated pixels common to all trials as the stimulus luminance contrast was increased, but no significant difference was found within them (F normal = 0.79, P > 0.05; F deaf = 1.6, P > 0.05). Conclusion: The effect of luminance contrast on occipital visual cortex of deaf is similar to but somewhat higher than that of normal hearing subjects. In addition, it also proved that fMRI is a feasible method in the study of the deaf visual cortex

Identification of Voxels Confounded by Venous Signals Using Resting-State fMRI Functional Connectivity Graph Clustering

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Klaudius eKalcher

2015-12-01

Full Text Available Identifying venous voxels in fMRI datasets is important to increase the specificity of fMRI analyses to microvasculature in the vicinity of the neural processes triggering the BOLD response. This is, however, difficult to achieve in particular in typical studies where magnitude images of BOLD EPI are the only data available. In this study, voxelwise functional connectivity graphs were computed on minimally preprocessed low TR (333 ms multiband resting-state fMRI data, using both high positive and negative correlations to define edges between nodes (voxels. A high correlation threshold for binarization ensures that most edges in the resulting sparse graph reflect the high coherence of signals in medium to large veins. Graph clustering based on the optimization of modularity was then employed to identify clusters of coherent voxels in this graph, and all clusters of 50 or more voxels were then interpreted as corresponding to medium to large veins. Indeed, a comparison with SWI reveals that 75.6 ± 5.9% of voxels within these large clusters overlap with veins visible in the SWI image or lie outside the brain parenchyma. Some of the remainingdifferences between the two modalities can be explained by imperfect alignment or geometric distortions between the two images. Overall, the graph clustering based method for identifying venous voxels has a high specificity as well as the additional advantages of being computed in the same voxel grid as the fMRI dataset itself and not needingany additional data beyond what is usually acquired (and exported in standard fMRI experiments.

Astrocyte-to-neuron signaling in response to photostimulation with a femtosecond laser

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Zhao, Yuan; Liu, Xiuli; Zhou, Wei; Zeng, Shaoqun

2010-08-01

Conventional stimulation techniques used in studies of astrocyte-to-neuron signaling are invasive or dependent on additional electrical devices or chemicals. Here, we applied photostimulation with a femtosecond laser to selectively stimulate astrocytes in the hippocampal neural network, and the neuronal responses were examined. The results showed that, after photostimulation, cell-specific astrocyte-to-neuron signaling was triggered; sometimes the neuronal responses were even synchronous. Since photostimulation with a femtosecond laser is noninvasive, agent-free, and highly precise, this method has been proved to be efficient in activating astrocytes for investigations of astrocytic functions in neural networks.

Teacherpreneurs: a bold brand of teacher leadership for 21st-century teaching and learning.

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Berry, Barnett

2013-04-19

Challenges facing our public schools demand a bold brand of teacher leadership. Teacherpreneurs, effective teachers who teach students regularly but also incubate and execute the kinds of policies and pedagogies students deserve, represent a new culture of training and ingenuity. Teachers who lead outside the classroom but do not lose their connection to students are best positioned to develop and disseminate best policies and practices for 21st-century teaching and learning.

Linear ubiquitination signals in adaptive immune responses.

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Ikeda, Fumiyo

2015-07-01

Ubiquitin can form eight different linkage types of chains using the intrinsic Met 1 residue or one of the seven intrinsic Lys residues. Each linkage type of ubiquitin chain has a distinct three-dimensional topology, functioning as a tag to attract specific signaling molecules, which are so-called ubiquitin readers, and regulates various biological functions. Ubiquitin chains linked via Met 1 in a head-to-tail manner are called linear ubiquitin chains. Linear ubiquitination plays an important role in the regulation of cellular signaling, including the best-characterized tumor necrosis factor (TNF)-induced canonical nuclear factor-κB (NF-κB) pathway. Linear ubiquitin chains are specifically generated by an E3 ligase complex called the linear ubiquitin chain assembly complex (LUBAC) and hydrolyzed by a deubiquitinase (DUB) called ovarian tumor (OTU) DUB with linear linkage specificity (OTULIN). LUBAC linearly ubiquitinates critical molecules in the TNF pathway, such as NEMO and RIPK1. The linear ubiquitin chains are then recognized by the ubiquitin readers, including NEMO, which control the TNF pathway. Accumulating evidence indicates an importance of the LUBAC complex in the regulation of apoptosis, development, and inflammation in mice. In this article, I focus on the role of linear ubiquitin chains in adaptive immune responses with an emphasis on the TNF-induced signaling pathways. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Mindfulness meditation modulates reward prediction errors in the striatum in a passive conditioning task

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Ulrich eKirk

2015-02-01

Full Text Available Reinforcement learning models have demonstrated that phasic activity of dopamine neurons during reward expectation encodes information about the predictability of rewards and cues that predict reward. Evidence indicates that mindfulness-based approaches reduce reward anticipation signal in the striatum to negative and positive incentives suggesting the hypothesis that such training influence basic reward processing. Using a passive conditioning task and fMRI in a group of experienced mindfulness meditators and age-matched controls, we tested the hypothesis that mindfulness meditation influence reward and reward prediction error signals. We found diminished positive and negative prediction error-related blood-oxygen level-dependent (BOLD responses in the putamen in meditators compared with controls. In the meditators, this decrease in striatal BOLD responses to reward prediction was paralleled by increased activity in posterior insula, a primary interoceptive region. Critically, responses in the putamen during early trials of the conditioning procedure (run 1 were elevated in both meditators and controls. These results provide evidence that experienced mindfulness meditators show attenuated reward prediction signals to valenced stimuli, which may be related to interoceptive processes encoded in the posterior insula.

Transcriptional Profiling of the Oral Pathogen Streptococcus mutans in Response to Competence Signaling Peptide XIP.

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Wenderska, Iwona B; Latos, Andrew; Pruitt, Benjamin; Palmer, Sara; Spatafora, Grace; Senadheera, Dilani B; Cvitkovitch, Dennis G

2017-01-01

In the cariogenic Streptococcus mutans , competence development is regulated by the ComRS signaling system comprised of the ComR regulator and the ComS prepeptide to the competence signaling peptide XIP (ComX-inducing peptide). Aside from competence development, XIP signaling has been demonstrated to regulate cell lysis, and recently, the expression of bacteriocins, small antimicrobial peptides used by bacteria to inhibit closely related species. Our study further explores the effect of XIP signaling on the S. mutans transcriptome. RNA sequencing revealed that XIP induction resulted in a global change in gene expression that was consistent with a stress response. An increase in several membrane-bound regulators, including HdrRM and BrsRM, involved in bacteriocin production, and the VicRKX system, involved in acid tolerance and biofilm formation, was observed. Furthermore, global changes in gene expression corresponded to changes observed during the stringent response to amino acid starvation. Effects were also observed on genes involved in sugar transport and carbon catabolite repression and included the levQRST and levDEFG operons. Finally, our work identified a novel heat shock-responsive intergenic region, encoding a small RNA, with a potential role in competence shutoff. IMPORTANCE Genetic competence provides bacteria with an opportunity to increase genetic diversity or acquire novel traits conferring a survival advantage. In the cariogenic pathogen Streptococcus mutans , DNA transformation is regulated by the competence stimulating peptide XIP (ComX-inducing peptide). The present study utilizes high-throughput RNA sequencing (RNAseq) to provide a greater understanding of how global gene expression patterns change in response to XIP. Overall, our work demonstrates that in S. mutans , XIP signaling induces a response that resembles the stringent response to amino acid starvation. We further identify a novel heat shock-responsive intergenic region with a

Age-related adaptations of brain function during a memory task are also present at rest

NARCIS (Netherlands)

Filippini, N.; Nickerson, L.D.; Beckmann, Christian; Ebmeier, K.P.; Frisoni, G.B.; Matthews, P.M.; Smith, S.M.; Mackay, C.E.

2012-01-01

Several studies have demonstrated age-related regional differences in the magnitude of the BOLD signal using task-based fMRI. It has been suggested that functional changes reflect either compensatory or de-differentiation mechanisms, both of which assume response to a specific stimulus. Here, we

Ethylene signaling renders the jasmonate response of Arabidopsis insensitive to future suppression by salicylic acid

OpenAIRE

Leon Reyes, H.A.; Du, Y.; Koornneef, A.; Proietti, S.; Körbes, A.P.; Memelink, J.; Pieterse, C.M.J.; Ritsema, T.

2010-01-01

Cross-talk between jasmonate (JA), ethylene (ET), and Salicylic acid (SA) signaling is thought to operate as a mechanism to fine-tune induced defenses that are activated in response to multiple attackers. Here, 43 Arabidopsis genotypes impaired in hormone signaling or defense-related processes were screened for their ability to express SA-mediated suppression of JA-responsive gene expression. Mutant cev1, which displays constitutive expression of JA and ET responses, appeared to be insensitiv...

Evoked responses of the superior olive to amplitude-modulated signals.

Science.gov (United States)

Andreeva, N G; Lang, T T

1977-01-01

Evoked potentials of some auditory centers of Rhinolophidae bats to amplitude-modulated signals were studied. A synchronization response was found in the cochlear nuclei (with respect to the fast component of the response) and in the superior olivary complex (with respect to both fast and slow components of the response) within the range of frequency modulation from 50 to 2000 Hz. In the inferior colliculus a synchronized response was recorded at modulation frequencies below 150 Hz, but in the medial geniculate bodies no such response was found. Evoked responses of the superior olivary complex were investigated in detail. The lowest frequencies of synchronization were recorded within the carrier frequency range of 15-30 and 80-86 kHz. The amplitude of the synchronized response is a function of the frequency and coefficient of modulation and also of the angle of stimulus presentation.

Serotonergic Chemosensory Neurons Modify the C. elegans Immune Response by Regulating G-Protein Signaling in Epithelial Cells

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Anderson, Alexandra; Laurenson-Schafer, Henry; Partridge, Frederick A.; Hodgkin, Jonathan; McMullan, Rachel

2013-01-01

The nervous and immune systems influence each other, allowing animals to rapidly protect themselves from changes in their internal and external environment. However, the complex nature of these systems in mammals makes it difficult to determine how neuronal signaling influences the immune response. Here we show that serotonin, synthesized in Caenorhabditis elegans chemosensory neurons, modulates the immune response. Serotonin released from these cells acts, directly or indirectly, to regulate G-protein signaling in epithelial cells. Signaling in these cells is required for the immune response to infection by the natural pathogen Microbacterium nematophilum. Here we show that serotonin signaling suppresses the innate immune response and limits the rate of pathogen clearance. We show that C. elegans uses classical neurotransmitters to alter the immune response. Serotonin released from sensory neurons may function to modify the immune system in response to changes in the animal's external environment such as the availability, or quality, of food. PMID:24348250

Unemployment in chronic airflow obstruction around the world: results from the BOLD study.

