Sample records for brainstem circuitry regulating

  1. Brainstem circuitry regulating phasic activation of trigeminal motoneurons during REM sleep.

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    Christelle Anaclet


    Full Text Available Rapid eye movement sleep (REMS is characterized by activation of the cortical and hippocampal electroencephalogram (EEG and atonia of non-respiratory muscles with superimposed phasic activity or twitching, particularly of cranial muscles such as those of the eye, tongue, face and jaw. While phasic activity is a characteristic feature of REMS, the neural substrates driving this activity remain unresolved. Here we investigated the neural circuits underlying masseter (jaw phasic activity during REMS. The trigeminal motor nucleus (Mo5, which controls masseter motor function, receives glutamatergic inputs mainly from the parvocellular reticular formation (PCRt, but also from the adjacent paramedian reticular area (PMnR. On the other hand, the Mo5 and PCRt do not receive direct input from the sublaterodorsal (SLD nucleus, a brainstem region critical for REMS atonia of postural muscles. We hypothesized that the PCRt-PMnR, but not the SLD, regulates masseter phasic activity during REMS.To test our hypothesis, we measured masseter electromyogram (EMG, neck muscle EMG, electrooculogram (EOG and EEG in rats with cell-body specific lesions of the SLD, PMnR, and PCRt. Bilateral lesions of the PMnR and rostral PCRt (rPCRt, but not the caudal PCRt or SLD, reduced and eliminated REMS phasic activity of the masseter, respectively. Lesions of the PMnR and rPCRt did not, however, alter the neck EMG or EOG. To determine if rPCRt neurons use glutamate to control masseter phasic movements, we selectively blocked glutamate release by rPCRt neurons using a Cre-lox mouse system. Genetic disruption of glutamate neurotransmission by rPCRt neurons blocked masseter phasic activity during REMS.These results indicate that (1 premotor glutamatergic neurons in the medullary rPCRt and PMnR are involved in generating phasic activity in the masseter muscles, but not phasic eye movements, during REMS; and (2 separate brainstem neural circuits control postural and cranial muscle

  2. Brainstem and spinal cord circuitry regulating REM sleep and muscle atonia.

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    Martina Krenzer

    Full Text Available Previous work has suggested, but not demonstrated directly, a critical role for both glutamatergic and GABAergic neurons of the pontine tegmentum in the regulation of rapid eye movement (REM sleep.To determine the in vivo roles of these fast-acting neurotransmitters in putative REM pontine circuits, we injected an adeno-associated viral vector expressing Cre recombinase (AAV-Cre into mice harboring lox-P modified alleles of either the vesicular glutamate transporter 2 (VGLUT2 or vesicular GABA-glycine transporter (VGAT genes. Our results show that glutamatergic neurons of the sublaterodorsal nucleus (SLD and glycinergic/GABAergic interneurons of the spinal ventral horn contribute to REM atonia, whereas a separate population of glutamatergic neurons in the caudal laterodorsal tegmental nucleus (cLDT and SLD are important for REM sleep generation. Our results further suggest that presynaptic GABA release in the cLDT-SLD, ventrolateral periaqueductal gray matter (vlPAG and lateral pontine tegmentum (LPT are not critically involved in REM sleep control.These findings reveal the critical and divergent in vivo role of pontine glutamate and spinal cord GABA/glycine in the regulation of REM sleep and atonia and suggest a possible etiological basis for REM sleep behavior disorder (RBD.

  3. Phytochemical regulation of Fyn and AMPK signaling circuitry. (United States)

    Lee, Chan Gyu; Koo, Ja Hyun; Kim, Sang Geon


    During the past decades, phytochemical terpenoids, polyphenols, lignans, flavonoids, and alkaloids have been identified as antioxidative and cytoprotective agents. Adenosine monophosphate-activated protein kinase (AMPK) is a kinase that controls redox-state and oxidative stress in the cell, and serves as a key molecule regulating energy metabolism. Many phytochemicals directly or indirectly alter the AMPK pathway in distinct manners, exerting catabolic metabolism. Some of them are considered promising in the treatment of metabolic diseases such as type II diabetes, obesity, and hyperlipidemia. Another important kinase that regulates energy metabolism is Fyn kinase, a member of the Src family kinases that plays a role in various cellular responses such as insulin signaling, cell growth, oxidative stress and apoptosis. Phytochemical inhibition of Fyn leads to AMPK-mediated protection of the cell in association with increased antioxidative capacity and mitochondrial biogenesis. The kinases may work together to form a signaling circuitry for the homeostasis of energy conservation and expenditure, and may serve as targets of phytochemicals. This review is intended as a compilation of recent advancements in the pharmacological research of phytochemicals targeting Fyn and AMPK circuitry, providing information for the prevention and treatment of metabolic diseases and the accompanying tissue injuries.

  4. Non-homeostatic body weight regulation through a brainstem-restricted receptor for GDF15

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    Hsu, Jer-Yuan; Crawley, Suzanne; Chen, Michael; Ayupova, Dina A.; Lindhout, Darrin A.; Higbee, Jared; Kutach, Alan; Joo, William; Gao, Zhengyu; Fu, Diana; To, Carmen; Mondal, Kalyani; Li, Betty; Kekatpure, Avantika; Wang, Marilyn; Laird, Teresa; Horner, Geoffrey; Chan, Jackie; McEntee, Michele; Lopez, Manuel; Lakshminarasimhan, Damodharan; White, Andre; Wang, Sheng-Ping; Yao, Jun; Yie, Junming; Matern, Hugo; Solloway, Mark; Haldankar, Raj; Parsons, Thomas; Tang, Jie; Shen, Wenyan D.; Alice Chen, Yu; Tian, Hui; Allan, Bernard B.


    Under homeostatic conditions, animals use well-defined hypothalamic neural circuits to help maintain stable body weight, by integrating metabolic and hormonal signals from the periphery to balance food consumption and energy expenditure1,2. In stressed or disease conditions, however, animals use alternative neuronal pathways to adapt to the metabolic challenges of altered energy demand3. Recent studies have identified brain areas outside the hypothalamus that are activated under these ‘non-homeostatic’ conditions4,5,6, but the molecular nature of the peripheral signals and brain-localized receptors that activate these circuits remains elusive. Here we identify glial cell-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL) as a brainstem-restricted receptor for growth and differentiation factor 15 (GDF15). GDF15 regulates food intake, energy expenditure and body weight in response to metabolic and toxin-induced stresses; we show that Gfral knockout mice are hyperphagic under stressed conditions and are resistant to chemotherapy-induced anorexia and body weight loss. GDF15 activates GFRAL-expressing neurons localized exclusively in the area postrema and nucleus tractus solitarius of the mouse brainstem. It then triggers the activation of neurons localized within the parabrachial nucleus and central amygdala, which constitute part of the ‘emergency circuit’ that shapes feeding responses to stressful conditions7. GDF15 levels increase in response to tissue stress and injury, and elevated levels are associated with body weight loss in numerous chronic human diseases8,9. By isolating GFRAL as the receptor for GDF15-induced anorexia and weight loss, we identify a mechanistic basis for the non-homeostatic regulation of neural circuitry by a peripheral signal associated with tissue damage and stress. These findings provide opportunities to develop therapeutic agents for the treatment of disorders with altered energy demand.

  5. Serotonin: a regulator of neuronal morphology and circuitry (United States)

    Daubert, Elizabeth A.; Condron, Barry G.


    Serotonin is an important neuromodulator associated with a wide range of physiological effects in the central nervous system. The exact mechanisms for how serotonin influences brain development are not well understood, although studies in invertebrate and vertebrate model organisms are beginning to unravel a regulatory role for serotonin in neuronal morphology and circuit formation. Recent data suggests a developmental window during which altered serotonin levels permanently impact circuitry, however, the temporal constraints and molecular mechanisms responsible are still under investigation. Growing evidence suggests that alterations in early serotonin signaling contribute to a number of neurodevelopmental and neuropsychiatric disorders. Thus, understanding how altered serotonin signaling affects neuronal morphology and plasticity, and ultimately animal physiology and pathophysiology, will be of great significance. PMID:20561690

  6. Corticostriatal circuitry in regulating diseases characterized by intrusive thinking. (United States)

    Kalivas, Benjamin C; Kalivas, Peter W


    Intrusive thinking triggers clinical symptoms in many neuropsychiatric disorders. Using drug addiction as an exemplar disorder sustained in part by intrusive thinking, we explore studies demonstrating that impairments in corticostriatal circuitry strongly contribute to intrusive thinking. Neuroimaging studies have long implicated this projection in cue-induced craving to use drugs, and preclinical models show that marked changes are produced at corticostriatal synapses in the nucleus accumbens during a relapse episode. We delineate an accumbens microcircuit that mediates cue-induced drug seeking becoming an intrusive event. This microcircuit harbors many potential therapeutic targets. We focus on preclinical and clinical studies, showing that administering N-acetylcysteine restores uptake of synaptic glutamate by astroglial glutamate transporters and thereby inhibits intrusive thinking. We posit that because intrusive thinking is a shared endophenotype in many disorders, N-acetylcysteine has positive effects in clinical trials for a variety of neuropsychiatric disorders, including drug addiction, gambling, trichotillomania, and depression.

  7. Dysfunction in the neural circuitry of emotional self-regulation in major depressive disorder. (United States)

    Beauregard, Mario; Paquette, Vincent; Lévesque, Johanne


    An inability to self-regulate negative emotions appears to play a pivotal role in the genesis of major depressive disorder. This inability may be related to a dysfunction of the neural circuitry underlying emotional self-regulation. This functional magnetic resonance imaging study was conducted to test this hypothesis. Depressed individuals and controls were scanned while they attempted to voluntarily down-regulate sad feelings. The degree of difficulty experienced during down-regulation of sadness was higher in depressed individuals. Furthermore, there was greater activation in the right dorsal anterior cingulate cortex, right anterior temporal pole, right amygdala, and right insula in depressed individuals. These results suggest that emotional dysregulation in major depressive disorder is related to a disturbance in the neural circuitry of emotional self-regulation.

  8. An extensive circuitry for cell wall regulation in Candida albicans.

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    Jill R Blankenship


    Full Text Available Protein kinases play key roles in signaling and response to changes in the external environment. The ability of Candida albicans to quickly sense and respond to changes in its environment is key to its survival in the human host. Our guiding hypothesis was that creating and screening a set of protein kinase mutant strains would reveal signaling pathways that mediate stress response in C. albicans. A library of protein kinase mutant strains was created and screened for sensitivity to a variety of stresses. For the majority of stresses tested, stress response was largely conserved between C. albicans, Saccharomyces cerevisiae, and Schizosaccharomyces pombe. However, we identified eight protein kinases whose roles in cell wall regulation (CWR were not expected from functions of their orthologs in the model fungi Saccharomyces cerevisiae and Schizosaccharomyces pombe. Analysis of the conserved roles of these protein kinases indicates that establishment of cell polarity is critical for CWR. In addition, we found that septins, crucial to budding, are both important for surviving and are mislocalized by cell wall stress. Our study shows an expanded role for protein kinase signaling in C. albicans cell wall integrity. Our studies suggest that in some cases, this expansion represents a greater importance for certain pathways in cell wall biogenesis. In other cases, it appears that signaling pathways have been rewired for a cell wall integrity response.

  9. Regulating Critical Period Plasticity: Insight from the Visual System to Fear Circuitry for Therapeutic Interventions

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    Elisa M. Nabel


    Full Text Available Early temporary windows of heightened brain plasticity called critical periods developmentally sculpt neural circuits and contribute to adult behavior. Regulatory mechanisms of visual cortex development –the preeminent model of experience-dependent critical period plasticity- actively limit adult plasticity and have proved fruitful therapeutic targets to reopen plasticity and rewire faulty visual system connections later in life. Interestingly, these molecular mechanisms have been implicated in the regulation of plasticity in other functions beyond vision. Applying mechanistic understandings of critical period plasticity in the visual cortex to fear circuitry may provide a conceptual framework for developing novel therapeutic tools to mitigate aberrant fear responses in post traumatic stress disorder. In this review, we turn to the model of experience-dependent visual plasticity to provide novel insights for the mechanisms regulating plasticity in the fear system. Fear circuitry, particularly fear memory erasure, also undergoes age-related changes in experience-dependent plasticity. We consider the contributions of molecular brakes that halt visual critical period plasticity to circuitry underlying fear memory erasure. A major molecular brake in the visual cortex, perineuronal net formation, recently has been identified in the development of fear systems that are resilient to fear memory erasure. The roles of other molecular brakes, myelin-related Nogo receptor signaling and Lynx family proteins– endogenous inhibitors for nicotinic acetylcholine receptor, are explored in the context of fear memory plasticity. Such fear plasticity regulators, including epigenetic effects, provide promising targets for therapeutic interventions.

  10. Glial cell contributions to auditory brainstem development

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    Karina S Cramer


    Full Text Available Glial cells, previously thought to have generally supporting roles in the central nervous system, are emerging as essential contributors to multiple aspects of neuronal circuit function and development. This review focuses on the contributions of glial cells to the development of specialized auditory pathways in the brainstem. These pathways display specialized synapses and an unusually high degree of precision in circuitry that enables sound source localization. The development of these pathways thus requires highly coordinated molecular and cellular mechanisms. Several classes of glial cells, including astrocytes, oligodendrocytes, and microglia, have now been explored in these circuits in both avian and mammalian brainstems. Distinct populations of astrocytes are found over the course of auditory brainstem maturation. Early appearing astrocytes are associated with spatial compartments in the avian auditory brainstem. Factors from late appearing astrocytes promote synaptogenesis and dendritic maturation, and astrocytes remain integral parts of specialized auditory synapses. Oligodendrocytes play a unique role in both birds and mammals in highly regulated myelination essential for proper timing to decipher interaural cues. Microglia arise early in brainstem development and may contribute to maturation of auditory pathways. Together these studies demonstrate the importance of non-neuronal cells in the assembly of specialized auditory brainstem circuits.

  11. Sensitive Periods of Emotion Regulation: Influences of Parental Care on Frontoamygdala Circuitry and Plasticity (United States)

    Gee, Dylan G.


    Early caregiving experiences play a central role in shaping emotional development, stress physiology, and refinement of limbic circuitry. Converging evidence across species delineates a sensitive period of heightened neuroplasticity when frontoamygdala circuitry is especially amenable to caregiver inputs early in life. During this period, parental…

  12. Triglyceride sensing in the reward circuitry: A new insight in feeding behaviour regulation. (United States)

    Cansell, Celine; Luquet, Serge


    In both developed and emerging countries, sedentary life style and over exposition to high energy dense foods has led to a thermodynamic imbalance and consequently obesity. Obesity often involves a behavioural component in which, similar to drugs abuse, compulsive consumption of palatable food rich in lipids and sugar drives energy intake far beyond metabolic demands. The hypothalamus is one of the primary integration sites of circulating energy-related signals like leptin or ghrelin and is therefore considered as one of the main central regulators of energy balance. However, food intake is also modulated by sensory inputs, such as tastes and odours, as well as by affective or emotional states. The mesolimbic pathway is well established as a key actor of the rewarding aspect of feeding. Particularly, the hedonic and motivational aspects of food are closely tied to the release of the neurotransmitter dopamine (DA) in striatal structure such as the Nucleus Accumbens (Nacc). In both rodent and humans several studies shows an attenuated activity of dopaminergic signal associated with obesity and there is evidence that consumption of palatable food per se leads to DA signalling alterations. Furthermore impaired cognition in obese mice is improved by selectively lowering triglycerides (TG) and intracerebroventricular administration of TG induces by itself acquisition impairment in several cognitive paradigms in normal body weight mice. Together, these observations raise the possibility that nutritional lipids, particularly TG, directly affect cognitive and reward processes by modulating the mesolimbic pathway and might contribute to the downward spiral of compulsive consumption of palatable food and obesity. This review is an attempt to capture recent evolution in the field that might point toward a direct action of nutritional lipid in the reward circuitry. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights

  13. Limbic circuitry activation in ethanol withdrawal is regulated by a chromosome 1 locus. (United States)

    Buck, Kari J; Chen, Gang; Kozell, Laura B


    Physiological dependence and associated withdrawal episodes are thought to constitute a motivational force sustaining alcohol use/abuse and contributing to relapse in alcoholics. Although no animal model exactly duplicates alcoholism, models for specific factors, including the withdrawal syndrome, are useful for identifying potential genetic and neural determinants of liability in humans. We previously identified highly significant quantitative trait loci (QTLs) with large effects on predisposition to withdrawal after chronic and acute alcohol exposure in mice and mapped these loci to the same region of chromosome 1 (Alcdp1 and Alcw1, respectively). The present studies utilize a novel Alcdp1/Alcw1 congenic model (in which an interval spanning Alcdp1 and Alcw1 from the C57BL/6J donor strain [build GRCm38 150.3-174.6 Mb] has been introgressed onto a uniform inbred DBA/2J genetic background) known to demonstrate significantly less severe chronic and acute withdrawal compared to appropriate background strain animals. Here, using c-Fos induction as a high-resolution marker of neuronal activation, we report that male Alcdp1/Alcw1 congenic animals demonstrate significantly less alcohol withdrawal-associated neural activation compared to appropriate background strain animals in the prelimbic and cingulate cortices of the prefrontal cortex as well as discrete regions of the extended amygdala (i.e., basolateral) and extended basal ganglia (i.e., dorsolateral striatum, and caudal substantia nigra pars reticulata). These studies are the first to begin to elucidate circuitry by which this confirmed addiction-relevant QTL could influence behavior. This circuitry overlaps limbic circuitry involved in stress, providing additional mechanistic information. Alcdp1/Alcw1 maps to a region syntenic with human chromosome 1q, where multiple studies find significant associations with risk for alcoholism. Published by Elsevier Inc.

  14. Role of basal ganglia in sleep-wake regulation: neural circuitry and clinical significance

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    Ramalingam Vetrivelan


    Full Text Available Researchers over the last decade have made substantial progress towards understanding the roles of dopamine and the basal ganglia in the control of sleep-wake behavior. In this review, we outline recent advancements regarding dopaminergic modulation of sleep through the basal ganglia (BG and extra-BG sites. Our main hypothesis is that dopamine promotes sleep by its action on the D2 receptors in the BG and promotes wakefulness by its action on D1 and D2 receptors in the extra-BG sites. This hypothesis implicates dopamine depletion in the BG (such as in Parkinson’s disease in causing frequent nighttime arousal and overall insomnia. Furthermore, the arousal effects of psychostimulants (methamphetamine, cocaine and modafinil may be linked to the ventral periaquductal grey (vPAG dopaminergic circuitry targeting the extra-BG sleep-wake network.

  15. Regulation of the neural circuitry of emotion by compassion meditation: effects of meditative expertise.

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    Antoine Lutz


    Full Text Available Recent brain imaging studies using functional magnetic resonance imaging (fMRI have implicated insula and anterior cingulate cortices in the empathic response to another's pain. However, virtually nothing is known about the impact of the voluntary generation of compassion on this network. To investigate these questions we assessed brain activity using fMRI while novice and expert meditation practitioners generated a loving-kindness-compassion meditation state. To probe affective reactivity, we presented emotional and neutral sounds during the meditation and comparison periods. Our main hypothesis was that the concern for others cultivated during this form of meditation enhances affective processing, in particular in response to sounds of distress, and that this response to emotional sounds is modulated by the degree of meditation training. The presentation of the emotional sounds was associated with increased pupil diameter and activation of limbic regions (insula and cingulate cortices during meditation (versus rest. During meditation, activation in insula was greater during presentation of negative sounds than positive or neutral sounds in expert than it was in novice meditators. The strength of activation in insula was also associated with self-reported intensity of the meditation for both groups. These results support the role of the limbic circuitry in emotion sharing. The comparison between meditation vs. rest states between experts and novices also showed increased activation in amygdala, right temporo-parietal junction (TPJ, and right posterior superior temporal sulcus (pSTS in response to all sounds, suggesting, greater detection of the emotional sounds, and enhanced mentation in response to emotional human vocalizations for experts than novices during meditation. Together these data indicate that the mental expertise to cultivate positive emotion alters the activation of circuitries previously linked to empathy and theory of mind in

  16. Neural circuitry of emotion regulation: Effects of appraisal, attention, and cortisol administration. (United States)

    Ma, Sean T; Abelson, James L; Okada, Go; Taylor, Stephan F; Liberzon, Israel


    Psychosocial well-being requires effective regulation of emotional responding in context of threat or stress. Neuroimaging studies have focused on instructed, volitional regulation (e.g., reappraisal or distancing), largely ignoring implicit regulation that does not involve purposeful effort to alter emotional experience. These implicit processes may or may not involve the same neural pathways as explicit regulatory strategies. We examined the neurobiology of implicit emotional regulation processes and the impact of the stress hormone cortisol on these processes. Our study task employed composite pictures of faces and places to examine neural activity during implicit emotional processing (of emotional faces), while these responses were implicitly regulated by attention shift away from the emotionally evocative stimuli, and while subjects reflectively appraised their own emotional response to them. Subjects completed the task in an fMRI scanner after random assignment to receive placebo or hydrocortisone (HCT), an orally administered version of cortisol. Implicit emotional processing activated insula/IFG, dACC/dMPFC, midbrain and amygdala. With attention shifting, we saw diminished signal in emotion generating/response regions (e.g., amygdala) and increased activations in task specific attention regions like parahippocampus. With appraisal of emotions, we observed robust activations in medial prefrontal areas, where activation is also seen in instructed reappraisal studies. We observed no main effects of HCT administration on brain, but males and females showed opposing neural effects in prefrontal areas. The data suggest that different types of emotion regulation utilize overlapping circuits, but with some strategy specific activation. Further study of the dimorphic sex response to cortisol is needed.

  17. Anorectic brainstem peptides: more pieces to the puzzle. (United States)

    Luckman, Simon M; Lawrence, Catherine B


    Eating a meal is a mechanical process involving autonomous pathways that relay sensory and motor information between the whole length of the digestive tract and the central nervous system. This circuitry is able to initiate and terminate the meal, primarily by gut-brainstem-gut reflex arcs, and is independent of the caloric content of a meal. However, as part of our ability to regulate body weight over time, we must be able to modulate the amount of energy that we take in as food and the amount of energy that we expend. Thus, the gut-brainstem axis must be coupled to other systems that take account of factors such as food availability and preference, changing energy requirements and our social habits. Here, we review the importance of the brainstem nucleus of the tractus solitarius as a site of integration and the routes by which it connects the gut-brainstem axis with regulatory neuronal and endocrine networks that allow for strict body weight management.

  18. Topology and Control of the Cell-Cycle-Regulated Transcriptional Circuitry (United States)

    Haase, Steven B.; Wittenberg, Curt


    Nearly 20% of the budding yeast genome is transcribed periodically during the cell division cycle. The precise temporal execution of this large transcriptional program is controlled by a large interacting network of transcriptional regulators, kinases, and ubiquitin ligases. Historically, this network has been viewed as a collection of four coregulated gene clusters that are associated with each phase of the cell cycle. Although the broad outlines of these gene clusters were described nearly 20 years ago, new technologies have enabled major advances in our understanding of the genes comprising those clusters, their regulation, and the complex regulatory interplay between clusters. More recently, advances are being made in understanding the roles of chromatin in the control of the transcriptional program. We are also beginning to discover important regulatory interactions between the cell-cycle transcriptional program and other cell-cycle regulatory mechanisms such as checkpoints and metabolic networks. Here we review recent advances and contemporary models of the transcriptional network and consider these models in the context of eukaryotic cell-cycle controls. PMID:24395825

  19. Neural emotion regulation circuitry underlying anxiolytic effects of perceived control over pain. (United States)

    Salomons, Tim V; Nusslock, Robin; Detloff, Allison; Johnstone, Tom; Davidson, Richard J


    Anxiolytic effects of perceived control have been observed across species. In humans, neuroimaging studies have suggested that perceived control and cognitive reappraisal reduce negative affect through similar mechanisms. An important limitation of extant neuroimaging studies of perceived control in terms of directly testing this hypothesis, however, is the use of within-subject designs, which confound participants' affective response to controllable and uncontrollable stress. To compare neural and affective responses when participants were exposed to either uncontrollable or controllable stress, two groups of participants received an identical series of stressors (thermal pain stimuli). One group ("controllable") was led to believe they had behavioral control over the pain stimuli, whereas another ("uncontrollable") believed they had no control. Controllable pain was associated with decreased state anxiety, decreased activation in amygdala, and increased activation in nucleus accumbens. In participants who perceived control over the pain, reduced state anxiety was associated with increased functional connectivity between each of these regions and ventral lateral/ventral medial pFC. The location of pFC findings is consistent with regions found to be critical for the anxiolytic effects of perceived control in rodents. Furthermore, interactions observed between pFC and both amygdala and nucleus accumbens are remarkably similar to neural mechanisms of emotion regulation through reappraisal in humans. These results suggest that perceived control reduces negative affect through a general mechanism involved in the cognitive regulation of emotion.

  20. Regulation of the galanin system in the brainstem and hypothalamus by electroconvulsive stimulation in mice

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    Christiansen, S H


    of the hypothalamus. Adult mice were treated with ECS once daily for 14 consecutive days, a paradigm previously shown to exert antidepressant-like effects. Significant increases in galanin transcription were found in the locus coeruleus and dorsomedial nuclei of the hypothalamus. In addition, GalR2 mRNA levels...... in the ventro- and dorsomedial nuclei of the hypothalamus were upregulated whereas no GalR1 mRNA upregulation was observed. [(125)I]-galanin receptor binding was downregulated in the ventromedial nuclei of the hypothalamus and dorsal raphe. These data show that the galanin system is regulated by repeated ECS...

  1. Sensory deprivation regulates the development of the hyperpolarization-activated current in auditory brainstem neurons. (United States)

    Hassfurth, Benjamin; Magnusson, Anna K; Grothe, Benedikt; Koch, Ursula


    Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels are highly expressed in the superior olivary complex, the primary locus for binaural information processing. This hyperpolarization-activated current (I(h)) regulates the excitability of neurons and enhances the temporally precise analysis of the binaural acoustic cues. By using the whole-cell patch-clamp technique, we examined the properties of I(h) current in neurons of the lateral superior olive (LSO) and the medial nucleus of the trapezoid body (MNTB) before and after hearing onset. Moreover, we tested the hypothesis that I(h) currents are actively regulated by sensory input activity by performing bilateral and unilateral cochlear ablations before hearing onset, resulting in a chronic auditory deprivation. The results show that after hearing onset, I(h) currents are rapidly upregulated in LSO neurons, but change only marginally in neurons of the MNTB. We also found a striking difference in maximal current density, voltage dependence and activation time constant between the LSO and the MNTB in mature-like animals. Following bilateral cochlear ablations before hearing onset, the I(h) currents were scaled up in the LSO and scaled down in the MNTB. Consequently, in the LSO this resulted in a depolarized resting membrane potential and a lower input resistance of these neurons. This type of activity-dependent homeostatic change could thus result in an augmented response to the remaining inputs.

  2. Eyelid Opening with Trigeminal Proprioceptive Activation Regulates a Brainstem Arousal Mechanism.

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    Kiyoshi Matsuo

    innervated sweat glands and appeared to induce rapid oxygen consumption in the ventromedial prefrontal cortex and to rapidly produce deoxyhemoglobin to regulate physiological arousal. Thus, eyelid opening with trigeminal proprioceptive evocation may activate the ventromedial prefrontal cortex via the mesencephalic trigeminal nucleus and locus coeruleus.

  3. PKC signaling regulates drug resistance of the fungal pathogen Candida albicans via circuitry comprised of Mkc1, calcineurin, and Hsp90.

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    Shantelle L LaFayette


    Full Text Available Fungal pathogens exploit diverse mechanisms to survive exposure to antifungal drugs. This poses concern given the limited number of clinically useful antifungals and the growing population of immunocompromised individuals vulnerable to life-threatening fungal infection. To identify molecules that abrogate resistance to the most widely deployed class of antifungals, the azoles, we conducted a screen of 1,280 pharmacologically active compounds. Three out of seven hits that abolished azole resistance of a resistant mutant of the model yeast Saccharomyces cerevisiae and a clinical isolate of the leading human fungal pathogen Candida albicans were inhibitors of protein kinase C (PKC, which regulates cell wall integrity during growth, morphogenesis, and response to cell wall stress. Pharmacological or genetic impairment of Pkc1 conferred hypersensitivity to multiple drugs that target synthesis of the key cell membrane sterol ergosterol, including azoles, allylamines, and morpholines. Pkc1 enabled survival of cell membrane stress at least in part via the mitogen activated protein kinase (MAPK cascade in both species, though through distinct downstream effectors. Strikingly, inhibition of Pkc1 phenocopied inhibition of the molecular chaperone Hsp90 or its client protein calcineurin. PKC signaling was required for calcineurin activation in response to drug exposure in S. cerevisiae. In contrast, Pkc1 and calcineurin independently regulate drug resistance via a common target in C. albicans. We identified an additional level of regulatory control in the C. albicans circuitry linking PKC signaling, Hsp90, and calcineurin as genetic reduction of Hsp90 led to depletion of the terminal MAPK, Mkc1. Deletion of C. albicans PKC1 rendered fungistatic ergosterol biosynthesis inhibitors fungicidal and attenuated virulence in a murine model of systemic candidiasis. This work establishes a new role for PKC signaling in drug resistance, novel circuitry through which

  4. The glucocorticoid receptor and KLF15 regulate gene expression dynamics and integrate signals through feed-forward circuitry. (United States)

    Sasse, Sarah K; Mailloux, Christina M; Barczak, Andrea J; Wang, Qian; Altonsy, Mohammed O; Jain, Mukesh K; Haldar, Saptarsi M; Gerber, Anthony N


    The glucocorticoid receptor (GR) regulates adaptive transcriptional programs that alter metabolism in response to stress. Network properties that allow GR to tune gene expression to match specific physiologic demands are poorly understood. We analyzed the transcriptional consequences of GR activation in murine lungs deficient for KLF15, a transcriptional regulator of amino acid metabolism that is induced by glucocorticoids and fasting. Approximately 7% of glucocorticoid-regulated genes had altered expression in Klf15-knockdown (Klf15(-/-)) mice. KLF15 formed coherent and incoherent feed-forward circuits with GR that correlated with the expression dynamics of the glucocorticoid response. Coherent feed-forward gene regulation by GR and KLF15 was characterized by combinatorial activation of linked GR-KLF15 regulatory elements by both factors and increased GR occupancy, while expression of KLF15 reduced GR occupancy at the incoherent target, MT2A. Serum deprivation, which increased KLF15 expression in a GR-independent manner in vitro, enhanced glucocorticoid-mediated induction of feed-forward targets of GR and KLF15, such as the loci for the amino acid-metabolizing enzymes proline dehydrogenase and alpha-aminoadipic semialdehyde synthase. Our results establish feed-forward architecture as an organizational principle for the GR network and provide a novel mechanism through which GR integrates signals and regulates expression dynamics.

  5. Focal brainstem gliomas (United States)

    Sabbagh, Abdulrahman J.; Alaqeel, Ahmed M.


    Improved neuronavigation guidance as well as intraoperative imaging and neurophysiologic monitoring technologies have enhanced the ability of neurosurgeons to resect focal brainstem gliomas. In contrast, diffuse brainstem gliomas are considered to be inoperable lesions. This article is a continuation of an article that discussed brainstem glioma diagnostics, imaging, and classification. Here, we address open surgical treatment of and approaches to focal, dorsally exophytic, and cervicomedullary brainstem gliomas. Intraoperative neuronavigation, intraoperative neurophysiologic monitoring, as well as intraoperative imaging are discussed as adjunctive measures to help render these procedures safer, more acute, and closer to achieving surgical goals. PMID:25864061

  6. NPR-9, a Galanin-Like G-Protein Coupled Receptor, and GLR-1 Regulate Interneuronal Circuitry Underlying Multisensory Integration of Environmental Cues in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Jason C Campbell


    Full Text Available C. elegans inhabit environments that require detection of diverse stimuli to modulate locomotion in order to avoid unfavourable conditions. In a mammalian context, a failure to appropriately integrate environmental signals can lead to Parkinson's, Alzheimer's, and epilepsy. Provided that the circuitry underlying mammalian sensory integration can be prohibitively complex, we analyzed nematode behavioral responses in differing environmental contexts to evaluate the regulation of context dependent circuit reconfiguration and sensorimotor control. Our work has added to the complexity of a known parallel circuit, mediated by interneurons AVA and AIB, that integrates sensory cues and is responsible for the initiation of backwards locomotion. Our analysis of the galanin-like G-protein coupled receptor NPR-9 in C. elegans revealed that upregulation of galanin signaling impedes the integration of sensory evoked neuronal signals. Although the expression pattern of npr-9 is limited to AIB, upregulation of the receptor appears to impede AIB and AVA circuits to broadly prevent backwards locomotion, i.e. reversals, suggesting that these two pathways functionally interact. Galanin signaling similarly plays a broadly inhibitory role in mammalian models. Moreover, our identification of a mutant, which rarely initiates backwards movement, allowed us to interrogate locomotory mechanisms underlying chemotaxis. In support of the pirouette model of chemotaxis, organisms that did not exhibit reversal behavior were unable to navigate towards an attractant peak. We also assessed ionotropic glutamate receptor GLR-1 cell-specifically within AIB and determined that GLR-1 fine-tunes AIB activity to modify locomotion following reversal events. Our research highlights that signal integration underlying the initiation and fine-tuning of backwards locomotion is AIB and NPR-9 dependent, and has demonstrated the suitability of C. elegans for analysis of multisensory integration

  7. Brainstem Cavernous Angioma (United States)

    ... in obliteration of the angioma. [9] At a minimum, radiosurgery treatment for brainstem cavernous angioma is controversial. Given the advancement in minimally invasive surgical techniques, more and more neurosurgeons are becoming ...

  8. The Homeostatic Regulation of REM Sleep: A role for Localized Expression of Brain-Derived Neurotrophic Factor in the Brainstem (United States)

    Datta, Subimal; Knapp, Clifford M.; Koul-Tiwari, Richa; Barnes, Abigail


    Homeostatic regulation of REM sleep plays a key role in neural plasticity and deficits in this process are implicated in the development of many neuropsychiatric disorders. Little is known, however, about the molecular mechanisms that underlie this homeostatic regulation process. This study examined the hypothesis that, during selective REM sleep deprivation (RSD), increased brain-derived neurotrophic factor (BDNF) expression in REM sleep regulating areas is critical for the development of homeostatic drive for REM sleep, as measured by an increase in the number of REM sleep transitions. Rats were assigned to RSD, non-sleep deprived (BSL), or total sleep deprivation (TSD) groups. Physiological recordings were obtained from cortical, hippocampal, and pontine EEG electrodes over a 6-hour period, in which sleep deprivation occurred during the first 3 hours. In the RSD, but not the other conditions, homeostatic drive for REM sleep increased progressively. BDNF protein expression was significantly greater in the pedunculopontine tegmentum (PPT) and subcoeruleus nucleus (SubCD) in the RSD as compared to the TSD and BSL groups, areas that regulate REM sleep, but not in the medial preoptic area, which regulates non-REM sleep. There was a significant positive correlation between RSD-induced increases in number of REM sleep episodes and increased BDNF expression in the PPT and SubCD. These increases positively correlated with levels of homeostatic drive for REM sleep. These results, for the first time, suggest that selective RSD-induced increased expression of BDNF in the PPT and SubCD are determinant factors in the development of the homeostatic drive for REM sleep. PMID:26146031

  9. The homeostatic regulation of REM sleep: A role for localized expression of brain-derived neurotrophic factor in the brainstem. (United States)

    Datta, Subimal; Knapp, Clifford M; Koul-Tiwari, Richa; Barnes, Abigail


    Homeostatic regulation of REM sleep plays a key role in neural plasticity and deficits in this process are implicated in the development of many neuropsychiatric disorders. Little is known, however, about the molecular mechanisms that underlie this homeostatic regulation process. This study examined the hypothesis that, during selective REM sleep deprivation (RSD), increased brain-derived neurotrophic factor (BDNF) expression in REM sleep regulating areas is critical for the development of homeostatic drive for REM sleep, as measured by an increase in the number of REM sleep transitions. Rats were assigned to RSD, non-sleep deprived (BSL), or total sleep deprivation (TSD) groups. Physiological recordings were obtained from cortical, hippocampal, and pontine EEG electrodes over a 6h period, in which sleep deprivation occurred during the first 3h. In the RSD, but not the other conditions, homeostatic drive for REM sleep increased progressively. BDNF protein expression was significantly greater in the pedunculopontine tegmentum (PPT) and subcoeruleus nucleus (SubCD) in the RSD as compared to the TSD and BSL groups, areas that regulate REM sleep, but not in the medial preoptic area, which regulates non-REM sleep. There was a significant positive correlation between RSD-induced increases in number of REM sleep episodes and increased BDNF expression in the PPT and SubCD. These increases positively correlated with levels of homeostatic drive for REM sleep. These results, for the first time, suggest that selective RSD-induced increased expression of BDNF in the PPT and SubCD are determinant factors in the development of the homeostatic drive for REM sleep. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. BAER - brainstem auditory evoked response (United States)

    ... auditory potentials; Brainstem auditory evoked potentials; Evoked response audiometry; Auditory brainstem response; ABR; BAEP ... Normal results vary. Results will depend on the person and the instruments used to perform the test.

  11. A brainstem anosognosia of hemiparesis

    Directory of Open Access Journals (Sweden)

    Kazuo Abe


    Full Text Available A woman had anosognosia for hemiplegia as a manifestation of brainstem infarction. She had no mental or neuropsychological disturbances, and had involvement of the brainstem in the frontal/parietal-subcortical circuits to the right cerebral hemisphere. Brainstem lesions that disrupt frontal/parietal-subcortical areas may affect anosognosia for hemiplegia.

  12. Tyrosine hydroxylase is short-term regulated by the ubiquitin-proteasome system in PC12 cells and hypothalamic and brainstem neurons from spontaneously hypertensive rats: possible implications in hypertension.

    Directory of Open Access Journals (Sweden)

    Nadia A Congo Carbajosa

    Full Text Available Aberrations in the ubiquitin-proteasome system (UPS are implicated in the pathogenesis of various diseases. Tyrosine hydroxylase (TH, the rate-limiting enzyme in catecholamines biosynthesis, is involved in hypertension development. In this study we investigated whether UPS regulated TH turnover in PC12 cells and hypothalamic and brainstem neurons from spontaneously hypertensive rats (SHR and whether this system was impaired in hypertension. PC12 cells were exposed to proteasome or lysosome inhibitors and TH protein level evaluated by Western blot. Lactacystin, a proteasome inhibitor, induced an increase of 86 ± 15% in TH levels after 30 min of incubation, then it started to decrease up to 6 h to reach control levels and finally it rose up to 35.2 ± 8.5% after 24 h. Bafilomycin, a lysosome inhibitor, did not alter TH protein levels during short times, but it increased TH by 92 ± 22% above basal after 6 h treatment. Before degradation proteasome substrates are labeled by conjugation with ubiquitin. Efficacy of proteasome inhibition on TH turnover was evidenced by accumulation of ubiquitinylated TH after 30 min. Further, the inhibition of proteasome increased the quantity of TH phosphorylated at Ser40, which is essential for TH activity, by 2.7 ± 0.3 fold above basal. TH protein level was upregulated in neurons from hypothalami and brainstem of SHR when the proteasome was inhibited during 30 min, supporting that neuronal TH is also short-term regulated by the proteasome. Since the increased TH levels reported in hypertension may result from proteasome dysfunction, we evaluate proteasome activity. Proteasome activity was significantly reduced by 67 ± 4% in hypothalamic and brainstem neurons from SHR while its protein levels did not change. Present findings show that TH is regulated by the UPS. The impairment in proteasome activity observed in SHR neurons may be one of the causes of the increased TH protein levels reported in hypertension.

  13. Congenital brainstem disconnection associated with a syrinx of the brainstem

    NARCIS (Netherlands)

    Barth, P. G.; de Vries, L. S.; Nikkels, P. G. J.; Troost, D.

    We report a case of congenital brainstem disconnection including the second detailed autopsy. A full-term newborn presented with irreversible apnoea and died on the fifth day. MRI revealed disconnection of the brainstem. The autopsy included a series of transverse sections of the mesencephalon,

  14. Brain imaging reveals neuronal circuitry underlying the crow’s perception of human faces (United States)

    Marzluff, John M.; Miyaoka, Robert; Minoshima, Satoshi; Cross, Donna J.


    Crows pay close attention to people and can remember specific faces for several years after a single encounter. In mammals, including humans, faces are evaluated by an integrated neural system involving the sensory cortex, limbic system, and striatum. Here we test the hypothesis that birds use a similar system by providing an imaging analysis of an awake, wild animal’s brain as it performs an adaptive, complex cognitive task. We show that in vivo imaging of crow brain activity during exposure to familiar human faces previously associated with either capture (threatening) or caretaking (caring) activated several brain regions that allow birds to discriminate, associate, and remember visual stimuli, including the rostral hyperpallium, nidopallium, mesopallium, and lateral striatum. Perception of threatening faces activated circuitry including amygdalar, thalamic, and brainstem regions, known in humans and other vertebrates to be related to emotion, motivation, and conditioned fear learning. In contrast, perception of caring faces activated motivation and striatal regions. In our experiments and in nature, when perceiving a threatening face, crows froze and fixed their gaze (decreased blink rate), which was associated with activation of brain regions known in birds to regulate perception, attention, fear, and escape behavior. These findings indicate that, similar to humans, crows use sophisticated visual sensory systems to recognize faces and modulate behavioral responses by integrating visual information with expectation and emotion. Our approach has wide applicability and potential to improve our understanding of the neural basis for animal behavior. PMID:22984177

  15. Optogenetic mapping of brain circuitry (United States)

    Augustine, George J.; Berglund, Ken; Gill, Harin; Hoffmann, Carolin; Katarya, Malvika; Kim, Jinsook; Kudolo, John; Lee, Li M.; Lee, Molly; Lo, Daniel; Nakajima, Ryuichi; Park, Min Yoon; Tan, Gregory; Tang, Yanxia; Teo, Peggy; Tsuda, Sachiko; Wen, Lei; Yoon, Su-In


    Studies of the brain promise to be revolutionized by new experimental strategies that harness the combined power of optical techniques and genetics. We have mapped the circuitry of the mouse brain by using both optogenetic actuators that control neuronal activity and optogenetic sensors that detect neuronal activity. Using the light-activated cation channel, channelrhodopsin-2, to locally photostimulate neurons allows high-speed mapping of local and long-range circuitry. For example, with this approach we have mapped local circuits in the cerebral cortex, cerebellum and many other brain regions. Using the fluorescent sensor for chloride ions, Clomeleon, allows imaging of the spatial and temporal dimensions of inhibitory circuits in the brain. This approach allows imaging of both conventional "phasic" synaptic inhibition as well as unconventional "tonic" inhibition. The combined use of light to both control and monitor neural activity creates unprecedented opportunities to explore brain function, screen pharmaceutical agents, and potentially to use light to ameliorate psychiatric and neurological disorders.

  16. Dynamic causal modeling in PTSD and its dissociative subtype: Bottom-up versus top-down processing within fear and emotion regulation circuitry. (United States)

    Nicholson, Andrew A; Friston, Karl J; Zeidman, Peter; Harricharan, Sherain; McKinnon, Margaret C; Densmore, Maria; Neufeld, Richard W J; Théberge, Jean; Corrigan, Frank; Jetly, Rakesh; Spiegel, David; Lanius, Ruth A


    Posttraumatic stress disorder (PTSD) is associated with decreased top-down emotion modulation from medial prefrontal cortex (mPFC) regions, a pathophysiology accompanied by hyperarousal and hyperactivation of the amygdala. By contrast, PTSD patients with the dissociative subtype (PTSD + DS) often exhibit increased mPFC top-down modulation and decreased amygdala activation associated with emotional detachment and hypoarousal. Crucially, PTSD and PTSD + DS display distinct functional connectivity within the PFC, amygdala complexes, and the periaqueductal gray (PAG), a region related to defensive responses/emotional coping. However, differences in directed connectivity between these regions have not been established in PTSD, PTSD + DS, or controls. To examine directed (effective) connectivity among these nodes, as well as group differences, we conducted resting-state stochastic dynamic causal modeling (sDCM) pairwise analyses of coupling between the ventromedial (vm)PFC, the bilateral basolateral and centromedial (CMA) amygdala complexes, and the PAG, in 155 participants (PTSD [n = 62]; PTSD + DS [n = 41]; age-matched healthy trauma-unexposed controls [n = 52]). PTSD was characterized by a pattern of predominant bottom-up connectivity from the amygdala to the vmPFC and from the PAG to the vmPFC and amygdala. Conversely, PTSD + DS exhibited predominant top-down connectivity between all node pairs (from the vmPFC to the amygdala and PAG, and from the amygdala to the PAG). Interestingly, the PTSD + DS group displayed the strongest intrinsic inhibitory connections within the vmPFC. These results suggest the contrasting symptom profiles of PTSD and its dissociative subtype (hyper- vs. hypo-emotionality, respectively) may be driven by complementary changes in directed connectivity corresponding to bottom-up defensive fear processing versus enhanced top-down regulation. Hum Brain Mapp 38:5551-5561, 2017. © 2017 Wiley Periodicals, Inc.

  17. Evidence for altered basal ganglia-brainstem connections in cervical dystonia.

    Directory of Open Access Journals (Sweden)

    Anne J Blood

    Full Text Available There has been increasing interest in the interaction of the basal ganglia with the cerebellum and the brainstem in motor control and movement disorders. In addition, it has been suggested that these subcortical connections with the basal ganglia may help to coordinate a network of regions involved in mediating posture and stabilization. While studies in animal models support a role for this circuitry in the pathophysiology of the movement disorder dystonia, thus far, there is only indirect evidence for this in humans with dystonia.In the current study we investigated probabilistic diffusion tractography in DYT1-negative patients with cervical dystonia and matched healthy control subjects, with the goal of showing that patients exhibit altered microstructure in the connectivity between the pallidum and brainstem. The brainstem regions investigated included nuclei that are known to exhibit strong connections with the cerebellum. We observed large clusters of tractography differences in patients relative to healthy controls, between the pallidum and the brainstem. Tractography was decreased in the left hemisphere and increased in the right hemisphere in patients, suggesting a potential basis for the left/right white matter asymmetry we previously observed in focal dystonia patients.These findings support the hypothesis that connections between the basal ganglia and brainstem play a role in the pathophysiology of dystonia.

  18. Memristor Circuitry via Material Implication (United States)

    Wright, Anna; Gergel-Hackett, Nadine

    Memristors are novel nanoelectronic devices that have advantages over traditional computer circuitry (eg., they are nonvolatile, two-terminal, and low power) and thus have potential circuit applications for both digital logic and memory. In this work, we used a simple memristor model that was designed to replicate the real-world electrical characteristics of previously fabricated and tested memristor devices. This model was developed and constructed with basic circuit elements using a free and widely available circuit simulator, LT Spice. We updated this model to more realistically simulate memristor behavior and then theoretically demonstrated that the model can be used to build memristor-based material implication gates (IMPLY gates). The development of these IMPLY gates is a critical step in the realization of memristor-based digital logic because they can be combined to act in place of any of the basic traditional logic gates (AND, NAND, etc), and thus enable efficient entirely memristor-based computing.

  19. Lyme disease of the brainstem

    Energy Technology Data Exchange (ETDEWEB)

    Kalina, Peter [Mayo Clinic, Department of Radiology, Rochester, MN (United States); Decker, Andrew [Northern Westchester Hospital Center, Department of Neurology, Mt. Kisco, NY (United States); Kornel, Ezriel [Northern Westchester Hospital Center, Division of Neurosurgery, Mt. Kisco, NY (United States); Halperin, John J. [North Shore University Hospital, Department of Neurology, Manhasset, NY (United States)


    Lyme disease is a multisystem infectious disease caused by the tick-borne spirochete, Borrelia burgdorferi. Central nervous system (CNS) involvement typically causes local inflammation, most commonly meningitis, but rarely parenchymal brain involvement. We describe a patient who presented with clinical findings suggesting a brainstem process. Magnetic resonance imaging (MRI) and positron emission tomography (PET) suggested a brainstem neoplasm. Prior to biopsy, laboratory evaluation led to the diagnosis of Lyme disease. Clinical and imaging abnormalities improved markedly following antimicrobial therapy. We describe Lyme disease involvement of the cerebellar peduncles with hypermetabolism on PET. Although MRI is the primary imaging modality for most suspected CNS pathology, the practical applications of PET continue to expand. (orig.)

  20. Pilomyxoid astrocytoma of the brainstem

    Directory of Open Access Journals (Sweden)

    Marco Antonio Zanini


    Full Text Available A pilomyxoid astrocytoma is a recently described tumor that occurs predominantly in the hypothalamic-chiasmatic region and is rarely found elsewhere. It has similar features as pilocytic astrocytomas, but has distinct histological characteristics and a poorer prognosis. A pilomyxoid astrocytoma is an aggressive tumor, and increased awareness is necessary with a suspect case. We present the first case of a pilomyxoid astrocytoma of the brainstem described after the newest World Health Organization classification of central nervous system tumors.

  1. Evolution of gustatory reflex systems in the brainstems of fishes. (United States)

    Finger, Thomas E


    The great number of species of teleosts permits highly specialized forms to evolve to occupy particular niches. This diversity allows for extreme variations in brain structure according to particular sensory or motor adaptations. In the case of the taste system, goldfish (Carassius auratus L., 1758) and some carps have evolved a specialized intraoral food-sorting apparatus along with corresponding specializations of gustatory centers in the brainstem. A comparison of circuitry within the complex vagal lobe of goldfish, and of the simpler gustatory lobes in catfish (Ictalurus punctatus Rafinesque, 1818) shows numerous similarities in organization and neurotransmitters. Double labeling studies using horseradish peroxidase and biotinylated dextran amine in catfish shows a direct projection from the vagal lobe to the motoneurons of nucleus ambiguous which innervate oropharyngeal musculature. Therefore, a three neuron reflex arc connects gustatory input to motor output. In the vagal lobe of goldfish, a similar three neuron arc can be identified: from primary gustatory afferent, to vagal lobe interneuron, thence to dendrites of the vagal motoneurons that innervate the pharyngeal muscles. Therefore, despite large differences in the gross appearance of the vagal gustatory systems in the brains of catfish and goldfish, the essential connectivity and circuitry is similar. This suggests that evolutionary change in the central nervous system largely proceeds by rearrangement and elaboration of existing systems, rather than by addition of new structures or circuits.

  2. Auditory brainstem implant program development. (United States)

    Schwartz, Marc S; Wilkinson, Eric P


    Auditory brainstem implants (ABIs), which have previously been used to restore auditory perception to deaf patients with neurofibromatosis type 2 (NF2), are now being utilized in other situations, including treatment of congenitally deaf children with cochlear malformations or cochlear nerve deficiencies. Concurrent with this expansion of indications, the number of centers placing and expressing interest in placing ABIs has proliferated. Because ABI placement involves posterior fossa craniotomy in order to access the site of implantation on the cochlear nucleus complex of the brainstem and is not without significant risk, we aim to highlight issues important in developing and maintaining successful ABI programs that would be in the best interests of patients. Especially with pediatric patients, the ultimate benefits of implantation will be known only after years of growth and development. These benefits have yet to be fully elucidated and continue to be an area of controversy. The limited number of publications in this area were reviewed. Review of the current literature was performed. Disease processes, risk/benefit analyses, degrees of evidence, and U.S. Food and Drug Administration approvals differ among various categories of patients in whom auditory brainstem implantation could be considered for use. We suggest sets of criteria necessary for the development of successful and sustaining ABI programs, including programs for NF2 patients, postlingually deafened adult nonneurofibromatosis type 2 patients, and congenitally deaf pediatric patients. Laryngoscope, 127:1909-1915, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  3. Robust Langmuir probe circuitry for fusion research (United States)

    Boedo, J.; Gunner, G.; Gray, D.; Conn, R.


    Langmuir probes attached to the plasma facing components of fusion experiments are biased with constant or swept voltages to obtain measurements of plasma parameters such as electron temperature and density. The circuitry used must be rugged and protect the power supplies and electronics against generally harsh conditions and sudden discharge terminations, or disruptions. Modularity, ease of repair and expandability are important because short-lived radiation from neutron activation is often present after the discharges, preventing access to the circuitry. We report the implementation of modular probe circuitry featuring robust protection, remote testing and reset and easy maintenance and expandability, achieved by using DIN-rail modules.

  4. Hyperekplexia and trismus due to brainstem encephalopathy (United States)

    Kellett, M.; Humphrey, P.; Tedman, B.; Steiger, M.


    The brainstem is said to be the generator of pathological startle responses due to reticular reflex myoclonus or hyperekplexia. A patient with facial weakness, nystagmus, and pyramidal tract signs had generalised reflex spasms in response to auditory, visual and tactile stimuli which clinically and neurophysiologically resembled hyperekplexia. The case is unusual because as well as hyperekplexia, the patient's initial presentation was with an equally rare manifestation of brainstem pathology—brainstem mediated trismus. The causes of brainstem trismus and exaggerated startle responses are discussed with respect to their underlying mechanisms. 


  5. Hypertensive Encephalopathy with Reversible Brainstem Edema

    National Research Council Canada - National Science Library

    Lee, Sungjoon; Cho, Byung-Kyu; Kim, Hoon


    .... The patient's condition was thus interpreted as hypertensive brainstem encephalopathy. While many consider this a vasogenic phenomenon, induced by sudden, severe hypertension, the precise mechanism remains unclear...

  6. Brainstem epidermoid cyst: An update (United States)

    Patibandla, M. R.; Yerramneni, Vamsi Krishna; Mudumba, Vijaya S.; Manisha, Nukavarapu; Addagada, Gokul Chowdary


    The incidence of epidermoid tumors is between 1% and 2% of all intracranial tumors. The usual locations of epidermoid tumor are the parasellar region and cerebellopontine angle, and it is less commonly located in sylvian fissure, suprasellar region, cerebral and cerebellar hemispheres, and lateral and fourth ventricles. Epidermoid cysts located in the posterior fossa usually arise in the lateral subarachnoid cisterns, and those located in the brain stem are rare. These epidermoids contain cheesy and flaky white soft putty like contents. Epidermoid cysts are very slow growing tumors having a similar growth pattern of the epidermal cells of the skin and develop from remnants of epidermal elements during closure of the neural groove and disjunction of the surface ectoderm with neural ectoderm between the third and fifth weeks of embryonic life. We are presenting an interesting case of intrinsic brainstem epidermoid cyst containing milky white liquefied material with flakes in a 5-year-old girl. Diffusion-weighted imaging is definitive for the diagnosis. Ideal treatment of choice is removal of cystic components with complete resection of capsule. Although radical resection will prevent recurrence, in view of very thin firmly adherent capsule to brainstem, it is not always possible to do complete resection of capsule without any neurological deficits. PMID:27366244

  7. Relationships between behavior, brainstem and cortical encoding of seen and heard speech in musicians and non-musicians (United States)

    Musacchia, Gabriella; Strait, Dana; Kraus, Nina


    Musicians have a variety of perceptual and cortical specializations compared to non-musicians. Recent studies have shown that potentials evoked from primarily brainstem structures are enhanced in musicians, compared to non-musicians. Specifically, musicians have more robust representations of pitch periodicity and faster neural timing to sound onset when listening to sounds or both listening to and viewing a speaker. However, it is not known whether musician-related enhancements at the subcortical level are correlated with specializations in the cortex. Does musical training shape the auditory system in a coordinated manner or in disparate ways at cortical and subcortical levels? To answer this question, we recorded simultaneous brainstem and cortical evoked responses in musician and non-musician subjects. Brainstem response periodicity was related to early cortical response timing across all subjects, and this relationship was stronger in musicians. Peaks of the brainstem response evoked by sound onset and timbre cues were also related to cortical timing. Neurophysiological measures at both levels correlated with musical skill scores across all subjects. In addition, brainstem and cortical measures correlated with the age musicians began their training and the years of musical practice. Taken together, these data imply that neural representations of pitch, timing and timbre cues and cortical response timing are shaped in a coordinated manner, and indicate corticofugal modulation of subcortical afferent circuitry. PMID:18562137

  8. Brainstem and cerebellar cavernous malformations. (United States)

    Atwal, Gursant S; Sarris, Christina E; Spetzler, Robert F


    Cavernous malformations are vascular lesions that occur throughout the central nervous system, most commonly in the supratentorial location, with brainstem and cerebellar cavernous malformations occurring more rarely. Cavernous malformations are associated with developmental venous anomalies that occur sporadically or in familial form. Patients with a cavernous malformation can present with headaches, seizures, sensorimotor disturbances, or focal neurologic deficits based on the anatomic location of the lesion. Patients with infratentorial lesions present more commonly with a focal neurologic deficit. Cavernous malformations are increasingly discovered incidentally due to the increasing use of magnetic resonance imaging. Understanding the natural history of these lesions is essential to their management. Observation and surgical resection are both reasonable options in the treatment of patients with these lesions. The clinical presentation of the patient, the location of the lesion, and the surgical risk assessment all play critical roles in management decision-making. © 2017 Elsevier B.V. All rights reserved.