Science.gov (United States)

Grønseth, Rune; Erdal, Marta; Tan, Wan C; Obaseki, Daniel O; Amaral, Andre F S; Gislason, Thorarinn; Juvekar, Sanjay K; Koul, Parvaiz A; Studnicka, Michael; Salvi, Sundeep; Burney, Peter; Buist, A Sonia; Vollmer, William M; Johannessen, Ane

2017-09-01

We aimed to examine associations between chronic airflow obstruction (CAO) and unemployment across the world.Cross-sectional data from 26 sites in the Burden of Obstructive Lung Disease (BOLD) study were used to analyse effects of CAO on unemployment. Odds ratios for unemployment in subjects aged 40-65 years were estimated using a multilevel mixed-effects generalised linear model with study site as random effect. Site-by-site heterogeneity was assessed using individual participant data meta-analyses.Out of 18 710 participants, 11.3% had CAO. The ratio of unemployed subjects with CAO divided by subjects without CAO showed large site discrepancies, although these were no longer significant after adjusting for age, sex, smoking and education. The site-adjusted odds ratio (95% CI) for unemployment was 1.79 (1.41-2.27) for CAO cases, decreasing to 1.43 (1.14-1.79) after adjusting for sociodemographic factors, comorbidities and forced vital capacity. Of other covariates that were associated with unemployment, age and education were important risk factors in high-income sites (4.02 (3.53-4.57) and 3.86 (2.80-5.30), respectively), while female sex was important in low- to middle-income sites (3.23 (2.66-3.91)).In the global BOLD study, CAO was associated with increased levels of unemployment, even after adjusting for sociodemographic factors, comorbidities and lung function. Copyright ©ERS 2017.

Brassinosteroid signaling-dependent root responses to prolonged elevated ambient temperature.

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Martins, Sara; Montiel-Jorda, Alvaro; Cayrel, Anne; Huguet, Stéphanie; Roux, Christine Paysant-Le; Ljung, Karin; Vert, Grégory

2017-08-21

Due to their sessile nature, plants have to cope with and adjust to their fluctuating environment. Temperature elevation stimulates the growth of Arabidopsis aerial parts. This process is mediated by increased biosynthesis of the growth-promoting hormone auxin. How plant roots respond to elevated ambient temperature is however still elusive. Here we present strong evidence that temperature elevation impinges on brassinosteroid hormone signaling to alter root growth. We show that elevated temperature leads to increased root elongation, independently of auxin or factors known to drive temperature-mediated shoot growth. We further demonstrate that brassinosteroid signaling regulates root responses to elevated ambient temperature. Increased growth temperature specifically impacts on the level of the brassinosteroid receptor BRI1 to downregulate brassinosteroid signaling and mediate root elongation. Our results establish that BRI1 integrates temperature and brassinosteroid signaling to regulate root growth upon long-term changes in environmental conditions associated with global warming.Moderate heat stimulates the growth of Arabidopsis shoots in an auxin-dependent manner. Here, Martins et al. show that elevated ambient temperature modifies root growth by reducing the BRI1 brassinosteroid-receptor protein level and downregulating brassinosteroid signaling.

Comparison of signaling interactions determining annual and perennial plant growth in response to low temperature

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Astrid eWingler

2015-01-01

Full Text Available Low temperature inhibits plant growth despite the fact that considerable rates of photosynthetic activity can be maintained. Instead of lower rates of photosynthesis, active inhibition of cell division and expansion is primarily responsible for reduced growth. This results in sink limitation and enables plants to accumulate carbohydrates that act as compatible solutes or are stored throughout the winter to enable re-growth in spring. Regulation of growth in response to temperature therefore requires coordination with carbon metabolism, e.g. via the signaling metabolite trehalose-6-phosphate. The phytohormones gibberellins (GA and jasmonate (JA play an important role in regulating growth in response to temperature. Growth restriction at low temperature is mainly mediated by DELLA proteins, whose degradation is promoted by GA. For annual plants, it has been shown that the GA/DELLA pathway interacts with JA signaling and C-repeat binding factor (CBF dependent cold acclimation, but these interactions have not been explored in detail for perennials. Growth regulation in response to seasonal factors is, however, particularly important in perennials, especially at high latitudes. In autumn, growth cessation in trees is caused by shortening of the daylength in interaction with phytohormone signaling. In perennial grasses seasonal differences in the sensitivity to GA may enable enhanced growth in spring. This review provides an overview of the signaling interactions that determine plant growth at low temperature and highlights gaps in our knowledge, especially concerning the seasonality of signaling responses in perennial plants.

Spatial-temporal-spectral EEG patterns of BOLD functional network connectivity dynamics

Science.gov (United States)

Lamoš, Martin; Mareček, Radek; Slavíček, Tomáš; Mikl, Michal; Rektor, Ivan; Jan, Jiří

2018-06-01

Objective. Growing interest in the examination of large-scale brain network functional connectivity dynamics is accompanied by an effort to find the electrophysiological correlates. The commonly used constraints applied to spatial and spectral domains during electroencephalogram (EEG) data analysis may leave part of the neural activity unrecognized. We propose an approach that blindly reveals multimodal EEG spectral patterns that are related to the dynamics of the BOLD functional network connectivity. Approach. The blind decomposition of EEG spectrogram by parallel factor analysis has been shown to be a useful technique for uncovering patterns of neural activity. The simultaneously acquired BOLD fMRI data were decomposed by independent component analysis. Dynamic functional connectivity was computed on the component’s time series using a sliding window correlation, and between-network connectivity states were then defined based on the values of the correlation coefficients. ANOVA tests were performed to assess the relationships between the dynamics of between-network connectivity states and the fluctuations of EEG spectral patterns. Main results. We found three patterns related to the dynamics of between-network connectivity states. The first pattern has dominant peaks in the alpha, beta, and gamma bands and is related to the dynamics between the auditory, sensorimotor, and attentional networks. The second pattern, with dominant peaks in the theta and low alpha bands, is related to the visual and default mode network. The third pattern, also with peaks in the theta and low alpha bands, is related to the auditory and frontal network. Significance. Our previous findings revealed a relationship between EEG spectral pattern fluctuations and the hemodynamics of large-scale brain networks. In this study, we suggest that the relationship also exists at the level of functional connectivity dynamics among large-scale brain networks when no standard spatial and spectral

The cellular response to vascular endothelial growth factors requires co-ordinated signal transduction, trafficking and proteolysis.

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Smith, Gina A; Fearnley, Gareth W; Tomlinson, Darren C; Harrison, Michael A; Ponnambalam, Sreenivasan

2015-08-18

VEGFs (vascular endothelial growth factors) are a family of conserved disulfide-linked soluble secretory glycoproteins found in higher eukaryotes. VEGFs mediate a wide range of responses in different tissues including metabolic homoeostasis, cell proliferation, migration and tubulogenesis. Such responses are initiated by VEGF binding to soluble and membrane-bound VEGFRs (VEGF receptor tyrosine kinases) and co-receptors. VEGF and receptor splice isoform diversity further enhances complexity of membrane protein assembly and function in signal transduction pathways that control multiple cellular responses. Different signal transduction pathways are simultaneously activated by VEGFR-VEGF complexes with membrane trafficking along the endosome-lysosome network further modulating signal output from multiple enzymatic events associated with such pathways. Balancing VEGFR-VEGF signal transduction with trafficking and proteolysis is essential in controlling the intensity and duration of different intracellular signalling events. Dysfunction in VEGF-regulated signal transduction is important in chronic disease states including cancer, atherosclerosis and blindness. This family of growth factors and receptors is an important model system for understanding human disease pathology and developing new therapeutics for treating such ailments. © 2015 Authors.

The effect of Rickia wasmannii (Ascomycota, Laboulbeniales on the aggression and boldness of Myrmica scabrinodis (Hymenoptera, Formicidae

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Ferenc Báthori

2017-08-01

Full Text Available The interactions of ectosymbiotic Laboulbeniales (Ascomycota fungi and their hosts are rather understudied. Rickia wasmannii Cavara is a common ant-associated Laboulbeniales species that has been reported in 17 countries of Europe, and frequently infects Myrmica scabrinodis Nylander, 1846 (Hymenoptera: Formicidae, a common ant species host, in high density. These make M. scabrinodis and R. wasmannii appropriate model organisms for studies on fungal host-ectosymbiont interactions. Aggressiveness and boldness of infected and uninfected M. scabrinodis workers from northern and eastern Hungary were studied in two laboratory-established behavioural experiments. Infected workers were significantly less aggressive and less bold (i.e. less likely to leave nest shelters than the uninfected ones. These results suggest that R. wasmannii has considerable effects on the behaviour of M. scabrinodis. Our study brings an evidence that infection of ants with Laboulbeniales might negatively affect the workers’ behaviour. In special, the competitive abilities might be affected most by these fungi, since remaining inside and behaving submissively is not effective behaviour in the case of significant competition for resources among colonies.

When BOLD is thicker than water: processing social information about kin and friends at different levels of the social network.

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Wlodarski, Rafael; Dunbar, Robin I M

2016-12-01

The aim of this study was to examine differences in the neural processing of social information about kin and friends at different levels of closeness and social network level. Twenty-five female participants engaged in a cognitive social task involving different individuals in their social network while undergoing functional magnetic resonance imaging scanning to detect BOLD (Blood Oxygen Level Dependent) signals changes. Greater levels of activation occurred in several regions of the brain previously associated with social cognition when thinking about friends than when thinking about kin, including the posterior cingulate cortex (PCC) and the ventral medial prefrontal cortex (vMPFC). Linear parametric analyses across network layers further showed that, when it came to thinking about friends, activation increased in the vMPFC, lingual gyrus, and sensorimotor cortex as individuals thought about friends at closer layers of the network. These findings suggest that maintaining friendships may be more cognitively exacting than maintaining kin relationships. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Interhemispheric differences of fMRI responses to visual stimuli in patients with side-fixed migraine aura

DEFF Research Database (Denmark)

Hougaard, Anders; Amin, Faisal Mohammad; Hoffmann, Michael B

2014-01-01

hemifield. We recruited 20 patients with frequent side-fixed visual aura attacks (≥90% of auras occurring in the same visual hemifield) and 20 age and sex matched healthy controls and compared the fMRI blood oxygenation level dependent (BOLD) responses to visual stimulation between symptomatic...... and asymptomatic hemispheres during the interictal phase and between migraine patients and controls. BOLD responses were selectively increased in the symptomatic hemispheres. This was found in the inferior parietal lobule (P = 0.002), the inferior frontal gyrus (P = 0.003), and the superior parietal lobule (P = 0.......017). The affected cortical areas comprise a visually driven functional network involved in oculomotor control, guidance of movement, motion perception, visual attention, and visual spatial memory. The patients also had significantly increased response in the same cortical areas when compared to controls (P

Radiation-induced adaptive response and intracellular signal transduction pathways

International Nuclear Information System (INIS)

Tachibana, Akira

2009-01-01

As an essential biological function, cells can sense the radiation even at low dose and respond to it, and which is one of bases of the radiation-induced adaptive response (AR) where effects caused by high dose radiation are reduced by prior exposure to low dose radiation (LDR). Here described are studies of AR in well established m5S cells on the intracellular signal transduction that involves sensing of LDR and transmitting of its signal within the cell network. The first signal for AR yielded by LDR on the cell membrane is exactly unknown though hydrogen peroxide and phorbol ester (PMA) can reportedly cause AR. As PMA activates protein kinase C (PKC) and its inhibitors suppress AR, participation of PKC in AR has been suggested and supported by studies showing PKCα activation by LDR. In addition, p38 mitogen-activated protein kinase (MAPK) is shown to participate in AR by those facts that the enzyme is activated by LDR, a p38 MAPK inhibitor suppresses AR, and PKC inhibitors suppress the enzyme activation, which also suggesting that the signaling from PKC to p38 MAPK can become operative by LDR. However, the possible reverse signaling is also suggested, and thus the activation of positive feedback mechanism is postulated in PKC/p38 MAPK/phospholipase δ1/ PKC pathway. Cells introduced with siRNA against Prkca gene (coding PKCs) produce reduced amount of the enzyme, particularly, of PKCα. In those cells, AR by 5 Gy X-ray is not observed and thereby PKCα is involved in AR. The signaling in AR is only partly elucidated at present as above, and more detailed studies including identification of more PKC subtypes and signaling to DNA repair system are considered necessary. (K.T.)

Reward acts as a signal to control delay-period activity in delayed-response tasks.

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Ichihara-Takeda, Satoe; Takeda, Kazuyoshi; Funahashi, Shintaro

2010-03-31

Prefrontal delay-period activity represents a neural mechanism for the active maintenance of information and needs to be controlled by some signal to appropriately operate working memory. To examine whether reward-delivery acts as this signal, the effects of delay-period activity in response to unexpected reward-delivery were examined by analyzing single-neuron activity recorded in the primate dorsolateral prefrontal cortex. Among neurons that showed delay-period activity, 34% showed inhibition of this activity in response to unexpected reward-delivery. The delay-period activity of these neurons was affected by the expectation of reward-delivery. The strength of the reward signal in controlling the delay-period activity is related to the strength of the effect of reward information on the delay-period activity. These results indicate that reward-delivery acts as a signal to control delay-period activity.

Hormone response element binding proteins: novel regulators of vitamin D and estrogen signaling.

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Lisse, Thomas S; Hewison, Martin; Adams, John S

2011-03-01

Insights from vitamin D-resistant New World primates and their human homologues as models of natural and pathological insensitivity to sterol/steroid action have uncovered a family of novel intracellular vitamin D and estrogen regulatory proteins involved in hormone action. The proteins, known as "vitamin D or estrogen response element-binding proteins", behave as potent cis-acting, transdominant regulators to inhibit steroid receptor binding to DNA response elements and is responsible for vitamin D and estrogen resistances. This set of interactors belongs to the heterogeneous nuclear ribonucleoprotein (hnRNP) family of previously known pre-mRNA-interacting proteins. This review provides new insights into the mechanism by which these novel regulators of signaling and metabolism can act to regulate responses to vitamin D and estrogen. In addition the review also describes other molecules that are known to influence nuclear receptor signaling through interaction with hormone response elements. Copyright © 2011 Elsevier Inc. All rights reserved.

Low prevalence of obstructive lung disease in a suburban population of Malaysia: A BOLD collaborative study.

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Loh, Li Cher; Rashid, Abdul; Sholehah, Siti; Gnatiuc, Louisa; Patel, Jaymini H; Burney, Peter

2016-08-01

As a Burden of Obstructive Lung Disease (BOLD) collaboration, we studied the prevalence of chronic obstructive pulmonary disease (COPD) and its associated risk factors in a suburban population in Malaysia. Nonhospitalized men or women of age ≥ 40 years from a Penang district were recruited by stratified simple random sampling. Participants completed detailed questionnaires on respiratory symptoms and exposure to COPD risk factors. Prebronchodilator and post-bronchodilator spirometry conducted was standardized across all international BOLD sites in device and data quality control. Of the 1218 individuals recruited for the study, 663 (340 men and 323 women) had complete questionnaire data and acceptable post-bronchodilator spirometry. The estimated population prevalence of Global Initiative for Chronic Obstructive Lung Disease (GOLD) ≥ stage I was 6.5% or 3.4% based on either fixed forced expiratory volume in 1 s/forced vital capacity ratio of population-based epidemiology data on COPD for Malaysia. Compared with other sites globally, our estimated population prevalence was relatively low. In addition to cigarette smoking, use of biomass fuel and exposure to dusty job represented significant risk to the development of COPD. © 2016 Asian Pacific Society of Respirology.

Nuclear and cytoplasmic signalling in the cellular response to ionising radiation

International Nuclear Information System (INIS)

Szumiel, Irena

2001-01-01

DNA is the universal primary target for ionising radiation; however, the cellular response is highly diversified not only by differential DNA repair ability. The monitoring system for the ionising radiation-inflicted DNA damage consists of 3 apparently independently acting enzymes which are activated by DNA breaks: two protein kinases, ATM (ataxia telangiectasia mutated) and DNA-PK (DNA-dependent protein kinase) and a poly(ADP-ribose) polymerase, PARP-1. These 3 enzymes are the source of alarm signals, which affect to various extents DNA repair, progression through the cell cycle and eventually the pathway to cell death. Their functions probably are partly overlapping. On the side of DNA repair their role consists in recruiting and/or activating the repair enzymes, as well as preventing illegitimate recombination of the damaged sites. A large part of the nuclear signalling pathway, including the integrating role of TP53 has been revealed. Two main signalling pathways start at the plasma membrane: the MAPK/ERK (mitogen and extracellular signal regulated protein kinase family) 'survival pathway' and the SAPK/JNK (stress-activated protein kinase/c-Jun N-terminal kinase) 'cell death pathway'. The balance between them is likely to determine the cell's fate. An additional important 'survival pathway' starts at the insulin-like growth factor type I receptor (IGF-IR), involves phosphoinositide- 3 kinase and Akt kinase and is targeted at inactivation of the pro-apoptotic BAD protein. Interestingly, over-expression of IGF-IR almost entirely abrogates the extreme radiation sensitivity of ataxia telangiectasia cells. When DNA break rejoining is impaired, the cell is unconditionally radiation sensitive. The fate of a repair-competent cell is determined by the time factor: the cell cycle arrest should be long enough to ensure the completion of repair. Incomplete repair or misrepair may be tolerated, when generation of the death signal is prevented. So, the character and timing

Brain activations related to saccadic response conflict are not sensitive to time on task

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Ewa eBeldzik

2015-12-01

Full Text Available Establishing a role of the dorsal medial frontal cortex in the performance monitoring and cognitive control has been a challenge to neuroscientists for the past decade. In light of recent findings, the conflict monitoring hypothesis has been elaborated to an action-outcome predictor theory. One of the findings that led to this re-evaluation was the fMRI study in which conflict-related brain activity was investigated in terms of the so-called time on task effect, i.e. a linear increase of the BOLD signal with longer response times. The aim of this study was to investigate brain regions involved in the processing of saccadic response conflict and to account for the time on task effect. A modified spatial cueing task was implemented in the event-related fMRI study with oculomotor responses. The results revealed several brain regions which show higher activity for incongruent trials in comparison to the congruent ones, including pre-supplementary motor area together with the frontal and parietal regions. Further analysis accounting for the effect of response time provided evidence that these brain activations were not sensitive to time on task but reflected purely the congruency effect.

Brain Activations Related to Saccadic Response Conflict are not Sensitive to Time on Task.

Science.gov (United States)

Beldzik, Ewa; Domagalik, Aleksandra; Oginska, Halszka; Marek, Tadeusz; Fafrowicz, Magdalena

2015-01-01

Establishing a role of the dorsal medial frontal cortex in the performance monitoring and cognitive control has been a challenge to neuroscientists for the past decade. In light of recent findings, the conflict monitoring hypothesis has been elaborated to an action-outcome predictor theory. One of the findings that led to this re-evaluation was the fMRI study in which conflict-related brain activity was investigated in terms of the so-called time on task effect, i.e., a linear increase of the BOLD signal with longer response times. The aim of this study was to investigate brain regions involved in the processing of saccadic response conflict and to account for the time on task effect. A modified spatial cueing task was implemented in the event-related fMRI study with oculomotor responses. The results revealed several brain regions which show higher activity for incongruent trials in comparison to the congruent ones, including pre-supplementary motor area together with the frontal and parietal regions. Further analysis accounting for the effect of response time provided evidence that these brain activations were not sensitive to time on task but reflected purely the congruency effect.

Simultaneous EEG/fMRI analysis of the resonance phenomena in steady-state visual evoked responses.