  9. Imaging of adult brainstem gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Purohit, Bela, E-mail:; Kamli, Ali A.; Kollias, Spyros S.


    Highlights: •BSG are classified on MRI into diffuse low-grade, malignant, focal tectal and exophytic subtypes. •Their prognosis and treatment is variable and is almost similar to adult supratentorial gliomas. •This article illustrates the imaging of adult BSGs on MRI and FET-PET. •We also describe prognostic factors and the treatment options of these tumours. -- Abstract: Brainstem gliomas (BSGs) are uncommon in adults accounting for about 2% of all intracranial neoplasms. They are often phenotypically low-grade as compared to their more common paediatric counterparts. Since brainstem biopsies are rarely performed, these tumours are commonly classified according to their MR imaging characteristics into 4 subgroups: (a) diffuse intrinsic low-grade gliomas, (b) enhancing malignant gliomas, (c) focal tectal gliomas and (d) exophytic gliomas/other subtypes. The prognosis and treatment is variable for the different types and is almost similar to adult supratentorial gliomas. Radiotherapy (RT) with adjuvant chemotherapy is the standard treatment of diffuse low-grade and malignant BSGs, whereas, surgical resection is limited to the exophytic subtypes. Review of previous literature shows that the detailed imaging of adult BSGs has not received significant attention. This review illustrates in detail the imaging features of adult BSGs using conventional and advanced MR techniques like diffusion weighted imaging (DWI), diffusion tensor imaging (DTI), MR perfusion weighted imaging (PWI), MR spectroscopy (MRS), as well as {sup 18}F-fluoro-ethyl-tyrosine positron emission tomography ({sup 18}F-FET/PET). We have discussed the pertinent differences between childhood and adult BSGs, imaging mimics, prognostic factors and briefly reviewed the treatment options of these tumours.

  10. Delayed neuronal cell death in brainstem after transient brainstem ischemia in gerbils

    Directory of Open Access Journals (Sweden)

    Hakuba Nobuhiro


    Full Text Available Abstract Background Because of the lack of reproducible brainstem ischemia models in rodents, the temporal profile of ischemic lesions in the brainstem after transient brainstem ischemia has not been evaluated intensively. Previously, we produced a reproducible brainstem ischemia model of Mongolian gerbils. Here, we showed the temporal profile of ischemic lesions after transient brainstem ischemia. Results Brainstem ischemia was produced by occlusion of the bilateral vertebral arteries just before their entry into the transverse foramina of the cervical vertebrae of Mongolian gerbils. Animals were subjected to brainstem ischemia for 15 min, and then reperfused for 0 d (just after ischemia, 1 d, 3 d and 7 d (n = 4 in each group. Sham-operated animals (n = 4 were used as control. After deep anesthesia, the gerbils were perfused with fixative for immunohistochemical investigation. Ischemic lesions were detected by immunostaining for microtubule-associated protein 2 (MAP2. Just after 15-min brainstem ischemia, ischemic lesions were detected in the lateral vestibular nucleus and the ventral part of the spinal trigeminal nucleus, and these ischemic lesions disappeared one day after reperfusion in all animals examined. However, 3 days and 7 days after reperfusion, ischemic lesions appeared again and clusters of ionized calcium-binding adapter molecule-1(IBA-1-positive cells were detected in the same areas in all animals. Conclusion These results suggest that delayed neuronal cell death took place in the brainstem after transient brainstem ischemia in gerbils.

  11. Signal conditioning circuitry design for instrumentation systems.

    Energy Technology Data Exchange (ETDEWEB)

    Larsen, Cory A.


    This report details the current progress in the design, implementation, and validation of the signal conditioning circuitry used in a measurement instrumentation system. The purpose of this text is to document the current progress of a particular design in signal conditioning circuitry in an instrumentation system. The input of the signal conditioning circuitry comes from a piezoresistive transducer and the output will be fed to a 250 ksps, 12-bit analog-to-digital converter (ADC) with an input range of 0-5 V. It is assumed that the maximum differential voltage amplitude input from the sensor is 20 mV with an unknown, but presumably high, sensor bandwidth. This text focuses on a specific design; however, the theory is presented in such a way that this text can be used as a basis for future designs.

  12. Influence of general anaesthesia on the brainstem. (United States)

    Bosch, L; Fernández-Candil, J; León, A; Gambús, P L


    The exact role of the brainstem in the control of body functions is not yet well known and the same applies to the influence of general anaesthesia on brainstem functions. Nevertheless in all general anaesthesia the anaesthesiologist should be aware of the interaction of anaesthetic drugs and brainstem function in relation to whole body homeostasis. As a result of this interaction there will be changes in consciousness, protective reflexes, breathing pattern, heart rate, temperature or arterial blood pressure to name a few. Brainstem function can be explored using three different approaches: clinically, analyzing changes in brain electric activity or using neuroimaging techniques. With the aim of providing the clinician anaesthesiologist with a global view of the interaction between the anaesthetic state and homeostatic changes related to brainstem function, the present review article addresses the influence of anaesthetic drug effects on brainstem function through clinical exploration of cranial nerves and reflexes, analysis of electric signals such as electroencephalographic changes and what it is known about brainstem through the use of imaging techniques, more specifically functional magnetic resonance imaging. Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Bayesian segmentation of brainstem structures in MRI

    DEFF Research Database (Denmark)

    Iglesias, Juan Eugenio; Van Leemput, Koen; Bhatt, Priyanka


    In this paper we present a method to segment four brainstem structures (midbrain, pons, medulla oblongata and superior cerebellar peduncle) from 3D brain MRI scans. The segmentation method relies on a probabilistic atlas of the brainstem and its neighboring brain structures. To build the atlas, we...... the brainstem structures in novel scans. Thanks to the generative nature of the scheme, the segmentation method is robust to changes in MRI contrast or acquisition hardware. Using cross validation, we show that the algorithm can segment the structures in previously unseen T1 and FLAIR scans with great accuracy...

  14. Current clinical management of brainstem cavernomas. (United States)

    Bozinov, Oliver; Hatano, Taketo; Sarnthein, Johannes; Burkhardt, Jan-Karl; Bertalanffy, Helmut


    Over the last two decades a favourable course for treated or nontreated brainstem cavernomas has become possible with enhanced diagnostic tools and clinical experience, as well as minimally invasive microsurgical improvements. Currently, brainstem cavernoma can be treated microsurgically with excellent results and an acceptable morbidity rate. The preferred surgical route has progressively shifted from a dorsal to a lateral approach, but this remains dependent on the location of the lesion in the brainstem. Surgical evaluation and management of all cases of this rare disease should be performed by experienced teams from the outset.

  15. Brainstem involvement in subacute sclerosing panencephalitis. (United States)

    Sharma, Pawan; Singh, Dileep; Singh, Maneesh Kumar; Garg, Ravindra Kumar; Kohli, Neera


    The parieto-occipital region of the brain is most frequently and severely affected in subacute sclerosing panencephalitis (SSPE). The basal ganglia, cerebellum and corpus callosum are less commonly involved. Brainstem involvement is rarely described in SSPE, and usually there is involvement of other regions of the brain. We describe a patient with subacute sclerosing panencephalitis with brain magnetic resonance imaging showing extensive brainstem involvement without significant involvement of other cortical structures. Though rarely described in SSPE, one should be aware of such brainstem and cerebellum involvement, and SSPE should be kept in mind when brainstem signal changes are seen in brain MRI with or without involvement of other regions of brain to avoid erroneous reporting.

  16. Optogenetic dissection of medial prefrontal cortex circuitry

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    Danai eRiga


    Full Text Available The medial prefrontal cortex (mPFC is critically involved in numerous cognitive functions, including attention, inhibitory control, habit formation, working memory and long-term memory. Moreover, through its dense interconnectivity with subcortical regions (e.g. thalamus, striatum, amygdala and hippocampus, the mPFC is thought to exert top-down executive control over the processing of aversive and appetitive stimuli. Because the mPFC has been implicated in the processing of a wide range of cognitive and emotional stimuli, it is thought to function as a central hub in the brain circuitry mediating symptoms of psychiatric disorders. New optogenetics technology enables anatomical and functional dissection of mPFC circuitry with unprecedented spatial and temporal resolution. This provides important novel insights in the contribution of specific neuronal subpopulations and their connectivity to mPFC function in health and disease states. In this review, we present the current knowledge obtained with optogenetic methods concerning mPFC function and dysfunction and integrate this with findings from traditional intervention approaches used to investigate the mPFC circuitry in animal models of cognitive processing and psychiatric disorders.

  17. Brainstem reflexes in patients with familial dysautonomia. (United States)

    Gutiérrez, Joel V; Norcliffe-Kaufmann, Lucy; Kaufmann, Horacio


    Several distinctive clinical features of patients with familial dysautonomia (FD) including dysarthria and dysphagia suggest a developmental defect in brainstem reflexes. Our aim was to characterize the neurophysiological profile of brainstem reflexes in these patients. We studied the function of sensory and motor trigeminal tracts in 28 patients with FD. All were homozygous for the common mutation in the IKAP gene. Each underwent a battery of electrophysiological tests including; blink reflexes, jaw jerk reflex, masseter silent periods and direct stimulation of the facial nerve. Responses were compared with 25 age-matched healthy controls. All patients had significantly prolonged latencies and decreased amplitudes of all examined brainstem reflexes. Similar abnormalities were seen in the early and late components. In contrast, direct stimulation of the facial nerve revealed relative preservation of motor responses. The brainstem reflex abnormalities in FD are best explained by impairment of the afferent and central pathways. A reduction in the number and/or excitability of trigeminal sensory axons is likely the main problem. These findings add further evidence to the concept that congenital mutations of the elongator-1 protein (or IKAP) affect the development of afferent neurons including those carrying information for the brainstem reflex pathways. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  18. Gamma Knife Treatment of Brainstem Metastases

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    Halloran E. Peterson


    Full Text Available The management of brainstem metastases is challenging. Surgical treatment is usually not an option, and chemotherapy is of limited utility. Stereotactic radiosurgery has emerged as a promising palliative treatment modality in these cases. The goal of this study is to assess our single institution experience treating brainstem metastases with Gamma Knife radiosurgery (GKRS. This retrospective chart review studied 41 patients with brainstem metastases treated with GKRS. The most common primary tumors were lung, breast, renal cell carcinoma, and melanoma. Median age at initial treatment was 59 years. Nineteen (46% of the patients received whole brain radiation therapy (WBRT prior to or concurrent with GKRS treatment. Thirty (73% of the patients had a single brainstem metastasis. The average GKRS dose was 17 Gy. Post-GKRS overall survival at six months was 42%, at 12 months was 22%, and at 24 months was 13%. Local tumor control was achieved in 91% of patients, and there was one patient who had a fatal brain hemorrhage after treatment. Karnofsky performance score (KPS >80 and the absence of prior WBRT were predictors for improved survival on multivariate analysis (HR 0.60 (p = 0.02, and HR 0.28 (p = 0.02, respectively. GKRS was an effective treatment for brainstem metastases, with excellent local tumor control.

  19. Is enhanced MRI helpful in brainstem infarction?

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    Jeong, Y. M.; Shin, G. H.; Choi, W. S. [Kyung Hee University Hospital, Seoul (Korea, Republic of)


    To determine the role of MR contrast enhancement in evaluating time course of brainstem infarction. MR imaging with IV administration of gadopentetate dimeglumine was retrospectively reviewed in 43 patients with clinically and radiologically documented brainstem infarctions. The pattern of infarction was classified into spotty and patchy. Presence of parenchymal enhancement in infarction was evaluated. By location, there were 34 pontine, 3 midbrain, 6 medullary infarctions. The age of the infarctions ranged from 1 day to 9 months, with 5 patients scanned within 3 days and 10 scanned within 2 weeks of clinical ictus. Abnormalities on T2-weighted images were encountered in every case, with spotty pattern in 14 cases and patchy pattern in 29 cases. Parenchymal contrast enhancement was seen in 9 cases(20%), primarily occurring between days 8 and 20. MR contrast enhancement in brainstem infarction was infrequent that it may not be useful in the estimation of the age of infarction.

  20. The development of micromachined gyroscope structure and circuitry technology. (United States)

    Xia, Dunzhu; Yu, Cheng; Kong, Lun


    This review surveys micromachined gyroscope structure and circuitry technology. The principle of micromachined gyroscopes is first introduced. Then, different kinds of MEMS gyroscope structures, materials and fabrication technologies are illustrated. Micromachined gyroscopes are mainly categorized into micromachined vibrating gyroscopes (MVGs), piezoelectric vibrating gyroscopes (PVGs), surface acoustic wave (SAW) gyroscopes, bulk acoustic wave (BAW) gyroscopes, micromachined electrostatically suspended gyroscopes (MESGs), magnetically suspended gyroscopes (MSGs), micro fiber optic gyroscopes (MFOGs), micro fluid gyroscopes (MFGs), micro atom gyroscopes (MAGs), and special micromachined gyroscopes. Next, the control electronics of micromachined gyroscopes are analyzed. The control circuits are categorized into typical circuitry and special circuitry technologies. The typical circuitry technologies include typical analog circuitry and digital circuitry, while the special circuitry consists of sigma delta, mode matching, temperature/quadrature compensation and novel special technologies. Finally, the characteristics of various typical gyroscopes and their development tendency are discussed and investigated in detail.

  1. The Development of Micromachined Gyroscope Structure and Circuitry Technology

    Directory of Open Access Journals (Sweden)

    Dunzhu Xia


    Full Text Available This review surveys micromachined gyroscope structure and circuitry technology. The principle of micromachined gyroscopes is first introduced. Then, different kinds of MEMS gyroscope structures, materials and fabrication technologies are illustrated. Micromachined gyroscopes are mainly categorized into micromachined vibrating gyroscopes (MVGs, piezoelectric vibrating gyroscopes (PVGs, surface acoustic wave (SAW gyroscopes, bulk acoustic wave (BAW gyroscopes, micromachined electrostatically suspended gyroscopes (MESGs, magnetically suspended gyroscopes (MSGs, micro fiber optic gyroscopes (MFOGs, micro fluid gyroscopes (MFGs, micro atom gyroscopes (MAGs, and special micromachined gyroscopes. Next, the control electronics of micromachined gyroscopes are analyzed. The control circuits are categorized into typical circuitry and special circuitry technologies. The typical circuitry technologies include typical analog circuitry and digital circuitry, while the special circuitry consists of sigma delta, mode matching, temperature/quadrature compensation and novel special technologies. Finally, the characteristics of various typical gyroscopes and their development tendency are discussed and investigated in detail.

  2. Auditory brain-stem responses in adrenomyeloneuropathy. (United States)

    Grimes, A M; Elks, M L; Grunberger, G; Pikus, A M


    We studied three patients with adrenomyeloneuropathy. Complete audiologic assessment was obtained: two patients showed unimpaired peripheral hearing and one showed a mild high-frequency hearing loss. Auditory brain-stem responses were abnormal in both ears of all subjects, with one subject showing no response above wave I, and the other two having significant wave I to III and wave III to V interval prolongations. We concluded that auditory brain-stem response testing provides a simple, valid, reliable method for demonstrating neurologic abnormality in adrenomyeloneuropathy even prior to evidence of clinical signs.

  3. Acute disseminated encephalomyelitis presenting as a solitary brainstem mass. (United States)

    Miller, D H; Scaravilli, F; Thomas, D C; Harvey, P; Hirsch, N P


    A 36 year old woman presented with a subacute brainstem syndrome. MRI showed a solitary, gadolinium enhancing brainstem mass, which on biopsy showed perivenous inflammation and demyelination compatible with acute disseminated encephalomyelitis. Images PMID:8350113

  4. Brainstem Encephalitis and ADEM Following Mumps

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    J Gordon Millichap


    Full Text Available Clinical manifestations of brainstem encephalitis (BSE with fever, decreased level of consciousness, and left facial and abducens paralysis developed 1 week after bilateral parotitis and mumps in a 4 year-old female child and were followed by symptoms of acute disseminated encephalomyelitis (ADEM within 20 days of recovery from BSE.

  5. Functional maps of neocortical local circuitry

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    Alex M Thomson


    Full Text Available This review aims to summarize data obtained with different techniques to provide a functional map of the local circuit connections made by neocortical neurones, a reference for those interested in cortical circuitry and the numerical information required by those wishing to model the circuit. A brief description of the main techniques used to study circuitry is followed by outline descriptions of the major classes of neocortical excitatory and inhibitory neurones and the connections that each layer makes with other cortical and subcortical regions. Maps summarizing the projection patterns of each class of neurone within the local circuit and tables of the properties of these local circuit connections are provided.This review relies primarily on anatomical studies that have identified the classes of neurones and their local and long distance connections and on paired intracellular and whole-cell recordings which have documented the properties of the connections between them. A large number of different types of synaptic connections have been described, but for some there are only a few published examples and for others the details that can only be obtained with paired recordings and dye-filling are lacking. A further complication is provided by the range of species, technical approaches and age groups used in these studies. Wherever possible the range of available data are summarised and compared. To fill some of the more obvious gaps for the less well-documented cases, data obtained with other methods are also summarized.

  6. Chemosensory pathways in the brainstem controlling cardiorespiratory activity. (United States)

    Spyer, K Michael; Gourine, Alexander V


    Cardiorespiratory activity is controlled by a network of neurons located within the lower brainstem. The basic rhythm of breathing is generated by neuronal circuits within the medullary pre-Bötzinger complex, modulated by pontine and other inputs from cell groups within the medulla oblongata and then transmitted to bulbospinal pre-motor neurons that relay the respiratory pattern to cranial and spinal motor neurons controlling respiratory muscles. Cardiovascular sympathetic and vagal activities have characteristic discharges that are patterned by respiratory activity. This patterning ensures ventilation-perfusion matching for optimal respiratory gas exchange within the lungs. Peripheral arterial chemoreceptors and central respiratory chemoreceptors are crucial for the maintenance of cardiorespiratory homeostasis. Inputs from these receptors ensure adaptive changes in the respiratory and cardiovascular motor outputs in various environmental and physiological conditions. Many of the connections in the reflex pathway that mediates the peripheral arterial chemoreceptor input have been established. The nucleus tractus solitarii, the ventral respiratory network, pre-sympathetic circuitry and vagal pre-ganglionic neurons at the level of the medulla oblongata are integral components, although supramedullary structures also play a role in patterning autonomic outflows according to behavioural requirements. These medullary structures mediate cardiorespiratory reflexes that are initiated by the carotid and aortic bodies in response to acute changes in PO(2), PCO(2) and pH in the arterial blood. The level of arterial PCO(2) is the primary factor in determining respiratory drive and although there is a significant role of the arterial chemoreceptors, the principal sensor is located either at or in close proximity to the ventral surface of the medulla. The cellular and molecular mechanisms of central chemosensitivity as well as the neural basis for the integration of central and

  7. Hypothalamic and brainstem neuronal circuits controlling homeostatic energy balance. (United States)

    Schneeberger, Marc; Gomis, Ramon; Claret, Marc


    Alterations in adequate energy balance maintenance result in serious metabolic disturbances such as obesity. In mammals, this complex process is orchestrated by multiple and distributed neuronal circuits. Hypothalamic and brainstem neuronal circuits are critically involved in the sensing of circulating and local factors conveying information about the energy status of the organism. The integration of these signals culminates in the generation of specific and coordinated physiological responses aimed at regulating energy balance through the modulation of appetite and energy expenditure. In this article, we review current knowledge on the homeostatic regulation of energy balance, emphasizing recent advances in mouse genetics, electrophysiology, and optogenetic techniques that have greatly contributed to improving our understanding of this central process.

  8. Optogenetic deconstruction of sleep-wake circuitry in the brain

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    Antoine Adamantidis


    Full Text Available How does the brain regulate the sleep-wake cycle? What are the temporal codes of sleep- and wake-promoting neural circuits? How do these circuits interact with each other across the light/dark cycle? Over the past few decades, many studies from a variety of disciplines have made substantial progress in answering these fundamental questions. For example, neurobiologists have identified multiple, redundant wake-promoting circuits in the brainstem, hypothalamus, and basal forebrain. Sleep-promoting circuits have been found in the preoptic area and hypothalamus. One of the greatest challenges in recent years has been to selectively record and manipulate these sleep-wake centers in vivo with high spatial and temporal resolution. Recent developments in microbial opsin-based neuromodulation tools, collectively referred to as “optogenetics,” have provided a novel method to demonstrate causal links between neural activity and specific behaviors. Here, we propose to use optogenetics as a fundamental tool to probe the necessity, sufficiency, and connectivity of defined neural circuits in the regulation of sleep and wakefulness.

  9. Presbycusis and auditory brainstem responses: a review

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    Shilpa Khullar


    Full Text Available Age-related hearing loss or presbycusis is a complex phenomenon consisting of elevation of hearing levels as well as changes in the auditory processing. It is commonly classified into four categories depending on the cause. Auditory brainstem responses (ABRs are a type of early evoked potentials recorded within the first 10 ms of stimulation. They represent the synchronized activity of the auditory nerve and the brainstem. Some of the changes that occur in the aging auditory system may significantly influence the interpretation of the ABRs in comparison with the ABRs of the young adults. The waves of ABRs are described in terms of amplitude, latencies and interpeak latency of the different waves. There is a tendency of the amplitude to decrease and the absolute latencies to increase with advancing age but these trends are not always clear due to increase in threshold with advancing age that act a major confounding factor in the interpretation of ABRs.

  10. Effects of Caffeine on Auditory Brainstem Response

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    Saleheh Soleimanian


    Full Text Available Background and Aim: Blocking of the adenosine receptor in central nervous system by caffeine can lead to increasing the level of neurotransmitters like glutamate. As the adenosine receptors are present in almost all brain areas like central auditory pathway, it seems caffeine can change conduction in this way. The purpose of this study was to evaluate the effects of caffeine on latency and amplitude of auditory brainstem response(ABR.Materials and Methods: In this clinical trial study 43 normal 18-25 years old male students were participated. The subjects consumed 0, 2 and 3 mg/kg BW caffeine in three different sessions. Auditory brainstem responses were recorded before and 30 minute after caffeine consumption. The results were analyzed by Friedman and Wilcoxone test to assess the effects of caffeine on auditory brainstem response.Results: Compared to control group the latencies of waves III,V and I-V interpeak interval of the cases decreased significantly after 2 and 3mg/kg BW caffeine consumption. Wave I latency significantly decreased after 3mg/kg BW caffeine consumption(p<0.01. Conclusion: Increasing of the glutamate level resulted from the adenosine receptor blocking brings about changes in conduction in the central auditory pathway.

  11. Involvement of a chromatin modifier in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell injury: Probably an indirect action via the regulation of NFκB/FasL circuitry

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    Chen, Shiwei [Department of Urology, 174th Hospital of PLA, Fujian 361001 (China); Dong, Yushu [Department of Neurosurgery, 463rd Hospital of PLA, Shenyang 110042 (China); Xu, Chun; Jiang, Liming; Chen, Yongjie; Jiang, Cheng [Department of Urology, 174th Hospital of PLA, Fujian 361001 (China); Hou, Wugang, E-mail: [Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032 (China); Li, Wei, E-mail: [Department of Human Anatomy, Histology and Embryology, Fourth Military Medical University, Xi’an 710032 (China)


    Highlights: •MTA1 expression is upregulated in SCs upon MEHP treatment. •Knockdown of MTA1 in SCs impairs the MEHP-induced NFκB signaling activation. •Knockdown of MTA1 inhibits recruitment of NFκB onto FasL promoter in MEHP-treated SCs. -- Abstract: The Fas/FasL signaling pathway, controlled by nuclear factor-κB (NFκB) at the transcriptional level, is critical for triggering germ cell apoptosis in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell (SC) injury, but the exact regulation mechanism remain unknown. Here, we discovered that expression level of Metastasis associated protein 1 (MTA1), a component of the Mi-2/nucleosome remodeling and deacetylase complex, was upregulated in SCs during the early recovery after MEHP exposure. This expression change was in line with the dynamic changes in germ cell apoptosis in response to MEHP treatment. Furthermore, a knockdown of MTA1 by RNAi in SCs was found to impair the MEHP-induced early activation of NFκB pathway and abolish the recruitment of NFκB onto FasL promoter, which consequently diminished the MEHP-triggered FasL induction. Considering that Fas/FasL is a well characterized apoptosis initiating signaling during SCs injury, our results point to a potential “switch on” effect of MTA1, which may govern the activation of NFκB/FasL cascade in MEHP-insulted SCs. Overall, the MTA1/NFκB/FasL circuit may serve as an important defensive/repairing mechanism to help to control the germ cell quality after SCs injury.

  12. Mapping the brain's metaphor circuitry: metaphorical thought in everyday reason (United States)

    Lakoff, George


    An overview of the basics of metaphorical thought and language from the perspective of Neurocognition, the integrated interdisciplinary study of how conceptual thought and language work in the brain. The paper outlines a theory of metaphor circuitry and discusses how everyday reason makes use of embodied metaphor circuitry. PMID:25566012

  13. How plastic are human spinal cord motor circuitries?

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    Christiansen, Lasse; Lundbye-Jensen, Jesper; Perez, Monica A


    Human and animal studies have documented that neural circuitries in the spinal cord show adaptive changes caused by altered supraspinal and/or afferent input to the spinal circuitry in relation to learning, immobilization, injury and neurorehabilitation. Reversible adaptations following, e...

  14. Subacute Sclerosing Panencephalitis of the Brainstem as a Clinical Entity. (United States)

    Upadhyayula, Pavan S; Yang, Jason; Yue, John K; Ciacci, Joseph D


    Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurological disorder of early adolescence caused by persistent infection of the measles virus, which remains prevalent worldwide despite an effective vaccine. SSPE is a devastating disease with a characteristic clinical course in subcortical white matter; however, atypical presentations of brainstem involvement may be seen in rare cases. This review summarizes reports to date on brainstem involvement in SSPE, including the clinical course of disease, neuroimaging presentations, and guidelines for treatment. A comprehensive literature search was performed for English-language publications with keywords "subacute sclerosing panencephalitis" and "brainstem" using the National Library of Medicine PubMed database (March 1981-September 2017). Eleven articles focusing on SSPE of the brainstem were included. Predominant brainstem involvement remains uncharacteristic of SSPE, which may lead to misdiagnosis and poor outcome. A number of case reports have demonstrated brainstem involvement associated with other intracranial lesions commonly presenting in later SSPE stages (III and IV). However, brainstem lesions can appear in all stages, independent of higher cortical structures. The varied clinical presentations complicate diagnosis from a neuroimaging perspective. SSPE of the brainstem is a rare but important clinical entity. It may present like canonical SSPE or with unique clinical features such as absence seizures and pronounced ataxia. While SSPE generally progresses to the brainstem, it can also begin with a primary focus of infection in the brainstem. Awareness of varied SSPE presentations can aid in early diagnosis as well as guide management and treatment.

  15. Interdisciplinary approaches of transcranial magnetic stimulation applied to a respiratory neuronal circuitry model.

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    Stéphane Vinit

    Full Text Available Respiratory related diseases associated with the neuronal control of breathing represent life-threatening issues and to date, no effective therapeutics are available to enhance the impaired function. The aim of this study was to determine whether a preclinical respiratory model could be used for further studies to develop a non-invasive therapeutic tool applied to rat diaphragmatic neuronal circuitry. Transcranial magnetic stimulation (TMS was performed on adult male Sprague-Dawley rats using a human figure-of-eight coil. The largest diaphragmatic motor evoked potentials (MEPdia were recorded when the center of the coil was positioned 6 mm caudal from Bregma, involving a stimulation of respiratory supraspinal pathways. Magnetic shielding of the coil with mu metal reduced magnetic field intensities and improved focality with increased motor threshold and lower amplitude recruitment curve. Moreover, transynaptic neuroanatomical tracing with pseudorabies virus (applied to the diaphragm suggest that connections exist between the motor cortex, the periaqueductal grey cell regions, several brainstem neurons and spinal phrenic motoneurons (distributed in the C3-4 spinal cord. These results reveal the anatomical substrate through which supraspinal stimulation can convey descending action potential volleys to the spinal motoneurons (directly or indirectly. We conclude that MEPdia following a single pulse of TMS can be successfully recorded in the rat and may be used in the assessment of respiratory supraspinal plasticity. Supraspinal non-invasive stimulations aimed to neuromodulate respiratory circuitry will enable new avenues of research into neuroplasticity and the development of therapies for respiratory dysfunction associated with neural injury and disease (e.g. spinal cord injury, amyotrophic lateral sclerosis.

  16. Superconducting circuitry for quantum electromechanical systems (United States)

    LaHaye, Matthew D.; Rouxinol, Francisco; Hao, Yu; Shim, Seung-Bo; Irish, Elinor K.


    Superconducting systems have a long history of use in experiments that push the frontiers of mechanical sensing. This includes both applied and fundamental research, which at present day ranges from quantum computing research and e orts to explore Planck-scale physics to fundamental studies on the nature of motion and the quantum limits on our ability to measure it. In this paper, we first provide a short history of the role of superconducting circuitry and devices in mechanical sensing, focusing primarily on efforts in the last decade to push the study of quantum mechanics to include motion on the scale of human-made structures. This background sets the stage for the remainder of the paper, which focuses on the development of quantum electromechanical systems (QEMS) that incorporate superconducting quantum bits (qubits), superconducting transmission line resonators and flexural nanomechanical elements. In addition to providing the motivation and relevant background on the physical behavior of these systems, we discuss our recent efforts to develop a particular type of QEMS that is based upon the Cooper-pair box (CPB) and superconducting coplanar waveguide (CPW) cavities, a system which has the potential to serve as a testbed for studying the quantum properties of motion in engineered systems.

  17. Subacute Sclerosing Panencephalitis of the Brainstem as a Clinical Entity

    Directory of Open Access Journals (Sweden)

    Pavan S. Upadhyayula


    Full Text Available Subacute sclerosing panencephalitis (SSPE is a rare progressive neurological disorder of early adolescence caused by persistent infection of the measles virus, which remains prevalent worldwide despite an effective vaccine. SSPE is a devastating disease with a characteristic clinical course in subcortical white matter; however, atypical presentations of brainstem involvement may be seen in rare cases. This review summarizes reports to date on brainstem involvement in SSPE, including the clinical course of disease, neuroimaging presentations, and guidelines for treatment. A comprehensive literature search was performed for English-language publications with keywords “subacute sclerosing panencephalitis” and “brainstem” using the National Library of Medicine PubMed database (March 1981–September 2017. Eleven articles focusing on SSPE of the brainstem were included. Predominant brainstem involvement remains uncharacteristic of SSPE, which may lead to misdiagnosis and poor outcome. A number of case reports have demonstrated brainstem involvement associated with other intracranial lesions commonly presenting in later SSPE stages (III and IV. However, brainstem lesions can appear in all stages, independent of higher cortical structures. The varied clinical presentations complicate diagnosis from a neuroimaging perspective. SSPE of the brainstem is a rare but important clinical entity. It may present like canonical SSPE or with unique clinical features such as absence seizures and pronounced ataxia. While SSPE generally progresses to the brainstem, it can also begin with a primary focus of infection in the brainstem. Awareness of varied SSPE presentations can aid in early diagnosis as well as guide management and treatment.

  18. Enhanced Excitatory Connectivity and Disturbed Sound Processing in the Auditory Brainstem of Fragile X Mice. (United States)

    Garcia-Pino, Elisabet; Gessele, Nikodemus; Koch, Ursula


    Hypersensitivity to sounds is one of the prevalent symptoms in individuals with Fragile X syndrome (FXS). It manifests behaviorally early during development and is often used as a landmark for treatment efficacy. However, the physiological mechanisms and circuit-level alterations underlying this aberrant behavior remain poorly understood. Using the mouse model of FXS ( Fmr1 KO ), we demonstrate that functional maturation of auditory brainstem synapses is impaired in FXS. Fmr1 KO mice showed a greatly enhanced excitatory synaptic input strength in neurons of the lateral superior olive (LSO), a prominent auditory brainstem nucleus, which integrates ipsilateral excitation and contralateral inhibition to compute interaural level differences. Conversely, the glycinergic, inhibitory input properties remained unaffected. The enhanced excitation was the result of an increased number of cochlear nucleus fibers converging onto one LSO neuron, without changing individual synapse properties. Concomitantly, immunolabeling of excitatory ending markers revealed an increase in the immunolabeled area, supporting abnormally elevated excitatory input numbers. Intrinsic firing properties were only slightly enhanced. In line with the disturbed development of LSO circuitry, auditory processing was also affected in adult Fmr1 KO mice as shown with single-unit recordings of LSO neurons. These processing deficits manifested as an increase in firing rate, a broadening of the frequency response area, and a shift in the interaural level difference function of LSO neurons. Our results suggest that this aberrant synaptic development of auditory brainstem circuits might be a major underlying cause of the auditory processing deficits in FXS. SIGNIFICANCE STATEMENT Fragile X Syndrome (FXS) is the most common inheritable form of intellectual impairment, including autism. A core symptom of FXS is extreme sensitivity to loud sounds. This is one reason why individuals with FXS tend to avoid social

  19. Resting-state functional magnetic resonance imaging of the subthalamic microlesion and stimulation effects in Parkinson's disease: Indications of a principal role of the brainstem

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    Štefan Holiga


    Full Text Available During implantation of deep-brain stimulation (DBS electrodes in the target structure, neurosurgeons and neurologists commonly observe a “microlesion effect” (MLE, which occurs well before initiating subthalamic DBS. This phenomenon typically leads to a transitory improvement of motor symptoms of patients suffering from Parkinson's disease (PD. Mechanisms behind MLE remain poorly understood. In this work, we exploited the notion of ranking to assess spontaneous brain activity in PD patients examined by resting-state functional magnetic resonance imaging in response to penetration of DBS electrodes in the subthalamic nucleus. In particular, we employed a hypothesis-free method, eigenvector centrality (EC, to reveal motor-communication-hubs of the highest rank and their reorganization following the surgery; providing a unique opportunity to evaluate the direct impact of disrupting the PD motor circuitry in vivo without prior assumptions. Penetration of electrodes was associated with increased EC of functional connectivity in the brainstem. Changes in connectivity were quantitatively related to motor improvement, which further emphasizes the clinical importance of the functional integrity of the brainstem. Surprisingly, MLE and DBS were associated with anatomically different EC maps despite their similar clinical benefit on motor functions. The DBS solely caused an increase in connectivity of the left premotor region suggesting separate pathophysiological mechanisms of both interventions. While the DBS acts at the cortical level suggesting compensatory activation of less affected motor regions, the MLE affects more fundamental circuitry as the dysfunctional brainstem predominates in the beginning of PD. These findings invigorate the overlooked brainstem perspective in the understanding of PD and support the current trend towards its early diagnosis.

  20. Resting-state functional magnetic resonance imaging of the subthalamic microlesion and stimulation effects in Parkinson's disease: Indications of a principal role of the brainstem. (United States)

    Holiga, Štefan; Mueller, Karsten; Möller, Harald E; Urgošík, Dušan; Růžička, Evžen; Schroeter, Matthias L; Jech, Robert


    During implantation of deep-brain stimulation (DBS) electrodes in the target structure, neurosurgeons and neurologists commonly observe a "microlesion effect" (MLE), which occurs well before initiating subthalamic DBS. This phenomenon typically leads to a transitory improvement of motor symptoms of patients suffering from Parkinson's disease (PD). Mechanisms behind MLE remain poorly understood. In this work, we exploited the notion of ranking to assess spontaneous brain activity in PD patients examined by resting-state functional magnetic resonance imaging in response to penetration of DBS electrodes in the subthalamic nucleus. In particular, we employed a hypothesis-free method, eigenvector centrality (EC), to reveal motor-communication-hubs of the highest rank and their reorganization following the surgery; providing a unique opportunity to evaluate the direct impact of disrupting the PD motor circuitry in vivo without prior assumptions. Penetration of electrodes was associated with increased EC of functional connectivity in the brainstem. Changes in connectivity were quantitatively related to motor improvement, which further emphasizes the clinical importance of the functional integrity of the brainstem. Surprisingly, MLE and DBS were associated with anatomically different EC maps despite their similar clinical benefit on motor functions. The DBS solely caused an increase in connectivity of the left premotor region suggesting separate pathophysiological mechanisms of both interventions. While the DBS acts at the cortical level suggesting compensatory activation of less affected motor regions, the MLE affects more fundamental circuitry as the dysfunctional brainstem predominates in the beginning of PD. These findings invigorate the overlooked brainstem perspective in the understanding of PD and support the current trend towards its early diagnosis.

  1. Studying respiratory rhythm generation in a developing bird: hatching a new experimental model using the classic in vitro brainstem-spinal cord preparatio


    Vincen-Brown, Michael A.; Whitesitt, Kaitlyn C.; Quick, Forrest G.; Pilarski, Jason Q.


    It has been more than thirty years since the in vitro brainstem-spinal cord preparation was first presented as a method to study automatic breathing behaviors in the neonatal rat. This straightforward preparation has led to an incredible burst of information about the location and coordination of several spontaneously active microcircuits that form the ventrolateral respiratory network of the brainstem. Despite these advances, our knowledge of the mechanisms that regulate central breathing be...

  2. Frontal-Brainstem Pathways Mediating Placebo Effects on Social Rejection. (United States)

    Koban, Leonie; Kross, Ethan; Woo, Choong-Wan; Ruzic, Luka; Wager, Tor D


    Placebo treatments can strongly affect clinical outcomes, but research on how they shape other life experiences and emotional well-being is in its infancy. We used fMRI in humans to examine placebo effects on a particularly impactful life experience, social pain elicited by a recent romantic rejection. We compared these effects with placebo effects on physical (heat) pain, which are thought to depend on pathways connecting prefrontal cortex and periaqueductal gray (PAG). Placebo treatment, compared with control, reduced both social and physical pain, and increased activity in the dorsolateral prefrontal cortex (dlPFC) in both modalities. Placebo further altered the relationship between affect and both dlPFC and PAG activity during social pain, and effects on behavior were mediated by a pathway connecting dlPFC to the PAG, building on recent work implicating opioidergic PAG activity in the regulation of social pain. These findings suggest that placebo treatments reduce emotional distress by altering affective representations in frontal-brainstem systems. SIGNIFICANCE STATEMENT Placebo effects are improvements due to expectations and the socio-medical context in which treatment takes place. Whereas they have been extensively studied in the context of somatic conditions such as pain, much less is known of how treatment expectations shape the emotional experience of other important stressors and life events. Here, we use brain imaging to show that placebo treatment reduces the painful feelings associated with a recent romantic rejection by recruiting a prefrontal-brainstem network and by shifting the relationship between brain activity and affect. Our findings suggest that this brain network may be important for nonspecific treatment effects across a wide range of therapeutic approaches and mental health conditions. Copyright © 2017 the authors 0270-6474/17/373621-11$15.00/0.

  3. Blueprints for behavior: genetic specification of neural circuitry for innate behaviors. (United States)

    Manoli, Devanand S; Meissner, Geoffrey W; Baker, Bruce S


    Innate behaviors offer a unique opportunity to use genetic analysis to dissect and characterize the neural substrates of complex behavioral programs. Courtship in Drosophila involves a complex series of stereotyped behaviors that include numerous exchanges of multimodal sensory information over time. As we will discuss in this review, recent work has demonstrated that male-specific expression of Fruitless transcription factors (Fru(M) proteins) is necessary and sufficient to confer the potential for male courtship behaviors. Fru(M) factors program neurons of the male central and peripheral nervous systems whose function is dedicated to sexual behaviors. This circuitry seems to integrate sensory information to define behavioral states and regulate conserved neural elements for sex-specific behavioral output. The principles that govern the circuitry specified by Fru(M) expression might also operate in subcortical networks that govern innate behaviors in mammals.

  4. Neurodynamics, tonality, and the auditory brainstem response. (United States)

    Large, Edward W; Almonte, Felix V


    Tonal relationships are foundational in music, providing the basis upon which musical structures, such as melodies, are constructed and perceived. A recent dynamic theory of musical tonality predicts that networks of auditory neurons resonate nonlinearly to musical stimuli. Nonlinear resonance leads to stability and attraction relationships among neural frequencies, and these neural dynamics give rise to the perception of relationships among tones that we collectively refer to as tonal cognition. Because this model describes the dynamics of neural populations, it makes specific predictions about human auditory neurophysiology. Here, we show how predictions about the auditory brainstem response (ABR) are derived from the model. To illustrate, we derive a prediction about population responses to musical intervals that has been observed in the human brainstem. Our modeled ABR shows qualitative agreement with important features of the human ABR. This provides a source of evidence that fundamental principles of auditory neurodynamics might underlie the perception of tonal relationships, and forces reevaluation of the role of learning and enculturation in tonal cognition. © 2012 New York Academy of Sciences.

  5. Brainstem projections to spinal motoneurons: an update. (United States)

    Holstege, J C; Kuypers, H G


    1. The existence of direct projections to spinal motoneurons and interneurons from the raphe pallidus and obscurus, the adjoining ventral medial reticular formation and the locus coeruleus and subcoeruleus is now well substantiated by various anatomical techniques. 2. The spinal projections from the raphe nuclei and the adjoining medial reticular formation contain serotonergic and non-serotonergic fibres. These projections also contain various peptides, several of which are contained within the serotonergic fibres. Whether still other transmitter substances (e.g. acetylcholine) are present in the various descending brainstem projections to motoneurons remains to be determined. 3. The spinal projections from the locus coeruleus and subcoeruleus are mainly noradrenergic, but there also exists a non-noradrenergic spinal projection. 4. Pharmacological, physiological and behavioural studies indicate an overall facilitatory action of noradrenaline and serotonin (including several peptides) on motoneurons. This may lead to an enhanced susceptibility for excitatory inputs from other sources. 5. The brainstem areas in question receive an important projection from several components of the limbic system. This suggests that the emotional brain can exert a powerful influence on all regions of the spinal cord and may thus control both its sensory input and motor output.

  6. Speech Evoked Auditory Brainstem Response in Stuttering

    Directory of Open Access Journals (Sweden)

    Ali Akbar Tahaei


    Full Text Available Auditory processing deficits have been hypothesized as an underlying mechanism for stuttering. Previous studies have demonstrated abnormal responses in subjects with persistent developmental stuttering (PDS at the higher level of the central auditory system using speech stimuli. Recently, the potential usefulness of speech evoked auditory brainstem responses in central auditory processing disorders has been emphasized. The current study used the speech evoked ABR to investigate the hypothesis that subjects with PDS have specific auditory perceptual dysfunction. Objectives. To determine whether brainstem responses to speech stimuli differ between PDS subjects and normal fluent speakers. Methods. Twenty-five subjects with PDS participated in this study. The speech-ABRs were elicited by the 5-formant synthesized syllable/da/, with duration of 40 ms. Results. There were significant group differences for the onset and offset transient peaks. Subjects with PDS had longer latencies for the onset and offset peaks relative to the control group. Conclusions. Subjects with PDS showed a deficient neural timing in the early stages of the auditory pathway consistent with temporal processing deficits and their abnormal timing may underlie to their disfluency.

  7. Circuitry, systems and methods for detecting magnetic fields (United States)

    Kotter, Dale K [Shelley, ID; Spencer, David F [Idaho Falls, ID; Roybal, Lyle G [Idaho Falls, ID; Rohrbaugh, David T [Idaho Falls, ID


    Circuitry for detecting magnetic fields includes a first magnetoresistive sensor and a second magnetoresistive sensor configured to form a gradiometer. The circuitry includes a digital signal processor and a first feedback loop coupled between the first magnetoresistive sensor and the digital signal processor. A second feedback loop which is discrete from the first feedback loop is coupled between the second magnetoresistive sensor and the digital signal processor.

  8. Morphometric study of the human brainstem and its neurovascular relations. (United States)

    Szabo, Bianca Aurora; Pascalau, Raluca; Padurean, Vlad Adrian


    The brainstem is a very complex segment of the central nervous system because it has a high density of nuclei and tracts with vital functional roles. This explains the considerable difficulty of surgery for lesions located in or around the brainstem. Our paper aims to provide a concise description of the external configuration, its internal correspondence and the neurovascular relations of the brainstem with morphometric data that can be useful in surgical planning. The study was conducted on formalin fixed brainstem specimens, which were harvested with respect to the topographic anatomy. Macroscopic measurements were performed with a Vernier caliper. The anatomical structures on the ventral and dorsal aspects of the brainstem are described and illustrated schematically. Their dimensions are also graphically represented using the mean values. Serial axial sections through the brainstem demonstrate the internal correspondence of its external features. Then there are presented the apparent origins and the proximal diameters of the cranial nerves and the arteries of the posterior circulation as well as their anatomical relations. The external morphometry of the brainstem correlated with the position of the internal structures provides landmarks with aplicability in neurosurgery especially in the fields of intrinsic brainstem lesions, posterior fossa and fourth ventricle surgery.

  9. Role of brainstem TRH/TRH-R1 receptors in the vagal gastric cholinergic response to various stimuli including sham-feeding. (United States)

    Taché, Y; Yang, H; Miampamba, M; Martinez, V; Yuan, P Q


    Pavlov's pioneering work established that sham-feeding induced by sight or smell of food or feeding in dogs with permanent esophagostomy stimulates gastric acid secretion through vagal pathways. Brain circuitries and transmitters involved in the central vagal regulation of gastric function have recently been unraveled. Neurons in the dorsal vagal complex including the dorsal motor nucleus of the vagus (DMN) express thyrotropin-releasing hormone (TRH) receptor and are innervated by TRH fibers originating from TRH synthesizing neurons in the raphe pallidus, raphe obscurus and the parapyramidal regions. TRH injected into the DMN or cisterna magna increases the firing of DMN neurons and gastric vagal efferent discharge, activates cholinergic neurons in gastric submucosal and myenteric plexuses, and induces a vagal-dependent, atropine-sensitive stimulation of gastric secretory (acid, pepsin) and motor functions. TRH antibody or TRH-R1 receptor oligodeoxynucleotide antisense pretreatment in the cisterna magna or DMN abolished vagal-dependent gastric secretory and motor responses to sham-feeding, 2-deoxy-D-glucose, cold exposure and chemical activation of cell bodies in medullary raphe nuclei. TRH excitatory action in the DMN is potentiated by co-released prepro-TRH-(160-169) flanking peptide, Ps4 and 5-HT, and inhibited by a number of peptides involved in the stress/immune response and inhibition of food-intake. These neuroanatomical, electrophysiological and neuropharmacological data are consistent with a physiological role of brainstem TRH in the central vagal stimulation of gastric myenteric cholinergic neurons in response to several vagal dependent stimuli including sham-feeding.

  10. Clinical Approach to Supranuclear Brainstem Saccadic Gaze Palsies

    Directory of Open Access Journals (Sweden)

    Alexandra Lloyd-Smith Sequeira


    Full Text Available Failure of brainstem supranuclear centers for saccadic eye movements results in the clinical presence of a brainstem-mediated supranuclear saccadic gaze palsy (SGP, which is manifested as slowing of saccades with or without range of motion limitation of eye movements and as loss of quick phases of optokinetic nystagmus. Limitation in the range of motion of eye movements is typically worse with saccades than with smooth pursuit and is overcome with vestibular–ocular reflexive eye movements. The differential diagnosis of SGPs is broad, although acute-onset SGP is most often from brainstem infarction and chronic vertical SGP is most commonly caused by the neurodegenerative condition progressive supranuclear palsy. In this review, we discuss the brainstem anatomy and physiology of the brainstem saccade-generating network; we discuss the clinical features of SGPs, with an emphasis on insights from quantitative ocular motor recordings; and we consider the broad differential diagnosis of SGPs.

  11. Circuitry linking the Csr and stringent response global regulatory systems. (United States)

    Edwards, Adrianne N; Patterson-Fortin, Laura M; Vakulskas, Christopher A; Mercante, Jeffrey W; Potrykus, Katarzyna; Vinella, Daniel; Camacho, Martha I; Fields, Joshua A; Thompson, Stuart A; Georgellis, Dimitris; Cashel, Michael; Babitzke, Paul; Romeo, Tony


    CsrA protein regulates important cellular processes by binding to target mRNAs and altering their translation and/or stability. In Escherichia coli, CsrA binds to sRNAs, CsrB and CsrC, which sequester CsrA and antagonize its activity. Here, mRNAs for relA, spoT and dksA of the stringent response system were found among 721 different transcripts that copurified with CsrA. Many of the transcripts that copurified with CsrA were previously determined to respond to ppGpp and/or DksA. We examined multiple regulatory interactions between the Csr and stringent response systems. Most importantly, DksA and ppGpp robustly activated csrB/C transcription (10-fold), while they modestly activated csrA expression. We propose that CsrA-mediated regulation is relieved during the stringent response. Gel shift assays confirmed high affinity binding of CsrA to relA mRNA leader and weaker interactions with dksA and spoT. Reporter fusions, qRT-PCR and immunoblotting showed that CsrA repressed relA expression, and (p)ppGpp accumulation during stringent response was enhanced in a csrA mutant. CsrA had modest to negligible effects on dksA and spoT expression. Transcription of dksA was negatively autoregulated via a feedback loop that tended to mask CsrA effects. We propose that the Csr system fine-tunes the stringent response and discuss biological implications of the composite circuitry. © Published 2011. This article is a US Government work and is in the public domain in the USA.

  12. Loss of Ptf1a Leads to a Widespread Cell-Fate Misspecification in the Brainstem, Affecting the Development of Somatosensory and Viscerosensory Nuclei (United States)

    Iskusnykh, Igor Y.; Steshina, Ekaterina Y.


    The brainstem contains diverse neuronal populations that regulate a wide range of processes vital to the organism. Proper cell-fate specification decisions are critical to achieve neuronal diversity in the CNS, but the mechanisms regulating cell-fate specification in the developing brainstem are poorly understood. Previously, it has been shown that basic helix-loop-helix transcription factor Ptf1a is required for the differentiation and survival of neurons of the inferior olivary and cochlear brainstem nuclei, which contribute to motor coordination and sound processing, respectively. In this study, we show that the loss of Ptf1a compromises the development of the nucleus of the solitary tract, which processes viscerosensory information, and the spinal and principal trigeminal nuclei, which integrate somatosensory information of the face. Combining genetic fate-mapping, birth-dating, and gene expression studies, we found that at least a subset of brainstem abnormalities in Ptf1a−/− mice are mediated by a dramatic cell-fate misspecification in rhombomeres 2–7, which results in the production of supernumerary viscerosensory and somatosensory neurons of the Lmx1b lineage at the expense of Pax2+ GABAergic viscerosensory and somatosensory neurons, and inferior olivary neurons. Our data identify Ptf1a as a major regulator of cell-fate specification decisions in the developing brainstem, and as a previously unrecognized developmental regulator of both viscerosensory and somatosensory brainstem nuclei. SIGNIFICANCE STATEMENT Cell-fate specification decisions are critical for normal CNS development. Although extensively studied in the cerebellum and spinal cord, the mechanisms mediating cell-fate decisions in the brainstem, which regulates a wide range of processes vital to the organism, remain largely unknown. Here we identified mouse Ptf1a as a novel regulator of cell-fate decisions during both early and late brainstem neurogenesis, which are critical for proper

  13. Intracranial neurenteric cyst traversing the brainstem

    Directory of Open Access Journals (Sweden)

    Jasmit Singh


    Full Text Available Neurenteric cysts (NECs, also called enterogenous cysts, are rare benign endodermal lesions of the central nervous system that probably result from separation failure of the notochord and upper gastrointestinal tract. Most frequently they are found in the lower cervical spine or the upper thoracic spine. Intracranial occurrence is rare and mostly confined to infratentorial compartment, in prepontine region [51%]. Other common locations are fourth ventricle and cerebellopontine angle. There are few reports of NEC in medulla or the cerebellum. Because of the rarity of the disease and common radiological findings, they are misinterpreted as arachnoid or simple cysts until the histopathological confirmation, unless suspected preoperatively. We herein report a rare yet interesting case of intracranial NEC traversing across the brainstem.

  14. A Developmental Shift from Positive to Negative Connectivity in Human Amygdala-Prefrontal Circuitry (United States)

    Gee, Dylan G.; Humphreys, Kathryn L.; Flannery, Jessica; Goff, Bonnie; Telzer, Eva H.; Shapiro, Mor; Hare, Todd A.; Bookheimer, Susan Y.; Tottenham, Nim


    Recent human imaging and animal studies highlight the importance of frontoamygdala circuitry in the regulation of emotional behavior and its disruption in anxiety-related disorders. While tracing studies have suggested changes in amygdala-cortical connectivity through the adolescent period in rodents, less is known about the reciprocal connections within this circuitry across human development, when these circuits are being fine-tuned and substantial changes in emotional control are observed. The present study examined developmental changes in amygdala-prefrontal circuitry across the ages of 4 to 22 years using task-based functional magnetic resonance imaging (fMRI). Results suggest positive amygdala-prefrontal connectivity in early childhood that switches to negative functional connectivity during the transition to adolescence. Amygdala-mPFC functional connectivity was significantly positive (greater than zero) among participants younger than ten, whereas functional connectivity was significantly negative (less than zero) among participants ten years and older, over and above the effect of amygdala reactivity. The developmental switch in functional connectivity was paralleled by a steady decline in amygdala reactivity. Moreover, the valence switch might explain age-related improvement in task performance and a developmentally normative decline in anxiety. Initial positive connectivity followed by a valence shift to negative connectivity provides a neurobiological basis for regulatory development and may present novel insight into a more general process of developing regulatory connections. PMID:23467374

  15. Method for integrating microelectromechanical devices with electronic circuitry (United States)

    Barron, Carole C.; Fleming, James G.; Montague, Stephen


    A method is disclosed for integrating one or more microelectromechanical (MEM) devices with electronic circuitry on a common substrate. The MEM device can be fabricated within a substrate cavity and encapsulated with a sacrificial material. This allows the MEM device to be annealed and the substrate planarized prior to forming electronic circuitry on the substrate using a series of standard processing steps. After fabrication of the electronic circuitry, the electronic circuitry can be protected by a two-ply protection layer of titanium nitride (TiN) and tungsten (W) during an etch release process whereby the MEM device is released for operation by etching away a portion of a sacrificial material (e.g. silicon dioxide or a silicate glass) that encapsulates the MEM device. The etch release process is preferably performed using a mixture of hydrofluoric acid (HF) and hydrochloric acid (HCI) which reduces the time for releasing the MEM device compared to use of a buffered oxide etchant. After release of the MEM device, the TiN:W protection layer can be removed with a peroxide-based etchant without damaging the electronic circuitry.