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Bayram, Ali; Bayraktaroglu, Zubeyir; Karahan, Esin; Erdogan, Basri; Bilgic, Basar; Ozker, Muge; Kasikci, Itir; Duru, Adil D; Ademoglu, Ahmet; Oztürk, Cengizhan; Arikan, Kemal; Tarhan, Nevzat; Demiralp, Tamer

2011-04-01

The stability of the steady-state visual evoked potentials (SSVEPs) across trials and subjects makes them a suitable tool for the investigation of the visual system. The reproducible pattern of the frequency characteristics of SSVEPs shows a global amplitude maximum around 10 Hz and additional local maxima around 20 and 40 Hz, which have been argued to represent resonant behavior of damped neuronal oscillators. Simultaneous electroencephalogram/functional magnetic resonance imaging (EEG/fMRI) measurement allows testing of the resonance hypothesis about the frequency-selective increases in SSVEP amplitudes in human subjects, because the total synaptic activity that is represented in the fMRI-Blood Oxygen Level Dependent (fMRI-BOLD) response would not increase but get synchronized at the resonance frequency. For this purpose, 40 healthy volunteers were visually stimulated with flickering light at systematically varying frequencies between 6 and 46 Hz, and the correlations between SSVEP amplitudes and the BOLD responses were computed. The SSVEP frequency characteristics of all subjects showed 3 frequency ranges with an amplitude maximum in each of them, which roughly correspond to alpha, beta and gamma bands of the EEG. The correlation maps between BOLD responses and SSVEP amplitude changes across the different stimulation frequencies within each frequency band showed no significant correlation in the alpha range, while significant correlations were obtained in the primary visual area for the beta and gamma bands. This non-linear relationship between the surface recorded SSVEP amplitudes and the BOLD responses of the visual cortex at stimulation frequencies around the alpha band supports the view that a resonance at the tuning frequency of the thalamo-cortical alpha oscillator in the visual system is responsible for the global amplitude maximum of the SSVEP around 10 Hz. Information gained from the SSVEP/fMRI analyses in the present study might be extrapolated to the

JAK/STAT signaling pathway-mediated immune response in silkworm (Bombyx mori) challenged by Beauveria bassiana.

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Geng, Tao; Lv, Ding-Ding; Huang, Yu-Xia; Hou, Cheng-Xiang; Qin, Guang-Xing; Guo, Xi-Jie

2016-12-20

Innate immunity was critical in insects defensive system and able to be induced by Janus kinase/signal transducer and activator of transcription cascade transduction (JAK/STAT) signaling pathway. Currently, it had been identified many JAK/STAT signaling pathway-related genes in silkworm, but little function was known on insect innate immunity. To explore the roles of JAK/STAT pathway in antifungal immune response in silkworm (Bombyx mori) against Beauveria bassiana infection, the expression patterns of B. mori C-type lectin 5 (BmCTL5) and genes encoding 6 components of JAK/STAT signaling pathway in silkworm challenged by B. bassiana were analyzed using quantitative real time PCR. Meanwhile the activation of JAK/STAT signaling pathway by various pathogenic micro-organisms and the affect of JAK/STAT signaling pathway inhibitors on antifungal activity in silkworm hemolymph was also detected. Moreover, RNAi assay of BmCTL5 and the affect on expression levels of signaling factors were also analyzed. We found that JAK/STAT pathway could be obviously activated in silkworm challenged with B. bassiana and had no response to bacteria and B. mori cytoplasmic polyhedrosis virus (BmCPV). However, the temporal expression patterns of JAK/STAT signaling pathway related genes were significantly different. B. mori downstream receptor kinase (BmDRK) might be a positive regulator of JAK/STAT signaling pathway in silkworm against B. bassiana infection. Moreover, antifungal activity assay showed that the suppression of JAK/STAT signaling pathway by inhibitors could significantly inhibit the antifungal activity in hemolymph and resulted in increased sensitivity of silkworm to B. bassiana infection, indicating that JAK/STAT signaling pathway might be involved in the synthesis and secretion of antifungal substances. The results of RNAi assays suggested that BmCTL5 might be one pattern recognition receptors for JAK/STAT signaling pathway in silkworm. These findings yield insights for better

Multivariate analysis of correlation between electrophysiological and hemodynamic responses during cognitive processing

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Kujala, Jan; Sudre, Gustavo; Vartiainen, Johanna; Liljeström, Mia; Mitchell, Tom; Salmelin, Riitta

2014-01-01

Animal and human studies have frequently shown that in primary sensory and motor regions the BOLD signal correlates positively with high-frequency and negatively with low-frequency neuronal activity. However, recent evidence suggests that this relationship may also vary across cortical areas. Detailed knowledge of the possible spectral diversity between electrophysiological and hemodynamic responses across the human cortex would be essential for neural-level interpretation of fMRI data and for informative multimodal combination of electromagnetic and hemodynamic imaging data, especially in cognitive tasks. We applied multivariate partial least squares correlation analysis to MEG–fMRI data recorded in a reading paradigm to determine the correlation patterns between the data types, at once, across the cortex. Our results revealed heterogeneous patterns of high-frequency correlation between MEG and fMRI responses, with marked dissociation between lower and higher order cortical regions. The low-frequency range showed substantial variance, with negative and positive correlations manifesting at different frequencies across cortical regions. These findings demonstrate the complexity of the neurophysiological counterparts of hemodynamic fluctuations in cognitive processing. PMID:24518260

ROS signaling and stomatal movement in plant responses to drought stress and pathogen attack.

Science.gov (United States)

Qi, Junsheng; Song, Chun-Peng; Wang, Baoshan; Zhou, Jianmin; Kangasjärvi, Jaakko; Zhu, Jian-Kang; Gong, Zhizhong

2018-04-16

Stomata, the pores formed by a pair of guard cells, are the main gateways for water transpiration and photosynthetic CO 2 exchange, as well as pathogen invasion in land plants. Guard cell movement is regulated by a combination of environmental factors including water status, light, CO 2 levels and pathogen attack, as well as endogenous signals such as abscisic acid and apoplastic reactive oxygen species (ROS). Under abiotic and biotic stress conditions, extracellular ROS are mainly produced by plasma membrane-localized NADPH oxidases, whereas intracellular ROS are produced in multiple organelles. These ROS form a sophisticated cellular signaling network, with the accumulation of apoplastic ROS an early hallmark of stomatal movement. Here, we review recent progress in understanding the molecular mechanisms of the ROS signaling network, primarily during drought stress and pathogen attack. We summarize the roles of apoplastic ROS in regulating stomatal movement, ABA and CO 2 signaling, and immunity responses. Finally, we discuss ROS accumulation and communication between organelles and cells. This information provides a conceptual framework for understanding how ROS signaling is integrated with various signaling pathways during plant responses to abiotic and biotic stress stimuli. This article is protected by copyright. All rights reserved.

Luminance and chromatic signals interact differently with melanopsin activation to control the pupil light response.

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Barrionuevo, Pablo A; Cao, Dingcai

2016-09-01

Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin. These cells receive afferent inputs from rods and cones, which provide inputs to the postreceptoral visual pathways. It is unknown, however, how melanopsin activation is integrated with postreceptoral signals to control the pupillary light reflex. This study reports human flicker pupillary responses measured using stimuli generated with a five-primary photostimulator that selectively modulated melanopsin, rod, S-, M-, and L-cone excitations in isolation, or in combination to produce postreceptoral signals. We first analyzed the light adaptation behavior of melanopsin activation and rod and cones signals. Second, we determined how melanopsin is integrated with postreceptoral signals by testing with cone luminance, chromatic blue-yellow, and chromatic red-green stimuli that were processed by magnocellular (MC), koniocellular (KC), and parvocellular (PC) pathways, respectively. A combined rod and melanopsin response was also measured. The relative phase of the postreceptoral signals was varied with respect to the melanopsin phase. The results showed that light adaptation behavior for all conditions was weaker than typical Weber adaptation. Melanopsin activation combined linearly with luminance, S-cone, and rod inputs, suggesting the locus of integration with MC and KC signals was retinal. The melanopsin contribution to phasic pupil responses was lower than luminance contributions, but much higher than S-cone contributions. Chromatic red-green modulation interacted with melanopsin activation nonlinearly as described by a "winner-takes-all" process, suggesting the integration with PC signals might be mediated by a postretinal site.

Integration of BOLD-fMRI and DTI into radiation treatment planning for high-grade gliomas located near the primary motor cortexes and corticospinal tracts

International Nuclear Information System (INIS)

Wang, Minglei; Ma, Hui; Wang, Xiaodong; Guo, Yanhong; Xia, Xinshe; Xia, Hechun; Guo, Yulin; Huang, Xueying; He, Hong; Jia, Xiaoxiong; Xie, Yan

2015-01-01

The main objective of this study was to evaluate the efficacy of integrating the blood oxygen level dependent functional magnetic resonance imaging (BOLD-fMRI) and diffusion tensor imaging (DTI) data into radiation treatment planning for high-grade gliomas located near the primary motor cortexes (PMCs) and corticospinal tracts (CSTs). A total of 20 patients with high-grade gliomas adjacent to PMCs and CSTs between 2012 and 2014 were recruited. The bilateral PMCs and CSTs were located in the normal regions without any overlapping with target volume of the lesions. BOLD-fMRI, DTI and conventional MRI were performed on patients (Karnofsky performance score ≥ 70) before radical radiotherapy treatment. Four different imaging studies were conducted in each patient: a planning computed tomography (CT), an anatomical MRI, a DTI and a BOLD-fMRI. For each case, three treatment plans (3DCRT, IMRT and IMRT-PMC&CST) were developed by 3 different physicists using the Pinnacle planning system. Our study has shown that there was no significant difference between the 3DCRT and IMRT plans in terms of dose homogeneity, but IMRT displayed better planning target volume (PTV) dose conformity. In addition, we have found that the Dmax and Dmean to the ipsilateral and contralateral PMC and CST regions were considerably decreased in IMRT-PMC&CST group (p < 0.001). In conclusion, integration of BOLD-fMRI and DTI into radiation treatment planning is feasible and beneficial. With the assistance of the above-described techniques, the bilateral PMCs and CSTs adjacent to the target volume could be clearly marked as OARs and spared during treatment

Cortical deactivation induced by visual stimulation in human slow-wave sleep

DEFF Research Database (Denmark)

Born, Alfred Peter; Law, Ian; Lund, Torben E

2002-01-01

. It is unresolved whether this negative BOLD response pattern is of developmental neurobiological origin particular to a given age or to a general effect of sleep or sedative drugs. To further elucidate this issue, we used fMRI and positron emission tomography (PET) to study the brain activation pattern during......It has previously been demonstrated that sleeping and sedated young children respond with a paradoxical decrease in the blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signal in the rostro-medial occipital visual cortex during visual stimulation...... visual stimulation in spontaneously sleeping adult volunteers. In five sleeping volunteers fMRI studies confirmed a robust signal decrease during stimulation in the rostro-medial occipital cortex. A similar relative decrease at the same location was found during visual stimulation...

Using fMRI to Detect Activation of the Cortical and Subcortical Auditory Centers: Development of a Standard Protocol for a Conventional 1.5-T MRI Scanner

International Nuclear Information System (INIS)

Tae, Woo Suk; Kim, Sam Soo; Lee, Kang Uk; Lee, Seung Hwan; Nam, Eui Cheol; Choi, Hyun Kyung

2009-01-01

We wanted to develop a standard protocol for auditory functional magnetic resonance imaging (fMRI) for detecting blood oxygenation level-dependent (BOLD) responses at the cortical and subcortical auditory centers with using a 1.5-T MRI scanner. Fourteen normal volunteers were enrolled in the study. The subjects were stimulated by four repetitions of 32 sec each with broadband white noise and silent period blocks as a run (34 echo planar images [EPIs]). Multiple regression analysis for the individual analysis and one-sample t-tests for the group analysis were applied (FDR, p <0.05). The auditory cortex was activated in most of the volunteers (left 100% and right 92.9% at an uncorrected p value <0.05, and left 92.9% and right 92.9% at an uncorreced p value <0.01). The cochlear nuclei (100%, 85.7%), inferior colliculi (71.4%, 64.3%), medial geniculate bodies (64.3%, 35.7%) and superior olivary complexes (35.7%, 35.7%) showed significant BOLD responses at uncorrected p values of <0.05 and p <0.01, respectively. On the group analysis, the cortical and subcortical auditory centers showed significant BOLD responses (FDR, p <0.05), except for the superior olivary complex. The signal intensity time courses of the auditory centers showed biphasic wave forms. We successfully visualized BOLD responses at the cortical and subcortical auditory centers using appropriate sound stimuli and an image acquisition method with a 1.5-T MRI scanner

Assessing signal-driven mechanism in neonates: brain responses to temporally and spectrally different sounds

Directory of Open Access Journals (Sweden)

Yasuyo eMinagawa-Kawai

2011-06-01

Full Text Available Past studies have found that in adults that acoustic properties of sound signals (such as fast vs. slow temporal features differentially activate the left and right hemispheres, and some have hypothesized that left-lateralization for speech processing may follow from left-lateralization to rapidly changing signals. Here, we tested whether newborns’ brains show some evidence of signal-specific lateralization responses using near-infrared spectroscopy (NIRS and auditory stimuli that elicits lateralized responses in adults, composed of segments that vary in duration and spectral diversity. We found significantly greater bilateral responses of oxygenated hemoglobin (oxy-Hb in the temporal areas for stimuli with a minimum segment duration of 21 ms, than stimuli with a minimum segment duration of 667 ms. However, we found no evidence for hemispheric asymmetries dependent on the stimulus characteristics. We hypothesize that acoustic-based functional brain asymmetries may develop throughout early infancy, and discuss their possible relationship with brain asymmetries for language.

Fructose downregulates miR-330 to induce renal inflammatory response and insulin signaling impairment: Attenuation by morin.

Science.gov (United States)

Gu, Ting-Ting; Song, Lin; Chen, Tian-Yu; Wang, Xing; Zhao, Xiao-Juan; Ding, Xiao-Qin; Yang, Yan-Zi; Pan, Ying; Zhang, Dong-Mei; Kong, Ling-Dong

2017-08-01

Fructose induces insulin resistance with kidney inflammation and injury. MicroRNAs are emerged as key regulators of insulin signaling. Morin has insulin-mimetic effect with the improvement of insulin resistance and kidney injury. This study investigated the protective mechanisms of morin against fructose-induced kidney injury, with particular focus on miR-330 expression change, inflammatory response, and insulin signaling impairment. miR-330, sphingosine kinase 1 (SphK1)/sphingosine-1-phosphate (S1P)/S1P receptor (S1PR)1/3 signaling, nuclear factor-κB (NF-κB)/NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome, and insulin signaling were detected in kidney cortex of fructose-fed rats and fructose-exposed HK-2 cells, respectively. Whether miR-330 mediated inflammatory response to affect insulin signaling was examined using SphK1 inhibitor, S1PR1/3 short interfering RNA, or miR-330 mimic/inhibitor, respectively. Fructose was found to downregulate miR-330 expression to increase SphK1/S1P/S1PR1/3 signaling, and then activate NF-κB/NLRP3 inflammasome to produce IL-1β, causing insulin signaling impairment. Moreover, morin upregulated miR-330 and partly attenuated inflammatory response and insulin signaling impairment to alleviate kidney injury. These findings suggest that morin protects against fructose-induced kidney insulin signaling impairment by upregulating miR-330 to reduce inflammatory response. Morin may be a potential therapeutic agent for the treatment of kidney injury associated with fructose-induced inflammation and insulin signaling impairment. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Noncanonical ATM Activation and Signaling in Response to Transcription-Blocking DNA Damage.

Science.gov (United States)

Marteijn, Jurgen A; Vermeulen, Wim; Tresini, Maria

2017-01-01

Environmental genotoxins and metabolic byproducts generate DNA lesions that can cause genomic instability and disrupt tissue homeostasis. To ensure genomic integrity, cells employ mechanisms that convert signals generated by stochastic DNA damage into organized responses, including activation of repair systems, cell cycle checkpoints, and apoptotic mechanisms. DNA damage response (DDR) signaling pathways coordinate these responses and determine cellular fates in part, by transducing signals that modulate RNA metabolism. One of the master DDR coordinators, the Ataxia Telangiectasia Mutated (ATM) kinase, has a fundamental role in mediating DNA damage-induced changes in mRNA synthesis. ATM acts by modulating a variety of RNA metabolic pathways including nascent RNA splicing, a process catalyzed by the spliceosome. Interestingly, ATM and the spliceosome influence each other's activity in a reciprocal manner by a pathway that initiates when transcribing RNA polymerase II (RNAPII) encounters DNA lesions that prohibit forward translocation. In response to stalling of RNAPII assembly of late-stage spliceosomes is disrupted resulting in increased splicing factor mobility. Displacement of spliceosomes from lesion-arrested RNA polymerases facilitates formation of R-loops between the nascent RNA and DNA adjacent to the transcription bubble. R-loops signal for noncanonical ATM activation which in quiescent cells occurs in absence of detectable dsDNA breaks. In turn, activated ATM signals to regulate spliceosome dynamics and AS genome wide.This chapter describes the use of fluorescence microscopy methods that can be used to evaluate noncanonical ATM activation by transcription-blocking DNA damage. First, we present an immunofluorescence-detection method that can be used to evaluate ATM activation by autophosphorylation, in fixed cells. Second, we present a protocol for Fluorescence Recovery After Photobleaching (FRAP) of GFP-tagged splicing factors, a highly sensitive and

Gamma-ray-induced bold seeded early maturing groundnut selections

International Nuclear Information System (INIS)

Manoharan, V.; Thangavelu, S.

1990-01-01

Full text: ''Chico'' is an early maturing (85-90 days) erect groundnut (Arachis hypogaea L.) genotype utilised in groundnut improvement to incorporate earliness in high yielding varieties. Though it has high shelling out-turn, its yield potential is low since it has small seeds. Mutation breeding was started with the objective of improving the seed size. In a preliminary experiment, dry seeds were treated with 20, 30, 40 or 50 kR of gamma rays. The M 1 generation was grown during the post rainy season of 1988-1989. The M 2 generation was planted as individual plant progeny rows during the rainy season of 1989. 105 progeny rows were studied, the total number of M 2 plants being 1,730. All the M 2 plants were harvested 90 days after sowing. Seven mutants with bold seed size were obtained. The mutants had 100 kernel weight ranging from 22.2 to 40.4 g compared to 21.1 g of control. The study is in progress. (author)

The octadecanoid signalling pathway in plants mediates a response to ultraviolet radiation

International Nuclear Information System (INIS)

Conconi, A.; Smerdon, M.J.; Howe, G.A.; Ryan, C.A.

1996-01-01

Many plant genes that respond to environmental and developmental changes are regulated by jasmonic acid, which is derived from linolenic acid via the octadecanoid pathway. Linolenic acid is an important fatty-acid constituent of membranes in most plant species and its intracellular levels increase in response to certain signals. Here we report that irradiation of tomato leaves with ultraviolet light induces the expression of several plant defensive genes that are normally activated through the octadecanoid pathway after wounding. The response to ultraviolet light is blocked by an inhibitor of the octadecanoid pathway and it does not occur in a tomato mutant defective in this pathway. The ultraviolet irradiation maximally induces the defence genes at levels where cyclobutane pyrimidine dimer formation, an indicator of DNA damage, is less than 0.2 dimers per gene. Our evidence indicates that this plant defence response to certain wavelengths of ultraviolet radiation requires the activation of the octadecanoid defence signalling pathway. (author)

The yeast Sks1p kinase signaling network regulates pseudohyphal growth and glucose response.

Directory of Open Access Journals (Sweden)

Cole Johnson

2014-03-01

Full Text Available The yeast Saccharomyces cerevisiae undergoes a dramatic growth transition from its unicellular form to a filamentous state, marked by the formation of pseudohyphal filaments of elongated and connected cells. Yeast pseudohyphal growth is regulated by signaling pathways responsive to reductions in the availability of nitrogen and glucose, but the molecular link between pseudohyphal filamentation and glucose signaling is not fully understood. Here, we identify the glucose-responsive Sks1p kinase as a signaling protein required for pseudohyphal growth induced by nitrogen limitation and coupled nitrogen/glucose limitation. To identify the Sks1p signaling network, we applied mass spectrometry-based quantitative phosphoproteomics, profiling over 900 phosphosites for phosphorylation changes dependent upon Sks1p kinase activity. From this analysis, we report a set of novel phosphorylation sites and highlight Sks1p-dependent phosphorylation in Bud6p, Itr1p, Lrg1p, Npr3p, and Pda1p. In particular, we analyzed the Y309 and S313 phosphosites in the pyruvate dehydrogenase subunit Pda1p; these residues are required for pseudohyphal growth, and Y309A mutants exhibit phenotypes indicative of impaired aerobic respiration and decreased mitochondrial number. Epistasis studies place SKS1 downstream of the G-protein coupled receptor GPR1 and the G-protein RAS2 but upstream of or at the level of cAMP-dependent PKA. The pseudohyphal growth and glucose signaling transcription factors Flo8p, Mss11p, and Rgt1p are required to achieve wild-type SKS1 transcript levels. SKS1 is conserved, and deletion of the SKS1 ortholog SHA3 in the pathogenic fungus Candida albicans results in abnormal colony morphology. Collectively, these results identify Sks1p as an important regulator of filamentation and glucose signaling, with additional relevance towards understanding stress-responsive signaling in C. albicans.