  16. Bickerstaff's brainstem encephalitis after an outbreak of Campylobacter jejuni enteritis. (United States)

    Mori, Masahiro; Koga, Michiaki; Yuki, Nobuhiro; Hattori, Takamichi; Kuwabara, Satoshi


    Twenty-eight patients suffered Campylobacter jejuni enteritis after eating raw chicken. Among them, only one patient developed Bickerstaff's brainstem encephalitis, who carried anti-GQ1b IgG antibodies. In contrast, none of the others did the autoantibodies. C. jejuni was cultured from all stool samples from five patients with enteritis alone. All the isolates had the same genotype, cst-II (Asn51), which are characteristic of strains isolated from Bickerstaff's brainstem encephalitis. These findings suggest that host susceptibility may play a role in inducing the production of anti-ganglioside antibodies and the development of Bickerstaff's brainstem encephalitis.

  17. Functional characterization of obesogenic neural circuitries

    NARCIS (Netherlands)

    Boender, A.J.


    Obesity can be characterized as a disorder in which affected individuals fail to properly regulate the balance between energy intake and expenditure. Recently, genome-wide association studies have identified over 30 genetic variants that associate with increased body weight and thus provide clues on

  18. Nanocantilever based mass sensor integrated with cmos circuitry

    DEFF Research Database (Denmark)

    Davis, Zachary James; Abadal, G.; Campabadal, F.


    We have demonstrated the successful integration of a cantilever based mass detector with standard CMOS circuitry. The purpose of the circuitry is to facilitate the readout of the cantilever's deflection in order to measure resonant frequency shifts of the cantilever. The principle and design...... to solve the problem, namely freeze-drying and resist-assisted release. The fabrication results of cantilevers defined by laser and E-beam lithography are shown. Finally, an AFM based characterization setup is presented and the electrical characterization of a laser-defined cantilever fully integrated...

  19. Brainstem and cerebellar changes after cerebrovascular accidents: magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Uchino, A.; Takase, Y.; Nomiyama, K.; Egashira, R.; Kudo, S. [Saga Medical School, Department of Radiology, Saga (Japan)


    We illustrate the various types of secondary degeneration in the brainstem and/or cerebellum detected on magnetic resonance (MR) images obtained after cerebrovascular accidents. The changes include: (a) ipsilateral nigral degeneration after striatal infarction; (b) Wallerian degeneration of the pyramidal tract in the brainstem after supratentorial pyramidal tract or motor cortex injury; (c) Wallerian degeneration of the corticopontine tract in the brainstem after frontal lobe infarction; (d) ipsilateral brainstem atrophy and crossed cerebellar atrophy due to an extensive supratentorial lesion; (e) ipsilateral superior cerebellar peduncle atrophy, contralateral rubral degeneration, contralateral inferior olivary degeneration and ipsilateral cerebellar atrophy after dentate nucleus hemorrhage; (f) ipsilateral inferior olivary degeneration after pontine tegmentum hemorrhage; (g) bilateral wallerian degeneration of the pontocerebellar tracts after ventromedial pontine infarction or basis pontis hemorrhage; and (h) ipsilateral cerebellar atrophy after middle cerebellar peduncle hemorrhage. (orig.)

  20. Enterovirus 71 Brainstem Encephalitis and Cognitive and Motor Deficits

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap


    Full Text Available Follow-up studies were conducted in 63 previously healthy children with enterovirus 71 brainstem encephalitis (49 stage II, 7 stage Ilia, and 7 stage Illb at National Cheng Kung University Hospital, Tainan, Taiwan.

  1. Peptidergic regulation of gastrointestinal motility in rodents. (United States)

    Fujimiya, M; Inui, A


    Peptides involved in the endocrine and enteric nervous systems as well as in the central nervous system exert concerted action on gastrointestinal motility. Mechanical and chemical stimuli which induce peptide release from the epithelial endocrine cells are the earliest step in the initiation of peristaltic activities. Gut peptides exert hormonal effects, but peptide-containing stimulatory (Ach/substance P/tachykinin) and inhibitory (VIP/PACAP/NO) neurons are also involved in the induction of ascending contraction and descending relaxation, respectively. The dorsal vagal complex (DVC), located in the medulla of the brainstem, constitutes the basic neural circuitry of vago-vagal reflex control of gastrointestinal motility. Several gut peptides act on the DVC to modify vagal cholinergic reflexes directly (PYY and PP) or indirectly via afferent fibers in the periphery (CCK and GLP-1). The DVC is also a primary site of action of many neuropeptides (such as TRH and NPY) in mediating gastrointestinal motor activities. The identification over the last few years of a number of neuropeptide systems has greatly changed the field of feeding and body weight regulation. By exploring the brain and gut systems that employ recently identified peptidergic molecules, it will be possible to elaborate on the central and peripheral pathways involved in the regulation of gastrointestinal motility.

  2. A case of pulmonary hypoplasia associated with intrauterine brainstem necrosis. (United States)

    Endo, A; Minato, M; Takada, M; Takahashi, S; Harada, K; Yamada, T; Takashima, S


    An infant with intrauterine brain death accompanied by pulmonary hypoplasia is reported. The fetus was delivered after 36 weeks gestation, 5 weeks after fetal movements ceased. The child died 4 h after birth. Pulmonary hypoplasia and remote brainstem necrosis associated with multicystic encephalomalacia were found at autopsy. These findings suggest that damage to brainstem respiratory centres had led to pulmonary hypoplasia through the absence of fetal respiratory movement.

  3. Brainstem variant of posterior reversible encephalopathy syndrome: A case report. (United States)

    Tortora, Fabio; Caranci, Ferdinando; Belfiore, Maria Paola; Manzi, Francesca; Pagliano, Pasquale; Cirillo, Sossio


    Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological condition, generally observed in conjunction with severe and acute hypertension, that involves mainly the posterior head areas (occipital and temporal lobes) and anterior "watershed" areas. In this syndrome it is rare to observe a predominant involvement of the brainstem. We describe the clinical and radiological findings in a patient with brainstem involvement, discussing its pathophysiological features and possible differential diagnosis. © The Author(s) 2015.

  4. Unique features of the human brainstem and cerebellum. (United States)

    Baizer, Joan S


    The cerebral cortex is greatly expanded in the human brain. There is a parallel expansion of the cerebellum, which is interconnected with the cerebral cortex. We have asked if there are accompanying changes in the organization of pre-cerebellar brainstem structures. We have examined the cytoarchitectonic and neurochemical organization of the human medulla and pons. We studied human cases from the Witelson Normal Brain Collection, analyzing Nissl sections and sections processed for immunohistochemistry for multiple markers including the calcium-binding proteins calbindin, calretinin, and parvalbumin, non-phosphorylated neurofilament protein, and the synthetic enzyme for nitric oxide, nitric oxide synthase. We have also compared the neurochemical organization of the human brainstem to that of several other species including the chimpanzee, macaque and squirrel monkey, cat, and rodent, again using Nissl staining and immunohistochemistry. We found that there are major differences in the human brainstem, ranging from relatively subtle differences in the neurochemical organization of structures found in each of the species studied to the emergence of altogether new structures in the human brainstem. Two aspects of human cortical organization, individual differences and left-right asymmetry, are also seen in the brainstem (principal nucleus of the inferior olive) and the cerebellum (the dentate nucleus). We suggest that uniquely human motor and cognitive abilities derive from changes at all levels of the central nervous system, including the cerebellum and brainstem, and not just the cerebral cortex.

  5. The auditory brainstem is a barometer of rapid auditory learning. (United States)

    Skoe, E; Krizman, J; Spitzer, E; Kraus, N


    To capture patterns in the environment, neurons in the auditory brainstem rapidly alter their firing based on the statistical properties of the soundscape. How this neural sensitivity relates to behavior is unclear. We tackled this question by combining neural and behavioral measures of statistical learning, a general-purpose learning mechanism governing many complex behaviors including language acquisition. We recorded complex auditory brainstem responses (cABRs) while human adults implicitly learned to segment patterns embedded in an uninterrupted sound sequence based on their statistical characteristics. The brainstem's sensitivity to statistical structure was measured as the change in the cABR between a patterned and a pseudo-randomized sequence composed from the same set of sounds but differing in their sound-to-sound probabilities. Using this methodology, we provide the first demonstration that behavioral-indices of rapid learning relate to individual differences in brainstem physiology. We found that neural sensitivity to statistical structure manifested along a continuum, from adaptation to enhancement, where cABR enhancement (patterned>pseudo-random) tracked with greater rapid statistical learning than adaptation. Short- and long-term auditory experiences (days to years) are known to promote brainstem plasticity and here we provide a conceptual advance by showing that the brainstem is also integral to rapid learning occurring over minutes. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Migraine with brainstem aura: Why not a cortical origin? (United States)

    Demarquay, Geneviève; Ducros, Anne; Montavont, Alexandra; Mauguiere, François


    Background Migraine with brainstem aura is defined as a migraine with aura including at least two of the following symptoms: dysarthria, vertigo, tinnitus, hypacusis, diplopia, ataxia and/or decreased level of consciousness. Aim The aim of this study is to review data coming from clinical observations and functional mapping that support the role of the cerebral cortex in the initiation of brainstem aura symptoms. Results Vertigo can result from a vestibular cortex dysfunction, while tinnitus and hypacusis can originate within the auditory cortex. Diplopia can reflect a parieto-occipital involvement. Dysarthria can be caused by dysfunctions located in precentral gyri. Ataxia can reflect abnormal processing of vestibular, sensory, or visual inputs by the parietal lobe. Alteration of consciousness can be caused by abnormal neural activation within specific consciousness networks that include prefrontal and posterior parietal cortices. Conclusion Any symptom of so-called brainstem aura can originate within the cortex. Based on these data, we suggest that brainstem aura could have a cortical origin. This hypothesis would explain the co-occurrence of typical and brainstem aura during attacks and would fit with the theory of cortical spreading depression. We propose that migraine with brainstem aura should be classified as a typical migraine aura.

  7. Unique Features of the Human Brainstem and Cerebellum

    Directory of Open Access Journals (Sweden)

    Joan S Baizer


    Full Text Available The cerebral cortex is greatly expanded in the human brain. There is a parallel expansion of the cerebellum, which is interconnected with the cerebral cortex. We have asked if there are accompanying changes in the organization of the precerebellar brainstem structures. We have examined the cytoarchitectonic and neurochemical organization of the human medulla and pons. We studied human cases from the Witelson Normal Brain Collection, analyzing Nissl sections and sections processed for immunohistochemistry for multiple markers including the calcium-binding proteins calbindin, calretinin and parvalbumin, nonphosphorylated neurofilament protein, and the synthetic enzyme for nitric oxide, nitric oxide synthase. We have also compared the neurochemical organization of the human brainstem to that of several other species including the chimpanzee, macaque and squirrel monkey, cat, and rodent, again using Nissl staining and immunohistochemistry. We found that there are major differences in the human brainstem, ranging from relatively subtle differences in the neurochemical organization of structures found in each of the species studied to the emergence of altogether new structures in the human brainstem. Two aspects of human cortical organization, individual differences and left-right asymmetry, are also seen in the brainstem (principal nucleus of the inferior olive and the cerebellum (the dentate nucleus. We suggest that uniquely human motor and cognitive abilities derive from changes at all levels of the central nervous system, including the cerebellum and brainstem, and not just the cerebral cortex.

  8. [How does the brain control eye movements? Motor and premotor neurons of the brainstem]. (United States)

    Coubard, O A


    Knowledge of cognitive and neural architecture and processes that control eye movements has advanced enough to allow precise and quantitative analysis of hitherto unsolved phenomena. In this review, we revisit from a neuropsychological viewpoint Hering vs. Helmholtz' hypotheses on binocular coordination. Specifically, we reexamine the behavior and the neural bases of saccade-vergence movement, to move the gaze in both direction and depth under natural conditions. From the psychophysical viewpoint, neo-Heringian and neo-Helmholtzian authors have accumulated arguments favoring distinct conjugate (for saccades) and disconjugate (for vergence) systems, as well as advocating for monocularly programmed eye movements. From the neurophysiological viewpoint, which reports brain cell recordings during the execution of a given task, neo-Heringian and neo-Helmholtzian physiologists have also provided arguments in favor of both hypotheses at the level of the brainstem premotor circuitry. Bridging the two, we propose that Hering and Helmholtz were both right. The emphasis placed by the latter on adaptive processes throughout life cycle is compatible with the importance of neurobiological constraints pointed out by the former. In the meanwhile, the study of saccade-vergence eye movements recalls how much the psychophysical definition of the task determines the interpretation that is made from neurophysiological data. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  9. Postmortem diffusion MRI of the human brainstem and thalamus for deep brain stimulator electrode localization. (United States)

    Calabrese, Evan; Hickey, Patrick; Hulette, Christine; Zhang, Jingxian; Parente, Beth; Lad, Shivanand P; Johnson, G Allan


    Deep brain stimulation (DBS) is an established surgical therapy for medically refractory tremor disorders including essential tremor (ET) and is currently under investigation for use in a variety of other neurologic and psychiatric disorders. There is growing evidence that the anti-tremor effects of DBS for ET are directly related to modulation of the dentatorubrothalamic tract (DRT), a white matter pathway that connects the cerebellum, red nucleus, and ventral intermediate nucleus of the thalamus. Emerging white matter targets for DBS, like the DRT, will require improved three-dimensional (3D) reference maps of deep brain anatomy and structural connectivity for accurate electrode targeting. High-resolution diffusion MRI of postmortem brain specimens can provide detailed volumetric images of important deep brain nuclei and 3D reconstructions of white matter pathways with probabilistic tractography techniques. We present a high spatial and angular resolution diffusion MRI template of the postmortem human brainstem and thalamus with 3D reconstructions of the nuclei and white matter tracts involved in ET circuitry. We demonstrate registration of these data to in vivo, clinical images from patients receiving DBS therapy, and correlate electrode proximity to tractography of the DRT with improvement of ET symptoms. © 2015 Wiley Periodicals, Inc.

  10. The origin of behavioral bursts in decision-making circuitry.

    Directory of Open Access Journals (Sweden)

    Amanda Sorribes


    Full Text Available From ants to humans, the timing of many animal behaviors comes in bursts of activity separated by long periods of inactivity. Recently, mathematical modeling has shown that simple algorithms of priority-driven behavioral choice can result in bursty behavior. To experimentally test this link between decision-making circuitry and bursty dynamics, we have turned to Drosophila melanogaster. We have found that the statistics of intervals between activity periods in endogenous activity-rest switches of wild-type Drosophila are very well described by the Weibull distribution, a common distribution of bursty dynamics in complex systems. The bursty dynamics of wild-type Drosophila walking activity are shown to be determined by this inter-event distribution alone and not by memory effects, thus resembling human dynamics. Further, using mutant flies that disrupt dopaminergic signaling or the mushroom body, circuitry implicated in decision-making, we show that the degree of behavioral burstiness can be modified. These results are thus consistent with the proposed link between decision-making circuitry and bursty dynamics, and highlight the importance of using simple experimental systems to test general theoretical models of behavior. The findings further suggest that analysis of bursts could prove useful for the study and evaluation of decision-making circuitry.

  11. Rugged microelectronic module package supports circuitry on heat sink (United States)

    Johnson, A. L.


    Rugged module package for thin film hybrid microcircuits incorporated a rigid, thermally conductive support structure, which serves as a heat sink, and a lead wire block in which T-shaped electrical connectors are potted. It protects the circuitry from shock and vibration loads, dissipates internal heat, and simplifies electrical connections between adjacent modules.

  12. Progress toward the maintenance and repair of degenerating retinal circuitry. (United States)

    Vugler, Anthony A


    Retinal diseases such as age-related macular degeneration and retinitis pigmentosa remain major causes of severe vision loss in humans. Clinical trials for treatment of retinal degenerations are underway and advancements in our understanding of retinal biology in health/disease have implications for novel therapies. A review of retinal biology is used to inform a discussion of current strategies to maintain/repair neural circuitry in age-related macular degeneration, retinitis pigmentosa, and Type 2 Leber congenital amaurosis. In age-related macular degeneration/retinitis pigmentosa, a progressive loss of rods/cones results in corruption of bipolar cell circuitry, although retinal output neurons/photoreceptive melanopsin cells survive. Visual function can be stabilized/enhanced after treatment in age-related macular degeneration, but in advanced degenerations, reorganization of retinal circuitry may preclude attempts to restore cone function. In Type 2 Leber congenital amaurosis, useful vision can be restored by gene therapy where central cones survive. Remarkable progress has been made in restoring vision to rodents using light-responsive ion channels inserted into bipolar cells/retinal ganglion cells. Advances in genetic, cellular, and prosthetic therapies show varying degrees of promise for treating retinal degenerations. While functional benefits can be obtained after early therapeutic interventions, efforts should be made to minimize circuitry changes as soon as possible after rod/cone loss. Advances in retinal anatomy/physiology and genetic technologies should allow refinement of future reparative strategies.

  13. Reward Circuitry Function in Autism during Face Anticipation and Outcomes (United States)

    Dichter, Gabriel S.; Richey, J. Anthony; Rittenberg, Alison M.; Sabatino, Antoinette; Bodfish, James W.


    The aim of this study was to investigate reward circuitry responses in autism during reward anticipation and outcomes for monetary and social rewards. During monetary anticipation, participants with autism spectrum disorders (ASDs) showed hypoactivation in right nucleus accumbens and hyperactivation in right hippocampus, whereas during monetary…

  14. Development and aging of human spinal cord circuitries

    DEFF Research Database (Denmark)

    Geertsen, Svend Sparre; Willerslev-Olsen, Maria; Lorentzen, Jakob


    development and to what extent they are shaped according to the demands of the body that they control and the environment that the body has to interact with. We also discuss how ageing processes and physiological changes in our body are reflected in adaptations of activity in the spinal cord motor circuitries...

  15. Does Alzheimer's disease begin in the brainstem? (United States)

    Simic, G; Stanic, G; Mladinov, M; Jovanov-Milosevic, N; Kostovic, I; Hof, P R


    Although substantial evidence indicates that the progression of pathological changes of the neuronal cytoskeleton is crucial in determining the severity of dementia in Alzheimer's disease (AD), the exact causes and evolution of these changes, the initial site at which they begin, and the neuronal susceptibility levels for their development are poorly understood. The current clinical criteria for diagnosis of AD are focused mostly on cognitive deficits produced by dysfunction of hippocampal and high-order neocortical areas, whereas noncognitive, behavioural and psychological symptoms of dementia such as disturbances in mood, emotion, appetite, and wake-sleep cycle, confusion, agitation and depression have been less considered. The early occurrence of these symptoms suggests brainstem involvement, and more specifically of the serotonergic nuclei. In spite of the fact that the Braak and Braak staging system and National Institutes of Aging - Reagan Institute (NIA-RI) criteria do not include their evaluation, several recent reports drew attention to the possibility of selective and early involvement of raphe nuclei, particularly the dorsal raphe nucleus (DRN), in the pathogenesis of AD. Based on these findings of differential susceptibility and anatomical connectivity, a novel pathogenetic scheme of AD progression was proposed. Although the precise mechanisms of neurofibrillary degeneration still await elucidation, we speculated that cumulative oxidative damage may be the main cause of DRN alterations, as the age is the main risk factor for sporadic AD. Within such a framework, beta-amyloid production is considered only as one of the factors (although a significant one in familial cases) that promotes molecular series of events underlying AD-related neuropathological changes.

  16. Neurosurgical considerations on highly eloquent brainstem cavernomas during pregnancy. (United States)

    Burkhardt, Jan-Karl; Bozinov, Oliver; Nürnberg, Johannes; Shin, Benjamin; Woernle, Christoph M; Ulrich, Nils H; Bertalanffy, Helmut


    Cerebral cavernous malformations (CCMs) and especially cavernous malformations (CMs) in highly eloquent brain areas such as brainstem CMs are rare but possible events during pregnancy. Due to the few published cases in literature clear recommendations regarding the management are rare. In this study we evaluate the proceeding decision in pregnant patients with highly eloquent brainstem CMs. In our series 43 patients with CMs in highly eloquent brain areas, including 39 patients with brainstem CMs, were surgically treated by the senior author between July 2007 and July 2010. Out of these, 29 patients were female and three of them presented with a symptomatic brainstem CMs during pregnancy and were included in this study. According to our experiences and to the available literature we analyzed demographic and clinical variables to provide recommendations for the management of pregnant patients with highly eloquent brainstem CMs. Only one patient was operated during pregnancy the other two patients were surgically treated after delivery, respectively. A thorough review of the literature revealed 12 patients with brainstem cavernomas during pregnancy there of only two patients were operated during pregnancy. Surgical treatment during pregnancy is rarely required, but needs to be performed right away in life-threatening and rapidly progressive clinical situations. Pregnant women with CMs in highly eloquent brain areas such as brainstem CMs need to be treated in specialized centers to assess the best point of time for surgery. Our study offers a useful tool to support the proceeding decision in this rare but important situation. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Do cognitive measures and brain circuitry predict outcomes of exercise in Parkinson Disease: a randomized clinical trial. (United States)

    King, L A; Peterson, D S; Mancini, M; Carlson-Kuhta, P; Fling, B W; Smulders, K; Nutt, J G; Dale, M; Carter, J; Winters-Stone, K M; Horak, F B


    There is emerging research detailing the relationship between balance/gait/falls and cognition. Imaging studies also suggest a link between structural and functional changes in the frontal lobe (a region commonly associated with cognitive function) and mobility. People with Parkinson's disease have important changes in cognitive function that may impact rehabilitation efficacy. Our underlying hypothesis is that cognitive function and frontal lobe connections with the basal ganglia and brainstem posture/locomotor centers are responsible for postural deficits in people with Parkinson's disease and play a role in rehabilitation efficacy. The purpose of this study is to 1) determine if people with Parkinson's disease can improve mobility and/or cognition after partaking in a cognitively challenging mobility exercise program and 2) determine if cognition and brain circuitry deficits predict responsiveness to exercise rehabilitation. This study is a randomized cross-over controlled intervention to take place at a University Balance Disorders Laboratory. The study participants will be people with Parkinson's disease who meet inclusion criteria for the study. The intervention will be 6 weeks of group exercise (case) and 6 weeks of group education (control). The exercise is a cognitively challenging program based on the Agility Boot Camp for people with PD. The education program is a 6-week program to teach people how to better live with a chronic disease. The primary outcome measure is the MiniBESTest and the secondary outcomes are measures of mobility, cognition and neural imaging. The results from this study will further our understanding of the relationship between cognition and mobility with a focus on brain circuitry as it relates to rehabilitation potential. This trial is registered at clinical (NCT02231073).

  18. Auditory brainstem responses in term newborns with hyperbilirubinemia

    Directory of Open Access Journals (Sweden)

    Mônica Jubran Chapchap


    Full Text Available Objective: To evaluate auditory brainstem responses in term newbornswith hyperbilirubinemia. Methods: Seventy-one newborns, 35 withaggravated physiological neonatal jaundice (group I, 24 with ABOblood incompatibility (group II and 12 not suffering from jaundice orany other disease were submitted to auditory brainstem responses.Statistical analysis of variance was performed to evaluate waveformreproducibility, absolute and interwave latencies, and Pearsoncoefficient was used to evaluate the association between the level ofserum bilirubin and abnormalities in the auditory brainstem responses.Results: According to the criteria assumed in the present paperwaveform alterations were more frequently found in group II than inthe control group (p = 0.023. No significant differences were observedbetween groups I and II (p = 0.083 or between control group andgroup I (p = 0.166. Wave I latency at 80 dBHL for good reproducibilityresponses and III-V interwave latency at 40 dBHL for poor reproducibilityresponses of newborns with hyperbilirubinemia showed significantfindings in relation to the control group (0.008 and 0.004 respectively.There was positive, weak (9% association between serum indirectbilirubin levels and auditory brainstem responses only when the twogroups were analyzed together. Conclusions: Neonatalhyperbilirubinemia changed the conduction of auditory stimulus interm newborns with jaundice caused by ABO blood incompatibility.There was poor positive association between plasma levels of bilirubinand abnormalities in auditory brainstem responses.

  19. Imaging conditioned fear circuitry using awake rodent fMRI.

    Directory of Open Access Journals (Sweden)

    Nichola M Brydges

    Full Text Available Functional magnetic resonance imaging (fMRI is a powerful method for exploring emotional and cognitive brain responses in humans. However rodent fMRI has not previously been applied to the analysis of learned behaviour in awake animals, limiting its use as a translational tool. Here we have developed a novel paradigm for studying brain activation in awake rats responding to conditioned stimuli using fMRI. Using this method we show activation of the amygdala and related fear circuitry in response to a fear-conditioned stimulus and demonstrate that the magnitude of fear circuitry activation is increased following early life stress, a rodent model of affective disorders. This technique provides a new translatable method for testing environmental, genetic and pharmacological manipulations on emotional and cognitive processes in awake rodent models.

  20. Clinical and radiological features of hypertensive brainstem encephalopathy

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    Xiao-qiu LI


    Full Text Available Objective To discuss the diagnosis and treatment of hypertensive brainstem encephalopathy. Methods  The clinical and imaging data of 3 cases of hypertensive brainstem encephalopathy were summarized and analyzed for the purpose of improving the acumen in diagnosis and treatment. Results All the 3 patients showed relatively mild clinical symptoms, and they were misdiagnosed in different degrees during the treatment, but their clinical symptoms were improved by rapid and effective antihypertensive therapy. Cerebral CT and MRI scans revealed extensive abnormal signals in brain stem, with or without supratentorial lesions and brain stem hemorrhage. The lesions as revealed by imaging were improved significantly after treatment. Conclusions Clinical-radiographic dissociation is the classic feature of hypertensive brainstem encephalopathy. The clinical symptoms and lesions as shown by imaging could be improved after active treatment. DOI: 10.11855/j.issn.0577-7402.2015.06.03

  1. A critical appraisal of neuroimaging studies of bipolar disorder: toward a new conceptualization of underlying neural circuitry and roadmap for future research (United States)

    Phillips, Mary L; Swartz, Holly A.


    Objective This critical review appraises neuroimaging findings in bipolar disorder in emotion processing, emotion regulation, and reward processing neural circuitry, to synthesize current knowledge of the neural underpinnings of bipolar disorder, and provide a neuroimaging research “roadmap” for future studies. Method We examined findings from all major studies in bipolar disorder that used fMRI, volumetric analyses, diffusion imaging, and resting state techniques, to inform current conceptual models of larger-scale neural circuitry abnormalities in bipolar disorder Results Bipolar disorder can be conceptualized in neural circuitry terms as parallel dysfunction in bilateral prefrontal cortical (especially ventrolateral prefrontal cortical)-hippocampal-amygdala emotion processing and emotion regulation neural circuitries, together with an “overactive” left-sided ventral striatal-ventrolateral and orbitofrontal cortical reward processing circuitry, that result in characteristic behavioral abnormalities associated with bipolar disorder: emotional lability, emotional dysregulation and heightened reward sensitivity. A potential structural basis for these functional abnormalities are gray matter decreases in prefrontal and temporal cortices, amygdala and hippocampus, and fractional anisotropy decreases in white matter tracts connecting prefrontal and subcortical regions. Conclusion Neuroimaging studies of bipolar disorder clearly demonstrate abnormalities in neural circuitries supporting emotion processing, emotion regulation and reward processing, although there are several limitations to these studies. Future neuroimaging research in bipolar disorder should include studies adopting dimensional approaches; larger studies examining neurodevelopmental trajectories in bipolar disorder and at-risk youth; multimodal neuroimaging studies using integrated systems approaches; and studies using pattern recognition approaches to provide clinically useful, individual

  2. Bispectral Index Changes during Acute Brainstem TIA/Ischemia

    Directory of Open Access Journals (Sweden)

    Chris P. Bleeker


    Full Text Available We describe a 76-year-old patient who suffered a brainstem TIA just before being anesthetised for cardiac surgery. The TIA was registered on BIS and resulted in a drop in BIS to a value of 60. When consciousness returned spontaneously, the BIS increased to 85. The relative use of the BIS during an operation is discussed. We believe that the lack of input from the brainstem to the frontal cortex resulted in the reduced cortical electrical activity as registered with the BIS.

  3. The reciprocal cerebellar circuitry in human hereditary ataxia. (United States)

    Koeppen, Arnulf H; Ramirez, R Liane; Bjork, Sarah T; Bauer, Peter; Feustel, Paul J


    Clinicoanatomic correlation in the spinocerebellar ataxias (SCA) and Friedreich's ataxia (FRDA) is difficult as these diseases differentially affect multiple sites in the central and peripheral nervous systems. A new way to study cerebellar ataxia is the systematic analysis of the "reciprocal cerebellar circuitry" that consists of tightly organized reciprocal connections between Purkinje cells, dentate nuclei (DN), and inferior olivary nuclei (ION). This circuitry is similar to but not identical with the "cerebellar module" in experimental animals. Neurohumoral transmitters operating in the circuitry are both inhibitory (γ-aminobutyric acid in corticonuclear and dentato-olivary fibers) and excitatory (glutamate in olivocerebellar or climbing fibers). Glutamatergic climbing fibers also issue collaterals to the DN. The present study applied five immunohistochemical markers in six types of SCA (1, 2, 3, 6, 7, 17), genetically undefined SCA, FRDA, and FRDA carriers to identify interruptions within the circuitry: calbindin-D28k, neuron-specific enolase, glutamic acid decarboxylase, and vesicular glutamate transporters 1 and 2. Lesions of the cerebellar cortex, DN, and ION were scored according to a guide as 0 (normal), 1 (mild), 2 (moderate), and 3 (severe). Results of each of the five immunohistochemical stains were examined separately for each of the three regions. Combining scores of each anatomical region and each stain yielded a total score as an indicator of pathological severity. Total scores ranged from 16 to 38 in SCA-1 (nine cases); 22 to 39 in SCA-2 (six cases); 9 to 15 in SCA-3 (four cases); and 13 and 25 in SCA-6 (two cases). In single cases of SCA-7 and SCA-17, scores were 16 and 31, respectively. In two genetically undefined SCA, scores were 36 and 37, respectively. In nine cases of FRDA, total scores ranged from 11 to 19. The low scores in SCA-3 and FRDA reflect selective atrophy of the DN. The FRDA carriers did not differ from normal controls. These

  4. Affective neural circuitry during facial emotion processing in pediatric bipolar disorder. (United States)

    Pavuluri, Mani N; O'Connor, Megan Marlow; Harral, Erin; Sweeney, John A


    Facial emotions are central to human interaction. Identifying pathophysiology in affect processing circuitry that supports the ability to assess facial emotions might facilitate understanding of affect regulation in pediatric bipolar disorder. Ten euthymic, unmedicated pediatric bipolar patients and 10 healthy control subjects matched for age, gender, race, socioeconomic status, and IQ were scanned with functional magnetic resonance imaging. Angry, happy, and neutral faces were presented in 30-sec blocks, with a 20-sec rest period between blocks. Subjects were asked to press a button when each face appeared, to ensure that attention was maintained on-task. In bipolar patients, in response to both angry and happy faces relative to neutral faces, we observed reduced activation of right rostral ventrolateral prefrontal cortex together with increased activity in right pregenual anterior cingulate, amygdala, and paralimbic cortex. Bipolar patients also showed reduced activation of visual areas in occipital cortex together with greater activation in higher-order visual perceptual areas, including superior temporal sulcus and fusiform gyrus with angry faces and posterior parietal cortex with happy faces. Findings document a disturbance in affective neurocircuitry in pediatric bipolar disorder. Reduced activation in ventrolateral prefrontal cortex might reflect diminished top-down control that leads to the observed exaggerated activation in amygdala and paralimbic areas. Changes in occipital areas might represent an effort to gate sensory input when affective responses to the faces could not be successfully modulated. Disturbances in affect processing circuitry could contribute to emotional dysregulation and social cognitive difficulties in bipolar youth.

  5. The Brainstem Tau Cytoskeletal Pathology of Alzheimer's Disease : A Brief Historical Overview and Description of its Anatomical Distribution Pattern, Evolutional Features, Pathogenetic and Clinical Relevance

    NARCIS (Netherlands)

    Rueb, Udo; Stratmann, Katharina; Heinsen, Helmut; Del Turco, Domenico; Seidel, Kay; Dunnen, den Wilfred; Korf, Horst-Werner


    The human brainstem is involved in the regulation of the sleep/waking cycle and normal sleep architectonics and is crucial for the performance of a variety of somatomotor, vital autonomic, oculomotor, vestibular, auditory, ingestive and somatosensory functions. It harbors the origins of the

  6. Mapping of pain circuitry in early post-natal development using manganese-enhanced MRI in rats. (United States)

    Sperry, M M; Kandel, B M; Wehrli, S; Bass, K N; Das, S R; Dhillon, P S; Gee, J C; Barr, G A


    Premature or ill full-term infants are subject to a number of noxious procedures as part of their necessary medical care. Although we know that human infants show neural changes in response to such procedures, we know little of the sensory or affective brain circuitry activated by pain. In rodent models, the focus has been on spinal cord and, more recently, midbrain and medulla. The present study assesses activation of brain circuits using manganese-enhanced magnetic resonance imaging (MEMRI). Uptake of manganese, a paramagnetic contrast agent that is transported across active synapses and along axons, was measured in response to a hindpaw injection of dilute formalin in 12-day-old rat pups, the age at which rats begin to show aversion learning and which is roughly the equivalent of full-term human infants. Formalin induced the oft-reported biphasic response at this age and induced a conditioned aversion to cues associated with its injection, thus demonstrating the aversiveness of the stimulation. Morphometric analyses, structural equation modeling and co-expression analysis showed that limbic and sensory paths were activated, the most prominent of which were the prefrontal and anterior cingulate cortices, nucleus accumbens, amygdala, hypothalamus, several brainstem structures, and the cerebellum. Therefore, both sensory and affective circuits, which are activated by pain in the adult, can also be activated by noxious stimulation in 12-day-old rat pups. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Intraparenchymal papillary meningioma of brainstem: case report and literature review

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    Jiang Xiao-Bing


    Full Text Available Abstract Both intraparenchymal papillary meningioma and papillary meningioma with cyst formation of brainstem have never been reported. The authors present an extremely rare case of patient with intraparenchymal papillary meningioma of brainstem. A 23-year-old Chinese male presented with a 4-month history of progressive left upper limb and facial nerve palsy. Magnetic resonance imaging revealed a cystic-solid, heterogeneously enhancing mass in pons and right cerebral peduncle with no dural attachment. The tumor was totally removed via subtemporal approach. During surgery, the lesion was found to be completely intraparenchymal. Histological and immunohistochemical examinations were compatible with the diagnosis of papillary meningioma. The lesion recurred nine months after primary surgery, a second surgery followed by radiotherapy was performed. Till to now (nearly 2 years after the treatment, the patient is tumor free survival. Intraparenchymal meningioma of brainstem with cystic formation is very rare, however, it should be considered as a differential diagnosis of a brainstem neoplasm. The present case strongly recommended that postoperative radiotherapy was essential for the patients with papillary meningiomas.

  8. Auditory Brainstem Responses to Continuous Natural Speech in Human Listeners. (United States)

    Maddox, Ross K; Lee, Adrian K C


    Speech is an ecologically essential signal, whose processing crucially involves the subcortical nuclei of the auditory brainstem, but there are few experimental options for studying these early responses in human listeners under natural conditions. While encoding of continuous natural speech has been successfully probed in the cortex with neurophysiological tools such as electroencephalography (EEG) and magnetoencephalography, the rapidity of subcortical response components combined with unfavorable signal-to-noise ratios signal-to-noise ratio has prevented application of those methods to the brainstem. Instead, experiments have used thousands of repetitions of simple stimuli such as clicks, tone-bursts, or brief spoken syllables, with deviations from those paradigms leading to ambiguity in the neural origins of measured responses. In this study we developed and tested a new way to measure the auditory brainstem response (ABR) to ongoing, naturally uttered speech, using EEG to record from human listeners. We found a high degree of morphological similarity between the speech-derived ABRs and the standard click-evoked ABR, in particular, a preserved Wave V, the most prominent voltage peak in the standard click-evoked ABR. Because this method yields distinct peaks that recapitulate the canonical ABR, at latencies too short to originate from the cortex, the responses measured can be unambiguously determined to be subcortical in origin. The use of naturally uttered speech to measure the ABR allows the design of engaging behavioral tasks, facilitating new investigations of the potential effects of cognitive processes like language and attention on brainstem processing.

  9. Brainstem cytokine changes in healthy ageing and Motor Neurone Disease. (United States)

    Tennakoon, Anuradha; Katharesan, Viythia; Johnson, Ian P


    Neuroinflammation is linked to healthy ageing, but its role in the development of age-related neurodegenerative diseases is unclear. In this pilot study we used a multiplex assay approach to compare 27 cytokines in 6 young adult and 6 ageing control brainstems with those in 6 MND brainstems. We report that healthy ageing is associated with significantly increased brainstem levels of IL-1β, IP-10 and MIP-1β which co-localise immunocytochemically to astrocytes. MND brainstem is also characterised by a general increase in both pro- and anti-cytokine levels, but fails to show the expected age-related increase in MIP-1β and IP-10. This pilot study is the first to show that MND is associated with a failure of specific features of the normal age-related neuroinflammatory process. We suggest that our pilot data indicates that neuroinflammation during healthy ageing may not always be detrimental to motoneuronal survival and that age-related neurodegenerative diseases, such as MND, may instead result from defective neuroinflammation. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Stance disturbance in multiple sclerosis: brainstem lesions and posturographic assessment

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    Peter Schalek


    Full Text Available

    Background. Balance disorders are commonly evidenced during the course of multiple sclerosis (MS. The aim of this study is to report characteristics of MS patient stance control disorders, measured by means of posturography and related to the brainstem lesions.

    Methods. Thirty-eight patients affected by MS, mildly to moderately disable according to Kurtzke’s Expanded Disability Status Scale, underwent a complete clinical neurological and vestibular evaluation and brain MRI scanning. All patients were then tested on a static posturography platform (Tetrax, Israel in four conditions: eyes open and closed standing on a firm surface and on a foam pad.

    Results. Clinical and/or MRI evidence of brainstem involvement was observed in 55.3 % of patients. When brainstem lesion was detected, Fourier analysis showed a typical pattern characterized by inversion of the  0- 0.1 Hz and  0.1 - 0.25 Hz. frequency bands.

    Conclusions. MS leads to pervasive postural disturbances in the majority of subjects, including the visuo-vestibular loops and proprioception involving vestibulo-spinal pathways in at least 55.3 % of patients. Our results may also suggest the presence of Fourier inversion in patients with brainstem lesions.

  11. Modeling auditory evoked brainstem responses to transient stimuli

    DEFF Research Database (Denmark)

    Rønne, Filip Munch; Dau, Torsten; Harte, James


    A quantitative model is presented that describes the formation of auditory brainstem responses (ABR) to tone pulses, clicks and rising chirps as a function of stimulation level. The model computes the convolution of the instantaneous discharge rates using the “humanized” nonlinear auditory-nerve ...

  12. Construction of Hindi Speech Stimuli for Eliciting Auditory Brainstem Responses. (United States)

    Ansari, Mohammad Shamim; Rangasayee, R


    Speech-evoked auditory brainstem responses (spABRs) provide considerable information of clinical relevance to describe auditory processing of complex stimuli at the sub cortical level. The substantial research data have suggested faithful representation of temporal and spectral characteristics of speech sounds. However, the spABR are known to be affected by acoustic properties of speech, language experiences and training. Hence, there exists indecisive literature with regards to brainstem speech processing. This warrants establishment of language specific speech stimulus to describe the brainstem processing in specific oral language user. The objective of current study is to develop Hindi speech stimuli for recording auditory brainstem responses. The Hindi stop speech of 40 ms containing five formants was constructed. Brainstem evoked responses to speech sound |da| were gained from 25 normal hearing (NH) adults having mean age of 20.9 years (SD = 2.7) in the age range of 18-25 years and ten subjects (HI) with mild SNHL of mean 21.3 years (SD = 3.2) in the age range of 18-25 years. The statistically significant differences in the mean identification scores of synthesized for speech stimuli |da| and |ga| between NH and HI were obtained. The mean, median, standard deviation, minimum, maximum and 95 % confidence interval for the discrete peaks and V-A complex values of electrophysiological responses to speech stimulus were measured and compared between NH and HI population. This paper delineates a comprehensive methodological approach for development of Hindi speech stimuli and recording of ABR to speech. The acoustic characteristic of stimulus |da| was faithfully represented at brainstem level in normal hearing adults. There was statistically significance difference between NH and HI individuals. This suggests that spABR offers an opportunity to segregate normal speech encoding from abnormal speech processing at sub cortical level, which implies that

  13. Microsurgical removal of brainstem cavernoma: A report of 42 cases

    Directory of Open Access Journals (Sweden)

    Jian-ning ZHANG


    Full Text Available Objective To summarize the clinical features and the surgical approach and techniques for microsurgical removal of brainstem cavernoma, and to evaluate the efficacy of surgical treatment of brainstem cavernoma. Methods The clinical data of 41 brainstem cavernoma patients treated by microsurgical resection from January 2003 to April 2011 were retrospectively analyzed, and they were 23 males and 18 females, aged 8 to 62 years. The clinical presentations included signs and symptoms of increased intracranial pressure, such as headache and dizziness, long-tract signs such as cranial nerve dysfunction, numbness and decrease in muscle strength, and ataxia. According to the site of the lesions, surgical approaches were selected following the principle of "the shortest distance between the incision and the lesion". Intraoperative short-latency somatosensory evoked potential (SSEP and auditory evoked potential (AEP were monitored. Results Total resection of cavernoma was achieved in 35 patients, small residual tumor was left in 6 with giant lesions. No death occurred. Twenty-seven patients showed improvement in nerve function. Aggravation of pre-existing neurological disorders or appearance of new neurological disorders was found in 14 patients, including 2 with respiratory dysfunction who regained spontaneous breathing after assisted respiration for one week. Follow-up was carried out for 38 months in average. Neurological deficits have been restored in most patients, and no recurrence was found except for 1 case of re-bleeding from residual tumor. Conclusions According to the lesion site and protruding direction, individualized surgical approach can be selected following the "shortest distance" principle for the resection of brainstem cavernoma. The application of intraoperative navigation and electrophysiological monitoring of the brainstem is helpful in reducing surgical injury and decreasing the complications.

  14. The Structural, Functional and Molecular Organization of the Brainstem

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    Rudolf eNieuwenhuys


    Full Text Available According to Wilhelm His (1891, 1893 the brainstem consists of two longitudinal zones, the dorsal alar plate (sensory in nature and the ventral basal plate (motor in nature. Johnston and Herrick indicated that both plates can be subdivided into separate somatic and visceral zones, distinguishing somatosensory and viscerosensory zones within the alar plate, and visceromotor and somatomotor zones within the basal plate. To test the validity of this ‘four-functional-zones’ concept, I developed a topological procedure, surveying the spatial relationships of the various cell masses in the brainstem in a single figure. Brainstems of 16 different anamniote species were analyzed, and revealed that the brainstems are clearly divisible into four morphological zones, which correspond largely with the functional zones of Johnston and Herrick. Exceptions include (1 the magnocellular vestibular nucleus situated in the viscerosensory zone; (2 the basal plate containing a number of evidently non-motor centres (superior and inferior olives. Nevertheless the ‘functional zonal model’ has explanatory value. Thus, it is possible to interpret certain brain specializations related to particular behavioural profiles, as ‘local hypertrophies’ of one or two functional columns. Recent developmental molecular studies on brains of birds and mammals confirmed the presence of longitudinal zones, and also showed molecularly defined transverse bands or neuromeres throughout development. The intersecting boundaries of the longitudinal zones and the transverse bands appeared to delimit radially arranged histogenetic domains. Because neuromeres have been observed in embryonic and larval stages of numerous anamniote species, it may be hypothesized that the brainstems of all vertebrates share a basic organizational plan, in which intersecting longitudinal and transverse zones form fundamental histogenetic and genoarchitectonic units.

  15. Inducing nonlinear dynamic response via piezoelectric circuitry integration (United States)

    Xu, J.; Tang, J.


    Owing to the two-way electro-mechanical coupling characteristics, piezoelectric transducers have been widely used as sensors and actuators in sensing and control applications. In this research, we explore the integration of piezoelectric transducer with the structure, in which the transducer is connected with a Wheatstone bridge based circuitry subjected to chaotic excitation. It is shown that a type of Wheatstone bridge circuit with proper parameters configuration can increase sensitivity in detecting structural anomaly. Such integration has the potential to significantly amplify the response change when the underlying structure is subject to property change. Comprehensive analytical and experimental studies are carried out to demonstrate the concept and validate the performance improvement.

  16. Advanced Data Acquisition Systems with Self-Healing Circuitry (United States)

    Larson, William E.; Ihlefeld, Curtis M.; Medelius, Pedro J.; Delgado, H. (Technical Monitor)


    Kennedy Space Center's Spaceport Engineering & Technology Directorate has developed a data acquisition system that will help drive down the cost of ground launch operations. This system automates both the physical measurement set-up function as well as configuration management documentation. The key element of the system is a self-configuring, self-calibrating, signal-conditioning amplifier that automatically adapts to any sensor to which it is connected. This paper will describe the core technology behind this device and the automated data system in which it has been integrated. The paper will also describe the revolutionary enhancements that are planned for this innovative measurement technology. All measurement electronics devices contain circuitry that, if it fails or degrades, requires the unit to be replaced, adding to the cost of operations. Kennedy Space Center is now developing analog circuits that will be able to detect their own failure and dynamically reconfigure their circuitry to restore themselves to normal operation. This technology will have wide ranging application in all electronic devices used in space and ground systems.

  17. Impedance-based damage identification enhancement via tunable piezoelectric circuitry (United States)

    Kim, Jinki; Wang, K. W.


    The piezoelectric impedance-based method for damage detection has been explored extensively for its high sensitivity to small-sized damages with low-cost measurement circuit which enables remote damage monitoring. While the method has good potential, the amount of feasible impedance data is usually much less than the number of required system parameters to accurately identify the damage location/severity via an inverse formulation. This data incompleteness forms a highly underdetermined problem and because of this numerical ill-conditioning, the predicted damage parameters will be significantly influenced by unavoidable measurement noise and the accuracy of the base-line model. In this study, the state of the art of impedance-based damage identification is advanced by incorporating a tunable piezoelectric circuitry with the structure to enrich the impedance measurements. This piezoelectric circuitry introduces additional degrees of freedom to the structure and changes the dynamics of the coupled system. By tuning the inductance value, it is possible to perform various measurements under different system dynamics which reflects the damage effect. Therefore, if performed systematically, notably increased sets of measurement can be obtained, which will improve the inverse problem to be less underdetermined. Clearly, we can expect the accuracy and robustness in damage identification to be significantly enhanced. Numerical case study on localizing damage in a fixed-fixed beam using spectral element method is performed to demonstrate the effectiveness of the new method for structural damage identification.

  18. Diffusion tensor imaging of the brainstem in children with achondroplasia. (United States)

    Bosemani, Thangamadhan; Orman, Gunes; Carson, Kathryn A; Meoded, Avner; Huisman, Thierry A G M; Poretti, Andrea


    The aims of this study were to compare, using diffusion tensor imaging (DTI) of the brainstem, microstructural integrity of the white matter in children with achondroplasia and age-matched participants and to correlate the severity of craniocervical junction (CCJ) narrowing and neurological findings with DTI scalars in children with achondroplasia. This study also aimed to assess the potential role of fibroblast growth factor receptor type 3 on white matter microstructure. Diffusion tensor imaging was performed using a 1.5T magnetic resonance scanner and balanced pairs of diffusion gradients along 20 non-collinear directions. Measurements were obtained from regions of interest, sampled in each pontine corticospinal tract (CST), medial lemniscus, and middle cerebellar peduncle, as well as in the lower brainstem and centrum semiovale, for fractional anisotropy and for mean, axial, and radial diffusivity. In addition, a severity score for achondroplasia was assessed by measuring CCJ narrowing. Eight patients with achondroplasia (seven males, one female; mean age 5y 6mo, range 1y 1mo-15y 1mo) and eight age- and sex-matched comparison participants (mean age 5y 2mo, range 1y 1mo-14y 11mo) were included in this study. Fractional anisotropy was lower and mean diffusivity and radial diffusivity were higher in the lower brainstem of patients with achondroplasia than in age-matched comparison participants. The CST and middle cerebellar peduncle of the participants showed increases in mean, axial, and radial diffusivity. Fractional anisotropy in the lower brainstem was negatively correlated with the degree of CCJ narrowing. No differences in the DTI metrics of the centrum semiovale were observed between the two groups. The reduction in fractional anisotropy and increase in diffusivities in the lower brainstem of participants with achondroplasia may reflect secondary encephalomalacic degeneration and cavitation of the affected white matter tracts as shown by histology. In

  19. Activation of autophagy at cerebral cortex and apoptosis at brainstem are differential responses to 835 MHz RF-EMF exposure. (United States)

    Kim, Ju Hwan; Yu, Da-Hyeon; Kim, Hak Rim


    With the explosive increase in exposure to radiofrequency electromagnetic fields (RF-EMF) emitted by mobile phones, public concerns have grown over the last few decades with regard to the potential effects of EMF exposure on the nervous system in the brain. Many researchers have suggested that RF-EMFs can effect diverse neuronal alterations in the brain, thereby affecting neuronal functions as well as behavior. Previously, we showed that long-term exposure to 835 MHz RF-EMF induces autophagy in the mice brain. In this study, we explore whether short-term exposure to RF-EMF leads to the autophagy pathway in the cerebral cortex and brainstem at 835 MHz with a specific absorption rate (SAR) of 4.0 W/kg for 4 weeks. Increased levels of autophagy genes and proteins such as LC3B-II and Beclin1 were demonstrated and the accumulation of autophagosomes and autolysosomes was observed in cortical neurons whereas apoptosis pathways were up-regulated in the brainstem but not in the cortex following 4 weeks of RF exposure. Taken together, the present study indicates that monthly exposure to RF-EMF induces autophagy in the cerebral cortex and suggests that autophagic degradation in cortical neurons against a stress of 835 MHz RF during 4 weeks could correspond to adaptation to the RF stress environment. However, activation of apoptosis rather than autophagy in the brainstem is suggesting the differential responses to the RF-EMF stresses in the brain system.

  20. The Brainstem and Serotonin in the Sudden Infant Death Syndrome (United States)

    Kinney, Hannah C.; Richerson, George B.; Dymecki, Susan M.; Darnall, Robert A.; Nattie, Eugene E.


    The sudden infant death syndrome (SIDS) is the sudden death of an infant under one year of age that is typically associated with sleep and that remains unexplained after a complete autopsy and death scene investigation. A leading hypothesis about its pathogenesis is that many cases result from defects in brainstem-mediated protective responses to homeostatic stressors occurring during sleep in a critical developmental period. Here we review the evidence for the brainstem hypothesis in SIDS with a focus upon abnormalities related to the neurotransmitter serotonin in the medulla oblongata, as these are the most robust pathologic findings to date. In this context, we synthesize the human autopsy data with genetic, whole-animal, and cellular data concerning the function and development of the medullary serotonergic system. These emerging data suggest an important underlying mechanism in SIDS that may help lead to identification of infants at risk and specific interventions to prevent death. PMID:19400695

  1. Brainstem electrical responses from selected tone pip stimuli. (United States)

    Wood, M H; Seitz, M R; Jacobson, J T


    Brainstem-electrical responses were obtained from 10 normal hearing adult subjects using frequency specific tone pips as stimuli. The four frequency specific tone pips (500, 1000, 2000, and 4000 Hz) were diamond shaped with a 2.5-msec rise/fall time. Each tone pip was presented at four intensity levels (70, 50, 30, and 10 dB hearing threshold level), and graphic recordings were made for each frequency at the specific intensity levels. Frequency specific Wave V intensity-latency functions were plotted, and these results were compared to tone pip data obtained in previous studies. In addition, suggested test procedures for obtaining tone pip brainstem-evoked responses under diagnostic conditions are discussed.

  2. Hemicrania continua secondary to an ipsilateral brainstem lesion. (United States)

    Valença, Marcelo M; Andrade-Valença, Luciana P A; da Silva, Wilson Farias; Dodick, David W


    We describe a 47-year-old woman with a 3-year history of a continuum mild-moderate right-side headache, with exacerbations, associated with stabbing volleys of pain on right orbit-temporal region (10/10) and right eye ptosis and lacrimation with conjunctival injection. The pain was completely abolished with indomethacin (100 mg per day). The diagnosis of hemicrania continua was made according to the International Headache Society (IHS) criteria. The headache presentation was precipitated by a stroke and a right-side brainstem lesion was present at magnetic resonance imaging. This case report shows anatomoclinical evidence of the involvement of brainstem structures on the pathophysiology of hemicrania continua.


    Directory of Open Access Journals (Sweden)

    Sowmiya R, Vinodha R


    Full Text Available Background: Migraine is worldwide common, chronic, Neurovascular disorder, characterized by attacks of severe headache and an Aura involving neurologic symptoms. Its pathogenesis was incompletely understood whether of cortical or brainstem origin. Aim: The present study was undertaken to investigate brainstem auditory functions in Migraine patients. Materials and Methods: The subjects were recruited based on International Headache Society classification for Migraine. Subjects with episodes of headache for at least 2yrs, 2 attacks per month in last quarter year were included in the study. Forty subjects (16 Migraine with Aura & 24 cases – Migraine without aura & forty age / sex matched controls were selected. Brainstem auditory evoked potential was recorded using 4-Channel polygraph (Neuro perfect plus. Electrodes were placed according to 10 – 20 electrode placement system. Auditory stimulus in the form of click sound is delivered through the headphones. Clicks were delivered at a rate of 8-10 /sec. The intensity of the stimulus is set at 30db. About 100 averages were recorded. BAEP waveforms – Wave I, III & V latencies and the interpeak latencies were measured. The results were analysed statistically using student‘t’ test. Results: BAEP recording shows significant prolongation in latencies of Wave I, III & V and the Interpeak latency (IPL I-III, III-V & I-V in Migraine with aura. In Migraine without aura, there was significant prolongation of Wave I, III & V and III-V & I-VIPL (P<0.05. Conclusion: Prolongation suggests that there is involvement of brainstem structures in Migraine, thus BAEP can be used as an effective tool in evaluation of Migraine.

  4. Automatic hearing loss detection system based on auditory brainstem response

    Energy Technology Data Exchange (ETDEWEB)

    Aldonate, J; Mercuri, C; Reta, J; Biurrun, J; Bonell, C; Gentiletti, G; Escobar, S; Acevedo, R [Laboratorio de Ingenieria en Rehabilitacion e Investigaciones Neuromusculares y Sensoriales (Argentina); Facultad de Ingenieria, Universidad Nacional de Entre Rios, Ruta 11 - Km 10, Oro Verde, Entre Rios (Argentina)


    Hearing loss is one of the pathologies with the highest prevalence in newborns. If it is not detected in time, it can affect the nervous system and cause problems in speech, language and cognitive development. The recommended methods for early detection are based on otoacoustic emissions (OAE) and/or auditory brainstem response (ABR). In this work, the design and implementation of an automated system based on ABR to detect hearing loss in newborns is presented. Preliminary evaluation in adults was satisfactory.

  5. Thalamic, brainstem, and cerebellar glucose metabolism in the hemiplegic monkey

    Energy Technology Data Exchange (ETDEWEB)

    Shimoyama, I.; Dauth, G.W.; Gilman, S.; Frey, K.A.; Penney, J.B. Jr.


    Unilateral ablation of cerebral cortical areas 4 and 6 of Brodmann in the macaque monkey results in a contralateral hemiplegia that resolves partially with time. During the phase of dense hemiplegia, local cerebral metabolic rate for glucose (1CMRG1c) is decreased significantly in most of the thalamic nuclei ipsilateral to the ablation, and there are slight contralateral decreases. The lCMRGlc is reduced bilaterally in most of the brainstem nuclei and bilaterally in the deep cerebellar nuclei, but only in the contralateral cerebellar cortex. During the phase of partial motor recovery, lCMRGlc is incompletely restored in many of the thalamic nuclei ipsilateral to the ablation and completely restored in the contralateral nuclei. In the brainstem and deep cerebellar nuclei, poor to moderate recovery occurs bilaterally. Moderate recovery occurs in the contralateral cerebellar cortex. The findings demonstrate that a unilateral cerebral cortical lesion strongly affects lCMRGlc in the thalamus ipsilaterally and in the cerebellar cortex contralaterally, but in the brainstem bilaterally. Partial recovery of lCMRGlc accompanies the progressive motor recovery. The structures affected include those with direct, and also those with indirect, connections to the areas ablated.