Bold Ideas for the 4th H in 4-H: Teen Identified Concerns and Actions

OpenAIRE

Virginia Brown; Bonnie Braun; JoAnne Leatherman

2015-01-01

This article summarizes a literature review; teen-identified health concerns and issues; and teen bold ideas for actions. Findings from the National 4-H Council and Molina Healthcare Teens Take on Health initiative are provided and implications for 4-H programming tied to the new Cooperative Extension National Framework for Health and Wellness are addressed. The article is intended as background for Extension educators, volunteers and administrators as they review the 4-H Healthy Living Missi...

Visual Working Memory Enhances the Neural Response to Matching Visual Input.

Science.gov (United States)

Gayet, Surya; Guggenmos, Matthias; Christophel, Thomas B; Haynes, John-Dylan; Paffen, Chris L E; Van der Stigchel, Stefan; Sterzer, Philipp

2017-07-12

Visual working memory (VWM) is used to maintain visual information available for subsequent goal-directed behavior. The content of VWM has been shown to affect the behavioral response to concurrent visual input, suggesting that visual representations originating from VWM and from sensory input draw upon a shared neural substrate (i.e., a sensory recruitment stance on VWM storage). Here, we hypothesized that visual information maintained in VWM would enhance the neural response to concurrent visual input that matches the content of VWM. To test this hypothesis, we measured fMRI BOLD responses to task-irrelevant stimuli acquired from 15 human participants (three males) performing a concurrent delayed match-to-sample task. In this task, observers were sequentially presented with two shape stimuli and a retro-cue indicating which of the two shapes should be memorized for subsequent recognition. During the retention interval, a task-irrelevant shape (the probe) was briefly presented in the peripheral visual field, which could either match or mismatch the shape category of the memorized stimulus. We show that this probe stimulus elicited a stronger BOLD response, and allowed for increased shape-classification performance, when it matched rather than mismatched the concurrently memorized content, despite identical visual stimulation. Our results demonstrate that VWM enhances the neural response to concurrent visual input in a content-specific way. This finding is consistent with the view that neural populations involved in sensory processing are recruited for VWM storage, and it provides a common explanation for a plethora of behavioral studies in which VWM-matching visual input elicits a stronger behavioral and perceptual response. SIGNIFICANCE STATEMENT Humans heavily rely on visual information to interact with their environment and frequently must memorize such information for later use. Visual working memory allows for maintaining such visual information in the mind

Frequency response testing at Experimental Breeder Reactor II using discrete-level periodic signals

International Nuclear Information System (INIS)

Rhodes, W.D.; Larson, H.A.

1990-01-01

The Experimental Breeder Reactor 2 (EBR-2) reactivity-to-power frequency-response function was measured with pseudo-random, discrete-level, periodic signals. The reactor power deviation was small with insignificant perturbation of normal operation and in-place irradiation experiments. Comparison of results with measured rod oscillator data and with theoretical predictions show good agreement. Moreover, measures of input signal quality (autocorrelation function and energy spectra) confirm the ability to enable this type of frequency response determination at EBR-2. Measurements were made with the pseudo-random binary sequence, quadratic residue binary sequence, pseudo-random ternary sequence, and the multifrequency binary sequence. 10 refs., 7 figs., 3 tabs

Ratio of dopamine synthesis capacity to D2 receptor availability in ventral striatum correlates with central processing of affective stimuli

International Nuclear Information System (INIS)

Kienast, Thorsten; Rapp, Michael; Siessmeier, Thomas; Buchholz, Hans G.; Schreckenberger, Mathias; Wrase, Jana; Heinz, Andreas; Braus, Dieter F.; Smolka, Michael N.; Mann, Karl; Roesch, Frank; Cumming, Paul; Gruender, Gerhard; Bartenstein, Peter

2008-01-01

Dopaminergic neurotransmission in the ventral striatum may interact with limbic processing of affective stimuli, whereas dorsal striatal dopaminergic neurotransmission can affect habitual processing of emotionally salient stimuli in the pre-frontal cortex. We investigated the dopaminergic neurotransmission in the ventral and dorsal striatum with respect to central processing of affective stimuli in healthy subjects. Subjects were investigated with positron emission tomography and [ 18 F]DOPA for measurements of dopamine synthesis capacity and [ 18 F]DMFP for estimation of dopamine D2 receptor binding potential. Functional magnetic resonance imaging was used to assess the blood-oxygen-level-dependent (BOLD) response to affective pictures, which was correlated with the ratio of [ 18 F]DOPA net influx constant K in app /[ 18 F]DMFP-binding potential (BP N D) in the ventral and dorsal striatum. The magnitude of the ratio in the ventral striatum was positively correlated with BOLD signal increases elicited by negative versus neutral pictures in the right medial frontal gyrus (BA10), right inferior parietal lobe and left post-central gyrus. In the dorsal striatum, the ratio was positively correlated with BOLD signal activation elicited by negative versus neutral stimuli in the left post-central gyrus. The BOLD signal elicited by positive versus neutral stimuli in the superior parietal gyrus was positively correlated with the dorsal and ventral striatal ratio. The correlations of the ratio in the ventral and dorsal striatum with processing of affective stimuli in the named cortical regions support the hypothesis that dopamine transmission in functional divisions of the striatum modulates processing of affective stimuli in specific cortical areas. (orig.)

Analysis of sensor impulse response effects on Cramèr–Rao lower bounds for signal parameter estimators

Directory of Open Access Journals (Sweden)

Ephraim S. Gower

2014-12-01

Full Text Available In this study, a generic analysis of sensor impulse response effects on linearly filtered channel noise is presented to illustrate the resulting variations to the Cramèr–Rao lower bounds (CRLBs of signal parameter estimators in signal processing and communication applications. The authors start by deriving the density function of a filtered signal, which is shown to be a mixture density, and hence the exact expressions for the mean and variance. Simulation results are used to confirm the derivations, which are then used to investigate the effects of impulse response length and variance, as well as channel noise length and variance effects on the resulting CRLBs. Results indicate that for non-zero-mean channel noise and impulse responses, the resulting mean of filtered noise can be relatively large causing adverse deviations to parameter estimations. The filtered noise variance is shown to be proportional to the impulse response energy, where for long duration of signal capture the CRLB is significantly increased.

Visible light communications using predistortion signal to enhance the response of passive optical receiver

Science.gov (United States)

Liu, Yang; Chen, Hung-Yu; Liang, Kevin; Wei, Liang-Yu; Chow, Chi-Wai; Yeh, Chien-Hung

2016-01-01

Traditional visible light communication (VLC) uses positive-intrinsic-negative photodiode (PD) or avalanche PD as the optical receivers (Rx). We demonstrate using a solar cell as the VLC Rx. The solar cell is flexible and low cost and converts the optical signal into an electrical signal directly without the need of external power supply. In addition to acting as the VLC passive Rx, the converted electrical signal from the solar cell can charge up the battery of the Rx nodes. Hence, the proposed scheme can be a promising candidate for the future Internet of Things network. However, a solar cell acting as a VLC Rx is very challenging, since the response of the solar cell is limited. Here, we propose and demonstrate using predistortion to significantly enhance the solar cell Rx response for the first time up to the authors' knowledge. Experimental results show that the response of the solar cell Rx is significantly enhanced; and the original 2-kHz detection bandwidth of the solar cell can be enhanced by 250 times for receiving 500-kbit/s VLC signal at a transmission distance of 1 m. The operation principle, the generated voltage by the solar cell, and the maximum data rates achieved at different transmission distances are also studied.

Cell responses to FGFR3 signalling: growth, differentiation and apoptosis

International Nuclear Information System (INIS)

L'Hote, Corine G.M.; Knowles, Margaret A.

2005-01-01

FGFR3 is a receptor tyrosine kinase (RTK) of the FGF receptor family, known to have a negative regulatory effect on long bone growth. Fgfr3 knockout mice display longer bones and, accordingly, most germline-activating mutations in man are associated with dwarfism. Somatically, some of the same activating mutations are associated with the human cancers multiple myeloma, cervical carcinoma and carcinoma of the bladder. How signalling through FGFR3 can lead to either chondrocyte apoptosis or cancer cell proliferation is not fully understood. Although FGFR3 can be expressed as two main splice isoforms (IIIb or IIIc), there is no apparent link with specific cell responses, which may rather be associated with the cell type or its differentiation status. Depending on cell type, differential activation of STAT proteins has been observed. STAT1 phosphorylation seems to be involved in inhibition of chondrocyte proliferation while activation of the ERK pathway inhibits chondrocyte differentiation and B-cell proliferation (as in multiple myeloma). The role of FGFR3 in epithelial cancers (bladder and cervix) is not known. Some of the cell specificity may arise via modulation of signalling by crosstalk with other signalling pathways. Recently, inhibition of the ERK pathway in achondroplastic mice has provided hope for an approach to the treatment of dwarfism. Further understanding of the ability of FGFR3 to trigger different responses depending on cell type and cellular context may lead to treatments for both skeletal dysplasias and cancer

A transfer function approach to the small-signal response of saturated semiconductor optical amplifiers

DEFF Research Database (Denmark)

Nielsen, Mads Lønstrup; Blumenthal, D. J.; Mørk, Jesper

2000-01-01

A theoretical analysis of the small-signal frequency response (SSFR) of a wavelength converter based on cross-gain modulation in a semiconductor optical amplifier with a finite waveguide loss is presented. We use a transfer function formalism to explain the resonant behavior of the frequency...... response. The limitations to the magnitude of the spectral overshoot are also accounted for. Operating with the data and CW signals in a co-propagating configuration, we End that the resonance only exists for a finite waveguide loss. In a counter-propagating scheme, a resonance can exist regardless...

Agreement and repeatability of vascular reactivity estimates based on a breath-hold task and a resting state scan.