  6. Acute disseminated encephalomyelitis presenting as a brainstem encephalitis. (United States)

    Atherton, Daniel S; Perez, Sarah R; Gundacker, Nathan D; Franco, Ricardo; Han, Xiaosi


    Acute disseminated encephalomyelitis (ADEM) is a disease characterized by inflammation and destruction of myelin. Acute hemorrhagic leukoencephalitis (AHLE) is a severe form of ADEM known for its particularly poor outcome. We present a case of a young Caucasian female who presented with drowsiness and slurred speech followed by rapid brainstem involvement resembling rhomboencephalitis. Despite multiple diagnostic tests and empiric therapy with immunosuppressants, immunoglobulins, and antimicrobials, she lost most brainstem reflexes within a few weeks and ultimately passed away. Magnetic resonance imaging (MRI) showed progression of lesions from the brainstem to eventually involve bilateral cerebral hemispheres. Autopsy and microscopic examination of the brain revealed several hemorrhagic lesions throughout the brain and rendered a diagnosis of AHLE. AHLE was initially described in 1941 and is thought to be autoimmune related, possibly related to cross reactivity between the immune system and CNS tissues like myelin. While a definitive inciting pathogen was not discovered, this case emphasizes the importance of considering AHLE in the differential diagnosis of patients with rapid loss of neurologic function and highlights an atypical presentation of ADEM/AHLE. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Mapping of neurokinin-like immunoreactivity in the human brainstem

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    Narvaez Jose


    Full Text Available Abstract Background Using an indirect immunoperoxidase technique, we have studied the distribution of immunoreactive fibers and cell bodies containing neurokinin in the adult human brainstem with no prior history of neurological or psychiatric disease. Results Clusters of immunoreactive cell bodies and high densities of neurokinin-immunoreactive fibers were located in the periaqueductal gray, the dorsal motor nucleus of the vagus and in the reticular formation of the medulla, pons and mesencephalon. Moreover, immunoreactive cell bodies were found in the inferior colliculus, the raphe obscurus, the nucleus prepositus hypoglossi, and in the midline of the anterior medulla oblongata. In general, immunoreactive fibers containing neurokinin were observed throughout the whole brainstem. In addition to the nuclei mentioned above, the highest densities of such immunoreactive fibers were located in the spinal trigeminal nucleus, the lateral reticular nucleus, the nucleus of the solitary tract, the superior colliculus, the substantia nigra, the nucleus ambiguus, the gracile nucleus, the cuneate nucleus, the motor hypoglossal nucleus, the medial and superior vestibular nuclei, the nucleus prepositus hypoglossi and the interpeduncular nucleus. Conclusion The widespread distribution of immunoreactive structures containing neurokinin in the human brainstem indicates that neurokinin might be involved in several physiological mechanisms, acting as a neurotransmitter and/or neuromodulator.

  8. Quality of life after brainstem cavernoma surgery in 71 patients. (United States)

    Dukatz, Thomas; Sarnthein, Johannes; Sitter, Helmut; Bozinov, Oliver; Benes, Ludwig; Sure, Ulrich; Bertalanffy, Helmut


    Symptomatic patients with a brainstem cavernoma are treated surgically with increasing frequency. Generally, the patient's benefit from this difficult surgical intervention is quantified by the assessment of neurological symptoms. To document the beneficial effect of surgery in a larger patient population by assessing the postoperative quality of life (QoL). In a series of 71 surgically treated patients, a detailed neurological status was assessed by Patzold Rating and Karnofsky Performance Status Scale. Patients rated their QoL with the Short Form 36 Health Survey. To document the effect of surgery on QoL, we devised a supplementary questionnaire. The last 24 patients completed Short Form 36 Health Survey pre- and postoperatively. Karnofsky Performance Status Scale improved in 44 of 71 surgical patients (62%), remained unchanged in 19 (27%), and deteriorated in 8 (11%) individuals. Patzold Rating showed a more detailed picture of the neurological symptoms. It correlated significantly with Karnofsky Performance Status Scale, which underscores its usefulness for patients with brainstem lesions. In the Short Form 36 Health Survey score, the Mental Component Summary improved with surgery (paired test, P = .015). In addition, 58 individuals (82%) declared a clear subjective benefit of surgery. The results of this large series support the notion that microsurgical removal of a brainstem cavernoma represents an effective therapy in experienced hands and is generally associated with good clinical outcome, both neurologically and in terms of QoL.

  9. Functional imaging of the human brainstem during somatosensory input and autonomic output

    Directory of Open Access Journals (Sweden)

    Luke Anthony Henderson


    Full Text Available Over the past half a century, many experimental animal investigations have explored the role of various brainstem regions in a variety of conditions. Despite the accumulation of a considerable body of knowledge in primarily anaesthetized preparations, relatively few investigations have explored brainstem function in awake humans. It is important that human brainstem function is explored given that many neurological conditions, from obstructive sleep apnea, chronic pain and hypertension, likely involve significant changes in the processing of information within the brainstem. Recent advances in the collection and processing of magnetic resonance images, has resulted in the possibility of exploring brainstem activity changes in awake healthy individuals and in those with various clinical conditions. We and others have begun to explore changes in brainstem activity in humans during a number of challenges, including during cutaneous and muscle pain, as well as during challenges that evoke increases in sympathetic activity. More recently we have successfully recorded sympathetic nerve activity concurrently with fMRI of the brainstem, which will allow us, for the first time to explore brainstem sites directly responsible for conditions such as hypertension. Since many conditions will involve changes in brainstem function and structure, defining brainstem changes will likely result in a greater ability to develop more effective treatment regimes.

  10. Metal Chelation as a Powerful Strategy to Probe Cellular Circuitry Governing Fungal Drug Resistance and Morphogenesis. (United States)

    Polvi, Elizabeth J; Averette, Anna F; Lee, Soo Chan; Kim, Taeyup; Bahn, Yong-Sun; Veri, Amanda O; Robbins, Nicole; Heitman, Joseph; Cowen, Leah E


    Fungal pathogens have evolved diverse strategies to sense host-relevant cues and coordinate cellular responses, which enable virulence and drug resistance. Defining circuitry controlling these traits opens new opportunities for chemical diversity in therapeutics, as the cognate inhibitors are rarely explored by conventional screening approaches. This has great potential to address the pressing need for new therapeutic strategies for invasive fungal infections, which have a staggering impact on human health. To explore this approach, we focused on a leading human fungal pathogen, Candida albicans, and screened 1,280 pharmacologically active compounds to identify those that potentiate the activity of echinocandins, which are front-line therapeutics that target fungal cell wall synthesis. We identified 19 compounds that enhance activity of the echinocandin caspofungin against an echinocandin-resistant clinical isolate, with the broad-spectrum chelator DTPA demonstrating the greatest synergistic activity. We found that DTPA increases susceptibility to echinocandins via chelation of magnesium. Whole genome sequencing of mutants resistant to the combination of DTPA and caspofungin identified mutations in the histidine kinase gene NIK1 that confer resistance to the combination. Functional analyses demonstrated that DTPA activates the mitogen-activated protein kinase Hog1, and that NIK1 mutations block Hog1 activation in response to both caspofungin and DTPA. The combination has therapeutic relevance as DTPA enhanced the efficacy of caspofungin in a mouse model of echinocandin-resistant candidiasis. We found that DTPA not only reduces drug resistance but also modulates morphogenesis, a key virulence trait that is normally regulated by environmental cues. DTPA induced filamentation via depletion of zinc, in a manner that is contingent upon Ras1-PKA signaling, as well as the transcription factors Brg1 and Rob1. Thus, we establish a new mechanism by which metal chelation

  11. Metal Chelation as a Powerful Strategy to Probe Cellular Circuitry Governing Fungal Drug Resistance and Morphogenesis.

    Directory of Open Access Journals (Sweden)

    Elizabeth J Polvi


    Full Text Available Fungal pathogens have evolved diverse strategies to sense host-relevant cues and coordinate cellular responses, which enable virulence and drug resistance. Defining circuitry controlling these traits opens new opportunities for chemical diversity in therapeutics, as the cognate inhibitors are rarely explored by conventional screening approaches. This has great potential to address the pressing need for new therapeutic strategies for invasive fungal infections, which have a staggering impact on human health. To explore this approach, we focused on a leading human fungal pathogen, Candida albicans, and screened 1,280 pharmacologically active compounds to identify those that potentiate the activity of echinocandins, which are front-line therapeutics that target fungal cell wall synthesis. We identified 19 compounds that enhance activity of the echinocandin caspofungin against an echinocandin-resistant clinical isolate, with the broad-spectrum chelator DTPA demonstrating the greatest synergistic activity. We found that DTPA increases susceptibility to echinocandins via chelation of magnesium. Whole genome sequencing of mutants resistant to the combination of DTPA and caspofungin identified mutations in the histidine kinase gene NIK1 that confer resistance to the combination. Functional analyses demonstrated that DTPA activates the mitogen-activated protein kinase Hog1, and that NIK1 mutations block Hog1 activation in response to both caspofungin and DTPA. The combination has therapeutic relevance as DTPA enhanced the efficacy of caspofungin in a mouse model of echinocandin-resistant candidiasis. We found that DTPA not only reduces drug resistance but also modulates morphogenesis, a key virulence trait that is normally regulated by environmental cues. DTPA induced filamentation via depletion of zinc, in a manner that is contingent upon Ras1-PKA signaling, as well as the transcription factors Brg1 and Rob1. Thus, we establish a new mechanism by which

  12. Construction of functional neuronal circuitry in the olfactory bulb. (United States)

    Imai, Takeshi


    Recent studies using molecular genetics, electrophysiology, in vivo imaging, and behavioral analyses have elucidated detailed connectivity and function of the mammalian olfactory circuits. The olfactory bulb is the first relay station of olfactory perception in the brain, but it is more than a simple relay: olfactory information is dynamically tuned by local olfactory bulb circuits and converted to spatiotemporal neural code for higher-order information processing. Because the olfactory bulb processes ∼1000 discrete input channels from different odorant receptors, it serves as a good model to study neuronal wiring specificity, from both functional and developmental aspects. This review summarizes our current understanding of the olfactory bulb circuitry from functional standpoint and discusses important future studies with particular focus on its development and plasticity. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Stretchable biocompatible electronics by embedding electrical circuitry in biocompatible elastomers. (United States)

    Jahanshahi, Amir; Salvo, Pietro; Vanfleteren, Jan


    Stretchable and curvilinear electronics has been used recently for the fabrication of micro systems interacting with the human body. The applications range from different kinds of implantable sensors inside the body to conformable electrodes and artificial skins. One of the key parameters in biocompatible stretchable electronics is the fabrication of reliable electrical interconnects. Although very recent literature has reported on the reliability of stretchable interconnects by cyclic loading, work still needs to be done on the integration of electrical circuitry composed of rigid components and stretchable interconnects in a biological environment. In this work, the feasibility of a developed technology to fabricate simple electrical circuits with meander shaped stretchable interconnects is presented. Stretchable interconnects are 200 nm thin Au layer supported with polyimide (PI). A stretchable array of light emitting diodes (LEDs) is embedded in biocompatible elastomer using this technology platform and it features a 50% total elongation.

  14. Perturbation of Serotonin Homeostasis during Adulthood Affects Serotonergic Neuronal Circuitry. (United States)

    Pratelli, Marta; Migliarini, Sara; Pelosi, Barbara; Napolitano, Francesco; Usiello, Alessandro; Pasqualetti, Massimo


    Growing evidence shows that the neurotransmitter serotonin (5-HT) modulates the fine-tuning of neuron development and the establishment of wiring patterns in the brain. However, whether serotonin is involved in the maintenance of neuronal circuitry in the adult brain remains elusive. Here, we use a Tph2(fl)°(x) conditional knockout (cKO) mouse line to assess the impact of serotonin depletion during adulthood on serotonergic system organization. Data show that the density of serotonergic fibers is increased in the hippocampus and decreased in the thalamic paraventricular nucleus (PVN) as a consequence of brain serotonin depletion. Strikingly, these defects are rescued following reestablishment of brain 5-HT signaling via administration of the serotonin precursor 5-hydroxytryptophan (5-HTP). Finally, 3D reconstruction of serotonergic fibers reveals that changes in serotonin homeostasis affect axonal branching complexity. These data demonstrate that maintaining proper serotonin homeostasis in the adult brain is crucial to preserve the correct serotonergic axonal wiring.

  15. Focusing on optic tectum circuitry through the lens of genetics

    Directory of Open Access Journals (Sweden)

    Nevin Linda M


    Full Text Available Abstract The visual pathway is tasked with processing incoming signals from the retina and converting this information into adaptive behavior. Recent studies of the larval zebrafish tectum have begun to clarify how the 'micro-circuitry' of this highly organized midbrain structure filters visual input, which arrives in the superficial layers and directs motor output through efferent projections from its deep layers. The new emphasis has been on the specific function of neuronal cell types, which can now be reproducibly labeled, imaged and manipulated using genetic and optical techniques. Here, we discuss recent advances and emerging experimental approaches for studying tectal circuits as models for visual processing and sensorimotor transformation by the vertebrate brain.

  16. Integrated circuit electrometer and sweep circuitry for an atmospheric probe (United States)

    Zimmerman, L. E.


    The design of electrometer circuitry using an integrated circuit operational amplifier with a MOSFET input is described. Input protection against static voltages is provided by a dual ultra low leakage diode or a neon lamp. Factors affecting frequency response leakage resistance, and current stability are discussed, and methods are suggested for increasing response speed and for eliminating leakage resistance and current instabilities. Based on the above, two practical circuits, one having a linear response and the other a logarithmic response, were designed and evaluated experimentally. The design of a sweep circuit to implement mobility measurements using atmospheric probes is presented. A triangular voltage waveform is generated and shaped to contain a step in voltage from zero volts in both positive and negative directions.

  17. Deciphering the transcriptional circuitry of microRNA genes expressed during human monocytic differentiation

    KAUST Repository

    Schmeier, Sebastian


    Background: Macrophages are immune cells involved in various biological processes including host defence, homeostasis, differentiation, and organogenesis. Disruption of macrophage biology has been linked to increased pathogen infection, inflammation and malignant diseases. Differential gene expression observed in monocytic differentiation is primarily regulated by interacting transcription factors (TFs). Current research suggests that microRNAs (miRNAs) degrade and repress translation of mRNA, but also may target genes involved in differentiation. We focus on getting insights into the transcriptional circuitry regulating miRNA genes expressed during monocytic differentiation. Results: We computationally analysed the transcriptional circuitry of miRNA genes during monocytic differentiation using in vitro time-course expression data for TFs and miRNAs. A set of TF?miRNA associations was derived from predicted TF binding sites in promoter regions of miRNA genes. Time-lagged expression correlation analysis was utilised to evaluate the TF?miRNA associations. Our analysis identified 12 TFs that potentially play a central role in regulating miRNAs throughout the differentiation process. Six of these 12 TFs (ATF2, E2F3, HOXA4, NFE2L1, SP3, and YY1) have not previously been described to be important for monocytic differentiation. The remaining six TFs are CEBPB, CREB1, ELK1, NFE2L2, RUNX1, and USF2. For several miRNAs (miR-21, miR-155, miR-424, and miR-17-92), we show how their inferred transcriptional regulation impacts monocytic differentiation. Conclusions: The study demonstrates that miRNAs and their transcriptional regulatory control are integral molecular mechanisms during differentiation. Furthermore, it is the first study to decipher on a large-scale, how miRNAs are controlled by TFs during human monocytic differentiation. Subsequently, we have identified 12 candidate key controllers of miRNAs during this differentiation process. 2009 Schmeier et al; licensee Bio

  18. Top-down gain control of the auditory space map by gaze control circuitry in the barn owl. (United States)

    Winkowski, Daniel E; Knudsen, Eric I


    High-level circuits in the brain that control the direction of gaze are intimately linked with the control of visual spatial attention. Immediately before an animal directs its gaze towards a stimulus, both psychophysical sensitivity to that visual stimulus and the responsiveness of high-order neurons in the cerebral cortex that represent the stimulus increase dramatically. Equivalent effects on behavioural sensitivity and neuronal responsiveness to visual stimuli result from focal electrical microstimulation of gaze control centres in monkeys. Whether the gaze control system modulates neuronal responsiveness in sensory modalities other than vision is unknown. Here we show that electrical microstimulation applied to gaze control circuitry in the forebrain of barn owls regulates the gain of midbrain auditory responses in an attention-like manner. When the forebrain circuit was activated, midbrain responses to auditory stimuli at the location encoded by the forebrain site were enhanced and spatial selectivity was sharpened. The same stimulation suppressed responses to auditory stimuli represented at other locations in the midbrain map. Such space-specific, top-down regulation of auditory responses by gaze control circuitry in the barn owl suggests that the central nervous system uses a common strategy for dynamically regulating sensory gain that applies across modalities, brain areas and classes of vertebrate species. This approach provides a path for discovering mechanisms that underlie top-down gain control in the central nervous system.

  19. 76 FR 79215 - Certain Semiconductor Chips With Dram Circuitry, and Modules and Products Containing Same... (United States)


    ... COMMISSION Certain Semiconductor Chips With Dram Circuitry, and Modules and Products Containing Same... importation of certain semiconductor chips with DRAM circuitry, and modules and products containing same by... containing same that infringe one or more of claims 1-6, 8-11, and 15- 18 of the `689 patent; claims 1-16 and...

  20. Stitching Codeable Circuits: High School Students' Learning about Circuitry and Coding with Electronic Textiles (United States)

    Litts, Breanne K.; Kafai, Yasmin B.; Lui, Debora A.; Walker, Justice T.; Widman, Sari A.


    Learning about circuitry by connecting a battery, light bulb, and wires is a common activity in many science classrooms. In this paper, we expand students' learning about circuitry with electronic textiles, which use conductive thread instead of wires and sewable LEDs instead of lightbulbs, by integrating programming sensor inputs and light…

  1. Mapping the Brain’s Metaphor Circuitry:Is Abstract Thought Metaphorical Thought?

    Directory of Open Access Journals (Sweden)

    George eLakoff


    Full Text Available An overview of the basics of metaphorical thought and language from the perspective of Neurocognition, the integrated interdisciplinary study of how conceptual thought and language work in the brain. The paper outlines a theory of metaphor circuitry and discusses how everyday reason makes use of embodied metaphor circuitry.

  2. Intrinsic brainstem schwannoma – A rare clinical entity and a histological enigma

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    Anil Kumar Sharma


    Full Text Available Intraparenchymal schwannomas arising in the brainstem are very rare, and only eight cases have been reported in literature till now. We report an intraparenchymal brainstem schwannoma presenting with the classical clinical presentation of an intrinsic brainstem lesion, and discuss its clinicoradiological characteristics and histological origins. We highlight the importance of an intraoperative frozen section diagnosis in such cases. Intraoperative tissue diagnosis significantly may alter the surgical strategy, which should be aimed at near total intracapsular decompression of the schwannoma.

  3. Enhanced brainstem encoding predicts musicians' perceptual advantages with pitch. (United States)

    Bidelman, Gavin M; Krishnan, Ananthanarayan; Gandour, Jackson T


    Important to Western tonal music is the relationship between pitches both within and between musical chords; melody and harmony are generated by combining pitches selected from the fixed hierarchical scales of music. It is of critical importance that musicians have the ability to detect and discriminate minute deviations in pitch in order to remain in tune with other members of their ensemble. Event-related potentials indicate that cortical mechanisms responsible for detecting mistuning and violations in pitch are more sensitive and accurate in musicians as compared with non-musicians. The aim of the present study was to address whether this superiority is also present at a subcortical stage of pitch processing. Brainstem frequency-following responses were recorded from musicians and non-musicians in response to tuned (i.e. major and minor) and detuned (± 4% difference in frequency) chordal arpeggios differing only in the pitch of their third. Results showed that musicians had faster neural synchronization and stronger brainstem encoding for defining characteristics of musical sequences regardless of whether they were in or out of tune. In contrast, non-musicians had relatively strong representation for major/minor chords but showed diminished responses for detuned chords. The close correspondence between the magnitude of brainstem responses and performance on two behavioral pitch discrimination tasks supports the idea that musicians' enhanced detection of chordal mistuning may be rooted at pre-attentive, sensory stages of processing. Findings suggest that perceptually salient aspects of musical pitch are not only represented at subcortical levels but that these representations are also enhanced by musical experience. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  4. SPARCL1-containing neurons in the human brainstem and sensory ganglion. (United States)

    Hashimoto, Naoya; Sato, Tadasu; Yajima, Takehiro; Fujita, Masatoshi; Sato, Ayumi; Shimizu, Yoshinaka; Shimada, Yusuke; Shoji, Noriaki; Sasano, Takashi; Ichikawa, Hiroyuki


    Secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) is a member of the osteonectin family of proteins. In this study, immunohistochemistry for SPARCL1 was performed to obtain its distribution in the human brainstem, cervical spinal cord, and sensory ganglion. SPARCL1-immunoreactivity was detected in neuronal cell bodies including perikarya and proximal dendrites, and the neuropil. The motor nuclei of the IIIrd, Vth, VIth, VIIth, IXth, Xth, XIth, and XIIth cranial nerves and spinal nerves contained many SPARCL1-immunoreactive (-IR) neurons with medium-sized to large cell bodies. Small and medium-sized SPARCL1-IR neurons were distributed in sensory nuclei of the Vth, VIIth, VIIIth, IXth, and Xth cranial nerves. In the medulla oblongata, the dorsal column nuclei also had small to medium-sized SPARCL1-IR neurons. In addition, SPARCL1-IR neurons were detected in the nucleus of the trapezoid body and pontine nucleus within the pons and the arcuate nucleus in the medulla oblongata. In the cervical spinal cord, the ventral horn contained some SPARCL1-IR neurons with large cell bodies. These findings suggest that SPARCL1-containing neurons function to relay and regulate motor and sensory signals in the human brainstem. In the dorsal root (DRG) and trigeminal ganglia (TG), primary sensory neurons contained SPARCL1-immunoreactivity. The proportion of SPARCL1-IR neurons in the TG (mean ± SD, 39.9 ± 2.4%) was higher than in the DRG (30.6 ± 2.1%). SPARCL1-IR neurons were mostly medium-sized to large (mean ± SD, 1494.5 ± 708.3 μm(2); range, 320.4-4353.4 μm(2)) in the DRG, whereas such neurons were of various cell body sizes in the TG (mean ± SD, 1291.2 ± 532.8 μm(2); range, 209.3-4326.4 μm(2)). There appears to be a SPARCL1-containing sensory pathway in the ganglion and brainstem of the spinal and trigeminal nervous systems.

  5. The development of descending projections from the brainstem to the spinal cord in the fetal sheep

    Directory of Open Access Journals (Sweden)

    Cooke Ian RC


    Full Text Available Abstract Background Although the fetal sheep is a favoured model for studying the ontogeny of physiological control systems, there are no descriptions of the timing of arrival of the projections of supraspinal origin that regulate somatic and visceral function. In the early development of birds and mammals, spontaneous motor activity is generated within spinal circuits, but as development proceeds, a distinct change occurs in spontaneous motor patterns that is dependent on the presence of intact, descending inputs to the spinal cord. In the fetal sheep, this change occurs at approximately 65 days gestation (G65, so we therefore hypothesised that spinally-projecting axons from the neurons responsible for transforming fetal behaviour must arrive at the spinal cord level shortly before G65. Accordingly we aimed to identify the brainstem neurons that send projections to the spinal cord in the mature sheep fetus at G140 (term = G147 with retrograde tracing, and thus to establish whether any projections from the brainstem were absent from the spinal cord at G55, an age prior to the marked change in fetal motor activity has occurred. Results At G140, CTB labelled cells were found within and around nuclei in the reticular formation of the medulla and pons, within the vestibular nucleus, raphe complex, red nucleus, and the nucleus of the solitary tract. This pattern of labelling is similar to that previously reported in other species. The distribution of CTB labelled neurons in the G55 fetus was similar to that of the G140 fetus. Conclusion The brainstem nuclei that contain neurons which project axons to the spinal cord in the fetal sheep are the same as in other mammalian species. All projections present in the mature fetus at G140 have already arrived at the spinal cord by approximately one third of the way through gestation. The demonstration that the neurons responsible for transforming fetal behaviour in early ontogeny have already reached the

  6. Adaptive hypofractionated gamma knife radiosurgery for a large brainstem metastasis

    DEFF Research Database (Denmark)

    Sinclair, Georges; Bartek, Jiri; Martin, Heather


    BACKGROUND: To demonstrate how adaptive hypofractionated radiosurgery by gamma knife (GK) can be successfully utilized to treat a large brainstem metastasis - a novel approach to a challenging clinical situation. CASE DESCRIPTION: A 42-year-old woman, diagnosed with metastatic nonsmall cell lung...... months and 18-fluoro-deoxyglucose positron emission tomography of the brain at 13 months showed decreased edema with no signs of tumor recurrence. Despite disease progression during the last months of her life, the patient's condition remained overall acceptable. CONCLUSION: GK-based stereotactic...

  7. Stereotactic LINAC radiosurgery for the treatment of brainstem cavernomas

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    Fuetsch, M.; El Majdoub, F.; Hoevels, M.; Sturm, V.; Maarouf, M. [Koeln Univ. (Germany). Dept. of Stereotaxy and Functional Neurosurgery; Mueller, R.P. [Koeln Univ. (Germany). Dept. of Radiation Oncology


    Background: The management of deep-seated cerebral cavernous malformations (CCMs) is still controversial. Although surgery remains the treatment of choice in patients with recurrent hemorrhage, patients with CCMs located in the brainstem are in many cases not eligible for resection due to high procedure-related morbidity and mortality. We evaluated the long-term outcome of LINAC radiosurgery (LINAC-RS) for the treatment of brainstem CCMs. Patients and methods: Between December 1992 and March 2008, 14 patients (6 men, 8 women) harboring brainstem CCMs underwent LINAC-RS. Pretreatment neuroimaging showed no associated developmental venous angiomas (DVAs) in any of our patients. Prior to treatment, all patients suffered at least from one symptomatic hemorrhage (median 1.8, range 1-3). A median follow-up of 7.1 years (range 2.0-16.8 years) could be obtained in 12 patients. We applied a median tumor surface dose of 13.9 Gy (range 11-18 Gy; median tumor volume 1.6 ml, range 0.4-4.3 ml). Results: Following LINAC-RS, neurological outcome improved in 4 (33.3%) and remained unchanged in 8 patients (66.7%). Rebleeding with subsequent transient neurological status deterioration occurred in 4 patients (33.3%), leading to additional surgical resection in 2 patients (16.7%). The corresponding annual hemorrhage rate was 4.8% (4/82.8 patient-years). Adverse radiation effects (ARE, defined by perilesional hyperintensity on T{sub 2}-weighted MR images) were revealed in 3 patients (25%), leading to transient neurological deficits in 2 patients (16.7%). There were no procedure-related complications leading to either permanent morbidity or mortality. Conclusion: Our results support the role of LINAC-RS as an efficient and safe treatment to significantly reduce the annual hemorrhage rate in patients suffering from brainstem CCMs not eligible to microsurgery. Compared with radiosurgery for arteriovenous malformations (AVMs), the intervention-related morbidity is higher. (orig.)

  8. Herpes simplex encephalitis with thalamic, brainstem and cerebellar involvement. (United States)

    Garg, Meenal; Kulkarni, Shilpa; Udwadia Hegde, Anaita


    Herpes simplex virus encephalitis is a common and treatable cause of acute encephalitis in all age groups. Certain radiological features such as temporal parenchymal involvement facilitate the diagnosis. The use of herpes simplex virus polymerase chain reaction has expanded the clinical and imaging spectrum. We report the case of a young patient who presented with a movement disorder and predominant involvement of thalami, brainstem and cerebellum on magnetic resonance imaging, and was diagnosed with herpes simplex virus encephalitis. Differentiation from Japanese encephalitis may be difficult in these patients, especially in endemic areas, and may necessitate the use of relevant investigations in all patients.

  9. Isolated Brainstem Involvement in a Patient with Hypertensive Encephalopathy

    Directory of Open Access Journals (Sweden)

    Y. Osman


    Full Text Available Hypertensive encephalopathy typically presents with headache, confusion, and bilateral parietooccipital vasogenic edema. Brainstem edema in hypertensive encephalopathy usually occurs in association with typical supratentorial parieto-occipital changes and is usually asymptomatic. We report here a patient with hypertensive encephalopathy, with isolated brain stem involvement on magnetic resonance imaging (MRI. Rapid treatment of hypertension resulted in clinical and radiological improvement. Prompt recognition of the condition and aggressive treatment of hypertension in such patients is crucial to relieve edema and prevent life-threatening progression.

  10. Pinpointing brainstem mechanisms responsible for autonomic dysfunction in Rett syndrome: therapeutic perspectives for 5-HT1A agonists (United States)

    Abdala, Ana P.; Bissonnette, John M.; Newman-Tancredi, Adrian


    Rett syndrome is a neurological disorder caused by loss of function of methyl-CpG-binding protein 2 (MeCP2). Reduced function of this ubiquitous transcriptional regulator has a devastating effect on the central nervous system. One of the most severe and life-threatening presentations of this syndrome is brainstem dysfunction, which results in autonomic disturbances such as breathing deficits, typified by episodes of breathing cessation intercalated with episodes of hyperventilation or irregular breathing. Defects in numerous neurotransmitter systems have been observed in Rett syndrome both in animal models and patients. Here we dedicate special attention to serotonin due to its role in promoting regular breathing, increasing vagal tone, regulating mood, alleviating Parkinsonian-like symptoms and potential for therapeutic translation. A promising new symptomatic strategy currently focuses on regulation of serotonergic function using highly selective serotonin type 1A (5-HT1A) “biased agonists.” We address this newly emerging therapy for respiratory brainstem dysfunction and challenges for translation with a holistic perspective of Rett syndrome, considering potential mood and motor effects. PMID:24910619

  11. NeuronBank: A Tool for Cataloging Neuronal Circuitry (United States)

    Katz, Paul S.; Calin-Jageman, Robert; Dhawan, Akshaye; Frederick, Chad; Guo, Shuman; Dissanayaka, Rasanjalee; Hiremath, Naveen; Ma, Wenjun; Shen, Xiuyn; Wang, Hsui C.; Yang, Hong; Prasad, Sushil; Sunderraman, Rajshekhar; Zhu, Ying


    The basic unit of any nervous system is the neuron. Therefore, understanding the operation of nervous systems ultimately requires an inventory of their constituent neurons and synaptic connectivity, which form neural circuits. The presence of uniquely identifiable neurons or classes of neurons in many invertebrates has facilitated the construction of cellular-level connectivity diagrams that can be generalized across individuals within a species. Homologous neurons can also be recognized across species. Here we describe, a web-based tool that we are developing for cataloging, searching, and analyzing neuronal circuitry within and across species. Information from a single species is represented in an individual branch of NeuronBank. Users can search within a branch or perform queries across branches to look for similarities in neuronal circuits across species. The branches allow for an extensible ontology so that additional characteristics can be added as knowledge grows. Each entry in NeuronBank generates a unique accession ID, allowing it to be easily cited. There is also an automatic link to a Wiki page allowing an encyclopedic explanation of the entry. All of the 44 previously published neurons plus one previously unpublished neuron from the mollusc, Tritonia diomedea, have been entered into a branch of NeuronBank as have 4 previously published neurons from the mollusc, Melibe leonina. The ability to organize information about neuronal circuits will make this information more accessible, ultimately aiding research on these important models. PMID:20428500

  12. Neural circuitry underlying affective response to peer feedback in adolescence. (United States)

    Guyer, Amanda E; Choate, Victoria R; Pine, Daniel S; Nelson, Eric E


    Peer feedback affects adolescents' behaviors, cognitions and emotions. We examined neural circuitry underlying adolescents' emotional response to peer feedback using a functional neuroimaging paradigm whereby, 36 adolescents (aged 9-17 years) believed they would interact with unknown peers postscan. Neural activity was expected to vary based on adolescents' perceptions of peers and feedback type. Ventrolateral prefrontal cortex (vlPFC) activity was found when adolescents indicated how they felt following feedback (acceptance or rejection) from peers of low vs high interest. Greater activation in both cortical (e.g. superior temporal gyrus, insula, anterior cingulate) and subcortical (e.g. striatum, thalamus) regions emerged in response to acceptance vs rejection feedback. Response to acceptance also varied by age and gender in similar regions (e.g. superior temporal gyrus, fusiform, insula), with greater age-related increases in activation to acceptance vs rejection for females than males. Affective response to rejection vs acceptance did not yield significantly greater neural activity in any region. vlPFC response suggests cognitive flexibility in reappraising initial perceptions of peers following feedback. Striatal response suggests that acceptance is a potent social reward for adolescents, an interpretation supported by more positive self-reported affective response to acceptance than rejection from high- but not low-interest peers.

  13. Autonomic correlations with MRI are abnormal in the brainstem vasomotor centre in Chronic Fatigue Syndrome. (United States)

    Barnden, Leighton R; Kwiatek, Richard; Crouch, Benjamin; Burnet, Richard; Del Fante, Peter


    Autonomic changes are often associated with the chronic fatigue syndrome (CFS), but their pathogenetic role is unclear and brain imaging investigations are lacking. The vasomotor centre and, through it, nuclei in the midbrain and hypothalamus play a key role in autonomic nervous system regulation of steady state blood pressure (BP) and heart rate (HR). In this exploratory cross-sectional study, BP and HR, as indicators of autonomic function, were correlated with volumetric and T1- and T2-weighted spin-echo (T1w and T2w) brain MRI in 25 CFS subjects and 25 normal controls (NC). Steady state BP (systolic, diastolic and pulse pressure) and HR in two postures were extracted from 24 h blood pressure monitoring. We performed (1) MRI versus autonomic score interaction-with-group regressions to detect locations where regression slopes differed in the CFS and NC groups (collectively indicating abnormality in CFS), and (2) MRI regressions in the CFS and NC groups alone to detect additional locations with abnormal correlations in CFS. Significant CFS regressions were repeated controlling for anxiety and depression (A&D). Abnormal regressions were detected in nuclei of the brainstem vasomotor centre, midbrain reticular formation and hypothalamus, but also in limbic nuclei involved in stress responses and in prefrontal white matter. Group comparisons of CFS and NC did not find MRI differences in these locations. We propose therefore that these regulatory nuclei are functioning correctly, but that two-way communication between them is impaired in CFS and this affects signalling to/from peripheral effectors/sensors, culminating in inverted or magnified correlations. This single explanation for the diverse abnormal correlations detected here consolidates the conclusion for a brainstem/midbrain nerve conduction deficit inferred earlier (Barnden et al., 2015). Strong correlations were also detected in isolated NC regressions.

  14. Autonomic correlations with MRI are abnormal in the brainstem vasomotor centre in Chronic Fatigue Syndrome

    Directory of Open Access Journals (Sweden)

    Leighton R. Barnden


    Full Text Available Autonomic changes are often associated with the chronic fatigue syndrome (CFS, but their pathogenetic role is unclear and brain imaging investigations are lacking. The vasomotor centre and, through it, nuclei in the midbrain and hypothalamus play a key role in autonomic nervous system regulation of steady state blood pressure (BP and heart rate (HR. In this exploratory cross-sectional study, BP and HR, as indicators of autonomic function, were correlated with volumetric and T1- and T2-weighted spin-echo (T1w and T2w brain MRI in 25 CFS subjects and 25 normal controls (NC. Steady state BP (systolic, diastolic and pulse pressure and HR in two postures were extracted from 24 h blood pressure monitoring. We performed (1 MRI versus autonomic score interaction-with-group regressions to detect locations where regression slopes differed in the CFS and NC groups (collectively indicating abnormality in CFS, and (2 MRI regressions in the CFS and NC groups alone to detect additional locations with abnormal correlations in CFS. Significant CFS regressions were repeated controlling for anxiety and depression (A&D. Abnormal regressions were detected in nuclei of the brainstem vasomotor centre, midbrain reticular formation and hypothalamus, but also in limbic nuclei involved in stress responses and in prefrontal white matter. Group comparisons of CFS and NC did not find MRI differences in these locations. We propose therefore that these regulatory nuclei are functioning correctly, but that two-way communication between them is impaired in CFS and this affects signalling to/from peripheral effectors/sensors, culminating in inverted or magnified correlations. This single explanation for the diverse abnormal correlations detected here consolidates the conclusion for a brainstem/midbrain nerve conduction deficit inferred earlier (Barnden et al., 2015. Strong correlations were also detected in isolated NC regressions.

  15. Layer 3 Excitatory and Inhibitory Circuitry in the Prefrontal Cortex: Developmental Trajectories and Alterations in Schizophrenia. (United States)

    Hoftman, Gil D; Datta, Dibyadeep; Lewis, David A


    Convergent evidence suggests that schizophrenia is a disorder of neurodevelopment with alterations in both early and late developmental processes hypothesized to contribute to the disease process. Abnormalities in certain clinical features of schizophrenia, such as working memory impairments, depend on distributed neural circuitry including the dorsolateral prefrontal cortex (DLPFC) and appear to arise during the protracted maturation of this circuitry across childhood and adolescence. In particular, the neural circuitry substrate for working memory in primates involves the coordinated activity of excitatory pyramidal neurons and a specific population of inhibitory gamma-aminobutyric acid neurons (i.e., parvalbumin-containing basket cells) in layer 3 of the DLPFC. Understanding the relationships between the normal development of-and the schizophrenia-associated alterations in-the DLPFC circuitry that subserves working memory could provide new insights into the nature of schizophrenia as a neurodevelopmental disorder. Consequently, we review the following in this article: 1) recent findings regarding alterations of DLPFC layer 3 circuitry in schizophrenia, 2) the developmental refinements in this circuitry that occur during the period when the working memory alterations in schizophrenia appear to arise and progress, and 3) how various adverse environmental exposures could contribute to developmental disturbances of this circuitry in individuals with schizophrenia. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  16. Comparative transcriptomics of the model mushroom Coprinopsis cinerea reveals tissue-specific armories and a conserved circuitry for sexual development. (United States)

    Plaza, David Fernando; Lin, Chia-Wei; van der Velden, Niels Sebastiaan Johannes; Aebi, Markus; Künzler, Markus


    It is well known that mushrooms produce defense proteins and secondary metabolites against predators and competitors; however, less is known about the correlation between the tissue-specific expression and the target organism (antagonist) specificity of these molecules. In addition, conserved transcriptional circuitries involved in developing sexual organs in fungi are not characterized, despite the growing number of gene expression datasets available from reproductive and vegetative tissue. The aims of this study were: first, to evaluate the tissue specificity of defense gene expression in the model mushroom Coprinopsis cinerea and, second, to assess the degree of conservation in transcriptional regulation during sexual development in basidiomycetes. In order to characterize the regulation in the expression of defense loci and the transcriptional circuitries controlling sexual reproduction in basidiomycetes, we sequenced the poly (A)-positive transcriptome of stage 1 primordia and vegetative mycelium of C. cinerea A43mutB43mut. Our data show that many genes encoding predicted and already characterized defense proteins are differentially expressed in these tissues. The predicted specificity of these proteins with regard to target organisms suggests that their expression pattern correlates with the type of antagonists these tissues are confronted with. Accordingly, we show that the stage 1 primordium-specific protein CC1G_11805 is toxic to insects and nematodes. Comparison of our data to analogous data from Laccaria bicolor and Schizophyllum commune revealed that the transcriptional regulation of nearly 70 loci is conserved and probably subjected to stabilizing selection. A Velvet domain-containing protein was found to be up-regulated in all three fungi, providing preliminary evidence of a possible role of the Velvet protein family in sexual development of basidiomycetes. The PBS-soluble proteome of C. cinerea primordia and mycelium was analyzed by shotgun LC

  17. Activation of Brainstem Neurons by Underwater Diving in the Rat (United States)

    Panneton, W. Michael; Gan, Qi; Le, Jason; Livergood, Robert S.; Clerc, Philip; Juric, Rajko


    The mammalian diving response is a powerful autonomic adjustment to underwater submersion greatly affecting heart rate, arterial blood pressure, and ventilation. The bradycardia is mediated by the parasympathetic nervous system, arterial blood pressure is mediated via the sympathetic system and still other circuits mediate the respiratory changes. In the present study we investigate the cardiorespiratory responses and the brainstem neurons activated by voluntary diving of trained rats, and, compare them to control and swimming animals which did not dive. We show that the bradycardia and increase in arterial blood pressure induced by diving were significantly different than that induced by swimming. Neuronal activation was calculated after immunohistochemical processing of brainstem sections for Fos protein. Labeled neurons were counted in the caudal pressor area, the medullary dorsal horn, subnuclei of the nucleus tractus solitarii (NTS), the nucleus raphe pallidus (RPa), the rostroventrolateral medulla, the A5 area, the nucleus locus coeruleus, the Kölliker–Fuse area, and the external lateral and superior lateral subnuclei of the parabrachial nucleus. All these areas showed significant increases in Fos labeling when data from voluntary diving rats were compared to control rats and all but the commissural subnucleus of the NTS, A5 area, and RPa were significantly different from swimming rats. These data provide a substrate for more precise experiments to determine the role of these nuclei in the reflex circuits driving the diving response. PMID:22563319

  18. Dopamine and the Brainstem Locomotor Networks: From Lamprey to Human

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    Dimitri Ryczko


    Full Text Available In vertebrates, dopamine neurons are classically known to modulate locomotion via their ascending projections to the basal ganglia that project to brainstem locomotor networks. An increased dopaminergic tone is associated with increase in locomotor activity. In pathological conditions where dopamine cells are lost, such as in Parkinson's disease, locomotor deficits are traditionally associated with the reduced ascending dopaminergic input to the basal ganglia. However, a descending dopaminergic pathway originating from the substantia nigra pars compacta was recently discovered. It innervates the mesencephalic locomotor region (MLR from basal vertebrates to mammals. This pathway was shown to increase locomotor output in lampreys, and could very well play an important role in mammals. Here, we provide a detailed account on the newly found dopaminergic pathway in lamprey, salamander, rat, monkey, and human. In lampreys and salamanders, dopamine release in the MLR is associated with the activation of reticulospinal neurons that carry the locomotor command to the spinal cord. Dopamine release in the MLR potentiates locomotor movements through a D1-receptor mechanism in lampreys. In rats, stimulation of the substantia nigra pars compacta elicited dopamine release in the pedunculopontine nucleus, a known part of the MLR. In a monkey model of Parkinson's disease, a reduced dopaminergic innervation of the brainstem locomotor networks was reported. Dopaminergic fibers are also present in human pedunculopontine nucleus. We discuss the conserved locomotor role of this pathway from lamprey to mammals, and the hypothesis that this pathway could play a role in the locomotor deficits reported in Parkinson's disease.

  19. Recurrent Diplopia in a Pediatric Patient with Bickerstaff Brainstem Encephalitis

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    Scott A. McLeod


    Full Text Available Introduction. Acute complete external ophthalmoplegia is a rare finding in clinical practice that is associated with diseases affecting the neuromuscular junction, the oculomotor nerves, or the brainstem. Ophthalmoplegia has been reported with acute ataxia in Miller Fisher syndrome (MFS and Bickerstaff brainstem encephalitis (BBE. Up to 95% of these cases are associated with anti-GQ1b antibodies. Only a small number of cases of anti-GQ1b negative MFS have been documented in pediatric patients. This is the first case reporting a recurrence of ocular symptoms in an anti-GQ1b antibody negative patient with BBE. Case Presentation. An 8-year-old Caucasian boy presented with complete external ophthalmoplegia without ptosis, cerebellar ataxia, and a disturbance of consciousness. He had recently recovered from a confirmed Campylobacter jejuni infection. On subsequent laboratory testing he was anti-GQ1b antibody negative. He had a recurrence of diplopia at four-week follow-up. Conclusions. This patient’s recurrence of diplopia was treated with a five-week course of oral corticosteroids which did not worsen his condition, and this may be a therapeutic option for similar patients. We will discuss the symptoms and treatment of reported pediatric cases of anti-GQ1b antibody negative cases of MFS and the variation between cases representing a spectrum of illness.

  20. Auditory Brainstem Responses in Children Treated with Cisplatin

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    Mohammad Kamali


    Full Text Available Background and Aim: In view of improvement in therapeutic outcome of cancer treatment in children resulting in increased survival rates and the importance of hearing in speech and language development, this research project was intended to assess the effects of cisplatin group on hearing ability in children aged 6 months to 12 years.Methods: In this cross-sectional study, hearing of 10 children on cisplatin group medication for cancer who met the inclusion criteria was examined by recording auditory brainstem responses (ABR using the three stimulants of click and 4 and 8 kHz tone bursts. All children were examined twice: before drug administration and within 72 hours after receiving the last dose. Then the results were compared with each other.Results: There was a significant difference between hearing thresholds before and after drug administration (p<0.05. Right and left ear threshold comparison revealed no significant difference.Conclusion: Ototoxic effects of cisplatin group were confirmed in this study. Insignificant difference observed in comparing right and left ear hearing thresholds could be due to small sample size. auditory brainstem responses test especially with frequency specificity proved to be a useful method in assessing cisplatin ototoxicity.

  1. The auditory brainstem response of aged guinea pigs. (United States)

    Ingham, N J; Thornton, S K; Comis, S D; Withington, D J


    The auditory brainstem response (ABR) technique was used to investigate potential dysfunctions in the auditory brainstem of the pigmented guinea pig (Cavia porcellus) associated with biological ageing. Animals aged from 58 days to 4 years 3 months were tested. ABRs were recorded at stimulation intensities from 85 dB HL to -10 dB HL. The auditory thresholds were found to undergo marked elevations in old animals, by an average of 32 dB. From the traces obtained, four positive deflection waves were reliably recorded. The latency of each of the four waves was evaluated at different stimulation intensities in guinea pigs of different ages. Although there was a trend for the latencies to increase in old age, these differences were not statistically significant. Similarly, there were no significant age-related changes in the inter-peak intervals. The latency/intensity functions of the four waves produced parallel curves. However, the curve from the old age group was shifted to the right, by an average of 35 dB, indicative of conductive hearing loss. There was no evidence of retro-cochlear hearing loss. Therefore, it appears that the threshold elevations in the old animals can be accounted for by conductive hearing loss, presumably in the middle ear. In 24% of the old animals tested, no ABR could be elicited. It would appear that these animals had suffered severe sensorineural hearing loss.

  2. A case of Bickerstaff's brainstem encephalitis in childhood

    Directory of Open Access Journals (Sweden)

    Ji Youn Kim


    Full Text Available Bickerstaff's brainstem encephalitis (BBE is a rare disease diagnosed by specific clinical features such as 'progressive, relatively symmetric external ophthalmoplegia and ataxia by 4 weeks' and 'disturbance of consciousness or hyperreflexia' after the exclusion of other diseases involving the brain stem. Anti-ganglioside antibodies (GM, GD and GQ in the serum or cerebrospinal fluid (CSF are sometimes informative for the diagnosis of BBE because of the rarity of positive findings in other diagnositic methods: brain magnetic resonance imaging (MRI, routine CSF examination, motor nerve conduction study, and needle electromyography. We report a rare case of childhood BBE with elevated anti-GM1 antibodies in the serum, who had specific clinical symptoms such as a cranial polyneuropathy presenting as ophthalmoplegia, dysarthria, dysphagia, and facial weakness; progressive motor weakness; altered mental status; and ataxia. However, the brain MRI, routine CSF examination, nerve conduction studies, electromyography, somatosensory evoked potentials, and brainstem auditory evoked potentials were normal. BBE was suspected and the patient was successfully treated with intravenous immunoglobulins.

  3. Development of Brainstem-Evoked Responses in Congenital Auditory Deprivation

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    J. Tillein


    Full Text Available To compare the development of the auditory system in hearing and completely acoustically deprived animals, naive congenitally deaf white cats (CDCs and hearing controls (HCs were investigated at different developmental stages from birth till adulthood. The CDCs had no hearing experience before the acute experiment. In both groups of animals, responses to cochlear implant stimulation were acutely assessed. Electrically evoked auditory brainstem responses (E-ABRs were recorded with monopolar stimulation at different current levels. CDCs demonstrated extensive development of E-ABRs, from first signs of responses at postnatal (p.n. day 3 through appearance of all waves of brainstem response at day 8 p.n. to mature responses around day 90 p.n.. Wave I of E-ABRs could not be distinguished from the artifact in majority of CDCs, whereas in HCs, it was clearly separated from the stimulus artifact. Waves II, III, and IV demonstrated higher thresholds in CDCs, whereas this difference was not found for wave V. Amplitudes of wave III were significantly higher in HCs, whereas wave V amplitudes were significantly higher in CDCs. No differences in latencies were observed between the animal groups. These data demonstrate significant postnatal subcortical development in absence of hearing, and also divergent effects of deafness on early waves II–IV and wave V of the E-ABR.

  4. The impact of maternal smoking on fast auditory brainstem responses. (United States)

    Kable, Julie A; Coles, Claire D; Lynch, Mary Ellen; Carroll, Julie


    Deficits in auditory processing have been posited as one of the underlying neurodevelopmental consequences of maternal smoking during pregnancy that leads to later language and reading deficits. Fast auditory brainstem responses were used to assess differences in the sensory processing of auditory stimuli among infants with varying degrees of prenatal cigarette exposure. Maternal report of consumption of cigarettes and blood samples were collected in the hospital to assess exposure levels and participants were then seen at 6-months. To participate in the study, all infants had to pass the newborn hearing exam or a clinically administered ABR and have no known health problems. After controlling for participant age, maternal smoking during pregnancy was negatively related to latency of auditory brainstem responses. Of several potential covariates, only perinatal complications and maternal alcohol use were also related to latency of the ABR responses and maternal smoking level accounted for significant unique variance after controlling for these factors. These results suggest that the relationship between maternal smoking may lead to disruption in the sensory encoding of auditory stimuli.

  5. Intraoperative Monitoring and Mapping of the Functional Integrity of the Brainstem (United States)

    Fernández-Conejero, Isabel


    The risk of iatrogenic damage is very high in surgical interventions in or around the brainstem. However, surgical techniques and intraoperative neuromonitoring (ION) have evolved sufficiently to increase the likelihood of successful functional outcomes in many patients. We present a critical review of the methodologies available for intraoperative monitoring and mapping of the brainstem. There are three main groups of techniques that can be used to assess the functional integrity of the brainstem: 1) mapping, which provides rapid anatomical identification of neural structures using electrical stimulation with a hand-held probe, 2) monitoring, which provides real-time information about the functional integrity of the nervous tissue, and 3) techniques involving the examination of brainstem reflexes in the operating room, which allows for the evaluation of the reflex responses that are known to be crucial for most brainstem functions. These include the blink reflex, which is already in use, and other brainstem reflexes that are being explored, such as the masseter H-reflex. This is still under development but is likely to have important functional consequences. Today an abundant armory of ION methods is available for the monitoring and mapping of the functional integrity of the brainstem during surgery. ION methods are essential in surgery either in or around the brainstem; they facilitate the removal of lesions and contribute to notable improvements in the functional outcomes of patients. PMID:27449909

  6. Delayed auditory brainstem responses in prelingually deaf and late-implanted cochlear implant users

    NARCIS (Netherlands)

    Lammers, Marc; van Eijl, Ruben; van Zanten, Gijsbert; Versnel, Huib; Grolman, Wilko


    Neurophysiological studies in animals and humans suggest that severe hearing loss during early development impairs the maturation of the auditory brainstem. To date, studies in humans have mainly focused on the neural activation of the auditory brainstem in children treated with a cochlear implant

  7. Auditory brainstem maturation in normal-hearing infants born preterm : a meta-analysis

    NARCIS (Netherlands)

    Stipdonk, Lottie W; Weisglas-Kuperus, Nynke; Franken, Marie-Christine Jp; Nasserinejad, Kazem; Dudink, Jeroen; Goedegebure, André


    AIM: Children born preterm often have neurodevelopmental problems later in life. Abnormal maturation of the auditory brainstem in the presence of normal hearing might be a marker for these problems. We conducted a meta-analysis of auditory brainstem response (ABR) latencies at term age to describe

  8. The Neural Circuitry of Expertise: Perceptual Learning and Social Cognition

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    Michael eHarre


    Full Text Available Amongst the most significant questions we are confronted with today include the integration of the brain's micro-circuitry, our ability to build the complex social networks that underpin society and how our society impacts on our ecological environment. In trying to unravel these issues one place to begin is at the level of the individual: to consider how we accumulate information about our environment, how this information leads to decisions and how our individual decisions in turn create our social environment. While this is an enormous task, we may already have at hand many of the tools we need. This article is intended to review some of the recent results in neuro-cognitive research and show how they can be extended to two very specific types of expertise: perceptual expertise and social cognition. These two cognitive skills span a vast range of our genetic heritage. Perceptual expertise developed very early in our evolutionary history and is likely a highly developed part of all mammals' cognitive ability. On the other hand social cognition is most highly developed in humans in that we are able to maintain larger and more stable long term social connections with more behaviourally diverse individuals than any other species. To illustrate these ideas I will discuss board games as a toy model of social interactions as they include many of the relevant concepts: perceptual learning, decision-making, long term planning and understanding the mental states of other people. Using techniques that have been developed in mathematical psychology, I show that we can represent some of the key features of expertise using stochastic differential equations. Such models demonstrate how an expert's long exposure to a particular context influences the information they accumulate in order to make a decision.These processes are not confined to board games, we are all experts in our daily lives through long exposure to the many regularities of daily tasks and

  9. The neural circuitry of expertise: perceptual learning and social cognition. (United States)

    Harré, Michael


    Amongst the most significant questions we are confronted with today include the integration of the brain's micro-circuitry, our ability to build the complex social networks that underpin society and how our society impacts on our ecological environment. In trying to unravel these issues one place to begin is at the level of the individual: to consider how we accumulate information about our environment, how this information leads to decisions and how our individual decisions in turn create our social environment. While this is an enormous task, we may already have at hand many of the tools we need. This article is intended to review some of the recent results in neuro-cognitive research and show how they can be extended to two very specific and interrelated types of expertise: perceptual expertise and social cognition. These two cognitive skills span a vast range of our genetic heritage. Perceptual expertise developed very early in our evolutionary history and is a highly developed part of all mammals' cognitive ability. On the other hand social cognition is most highly developed in humans in that we are able to maintain larger and more stable long term social connections with more behaviorally diverse individuals than any other species. To illustrate these ideas I will discuss board games as a toy model of social interactions as they include many of the relevant concepts: perceptual learning, decision-making, long term planning and understanding the mental states of other people. Using techniques that have been developed in mathematical psychology, I show that we can represent some of the key features of expertise using stochastic differential equations (SDEs). Such models demonstrate how an expert's long exposure to a particular context influences the information they accumulate in order to make a decision.These processes are not confined to board games, we are all experts in our daily lives through long exposure to the many regularities of daily tasks and social

  10. Beautiful friendship: Social sharing of emotions improves subjective feelings and activates the neural reward circuitry. (United States)

    Wagner, Ullrich; Galli, Lisa; Schott, Björn H; Wold, Andrew; van der Schalk, Job; Manstead, Antony S R; Scherer, Klaus; Walter, Henrik


    Humans have a strong tendency to affiliate with other people, especially in emotional situations. Here, we suggest that a critical mechanism underlying this tendency is that socially sharing emotional experiences is in itself perceived as hedonically positive and thereby contributes to the regulation of individual emotions. We investigated the effect of social sharing of emotions on subjective feelings and neural activity by having pairs of friends view emotional (negative and positive) and neutral pictures either alone or with the friend. While the two friends remained physically separated throughout the experiment-with one undergoing functional magnetic resonance imaging and the other performing the task in an adjacent room-they were made aware on a trial-by-trial basis whether they were seeing pictures simultaneously with their friend (shared) or alone (unshared). Ratings of subjective feelings were improved significantly when participants viewed emotional pictures together than alone, an effect that was accompanied by activity increase in ventral striatum and medial orbitofrontal cortex, two important components of the reward circuitry. Because these effects occurred without any communication or interaction between the friends, they point to an important proximate explanation for the basic human motivation to affiliate with others, particularly in emotional situations. © The Author (2014). Published by Oxford University Press.

  11. Nuclear receptor/microRNA circuitry links muscle fiber type to energy metabolism. (United States)

    Gan, Zhenji; Rumsey, John; Hazen, Bethany C; Lai, Ling; Leone, Teresa C; Vega, Rick B; Xie, Hui; Conley, Kevin E; Auwerx, Johan; Smith, Steven R; Olson, Eric N; Kralli, Anastasia; Kelly, Daniel P


    The mechanisms involved in the coordinate regulation of the metabolic and structural programs controlling muscle fitness and endurance are unknown. Recently, the nuclear receptor PPARβ/δ was shown to activate muscle endurance programs in transgenic mice. In contrast, muscle-specific transgenic overexpression of the related nuclear receptor, PPARα, results in reduced capacity for endurance exercise. We took advantage of the divergent actions of PPARβ/δ and PPARα to explore the downstream regulatory circuitry that orchestrates the programs linking muscle fiber type with energy metabolism. Our results indicate that, in addition to the well-established role in transcriptional control of muscle metabolic genes, PPARβ/δ and PPARα participate in programs that exert opposing actions upon the type I fiber program through a distinct muscle microRNA (miRNA) network, dependent on the actions of another nuclear receptor, estrogen-related receptor γ (ERRγ). Gain-of-function and loss-of-function strategies in mice, together with assessment of muscle biopsies from humans, demonstrated that type I muscle fiber proportion is increased via the stimulatory actions of ERRγ on the expression of miR-499 and miR-208b. This nuclear receptor/miRNA regulatory circuit shows promise for the identification of therapeutic targets aimed at maintaining muscle fitness in a variety of chronic disease states, such as obesity, skeletal myopathies, and heart failure.

  12. A RAB5/RAB4 recycling circuitry induces a proteolytic invasive program and promotes tumor dissemination (United States)

    Frittoli, Emanuela; Palamidessi, Andrea; Marighetti, Paola; Confalonieri, Stefano; Bianchi, Fabrizio; Malinverno, Chiara; Mazzarol, Giovanni; Viale, Giuseppe; Martin-Padura, Ines; Garré, Massimilliano; Parazzoli, Dario; Mattei, Valentina; Cortellino, Salvatore; Bertalot, Giovanni


    The mechanisms by which tumor cells metastasize and the role of endocytic proteins in this process are not well understood. We report that overexpression of the GTPase RAB5A, a master regulator of endocytosis, is predictive of aggressive behavior and metastatic ability in human breast cancers. RAB5A is necessary and sufficient to promote local invasion and distant dissemination of various mammary and nonmammary tumor cell lines, and this prometastatic behavior is associated with increased intratumoral cell motility. Specifically, RAB5A is necessary for the formation of invadosomes, membrane protrusions specialized in extracellular matrix (ECM) degradation. RAB5A promotes RAB4- and RABENOSYN-5–dependent endo/exocytic cycles (EECs) of critical cargos (membrane-type 1 matrix metalloprotease [MT1-MMP] and β3 integrin) required for invadosome formation in response to motogenic stimuli. This trafficking circuitry is necessary for spatially localized hepatocyte growth factor (HGF)/MET signaling that drives invasive, proteolysis-dependent chemotaxis in vitro and for conversion of ductal carcinoma in situ to invasive ductal carcinoma in vivo. Thus, RAB5A/RAB4 EECs promote tumor dissemination by controlling a proteolytic, mesenchymal invasive program. PMID:25049275

  13. Corticospinal tract insult alters GABAergic circuitry in the mammalian spinal cord

    Directory of Open Access Journals (Sweden)

    Jeffrey B. Russ


    Full Text Available During perinatal development, corticospinal tract (CST projections into the spinal cord help refine spinal circuitry. Although the normal developmental processes that are controlled by the arrival of corticospinal input are becoming clear, little is known about how perinatal cortical damage impacts specific aspects of spinal circuit development, particularly the inhibitory microcircuitry that regulates spinal reflex circuits. In this study, we sought to determine how ischemic cortical damage impacts the synaptic attributes of a well-characterized population of inhibitory, GABAergic interneurons, called GABApre neurons, which modulates the efficiency of proprioceptive sensory terminals in the sensorimotor reflex circuit. We found that putative GABApre interneurons receive CST input and, using an established mouse model of perinatal stroke, that cortical ischemic injury results in a reduction of CST density within the intermediate region of the spinal cord, where these interneurons reside. Importantly, CST alterations were restricted to the side contralateral to the injury. Within the synaptic terminals of the GABApre interneurons, we observed a dramatic upregulation of the 65-isoform of the GABA synthetic enzyme glutamic acid decarboxylase (GAD65. In accordance with the CST density reduction, GAD65 was elevated on the side of the spinal cord contralateral to cortical injury. This effect was not seen for other GABApre synaptic markers or in animals that received sham surgery. Our data reveal a novel effect of perinatal stroke that involves severe deficits in the architecture of descending spinal pathways, which in turn appear to promote molecular alterations in a specific spinal GABAergic circuit.

  14. Tractography of the brainstem in major depressive disorder using diffusion tensor imaging.

    Directory of Open Access Journals (Sweden)

    Yun Ju C Song

    Full Text Available BACKGROUND: The brainstem is the main region that innervates neurotransmitter release to the Hypothalamic-Pituitary Adrenal (HPA axis and fronto-limbic circuits, two key brain circuits found to be dysfunctional in Major Depressive Disorder (MDD. However, the brainstem's role in MDD has only been evaluated in limited reports. Using Diffusion Tensor Imaging (DTI, we investigated whether major brainstem white matter tracts that relate to these two circuits differ in MDD patients compared to healthy controls. METHODS: MDD patients (n = 95 and age- and gender-matched controls (n = 34 were assessed using probabilistic tractography of DTI to delineate three distinct brainstem tracts: the nigrostriatal tract (connecting brainstem to striatum, solitary tract (connecting brainstem to amygdala and corticospinal tract (connecting brainstem to precentral cortex. Fractional anisotropy (FA was used to measure the white matter integrity of these tracts, and measures were compared between MDD and control participants. RESULTS: MDD participants were characterized by a significant and specific decrease in white matter integrity of the right solitary tract (p<0.009 using independent t-test, which is a "bottom up" afferent pathway that connects the brainstem to the amygdala. This decrease was not related to symptom severity. CONCLUSIONS: The results provide new evidence to suggest that structural connectivity between the brainstem and the amygdala is altered in MDD. These results are interesting in light of predominant theories regarding amygdala-mediated emotional reactivity observed in functional imaging studies of MDD. The characterization of altered white matter integrity in the solitary tract in MDD supports the possibility of dysfunctional brainstem-amygdala connectivity impacting vulnerable circuits in MDD.

  15. Positive autoregulation of cI is a dispensable feature of the phage lambda gene regulatory circuitry. (United States)

    Michalowski, Christine B; Little, John W


    Complex gene regulatory circuits contain many features that are likely to contribute to their operation. It is unclear, however, whether all these features are necessary for proper circuit behavior or whether certain ones are refinements that make the circuit work better but are dispensable for qualitatively normal behavior. We have addressed this question using the phage lambda regulatory circuit, which can persist in two stable states, the lytic state and the lysogenic state. In the lysogenic state, the CI repressor positively regulates its own expression by stimulating transcription from the P(RM) promoter. We tested whether this feature is an essential part of the regulatory circuitry. Several phages with a cI mutation preventing positive autoregulation and an up mutation in the P(RM) promoter showed near-normal behavior. We conclude that positive autoregulation is not necessary for proper operation of the lambda circuitry and speculate that it serves a partially redundant function of stabilizing a bistable circuit, a form of redundancy we term "circuit-level redundancy." We discuss our findings in the context of a two-stage model for evolution and elaboration of regulatory circuits from simpler to more complex forms.

  16. Apparatus, system and method for providing cryptographic key information with physically unclonable function circuitry (United States)

    Areno, Matthew


    Techniques and mechanisms for providing a value from physically unclonable function (PUF) circuitry for a cryptographic operation of a security module. In an embodiment, a cryptographic engine receives a value from PUF circuitry and based on the value, outputs a result of a cryptographic operation to a bus of the security module. The bus couples the cryptographic engine to control logic or interface logic of the security module. In another embodiment, the value is provided to the cryptographic engine from the PUF circuitry via a signal line which is distinct from the bus, where any exchange of the value by either of the cryptographic engine and the PUF circuitry is for communication of the first value independent of the bus.

  17. Brainstem Influence on Thalamocortical Oscillations during Anesthesia Emergence

    Directory of Open Access Journals (Sweden)

    Christopher M. Scheib


    mechanisms can occur and that brainstem activity may influence the characteristics of emergence. The brainstem activity in question may be influenced by nociception and analgesic supplementation. It may be possible to control the path of emergence by controlling brainstem activity with opioids and other agents in order to allow the patient to awaken without going through an excitement phase or delirium at the transition to consciousness.

  18. The relationship of the brainstem ischemia and chronicity of lumboischialgia

    Directory of Open Access Journals (Sweden)

    D. G. Smolko


    Full Text Available We analyzed 60 patients aged from 30 up to 75 years with any of low-lumbar herniated intervertebral disks. Pain intensity was compared with the concomitant presence of chronic circulatory failure in the vertebral-basilar basin as a result of clinically significant abnormalities of blood vessels in the form of hypoplasia of vertebral artery and its tortuosity. We investigated dynamics of patient's pain under the influence of low-dose treatment by Cortexin (neurocytoprotector. In patients with chronic brainstem ischemia the herniated discs cause more intense and prolonged pain (radicular and local. More effective in these patients is a treatment with inclusion of Cortexin 20 mg intramuscularly within 10 days.

  19. Posterior hypothalamic and brainstem activation in hemicrania continua. (United States)

    Matharu, Manjit S; Cohen, Anna S; McGonigle, David J; Ward, Nick; Frackowiak, Richard S; Goadsby, Peter J


    To determine the brain structures involved in mediating the pain of hemicrania continua using positron emission tomography. Hemicrania continua is a strictly unilateral, continuous headache of moderate intensity, with superimposed exacerbations of severe intensity that are accompanied by trigeminal autonomic features and migrainous symptoms. The syndrome is exquisitely responsive to indomethacin. Its clinical phenotype overlaps with that of the trigeminal autonomic headaches and migraine in which the hypothalamus and the brainstem, respectively, have been postulated to play central pathophysiologic roles. We hypothesized, based on the clinical phenotype, that hemicrania continua may involve activations in the hypothalamus, or dorsal rostral pons, or both. Seven patients with hemicrania continua were studied in two sessions each. In one session, the patients were scanned during baseline pain and when rendered completely pain free after being administered indomethacin 100 mg intramuscularly. In the other session, the patients were scanned during baseline pain and when still in pain after being administered placebo intramuscularly. Seven age- and sex-matched nonheadache subjects acted as the control group. The scan images were processed and analyzed using SPM99. There was a significant activation of the contralateral posterior hypothalamus and ipsilateral dorsal rostral pons in association with the headache of hemicrania continua. In addition, there was activation of the ipsilateral ventrolateral midbrain, which extended over the red nucleus and the substantia nigra, and bilateral pontomedullary junction. No intracranial vessel dilatation was obvious. This study demonstrated activations of various subcortical structures, in particular the posterior hypothalamus and the dorsal rostral pons. If posterior hypothalamic and brainstem activation are considered as markers of trigeminal autonomic headaches and migrainous syndromes, respectively, then the activation pattern

  20. Lessons from sleeping flies: insights from Drosophila melanogaster on the neuronal circuitry and importance of sleep. (United States)

    Potdar, Sheetal; Sheeba, Vasu


    Sleep is a highly conserved behavior whose role is as yet unknown, although it is widely acknowledged as being important. Here we provide an overview of many vital questions regarding this behavior, that have been addressed in recent years using the genetically tractable model organism Drosophila melanogaster in several laboratories around the world. Rest in D. melanogaster has been compared to mammalian sleep and its homeostatic and circadian regulation have been shown to be controlled by intricate neuronal circuitry involving circadian clock neurons, mushroom bodies, and pars intercerebralis, although their exact roles are not entirely clear. We draw attention to the yet unanswered questions and contradictions regarding the nature of the interactions between the brain regions implicated in the control of sleep. Dopamine, octopamine, γ-aminobutyric acid (GABA), and serotonin are the chief neurotransmitters identified as functioning in different limbs of this circuit, either promoting arousal or sleep by modulating membrane excitability of underlying neurons. Some studies have suggested that certain brain areas may contribute towards both sleep and arousal depending on activation of specific subsets of neurons. Signaling pathways implicated in the sleep circuit include cyclic adenosine monophosphate (cAMP) and epidermal growth factor receptor-extracellular signal-regulated kinase (EGFR-ERK) signaling pathways that operate on different neural substrates. Thus, this field of research appears to be on the cusp of many new and exciting findings that may eventually help in understanding how this complex physiological phenomenon is modulated by various neuronal circuits in the brain. Finally, some efforts to approach the "Holy Grail" of why we sleep have been summarized.

  1. Synaptic plasticity in the medial vestibular nuclei: role of glutamate receptors and retrograde messengers in rat brainstem slices. (United States)

    Grassi, S; Pettorossi, V E


    The analysis of cellular-molecular events mediating synaptic plasticity within vestibular nuclei is an attempt to explain the mechanisms underlying vestibular plasticity phenomena. The present review is meant to illustrate the main results, obtained in vitro, on the mechanisms underlying long-term changes in synaptic strength within the medial vestibular nuclei. The synaptic plasticity phenomena taking place at the level of vestibular nuclei could be useful for adapting and consolidating the efficacy of vestibular neuron responsiveness to environmental requirements, as during visuo-vestibular recalibration and vestibular compensation. Following a general introduction on the most salient features of vestibular compensation and visuo-vestibular adaptation, which are two plastic events involving neuronal circuitry within the medial vestibular nuclei, the second and third sections describe the results from rat brainstem slice studies, demonstrating the possibility to induce long-term potentiation and depression in the medial vestibular nuclei, following high frequency stimulation of the primary vestibular afferents. In particular the mechanisms sustaining the induction and expression of vestibular long-term potentiation and depression, such as the role of various glutamate receptors and retrograde messengers have been described. The relevant role of the interaction between the platelet-activating factor, acting as a retrograde messenger, and the presynaptic metabotropic glutamate receptors, in determining the full expression of vestibular long-term potentiation is also underlined. In addition, the mechanisms involved in vestibular long-term potentiation have been compared with those leading to long-term potentiation in the hippocampus to emphasize the most significant differences emerging from vestibular studies. The fourth part, describes recent results demonstrating the essential role of nitric oxide, another retrograde messenger, in the induction of vestibular

  2. A Clinical Research Study of Cognitive Dysfunction and Affective Impairment after Isolated Brainstem Stroke

    Directory of Open Access Journals (Sweden)

    Xiujuan Fu


    Full Text Available Although the function of the cerebellum in neurocognition has been well-documented, the similar role of the brainstem has yet to be fully elucidated. This clinical research study aimed to combine data relating to neuropsychological assessments and P300 to explore cognitive dysfunction and affective impairment following brainstem stroke. Thirty-four patients with isolated brainstem stroke and twenty-six healthy controls were recruited; for each patient, we collated data pertaining to the P300, Addenbrooke's Cognitive Examination III (ACE-III, Montreal Cognitive Assessment Chinese version (MoCA, trail-making test (TMT, Symbol Digit Modalities Test (SDMT, Wechsler Adult Intelligence Scale-Digit Spans (DS, Stroop test, Self Rating Depression Scale (SDS, and Self Rating Anxiety Scale (SAS. Significance was analyzed using an independent T-test or the Mann-Whitney U-test. Correlation was analyzed using Pearson's correlation analysis or Spearman's correlation analysis. Collectively, data revealed that brainstem stroke caused mild cognitive impairment (MCI, and that visuospatial, attention, linguistic, and emotional disturbances may occur after isolated brainstem stroke. Cognitive decline was linked to P300 latency, ACE-III, and MoCA; P300 latency was correlated with ACE-III. Patients with right brainstem lesions were more likely to suffer memory decline. The present study provides initial data relating to the role of the brainstem in neurocognition, and will be useful for further understanding of vascular cognitive and affective impairment.

  3. Inverse activity of masticatory muscles with and without trismus: a brainstem syndrome. (United States)

    Jelasic, F; Freitag, V


    Clinical and EMG findings in 10 cases of intrinsic brainstem lesions are reported with paradoxical activity of jaw closing muscles during jaw opening, with and without trismus. In five cases with trigeminal anaesthesia, the inverse activity of jaw closers is interpreted as a manifestation of disturbance in the central programming of mastication in the motor trigeminal area of the brainstem. Stretch reflex mechanisms and disinhibition of the trigeminal motor neurones play no part in the origin of inverse activity. The distinct brainstem syndrome can only be detected by EMG and the special clinical features. Images PMID:690651

  4. How Does Brainstem Involvement Affect Prognosis in Patients with Limited Brain Metastases? Results of a Matched-Cohort Analysis. (United States)

    Trifiletti, Daniel M; Lee, Cheng-Chia; Shah, Neil; Patel, Nirav V; Chen, Shao-Ching; Sheehan, Jason P


    Although brainstem metastases are thought to portend an inferior prognosis compared to non-brainstem brain metastases, there is limited evidence to support this claim, particularly in the modern radiosurgical era. We collected the clinical data for 500 patients with brain metastases treated at our institution with stereotactic radiosurgery (SRS). All patients received SRS to at least one brain metastasis, and all brainstem metastases underwent SRS. After propensity score matching, clinical characteristics and overall survival were calculated and compared between groups. Three hundred sixteen patients with brain metastases were analyzed after matching (143 with brainstem involvement and 173 without). Patients with brainstem metastases lived shorter after first SRS than patients without brainstem metastases did (median 4.4 and 6.5 months, respectively; P = 0.01), and they were more likely to have received whole brain irradiation (P = 0.003). Patients with a single metastasis did not survive longer than patients with multiple brain metastases if there was brainstem involvement (P = 0.45). The incidence of new extracranial disease and severe toxicity after SRS did not differ between groups. The survival of patients with brain metastases is inferior after a metastatic lesion develops within the brainstem, despite favorable local control with brainstem SRS. The brainstem location should be considered a negative prognostic factor for survival after SRS, and it could result from the eloquence of this location. Future research could identify the clinically life-limiting component of brainstem metastases. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. The thalamus and brainstem act as key hubs in alterations of human brain network connectivity induced by mild propofol sedation. (United States)

    Gili, Tommaso; Saxena, Neeraj; Diukova, Ana; Murphy, Kevin; Hall, Judith E; Wise, Richard G


    Despite their routine use during surgical procedures, no consensus has yet been reached on the precise mechanisms by which hypnotic anesthetic agents produce their effects. Molecular, animal and human studies have suggested disruption of thalamocortical communication as a key component of anesthetic action at the brain systems level. Here, we used the anesthetic agent, propofol, to modulate consciousness and to evaluate differences in the interactions of remote neural networks during altered consciousness. We investigated the effects of propofol, at a dose that produced mild sedation without loss of consciousness, on spontaneous cerebral activity of 15 healthy volunteers using functional magnetic resonance imaging (fMRI), exploiting oscillations (eigenvector centrality (EC) to characterize brain network properties. The EC mapping of fMRI data in healthy humans under propofol mild sedation demonstrated a decrease of centrality of the thalamus versus an increase of centrality within the pons of the brainstem, highlighting the important role of these two structures in regulating consciousness. Specifically, the decrease of thalamus centrality results from its disconnection from a widespread set of cortical and subcortical regions, while the increase of brainstem centrality may be a consequence of its increased influence, in the mildly sedated state, over a few highly central cortical regions key to the default mode network such as the posterior and anterior cingulate cortices.

  6. Radiotherapy for diffuse brainstem glioma in children and young adults. (United States)

    Hu, Xin; Fang, Yuan; Hui, Xuhui; Jv, Yan; You, Chao


    Diffuse brainstem glioma is a devastating disease with very poor prognosis. The most commonly used radiological treatment is conventional fractionated radiation. So far, there is no meta-analysis or systematic review available that assesses the benefits or harms of radiation in people with diffuse brainstem glioma. To assess the effects of conventional fractionated radiotherapy (with or without chemotherapy) versus other therapies (including different radiotherapy techniques) for newly diagnosed diffuse brainstem gliomas in children and young adults aged 0 to 21 years. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE/PubMed, and EMBASE to 19 August 2015. We scanned conference proceedings from the International Society for Paediatric Oncology (SIOP), International Symposium on Paediatric Neuro-Oncology (ISPNO), Society of Neuro-Oncology (SNO), and European Association of Neuro-Oncology (EANO) from 1 January 2010 to 19 August 2015. We searched trial registers including the International Standard Randomised Controlled Trial Number (ISRCTN) Register, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and the register of the National Institutes of Health to 19 August 2015. We imposed no language restrictions. All randomised controlled trials (RCTs), quasi-randomised trials (QRCTs), or controlled clinical trials (CCTs) that compared conventional fractionated radiotherapy (with or without chemotherapy) versus other therapies (including different radiotherapy techniques) for newly diagnosed diffuse brainstem glioma in children and young adults aged 0 to 21 years. Two review authors independently screened studies for inclusion, extracted data, assessed the risk of bias in each eligible trial, and conducted GRADE assessment of included studies. We resolved disagreements through discussion. We performed analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of

  7. TPX2-p53-GLIPR1 regulatory circuitry in cell proliferation, invasion, and tumor growth of bladder cancer. (United States)

    Yan, Liang; Li, Qi; Yang, Juan; Qiao, Baoping


    The targeting protein for Xenopus kinesin-like protein 2 (TPX2) is associated with the metastasis and prognosis of bladder cancer. p53 is closely related to the progression of bladder cancer. Human glioma pathogenesis-related protein 1 (GLIPR1) is a p53 target gene with antitumor activity. This study aims to explore the interplay between TPX2, p53, and GLIPR1 and its correlation with cell proliferation, invasion, and tumor growth in bladder cancer. Here, Western blot and qRT-PCR analysis revealed that TPX2 at both mRNA and protein levels was up-regulated in bladder carcinoma tissues compared to their paired adjacent normal tissues. Additionally, tissues expressing high TPX2 level exhibited high p53 level and low GLIPR1 level. The expressions of TPX2 and p53 in non-muscle-invasive bladder cancer cells (KK47 and RT4) were lower than those in muscle-invasive bladder cancer cells (T24, 5637, and UM-UC-3), while GLIPR1 showed the converse expression pattern. Further investigation revealed that TPX2 activated the synthesis of p53; and GLIPR1 is up-regulated by wild-type (wt)-p53 but not affected by mutated p53; Additionally, GLIPR1 inhibited TPX2. These data suggested a TPX2-p53-GLIPR1 regulatory circuitry. Meanwhile, TPX2 overexpression promoted while overexpression of GLIPR1 or p53 inhibited bladder cancer growth. Interestingly, in T24 cells with mutated p53, p53 silence suppressed bladder cancer growth. This study identified a novel TPX2-p53-GLIPR1 regulatory circuitry which modulated cell proliferation, migration, invasion, and tumorigenicity of bladder cancer. Our findings provide new insight into underlying mechanisms of tumorigenesis and novel therapeutic options in bladder cancer. © 2017 Wiley Periodicals, Inc.

  8. Binaural interaction in the auditory brainstem response: a normative study. (United States)

    Van Yper, Lindsey N; Vermeire, Katrien; De Vel, Eddy F J; Battmer, Rolf-Dieter; Dhooge, Ingeborg J M


    Binaural interaction can be investigated using auditory evoked potentials. A binaural interaction component can be derived from the auditory brainstem response (ABR-BIC) and is considered evidence for binaural interaction at the level of the brainstem. Although click ABR-BIC has been investigated thoroughly, data on 500 Hz tone-burst (TB) ABR-BICs are scarce. In this study, characteristics of click and 500 Hz TB ABR-BICs are described. Furthermore, reliability of both click and 500 Hz TB ABR-BIC are investigated. Eighteen normal hearing young adults (eight women, ten men) were included. ABRs were recorded in response to clicks and 500 Hz TBs. ABR-BICs were derived by subtracting the binaural response from the sum of the monaural responses measured in opposite ears. Good inter-rater reliability is obtained for both click and 500 Hz TB ABR-BICs. The most reliable peak in click ABR-BIC occurs at a mean latency of 6.06 ms (SD 0.354 ms). Reliable 500 Hz TB ABR-BIC are obtained with a mean latency of 9.47 ms (SD 0.678 ms). Amplitudes are larger for 500 Hz TB ABR-BIC than for clicks. The most reliable peak in click ABR-BIC occurs at the downslope of wave V. Five hundred Hertz TB ABR-BIC is characterized by a broad positivity occurring at the level of wave V. The ABR-BIC is a useful technique to investigate binaural interaction in certain populations. Examples are bilateral hearing aid users, bilateral cochlear implant users and bimodal listeners. The latter refers to the combination of unilateral cochlear implantation and contralateral residual hearing. The majority of these patients have residual hearing in the low frequencies. The current study suggests that 500 Hz TB ABR-BIC may be a suitable technique to assess binaural interaction in this specific population of cochlear implant users. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  9. Rapid Increase in Neural Conduction Time in the Adult Human Auditory Brainstem Following Sudden Unilateral Deafness

    National Research Council Canada - National Science Library

    Maslin, M R. D; Lloyd, S K; Rutherford, S; Freeman, S; King, A; Moore, D R; Munro, K J


    .... Click-evoked auditory brainstem responses (ABRs) to stimulation of the healthy ear were recorded from ten adults during the course of translabyrinthine surgery for the removal of a unilateral acoustic neuroma...

  10. Electrically evoked auditory brainstem responses in children with sequential bilateral cochlear implants.

    NARCIS (Netherlands)

    Sparreboom, M.; Beynon, A.J.; Snik, A.F.M.; Mylanus, E.A.M.


    OBJECTIVE: To examine the effect of sequential bilateral cochlear implantation on auditory brainstem maturation and the effect of age in receiving the second implant (CI2). STUDY DESIGN: Prospective cohort study. SETTING: Tertiary academic referral center. PATIENTS: Thirty prelingually deaf

  11. Herpetic brainstem encephalitis: report of a post-mortem case studied electron microscopically and immunohisiochemically

    Directory of Open Access Journals (Sweden)

    José Eymard Homem Pitella


    Full Text Available A post-mortem examined case of herpetic brainstem encephalitis is presented. Clinically, the patient had cephalea followed by ataxia, drowsiness and multiple palsies of some cranial nerves, developing into death in eight days. The pathologic examination of the brain showed necrotizing encephalitis in multiple foci limited to the brainstem, more distinctly in the pons and medula oblongata. The technique of immunoperoxidase revealed rare glial cells with intranuclear immunoreactivity for herpes antigen. Rare viral particles with the morphological characteristics of the herpesvirus were identified in the nuclei of neurons in 10% formol fixed material. This is the second reported case of herpetic brainstem encephalitis confirmed by post-mortem examination. The pathway used by the virus to reach the central nervous system and its posterior dissemination to the oral cavity, the orbitofrontal region and the temporal lobes as well as to the brainstem, after a period of latency and reactivation, are discussed.

  12. Reading ability reflects individual differences in auditory brainstem function, even into adulthood. (United States)

    Skoe, Erika; Brody, Lisa; Theodore, Rachel M


    Research with developmental populations suggests that the maturational state of auditory brainstem encoding is linked to reading ability. Specifically, children with poor reading skills resemble biologically younger children with respect to their auditory brainstem responses (ABRs) to speech stimulation. Because ABR development continues into adolescence, it is possible that the link between ABRs and reading ability changes or resolves as the brainstem matures. To examine these possibilities, ABRs were recorded at varying presentation rates in adults with diverse, yet unimpaired reading levels. We found that reading ability in adulthood related to ABR Wave V latency, with more juvenile response morphology linked to less proficient reading ability, as has been observed for children. These data add to the evidence indicating that auditory brainstem responses serve as an index of the sound-based skills that underlie reading, even into adulthood. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Mapping of somatostatin-28 (1-12) in the alpaca (Lama pacos) brainstem. (United States)

    De Souza, Eliana; Sánchez, Manuel Lisardo; Aguilar, Luís Ángel; Díaz-Cabiale, Zaida; Narváez, José Ángel; Coveñas, Rafael


    Using an indirect immunoperoxidase technique, we studied the distribution of cell bodies and fibers containing somatostatin-28 (1-12) in the alpaca brainstem. Immunoreactive fibers were widely distributed throughout the whole brainstem: 34 brainstem nuclei/regions showed a high or a moderate density of these fibers. Perikarya containing the peptide were widely distributed throughout the mesencephalon, pons and medulla oblongata. Cell bodies containing somatostatin-28 (1-12) were observed in the lateral and medial divisions of the marginal nucleus of the brachium conjunctivum, reticular formation (mesencephalon, pons and medulla oblongata), inferior colliculus, periaqueductal gray, superior colliculus, pericentral division of the dorsal tegmental nucleus, interpeduncular nucleus, nucleus of the trapezoid body, vestibular nucleus, motor dorsal nucleus of the vagus, nucleus of the solitary tract, nucleus praepositus hypoglossi, and in the substantia nigra. This widespread distribution indicates that somatostatin-28 (1-12) is involved in multiple physiological actions in the alpaca brainstem. © 2015 Wiley Periodicals, Inc.

  14. Organization of diencephalic and brainstem afferent projections to the lateral septum in the rat

    NARCIS (Netherlands)

    Luiten, Paul G.M.; Kuipers, Folkert; Schuitmaker, Hans


    Ascending diencephalic and brainstem afferents to the lateral septal column were studied by retrograde transport of horseradish peroxidase following microiontophoretic injections in the various subdivisions of the lateral septal area. Predominantly ispilateral cells, of which several coincide with

  15. Brainstem ganglioglioma in an infant: Case report and review of literature. (United States)

    Gopalakrishnan, C V; Shrivastava, Adesh; Nair, Suresh; Radhakrishnan, Neelima


    Gangliogliomas are well differentiated, usually low grade, neuroepithelial tumors that comprise of neoplastic ganglion cells in combination with neoplastic glial cells. Occasionally, glial cells may show anaplastic features and are then labeled as anaplastic gangliogliomas. Most of the reported gangliogliomas are supratentorial tumors, predominantly in the temporal lobe. Brainstem location has been reported infrequently. As with cortically based gangliogliomas, though the primary treatment is resection, this is often not possible due to the eloquence of surrounding involved parenchyma. Here, we report a case of brainstem tumor in an 8-month-old child that was substantially resected and was histopathologically Grade 1 ganglioglioma. As per review of English literature, there has been no case of brainstem ganglioglioma reported in an infant (less than 1 year age). We discuss the surgical difficulties in the radical excision of such benign tumors and review literature on pediatric brainstem gangliogliomas.

  16. Visualization of brainstem perfusion using a high spatial resolution SPECT system. (United States)

    Dierckx, R; Dobbeleir, A; Vandevivere, J; Abts, H; DeDeyn, P P


    The authors explored the high spatial resolution of a three-head rotating SPECT system, equipped with lead super-fine fanbeam collimator. The brainstem was high-lighted in a three-dimensional reconstruction, showing perfusion small structures such as mesencephalon, pons, and medulla oblongata. The visualization of brainstem perfusion sets new landmarks in functional neuroimaging and, moreover, was obtained with a commercially available three-head SPECT system.

  17. The brainstem pathologies of Parkinson's disease and dementia with Lewy bodies. (United States)

    Seidel, Kay; Mahlke, Josefine; Siswanto, Sonny; Krüger, Reijko; Heinsen, Helmut; Auburger, Georg; Bouzrou, Mohamed; Grinberg, Lea T; Wicht, Helmut; Korf, Horst-Werner; den Dunnen, Wilfred; Rüb, Udo


    Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are among the human synucleinopathies, which show alpha-synuclein immunoreactive neuronal and/or glial aggregations and progressive neuronal loss in selected brain regions (eg, substantia nigra, ventral tegmental area, pedunculopontine nucleus). Despite several studies about brainstem pathologies in PD and DLB, there is currently no detailed information available regarding the presence of alpha-synuclein immunoreactive inclusions (i) in the cranial nerve, precerebellar, vestibular and oculomotor brainstem nuclei and (ii) in brainstem fiber tracts and oligodendroctyes. Therefore, we analyzed the inclusion pathologies in the brainstem nuclei (Lewy bodies, LB; Lewy neurites, LN; coiled bodies, CB) and fiber tracts (LN, CB) of PD and DLB patients. As reported in previous studies, LB and LN were most prevalent in the substantia nigra, ventral tegmental area, pedunculopontine and raphe nuclei, periaqueductal gray, locus coeruleus, parabrachial nuclei, reticular formation, prepositus hypoglossal, dorsal motor vagal and solitary nuclei. Additionally we were able to demonstrate LB and LN in all cranial nerve nuclei, premotor oculomotor, precerebellar and vestibular brainstem nuclei, as well as LN in all brainstem fiber tracts. CB were present in nearly all brainstem nuclei and brainstem fiber tracts containing LB and/or LN. These findings can contribute to a large variety of less well-explained PD and DLB symptoms (eg, gait and postural instability, impaired balance and postural reflexes, falls, ingestive and oculomotor dysfunctions) and point to the occurrence of disturbances of intra-axonal transport processes and transneuronal spread of the underlying pathological processes of PD and DLB along anatomical pathways. © 2014 International Society of Neuropathology.

  18. Relative numbers of cortical and brainstem inputs to the lateral geniculate nucleus (United States)

    Erişir, Alev; Van Horn, Susan C.; Sherman, S. Murray


    Terminals of a morphological type known as RD (for round vesicles and dense mitochondria, which we define here as the aggregate of types formerly known as RSD and RLD, where “S” is small and “L” is large) constitute at least half of the synaptic inputs to the feline lateral geniculate nucleus, which represents the thalamic relay of retinal input to cortex. It had been thought that the vast majority of these RD terminals were of cortical origin, making the corticogeniculate pathway by far the largest source of input to geniculate relay cells. However, another source of RD terminals recently identified derives from cholinergic cells of the brainstem parabrachial region. (These cells also contain NO.) We used techniques of electron microscopy to determine quantitatively the relative contribution of cortex and brainstem to the population of RD terminals. We identified corticogeniculate terminals by orthograde transport of biocytin injected into the visual cortex and identified brainstem terminals by immunocytochemical labeling for choline acetyltransferase or brain NO synthase (the synthesizing enzymes for acetylcholine and NO, respectively). We estimated the relative numbers of corticogeniculate and brainstem terminals with a two-step algorithm: First, we determined the relative probability of sampling each terminal type in our material, and then we calculated what mixture of identified corticogeniculate and brainstem terminals was needed to recreate the size distribution of the parent RD terminal population. We conclude that brainstem terminals comprise roughly one-half of the RD population. Thus, the cortical input is perhaps half as large and the brainstem input is an order of magnitude larger than had been thought. This further suggests that the brainstem inputs might play a surprisingly complex and subtle role in the control of the geniculocortical relay. PMID:9037085

  19. Studying respiratory rhythm generation in a developing bird: hatching a new experimental model using the classic in vitro brainstem-spinal cord preparatio (United States)

    Vincen-Brown, Michael A.; Whitesitt, Kaitlyn C.; Quick, Forrest G.; Pilarski, Jason Q.


    It has been more than thirty years since the in vitro brainstem-spinal cord preparation was first presented as a method to study automatic breathing behaviors in the neonatal rat. This straightforward preparation has led to an incredible burst of information about the location and coordination of several spontaneously active microcircuits that form the ventrolateral respiratory network of the brainstem. Despite these advances, our knowledge of the mechanisms that regulate central breathing behaviors is still incomplete. Investigations into the nature of spontaneous breathing rhythmicity have almost exclusively focused on mammals, and there is a need for comparative experimental models to evaluate several unresolved issues from a different perspective. With this in mind, we sought to develop a new avian in vitro model with the long term goal to better understand questions associated with the ontogeny of respiratory rhythm generation, neuroplasticity, and whether multiple, independent oscillators drive the major phases of breathing. The fact that birds develop in ovo provides unparalleled access to central neuronal networks throughout the prenatal period—from embryo to hatchling—that are free from confounding interactions with mother. Previous studies using in vitro avian models have been strictly limited to the early embryonic period. Consequently, the details and even the presence of brainstem derived breathing-related rhythmogenesis in birds have never been described. In the present study, we used the altricial zebra finch (Taeniopygia guttata) and show robust spontaneous motor outflow through cranial motor nerve IX, which is first detectable on embryonic day four and continues through prenatal and early postnatal development without interruption. We also show that brainstem oscillations change dramatically over the course of prenatal development, sometimes within hours, which suggests rapid maturational modifications in growth and connectivity. We propose

  20. Functional abnormality of the auditory brainstem in high-risk late preterm infants. (United States)

    Jiang, Ze D; Ping, Li L; Wilkinson, Andrew R


    To examine whether late preterm infants with perinatal problems are at risk of brainstem auditory impairment. 68 high-risk late preterm infants (gestation 33-36 weeks) with perinatal problems or conditions were studied at term using maximum length sequence brainstem auditory evoked response. The controls were 41 normal term infants and 37 low-risk late preterm infants. Compared with normal term infants, the high-risk late preterm infants demonstrated a significant abnormal increase in MLS BAER variables that mainly reflect more central function of the brainstem auditory pathway, including wave V latency, III-V and I-V interpeak intervals, and III-V/I-III interval ratio. The abnormalities were more significant at higher than at lower click rates. The slopes of MLS BAER-rate function for these variables were increased. Compared with low-risk late preterm infants, the high-risk infants showed similar, though slightly less significant, abnormalities, mainly a significant increase in III-V and I-V intervals. Maximum length sequence brainstem auditory evoked response components that mainly reflect central function of the auditory brainstem were abnormal at term in high-risk late preterm infants. More central regions of the auditory brainstem are impaired in high-risk late preterm infants, which is mainly caused by associated perinatal problems or conditions. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  1. A human brain network derived from coma-causing brainstem lesions. (United States)

    Fischer, David B; Boes, Aaron D; Demertzi, Athena; Evrard, Henry C; Laureys, Steven; Edlow, Brian L; Liu, Hesheng; Saper, Clifford B; Pascual-Leone, Alvaro; Fox, Michael D; Geerling, Joel C


    To characterize a brainstem location specific to coma-causing lesions, and its functional connectivity network. We compared 12 coma-causing brainstem lesions to 24 control brainstem lesions using voxel-based lesion-symptom mapping in a case-control design to identify a site significantly associated with coma. We next used resting-state functional connectivity from a healthy cohort to identify a network of regions functionally connected to this brainstem site. We further investigated the cortical regions of this network by comparing their spatial topography to that of known networks and by evaluating their functional connectivity in patients with disorders of consciousness. A small region in the rostral dorsolateral pontine tegmentum was significantly associated with coma-causing lesions. In healthy adults, this brainstem site was functionally connected to the ventral anterior insula (AI) and pregenual anterior cingulate cortex (pACC). These cortical areas aligned poorly with previously defined resting-state networks, better matching the distribution of von Economo neurons. Finally, connectivity between the AI and pACC was disrupted in patients with disorders of consciousness, and to a greater degree than other brain networks. Injury to a small region in the pontine tegmentum is significantly associated with coma. This brainstem site is functionally connected to 2 cortical regions, the AI and pACC, which become disconnected in disorders of consciousness. This network of brain regions may have a role in the maintenance of human consciousness. © 2016 American Academy of Neurology.

  2. Abnormal cortical excitability with preserved brainstem and spinal reflexes in sialidosis type I. (United States)

    Huang, Ying-Zu; Lai, Szu-Chia; Lu, Chin-Song; Weng, Yi-Hsin; Chuang, Wen-Li; Chen, Rou-Shayn


    To examine neurophysiological evidence of functional involvement of the brainstem and spinal cord and motor cortical excitability in sialidosis type I, a rare inherited neurodegenerative disorder caused by mutations in the NEU1 gene. We investigated particular pathways in the brainstem, spinal cord and motor cortex in 12 genetically proven cases of sialidosis type I by assessing blink reflex recovery cycle (BR), spinal reciprocal inhibition (RI), input-output curves (I/O), short interval intracortical inhibition (SICI), intracortical facilitation (ICF) and silent period (SP). The BR and RI were normal. The slope of I/O was significantly increased, and SICI and the duration of SP were reduced in sialidosis patients. Despite reports of pathology involving brainstem and anterior horn neurones, there were no obvious abnormalities in spinal and brainstem reflexes in the present patients, suggesting that the major clinical effects may be caused by changes at a level above the brainstem. For the first time, the integrity of certain brainstem and spinal cord reflexes in addition to motor cortical facilitatory and inhibitory circuits has been assessed in genetically proven type I sialidosis. This provides new data to aid in understanding of the pathophysiology of motor system dysfunction in this condition.

  3. Lifelong expression of apolipoprotein D in the human brainstem: correlation with reduced age-related neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Ana Navarro

    Full Text Available The lipocalin apolipoprotein D (Apo D is upregulated in peripheral nerves following injury and in regions of the central nervous system, such as the cerebral cortex, hippocampus, and cerebellum, during aging and progression of certain neurological diseases. In contrast, few studies have examined Apo D expression in the brainstem, a region necessary for survival and generally less prone to age-related degeneration. We measured Apo D expression in whole human brainstem lysates by slot-blot and at higher spatial resolution by quantitative immunohistochemistry in eleven brainstem nuclei (the 4 nuclei of the vestibular nuclear complex, inferior olive, hypoglossal nucleus, oculomotor nucleus, facial motor nucleus, nucleus of the solitary tract, dorsal motor nucleus of the vagus nerve, and Roller`s nucleus. In contrast to cortex, hippocampus, and cerebellum, apolipoprotein D was highly expressed in brainstem tissue from subjects (N = 26, 32-96 years of age with no history of neurological disease, and expression showed little variation with age. Expression was significantly stronger in somatomotor nuclei (hypoglossal, oculomotor, facial than visceromotor or sensory nuclei. Both neurons and glia expressed Apo D, particularly neurons with larger somata and glia in the periphery of these brainstem centers. Immunostaining was strongest in the neuronal perinuclear region and absent in the nucleus. We propose that strong brainstem expression of Apo D throughout adult life contributes to resistance against neurodegenerative disease and age-related degeneration, possibly by preventing oxidative stress and ensuing lipid peroxidation.

  4. Diagnostic Yield and Safety of Cerebellar and Brainstem Parenchymal Biopsy. (United States)

    Tobin, W Oliver; Meyer, Fredric B; Keegan, B Mark


    We aimed to determine the diagnostic yield and safety of posterior fossa parenchymal biopsy. One-hundred-thirty-six patients who underwent 137 posterior fossa (brainstem or cerebellar) parenchymal biopsies at Mayo Clinic (Rochester, Minnesota, USA) between 1996 and 2009 were identified by chart review. Case histories; radiologic, surgical, and pathologic reports; and safety outcomes were assessed. Posterior fossa parenchymal biopsies were performed on 78 male and 58 female patients of median age 47 years (interquartile range 28-61). Preoperative clinical diagnosis in the majority of cases was of a malignant neoplasm. Glial neoplasm (51%) was the most common finding followed by lymphoma (7%) and neurosarcoidosis (7%). Normal tissue or nonspecific changes were observed in 28 cases (20%). Three deaths occurred: 2 at the time of biopsy (1%) and 1 due to underlying disease. All deaths occurred in patients who had a cerebellar biopsy. Transient neurologic deficits occurred in 15 patients (11%): worsening of presenting symptoms (4), cardiac arrhythmia (3), vertigo (2), diplopia (2), ataxia (3), seizure (1), decreased consciousness (1), and limb numbness (3). Sustained neurologic deficits occurred in 3 patients: fourth nerve palsy (1), hemiparesis (1), and facial numbness (1). The diagnostic yield of posterior fossa parenchymal biopsy in Mayo Clinic patients with diverse pathologies was 80%. The complication rate was 11% with the majority being transient, but 2 deaths were attributed to biopsy. Evaluation of the diagnostic yield and complication rate at individual neurosurgical centers is needed to determine generalizability of these results. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Auditory brainstem responses to stop consonants predict literacy. (United States)

    Neef, Nicole E; Schaadt, Gesa; Friederici, Angela D


    Precise temporal coding of speech plays a pivotal role in sound processing throughout the central auditory system, which, in turn, influences literacy acquisition. The current study tests whether an electrophysiological measure of this precision predicts literacy skills. Complex auditory brainstem responses were analysed from 62 native German-speaking children aged 11-13years. We employed the cross-phaseogram approach to compute the quality of the electrophysiological stimulus contrast [da] and [ba]. Phase shifts were expected to vary with literacy. Receiver operating curves demonstrated a feasible sensitivity and specificity of the electrophysiological measure. A multiple regression analysis resulted in a significant prediction of literacy by delta cross-phase as well as phonological awareness. A further commonality analysis separated a unique variance that was explained by the physiological measure, from a unique variance that was explained by the behavioral measure, and common effects of both. Despite multicollinearities between literacy, phonological awareness, and subcortical differentiation of stop consonants, a combined assessment of behavior and physiology strongly increases the ability to predict literacy skills. The strong link between the neurophysiological signature of sound encoding and literacy outcome suggests that the delta cross-phase could indicate the risk of dyslexia and thereby complement subjective psychometric measures for early diagnoses. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  6. Evaluation of an auditory brainstem response in icteric neonates

    Directory of Open Access Journals (Sweden)

    Ahmad Talebian


    Full Text Available Background: Neonatal hyperbilirubinemia is a common and preventable cause of sensory-neural hearing impairment, which can cause difficulties in the development of speech and communication. This study was conducted to detect the toxic effect of hyperbilirubinemia on the brain stem and auditory tract in neonates with icterus admitted to Shahid Beheshti Hospital in Kashan, Iran. Materials and Methods: This cross-sectional study was conducted on 98 neonates with increased indirect bilirubin admitted to Shahid Beheshti Hospital in Kashan during 2014-2015. The patients were referred to Matini Hospital for the assessment of the auditory brainstem response (ABR; wave latency and interpeak intervals of the waves were also evaluated. According to the serum bilirubin level, the neonates were allocated into two groups; one group had a serum bilirubin level of 13-20 mg/d and another group had a bilirubin level more than 20 mg/d. Results: From 98 neonates, 26 (26.5% had a bilirubin level more than 20 mg/d and 72 (73.5% had a bilirubin level of 13-20 mg/d. Also, 46.1% of the neonates in the first group (bilirubin20 mg/d can cause an auditory processing disorder in neonates. So, performing ABR for screening and early detection of bilirubin toxicity can be recommended as a necessary audiologic intervention in all cases of severe neonatal hyperbilirubinemia.

  7. Brainstem Auditory Evoked Potentials in Patients with Subarachnoid Haemorrhage

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    Mikhail Matveev


    Full Text Available Objective. The aim of the present study is to typify BAEPs configurations of patients with different location of lesions caused by subarachnoid haemorrhage (SAH and the ensuing complications, in view of assessing the auditory-brainstem system disturbance.Methods. The typization was performed by comparing BAEPs with standard patterns from two sets of types of BAEPs by ipsilateral and binaural stimulation and by cross-stimulation.Results. 94 BAEPs were used for collection of normal referential values: for the absolute latencies and the absolute amplitudes of waves I, II, III, IV and V; for inter-peak latencies I-III, II-III, III-V, I-V and II-V; for amplitude ratios I/V and III/V. 146 BAEPs of patients with mild SAH and 55 from patients with severe SAH, were typified. In 5 types of BAEPs out of a total of 11, the percentage of the potentials in patients with mild SAH and severe SAH differed significantly (p<0.01.Conclusions. The use of sets of types of BAEPs by ipsilateral, binaural and cross-stimulation correctly classifies the potentials in patients with mild and severe SAH.

  8. Brainstem auditory evoked potentials in children with lead exposure

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    Katia de Freitas Alvarenga


    Full Text Available Introduction: Earlier studies have demonstrated an auditory effect of lead exposure in children, but information on the effects of low chronic exposures needs to be further elucidated. Objective: To investigate the effect of low chronic exposures of the auditory system in children with a history of low blood lead levels, using an auditory electrophysiological test. Methods: Contemporary cross-sectional cohort. Study participants underwent tympanometry, pure tone and speech audiometry, transient evoked otoacoustic emissions, and brainstem auditory evoked potentials, with blood lead monitoring over a period of 35.5 months. The study included 130 children, with ages ranging from 18 months to 14 years, 5 months (mean age 6 years, 8 months ± 3 years, 2 months. Results: The mean time-integrated cumulative blood lead index was 12 µg/dL (SD ± 5.7, range:2.433. All participants had hearing thresholds equal to or below 20 dBHL and normal amplitudes of transient evoked otoacoustic emissions. No association was found between the absolute latencies of waves I, III, and V, the interpeak latencies I-III, III-V, and I-V, and the cumulative lead values. Conclusion: No evidence of toxic effects from chronic low lead exposures was observed on the auditory function of children living in a lead contaminated area.

  9. Brainstem auditory evoked potentials in children with lead exposure. (United States)

    Alvarenga, Katia de Freitas; Morata, Thais Catalani; Lopes, Andrea Cintra; Feniman, Mariza Ribeiro; Corteletti, Lilian Cassia Bornia Jacob


    Earlier studies have demonstrated an auditory effect of lead exposure in children, but information on the effects of low chronic exposures needs to be further elucidated. To investigate the effect of low chronic exposures of the auditory system in children with a history of low blood lead levels, using an auditory electrophysiological test. Contemporary cross-sectional cohort. Study participants underwent tympanometry, pure tone and speech audiometry, transient evoked otoacoustic emissions, and brainstem auditory evoked potentials, with blood lead monitoring over a period of 35.5 months. The study included 130 children, with ages ranging from 18 months to 14 years, 5 months (mean age 6 years, 8 months ± 3 years, 2 months). The mean time-integrated cumulative blood lead index was 12 μg/dL (SD ± 5.7, range: 2.433). All participants had hearing thresholds equal to or below 20 dBHL and normal amplitudes of transient evoked otoacoustic emissions. No association was found between the absolute latencies of waves I, III, and V, the interpeak latencies I-III, III-V, and I-V, and the cumulative lead values. No evidence of toxic effects from chronic low lead exposures was observed on the auditory function of children living in a lead contaminated area. Copyright © 2014 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  10. [On the reliability of brainstem electric response audiometry (BERA)]. (United States)

    Renne, C; Olthoff, A


    Brainstem electric response audiometries (BERA) are in clinical use for a number of years. The aim of our study was to evaluate data regarding the long-term reliability of BERA-determined frequency specific thresholds in hearing disabled children. In a group of 97 hearing disabled children we sought to compare Notched-Noise- (NN) BERA threshold as well as Click-BERA thresholds taken shortly after birth with behavioral audiometry thresholds determined after 3.2 years (mean). We found a significant correlation between both BERA methods and the behavioral tests. However, the correlation coefficients for NN-BERA were higher than for Click-BERA thresholds. Our results provide evidence for a high reliability of the NN-BERA for characterization of early onset hearing disabilities in children. Our data suggest that pathologic findings in the Click-BERA should always be followed by a frequency specific analysis with NN-BERA. © Georg Thieme Verlag KG Stuttgart · New York.

  11. Auditory Brainstem Responses and EMFs Generated by Mobile Phones. (United States)

    Khullar, Shilpa; Sood, Archana; Sood, Sanjay


    There has been a manifold increase in the number of mobile phone users throughout the world with the current number of users exceeding 2 billion. However this advancement in technology like many others is accompanied by a progressive increase in the frequency and intensity of electromagnetic waves without consideration of the health consequences. The aim of our study was to advance our understanding of the potential adverse effects of GSM mobile phones on auditory brainstem responses (ABRs). 60 subjects were selected for the study and divided into three groups of 20 each based on their usage of mobile phones. Their ABRs were recorded and analysed for latency of waves I-V as well as interpeak latencies I-III, I-V and III-V (in ms). Results revealed no significant difference in the ABR parameters between group A (control group) and group B (subjects using mobile phones for maximum 30 min/day for 5 years). However the latency of waves was significantly prolonged in group C (subjects using mobile phones for 10 years for a maximum of 30 min/day) as compared to the control group. Based on our findings we concluded that long term exposure to mobile phones may affect conduction in the peripheral portion of the auditory pathway. However more research needs to be done to study the long term effects of mobile phones particularly of newer technologies like smart phones and 3G.

  12. A comparison of auditory brainstem responses across diving bird species (United States)

    Crowell, Sara E.; Berlin, Alicia; Carr, Catherine E; Olsen, Glenn H.; Therrien, Ronald E; Yannuzzi, Sally E; Ketten, Darlene R


    There is little biological data available for diving birds because many live in hard-to-study, remote habitats. Only one species of diving bird, the black-footed penguin (Spheniscus demersus), has been studied in respect to auditory capabilities (Wever et al., Proc Natl Acad Sci USA 63:676–680, 1969). We, therefore, measured in-air auditory threshold in ten species of diving birds, using the auditory brainstem response (ABR). The average audiogram obtained for each species followed the U-shape typical of birds and many other animals. All species tested shared a common region of the greatest sensitivity, from 1000 to 3000 Hz, although audiograms differed significantly across species. Thresholds of all duck species tested were more similar to each other than to the two non-duck species tested. The red-throated loon (Gavia stellata) and northern gannet (Morus bassanus) exhibited the highest thresholds while the lowest thresholds belonged to the duck species, specifically the lesser scaup (Aythya affinis) and ruddy duck (Oxyura jamaicensis). Vocalization parameters were also measured for each species, and showed that with the exception of the common eider (Somateria mollisima), the peak frequency, i.e., frequency at the greatest intensity, of all species' vocalizations measured here fell between 1000 and 3000 Hz, matching the bandwidth of the most sensitive hearing range.

  13. Method, apparatus and system to compensate for drift by physically unclonable function circuitry

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    Hamlet, Jason


    Techniques and mechanisms to detect and compensate for drift by a physically uncloneable function (PUF) circuit. In an embodiment, first state information is registered as reference information to be made available for subsequent evaluation of whether drift by PUF circuitry has occurred. The first state information is associated with a first error correction strength. The first state information is generated based on a first PUF value output by the PUF circuitry. In another embodiment, second state information is determined based on a second PUF value that is output by the PUF circuitry. An evaluation of whether drift has occurred is performed based on the first state information and the second state information, the evaluation including determining whether a threshold error correction strength is exceeded concurrent with a magnitude of error being less than the first error correction strength.

  14. Neural Emotion Regulation Circuitry Underlying Anxiolytic Effects of Perceived Control Over Pain


    Salomons, Tim V.; Nusslock, Robin; Detloff, Allison; Johnstone, Tom; Davidson, Richard J.


    Anxiolytic effects of perceived control have been observed across species. In humans, neuroimaging studies have suggested that perceived control and cognitive reappraisal reduce negative affect through similar mechanisms. An important limitation of extant neuroimaging studies of perceived control in terms of directly testing this hypothesis, however, is the use of within subjects-designs, which confound participants' affective response to controllable and uncontrollable stress. To compare neu...