Science.gov (United States)

Lipp, Ilona; Murphy, Kevin; Caseras, Xavier; Wise, Richard G

2015-06-01

FMRI BOLD responses to changes in neural activity are influenced by the reactivity of the vasculature. By complementing a task-related BOLD acquisition with a vascular reactivity measure obtained through breath-holding or hypercapnia, this unwanted variance can be statistically reduced in the BOLD responses of interest. Recently, it has been suggested that vascular reactivity can also be estimated using a resting state scan. This study aimed to compare three breath-hold based analysis approaches (block design, sine-cosine regressor and CO2 regressor) and a resting state approach (CO2 regressor) to measure vascular reactivity. We tested BOLD variance explained by the model and repeatability of the measures. Fifteen healthy participants underwent a breath-hold task and a resting state scan with end-tidal CO2 being recorded during both. Vascular reactivity was defined as CO2-related BOLD percent signal change/mmHg change in CO2. Maps and regional vascular reactivity estimates showed high repeatability when the breath-hold task was used. Repeatability and variance explained by the CO2 trace regressor were lower for the resting state data based approach, which resulted in highly variable measures of vascular reactivity. We conclude that breath-hold based vascular reactivity estimations are more repeatable than resting-based estimates, and that there are limitations with replacing breath-hold scans by resting state scans for vascular reactivity assessment. Copyright © 2015. Published by Elsevier Inc.

Rearing environment influences boldness and prey acquisition behavior, and brain and lens development of bull trout

Science.gov (United States)

Brignon, William R.; Pike, Martin M.; Ebbesson, Lars O.E.; Schaller, Howard A.; Peterson, James T.; Schreck, Carl B.

2018-01-01

Animals reared in barren captive environments exhibit different developmental trajectories and behaviors than wild counterparts. Hence, the captive phenotypes may influence the success of reintroduction and recovery programs for threatened and endangered species. We collected wild bull trout embryos from the Metolius River Basin, Oregon and reared them in differing environments to better understand how captivity affects the bull trout Salvelinus confluentusphenotype. We compared the boldness and prey acquisition behaviors and development of the brain and eye lens of bull trout reared in conventional barren and more structurally complex captive environments with that of wild fish. Wild fish and captive reared fish from complex habitats exhibited a greater level of boldness and prey acquisition ability, than fish reared in conventional captive environments. In addition, the eye lens of conventionally reared bull trout was larger than complex reared captive fish or same age wild fish. Interestingly, we detected wild fish had a smaller relative cerebellum than either captive reared treatment. Our results suggest that rearing fish in more complex captive environments can create a more wild-like phenotype than conventional rearing practices. A better understanding of the effects of captivity on the development and behavior of bull trout can inform rearing and reintroduction programs though prediction of the performance of released individuals.

Neurochemical responses to chromatic and achromatic stimuli in the human visual cortex.

Science.gov (United States)

Bednařík, Petr; Tkáč, Ivan; Giove, Federico; Eberly, Lynn E; Deelchand, Dinesh K; Barreto, Felipe R; Mangia, Silvia

2018-02-01

In the present study, we aimed at determining the metabolic responses of the human visual cortex during the presentation of chromatic and achromatic stimuli, known to preferentially activate two separate clusters of neuronal populations (called "blobs" and "interblobs") with distinct sensitivity to color or luminance features. Since blobs and interblobs have different cytochrome-oxidase (COX) content and micro-vascularization level (i.e., different capacities for glucose oxidation), different functional metabolic responses during chromatic vs. achromatic stimuli may be expected. The stimuli were optimized to evoke a similar load of neuronal activation as measured by the bold oxygenation level dependent (BOLD) contrast. Metabolic responses were assessed using functional 1 H MRS at 7 T in 12 subjects. During both chromatic and achromatic stimuli, we observed the typical increases in glutamate and lactate concentration, and decreases in aspartate and glucose concentration, that are indicative of increased glucose oxidation. However, within the detection sensitivity limits, we did not observe any difference between metabolic responses elicited by chromatic and achromatic stimuli. We conclude that the higher energy demands of activated blobs and interblobs are supported by similar increases in oxidative metabolism despite the different capacities of these neuronal populations.

Sensor response time calculation with no stationary signals from a Nuclear Power Plant

International Nuclear Information System (INIS)

Vela, O.; Vallejo, I.

1998-01-01

Protection systems in a Nuclear Power Plant have to response in a specific time fixed by design requirements. This time includes the event detection (sensor delay) and the actuation time system. This time is obtained in refuel simulating the physics event, which trigger the protection system, with an electric signal and measuring the protection system actuation time. Nowadays sensor delay is calculated with noise analysis techniques. The signals are measured in Control Room during the normal operation of the Plant, decreasing both the cost in time and personal radioactive exposure. The noise analysis techniques require stationary signals but normally the data collected are mixed with process signals that are no stationary. This work shows the signals processing to avoid no-stationary components using conventional filters and new wavelets analysis. (Author) 2 refs

Simultaneous fMRI-PET of the opioidergic pain system in human brain

DEFF Research Database (Denmark)

Wey, Hsiao-Ying; Catana, Ciprian; Hooker, Jacob M

2014-01-01

distinct components of the blood oxygenation level dependent (BOLD) fMRI signal has not yet been shown. We obtained sixteen fMRI-PET data sets from eight healthy volunteers. Each subject participated in randomized order in a pain scan and a control (nonpainful pressure) scan on the same day. Dynamic PET......MRI and PET provide complementary information for studying brain function. While the potential use of simultaneous MRI/PET for clinical diagnostic and disease staging has been demonstrated recently; the biological relevance of concurrent functional MRI-PET brain imaging to dissect neurochemically...... data were acquired with an opioid radioligand, [(11)C]diprenorphine, to detect endogenous opioid releases in response to pain. BOLD fMRI data were collected at the same time to capture hemodynamic responses. In this simultaneous human fMRI-PET imaging study, we show co-localized responses in thalamus...

Filter frequency response of time dependent signal using Laplace transform

Energy Technology Data Exchange (ETDEWEB)

Shestakov, Aleksei I. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2018-01-16

We analyze the effect a filter has on a time dependent signal x(t). If X(s) is the Laplace transform of x and H (s) is the filter Transfer function, the response in frequency space is X (s) H (s). Consequently, in real space, the response is the convolution (x*h) (t), where hi is the Laplace inverse of H. Effects are analyzed and analytically for functions such as (t/t_c)² e^-t/t$_c$, where t_c = const. We consider lowpass, highpass and bandpass filters.

Phospholipase D and phosphatidic acid in plant defence response: from protein–protein and lipid–protein interactions to hormone signalling

Science.gov (United States)

Zhao, Jian

2015-01-01

Phospholipase Ds (PLDs) and PLD-derived phosphatidic acids (PAs) play vital roles in plant hormonal and environmental responses and various cellular dynamics. Recent studies have further expanded the functions of PLDs and PAs into plant–microbe interaction. The molecular diversities and redundant functions make PLD–PA an important signalling complex regulating lipid metabolism, cytoskeleton dynamics, vesicle trafficking, and hormonal signalling in plant defence through protein–protein and protein–lipid interactions or hormone signalling. Different PLD–PA signalling complexes and their targets have emerged as fast-growing research topics for understanding their numerous but not yet established roles in modifying pathogen perception, signal transduction, and downstream defence responses. Meanwhile, advanced lipidomics tools have allowed researchers to reveal further the mechanisms of PLD–PA signalling complexes in regulating lipid metabolism and signalling, and their impacts on jasmonic acid/oxylipins, salicylic acid, and other hormone signalling pathways that essentially mediate plant defence responses. This review attempts to summarize the progress made in spatial and temporal PLD/PA signalling as well as PLD/PA-mediated modification of plant defence. It presents an in-depth discussion on the functions and potential mechanisms of PLD–PA complexes in regulating actin filament/microtubule cytoskeleton, vesicle trafficking, and hormonal signalling, and in influencing lipid metabolism-derived metabolites as critical signalling components in plant defence responses. The discussion puts PLD–PA in a broader context in order to guide future research. PMID:25680793

Unique responsiveness of angiosperm stomata to elevated CO2 explained by calcium signalling.

Directory of Open Access Journals (Sweden)

Timothy J Brodribb

Full Text Available Angiosperm and conifer tree species respond differently when exposed to elevated CO2, with angiosperms found to dynamically reduce water loss while conifers appear insensitive. Such distinct responses are likely to affect competition between these tree groups as atmospheric CO2 concentration rises. Seeking the mechanism behind this globally important phenomenon we targeted the Ca(2+-dependent signalling pathway, a mediator of stomatal closure in response to elevated CO2, as a possible explanation for the differentiation of stomatal behaviours. Sampling across the diversity of vascular plants including lycophytes, ferns, gymnosperms and angiosperms we show that only angiosperms possess the stomatal behaviour and prerequisite genetic coding, linked to Ca(2+-dependent stomatal signalling. We conclude that the evolution of Ca(2+-dependent stomatal signalling gives angiosperms adaptive benefits in terms of highly efficient water use, but that stomatal sensitivity to high CO2 may penalise angiosperm productivity relative to other plant groups in the current era of soaring atmospheric CO2.

Small Signal Stability Improvement of Power Systems Using Optimal Load Responses in Competitive Electricity Markets

DEFF Research Database (Denmark)

Hu, Weihao; Su, Chi; Chen, Zhe

2011-01-01

Since the hourly spot market price is available one day ahead in Denmark, the price could be transferred to the consumers and they may shift some of their loads from high price periods to the low price periods in order to save their energy costs. The optimal load response to an electricity price...... price is proposed. A 17-bus power system with high wind power penetrations, which resembles the Eastern Danish power system, is chosen as the study case. Simulation results show that the optimal load response to electricity prices is an effective measure to improve the small signal stability of power...... for demand side management generates different load profiles and may provide an opportunity to improve the small signal stability of power systems with high wind power penetrations. In this paper, the idea of power system small signal stability improvement by using optimal load response to the electricity...

The Rule of Three for Prizes in Science and the Bold Triptychs of Francis Bacon.

Science.gov (United States)

Goldstein, Joseph L

2016-09-22

For many scientific awards, such as Nobels and Laskers, the maximum number of recipients is three. This Rule of Three forces selection committees to make difficult decisions that increase the likelihood of singling out those individuals who open a new field and continue to lead it. The Rule of Three is reminiscent of art's three-panel triptych, a form that the modern master Francis Bacon used to distill complex stories in a bold way. Copyright © 2016 Elsevier Inc. All rights reserved.

Neural responses to nostalgia-evoking music modeled by elements of dynamic musical structure and individual differences in affective traits.

Science.gov (United States)

Barrett, Frederick S; Janata, Petr

2016-10-01

Nostalgia is an emotion that is most commonly associated with personally and socially relevant memories. It is primarily positive in valence and is readily evoked by music. It is also an idiosyncratic experience that varies between individuals based on affective traits. We identified frontal, limbic, paralimbic, and midbrain brain regions in which the strength of the relationship between ratings of nostalgia evoked by music and blood-oxygen-level-dependent (BOLD) signal was predicted by affective personality measures (nostalgia proneness and the sadness scale of the Affective Neuroscience Personality Scales) that are known to modulate the strength of nostalgic experiences. We also identified brain areas including the inferior frontal gyrus, substantia nigra, cerebellum, and insula in which time-varying BOLD activity correlated more strongly with the time-varying tonal structure of nostalgia-evoking music than with music that evoked no or little nostalgia. These findings illustrate one way in which the reward and emotion regulation networks of the brain are recruited during the experiencing of complex emotional experiences triggered by music. These findings also highlight the importance of considering individual differences when examining the neural responses to strong and idiosyncratic emotional experiences. Finally, these findings provide a further demonstration of the use of time-varying stimulus-specific information in the investigation of music-evoked experiences. Copyright © 2016 Elsevier Ltd. All rights reserved.

Abnormal GABAergic function and negative affect in schizophrenia.

Science.gov (United States)

Taylor, Stephan F; Demeter, Elise; Phan, K Luan; Tso, Ivy F; Welsh, Robert C

2014-03-01

Deficits in the γ-aminobutyric acid (GABA) system have been reported in postmortem studies of schizophrenia, and therapeutic interventions in schizophrenia often involve potentiation of GABA receptors (GABAR) to augment antipsychotic therapy and treat negative affect such as anxiety. To map GABAergic mechanisms associated with processing affect, we used a benzodiazepine challenge while subjects viewed salient visual stimuli. Fourteen stable, medicated schizophrenia/schizoaffective patients and 13 healthy comparison subjects underwent functional magnetic resonance imaging using the blood oxygenation level-dependent (BOLD) technique while they viewed salient emotional images. Subjects received intravenous lorazepam (LRZ; 0.01 mg/kg) or saline in a single-blinded, cross-over design (two sessions separated by 1-3 weeks). A predicted group by drug interaction was noted in the dorsal medial prefrontal cortex (dmPFC) as well as right superior frontal gyrus and left and right occipital regions, such that psychosis patients showed an increased BOLD signal to LRZ challenge, rather than the decreased signal exhibited by the comparison group. A main effect of reduced BOLD signal in bilateral occipital areas was noted across groups. Consistent with the role of the dmPFC in processing emotion, state negative affect positively correlated with the response to the LRZ challenge in the dmPFC for the patients and comparison subjects. The altered response to LRZ challenge is consistent with altered inhibition predicted by postmortem findings of altered GABAR in schizophrenia. These results also suggest that negative affect in schizophrenia/schizoaffective disorder is associated-directly or indirectly-with GABAergic function on a continuum with normal behavior.

Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance.

Science.gov (United States)

Bertolino, Alessandro; Taurisano, Paolo; Pisciotta, Nicola Marco; Blasi, Giuseppe; Fazio, Leonardo; Romano, Raffaella; Gelao, Barbara; Lo Bianco, Luciana; Lozupone, Madia; Di Giorgio, Annabella; Caforio, Grazia; Sambataro, Fabio; Niccoli-Asabella, Artor; Papp, Audrey; Ursini, Gianluca; Sinibaldi, Lorenzo; Popolizio, Teresa; Sadee, Wolfgang; Rubini, Giuseppe

2010-02-22

Variation of the gene coding for D2 receptors (DRD2) has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560) predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic) and D2L (mainly post-synaptic). However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known. Thirty-seven healthy subjects were genotyped for rs1076560 (G>T) and underwent SPECT with [123I]IBZM (which binds primarily to post-synaptic D2 receptors) and with [123I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors), as well as BOLD fMRI during N-Back working memory. Subjects carrying the T allele (previously associated with reduced D2S expression) had striatal reductions of [123I]IBZM and of [123I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers) and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT. Our results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway.

Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance.

Directory of Open Access Journals (Sweden)

Alessandro Bertolino

2010-02-01

Full Text Available Variation of the gene coding for D2 receptors (DRD2 has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560 predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic and D2L (mainly post-synaptic. However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known.Thirty-seven healthy subjects were genotyped for rs1076560 (G>T and underwent SPECT with [123I]IBZM (which binds primarily to post-synaptic D2 receptors and with [123I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors, as well as BOLD fMRI during N-Back working memory.Subjects carrying the T allele (previously associated with reduced D2S expression had striatal reductions of [123I]IBZM and of [123I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT.Our results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway.

Reduced error signalling in medication-naive children with ADHD

DEFF Research Database (Denmark)

Plessen, Kerstin J; Allen, Elena A; Eichele, Heike

2016-01-01

BACKGROUND: We examined the blood-oxygen level-dependent (BOLD) activation in brain regions that signal errors and their association with intraindividual behavioural variability and adaptation to errors in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: We acquired...... functional MRI data during a Flanker task in medication-naive children with ADHD and healthy controls aged 8-12 years and analyzed the data using independent component analysis. For components corresponding to performance monitoring networks, we compared activations across groups and conditions...... and correlated them with reaction times (RT). Additionally, we analyzed post-error adaptations in behaviour and motor component activations. RESULTS: We included 25 children with ADHD and 29 controls in our analysis. Children with ADHD displayed reduced activation to errors in cingulo-opercular regions...

Effects of exogenous testosterone on the ventral striatal BOLD response during reward anticipation in healthy women.

Science.gov (United States)

Hermans, Erno J; Bos, Peter A; Ossewaarde, Lindsey; Ramsey, Nick F; Fernández, Guillén; van Honk, Jack

2010-08-01

Correlational evidence in humans shows that levels of the androgen hormone testosterone are positively related to reinforcement sensitivity and competitive drive. Structurally similar anabolic-androgenic steroids (AAS) are moreover widely abused, and animal studies show that rodents self-administer testosterone. These observations suggest that testosterone exerts activational effects on mesolimbic dopaminergic pathways involved in incentive processing and reinforcement regulation. However, there are no data on humans supporting this hypothesis. We used functional magnetic resonance imaging (fMRI) to investigate the effects of testosterone administration on neural activity in terminal regions of the mesolimbic pathway. In a placebo-controlled double-blind crossover design, 12 healthy women received a single sublingual administration of .5 mg of testosterone. During MRI scanning, participants performed a monetary incentive delay task, which is known to elicit robust activation of the ventral striatum during reward anticipation. Results show a positive main effect of testosterone on the differential response in the ventral striatum to cues signaling potential reward versus nonreward. Notably, this effect interacted with levels self-reported intrinsic appetitive motivation: individuals with low intrinsic appetitive motivation exhibited larger testosterone-induced increases but had smaller differential responses after placebo. Thus, the present study lends support to the hypothesis that testosterone affects activity in terminal regions of the mesolimbic dopamine system but suggests that such effects may be specific to individuals with low intrinsic appetitive motivation. By showing a potential mechanism underlying central reinforcement of androgen use, the present findings may moreover have implications for our understanding of the pathophysiology of AAS dependency. Copyright 2010 Elsevier Inc. All rights reserved.

Brushless DC motor control system responsive to control signals generated by a computer or the like

Science.gov (United States)

Packard, Douglas T. (Inventor); Schmitt, Donald E. (Inventor)

1987-01-01

A control system for a brushless DC motor responsive to digital control signals is disclosed. The motor includes a multiphase wound stator and a permanent magnet rotor. The rotor is arranged so that each phase winding, when energized from a DC source, will drive the rotor through a predetermined angular position or step. A commutation signal generator responsive to the shaft position provides a commutation signal for each winding. A programmable control signal generator such as a computer or microprocessor produces individual digital control signals for each phase winding. The control signals and commutation signals associated with each winding are applied to an AND gate for that phase winding. Each gate controls a switch connected in series with the associated phase winding and the DC source so that each phase winding is energized only when the commutation signal and the control signal associated with that phase winding are present. The motor shaft may be advanced one step at a time to a desired position by applying a predetermined number of control signals in the proper sequence to the AND gates and the torque generated by the motor may be regulated by applying a separate control signal to each AND gate which is pulse width modulated to control the total time that each switch connects its associated winding to the DC source during each commutation period.

Fuz regulates craniofacial development through tissue specific responses to signaling factors.

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Zichao Zhang

Full Text Available The planar cell polarity effector gene Fuz regulates ciliogenesis and Fuz loss of function studies reveal an array of embryonic phenotypes. However, cilia defects can affect many signaling pathways and, in humans, cilia defects underlie several craniofacial anomalies. To address this, we analyzed the craniofacial phenotype and signaling responses of the Fuz(-/- mice. We demonstrate a unique role for Fuz in regulating both Hedgehog (Hh and Wnt/β-catenin signaling during craniofacial development. Fuz expression first appears in the dorsal tissues and later in ventral tissues and craniofacial regions during embryonic development coincident with cilia development. The Fuz(-/- mice exhibit severe craniofacial deformities including anophthalmia, agenesis of the tongue and incisors, a hypoplastic mandible, cleft palate, ossification/skeletal defects and hyperplastic malformed Meckel's cartilage. Hh signaling is down-regulated in the Fuz null mice, while canonical Wnt signaling is up-regulated revealing the antagonistic relationship of these two pathways. Meckel's cartilage is expanded in the Fuz(-/- mice due to increased cell proliferation associated with the up-regulation of Wnt canonical target genes and decreased non-canonical pathway genes. Interestingly, cilia development was decreased in the mandible mesenchyme of Fuz null mice, suggesting that cilia may antagonize Wnt signaling in this tissue. Furthermore, expression of Fuz decreased expression of Wnt pathway genes as well as a Wnt-dependent reporter. Finally, chromatin IP experiments demonstrate that β-catenin/TCF-binding directly regulates Fuz expression. These data demonstrate a new model for coordination of Hh and Wnt signaling and reveal a Fuz-dependent negative feedback loop controlling Wnt/β-catenin signaling.