  15. Resurgent sodium current promotes action potential firing in the avian auditory brainstem. (United States)

    Hong, Hui; Lu, Ting; Wang, Xiaoyu; Wang, Yuan; Sanchez, Jason Tait


    Auditory brainstem neurons are functionally primed to fire action potentials (APs) at markedly high-rates in order to rapidly encode acoustic information of sound. This specialization is critical for survival and the comprehension of behaviourally relevant communication functions, including sound localization and understanding speech in noise. Here, we investigated underlying ion channel mechanisms essential for high-rate AP firing in neurons of the chicken nucleus magnocellularis (NM) - the avian analog of bushy cells of the mammalian anteroventral cochlear nucleus. In addition to the established function of high-voltage activated potassium channels, we found that resurgent sodium current (INaR ) plays a role in regulating rapid firing activity of late-developing (embryonic [E] days 19-21) NM neurons. INaR of late-developing NM neurons showed similar properties with mammalian neurons in that its unique mechanism of an "open channel block state" facilitated the recovery and increased the availability of sodium (NaV ) channels after depolarization. Using a computational model of NM neurons, we demonstrated that removal of INaR reduced high-rate AP firing. We found weak INaR during a prehearing period (E11-12), which transformed to resemble late-developing INaR properties around hearing onset (E14-16). Anatomically, we detected strong NaV 1.6 expression near maturation, which became increasingly less distinct at hearing onset and prehearing periods, suggesting that multiple NaV channel subtypes may contribute to INaR during development. We conclude that INaR plays an important role in regulating rapid AP firing for NM neurons, a property that may be evolutionarily conserved for functions related to similar avian and mammalian hearing. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. Prolonged auditory brainstem responses in infants with autism (United States)

    Miron, Oren; Ari‐Even Roth, Daphne; Gabis, Lidia V.; Henkin, Yael; Shefer, Shahar; Dinstein, Ilan


    Numerous studies have attempted to identify early physiological abnormalities in infants and toddlers who later develop autism spectrum disorder (ASD). One potential measure of early neurophysiology is the auditory brainstem response (ABR), which has been reported to exhibit prolonged latencies in children with ASD. We examined whether prolonged ABR latencies appear in infancy, before the onset of ASD symptoms, and irrespective of hearing thresholds. To determine how early in development these differences appear, we retrospectively examined clinical ABR recordings of infants who were later diagnosed with ASD. Of the 118 children in the participant pool, 48 were excluded due to elevated ABR thresholds, genetic aberrations, or old testing age, leaving a sample of 70 children: 30 of which were tested at 0–3 months, and 40 were tested at toddlerhood (1.5–3.5 years). In the infant group, the ABR wave‐V was significantly prolonged in those who later developed ASD as compared with case‐matched controls (n = 30). Classification of infants who later developed ASD and case‐matched controls using this measure enabled accurate identification of ASD infants with 80% specificity and 70% sensitivity. In the group of toddlers with ASD, absolute and interpeak latencies were prolonged compared to clinical norms. Findings indicate that ABR latencies are significantly prolonged in infants who are later diagnosed with ASD irrespective of their hearing thresholds; suggesting that abnormal responses might be detected soon after birth. Further research is needed to determine if ABR might be a valid marker for ASD risk. Autism Res 2016, 9: 689–695. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research PMID:26477791

  17. Brainstem auditory-evoked potential in Boxer dogs

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    Mariana Isa Poci Palumbo


    Full Text Available Brainstem auditory-evoked potential (BAEP has been widely used for different purposes in veterinary practice and is commonly used to identify inherited deafness and presbycusis. In this study, 43 Boxer dogs were evaluated using the BAEP. Deafness was diagnosed in 3 dogs (2 bilateral and 1 unilateral allowing the remaining 40 Boxers to be included for normative data analysis including an evaluation on the influence of age on the BAEP. The animals were divided into 2 groups of 20 Boxers each based on age. The mean age was 4.54 years (range, 1-8 in group I, and 9.83 years (range, 8.5-12 in group II. The mean latency for I, III, and V waves were 1.14 (±0.07, 2.64 (±0.11, and 3.48 (±0.10 ms in group I, and 1.20 (±0.12, 2.73 (±0.15, and 3.58 (±0.22 ms in group II, respectively. The mean inter-peak latencies for the I-III, III-V and I-V intervals were 1.50 (±0.15, 0.84 (±0.15, and 2.34 (±0.11 ms in group I, and 1.53 (±0.16, 0.85 (±0.15, and 2.38 (±0.19 ms in group II, respectively. Latencies of waves I and III were significant different between group I and II. For the I-III, III-V and I-V intervals, no significant differences were observed between the 2 groups. As far as we know, this is the first normative study of BAEP obtained from Boxer dogs.

  18. Speech Auditory Brainstem Response through hearing aid stimulation. (United States)

    Bellier, Ludovic; Veuillet, Evelyne; Vesson, Jean-François; Bouchet, Patrick; Caclin, Anne; Thai-Van, Hung


    Millions of people across the world are hearing impaired, and rely on hearing aids to improve their everyday life. Objective audiometry could optimize hearing aid fitting, and is of particular interest for non-communicative patients. Speech Auditory Brainstem Response (speech ABR), a fine electrophysiological marker of speech encoding, is presently seen as a promising candidate for implementing objective audiometry; yet, unlike lower-frequency auditory-evoked potentials (AEPs) such as cortical AEPs or auditory steady-state responses (ASSRs), aided-speech ABRs (i.e., speech ABRs through hearing aid stimulation) have almost never been recorded. This may be due to their high-frequency components requesting a high temporal precision of the stimulation. We assess here a new approach to record high-quality and artifact-free speech ABR while stimulating directly through hearing aids. In 4 normal-hearing adults, we recorded speech ABR evoked by a /ba/ syllable binaurally delivered through insert earphones for quality control or through hearing aids. To assess the presence of a potential stimulus artifact, recordings were also done in mute conditions with the exact same potential sources of stimulus artifacts as in the main runs. Hearing aid stimulation led to artifact-free speech ABR in each participant, with the same quality as when using insert earphones, as shown with signal-to-noise (SNR) measurements. Our new approach consisting in directly transmitting speech stimuli through hearing aids allowed for a perfect temporal precision mandatory in speech ABR recordings, and could thus constitute a decisive step in hearing impairment investigation and in hearing aid fitting improvement. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Localization of the brainstem GABAergic neurons controlling paradoxical (REM) sleep. (United States)

    Sapin, Emilie; Lapray, Damien; Bérod, Anne; Goutagny, Romain; Léger, Lucienne; Ravassard, Pascal; Clément, Olivier; Hanriot, Lucie; Fort, Patrice; Luppi, Pierre-Hervé


    Paradoxical sleep (PS) is a state characterized by cortical activation, rapid eye movements and muscle atonia. Fifty years after its discovery, the neuronal network responsible for the genesis of PS has been only partially identified. We recently proposed that GABAergic neurons would have a pivotal role in that network. To localize these GABAergic neurons, we combined immunohistochemical detection of Fos with non-radioactive in situ hybridization of GAD67 mRNA (GABA synthesis enzyme) in control rats, rats deprived of PS for 72 h and rats allowed to recover after such deprivation. Here we show that GABAergic neurons gating PS (PS-off neurons) are principally located in the ventrolateral periaqueductal gray (vlPAG) and the dorsal part of the deep mesencephalic reticular nucleus immediately ventral to it (dDpMe). Furthermore, iontophoretic application of muscimol for 20 min in this area in head-restrained rats induced a strong and significant increase in PS quantities compared to saline. In addition, we found a large number of GABAergic PS-on neurons in the vlPAG/dDPMe region and the medullary reticular nuclei known to generate muscle atonia during PS. Finally, we showed that PS-on neurons triggering PS localized in the SLD are not GABAergic. Altogether, our results indicate that multiple populations of PS-on GABAergic neurons are distributed in the brainstem while only one population of PS-off GABAergic neurons localized in the vlPAG/dDpMe region exist. From these results, we propose a revised model for PS control in which GABAergic PS-on and PS-off neurons localized in the vlPAG/dDPMe region play leading roles.

  20. Localization of the brainstem GABAergic neurons controlling paradoxical (REM sleep.

    Directory of Open Access Journals (Sweden)

    Emilie Sapin

    Full Text Available Paradoxical sleep (PS is a state characterized by cortical activation, rapid eye movements and muscle atonia. Fifty years after its discovery, the neuronal network responsible for the genesis of PS has been only partially identified. We recently proposed that GABAergic neurons would have a pivotal role in that network. To localize these GABAergic neurons, we combined immunohistochemical detection of Fos with non-radioactive in situ hybridization of GAD67 mRNA (GABA synthesis enzyme in control rats, rats deprived of PS for 72 h and rats allowed to recover after such deprivation. Here we show that GABAergic neurons gating PS (PS-off neurons are principally located in the ventrolateral periaqueductal gray (vlPAG and the dorsal part of the deep mesencephalic reticular nucleus immediately ventral to it (dDpMe. Furthermore, iontophoretic application of muscimol for 20 min in this area in head-restrained rats induced a strong and significant increase in PS quantities compared to saline. In addition, we found a large number of GABAergic PS-on neurons in the vlPAG/dDPMe region and the medullary reticular nuclei known to generate muscle atonia during PS. Finally, we showed that PS-on neurons triggering PS localized in the SLD are not GABAergic. Altogether, our results indicate that multiple populations of PS-on GABAergic neurons are distributed in the brainstem while only one population of PS-off GABAergic neurons localized in the vlPAG/dDpMe region exist. From these results, we propose a revised model for PS control in which GABAergic PS-on and PS-off neurons localized in the vlPAG/dDPMe region play leading roles.

  1. Physiological brainstem mechanisms of trigeminal nociception: An fMRI study at 3T. (United States)

    Schulte, Laura H; Sprenger, Christian; May, Arne


    The brainstem is a major site of processing and modulation of nociceptive input and plays a key role in the pathophysiology of various headache disorders. However, human imaging studies on brainstem function following trigeminal nociceptive stimulation are scarce as brainstem specific imaging approaches have to address multiple challenges such as magnetic field inhomogeneities and an enhanced level of physiological noise. In this study we used a viable protocol for brainstem fMRI of standardized trigeminal nociceptive stimulation to achieve detailed insight into physiological brainstem mechanisms of trigeminal nociception. We conducted a study of 21 healthy participants using a nociceptive ammonia stimulation of the left nasal mucosa with an optimized MR acquisition protocol for high resolution brainstem echoplanar imaging in combination with two different noise correction techniques. Significant BOLD responses to noxious ammonia stimulation were observed in areas typically involved in trigeminal nociceptive processing such as the spinal trigeminal nuclei (sTN), thalamus, secondary somatosensory cortex, insular cortex and cerebellum as well as in a pain modulating network including the periaqueductal gray area, hypothalamus (HT), locus coeruleus and cuneiform nucleus (CNF). Activations of the left CNF were positively correlated with pain intensity ratings. Employing psychophysiological interaction (PPI) analysis we found enhanced functional connectivity of the sTN with the contralateral sTN and HT following trigeminal nociception. We also observed enhanced functional connectivity of the CNF with the RVM during painful stimulation thus implying an important role of these two brainstem regions in central pain processing. The chosen approach to study trigeminal nociception with high-resolution fMRI offers new insight into human pain processing and might thus lead to a better understanding of headache pathophysiology. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Revised Nomenclature for Avian Telencephalon and Some Related Brainstem Nuclei (United States)



    The standard nomenclature that has been used for many telencephalic and related brainstem structures in birds is based on flawed assumptions of homology to mammals. In particular, the outdated terminology implies that most of the avian telencephalon is a hypertrophied basal ganglia, when it is now clear that most of the avian telencephalon is neurochemically, hodologically, and functionally comparable to the mammalian neocortex, claustrum, and pallial amygdala (all of which derive from the pallial sector of the developing telencephalon). Recognizing that this promotes misunderstanding of the functional organization of avian brains and their evolutionary relationship to mammalian brains, avian brain specialists began discussions to rectify this problem, culminating in the Avian Brain Nomenclature Forum held at Duke University in July 2002, which approved a new terminology for avian telencephalon and some allied brainstem cell groups. Details of this new terminology are presented here, as is a rationale for each name change and evidence for any homologies implied by the new names. Revisions for the brainstem focused on vocal control, catecholaminergic, cholinergic, and basal ganglia-related nuclei. For example, the Forum recognized that the hypoglossal nucleus had been incorrectly identified as the nucleus intermedius in the Karten and Hodos (1967) pigeon brain atlas, and what was identified as the hypoglossal nucleus in that atlas should instead be called the supraspinal nucleus. The locus ceruleus of this and other avian atlases was noted to consist of a caudal noradrenergic part homologous to the mammalian locus coeruleus and a rostral region corresponding to the mammalian A8 dopaminergic cell group. The midbrain dopaminergic cell group in birds known as the nucleus tegmenti pedunculopontinus pars compacta was recognized as homologous to the mammalian substantia nigra pars compacta and was renamed accordingly; a group of γ-aminobutyric acid (GABA)ergic neurons at

  3. Some modifications of electric circuitry for internal friction measurements of U-shape specimens


    Osamu, Yoshinari; M., KOIWA; H., Sugawara; I., SATO


    Some modifications of the electric circuitry are described for the apparatus of the internal friction measurement of thin wire specimens; the apparatus has been developed by Franklin et al. The improved apparatus has been successfully used in the internal friction measurements of cold‐worked vanadium specimens.

  4. Analysis and simulation of the SLD WIC (Warm Iron Calorimeter) PADS hybrid preamplifier circuitry

    Energy Technology Data Exchange (ETDEWEB)

    Fox, J.D.; Horelick, D.


    The SLD PADS electronics consist of over 9000 channels of charge-sensitive preamplifiers followed by integrated sample/hold data storage, digitizing, and readout circuitry. This paper uses computer simulation techniques to analyze critical performance parameters of the preamplifier hybrid including its interactions with the detector system. Simulation results are presented and verified with measured performance. 6 refs., 9 figs.

  5. Synaptic defects in the spinal and neuromuscular circuitry in a mouse model of spinal muscular atrophy.

    Directory of Open Access Journals (Sweden)

    Karen K Y Ling


    Full Text Available Spinal muscular atrophy (SMA is a major genetic cause of death in childhood characterized by marked muscle weakness. To investigate mechanisms underlying motor impairment in SMA, we examined the spinal and neuromuscular circuitry governing hindlimb ambulatory behavior in SMA model mice (SMNΔ7. In the neuromuscular circuitry, we found that nearly all neuromuscular junctions (NMJs in hindlimb muscles of SMNΔ7 mice remained fully innervated at the disease end stage and were capable of eliciting muscle contraction, despite a modest reduction in quantal content. In the spinal circuitry, we observed a ∼28% loss of synapses onto spinal motoneurons in the lateral column of lumbar segments 3-5, and a significant reduction in proprioceptive sensory neurons, which may contribute to the 50% reduction in vesicular glutamate transporter 1(VGLUT1-positive synapses onto SMNΔ7 motoneurons. In addition, there was an increase in the association of activated microglia with SMNΔ7 motoneurons. Together, our results present a novel concept that synaptic defects occur at multiple levels of the spinal and neuromuscular circuitry in SMNΔ7 mice, and that proprioceptive spinal synapses could be a potential target for SMA therapy.

  6. 78 FR 41079 - Certain Semiconductor Chips With Dram Circuitry, and Modules and Products Containing Same (United States)


    ... COMMISSION Certain Semiconductor Chips With Dram Circuitry, and Modules and Products Containing Same AGENCY... invalid. The same day Nanya filed a petition for review of a number of the determinations in the ID that.... Patent Publication No. 2006/0126401 to Ba (RX-107) should or should not have the same number of legs? b...

  7. Cpeb4-mediated translational regulatory circuitry controls terminal erythroid differentiation. (United States)

    Hu, Wenqian; Yuan, Bingbing; Lodish, Harvey F


    While we have considerable understanding of the transcriptional networks controlling mammalian cell differentiation, our knowledge of posttranscriptional regulatory events is very limited. Using differentiation of primary erythroid cells as a model, we show that the sequence-specific mRNA-binding protein Cpeb4 is strongly induced by the erythroid-important transcription factors Gata1 and Tal1 and is essential for terminal erythropoiesis. By interacting with the translation initiation factor eIF3, Cpeb4 represses the translation of a large set of mRNAs, including its own mRNA. Thus, transcriptional induction and translational repression combine to form a negative feedback loop to control Cpeb4 protein levels within a specific range that is required for terminal erythropoiesis. Our study provides an example of how translational control is integrated with transcriptional regulation to precisely control gene expression during mammalian cell differentiation. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Mild Cognitive Impairment Is Characterized by Deficient Brainstem and Cortical Representations of Speech. (United States)

    Bidelman, Gavin M; Lowther, Jill E; Tak, Sunghee H; Alain, Claude


    Mild cognitive impairment (MCI) is recognized as a transitional phase in the progression toward more severe forms of dementia and is an early precursor to Alzheimer's disease. Previous neuroimaging studies reveal that MCI is associated with aberrant sensory-perceptual processing in cortical brain regions subserving auditory and language function. However, whether the pathophysiology of MCI extends to speech processing before conscious awareness (brainstem) is unknown. Using a novel electrophysiological approach, we recorded both brainstem and cortical speech-evoked brain event-related potentials (ERPs) in older, hearing-matched human listeners who did and did not present with subtle cognitive impairment revealed through behavioral neuropsychological testing. We found that MCI was associated with changes in neural speech processing characterized as hypersensitivity (larger) brainstem and cortical speech encoding in MCI compared with controls in the absence of any perceptual speech deficits. Group differences also interacted with age differentially across the auditory pathway; brainstem responses became larger and cortical ERPs smaller with advancing age. Multivariate classification revealed that dual brainstem-cortical speech activity correctly identified MCI listeners with 80% accuracy, suggesting its application as a biomarker of early cognitive decline. Brainstem responses were also a more robust predictor of individuals' MCI severity than cortical activity. Our findings suggest that MCI is associated with poorer encoding and transfer of speech signals between functional levels of the auditory system and advance the pathophysiological understanding of cognitive aging by identifying subcortical deficits in auditory sensory processing mere milliseconds (declines in communication skills. Whether MCI pathophysiology extends below cerebral cortex to affect speech processing before conscious awareness (brainstem) is unknown. By recording neuroelectric brain activity to

  9. Macrovascular Decompression of the Brainstem and Cranial Nerves: Evolution of an Anteromedial Vertebrobasilar Artery Transposition Technique. (United States)

    Choudhri, Omar; Connolly, Ian D; Lawton, Michael T


    Tortuous and dolichoectatic vertebrobasilar arteries can impinge on the brainstem and cranial nerves to cause compression syndromes. Transposition techniques are often required to decompress the brainstem with dolichoectatic pathology. We describe our evolution of an anteromedial transposition technique and its efficacy in decompressing the brainstem and relieving symptoms. To present the anteromedial vertebrobasilar artery transposition technique for macrovascular decompression of the brainstem and cranial nerves. All patients who underwent vertebrobasilar artery transposition were identified from the prospectively maintained database of the Vascular Neurosurgery service, and their medical records were reviewed retrospectively. The extent of arterial displacement was measured pre- and postoperatively on imaging. Vertebrobasilar arterial transposition and macrovascular decompression was performed in 12 patients. Evolution in technique was characterized by gradual preference for the far-lateral approach, use of a sling technique with muslin wrap, and an anteromedial direction of pull on the vertebrobasilar artery with clip-assisted tethering to the clival dura. With this technique, mean lateral displacement decreased from 6.6 mm in the first half of the series to 3.8 mm in the last half of the series, and mean anterior displacement increased from 0.8 to 2.5 mm, with corresponding increases in satisfaction and relief of symptoms. Compressive dolichoectatic pathology directed laterally into cranial nerves and posteriorly into the brainstem can be corrected with anteromedial transposition towards the clivus. Our technique accomplishes this anteromedial transposition from an inferolateral surgical approach through the vagoaccessory triangle, with sling fixation to clival dura using aneurysm clips.

  10. Dyslexia risk gene relates to representation of sound in the auditory brainstem. (United States)

    Neef, Nicole E; Müller, Bent; Liebig, Johanna; Schaadt, Gesa; Grigutsch, Maren; Gunter, Thomas C; Wilcke, Arndt; Kirsten, Holger; Skeide, Michael A; Kraft, Indra; Kraus, Nina; Emmrich, Frank; Brauer, Jens; Boltze, Johannes; Friederici, Angela D


    Dyslexia is a reading disorder with strong associations with KIAA0319 and DCDC2. Both genes play a functional role in spike time precision of neurons. Strikingly, poor readers show an imprecise encoding of fast transients of speech in the auditory brainstem. Whether dyslexia risk genes are related to the quality of sound encoding in the auditory brainstem remains to be investigated. Here, we quantified the response consistency of speech-evoked brainstem responses to the acoustically presented syllable [da] in 159 genotyped, literate and preliterate children. When controlling for age, sex, familial risk and intelligence, partial correlation analyses associated a higher dyslexia risk loading with KIAA0319 with noisier responses. In contrast, a higher risk loading with DCDC2 was associated with a trend towards more stable responses. These results suggest that unstable representation of sound, and thus, reduced neural discrimination ability of stop consonants, occurred in genotypes carrying a higher amount of KIAA0319 risk alleles. Current data provide the first evidence that the dyslexia-associated gene KIAA0319 can alter brainstem responses and impair phoneme processing in the auditory brainstem. This brain-gene relationship provides insight into the complex relationships between phenotype and genotype thereby improving the understanding of the dyslexia-inherent complex multifactorial condition. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Neonatal neurological disorders involving the brainstem: neurosonographic approaches through the squamous suture and the foramen magnum

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    Tu, Yi-Fang [National Cheng Kung University Hospital, Department of Emergency Medicine, Tainan (Taiwan); Chen, Cheng-Yu [National Defense Medical Center, Department of Radiology, Taipei (Taiwan); Lin, Yuh-Jey [National Cheng Kung University Hospital, Department of Pediatrics, Tainan (Taiwan); Chang, Ying-Chao [Kaohsiung Chang Gung Children Hospital, Department of Pediatrics, Kaohsiung (Taiwan); Huang, Chao-Ching [National Cheng Kung University Hospital, Department of Pediatrics, Tainan (Taiwan); National Cheng Kung University Hospital, Department of Institute of Molecular Medicine, Tainan (Taiwan)


    Brainstem damage which often indicates a critical condition is usually underestimated by trans-anterior-fontanel neurosonography (NS) owing to the far-field limitations. Instead, NS alternately scanning through the squamous suture of the temporal bones and the foramen magnum could provide a better visualization of the brainstem structures. The NS characteristics of brainstem lesions caused by various neonatal neurological disorders, such as hypoxic-ischemic encephalopathy (HIE), metabolic encephalopathy, birth trauma and bacterial meningoencephalitis, can be depicted at the acute stage. An echogenic change in the midbrain was found in patients with HIE or metabolic encephalopathy. In addition to the echogenic change, bilateral transtentorial temporal lobe herniation distorting the contour of the midbrain was observed in a patient with group B streptococcus meningoencephalitis, whereas echogenic changes at the level of the pons and/or the medulla oblongata, mainly localized in the dorsal part, could be observed in newborns with severe HIE, maple syrup urine disease or birth trauma. In this pictorial assay, we demonstrate the feasibility of NS imaging in evaluating the entire brainstem structure of critically ill neonates in the near field and illustrate the characteristic features of brainstem involvement in various neonatal neurological disorders along with computed tomography or magnetic resonance imaging correlation. (orig.)

  12. Impairments in musical abilities reflected in the auditory brainstem: evidence from congenital amusia. (United States)

    Lehmann, Alexandre; Skoe, Erika; Moreau, Patricia; Peretz, Isabelle; Kraus, Nina


    Congenital amusia is a neurogenetic condition, characterized by a deficit in music perception and production, not explained by hearing loss, brain damage or lack of exposure to music. Despite inferior musical performance, amusics exhibit normal auditory cortical responses, with abnormal neural correlates suggested to lie beyond auditory cortices. Here we show, using auditory brainstem responses to complex sounds in humans, that fine-grained automatic processing of sounds is impoverished in amusia. Compared with matched non-musician controls, spectral amplitude was decreased in amusics for higher harmonic components of the auditory brainstem response. We also found a delayed response to the early transient aspects of the auditory stimulus in amusics. Neural measures of spectral amplitude and response timing correlated with participants' behavioral assessments of music processing. We demonstrate, for the first time, that amusia affects how complex acoustic signals are processed in the auditory brainstem. This neural signature of amusia mirrors what is observed in musicians, such that the aspects of the auditory brainstem responses that are enhanced in musicians are degraded in amusics. By showing that gradients of music abilities are reflected in the auditory brainstem, our findings have implications not only for current models of amusia but also for auditory functioning in general. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  13. Auditory Brainstem Responses in Autistic Children in Comparison with Normal Children

    Directory of Open Access Journals (Sweden)

    Saeed Sarough Farahani


    Full Text Available Background and Aim: One of the most important problems of children who suffer from autism is abnormality in receiving and integrating sensory inputs, especially hearing input. It has been shown that brainstem has a key role in receiving, encoding and integrating hearing input. Auditory brainstem response (ABR is a tool by which we can evaluate this function. The purpose of this study was to assess and to compare autistic and normal children brainstem hearing function. Materials and Methods: This case-control study was conducted on thirty (58 ears autistic and thirty (57 ears normal 6-12 years old children. The children with autism were divided into slight and severe subgroups according to Autism Diagnostic Interview-Revised questionnaire. Click-evoked ABR was recorded and compared between groups. Results: There was significant difference between two groups V and III wave latencies and I-III and I-V interpeak latencies (p<0.05. In fact, comparison of the results of autism subgroups with normal children indicated that the latencies of the severe subgroup significantly prolonged. Conclusion: Increasing latencies of ABR waves in severe subgroup maybe due to abnormality in low level of brainstem. Brainstem abnormality may result in exacerbating the symptom of autism. It is therefore suggested that ABR is included in diagnostic test batteries for these patients.

  14. Abnormal trajectories in cerebellum and brainstem volumes in carriers of the fragile X premutation. (United States)

    Wang, Jun Yi; Hessl, David; Hagerman, Randi J; Simon, Tony J; Tassone, Flora; Ferrer, Emilio; Rivera, Susan M


    Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder typically affecting male premutation carriers with 55-200 CGG trinucleotide repeat expansions in the FMR1 gene after age 50. The aim of this study was to examine whether cerebellar and brainstem changes emerge during development or aging in late life. We retrospectively analyzed magnetic resonance imaging scans from 322 males (age 8-81 years). Volume changes in the cerebellum and brainstem were contrasted with those in the ventricles and whole brain. Compared to the controls, premutation carriers without FXTAS showed significantly accelerated volume decrease in the cerebellum and whole brain, flatter inverted U-shaped trajectory of the brainstem, and larger ventricles. Compared to both older controls and premutation carriers without FXTAS, carriers with FXTAS exhibited significant volume decrease in the cerebellum and whole brain and accelerated volume decrease in the brainstem. We therefore conclude that cerebellar and brainstem volumes were likely affected during both development and progression of neurodegeneration in premutation carriers, suggesting that interventions may need to start early in adulthood to be most effective. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Stereotactic Radiosurgery for Brainstem Metastases: An International Cooperative Study to Define Response and Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Trifiletti, Daniel M., E-mail: [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia (United States); Lee, Cheng-Chia [Department of Neurosurgery, Neurological Institute, Taipei Veteran General Hospital, Taipei, Taiwan (China); Kano, Hideyuki; Cohen, Jonathan [Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (United States); Janopaul-Naylor, James; Alonso-Basanta, Michelle; Lee, John Y.K. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Simonova, Gabriela; Liscak, Roman [Department of Radiation and Stereotactic Neurosurgery, Na Homolce Hospital, Prague (Czech Republic); Wolf, Amparo; Kvint, Svetlana [Department of Neurosurgery, New York University Lagone Medical Center, New York, New York (United States); Grills, Inga S.; Johnson, Matthew [Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan (United States); Liu, Kang-Du; Lin, Chung-Jung [Department of Neurosurgery, Neurological Institute, Taipei Veteran General Hospital, Taipei, Taiwan (China); Mathieu, David; Héroux, France [Division of Neurosurgery, Université de Sherbrooke, Centre de recherche du CHUS, Sherbrooke, Québec (Canada); Silva, Danilo; Sharma, Mayur [Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio (United States); Cifarelli, Christopher P. [Departments of Neurosurgery and Radiation Oncology, West Virginia University, Morgantown, West Virginia (United States); and others


    Purpose: To pool data across multiple institutions internationally and report on the cumulative experience of brainstem stereotactic radiosurgery (SRS). Methods and Materials: Data on patients with brainstem metastases treated with SRS were collected through the International Gamma Knife Research Foundation. Clinical, radiographic, and dosimetric characteristics were compared for factors prognostic for local control (LC) and overall survival (OS) using univariate and multivariate analyses. Results: Of 547 patients with 596 brainstem metastases treated with SRS, treatment of 7.4% of tumors resulted in severe SRS-induced toxicity (grade ≥3, increased odds with increasing tumor volume, margin dose, and whole-brain irradiation). Local control at 12 months after SRS was 81.8% and was improved with increasing margin dose and maximum dose. Overall survival at 12 months after SRS was 32.7% and impacted by age, gender, number of metastases, tumor histology, and performance score. Conclusions: Our study provides additional evidence that SRS has become an option for patients with brainstem metastases, with an excellent benefit-to-risk ratio in the hands of experienced clinicians. Prior whole-brain irradiation increases the risk of severe toxicity in brainstem metastasis patients undergoing SRS.

  16. Brainstem cavernous malformations resected via miniature craniotomies: technique and approach selection. (United States)

    Maurer, Adrian J; Bonney, Phillip A; Strickland, Allison E; Safavi-Abbasi, Sam; Sughrue, Michael E


    Brainstem cavernous malformations can cause devastating neurologic disability when they hemorrhage, which occurs at a higher rate in the brainstem than in other locations. Traditional access to these lesions requires a large craniotomy with extensive exposure and manipulation of vital structures. We present a case series of patients who underwent surgical resection of brainstem cavernous malformations using minimally invasive approaches at our institution from January 2012 to August 2014, all of whom had experienced at least one hemorrhage prior to presentation. Approach choice was determined by location of the cavernous malformation in relation to the brainstem surface. Resection occurred through our described standardized method. Postoperatively, there were three instances of transient neurologic symptoms, all of which resolved at time of last follow-up. All eight patients experienced neurologic improvement after surgery, with four patients showing no deficits at last follow-up. Approach selection rationale and technical nuances are presented on a case-by-case basis. With carefully planned keyhole approaches to cavernous malformations presenting to the brainstem surface, excellent results may be achieved without the necessity of larger conventional craniotomies. We believe the nuances presented may be of use to others in the surgical treatment of these lesions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. A Role for the Lateral Dorsal Tegmentum in Memory and Decision Neural Circuitry (United States)

    Redila, Van; Kinzel, Chantelle; Jo, Yong Sang; Puryear, Corey B.; Mizumori, Sheri J.Y.


    A role for the hippocampus in memory is clear, although the mechanism for its contribution remains a matter of debate. Converging evidence suggests that hippocampus evaluates the extent to which context-defining features of events occur as expected. The consequence of mismatches, or prediction error, signals from hippocampus is discussed in terms of its impact on neural circuitry that evaluates the significance of prediction errors: Ventral tegmental area (VTA) dopamine cells burst fire to rewards or cues that predict rewards (Schultz et al., 1997). Although the lateral dorsal tegmentum (LDTg) importantly controls dopamine cell burst firing (Lodge & Grace, 2006) the behavioral significance of the LDTg control is not known. Therefore, we evaluated LDTg functional activity as rats performed a spatial memory task that generates task-dependent reward codes in VTA (Jo et al., 2013; Puryear et al., 2010) and another VTA afferent, the pedunculopontine nucleus (PPTg, Norton et al., 2011). Reversible inactivation of the LDTg significantly impaired choice accuracy. LDTg neurons coded primarily egocentric information in the form of movement velocity, turning behaviors, and behaviors leading up to expected reward locations. A subset of the velocity-tuned LDTg cells also showed high frequency bursts shortly before or after reward encounters, after which they showed tonic elevated firing during consumption of small, but not large, rewards. Cells that fired before reward encounters showed stronger correlations with velocity as rats moved toward, rather than away from, rewarded sites. LDTg neural activity was more strongly regulated by egocentric behaviors than that observed for PPTg or VTA cells that were recorded by Puryear et al. and Norton et al. While PPTg activity was uniquely sensitive to ongoing sensory input, all three regions encoded reward magnitude (although in different ways), reward expectation, and reward encounters. Only VTA encoded reward prediction errors. LDTg

  18. Correlation of Acute and Late Brainstem Toxicities With Dose-Volume Data for Pediatric Patients With Posterior Fossa Malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Nanda, Ronica H., E-mail: [Department of Radiation Oncology, Winship Cancer Institute, Emory University College of Medicine, Atlanta, Georgia (United States); Ganju, Rohit G.; Schreibmann, Edward [Department of Radiation Oncology, Winship Cancer Institute, Emory University College of Medicine, Atlanta, Georgia (United States); Chen, Zhengjia; Zhang, Chao [Department of Biostatistics and Bioinformatics Shared Resource, Winship Cancer Institute, Emory University Rollins School of Public Health, Atlanta, Georgia (United States); Jegadeesh, Naresh; Cassidy, Richard; Deng, Claudia; Eaton, Bree R.; Esiashvili, Natia [Department of Radiation Oncology, Winship Cancer Institute, Emory University College of Medicine, Atlanta, Georgia (United States)


    Purpose: Radiation-induced brainstem toxicity after treatment of pediatric posterior fossa malignancies is incompletely understood, especially in the era of intensity modulated radiation therapy (IMRT). The rates of, and predictive factors for, brainstem toxicity after photon RT for posterior fossa tumors were examined. Methods and Materials: After institutional review board approval, 60 pediatric patients treated at our institution for nonmetastatic infratentorial ependymoma and medulloblastoma with IMRT were included in the present analysis. Dosimetric variables, including the mean and maximum dose to the brainstem, the dose to 10% to 90% of the brainstem (in 10% increments), and the volume of the brainstem receiving 40, 45, 50, and 55 Gy were recorded for each patient. Acute (onset within 3 months) and late (>3 months of RT completion) RT-induced brainstem toxicities with clinical and radiographic correlates were scored using Common Terminology Criteria for Adverse Events, version 4.0. Results: Patients aged 1.4 to 21.8 years underwent IMRT or volumetric arc therapy postoperatively to the posterior fossa or tumor bed. At a median clinical follow-up period of 2.8 years, 14 patients had developed symptomatic brainstem toxicity (crude incidence 23.3%). No correlation was found between the dosimetric variables examined and brainstem toxicity. Vascular injury or ischemia showed a strong trend toward predicting brainstem toxicity (P=.054). Patients with grade 3 to 5 brainstem toxicity had undergone treatment to significant volumes of the posterior fossa. Conclusion: The results of the present series demonstrate a low, but not negligible, risk of brainstem radiation necrosis for pediatric patients with posterior fossa malignancies treated with IMRT. No specific dose-volume correlations were identified; however, modern treatment volumes might help limit the incidence of severe toxicity. Additional work investigating inherent biologic sensitivity might also provide

  19. Congenital Trismus From Brainstem Dysgenesis: Case Report and Review of Literature. (United States)

    Hong, Chris J; Caulley, Lisa; Kohlert, Scott; Graham, Gail E; McMillan, Hugh J; Michaud, Jean; Vaccani, Jean-Philippe


    Trismus refers to any condition inducing limited mouth opening and may present as a result of acquired or congenital pathology. We present the case of a newborn who presented with severe, congenital trismus due to brainstem dysgenesis. We describe the course of his investigations, and a multidisciplinary approach to the management of his care and follow-up. To our knowledge, this is one of the earliest reported cases of congenital trismus attributable to brainstem dysgenesis. A literature review was conducted to provide an overview of the differential pathogenesis as it presents in congenital cases and discuss the complexity of managing congenital trismus due to brainstem dysgenesis in a neonate and infant. Copyright © 2016 by the American Academy of Pediatrics.

  20. Pathophysiological mechanism of ipsilateral cerebral and brainstem hemiatrophy in basal ganglia germ cell tumors: case report. (United States)

    Wong, Sui-To; Yuen, Shing-Chau; Fong, Dawson


    The basal ganglia is an uncommon location for germ cell tumors. It has been reported that basal ganglia germinomas and mixed germ cell tumors are associated with ipsilateral cerebral and brainstem hemiatrophy on presentation. Several pathophysiological mechanisms including autoimmune process and direct tumor infiltration of the thalamus or the internal capsule have been postulated to explain this association. The authors report two boys, aged 7 and 10, with basal ganglia germ cell tumors. Both of them presented with gradual onset of hemiparesis and had features of ipsilateral cerebral and brainstem hemiatrophy on imaging studies. They underwent chemotherapy followed by reduced dose radiotherapy with good response. Pathophysiological mechanisms of the associated ipsilateral cerebral and brainstem hemiatrophy are discussed. The authors postulate that the gradual obliteration of the perforating arteries to the diencephalon especially the lenticulostriate arteries of the prebifurcation middle cerebral artery may be the major mechanism of the associated hemiatrophy.

  1. Surgical Approaches for Symptomatic Cerebral Cavernous Malformations of the Thalamus and Brainstem (United States)

    Starke, Robert M.; Crowley, R. Webster; Liu, Kenneth C.


    Objective Surgical resection of thalamic and brainstem cerebral cavernous malformations (CCMs) is associated with significant operative morbidity, but it may be outweighed, in some cases, by the neurological damage from recurrent hemorrhage in these eloquent areas. The goals of this retrospective cohort study are to describe the technical nuances of surgical approaches and determine the postoperative outcomes for CCMs of the thalamus and brainstem. Materials and Methods We reviewed an institutional database of patients harboring thalamic or brainstem CCMs, who underwent surgical resection from 2010 to 2014. The baseline and follow-up neuroimaging and clinical findings of each patient and the operative details of each case were evaluated. Results A total of eight patients, including two with thalamic and six with brainstem CCMs, were included in the study cohort. All patients had progressive neurological deterioration from recurrent CCM hemorrhage, and the median modified Rankin Scale (mRS) at presentation was 3. The median CCM maximum diameter and volume were 1.7 cm and 1.8 cm3, respectively. The thalamic CCMs were resected using the anterior transcallosal transchoroidal and supracerebellar infratentorial approaches each in one case (13%). The brainstem CCMs were resected using the retrosigmoid and suboccipital trans-cerebellomedullary fissure approaches each in three cases (38%). After a median follow-up of 11.5 months, all patients were neurologically stable or improved, with a median mRS of 2. The rate of functional independence (mRS 0-2) was 63%. Conclusion Microneurosurgical techniques and approaches can be safely and effectively employed for the management of thalamic and brainstem CCMs in appropriately selected patients. PMID:28503485

  2. A micromechanical procedure for viscoelastic characterization of the axons and ECM of the brainstem. (United States)

    Javid, Samad; Rezaei, Asghar; Karami, Ghodrat


    In this study, the optimal viscoelastic material parameters of axon and extracellular matrix (ECM) in porcine brain white matter were identified using a genetic algorithm (GA) optimization procedure. The procedure was combined with micromechanical finite element analysis (FEA) of brain tissue and experimental stress relaxation tests on brainstem specimens to find the optimal material coefficients of axon and ECM. The stress relaxation tests were performed in tension on 10 brainstem specimens at 3% strain level. The axonal volume fraction in brainstem was measured from the Scanning Electron Microscopy images of the brain tissue. A square periodic volume element was selected to represent the microscale homogenized brainstem tissue. Periodic boundary conditions were applied on the square volume element to mimics the repetitive nature of the volume element. Linear viscoelastic material properties were assumed for the brain tissue constituents under small deformation. The constitutive behavior was expressed in terms of Prony series. The GA procedure searched for the optimal material parameters by fitting the time-dependent tissue stresses of brain tissue FEA to the stresses of relaxation tests under the same loading conditions. The optimization procedure converged after 60 iterations. The initial elastic modulus of axon was found to be 12.86kPa, three times larger than that of ECM. The long-term elastic modulus of axon was 3.7kPa, while for ECM this value was 1.03kPa. The concordance correlation coefficient between FEA estimated elastic modulus of brainstem tissue using the optimal material properties and the experimental elastic modulus of brainstem specimens was 0.952, showing a strong agreement. The optimal material properties of brain tissue constituents can find applications in micromechanical analysis of brain tissue to gain insight into diffuse axonal injures (DAIs). © 2013 Published by Elsevier Ltd.

  3. Delayed Brainstem Hemorrhage Secondary to Mild Traumatic Head Injury: Report of Case with Good Recovery. (United States)

    Hou, Kun; Zhao, Jinchuan; Gao, Xianfeng; Zhu, Xiaobo; Li, Guichen


    In clinical practice, secondary traumatic brainstem hemorrhage often develops during descending transtentorial herniation due to raised intracranial pressure, which is known as Duret hemorrhage. Although usually considered a fatal and irreversible event, in rare circumstances, victims of Duret hemorrhage could gain favorable outcomes. To our knowledge, secondary brainstem hemorrhage due to mild traumatic head injury without descending transtentorial herniation has never been reported. In this report, we present a case of delayed brainstem hemorrhage secondary to a relatively mild traumatic brain injury that experienced a rapid and favorable recovery. A 48-year-old man was admitted for a motorcycle accident. Head computed tomography 2 hours after the accident revealed mild subarachnoid hemorrhage at the interpeduncular cistern. In the following in-hospital days, he experienced 2 episodes of mental state deterioration and increase of the SAH and hematoma extension to the brainstem. A digital subtraction angiography was performed with no positive finding of vascular anomaly and evident cerebral vasospasm. He experienced a rapid and favorable recovery. His Glasgow Outcome Scale score was 5 at 3 months' follow-up. We present a rare case of secondary traumatic brainstem hemorrhage that experienced a rapid and good recovery process. The mechanism is still obscure to us and needs to be further studied. Although traumatic brainstem hemorrhage usually means a fatal event to most of the patients, some patients may experience a favorable recovery. This rare circumstance should be stressed in prognosis consultation and clinical management of these kinds of patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Convection enhanced delivery of carmustine to the murine brainstem: a feasibility study. (United States)

    Sewing, A Charlotte P; Caretti, Viola; Lagerweij, Tonny; Schellen, Pepijn; Jansen, Marc H A; van Vuurden, Dannis G; Idema, Sander; Molthoff, Carla F M; Vandertop, W Peter; Kaspers, Gertjan J L; Noske, David P; Hulleman, Esther


    Systemic delivery of therapeutic agents remains ineffective against diffuse intrinsic pontine glioma (DIPG), possibly due to an intact blood-brain-barrier (BBB) and to dose-limiting toxicity of systemic chemotherapeutic agents. Convection-enhanced delivery (CED) into the brainstem may provide an effective local delivery alternative for DIPG patients. The aim of this study is to develop a method to perform CED into the murine brainstem and to test this method using the chemotherapeutic agent carmustine (BiCNU). To this end, a newly designed murine CED catheter was tested in vitro and in vivo. After determination of safety and distribution, mice bearing VUMC-DIPG-3 and E98FM-DIPG brainstem tumors were treated with carmustine dissolved in DW 5% or carmustine dissolved in 10% ethanol. Our results show that CED into the murine brainstem is feasible and well tolerated by mice with and without brainstem tumors. CED of carmustine dissolved in 5% DW increased median survival of mice with VUMC-DIPG-3 and E98FM-DIPG tumors with 35% and 25% respectively. Dissolving carmustine in 10% ethanol further improved survival to 45% in mice with E98FM-DIPG tumors. Since genetically engineered and primary DIPG models are currently only available in mice, murine CED studies have clear advantages over CED studies in other animals. CED in the murine brainstem can be performed safely, is well tolerated and can be used to study efficacy of chemotherapeutic agents orthotopically. These results set the foundation for more CED studies in murine DIPG models. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. [Forensic application of brainstem auditory evoked potential in patients with brain concussion]. (United States)

    Zheng, Xing-Bin; Li, Sheng-Yan; Huang, Si-Xing; Ma, Ke-Xin


    To investigate changes of brainstem auditory evoked potential (BAEP) in patients with brain concussion. Nineteen patients with brain concussion were studied with BAEP examination. The data was compared to the healthy persons reported in literatures. The abnormal rate of BAEP for patients with brain concussion was 89.5%. There was a statistically significant difference between the abnormal rate of patients and that of healthy persons (Pbrain concussion was 73.7%, indicating dysfunction of the brainstem in those patients. BAEP might be helpful in forensic diagnosis of brain concussion.

  6. Circuitry Linking the Catabolite Repression and Csr Global Regulatory Systems of Escherichia coli. (United States)

    Pannuri, Archana; Vakulskas, Christopher A; Zere, Tesfalem; McGibbon, Louise C; Edwards, Adrianne N; Georgellis, Dimitris; Babitzke, Paul; Romeo, Tony


    Cyclic AMP (cAMP) and the cAMP receptor protein (cAMP-CRP) and CsrA are the principal regulators of the catabolite repression and carbon storage global regulatory systems, respectively. cAMP-CRP controls the transcription of genes for carbohydrate metabolism and other processes in response to carbon nutritional status, while CsrA binds to diverse mRNAs and regulates translation, RNA stability, and/or transcription elongation. CsrA also binds to the regulatory small RNAs (sRNAs) CsrB and CsrC, which antagonize its activity. The BarA-UvrY two-component signal transduction system (TCS) directly activates csrB and csrC (csrB/C) transcription, while CsrA does so indirectly. We show that cAMP-CRP inhibits csrB/C transcription without negatively regulating phosphorylated UvrY (P-UvrY) or CsrA levels. A crp deletion caused an elevation in CsrB/C levels in the stationary phase of growth and increased the expression of csrB-lacZ and csrC-lacZ transcriptional fusions, although modest stimulation of CsrB/C turnover by the crp deletion partially masked the former effects. DNase I footprinting and other studies demonstrated that cAMP-CRP bound specifically to three sites located upstream from the csrC promoter, two of which overlapped the P-UvrY binding site. These two proteins competed for binding at the overlapping sites. In vitro transcription-translation experiments confirmed direct repression of csrC-lacZ expression by cAMP-CRP. In contrast, cAMP-CRP effects on csrB transcription may be mediated indirectly, as it bound nonspecifically to csrB DNA. In the reciprocal direction, CsrA bound to crp mRNA with high affinity and specificity and yet exhibited only modest, conditional effects on expression. Our findings are incorporated into an emerging model for the response of Csr circuitry to carbon nutritional status. Csr (Rsm) noncoding small RNAs (sRNAs) CsrB and CsrC of Escherichia coli use molecular mimicry to sequester the RNA binding protein CsrA (RsmA) away from lower

  7. Functional Ear (A)Symmetry in Brainstem Neural Activity Relevant to Encoding of Voice Pitch: A Precursor for Hemispheric Specialization? (United States)

    Krishnan, Ananthanarayan; Gandour, Jackson T.; Ananthakrishnan, Saradha; Bidelman, Gavin M.; Smalt, Christopher J.


    Pitch processing is lateralized to the right hemisphere; linguistic pitch is further mediated by left cortical areas. This experiment investigates whether ear asymmetries vary in brainstem representation of pitch depending on linguistic status. Brainstem frequency-following responses (FFRs) were elicited by monaural stimulation of the left and…

  8. Auditory brainstem response recording to multiple interleaved broadband chirps. (United States)

    Cebulla, Mario; Stürzebecher, Ekkehard; Don, Manuel; Müller-Mazzotta, Jochen


    The simultaneous application of multiple stimuli that excite different frequency regions of the cochlea is a well-established method for recording frequency-specific auditory steady state responses. Because the stimuli are applied at different repetition rates, they actually do not appear exactly simultaneously. There is always a certain time difference between the multiple frequency-specific stimuli. This is true also for multiple interleaved broadband stimuli. Therefore, because of this time difference, one may expect a successful recording of responses to multiple broadband chirp stimuli even when such stimuli activate the whole cochlear partition. This article describes a technique for recording auditory brainstem responses evoked by trains of broadband chirps presented simultaneously at equal stimulus levels but at different repetition rates. The interactions between the interleaved stimulus trains were studied to lay the foundation for a rapid method of assessing temporal aspects of peripheral auditory processing. The first step in laying this foundation is to determine the characteristics of responses from an intact and normal-hearing system to these interleaved chirp trains. Subsequently, the studied interactions between the interleaved applied stimuli may provide a referential framework for future clinical studies aimed at assessing pathological populations. Two chirp trains were applied concurrently at the same stimulus level but at different repetition rates of 20/sec and 22/sec, respectively. Two overall stimulus levels were investigated: 50 and 30 dB nHL. Because of the 2 Hz difference between the repetition rates, the time difference between the stimuli of the two stimulus trains followed a periodic cycling. The cycling period of 0.5 sec contained ten 20/sec stimuli and eleven 22/sec-stimuli. The response to a single train of chirps with the repetition rate of 20/sec was also recorded. The test group consisted of 11 young adult subjects, all with

  9. Mechanisms of Long Non-Coding RNAs in the Assembly and Plasticity of Neural Circuitry. (United States)

    Wang, Andi; Wang, Junbao; Liu, Ying; Zhou, Yan


    The mechanisms underlying development processes and functional dynamics of neural circuits are far from understood. Long non-coding RNAs (lncRNAs) have emerged as essential players in defining identities of neural cells, and in modulating neural activities. In this review, we summarized latest advances concerning roles and mechanisms of lncRNAs in assembly, maintenance and plasticity of neural circuitry, as well as lncRNAs' implications in neurological disorders. We also discussed technical advances and challenges in studying functions and mechanisms of lncRNAs in neural circuitry. Finally, we proposed that lncRNA studies would advance our understanding on how neural circuits develop and function in physiology and disease conditions.

  10. Epsilon-Near-Zero Photonics Wires for Mid-Infrared Optical Lumped Circuitry

    CERN Document Server

    Liu, Runyu; Zhong, Yujun; Podolskiy, Viktor; Wasserman, Daniel


    There has been recent interest in the development of optical analogues of lumped element circuitry, where optical elements act as effective optical inductors, capacitors, and resistors. Such optical circuitry requires the photonic equivalent of electrical wires, structures able carry optical frequency signals to and from the lumped circuit elements while simultaneously maintaining signal carrier wavelengths much larger than the size of the lumped elements. Here we demonstrate the design, fabrication, and characterization of hybrid metal/doped-semiconductor 'photonic wires' operating at optical frequencies with effective indices of propagation near-zero. Our samples are characterized by polarization and angle-dependent FTIR spectroscopy and modeled by finite element methods and rigorous coupled wave analysis. We demonstrate coupling to such photonic wires from free space, and show the effective wavelength of the excited mode to be approximately an order of magnitude larger than the free-space wavelength of our...

  11. Stitching Codeable Circuits: High School Students' Learning About Circuitry and Coding with Electronic Textiles (United States)

    Litts, Breanne K.; Kafai, Yasmin B.; Lui, Debora A.; Walker, Justice T.; Widman, Sari A.


    Learning about circuitry by connecting a battery, light bulb, and wires is a common activity in many science classrooms. In this paper, we expand students' learning about circuitry with electronic textiles, which use conductive thread instead of wires and sewable LEDs instead of lightbulbs, by integrating programming sensor inputs and light outputs and examining how the two domains interact. We implemented an electronic textiles unit with 23 high school students ages 16-17 years who learned how to craft and code circuits with the LilyPad Arduino, an electronic textile construction kit. Our analyses not only confirm significant increases in students' understanding of functional circuits but also showcase students' ability in designing and remixing program code for controlling circuits. In our discussion, we address opportunities and challenges of introducing codeable circuit design for integrating maker activities that include engineering and computing into classrooms.

  12. Functional role for cortical-striatal circuitry in modulating alcohol self-administration. (United States)

    Jaramillo, Anel A; Randall, Patrick A; Stewart, Spencer; Fortino, Brayden; Van Voorhies, Kalynn; Besheer, Joyce


    The cortical-striatal brain circuitry is heavily implicated in drug-use. As such, the present study investigated the functional role of cortical-striatal circuitry in modulating alcohol self-administration. Given that a functional role for the nucleus accumbens core (AcbC) in modulating alcohol-reinforced responding has been established, we sought to test the role of cortical brain regions with afferent projections to the AcbC: the medial prefrontal cortex (mPFC) and the insular cortex (IC). Long-Evans rats were trained to self-administer alcohol (15% alcohol (v/v)+2% sucrose (w/v)) during 30 min sessions. To test the functional role of the mPFC or IC, we utilized a chemogenetic technique (hM4D i -Designer Receptors Activation by Designer Drugs) to silence neuronal activity prior to an alcohol self-administration session. Additionally, we chemogenetically silenced mPFC→AcbC or IC→AcbC projections, to investigate the role of cortical-striatal circuitry in modulating alcohol self-administration. Chemogenetically silencing the mPFC decreased alcohol self-administration, while silencing the IC increased alcohol self-administration, an effect absent in mCherry-Controls. Interestingly, silencing mPFC→AcbC projections had no effect on alcohol self-administration. In contrast, silencing IC→AcbC projections decreased alcohol self-administration, in a reinforcer-specific manner as there was no effect in rats trained to self-administer sucrose (0.8%, w/v). Additionally, no change in self-administration was observed in the mCherry-Controls. Together these data demonstrate the complex role of the cortical-striatal circuitry while implicating a role for the insula-striatal circuit in modulating ongoing alcohol self-administration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Impulsivity and aggression in schizophrenia: a neural circuitry perspective with implications for treatment. (United States)

    Hoptman, Matthew J


    Elevations of impulsive behavior have been observed in a number of serious mental illnesses. These phenomena can lead to harmful behaviors, including violence, and thus represent a serious public health concern. Such violence is often a reason for psychiatric hospitalization, and it often leads to prolonged hospital stays, suffering by patients and their victims, and increased stigmatization. Despite the attention paid to violence, little is understood about its neural basis in schizophrenia. On a psychological level, aggression in schizophrenia has been primarily attributed to psychotic symptoms, desires for instrumental gain, or impulsive responses to perceived personal slights. Often, multiple attributions can coexist during a single aggressive incident. In this review, I discuss the neural circuitry associated with impulsivity and aggression in schizophrenia, with an emphasis on implications for treatment. Impulsivity appears to account for a great deal of aggression in schizophrenia, especially in inpatient settings. Urgency, defined as impulsivity in the context of strong emotion, is the primary focus of this article. It is elevated in several psychiatric disorders, and in schizophrenia, it has been related to aggression. Many studies have implicated dysfunctional frontotemporal circuitry in impulsivity and aggression in schizophrenia, and pharmacological treatments may act via that circuitry to reduce urgency and aggressive behaviors; however, more mechanistic studies are critically needed. Recent studies point toward manipulable neurobehavioral targets and suggest that cognitive, pharmacological, neuromodulatory, and neurofeedback treatment approaches can be developed to ameliorate urgency and aggression in schizophrenia. It is hoped that these approaches will improve treatment efficacy.

  14. Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

    Directory of Open Access Journals (Sweden)

    Dichter Gabriel S


    Full Text Available Abstract This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders, neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette’s syndrome, conduct disorder/oppositional defiant disorder, and genetic syndromes (i.e., Fragile X syndrome, Prader–Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome. We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies.

  15. Adolescent gain in positive valence of a socially relevant stimulus: engagement of the mesocorticolimbic reward circuitry. (United States)

    Bell, Margaret R; De Lorme, Kayla C; Figueira, Rayson J; Kashy, Deborah A; Sisk, Cheryl L


    A successful transition from childhood to adulthood requires adolescent maturation of social information processing. The neurobiological underpinnings of this maturational process remain elusive. This research employed the male Syrian hamster as a tractable animal model for investigating the neural circuitry involved in this critical transition. In this species, adult and juvenile males display different behavioral and neural responses to vaginal secretions, which contain pheromones essential for expression of sexual behavior in adulthood. These studies tested the hypothesis that vaginal secretions acquire positive valence over adolescent development via remodeling of neural circuits underlying sexual reward. Sexually naïve adult, but not juvenile, hamsters showed a conditioned place preference for vaginal secretions. Differences in behavioral response to vaginal secretions between juveniles and adults correlated with a difference in the vaginal secretion-induced neural activation pattern in mesocorticolimbic reward circuitry. Fos immunoreactivity increased in response to vaginal secretions in the medial amygdala and ventral tegmental dopaminergic cells of both juvenile and adult males. However, only in adults was there a Fos response to vaginal secretions in non-dopaminergic cells in interfascicular ventral tegmental area, nucleus accumbens core and infralimbic medial prefrontal cortex. These results demonstrate that a socially relevant chemosensory stimulus acquires the status of an unconditioned reward during adolescence, and that this adolescent gain in social reward is correlated with experience-independent engagement of specific cell groups in reward circuitry. © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  16. Brainstem response audiometry in the determination of low-frequency hearing loss : a study of various methods for frequency-specific ABR-threshold assessment

    NARCIS (Netherlands)

    E.A.G.J. Conijn


    textabstractBrainstem Electric Response Audiometry (BERA) is a method to visualize some of the electric activity generated in the auditory nerve and the brainstem during the processing of sound. The amplitude of the Auditory Brainstem Response (ABR) is very small (0.05-0.5 flV). The potentials

  17. Increased astrocytic expression of metallothioneins I + II in brainstem of adult rats treated with 6-aminonicotinamide

    DEFF Research Database (Denmark)

    Penkowa, Milena; Hidalgo, Juan; Moos, Torben


    The cerebral distribution of metallothioneins I and II (MT-I + II) was studied in adult rats subjected to i.p. injection with the gliotoxin 6-aminonicotinamide (6-AN). Grey matter regions of the brainstem heralded numerous OX-42-positive macrophages and microglia, indicating that 6-AN primarily c...

  18. Developmental alterations of the auditory brainstem centers--pathogenetic implications in Sudden Infant Death Syndrome. (United States)

    Lavezzi, Anna M; Ottaviani, Giulia; Matturri, Luigi


    Sudden Infant Death Syndrome (SIDS), despite the success of campaigns to reduce its risks, is the leading cause of infant death in the Western world. Even though the pathogenesis remains unexplained, brainstem abnormalities of the neuronal network that mediates breathing and protective responses to asphyxia, particularly in the arousal phase from sleep, are believed to play a fundamental role. This is the first study to identify, in SIDS, developmental defects of specific brainstem centers involved in hearing pathways, particularly in the cochlear and vestibular nuclei, in the superior olivary complex and in the inferior colliculus, suggesting a possible influence of the acoustic system on respiratory activity. In 49 SIDS cases and 20 controls an in-depth anatomopathological examination of the autonomic nervous system was performed, with the main aim of detecting developmental alterations of brainstem structures controlling both the respiratory and auditory activities. Overall, a significantly higher incidence of cytoarchitectural alterations of both the auditory and respiratory network components were observed in SIDS victims compared with matched controls. Even if there is not sufficient evidence to presume that developmental defects of brainstem auditory structures can affect breathing, our findings, showing that developmental deficit in the control respiratory areas are frequently accompanied by alterations of auditory structures, highlight an additional important element for the understanding the pathogenetic mechanism of SIDS. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Neurochemical abnormalities in the brainstem of the Sudden Infant Death Syndrome (SIDS). (United States)

    Machaalani, Rita; Waters, Karen A


    The brainstem has been a focus in Sudden Infant Death Syndrome (SIDS) research for 30 years. Physiological and animal model data show that cardiorespiratory, sleep, and arousal mechanisms are abnormal after exposure to SIDS risk factors or in infants who subsequently die from SIDS. As the brainstem houses the regulatory centres for these functions, it is the most likely site to find abnormalities. True to this hypothesis, data derived over the last 30 years shows that the brainstem of infants who died from SIDS exhibits abnormalities in a number of major neurotransmitter and receptor systems including: catecholamines, neuropeptides, acetylcholinergic, indole amines (predominantly serotonin and its receptors), amino acids (predominantly glutamate), brain derived neurotrophic growth factor (BDNF), and some cytokines. A pattern is emerging of particular brainstem nuclei being consistently affected including the dorsal motor nucleus of the vagus (DMNV), nucleus of the solitary tract (NTS), arcuate nucleus (AN) and raphe. We discuss the implications of these findings and directions that this may lead in future research. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. The human premotor oculomotor brainstem system - can it help to understand oculomotor symptoms in Huntington's disease?

    NARCIS (Netherlands)

    Rueb, U.; Heinsen, H.; Brunt, E. R.; Landwehrmeyer, B.; Den Dunnen, W. F. A.; Gierga, K.; Deller, T.

    Recent progress in oculomotor research has enabled new insights into the functional neuroanatomy of the human premotor oculomotor brainstem network. In the present review, we provide an overview of its functional neuroanatomy and summarize the broad range of oculomotor dysfunctions that may occur in

  1. Relationship between brainstem neurodegeneration and clinical impairment in traumatic spinal cord injury

    Directory of Open Access Journals (Sweden)

    Patrick Grabher


    Conclusion: Neurodegeneration, indicated by volume loss and myelin reductions, is evident in major brainstem pathways and nuclei following traumatic SCI; the magnitude of these changes relating to clinical impairment. Thus, quantitative MRI protocols offer new targets, which may be used as neuroimaging biomarkers in treatment trials.

  2. Ventilation induced apnea and its effect on dorsal brainstem inspiratory neurones in the rat

    NARCIS (Netherlands)

    Subramanian, Hari H.; Balnave, Ron J.; Chow, Chin M.


    The purpose of this study was to examine the effect of mechanical ventilation (MV) on inherent breathing and on dorsal brainstem nucleus tractus solitarius (NTS) respiratory cell function. In pentobarbitone-anaesthetised rats, application of MV at combined high frequencies and volumes (representing

  3. Brainstem Transcription of Speech Is Disrupted in Children with Autism Spectrum Disorders (United States)

    Russo, Nicole; Nicol, Trent; Trommer, Barbara; Zecker, Steve; Kraus, Nina


    Language impairment is a hallmark of autism spectrum disorders (ASD). The origin of the deficit is poorly understood although deficiencies in auditory processing have been detected in both perception and cortical encoding of speech sounds. Little is known about the processing and transcription of speech sounds at earlier (brainstem) levels or…

  4. Investigation of auditory brainstem function in elderly diabetic patients with presbycusis. (United States)

    Kovacií, Jelena; Lajtman, Zoran; Ozegović, Ivan; Knezević, Predrag; Carić, Tomislav; Vlasić, Ana


    We performed brainstem auditory evoked potential (BAEP) examinations in 100 patients older than 60 years and having type I diabetes mellitus and presbycusis. The aim of our investigation was to compare the BAEP results of this group with those of healthy controls with presbycusis and to look for possible correlations between alteration of the auditory brainstem function and the aging of elderly diabetic patients. Absolute and interpeak latencies of all waves were prolonged significantly in the study group of diabetic patients. The amplitudes of all waves I through V were diminished in the study group as compared to those in the control group, with statistical significance present for all waves. Analysis of the latencies (waves I, II, I, and V), interpeak latencies (I-V), and amplitudes (I, II, III, and V) of BAEP revealed a significant difference between those of diabetics and those of healthy elderly controls with presbycusis. These data support a hypothesis that there is a brainstem neuropathy in diabetes mellitus that can be assessed with auditory brainstem response testing even in the group of elderly patients with sensorineural hearing loss.

  5. Brainstem auditory evoked responses in 37 dogs with otitis media before and after topical therapy. (United States)

    Paterson, S


    The objective of this study was to determine whether intra-aural administration of aqueous solutions of marbofloxacin, gentamicin, tobramycin and ticarcillin (used off-licence) was associated with changes in hearing as measured by brainstem auditory evoked responses. Dogs diagnosed with otitis media (n=37) underwent brainstem auditory evoked response testing and then were treated for their ear disease. First, the external ear canal and middle ear were flushed with sterile saline followed by EDTA tris with 0·15% chlorhexidine. Then, a combination of aqueous antibiotic mixed with an aqueous solution of EDTA tris was instilled into the middle ear. Follow-up examinations were undertaken for each dog, and treatment was continued until there were no detected infectious organisms or inflammatory infiltrate. Brainstem auditory evoked response testing was repeated after resolution of the infection and discontinuation of therapy. Brainstem auditory evoked responses in dogs treated with aqueous solutions of marbofloxacin or gentamicin remained unchanged or improved after therapy of otitis media but were impaired in dogs treated with ticarcillin or tobramycin. If off-licence use of topical antibiotics is deemed necessary in cases of otitis media, aqueous solutions of marbofloxacin and gentamicin appear to be less ototoxic than aqueous solutions of ticarcillin or tobramycin. © 2017 British Small Animal Veterinary Association.

  6. Albumin administration protects against bilirubin-induced auditory brainstem dysfunction in Gunn rat pups

    NARCIS (Netherlands)

    Schreuder, Andrea B.; Rice, Ann C.; Vanikova, Jana; Vitek, Libor; Shapiro, Steven M.; Verkade, Henkjan J.


    Background Free bilirubin (Bf), the unbound fraction of unconjugated bilirubin (UCB), can induce neurotoxicity, including impairment of the auditory system, which can be assessed by brainstem auditory evoked potentials (BAEPs). We hypothesized that albumin might reduce the risk of neurotoxicity by

  7. Auditory brainstem response – a valid and cost-effective screening tool for vestibular schwannoma?

    DEFF Research Database (Denmark)

    Rafique, Irfan; Wennervaldt, Kasper; Melchiors, Jacob


    Abstract: Conclusion: Contemporary auditory brainstem response (ABR) is not valid as a screening tool for VS, when considering the sensitivity of 80%, the specificity of 77%, and the positive predictive value of 3.4%, MRI screening is superior to ABR in Denmark when considering cost-effectiveness...

  8. Motor-evoked potentials (MEP) during brainstem surgery to preserve corticospinal function. (United States)

    Sarnthein, Johannes; Bozinov, Oliver; Melone, Angelina Graziella; Bertalanffy, Helmut


    Brainstem surgery bears a risk of damage to the corticospinal tract (CST). Motor-evoked potentials (MEPs) are used intraoperatively to monitor CST function in order to detect CST damage at a reversible stage and thus impede permanent neurological deficits. While the method of MEP is generally accepted, warning criteria in the context of brainstem surgery still have to be agreed on. We analyzed 104 consecutive patients who underwent microsurgical resection of lesions affecting the brainstem. Motor grade was documented prior to surgery, early postoperatively and at discharge. A baseline MEP stimulation intensity threshold was defined and intraoperative testing aimed to keep MEP response amplitude constant. MEPs were considered deteriorated and the surgical team was notified whenever the threshold was elevated by ≥20 mA or MEP response fell under 50%. On the first postoperative day, 18 patients experienced new paresis that resolved by discharge in 11. MEPs deteriorated in 39 patients, and 16 of these showed new postoperative paresis, indicating a 41% risk of new paresis. In the remaining 2/18 patients, intraoperative MEPs were stable, although new paresis appeared postoperatively. In one of these patients, intraoperative hemorrhage caused postoperative swelling, and the new motor deficit persisted until discharge. Of all 104 patients, 7 deteriorated in motor grade at discharge, 92 remained unchanged, and 5 patients have improved. Adjustment of surgical strategy contributed to good motor outcome in 33/39 patients. MEP monitoring may help significantly to prevent motor deficits during demanding neurosurgical procedures on the brainstem.

  9. Low-frequency versus high-frequency synchronisation in chirp-evoked auditory brainstem responses

    DEFF Research Database (Denmark)

    Rønne, Filip Munch; Gøtsche-Rasmussen, Kristian


    This study investigates the frequency specific contribution to the auditory brainstem response (ABR) of chirp stimuli. Frequency rising chirps were designed to compensate for the cochlear traveling wave delay, and lead to larger wave-V amplitudes than for click stimuli as more auditory nerve fibres...

  10. Functional Circuitry Effect of Ventral Tegmental Area Deep Brain Stimulation: Imaging and Neurochemical Evidence of Mesocortical and Mesolimbic Pathway Modulation. (United States)

    Settell, Megan L; Testini, Paola; Cho, Shinho; Lee, Jannifer H; Blaha, Charles D; Jo, Hang J; Lee, Kendall H; Min, Hoon-Ki


    reward, mood regulation, and in the pathophysiology of MDD. In addition, we showed that a combination of fMRI and electrochemically-based neurochemical detection platform is an effective investigative tool for elucidating the circuitry involved in VTA-DBS.

  11. Exposures to fine particulate matter (PM2.5) and ozone above USA standards are associated with auditory brainstem dysmorphology and abnormal auditory brainstem evoked potentials in healthy young dogs. (United States)

    Calderón-Garcidueñas, Lilian; González-González, Luis O; Kulesza, Randy J; Fech, Tatiana M; Pérez-Guillé, Gabriela; Luna, Miguel Angel Jiménez-Bravo; Soriano-Rosales, Rosa Eugenia; Solorio, Edelmira; Miramontes-Higuera, José de Jesús; Gómez-Maqueo Chew, Aline; Bernal-Morúa, Alexia F; Mukherjee, Partha S; Torres-Jardón, Ricardo; Mills, Paul C; Wilson, Wayne J; Pérez-Guillé, Beatriz; D'Angiulli, Amedeo


    Delayed central conduction times in the auditory brainstem have been observed in Mexico City (MC) healthy children exposed to fine particulate matter (PM 2.5 ) and ozone (O 3 ) above the current United States Environmental Protection Agency (US-EPA) standards. MC children have α synuclein brainstem accumulation and medial superior olivary complex (MSO) dysmorphology. The present study used a dog model to investigate the potential effects of air pollution on the function and morphology of the auditory brainstem. Twenty-four dogs living in clean air v MC, average age 37.1 ± 26.3 months, underwent brainstem auditory evoked potential (BAEP) measurements. Eight dogs (4 MC, 4 Controls) were analysed for auditory brainstem morphology and histopathology. MC dogs showed ventral cochlear nuclei hypotrophy and MSO dysmorphology with a significant decrease in cell body size, decreased neuronal packing density with regions in the nucleus devoid of neurons and marked gliosis. MC dogs showed significant delayed BAEP absolute wave I, III and V latencies compared to controls. MC dogs show auditory nuclei dysmorphology and BAEPs consistent with an alteration of the generator sites of the auditory brainstem response waveform. This study puts forward the usefulness of BAEPs to study auditory brainstem neurodegenerative changes associated with air pollution in dogs. Recognition of the role of non-invasive BAEPs in urban dogs is warranted to elucidate novel neurodegenerative pathways link to air pollution and a promising early diagnostic strategy for Alzheimer's Disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Assessment of brainstem auditory evoked potentials (BAEPs) in patients with acromegaly. (United States)

    Pilecki, Witold; Bolanowski, Marek; Janocha, Anna; Daroszewski, Jacek; Kałuzny, Marcin; Sebzda, Tadeusz; Kałka, Dariusz; Sobieszczańska, Małgorzata


    Acromegaly is associated by various systemic complications, involving also the nervous system. Other studies revealed peripheral but not central nervous system impairment with somatosensory evoked potentials examinations in acromegaly. Aim of the present study was to assess whether brainstem transmission in acromegaly is disturbed. The study was carried out in 37 patients. The control group consisted of 47 healthy persons. In all of the subjects, peripheral transmission, reflected by peak I latency, and brainstem transmission, tested by interpeak latency I-V (IPL I-V), were examined. Peak I latency was delayed in 6 out of 37 patients (1 - bilaterally, 2 - right side, 3 - left side). The group-mean latency of peak I was 1.53 msec and 1.56 msec, for the right and left side, respectively. There were found no statistically significant differences between the right and left side, likewise in comparison with control group. In turn, as compared with the controls, IPL I-V was disturbed in 25 out of 37 patients: in most of the cases IPL I-V prolongation was observed (8 - bilateral prolongation, 11 - right side, 6 - left side). Moreover, the statistically significant difference between the brainstem sides (4.27 vs. 4.11 msec; p<0.05) was observed. In the examined patients with acromegaly, there was no peripheral disturbance in transmission, as examined by BAEPs registrations. Conversely, in nearly half of the patients with acromegaly, brainstem transmission was found to be delayed, and significant difference between responses from the both sides of the brainstem were noted.

  13. 7 Tesla 22-channel wrap-around coil array for cervical spinal cord and brainstem imaging. (United States)

    Zhang, Bei; Seifert, Alan C; Kim, Joo-Won; Borrello, Joseph; Xu, Junqian


    Increased signal-to-noise ratio and blood oxygenation level-dependent sensitivity at 7 Tesla (T) have the potential to enable high-resolution imaging of the human cervical spinal cord and brainstem. We propose a new two-panel radiofrequency coil design for these regions to fully exploit the advantages of ultra-high field. A two-panel array, containing four transmit/receive and 18 receive-only elements fully encircling the head and neck, was constructed following simulations demonstrating the B1+ and specific absorption rate (SAR) benefits of two-panel over one-panel arrays. This array was compared with a previously reported posterior-only array and tested for safety using a phantom. Its anatomical, functional, and diffusion MRI performance was demonstrated in vivo. The two-panel array produced more uniform B1+ across the brainstem and cervical spinal cord without compromising SAR, and achieved 70% greater receive sensitivity than the posterior-only array. The two-panel design enabled acceleration of R = 2 × 2 in two dimensions or R = 3 in a single dimension. High quality in vivo anatomical, functional, and diffusion images of the human cervical spinal cord and brainstem were acquired. We have designed and constructed a wrap-around coil array with excellent performance for cervical spinal cord and brainstem MRI at 7T, which enables simultaneous human cervical spinal cord and brainstem functional MRI. Magn Reson Med 78:1623-1634, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  14. Hypothyroidism alters antioxidant defence system in rat brainstem during postnatal development and adulthood. (United States)

    Jena, Srikanta; Bhanja, Shravani


    The present investigation was carried out to evaluate alterations in oxidative stress parameter [lipid peroxidation (LPx)] and antioxidant enzyme activities [superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)] in rat brainstem in response to neonatal hypothyroidism during development (from birth to 7, 15 and 30 days old) and adulthood (90 days old). Hypothyroidism in rats was induced by feeding the lactating mothers (from the day of parturition till weaning, 25 days old) or directly to the pups with 0.05 % [6-n-propyl 2-thiouracil (PTU)] in drinking water. Increased level of LPx was observed in brainstem of 7 days old hypothyroid rats, accompanied by augmented activities of SOD and GPx. In 15 and 30 days old hypothyroid rat brainstem, a significant decline in LPx was observed. Significantly increased activities of CAT and GPx were observed in 15 and 30 days PTU-treated rats. Decreased level of LPx was observed in brainstem of rats treated with PTU from birth to 30 days followed by withdrawal up to 90 days of age (transient hypothyroidism) as compared to control and persistent treatment of PTU up to 90 days of age. Activities of CAT and GPx were decreased in persistent hypothyroid rats of 90 days old with respect to control and transient hypothyroid rats. On the other hand, SOD activity was decreased in both persistent and transient hypothyroid rats with respect to control rats. These results suggest that the PTU-induced neonatal hypothyroidism modulates the antioxidant defence system during postnatal development and adulthood in brainstem of rats.

  15. Brainstem response to speech and non-speech stimuli in children with learning problems. (United States)

    Malayeri, Saeed; Lotfi, Yones; Moossavi, Seyed Abdollah; Rostami, Reza; Faghihzadeh, Soghrat


    Neuronal firing synchronization is critical for recording auditory responses from the brainstem. Recent studies have shown that both click and/da/synthetic syllable (speech) stimuli perform well in evoking neuronal synchronization at the brainstem level. In the present study, brainstem responses to click and speech stimuli were compared between children with learning problems (LP) and those with normal learning (NL) abilities. The study included 49 children with LP and 34 children with NL. Auditory brainstem response (ABR) to 100-μs click stimulus and speech ABR (sABR) to/da/40-ms stimulus were tested in these children. Wave latencies III, V, and Vn and inter-peak latency (IPL) V-Vn in click ABR and wave latencies I, V, and A and IPL V-A in sABR were significantly longer in children with LP than children with NL. Except IPL of I-III, a significant positive correlation was observed between click ABR and sABR wave latencies and IPLs in children with NL; this correlation was weaker or not observed in children with LP. In this regard, the difference between correlation coefficients of wave latencies I, III, and V and IPLs I-V and V-Vn/V-A was significant in the two groups. Deficits in auditory processing timing in children with LP may have probably affected ABR for both click and speech stimuli. This finding emphasizes the possibility of shared connections between processing timing for speech and non-speech stimuli in auditory brainstem pathways. Weak or no correlation between click and speech ABR parameters in children with LP may have a clinical relevance and may be effectively used for objective diagnoses after confirming its sufficient sensitivity and specificity and demonstrating its acceptable validity with more scientific evidence. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. The usefulness of a computerized tomographic scan taken parallel to the clivus in the management of brain-stem lesions

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    Morita, Akio; Mishima, Kazuhiko; Miyagawa, Naohisa; Aritake, Kouichi; Segawa, Hiromu; Sano, Keiji (Fuji Brain Instutue and Hospital, Shizuoka (Japan))


    It is important to detect the definite sites and extent of lesions in the management of brainstem infarction. While axial computerized tomographic scan (axial CT) has usually been used to map brain-stem lesions, it often fails to show small lesions or their longitudinal extent. In this report, the usefulness of CT scan using scan slices taken parallel to the clivus (clival CT) is evaluated in cases of brain-stem infarction. Clival CT was performed with the patient in a supine position, with as much neck flexion as possible. CT slices were taken parallel to the clivus (orbito-meatal line, 35-50 deg.). Both axial and clival CT scans were performed in 25 patients with brain-stem infarctions. Axial CT was most useful in detecting small lesions located in the ventral pons and in showing the anatomical structure which was involved. On the other hand, clival CT was superior in demonstrating the longitudinal extent of infarctions, especially in the midbrain or thalamus. In cases with major brain-stem infarctions or in cases with associated cerebellar lesions, the combination of axial and clival CT shows the configuration and continuity of the lesions clearly. Therefore, clival CT, when used with axial CT, clearly shows the three-dimensional extent of brain-stem infarctions; this technique is also recommended when managing other types of brain-stem disease. In addition, it is important to select appropriate CT slice angles in order to demonstrate the anatomical structure of interest. (author).

  17. Studying respiratory rhythm generation in a developing bird: Hatching a new experimental model using the classic in vitro brainstem-spinal cord preparation. (United States)

    Vincen-Brown, Michael A; Whitesitt, Kaitlyn C; Quick, Forrest G; Pilarski, Jason Q


    It has been more than thirty years since the in vitro brainstem-spinal cord preparation was first presented as a method to study automatic breathing behaviors in the neonatal rat. This straightforward preparation has led to an incredible burst of information about the location and coordination of several spontaneously active microcircuits that form the ventrolateral respiratory network of the brainstem. Despite these advances, our knowledge of the mechanisms that regulate central breathing behaviors is still incomplete. Investigations into the nature of spontaneous breathing rhythmicity have almost exclusively focused on mammals, and there is a need for comparative experimental models to evaluate several unresolved issues from a different perspective. With this in mind, we sought to develop a new avian in vitro model with the long term goal to better understand questions associated with the ontogeny of respiratory rhythm generation, neuroplasticity, and whether multiple, independent oscillators drive the major phases of breathing. The fact that birds develop in ovo provides unparalleled access to central neuronal networks throughout the prenatal period - from embryo to hatchling - that are free from confounding interactions with mother. Previous studies using in vitro avian models have been strictly limited to the early embryonic period. Consequently, the details and even the presence of brainstem derived breathing-related rhythmogenesis in birds have never been described. In the present study, we used the altricial zebra finch (Taeniopygia guttata) and show robust spontaneous motor outflow through cranial motor nerve IX, which is first detectable on embryonic day four and continues through prenatal and early postnatal development without interruption. We also show that brainstem oscillations change dramatically over the course of prenatal development, sometimes within hours, which suggests rapid maturational modifications in growth and connectivity. We propose

  18. Dissociation of spontaneous seizures and brainstem seizure thresholds in mice exposed to eight flurothyl-induced generalized seizures. (United States)

    Kadiyala, Sridhar B; Ferland, Russell J


    C57BL/6J mice exposed to eight flurothyl-induced generalized clonic seizures exhibit a change in seizure phenotype following a 28-day incubation period and subsequent flurothyl rechallenge. Mice now develop a complex seizure semiology originating in the forebrain and propagating into the brainstem seizure network (a forebrain→brainstem seizure). In contrast, this phenotype change does not occur in seizure-sensitive DBA/2J mice. The underlying mechanism(s) was the focus of these studies. DBA2/J mice were exposed to eight flurothyl-induced seizures (1/day) followed by 24-hour video-electroencephalographic recordings for 28-days. Forebrain and brainstem seizure thresholds were determined in C57BL/6J and DBA/2J mice following one or eight flurothyl-induced seizures, or after eight flurothyl-induced seizures, a 28-day incubation period, and final flurothyl rechallenge. Similar to C57BL/6J mice, DBA2/J mice expressed spontaneous seizures. However, unlike C57BL/6J mice, DBA2/J mice continued to have spontaneous seizures without remission. Because DBA2/J mice do not express forebrain→brainstem seizures following flurothyl rechallenge after a 28-day incubation period, this indicated that spontaneous seizures were not sufficient for the evolution of forebrain→brainstem seizures. Therefore, we determined whether brainstem seizure thresholds were changing during this repeated-flurothyl model and whether this could account for the expression of forebrain→brainstem seizures. Brainstem seizure thresholds were not different between C57BL/6J and DBA/2J mice on day one or on the last induction seizure trial (day eight). However, brainstem seizure thresholds did differ significantly on flurothyl rechallenge (day 28) with DBA/2J mice showing no lowering of their brainstem seizure thresholds. These results demonstrated that DBA/2J mice exposed to the repeated-flurothyl model develop spontaneous seizures without evidence of seizure remission and provide a new model of

  19. Idiopathic Brainstem Neuronal Chromatolysis (IBNC: a novel prion protein related disorder of cattle?

    Directory of Open Access Journals (Sweden)

    Martin Stuart


    Full Text Available Abstract Background The epidemic form of Bovine Spongiform Encephalopathy (BSE is generally considered to have been caused by a single prion strain but at least two strain variants of cattle prion disorders have recently been recognized. An additional neurodegenerative condition, idiopathic brainstem neuronal chromatolysis and hippocampal sclerosis (IBNC, a rare neurological disease of adult cattle, was also recognised in a sub-set of cattle submitted under the BSE Orders in which lesions of BSE were absent. Between the years of 1988 and 1991 IBNC occurred in Scotland with an incidence of 7 cases per 100,000 beef suckler cows over the age of 6 years. Results When the brains of 15 IBNC cases were each tested by immunohistochemistry, all showed abnormal labelling for prion protein (PrP. Immunohistological labelling for PrP was also present in the retina of a single case available for examination. The pattern of PrP labelling in brain is distinct from that seen in other ruminant prion diseases and is absent from brains with other inflammatory conditions and from normal control brains. Brains of IBNC cattle do not reveal abnormal PrP isoforms when tested by the commercial BioRad or Idexx test kits and do not reveal PrPres when tested by Western blotting using stringent proteinase digestion methods. However, some weakly protease resistant isoforms of PrP may be detected when tissues are examined using mild proteinase digestion techniques. Conclusion The study shows that a distinctive neurological disorder of cattle, which has some clinical similarities to BSE, is associated with abnormal PrP labelling in brain but the pathology and biochemistry of IBNC are distinct from BSE. The study is important either because it raises the possibility of a significant increase in the scope of prion disease or because it demonstrates that widespread and consistent PrP alterations may not be confined to prion diseases. Further studies, including transmission

  20. Localization of Kv1.3 channels in presynaptic terminals of brainstem auditory neurons. (United States)

    Gazula, Valeswara-Rao; Strumbos, John G; Mei, Xiaofeng; Chen, Haijun; Rahner, Christoph; Kaczmarek, Leonard K


    Elimination of the Kv1.3 voltage-dependent potassium channel gene produces striking changes in the function of the olfactory bulb, raising the possibility that this channel also influences other sensory systems. We have examined the cellular and subcellular localization of Kv1.3 in the medial nucleus of the trapezoid body (MNTB) in the auditory brainstem, a nucleus in which neurons fire at high rates with high temporal precision. A clear gradient of Kv1.3 immunostaining along the lateral to medial tonotopic axis of the MNTB was detected. Highest levels were found in the lateral region of the MNTB, which corresponds to neurons that respond selectively to low-frequency auditory stimuli. Previous studies have demonstrated that MNTB neurons and their afferent inputs from the cochlear nucleus express three other members of the Kv1 family, Kv1.1, Kv1.2, and Kv1.6. Nevertheless, confocal microscopy of MNTB sections coimmunostained for Kv1.3 with these subunits revealed that the distribution of Kv1.3 differed significantly from other Kv1 family subunits. In particular, no axonal staining of Kv1.3 was detected, and most prominent labeling was in structures surrounding the somata of the principal neurons, suggesting specific localization to the large calyx of Held presynaptic endings that envelop the principal cells. The presence of Kv1.3 in presynaptic terminals was confirmed by coimmunolocalization with the synaptic markers synaptophysin, syntaxin, and synaptotagmin and by immunogold electron microscopy. Kv1.3 immunogold particles in the terminals were arrayed along the plasma membrane and on internal vesicular structures. To confirm these patterns of staining, we carried out immunolabeling on sections from Kv1.3(-/-) mice. No immunoreactivity could be detected in Kv1.3(-/-) mice either at the light level or in immunogold experiments. The finding of a tonotopic gradient in presynaptic terminals suggests that Kv1.3 may regulate neurotransmitter release differentially in

  1. Optimal technique of linear accelerator-based stereotactic radiosurgery for tumors adjacent to brainstem. (United States)

    Chang, Chiou-Shiung; Hwang, Jing-Min; Tai, Po-An; Chang, You-Kang; Wang, Yu-Nong; Shih, Rompin; Chuang, Keh-Shih


    Stereotactic radiosurgery (SRS) is a well-established technique that is replacing whole-brain irradiation in the treatment of intracranial lesions, which leads to better preservation of brain functions, and therefore a better quality of life for the patient. There are several available forms of linear accelerator (LINAC)-based SRS, and the goal of the present study is to identify which of these techniques is best (as evaluated by dosimetric outcomes statistically) when the target is located adjacent to brainstem. We collected the records of 17 patients with lesions close to the brainstem who had previously been treated with single-fraction radiosurgery. In all, 5 different lesion catalogs were collected, and the patients were divided into 2 distance groups-1 consisting of 7 patients with a target-to-brainstem distance of less than 0.5cm, and the other of 10 patients with a target-to-brainstem distance of ≥ 0.5 and radiosurgery: dynamic conformal arcs (DCA), intensity-modulated radiosurgery (IMRS), and volumetric modulated arc radiotherapy (VMAT). All techniques included multiple noncoplanar beams or arcs with or without intensity-modulated delivery. The volume of gross tumor volume (GTV) ranged from 0.2cm(3) to 21.9cm(3). Regarding the dose homogeneity index (HIICRU) and conformity index (CIICRU) were without significant difference between techniques statistically. However, the average CIICRU = 1.09 ± 0.56 achieved by VMAT was the best of the 3 techniques. Moreover, notable improvement in gradient index (GI) was observed when VMAT was used (0.74 ± 0.13), and this result was significantly better than those achieved by the 2 other techniques (p < 0.05). For V4Gy of brainstem, both VMAT (2.5%) and IMRS (2.7%) were significantly lower than DCA (4.9%), both at the p < 0.05 level. Regarding V2Gy of normal brain, VMAT plans had attained 6.4 ± 5%; this was significantly better (p < 0.05) than either DCA or IMRS plans, at 9.2 ± 7% and 8.2 ± 6%, respectively. Owing to

  2. Improved mapping and quantification of serotonin transporter availability in the human brainstem with the HRRT. (United States)

    Schain, Martin; Tóth, Miklós; Cselényi, Zsolt; Arakawa, Ryosuke; Halldin, Christer; Farde, Lars; Varrone, Andrea


    The serotonin system is involved in many physiological functions and clinical conditions. Serotonergic neurons originate from the raphe nuclei in the brainstem, and reliable estimates of receptor/transporter availability in the raphe in vivo are thus of interest. Though positron emission tomography (PET) can be used to quantify receptor distribution in the brain, high noise levels prevent reliable estimation of radioligand binding in small regions such as the raphe. For this purpose, parametric imaging in combination with high-resolution PET systems may provide images with reduced noise levels and sufficient contrast for reliable quantification. This study examined the potential to evaluate radioligand binding in brainstem nuclei, and assessed the effect of improved resolution on the outcome measures. For comparative purposes, radioligand binding was measured with an ECAT EXACT HR PET system (resolution about 4.5 mm FWHM) and a high-resolution research tomograph (HRRT) system (resolution about 1.5 mm FWHM). Six subjects were examined with both systems on the same day using the serotonin transporter radioligand [(11)C]MADAM. Parametric images of binding potential (BP (ND)) were obtained using a wavelet-aided approach. Regions of interest (ROIs) were delineated using a threshold-based semiautomatic delineation procedure for five brainstem structures. Regional BP (ND) values were estimated by applying the ROIs to the parametric images, and the percentage difference in BP (ND) between the systems was calculated. Signals for [(11)C]MADAM binding were obtained for all five brainstem structures. Overall, the HRRT provided 30-40 % higher BP (ND) values than the HR (p = 0.0017), independent of thresholds used in the ROI delineation procedure. The methodology used enabled the estimation of [(11)C]MADAM binding in the small nuclei of the brainstem. Differences in the BP (ND) values calculated using data from the two systems were mainly attributable to their differing

  3. Transient isolated brainstem symptoms preceding posterior circulation stroke: a population-based study. (United States)

    Paul, Nicola L M; Simoni, Michela; Rothwell, Peter M


    Transient isolated brainstem symptoms (eg, isolated vertigo, dysarthria, diplopia) are not consistently classified as transient ischaemic attacks (TIAs) and data for prognosis are limited. If some of these transient neurological attacks (TNAs) are due to vertebrobasilar ischaemia, then they should be common during the days and weeks preceding posterior circulation strokes. We aimed to assess the frequency of TNAs before vertebrobasilar ischaemic stroke. We studied all potential ischaemic events during the 90 days preceding an ischaemic stroke in patients ascertained within a prospective, population-based incidence study in Oxfordshire, UK (Oxford Vascular Study; 2002-2010) and compared rates of TNA preceding vertebrobasilar stroke versus carotid stroke. We classified the brainstem symptoms isolated vertigo, vertigo with non-focal symptoms, isolated double vision, transient generalised weakness, and binocular visual disturbance as TNAs in the vertebrobasilar territory; atypical amaurosis fugax and limb-shaking as TNAs in the carotid territory; and isolated slurred speech, migraine variants, transient confusion, and hemisensory tingling symptoms as TNAs in uncertain territory. Of the 1141 patients with ischaemic stroke, vascular territory was categorisable in 1034 (91%) cases, with 275 vertebrobasilar strokes and 759 carotid strokes. Isolated brainstem TNAs were more frequent before a vertebrobasilar stroke (45 of 275 events) than before a carotid stroke (10 of 759; OR 14·7, 95% CI 7·3-29·5, pstroke vs two of 751 before a carotid stroke, OR 35·8, 8·4-153·5, pstroke, only five (8%) fulfilled the National Institute of Neurological Disorders and Stroke (NINDS) criteria for TIA. The other 54 cases were isolated vertigo (n=23), non-NINDS binocular visual disturbance (n=9), vertigo with other non-focal symptoms (n=10), isolated slurred speech, hemisensory tingling, or diplopia (n=8), and non-focal events (n=4). Only 10 (22%) of the 45 patients with isolated brainstem

  4. Sequence tolerance of the phage lambda PRM promoter: implications for evolution of gene regulatory circuitry. (United States)

    Michalowski, Christine B; Short, Megan D; Little, John W


    Much of the gene regulatory circuitry of phage lambda centers on a complex region called the O(R) region. This approximately 100-bp region is densely packed with regulatory sites, including two promoters and three repressor-binding sites. The dense packing of this region is likely to impose severe constraints on its ability to change during evolution, raising the question of how the specific arrangement of sites and their exact sequences could evolve to their present form. Here we ask whether the sequence of a cis-acting site can be widely varied while retaining its function; if it can, evolution could proceed by a larger number of paths. To help address this question, we developed a lambda cloning vector that allowed us to clone fragments spanning the O(R) region. By using this vector, we carried out intensive mutagenesis of the P(RM) promoter, which drives expression of CI repressor and is activated by CI itself. We made a pool of fragments in which 8 of the 12 positions in the -35 and -10 regions were randomized and cloned this pool into the vector, making a pool of P(RM) variant phage. About 10% of the P(RM) variants were able to lysogenize, suggesting that the lambda regulatory circuitry is compatible with a wide range of P(RM) sequences. Analysis of several of these phages indicated a range of behaviors in prophage induction. Several isolates had induction properties similar to those of the wild type, and their promoters resembled the wild type in their responses to CI. We term this property of different sequences allowing roughly equivalent function "sequence tolerance " and discuss its role in the evolution of gene regulatory circuitry.

  5. Pain relief produces negative reinforcement through activation of mesolimbic reward-valuation circuitry. (United States)

    Navratilova, Edita; Xie, Jennifer Y; Okun, Alec; Qu, Chaoling; Eyde, Nathan; Ci, Shuang; Ossipov, Michael H; King, Tamara; Fields, Howard L; Porreca, Frank


    Relief of pain is rewarding. Using a model of experimental postsurgical pain we show that blockade of afferent input from the injury with local anesthetic elicits conditioned place preference, activates ventral tegmental dopaminergic cells, and increases dopamine release in the nucleus accumbens. Importantly, place preference is associated with increased activity in midbrain dopaminergic neurons and blocked by dopamine antagonists injected into the nucleus accumbens. The data directly support the hypothesis that relief of pain produces negative reinforcement through activation of the mesolimbic reward-valuation circuitry.

  6. Fabrication and Measurement of a Suspended Nanochannel Microbridge Resonator Monolithically Integrated with CMOS Readout Circuitry

    Directory of Open Access Journals (Sweden)

    Gabriel Vidal-Álvarez


    Full Text Available We present the fabrication and characterization of a suspended microbridge resonator with an embedded nanochannel. The suspended microbridge resonator is electrostatically actuated, capacitively sensed, and monolithically integrated with complementary metal-oxide-semiconductor (CMOS readout circuitry. The device is fabricated using the back end of line (BEOL layers of the AMS 0.35 μm commercial CMOS technology, interconnecting two metal layers with a contact layer. The fabricated device has a 6 fL capacity and has one of the smallest embedded channels so far. It is able to attain a mass sensitivity of 25 ag/Hz using a fully integrable electrical transduction.

  7. Neural Circuitry Based on Single Electron Transistors and Single Electron Memories

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    Aïmen BOUBAKER


    Full Text Available In this paper, we propose and explain a neural circuitry based on single electron transistors ‘SET’ which can be used in classification and recognition. We implement, after that, a Winner-Take-All ‘WTA’ neural network with lateral inhibition architecture. The original idea of this work is reflected, first, in the proposed new single electron memory ‘SEM’ design by hybridising two promising Single Electron Memory ‘SEM’ and the MTJ/Ring memory and second, in modeling and simulation results of neural memory based on SET. We prove the charge storage in quantum dot in two types of memories.

  8. Neurodegenerative changes in the brainstem and olfactory bulb in people older than 50 years old: a descriptive study

    Directory of Open Access Journals (Sweden)

    Francine Hehn de Oliveira


    Full Text Available With the increase in life expectancy in Brazil, concerns have grown about the most prevalent diseases in elderly people. Among these diseases are neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. Protein deposits related to the development of these diseases can pre-date the symptomatic phases by years. The tau protein is particularly interesting: it might be found in the brainstem and olfactory bulb long before it reaches the limbic cortex, at which point symptoms occur. Of the 14 brains collected in this study, the tau protein was found in the brainstems of 10 (71.42% and in olfactory bulbs of 3 out 11. Of the 7 individuals who had a final diagnosis of Alzheimer’s disease (AD, 6 presented tau deposits in some region of the brainstem. Our data support the idea of the presence of tau protein in the brainstem and olfactory bulb in the earliest stages of AD.

  9. Population calcium imaging of spontaneous respiratory and novel motor activity in the facial nucleus and ventral brainstem in newborn mice

    DEFF Research Database (Denmark)

    Persson, Karin; Rekling, Jens C


    and in the facial nucleus. In Fluo-8AM loaded brainstem-spinal cord preparations, respiratory activity on cervical nerves was synchronized with calcium signals at the ventrolateral brainstem surface. Individual ventrolateral neurons at the level of the parafacial respiratory group showed perfect or partial...... synchrony with respiratory nerve bursts. In brainstem-spinal cord preparations, cut at the level of the mid-facial nucleus, calcium signals were recorded in the dorsal, lateral and medial facial subnuclei during respiratory activity. Strong activity initiated in the dorsal subnucleus, followed by activity......, and were predominantly located dorsomedial to the facial nucleus. A novel motor activity on facial, cervical and thoracic nerves was synchronized with calcium signals at the ventromedial brainstem extending from the level of the facial nucleus to the medulla–spinal cord border. Cervical dorsal root...

  10. A case of bulbar type cerebral palsy: representative symptoms of dorsal brainstem syndrome. (United States)

    Hiyane, Masato; Saito, Yoshiaki; Saito, Takashi; Komaki, Hirofumi; Nakagawa, Eiji; Sugai, Kenji; Sasaki, Masayuki; Sato, Noriko; Yamamoto, Toshiyuki; Imai, Yoko


    In this study, we present the case of a 2-year-old boy who exhibited facial and bulbar paralysis since birth, severe dysphagia, signs of oculomotor disturbance, jaw jerks, pyramidal signs on both toes, intellectual disability, and severe gastroesophageal reflux. His blink reflex and auditory/somatosensory evoked potentials suggested abnormalities in the lower brainstem, and magnetic resonance imaging showed a T2 hyperintense area in the pontine tegmentum. These findings combined with the patient's symptoms suggested "dorsal brainstem syndrome" and indicated a possibility of prenatal asphyxia in this patient. Nosologic issues regarding this subgroup of cerebral palsy are discussed here. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  11. Abnormal Auditory Brainstem Response (ABR Findings in a Near-Normal Hearing Child with Noonan Syndrome

    Directory of Open Access Journals (Sweden)

    Bahram Jalaei


    Full Text Available Introduction: Noonan syndrome (NS is a heterogeneous genetic disease that affects many parts of the body. It was named after Dr. Jacqueline Anne Noonan, a paediatric cardiologist.Case Report: We report audiological tests and auditory brainstem response (ABR findings in a 5-year old Malay boy with NS. Despite showing the marked signs of NS, the child could only produce a few meaningful words. Audiological tests found him to have bilateral mild conductive hearing loss at low frequencies. In ABR testing, despite having good waveform morphology, the results were atypical. Absolute latency of wave V was normal but interpeak latencies of wave’s I-V, I-II, II-III were prolonged. Interestingly, interpeak latency of waves III-V was abnormally shorter.Conclusion:Abnormal ABR results are possibly due to abnormal anatomical condition of brainstem and might contribute to speech delay.

  12. Infant temperament and the brainstem auditory evoked response in later childhood. (United States)

    Woodward, S A; McManis, M H; Kagan, J; Deldin, P; Snidman, N; Lewis, M; Kahn, V


    Brainstem auditory evoked responses (BAERs) were evaluated on 10-12-year-old children (N = 56) who had been classified as high or low reactive to unfamiliar stimuli at 4 months of age. BAER measurement was selected because high reactive infants tend to become inhibited or fearful young children, and adult introverts have a faster latency to wave V of the BAER than do extroverts. Children previously classified as high reactive at 4 months had larger wave V components than did low reactive children, a finding that possibly suggests greater excitability in projections to the inferior colliculus. The fact that a fundamental feature of brainstem activity differentiated preadolescent children belonging to two early temperamental groups supports the value of gathering physiological data in temperament research.

  13. Hypertensive brainstem encephalopathy involving deep supratentorial regions: does only blood pressure matter?

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    Jong-Ho Park


    Full Text Available We report on a 42-year-old female patient who presented with high arterial blood pressure of 245/150 mmHg and hypertensive brainstem encephalopathy that involved the brainstem and extensive supratentorial deep gray and white matter. The lesions were nearly completely resolved several days after stabilization of the arterial blood pressure. Normal diffusion-weighted imaging findings and high apparent diffusion coefficient values suggested that the main pathomechanism was vasogenic edema owing to severe hypertension. On the basis of a literature review, the absolute value of blood pressure or whether the patient can control his/her blood pressure seems not to be associated with the degree of the lesions evident on magnetic resonance imaging. It remains to be determined if the acceleration rate and the duration of elevated arterial blood pressure might play a key role in the development of the hypertensive encephalopathy pattern.

  14. Effect of Infant Prematurity on Auditory Brainstem Response at Preschool Age

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    Sara Hasani


    Full Text Available Introduction: Preterm birth is a risk factor for a number of conditions that requires comprehensive examination. Our study was designed to investigate the impact of preterm birth on the processing of auditory stimuli and brain structures at the brainstem level at a preschool age.   Materials and Methods: An auditory brainstem response (ABR test was performed with low rates of stimuli in 60 children aged 4 to 6 years. Thirty subjects had been born following a very preterm labor or late-preterm labor and 30 control subjects had been born following a full-term labor.   Results: Significant differences in the ABR test result were observed in terms of the inter-peak intervals of the I–III and III–V waves, and the absolute latency of the III wave (P

  15. Time-Dependent Compensatory Responses to Chronic Neuroinflammation in Hippocampus and Brainstem: The Potential Role of Glutamate Neurotransmission. (United States)

    Brothers, Holly M; Bardou, Isabelle; Hopp, Sarah C; Marchalant, Yannick; Kaercher, Roxanne M; Turner, Sarah M; Mitchem, Mollie R; Kigerl, Kristina; Wenk, Gary L


    Chronic neuroinflammation is characteristic of neurodegenerative diseases and is present during very early stages, yet significant pathology and behavioral deficits do not manifest until advanced age. We investigated the consequences of experimentally-induced chronic neuroinflammation within the hippocampus and brainstem of young (4 mo) F-344 rats. Lipopolysaccharide (LPS) was infused continuously into the IV th ventricle for 2, 4 or 8 weeks. The number of MHC II immunoreactive microglia in the brain continued to increase throughout the infusion period. In contrast, performance in the Morris water maze was impaired after 4 weeks but recovered by 8 weeks. Likewise, a transient loss of tyrosine hydroxylase immunoreactivity in the substantia nigra and locus coeruleus was observed after 2 weeks, but returned to control levels by 4 weeks of continuous LPS infusion. These data suggest that direct activation of microglia is sufficient to drive, but not sustain, spatial memory impairment and a decrease in tyrosine hydroxylase production in young rats. Our previous studies suggest that chronic neuroinflammation elevates extracellular glutamate and that this elevation underlies the spatial memory impairment. In the current study, increased levels of GLT1 and SNAP25 in the hippocampus corresponded with the resolution of performance deficit. Increased expression of SNAP25 is consistent with reduced glutamate release from axonal terminals while increased GLT1 is consistent with enhanced clearance of extracellular glutamate. These data demonstrate the capacity of the brain to compensate for the presence of chronic neuroinflammation, despite continued activation of microglia, through changes in the regulation of the glutamatergic system.

  16. Mode-locking neurodynamics predict human auditory brainstem responses to musical intervals. (United States)

    Lerud, Karl D; Almonte, Felix V; Kim, Ji Chul; Large, Edward W


    The auditory nervous system is highly nonlinear. Some nonlinear responses arise through active processes in the cochlea, while others may arise in neural populations of the cochlear nucleus, inferior colliculus and higher auditory areas. In humans, auditory brainstem recordings reveal nonlinear population responses to combinations of pure tones, and to musical intervals composed of complex tones. Yet the biophysical origin of central auditory nonlinearities, their signal processing properties, and their relationship to auditory perception remain largely unknown. Both stimulus components and nonlinear resonances are well represented in auditory brainstem nuclei due to neural phase-locking. Recently mode-locking, a generalization of phase-locking that implies an intrinsically nonlinear processing of sound, has been observed in mammalian auditory brainstem nuclei. Here we show that a canonical model of mode-locked neural oscillation predicts the complex nonlinear population responses to musical intervals that have been observed in the human brainstem. The model makes predictions about auditory signal processing and perception that are different from traditional delay-based models, and may provide insight into the nature of auditory population responses. We anticipate that the application of dynamical systems analysis will provide the starting point for generic models of auditory population dynamics, and lead to a deeper understanding of nonlinear auditory signal processing possibly arising in excitatory-inhibitory networks of the central auditory nervous system. This approach has the potential to link neural dynamics with the perception of pitch, music, and speech, and lead to dynamical models of auditory system development. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Brainstem encoding of speech and musical stimuli in congenital amusia: Evidence from Cantonese speakers

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    Fang eLiu


    Full Text Available Congenital amusia is a neurodevelopmental disorder of musical processing that also impacts subtle aspects of speech processing. It remains debated at what stage(s of auditory processing deficits in amusia arise. In this study, we investigated whether amusia originates from impaired subcortical encoding of speech (in quiet and noise and musical sounds in the brainstem. Fourteen Cantonese-speaking amusics and 14 matched controls passively listened to six Cantonese lexical tones in quiet, two Cantonese tones in noise (signal-to-noise ratios at 0 and 20 dB, and two cello tones in quiet while their frequency-following responses (FFRs to these tones were recorded. All participants also completed a behavioral lexical tone identification task. The results indicated normal brainstem encoding of pitch in speech (in quiet and noise and musical stimuli in amusics relative to controls, as measured by FFR pitch strength, pitch error, and stimulus-to-response correlation. There was also no group difference in neural conduction time or FFR amplitudes. Both groups demonstrated better FFRs to speech (in quiet and noise than to musical stimuli. However, a significant group difference was observed for tone identification, with amusics showing significantly lower accuracy than controls. Analysis of the tone confusion matrices suggested that amusics were more likely than controls to confuse between tones that shared similar acoustic features. Interestingly, this deficit in lexical tone identification was not coupled with brainstem abnormality for either speech or musical stimuli. Together, our results suggest that the amusic brainstem is not functioning abnormally, although higher-order linguistic pitch processing is impaired in amusia. This finding has significant implications for theories of central auditory processing, requiring further investigations into how different stages of auditory processing interact in the human brain.

  18. Nonphosphorylated neurofilament protein is expressed by scattered neurons in the vestibular and precerebellar brainstem


    Baizer, Joan S.


    Vestibular information is essential for the control of posture, balance, and eye movements. The vestibular nerve projects to the four nuclei of the vestibular nuclear complex (VNC), as well as to several additional brainstem nuclei and the cerebellum. We have found that expression of the calcium-binding proteins calretinin (CR) and calbindin (CB), and the synthetic enzyme for nitric oxide synthase (nNOS) define subdivisions of the medial vestibular nucleus (MVe) and the nucleus prepositus (Pr...

  19. Perioperative problems in patients with brainstem tumors and their influence on patient outcome

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    Sachidanand J Bharati


    Full Text Available Background and Aims: Patients with brainstem tumors have many associated systemic abnormalities and are prone to develop perioperative complications. We studied the problems associated with brainstem tumors and their influence on the postoperative neurological outcome. Material and Methods: Retrospective review of records of patients who underwent surgery for brainstem tumors over a period of 8 years was done. Preoperative variables, perioperative complications and neurological outcome as assessed by Glasgow Outcome Scale at the time of hospital discharge were noted. Association between perioperative factors and the unfavorable neurological outcome was evaluated. Results: Data of 70 patients were retrieved, 7 patients were excluded from the study because of incomplete data and data analysis was carried out for 63 patients. We found that lower cranial nerve palsies (32% and hydrocephalus (43% were common preoperatively. Various intraoperative problems encountered were hemodynamic instability (56%, major blood loss requiring blood transfusion (40% and venous air embolism (11%, and postoperative problems were meningitis (51%, hypokalemia (38%, chest infection (21%, seizure (11%, deterioration of Glasgow Coma Scale (GCS, 11%, hyponatremia (8%, hydrocephalus (6%, respiratory distress (3% and operatives site hematoma (3%. Fifty-six (89% patients had favorable outcome at hospital discharge whereas, 7 (11% had an unfavorable outcome. There was no association between pre- and intra-operative factors and the neurological outcome. Deterioration of GCS, chest infection, and the need for reintubation and tracheostomy were associated with unfavorable neurological outcome. Conclusion: Patients of brainstem tumors are at increased risk of perioperative complications. Some of the postoperative complications were associated with unfavorable neurological outcome.

  20. Coordinated plasticity in brainstem and auditory cortex contributes to enhanced categorical speech perception in musicians. (United States)

    Bidelman, Gavin M; Weiss, Michael W; Moreno, Sylvain; Alain, Claude


    Musicianship is associated with neuroplastic changes in brainstem and cortical structures, as well as improved acuity for behaviorally relevant sounds including speech. However, further advance in the field depends on characterizing how neuroplastic changes in brainstem and cortical speech processing relate to one another and to speech-listening behaviors. Here, we show that subcortical and cortical neural plasticity interact to yield the linguistic advantages observed with musicianship. We compared brainstem and cortical neuroelectric responses elicited by a series of vowels that differed along a categorical speech continuum in amateur musicians and non-musicians. Musicians obtained steeper identification functions and classified speech sounds more rapidly than non-musicians. Behavioral advantages coincided with more robust and temporally coherent brainstem phase-locking to salient speech cues (voice pitch and formant information) coupled with increased amplitude in cortical-evoked responses, implying an overall enhancement in the nervous system's responsiveness to speech. Musicians' subcortical and cortical neural enhancements (but not behavioral measures) were correlated with their years of formal music training. Associations between multi-level neural responses were also stronger in musically trained listeners, and were better predictors of speech perception than in non-musicians. Results suggest that musicianship modulates speech representations at multiple tiers of the auditory pathway, and strengthens the correspondence of processing between subcortical and cortical areas to allow neural activity to carry more behaviorally relevant information. We infer that musicians have a refined hierarchy of internalized representations for auditory objects at both pre-attentive and attentive levels that supplies more faithful phonemic templates to decision mechanisms governing linguistic operations. © 2014 Federation of European Neuroscience Societies and John Wiley

  1. Limbic encephalitis with antibodies to glutamic acid decarboxylase presenting with brainstem symptoms

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    Faruk Incecik


    Full Text Available Limbic encephalitis (LE is a neurological syndrome that may present in association with cancer, infection, or as an isolate clinical condition often accompanying autoimmune disorders. LE associated with glutamic acid decarboxylase antibodies (anti-GAD is rare in children. Here, we characterized the clinical and laboratory features of a patient presenting with brainstem involvement with non-paraneoplastic LE associated with anti-GAD antibodies. In our patient, after plasma exchange, we determined a dramatic improvement of the neurological deficits.

  2. Prenatal valproic acid exposure disrupts tonotopic c-Fos expression in the rat brainstem. (United States)

    Dubiel, A; Kulesza, R J


    Autism spectrum disorder (ASD) is a group of neurodevelopmental conditions characterized by difficulties in communication and social interactions, restricted, repetitive behaviors and sensory abnormalities. Notably, the vast majority of individuals with ASD experience some degree of auditory dysfunction and we have recently reported consistent hypoplasia and dysmorphology in auditory brainstem centers in individuals with ASD. Prenatal exposure to the antiepileptic drug valproic acid (VPA) is associated with an increased risk of ASD. In rodents, prenatal exposure to VPA is employed as an animal model of ASD and is associated with a number of anatomical, physiological and behavioral deficits, including hypoplasia and dysmorphology of auditory brainstem centers. Based on these observations, we hypothesized that such dysmorphology in VPA-exposed animals would translate into abnormal neuronal activity in brainstem circuits and irregular tonotopic maps. Herein, we have subjected control and VPA-exposed animals to 4- or 16-kHz tones and examined neuronal activation with immunohistochemistry for c-Fos. After these exposures, we identified significantly more c-Fos-positive neurons in the auditory brainstem of VPA-exposed animals. Additionally, we observed a larger dispersion of c-Fos-positive neurons and shifted tonotopic bands in VPA-exposed rats. We interpret these findings to suggest hyper-responsiveness to sounds and disrupted mapping of sound frequencies after prenatal VPA exposure. Based on these findings, we suggest that such abnormal patterns of activation may play a role in auditory processing deficits in ASD. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. A rare case of acute poster ior reversible encephalopathy syndrome involving brainstem in a child


    Olfa Chakroun-Walha; Ichrak Bacha; Mehdi Frikha; Kheireddine Ben Mahfoudh; Noureddine Rekik


    Posterior reversible encephalopathy syndrome (PRES) is a rare entity involving brainstem in very rare reported cases. We describe here the case of a boy who presented to the emergency department for headaches and strabismus. Diagnosis of PRES was retained by magnetic resonance imaging. The causes were blood pressure urgency and renal failure. Location of lesions was very rarely reported in literature and neurological troubles were persistent. Emergency physicians should evocate...

  4. Neurochemical dynamics of acute orofacial pain in the human trigeminal brainstem nuclear complex. (United States)

    de Matos, Nuno M P; Hock, Andreas; Wyss, Michael; Ettlin, Dominik A; Brügger, Mike


    The trigeminal brainstem sensory nuclear complex is the first central relay structure mediating orofacial somatosensory and nociceptive perception. Animal studies suggest a substantial involvement of neurochemical alterations at such basal CNS levels in acute and chronic pain processing. Translating this animal based knowledge to humans is challenging. Human related examining of brainstem functions are challenged by MR related peculiarities as well as applicability aspects of experimentally standardized paradigms. Based on our experience with an MR compatible human orofacial pain model, the aims of the present study were twofold: 1) from a technical perspective, the evaluation of proton magnetic resonance spectroscopy at 3 T regarding measurement accuracy of neurochemical profiles in this small brainstem nuclear complex and 2) the examination of possible neurochemical alterations induced by an experimental orofacial pain model. Data from 13 healthy volunteers aged 19-46 years were analyzed and revealed high quality spectra with significant reductions in total N-acetylaspartate (N-acetylaspartate + N-acetylaspartylglutamate) (-3.7%, p = 0.009) and GABA (-10.88%, p = 0.041) during the pain condition. These results might reflect contributions of N-acetylaspartate and N-acetylaspartylglutamate in neuronal activity-dependent physiologic processes and/or excitatory neurotransmission, whereas changes in GABA might indicate towards a reduction in tonic GABAergic functioning during nociceptive signaling. Summarized, the present study indicates the applicability of (1)H-MRS to obtain neurochemical dynamics within the human trigeminal brainstem sensory nuclear complex. Further developments are needed to pave the way towards bridging important animal based knowledge with human research to understand the neurochemistry of orofacial nociception and pain. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Combined driving and sensing circuitry for dielectric elastomer actuators in mobile applications (United States)

    Matysek, Marc; Haus, Henry; Moessinger, Holger; Brokken, Dirk; Lotz, Peter; Schlaak, Helmut F.


    Dielectric elastomer stack actuators (DESA) promise breakthrough functionality in user interfaces by enabling freely programmable surfaces with various shapes. Besides the fundamental advantages of this technology, like comparatively low energy consumption, it is well known that these actuators can be used as sensors simultaneously. The work we present in this paper is focused on the implementation of a DEA-based tactile display into a mobile device. The generation of the driving voltage of up to 1.1 kV out of a common rechargeable battery and the implementation of the sensor functionality are the most challenging tasks. To realize a large range of tactile experiences, both static and dynamic driving voltages are required. We present a structure combining different step-up topologies to realize the driving unit. The final circuitry complies with typical requirements for mobile devices, like small size, low weight, high efficiency and low costs. The sensing functionality has to be realized for different actuator elements regardless of their actual state. An additional sensing layer on top or within the actuators would cause a higher fabrication effort and additional interconnections. Therefore, we developed a high voltage compatible sensing system. The circuitry allows sensing of user input at every actuator element. Both circuits are implemented into a handheld-like device.

  6. A Wirelessly Powered Smart Contact Lens with Reconfigurable Wide Range and Tunable Sensitivity Sensor Readout Circuitry. (United States)

    Chiou, Jin-Chern; Hsu, Shun-Hsi; Huang, Yu-Chieh; Yeh, Guan-Ting; Liou, Wei-Ting; Kuei, Cheng-Kai


    This study presented a wireless smart contact lens system that was composed of a reconfigurable capacitive sensor interface circuitry and wirelessly powered radio-frequency identification (RFID) addressable system for sensor control and data communication. In order to improve compliance and reduce user discomfort, a capacitive sensor was embedded on a soft contact lens of 200 μm thickness using commercially available bio-compatible lens material and a standard manufacturing process. The results indicated that the reconfigurable sensor interface achieved sensitivity and baseline tuning up to 120 pF while consuming only 110 μW power. The range and sensitivity tuning of the readout circuitry ensured a reliable operation with respect to sensor fabrication variations and independent calibration of the sensor baseline for individuals. The on-chip voltage scaling allowed the further extension of the detection range and prevented the implementation of large on-chip elements. The on-lens system enabled the detection of capacitive variation caused by pressure changes in the range of 2.25 to 30 mmHg and hydration level variation from a distance of 1 cm using incident power from an RFID reader at 26.5 dBm.

  7. Reading acceleration training changes brain circuitry in children with reading difficulties (United States)

    Horowitz-Kraus, Tzipi; Vannest, Jennifer J; Kadis, Darren; Cicchino, Nicole; Wang, Yingying Y; Holland, Scott K


    Introduction Dyslexia is characterized by slow, inaccurate reading. Previous studies have shown that the Reading Acceleration Program (RAP) improves reading speed and accuracy in children and adults with dyslexia and in typical readers across different orthographies. However, the effect of the RAP on the neural circuitry of reading has not been established. In the current study, we examined the effect of the RAP training on regions of interest in the neural circuitry for reading using a lexical decision task during fMRI in children with reading difficulties and typical readers. Methods Children (8–12 years old) with reading difficulties and typical readers were studied before and after 4 weeks of training with the RAP in both groups. Results In addition to improvements in oral and silent contextual reading speed, training-related gains were associated with increased activation of the left hemisphere in both children with reading difficulties and typical readers. However, only children with reading difficulties showed improvements in reading comprehension, which were associated with significant increases in right frontal lobe activation. Conclusions Our results demonstrate differential effects of the RAP on neural circuits supporting reading in both children with reading difficulties and typical readers and suggest that the intervention may stimulate use of typical neural circuits for reading and engage compensatory pathways to support reading in the developing brain of children with reading difficulties. PMID:25365797

  8. Microstructural abnormalities in subcortical reward circuitry of subjects with major depressive disorder.

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    Anne J Blood


    Full Text Available Previous studies of major depressive disorder (MDD have focused on abnormalities in the prefrontal cortex and medial temporal regions. There has been little investigation in MDD of midbrain and subcortical regions central to reward/aversion function, such as the ventral tegmental area/substantia nigra (VTA/SN, and medial forebrain bundle (MFB.We investigated the microstructural integrity of this circuitry using diffusion tensor imaging (DTI in 22 MDD subjects and compared them with 22 matched healthy control subjects. Fractional anisotropy (FA values were increased in the right VT and reduced in dorsolateral prefrontal white matter in MDD subjects. Follow-up analysis suggested two distinct subgroups of MDD patients, which exhibited non-overlapping abnormalities in reward/aversion circuitry. The MDD subgroup with abnormal FA values in VT exhibited significantly greater trait anxiety than the subgroup with normal FA values in VT, but the subgroups did not differ in levels of anhedonia, sadness, or overall depression severity.These findings suggest that MDD may be associated with abnormal microstructure in brain reward/aversion regions, and that there may be at least two subtypes of microstructural abnormalities which each impact core symptoms of depression.

  9. PER2 rs2304672 polymorphism moderates circadian-relevant reward circuitry activity in adolescents. (United States)

    Forbes, Erika E; Dahl, Ronald E; Almeida, Jorge R C; Ferrell, Robert E; Nimgaonkar, Vishwajit L; Mansour, Hader; Sciarrillo, Samantha R; Holm, Stephanie M; Rodriguez, Eric E; Phillips, Mary L


    Reward behavior in animals is influenced by circadian genes, including clock-pathway genes such as Period2 (PER2). Several forms of psychiatric illness are associated with both altered reward function and disturbances in circadian function. The PER2 single nucleotide polymorphism (SNP) rs2304672 has been associated with psychiatric illnesses involving reward dysfunction. Associations among circadian genes, function in neural reward circuits, and circadian-influenced behavior have not yet been studied in humans, however. 90 healthy adolescents underwent functional magnetic resonance imaging during a guessing task with monetary reward, genotyping for two PER2 SNPs (rs2304672, rs2304674), and actigraphy to measure sleep in their home environments. Weekend sleep midpoint, a behavioral index of circadian function, was derived from actigraphy. Puberty was measured by physical exam. The rs2304672 SNP predicted blood oxygenation level-dependent response to monetary reward as constrained by sleep midpoint. Later sleep midpoint was associated with reduced activity in a key component of reward circuitry, medial prefrontal cortex (mPFC; Brodmann area 9/10/32), to reward outcome (p(corrected) circadian genes have a significant impact upon circadian-relevant reward circuitry in humans. These findings have the potential to elucidate gene-brain-behavior relationships underlying reward processing and psychopathology.

  10. Targeting Lumbar Spinal Neural Circuitry by Epidural Stimulation to Restore Motor Function After Spinal Cord Injury. (United States)

    Minassian, Karen; McKay, W Barry; Binder, Heinrich; Hofstoetter, Ursula S


    Epidural spinal cord stimulation has a long history of application for improving motor control in spinal cord injury. This review focuses on its resurgence following the progress made in understanding the underlying neurophysiological mechanisms and on recent reports of its augmentative effects upon otherwise subfunctional volitional motor control. Early work revealed that the spinal circuitry involved in lower-limb motor control can be accessed by stimulating through electrodes placed epidurally over the posterior aspect of the lumbar spinal cord below a paralyzing injury. Current understanding is that such stimulation activates large-to-medium-diameter sensory fibers within the posterior roots. Those fibers then trans-synaptically activate various spinal reflex circuits and plurisegmentally organized interneuronal networks that control more complex contraction and relaxation patterns involving multiple muscles. The induced change in responsiveness of this spinal motor circuitry to any residual supraspinal input via clinically silent translesional neural connections that have survived the injury may be a likely explanation for rudimentary volitional control enabled by epidural stimulation in otherwise paralyzed muscles. Technological developments that allow dynamic control of stimulation parameters and the potential for activity-dependent beneficial plasticity may further unveil the remarkable capacity of spinal motor processing that remains even after severe spinal cord injuries.

  11. Childhood maltreatment is associated with altered fear circuitry and increased internalizing symptoms by late adolescence. (United States)

    Herringa, Ryan J; Birn, Rasmus M; Ruttle, Paula L; Burghy, Cory A; Stodola, Diane E; Davidson, Richard J; Essex, Marilyn J


    Maltreatment during childhood is a major risk factor for anxiety and depression, which are major public health problems. However, the underlying brain mechanism linking maltreatment and internalizing disorders remains poorly understood. Maltreatment may alter the activation of fear circuitry, but little is known about its impact on the connectivity of this circuitry in adolescence and whether such brain changes actually lead to internalizing symptoms. We examined the associations between experiences of maltreatment during childhood, resting-state functional brain connectivity (rs-FC) of the amygdala and hippocampus, and internalizing symptoms in 64 adolescents participating in a longitudinal community study. Childhood experiences of maltreatment were associated with lower hippocampus-subgenual cingulate rs-FC in both adolescent females and males and lower amygdala-subgenual cingulate rs-FC in females only. Furthermore, rs-FC mediated the association of maltreatment during childhood with adolescent internalizing symptoms. Thus, maltreatment in childhood, even at the lower severity levels found in a community sample, may alter the regulatory capacity of the brain's fear circuit, leading to increased internalizing symptoms by late adolescence. These findings highlight the importance of fronto-hippocampal connectivity for both sexes in internalizing symptoms following maltreatment in childhood. Furthermore, the impact of maltreatment during childhood on both fronto-amygdala and -hippocampal connectivity in females may help explain their higher risk for internalizing disorders such as anxiety and depression.

  12. Testing the connections within face processing circuitry in Capgras delusion with diffusion imaging tractography

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    Maria A. Bobes


    Full Text Available Although Capgras delusion (CD patients are capable of recognizing familiar faces, they present a delusional belief that some relatives have been replaced by impostors. CD has been explained as a selective disruption of a pathway processing affective values of familiar faces. To test the integrity of connections within face processing circuitry, diffusion tensor imaging was performed in a CD patient and 10 age-matched controls. Voxel-based morphometry indicated gray matter damage in right frontal areas. Tractography was used to examine two important tracts of the face processing circuitry: the inferior fronto-occipital fasciculus (IFOF and the inferior longitudinal (ILF. The superior longitudinal fasciculus (SLF and commissural tracts were also assessed. CD patient did not differ from controls in the commissural fibers, or the SLF. Right and left ILF, and right IFOF were also equivalent to those of controls. However, the left IFOF was significantly reduced respect to controls, also showing a significant dissociation with the ILF, which represents a selective impairment in the fiber-tract connecting occipital and frontal areas. This suggests a possible involvement of the IFOF in affective processing of faces in typical observers and in covert recognition in some cases with prosopagnosia.

  13. Reading acceleration training changes brain circuitry in children with reading difficulties. (United States)

    Horowitz-Kraus, Tzipi; Vannest, Jennifer J; Kadis, Darren; Cicchino, Nicole; Wang, Yingying Y; Holland, Scott K


    Dyslexia is characterized by slow, inaccurate reading. Previous studies have shown that the Reading Acceleration Program (RAP) improves reading speed and accuracy in children and adults with dyslexia and in typical readers across different orthographies. However, the effect of the RAP on the neural circuitry of reading has not been established. In the current study, we examined the effect of the RAP training on regions of interest in the neural circuitry for reading using a lexical decision task during fMRI in children with reading difficulties and typical readers. Children (8-12 years old) with reading difficulties and typical readers were studied before and after 4 weeks of training with the RAP in both groups. In addition to improvements in oral and silent contextual reading speed, training-related gains were associated with increased activation of the left hemisphere in both children with reading difficulties and typical readers. However, only children with reading difficulties showed improvements in reading comprehension, which were associated with significant increases in right frontal lobe activation. Our results demonstrate differential effects of the RAP on neural circuits supporting reading in both children with reading difficulties and typical readers and suggest that the intervention may stimulate use of typical neural circuits for reading and engage compensatory pathways to support reading in the developing brain of children with reading difficulties.

  14. Selective attention modulates human auditory brainstem responses: relative contributions of frequency and spatial cues.

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    Alexandre Lehmann

    Full Text Available Selective attention is the mechanism that allows focusing one's attention on a particular stimulus while filtering out a range of other stimuli, for instance, on a single conversation in a noisy room. Attending to one sound source rather than another changes activity in the human auditory cortex, but it is unclear whether attention to different acoustic features, such as voice pitch and speaker location, modulates subcortical activity. Studies using a dichotic listening paradigm indicated that auditory brainstem processing may be modulated by the direction of attention. We investigated whether endogenous selective attention to one of two speech signals affects amplitude and phase locking in auditory brainstem responses when the signals were either discriminable by frequency content alone, or by frequency content and spatial location. Frequency-following responses to the speech sounds were significantly modulated in both conditions. The modulation was specific to the task-relevant frequency band. The effect was stronger when both frequency and spatial information were available. Patterns of response were variable between participants, and were correlated with psychophysical discriminability of the stimuli, suggesting that the modulation was biologically relevant. Our results demonstrate that auditory brainstem responses are susceptible to efferent modulation related to behavioral goals. Furthermore they suggest that mechanisms of selective attention actively shape activity at early subcortical processing stages according to task relevance and based on frequency and spatial cues.

  15. [Brainstem encephalitis and myelitis due to Listeria monocytogenes: a case report and literature review]. (United States)

    Castro, Aracelly; Hernández, Olga Helena; Uribe, Carlos Santiago; Guerra, Alejandro; Urueña, Piedad


    Brainstem encephalitis caused by Listeria monocytogenes is an uncommon form of central nervous system listeriosis; however, it is the most common presentation in immunocompetent individuals. Here, we describe an even more rare combination of rhombencephalitis with severe myelitis caused by L. monocytogenes in an immunocompetent patient. We report the case of a 21-year-old immunocompetent patient who consumed unpasteurized dairy products and experienced headache and vomiting that progressed to an impaired general condition, altered consciousness and ultimately death. The patient had presented to the Neurological Institute of Colombia (INDEC in Spanish) for consultation and was diagnosed with brainstem encephalitis and myelitis caused by Listeria monocytogenes . The differences between this particular case and those reported in the literature will be discussed. It is advisable to initiate antibiotic treatment for Listeria monocytogenes if a patient shows signs of brainstem compromise of possible infectious origin and quickly intensify treatment if there is no or minimal response. It is also necessary to extend radiological assessment to include the spinal column to rule out spinal cord involvement.

  16. Potential Asphyxia and Brainstem Abnormalities in Sudden and Unexpected Death in Infants (United States)

    Randall, Bradley B.; Paterson, David S.; Haas, Elisabeth A.; Broadbelt, Kevin G.; Duncan, Jhodie R.; Mena, Othon J.; Krous, Henry F.; Trachtenberg, Felicia L.


    OBJECTIVE: Sudden and unexplained death is a leading cause of infant mortality. Certain characteristics of the sleep environment increase the risk for sleep-related sudden and unexplained infant death. These characteristics have the potential to generate asphyxial conditions. We tested the hypothesis that infants may be exposed to differing degrees of asphyxia in sleep environments, such that vulnerable infants with a severe underlying brainstem deficiency in serotonergic, γ-aminobutyric acid-ergic, or 14-3-3 transduction proteins succumb even without asphyxial triggers (eg, supine), whereas infants with intermediate or borderline brainstem deficiencies require asphyxial stressors to precipitate death. METHODS: We classified cases of sudden infant death into categories relative to a “potential asphyxia” schema in a cohort autopsied at the San Diego County Medical Examiner’s Office. Controls were infants who died with known causes of death established at autopsy. Analysis of covariance tested for differences between groups. RESULTS: Medullary neurochemical abnormalities were present in both infants dying suddenly in circumstances consistent with asphyxia and infants dying suddenly without obvious asphyxia-generating circumstances. There were no differences in the mean neurochemical measures between these 2 groups, although mean measures were both significantly lower (P infants dying suddenly and unexpectedly. Brainstem abnormalities were associated with both asphyxia-generating and non–asphyxia generating conditions. Heeding safe sleep messages is essential for all infants, especially given our current inability to detect underlying vulnerabilities. PMID:24218471

  17. Interaural delay-dependent changes in the binaural interaction component of the guinea pig brainstem responses. (United States)

    Goksoy, Cuneyt; Demirtas, Serdar; Yagcioglu, Suha; Ungan, Pekcan


    Auditory brainstem responses to monaural and binaural clicks with 23 different interaural time differences (ITDs) were recorded from ten guinea pigs without anesthesia. Binaural interaction component was obtained by subtracting the sum of the appropriately time-shifted left and right monaural responses from the binaural one. With increasing ITD, the most prominent peak of the binaural difference potential so obtained shifted to longer latencies and its amplitude gradually decreased. The way these changes depended on binaural delay was basically similar to that previously observed in a cat study [P. Ungan, S. Yagcioglu, B. Ozmen. Interaural delay-dependent changes in the binaural difference potential in cat auditory brainstem response: implications about the origin of the binaural interaction component. Hear. Res. 106 (1997) 66-82]. The data were successfully simulated by the model suggested in that report. We therefore concluded that the same model, which was based on the difference between the mean onset latencies of the ipsilateral excitation and contralateral inhibition in a typical neuron in the lateral superior olive, their standard deviations, and the duration of the contralateral inhibition, should also be valid for the binaural interaction in the guinea pig brainstem. The results, which were discussed in connection with sound lateralization models, supported a model based on population coding, where the lateral position of a sound source is coded by the ratio of the discharge intensity in the left and right lateral superior olives, rather than the models based on coincidence detection.

  18. Evaluting the effect of long-term monaural hearing aid usage via auditory brainstem response

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    Tayebeh Ahmadi


    Full Text Available Background and Aim: Studies have shown that long-term use of monaural hearing aid in symmetrical hearing losses may lead to physiological changes. In this research, the possibility of plasticity occurrence in bilaterally hearing impaired listeners fitted with only one hearing aid was investigated.Methods: Our study was carried out on 12 elderly listeners with a mean age of 61.92 years who had symmetrical moderate to severe sensory neural hearing loss in both ears. All of the participants had minimum monaural hearing aid experience of 2 years. We used auditory brainstem response (ABR testing in order to compare absolute latency and amplitude of wave V between the two ears of cases. Air conduction click stimuli were presented monaurally at 80, 90 and 100 dB nHL.Results: Despite the shorter absolute latency of wave V in the fitted ear, no significant difference was found between the two ears (p>0.389. The difference between wave V amplitude of both ears was greater in 90 dB nHL level (p=0.043. Women showed shorter mean latency than men and the mean amplitude of women was greater than men. Significant gender difference was observed in absolute latency of wave V (p<0.037.Conclusion: Our findings indicate that the use of monaural hearing aid in symmetrical hearing losses can induce neural plasticity within auditory brainstem pathways which can be displayed by auditory brainstem response test.

  19. Impact of monaural frequency compression on binaural fusion at the brainstem level. (United States)

    Klauke, Isabelle; Kohl, Manuel C; Hannemann, Ronny; Kornagel, Ulrich; Strauss, Daniel J; Corona-Strauss, Farah I


    A classical objective measure for binaural fusion at the brainstem level is the so-called β-wave of the binaural interaction component (BIC) in the auditory brainstem response (ABR). However, in some cases it appeared that a reliable detection of this component still remains a challenge. In this study, we investigate the wavelet phase synchronization stability (WPSS) of ABR data for the analysis of binaural fusion and compare it to the BIC. In particular, we examine the impact of monaural nonlinear frequency compression on binaural fusion. As the auditory system is tonotopically organized, an interaural frequency mismatch caused by monaural frequency compression could negatively effect binaural fusion. In this study, only few subjects showed a detectable β-wave and in most cases only for low ITDs. However, we present a novel objective measure for binaural fusion that outperforms the current state-of-the-art technique (BIC): the WPSS analysis showed a significant difference between the phase stability of the sum of the monaurally evoked responses and the phase stability of the binaurally evoked ABR. This difference could be an indicator for binaural fusion in the brainstem. Furthermore, we observed that monaural frequency compression could indeed effect binaural fusion, as the WPSS results for this condition vary strongly from the results obtained without frequency compression.

  20. Effectiveness of interferon-[beta], ACNU, and radiation therapy in pediatric patients with brainstem glioma

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    Wakabayashi, Toshihiko; Yoshida, Jun; Mizuno, Masaaki; Sugita, Kenichiro (Nagoya Univ. (Japan). Faculty of Medicine); Kito, Akira


    Sixteen pediatric patients with brainstem glioma were treated with a combination of interferon-[beta], 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl -3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), and radiation therapy (IAR therapy). All patients received 1-1.5 million IU/day of interferon-[beta] intravenously for 1 week of each 6-week cycle. In addition, ACNU (2-3 mg/kg) was given on the 2nd day of each cycle. Conventional focal irradiation (1.5-2 Gy/day for 5 days to a total dosage of 40-60 Gy) was administered beginning on day 3. Patients underwent at least two 6-week cycles. Adverse effects included nausea, vomiting, and myelosuppression, but were mild and transient. Response to treatment was evaluated by the reduction in tumor size measured on postcontrast computed tomographic scans and magnetic resonance images. Responses occurred in 10 of 11 patients with the intrinsic type of brainstem glioma, including three complete and seven partial responses. Two of the five patients with exophytic type gliomas partially responded. The median survival was 15.7 months, a remarkable improvement over the natural course of this disease. These results indicate that IAR therapy is a useful primary treatment for pediatric patients with brainstem gliomas. (author).

  1. Blast overpressure induced axonal injury changes in rat brainstem and spinal cord

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    Srinivasu Kallakuri


    Full Text Available Introduction: Blast induced neurotrauma has been the signature wound in returning soldiers from the ongoing wars in Iraq and Afghanistan. Of importance is understanding the pathomechansim(s of blast overpressure (OP induced axonal injury. Although several recent animal models of blast injury indicate the neuronal and axonal injury in various brain regions, animal studies related to axonal injury in the white matter (WM tracts of cervical spinal cord are limited. Objective: The purpose of this study was to assess the extent of axonal injury in WM tracts of cervical spinal cord in male Sprague Dawley rats subjected to a single insult of blast OP. Materials and Methods: Sagittal brainstem sections and horizontal cervical spinal cord sections from blast and sham animals were stained by neurofilament light (NF-L chain and beta amyloid precursor protein immunocytochemistry and observed for axonal injury changes. Results: Observations from this preliminary study demonstrate axonal injury changes in the form of prominent swellings, retraction bulbs, and putative signs of membrane disruptions in the brainstem and cervical spinal cord WM tracts of rats subjected to blast OP. Conclusions: Prominent axonal injury changes following the blast OP exposure in brainstem and cervical spinal WM tracts underscores the need for careful evaluation of blast induced injury changes and associated symptoms. NF-L immunocytochemistry can be considered as an additional tool to assess the blast OP induced axonal injury.

  2. Relationship between brainstem auditory function during the neonatal period and depressed Apgar score. (United States)

    Jiang, Ze Dong; Wilkinson, Andrew Robert


    To understand whether infants with depressed Apgar scores are at high risk of brainstem auditory impairment, we examined the relationship between brainstem auditory function during the neonatal period and depressed Apgar score. Brainstem auditory evoked responses (BAERs) were recorded from day 1 to day 30 in 145 term infants with Apgar scores Apgar score none of BAER response wave latencies and interpeak intervals during the first 15 days correlated significantly with the score. On day 30, all wave latencies but no intervals correlated negatively with the score (all p Apgar score, only on day 3 wave V latency and I-V and III-V intervals correlated negatively with the score (all p Apgar score, only III-V interval correlated negatively with the score (p Apgar scores. Wave V latency and I-V and III-V intervals on day 3 were all significantly longer in infants with 5-min Apgar scores 6. During the neonatal period, only on day 3 after birth a depressed 5-min Apgar score is an indicator associated with central auditory impairment. A depressed 1-min score may be associated with later peripheral auditory impairment.

  3. A case study of the resolution of paediatric dysphagia following brainstem injury: clinical and instrumental assessment. (United States)

    Morgan, Angela; Ward, Elizabeth; Murdoch, Bruce


    The coexistance of a swallowing impairment can severely impact upon the medical condition and recovery of a child with traumatic brain injury [ref.: Journal of Head Trauma Rehabilitation 9 (1) (1994) 43]. Limited data exist on the progression or outcome of dysphagia in the paediatric population with brainstem injury. The present prospective study documents the resolution of dysphagia in a 14-year-old female post-brainstem injury using clinical, radiological and endoscopic evaluations of swallowing. The subject presented with a pattern of severe oral-motor and oropharyngeal swallowing impairment post-injury that resolved rapidly for the initial 12 weeks, slowed to gradual progress for weeks 12-20, and then plateaued at 20 weeks post-injury. Whilst a clinically functional swallow was present at 10 months post-injury, radiological examination revealed a number of residual physiological impairments, reduced swallowing efficiency, and reduced independence for feeding, indicating a potential increased risk for aspiration. The data highlight the need for early and continued evaluation and intensive treatment programs, to focus on the underlying physiological swallowing impairment post-brainstem injury, and to help offset any potential deleterious effects of aspiration that may affect patient recovery, such as pneumonia.

  4. Catecholaminergic innervation of central and peripheral auditory circuitry varies with reproductive state in female midshipman fish, Porichthys notatus.

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    Paul M Forlano

    Full Text Available In seasonal breeding vertebrates, hormone regulation of catecholamines, which include dopamine and noradrenaline, may function, in part, to modulate behavioral responses to conspecific vocalizations. However, natural seasonal changes in catecholamine innervation of auditory nuclei is largely unexplored, especially in the peripheral auditory system, where encoding of social acoustic stimuli is initiated. The plainfin midshipman fish, Porichthys notatus, has proven to be an excellent model to explore mechanisms underlying seasonal peripheral auditory plasticity related to reproductive social behavior. Recently, we demonstrated robust catecholaminergic (CA innervation throughout the auditory system in midshipman. Most notably, dopaminergic neurons in the diencephalon have widespread projections to auditory circuitry including direct innervation of the saccule, the main endorgan of hearing, and the cholinergic octavolateralis efferent nucleus (OE which also projects to the inner ear. Here, we tested the hypothesis that gravid, reproductive summer females show differential CA innervation of the auditory system compared to non-reproductive winter females. We utilized quantitative immunofluorescence to measure tyrosine hydroxylase immunoreactive (TH-ir fiber density throughout central auditory nuclei and the sensory epithelium of the saccule. Reproductive females exhibited greater density of TH-ir innervation in two forebrain areas including the auditory thalamus and greater density of TH-ir on somata and dendrites of the OE. In contrast, non-reproductive females had greater numbers of TH-ir terminals in the saccule and greater TH-ir fiber density in a region of the auditory hindbrain as well as greater numbers of TH-ir neurons in the preoptic area. These data provide evidence that catecholamines may function, in part, to seasonally modulate the sensitivity of the inner ear and, in turn, the appropriate behavioral response to reproductive acoustic

  5. The periaqueductal gray controls brainstem emotional motor systems including respiration. (United States)

    Holstege, Gert


    Respiration is a motor system essential for the survival of the individual and of the species. Because of its vital significance, studies on respiration often assume that breathing takes place independent of other motor systems. However, motor systems generating vocalization, coughing, sneezing, vomiting, as well as parturition, ejaculation, and defecation encompass abdominal pressure control, which involves changes in the respiratory pattern. The mesencephalic periaqueductal gray (PAG) controls all these motor systems. It determines the level setting of the whole body by means of its very strong projections to the ventromedial medullary tegmentum, but it also controls the cell groups that generate vocalization, coughing, sneezing, vomiting, as well as respiration. For this control, the PAG maintains very strong connections with the nucleus retroambiguus, which enables it to control abdominal and intrathoracic pressure. In this same context, the PAG also runs the pelvic organs, bladder, uterus, prostate, seminal vesicles, and the distal colon and rectum via its projections to the pelvic organ stimulating center and the pelvic floor stimulating center. These cell groups, via long descending projections, have direct control of the parasympathetic motoneurons in the sacral cord as well as of the somatic motoneurons in the nucleus of Onuf, innervating the pelvic floor. Respiration, therefore, is not a motor system that functions by itself, but is strongly regulated by the same systems that also control the other motor output systems. © 2014 Elsevier B.V. All rights reserved.

  6. Robust Machine Learning-Based Correction on Automatic Segmentation of the Cerebellum and Brainstem.

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    Jun Yi Wang

    Full Text Available Automated segmentation is a useful method for studying large brain structures such as the cerebellum and brainstem. However, automated segmentation may lead to inaccuracy and/or undesirable boundary. The goal of the present study was to investigate whether SegAdapter, a machine learning-based method, is useful for automatically correcting large segmentation errors and disagreement in anatomical definition. We further assessed the robustness of the method in handling size of training set, differences in head coil usage, and amount of brain atrophy. High resolution T1-weighted images were acquired from 30 healthy controls scanned with either an 8-channel or 32-channel head coil. Ten patients, who suffered from brain atrophy because of fragile X-associated tremor/ataxia syndrome, were scanned using the 32-channel head coil. The initial segmentations of the cerebellum and brainstem were generated automatically using Freesurfer. Subsequently, Freesurfer's segmentations were both manually corrected to serve as the gold standard and automatically corrected by SegAdapter. Using only 5 scans in the training set, spatial overlap with manual segmentation in Dice coefficient improved significantly from 0.956 (for Freesurfer segmentation to 0.978 (for SegAdapter-corrected segmentation for the cerebellum and from 0.821 to 0.954 for the brainstem. Reducing the training set size to 2 scans only decreased the Dice coefficient ≤0.002 for the cerebellum and ≤ 0.005 for the brainstem compared to the use of training set size of 5 scans in corrective learning. The method was also robust in handling differences between the training set and the test set in head coil usage and the amount of brain atrophy, which reduced spatial overlap only by <0.01. These results suggest that the combination of automated segmentation and corrective learning provides a valuable method for accurate and efficient segmentation of the cerebellum and brainstem, particularly in large

  7. Hypoxia attenuates purinergic P2X receptor-induced inflammatory gene expression in brainstem microglia

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    Smith SMC


    Full Text Available Stephanie MC Smith,1,2 Gordon S Mitchell,1,2 Scott A Friedle,3 Christine M Sibigtroth,1 Stéphane Vinit,1 Jyoti J Watters1–31Department of Comparative Biosciences, 2Comparative Biomedical Sciences Training Program, 3Program in Cellular and Molecular Biology, University of Wisconsin, Madison, WI, USAAbstract: Hypoxia and increased extracellular nucleotides are frequently coincident in the brainstem. Extracellular nucleotides are potent modulators of microglial inflammatory gene expression via P2X purinergic receptor activation. Although hypoxia is also known to modulate inflammatory gene expression, little is known about how hypoxia or P2X receptor activation alone affects inflammatory molecule production in brainstem microglia, nor how hypoxia and P2X receptor signaling interact when they occur together. In the study reported here, we investigated the ability of a brief episode of hypoxia (2 hours in the presence and absence of the nonselective P2X receptor agonist 2′(3′-O-(4-benzoylbenzoyladenosine-5′-triphosphate (BzATP to promote inflammatory gene expression in brainstem microglia in adult rats. We evaluated inducible nitric oxide synthase (iNOS, tumor necrosis factor alpha (TNFα, and interleukin (IL-6 messenger RNA levels in immunomagnetically isolated brainstem microglia. While iNOS and IL-6 gene expression increased with hypoxia and BzATP alone, TNFα expression was unaffected. Surprisingly, BzATP-induced inflammatory effects were lost after hypoxia, suggesting that hypoxia impairs proinflammatory P2X-receptor signaling. We also evaluated the expression of key P2X receptors activated by BzATP, namely P2X1, P2X4, and P2X7. While hypoxia did not alter their expression, BzATP upregulated P2X4 and P2X7 mRNAs; these effects were ablated in hypoxia. Although both P2X4 and P2X7 receptor expression correlated with increased microglial iNOS and IL-6 levels in microglia from normoxic rats, in hypoxia, P2X7 only correlated with IL-6, and P2X

  8. Parametric study of dielectric loaded surface plasmon polariton add-drop filters for hybrid silicon/plasmonic optical circuitry (United States)

    Dereux, A.; Hassan, K.; Weeber, J.-C.; Djellali, N.; Bozhevolnyi, S. I.; Tsilipakos, O.; Pitilakis, A.; Kriezis, E.; Papaioannou, S.; Vyrsokinos, K.; Pleros, N.; Tekin, T.; Baus, M.; Kalavrouziotis, D.; Giannoulis, G.; Avramopoulos, H.


    Surface plasmons polaritons are electromagnetic waves propagating along the surface of a conductor. Surface plasmons photonics is a promising candidate to satisfy the constraints of miniaturization of optical interconnects. This contribution reviews an experimental parametric study of dielectric loaded surface plasmon waveguides ring resonators and add-drop filters within the perspective of the recently suggested hybrid technology merging plasmonic and silicon photonics on a single board (European FP7 project PLATON "Merging Plasmonic and Silicon Photonics Technology towards Tb/s routing in optical interconnects"). Conclusions relevant for dielectric loaded surface plasmon switches to be integrated in silicon photonic circuitry will be drawn. They rely on the opportunity offered by plasmonic circuitry to carry optical signals and electric currents through the same thin metal circuitry. The heating of the dielectric loading by the electric current enables to design low foot-print thermo-optical switches driving the optical signal flow.

  9. Electro-active sensor, method for constructing the same; apparatus and circuitry for detection of electro-active species (United States)

    Buehler, Martin (Inventor)


    An electro-active sensor includes a nonconductive platform with a first electrode set attached with a first side of a nonconductive platform. The first electrode set serves as an electrochemical cell that may be utilized to detect electro-active species in solution. A plurality of electrode sets and a variety of additional electrochemical cells and sensors may be attached with the nonconductive platform. The present invention also includes a method for constructing the aforementioned electro-active sensor. Additionally, an apparatus for detection and observation is disclosed, where the apparatus includes a sealable chamber for insertion of a portion of an electro-active sensor. The apparatus allows for monitoring and detection activities. Allowing for control of attached cells and sensors, a dual-mode circuitry is also disclosed. The dual-mode circuitry includes a switch, allowing the circuitry to be switched from a potentiostat to a galvanostat mode.

  10. Population calcium imaging of spontaneous respiratory and novel motor activity in the facial nucleus and ventral brainstem in newborn mice. (United States)

    Persson, Karin; Rekling, Jens C


    The brainstem contains rhythm and pattern forming circuits, which drive cranial and spinal motor pools to produce respiratory and other motor patterns. Here we used calcium imaging combined with nerve recordings in newborn mice to reveal spontaneous population activity in the ventral brainstem and in the facial nucleus. In Fluo-8AM loaded brainstem-spinal cord preparations, respiratory activity on cervical nerves was synchronized with calcium signals at the ventrolateral brainstem surface. Individual ventrolateral neurons at the level of the parafacial respiratory group showed perfect or partial synchrony with respiratory nerve bursts. In brainstem-spinal cord preparations, cut at the level of the mid-facial nucleus, calcium signals were recorded in the dorsal, lateral and medial facial subnuclei during respiratory activity. Strong activity initiated in the dorsal subnucleus, followed by activity in lateral and medial subnuclei. Whole-cell recordings from facial motoneurons showed weak respiratory drives, and electrical field potential recordings confirmed respiratory drive to particularly the dorsal and lateral subnuclei. Putative facial premotoneurons showed respiratory-related calcium signals, and were predominantly located dorsomedial to the facial nucleus. A novel motor activity on facial, cervical and thoracic nerves was synchronized with calcium signals at the ventromedial brainstem extending from the level of the facial nucleus to the medulla–spinal cord border. Cervical dorsal root stimulation induced similar ventromedial activity. The medial facial subnucleus showed calcium signals synchronized with this novel motor activity on cervical nerves, and cervical dorsal root stimulation induced similar medial facial subnucleus activity. In conclusion, the dorsal and lateral facial subnuclei are strongly respiratory-modulated, and the brainstem contains a novel pattern forming circuit that drives the medial facial subnucleus and cervical motor pools.

  11. Exercise-enhanced Neuroplasticity Targeting Motor and Cognitive Circuitry in Parkinson’s Disease (United States)

    Petzinger, G. M.; Fisher, B. E.; McEwen, S.; Beeler, J. A.; Walsh, J. P.; Jakowec, M. W.


    The purpose of this review is to highlight the potential role of exercise in promoting neuroplasticity and repair in Parkinson’s disease (PD). Exercise interventions in individuals with PD incorporate goal-based motor skill training in order to engage cognitive circuitry important in motor learning. Using this exercise approach, physical therapy facilitates learning through instruction and feedback (reinforcement), and encouragement to perform beyond self-perceived capability. Individuals with PD become more cognitively engaged with the practice and learning of movements and skills that were previously automatic and unconscious. Studies that have incorporated both goal-based training and aerobic exercise have supported the potential for improving both cognitive and automatic components of motor control. Utilizing animal models, basic research is beginning to reveal exercise-induced effects on neuroplasticity. Since neuroplasticity occurs at the level of circuits and synaptic connections, we examine the effects of exercise from this perspective. PMID:23769598

  12. Exploiting the dynamic properties of covalent modification cycle for the design of synthetic analog biomolecular circuitry. (United States)

    Foo, Mathias; Sawlekar, Rucha; Bates, Declan G


    Cycles of covalent modification are ubiquitous motifs in cellular signalling. Although such signalling cycles are implemented via a highly concise set of chemical reactions, they have been shown to be capable of producing multiple distinct input-output mapping behaviours - ultrasensitive, hyperbolic, signal-transducing and threshold-hyperbolic. In this paper, we show how the set of chemical reactions underlying covalent modification cycles can be exploited for the design of synthetic analog biomolecular circuitry. We show that biomolecular circuits based on the dynamics of covalent modification cycles allow (a) the computation of nonlinear operators using far fewer chemical reactions than purely abstract designs based on chemical reaction network theory, and (b) the design of nonlinear feedback controllers with strong performance and robustness properties. Our designs provide a more efficient route for translation of complex circuits and systems from chemical reactions to DNA strand displacement-based chemistry, thus facilitating their experimental implementation in future Synthetic Biology applications.

  13. Speech and music quality ratings for linear and nonlinear hearing aid circuitry. (United States)

    Davies-Venn, Evelyn; Souza, Pamela; Fabry, David


    This study evaluated quality ratings for speech and music stimuli processed using peak clipping (PC), compression limiting (CL), and wide-dynamic range compression (WDRC) hearing aid circuitry. Eighteen listeners with mild-to-moderate hearing loss were binaurally fitted with behind-the-ear (BTE) hearing aids and instructed to rate the quality of speech under various conditions in quiet and noise and two genres of music. Results for speech revealed a slight preference for WDRC at 80 dB SPL, and equivalent ratings for the three circuits under all other listening conditions. Music ratings revealed a marginally significant preference for WDRC and a preference for classical over popular music. For music, judgments on pleasantness were the most influential on overall circuit preference.

  14. Radiation-Hardened Circuitry Using Mask-Programmable Analog Arrays. Final Report

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    Britton, Jr., Charles L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Ericson, Milton Nance [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bobrek, Miljko [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Blalock, Benjamin [Univ. of Tennessee, Knoxville, TN (United States)


    As the recent accident at Fukushima Daiichi so vividly demonstrated, telerobotic technologies capable of withstanding high radiation environments need to be readily available to enable operations, repair, and recovery under severe accident scenarios where human entry is extremely dangerous or not possible. Telerobotic technologies that enable remote operation in high dose rate environments have undergone revolutionary improvement over the past few decades. However, much of this technology cannot be employed in nuclear power environments due the radiation sensitivity of the electronics and the organic insulator materials currently in use. This is the final report of the activities involving the NEET 2 project Radiation Hardened Circuitry Using Mask-Programmable Analog Arrays. We present a detailed functional block diagram of the proposed data acquisition system, the thought process leading to technical decisions, the implemented system, and the tested results from the systems. This system will be capable of monitoring at least three parameters of importance to nuclear reactor monitoring: temperature, radiation level, and pressure.

  15. Understanding the Molecular Circuitry of Cell Lineage Specification in the Early Mouse Embryo (United States)

    Bergsmedh, Anna; Donohoe, Mary E.; Hughes, Rebecca-Ayme; Hadjantonakis, Anna-Katerina


    Pluripotent stem cells hold great promise for cell-based therapies in regenerative medicine. However, critical to understanding and exploiting mechanisms of cell lineage specification, epigenetic reprogramming, and the optimal environment for maintaining and differentiating pluripotent stem cells is a fundamental knowledge of how these events occur in normal embryogenesis. The early mouse embryo has provided an excellent model to interrogate events crucial in cell lineage commitment and plasticity, as well as for embryo-derived lineage-specific stem cells and induced pluripotent stem (iPS) cells. Here we provide an overview of cell lineage specification in the early (preimplantation) mouse embryo focusing on the transcriptional circuitry and epigenetic marks necessary for successive differentiation events leading to the formation of the blastocyst. PMID:24710206

  16. Engineering nucleic acid structures for programmable molecular circuitry and intracellular biocomputation (United States)

    Li, Jiang; Green, Alexander A.; Yan, Hao; Fan, Chunhai


    Nucleic acids have attracted widespread attention due to the simplicity with which they can be designed to form discrete structures and programmed to perform specific functions at the nanoscale. The advantages of DNA/RNA nanotechnology offer numerous opportunities for in-cell and in-vivo applications, and the technology holds great promise to advance the growing field of synthetic biology. Many elegant examples have revealed the potential in integrating nucleic acid nanostructures in cells and in vivo where they can perform important physiological functions. In this Review, we summarize the current abilities of DNA/RNA nanotechnology to realize applications in live cells and then discuss the key problems that must be solved to fully exploit the useful properties of nanostructures. Finally, we provide viewpoints on how to integrate the tools provided by DNA/RNA nanotechnology and related new technologies to construct nucleic acid nanostructure-based molecular circuitry for synthetic biology.

  17. Trigeminal-Rostral Ventromedial Medulla circuitry is involved in orofacial hyperalgesia contralateral to tissue injury

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    Chai Bryan


    Full Text Available Abstract Background Our previous studies have shown that complete Freund’s adjuvant (CFA-induced masseter inflammation and microinjection of the pro-inflammatory cytokine interleukin-1β (IL-1β into the subnucleus interpolaris/subnucleus caudalis transition zone of the spinal trigeminal nucleus (Vi/Vc can induce contralateral orofacial hyperalgesia in rat models. We have also shown that contralateral hyperalgesia is attenuated with a lesion of the rostral ventromedial medulla (RVM, a critical site of descending pain modulation. Here we investigated the involvement of the RVM-Vi/Vc circuitry in mediating contralateral orofacial hyperalgesia after an injection of CFA into the masseter muscle. Results Microinjection of the IL-1 receptor antagonist (5 nmol, n=6 into the ipsilateral Vi/Vc attenuated the CFA-induced contralateral hyperalgesia but not the ipsilateral hyperalgesia. Intra-RVM post-treatment injection of the NK1 receptor antagonists, RP67580 (0.5-11.4 nmol and L-733,060 (0.5-11.4 nmol, attenuated CFA-induced bilateral hyperalgesia and IL-1β induced bilateral hyperalgesia. Serotonin depletion in RVM neurons prior to intra-masseter CFA injection prevented the development of contralateral hyperalgesia 1–3 days after CFA injection. Inhibition of 5-HT3 receptors in the contralateral Vi/Vc with direct microinjection of the select 5-HT3 receptor antagonist, Y-25130 (2.6-12.9 nmol, attenuated CFA-induced contralateral hyperalgesia. Lesions to the ipsilateral Vc prevented the development of ipsilateral hyperalgesia but did not prevent the development of contralateral hyperalgesia. Conclusions These results suggest that the development of CFA-induced contralateral orofacial hyperalgesia is mediated through descending facilitatory mechanisms of the RVM-Vi/Vc circuitry.

  18. Neuroanatomical circuitry associated with exploratory eye movement in schizophrenia: a voxel-based morphometric study.

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    Linlin Qiu

    Full Text Available Schizophrenic patients present abnormalities in a variety of eye movement tasks. Exploratory eye movement (EEM dysfunction appears to be particularly specific to schizophrenia. However, the underlying mechanisms of EEM dysfunction in schizophrenia are not clearly understood. To assess the potential neuroanatomical substrates of EEM, we recorded EEM performance and conducted a voxel-based morphometric analysis of gray matter in 33 schizophrenic patients and 29 well matched healthy controls. In schizophrenic patients, decreased responsive search score (RSS and widespread gray matter density (GMD reductions were observed. Moreover, the RSS was positively correlated with GMD in distributed brain regions in schizophrenic patients. Furthermore, in schizophrenic patients, some brain regions with neuroanatomical deficits overlapped with some ones associated with RSS. These brain regions constituted an occipito-tempro-frontal circuitry involved in visual information processing and eye movement control, including the left calcarine cortex [Brodmann area (BA 17], the left cuneus (BA 18, the left superior occipital cortex (BA 18/19, the left superior frontal gyrus (BA 6, the left cerebellum, the right lingual cortex (BA 17/18, the right middle occipital cortex (BA19, the right inferior temporal cortex (BA 37, the right dorsolateral prefrontal cortex (BA 46 and bilateral precentral gyri (BA 6 extending to the frontal eye fields (FEF, BA 8. To our knowledge, we firstly reported empirical evidence that gray matter loss in the occipito-tempro-frontal neuroanatomical circuitry of visual processing system was associated with EEM performance in schizophrenia, which may be helpful for the future effort to reveal the underlying neural mechanisms for EEM disturbances in schizophrenia.

  19. Nonphosphorylated neurofilament protein is expressed by scattered neurons in the vestibular and precerebellar brainstem. (United States)

    Baizer, Joan S


    Vestibular information is essential for the control of posture, balance, and eye movements. The vestibular nerve projects to the four nuclei of the vestibular nuclear complex (VNC), as well as to several additional brainstem nuclei and the cerebellum. We have found that expression of the calcium-binding proteins calretinin (CR) and calbindin (CB), and the synthetic enzyme for nitric oxide synthase (nNOS) define subdivisions of the medial vestibular nucleus (MVe) and the nucleus prepositus (PrH), in cat, monkey, and human. We have asked if the pattern of expression of nonphosphorylated neurofilament protein (NPNFP) might define additional subdivisions of these or other nuclei that participate in vestibular function. We studied the distribution of cells immunoreactive to NPNFP in the brainstems of 5 cats and one squirrel monkey. Labeled cells were scattered throughout the four nuclei of the VNC, as well as in PrH, the reticular formation (RF) and the external cuneate nucleus. We used double-label immunofluorescence to visualize the distribution of these cells relative to other neurochemically defined subdivisions. NPNFP cells were excluded from the CR and CB regions of the MVe. In PrH, NPNFP and nNOS were not colocalized. Cells in the lateral vestibular nucleus and RF colocalized NPNFP and a marker for glutamatergic neurons. We also found that the cholinergic cells and axons of cranial nerve nuclei 3, 4, 6, 7,10 and 12 colocalize NPNFP. The data suggest that NPNFP is expressed by a subset of glutamatergic projection neurons of the vestibular brainstem. NPNFP may be a marker for those cells that are especially vulnerable to the effects of normal aging, neurological disease or disruption of sensory input.

  20. Impaired neural conduction in the auditory brainstem of high-risk very preterm infants. (United States)

    Jiang, Ze D; Chen, Chao


    To test the hypothesis that neural conduction in the auditory brainstem is impaired in high-risk very preterm infants. Eighty-two very preterm infants (gestation 28-32 weeks) with various perinatal problems or complications were studied at term using maximum length sequence (MLS) brainstem auditory evoked response (BAER) with click rates 91-910/s. The data were compared with those in 31 age-matched low-risk very preterm infants and 44 normal gestation (term) infants. High-risk very preterm infants showed a general increase in MLS BAER wave latencies and interpeak intervals. Wave V latency, and III-V and I-V intervals in high-risk very preterm infants were significantly longer than in normal term infants at all click rates, particularly higher rates. I-III interval was significantly longer, and III-V/I-III interval ratio was significantly greater at higher rates. These latency and intervals in high-risk very preterm infants were also longer, though relatively less significantly, than in low-risk very preterm infants. Click rate-related changes in major MLS BAER variables in high-risk infants were more significant than in the two groups of controls. There were major abnormalities in MLS BAER variables that mainly reflect central neural conduction in high-risk very preterm infants. The abnormalities were relatively less significant when compared with low-risk very preterm infants than with normal term infants. Neural conduction in the auditory brainstem, mainly the more central regions, is impaired in high-risk very preterm infants. The impairment is largely attributed to the associated perinatal problems, and partially related to very preterm birth. Copyright © 2013. Published by Elsevier Ireland Ltd.

  1. Cortical and brainstem plasticity in Tourette syndrome and obsessive-compulsive disorder. (United States)

    Suppa, Antonio; Marsili, Luca; Di Stasio, Flavio; Berardelli, Isabella; Roselli, Valentina; Pasquini, Massimo; Cardona, Francesco; Berardelli, Alfredo


    Gilles de la Tourette syndrome is characterized by motor/vocal tics commonly associated with psychiatric disorders, including obsessive-compulsive disorder. We investigated primary motor cortex and brainstem plasticity in Tourette patients, exposed and unexposed to chronic drug treatment, with and without psychiatric disturbances. We also investigated primary motor cortex and brainstem plasticity in obsessive-compulsive disorder. We studied 20 Tourette patients with and without psychiatric disturbances, 15 with obsessive-compulsive disorder, and 20 healthy subjects. All groups included drug-naïve patients. We conditioned the left primary motor cortex with intermittent/continuous theta-burst stimulation and recorded motor evoked potentials. We conditioned the supraorbital nerve with facilitatory/inhibitory high-frequency stimulation and recorded the blink reflex late response area. In healthy subjects, intermittent theta-burst increased and continuous theta-burst stimulation decreased motor evoked potentials. Differently, intermittent theta-burst failed to increase and continuous theta-burst stimulation failed to decrease motor evoked potentials in Tourette patients, with and without psychiatric disturbances. In obsessive-compulsive disorder, intermittent/continuous theta-burst stimulation elicited normal responses. In healthy subjects and in subjects with obsessive-compulsive disorder, the blink reflex late response area increased after facilitatory high-frequency and decreased after inhibitory high-frequency stimulation. Conversely, in Tourette patients, with and without psychiatric disturbances, facilitatory/inhibitory high-frequency stimulation left the blink reflex late response area unchanged. Theta-burst and high-frequency stimulation elicited similar responses in drug-naïve and chronically treated patients. Tourette patients have reduced plasticity regardless of psychiatric disturbances. These findings suggest that abnormal plasticity contributes to the

  2. Trigeminal nerve stimulation modulates brainstem more than cortical excitability in healthy humans. (United States)

    Mercante, B; Pilurzi, G; Ginatempo, F; Manca, A; Follesa, P; Tolu, E; Deriu, F


    Multiple sites in the central nervous system (CNS) have been hypothesized to explain the beneficial effects of transcutaneous trigeminal nerve stimulation (TNS) on several disorders. This work investigated the acute effects of TNS on the excitability of brainstem and intracortical circuits, as well as on sensorimotor integration processes at cortical level in physiological conditions. Brainstem excitability was evaluated in seventeen healthy subjects measuring the R1 and R2 areas of the blink reflex (BR) and its recovery cycle, with cortical excitability and sensorimotor integration assessed by probing short-interval (SICI) and long-interval (LICI) intracortical inhibition, with short-interval (SICF), intracortical facilitation (ICF), short-latency (SAI) and long-latency (LAI) inhibition measuring motor potentials evoked in the first dorsal interosseous muscle by TMS of the contralateral motor cortex. Neurophysiological parameters were assessed, in seventeen healthy subjects, before and after cyclic 20-min TNS delivered bilaterally to the infraorbital nerve. After TNS, the area of the R2 was significantly reduced (p = 0.018). By contrast, R1 area and R2 recovery cycle were unaffected. Similarly, SICI, ICF, LICI, SICF, SAI and LAI appeared unaltered after TNS. These data suggest that, in normal subjects, TNS mainly acts on brainstem polysynaptic circuits mediating the R2 component of the BR and plays a minor role in modifying the activity of higher-level structures involved in the R2 recovery cycle and in modulation of cortical excitability. A further investigation of a chronic TNS-induced effect may disclose a higher potential for TNS in producing measurable after effects on its CNS targets.

  3. Control of Vocal and Respiratory Patterns in Birdsong: Dissection of Forebrain and Brainstem Mechanisms Using Temperature (United States)

    Fee, Michale S.


    Learned motor behaviors require descending forebrain control to be coordinated with midbrain and brainstem motor systems. In songbirds, such as the zebra finch, regular breathing is controlled by brainstem centers, but when the adult songbird begins to sing, its breathing becomes tightly coordinated with forebrain-controlled vocalizations. The periods of silence (gaps) between song syllables are typically filled with brief breaths, allowing the bird to sing uninterrupted for many seconds. While substantial progress has been made in identifying the brain areas and pathways involved in vocal and respiratory control, it is not understood how respiratory and vocal control is coordinated by forebrain motor circuits. Here we combine a recently developed technique for localized brain cooling, together with recordings of thoracic air sac pressure, to examine the role of cortical premotor nucleus HVC (proper name) in respiratory-vocal coordination. We found that HVC cooling, in addition to slowing all song timescales as previously reported, also increased the duration of expiratory pulses (EPs) and inspiratory pulses (IPs). Expiratory pulses, like song syllables, were stretched uniformly by HVC cooling, but most inspiratory pulses exhibited non-uniform stretch of pressure waveform such that the majority of stretch occurred late in the IP. Indeed, some IPs appeared to change duration by the earlier or later truncation of an underlying inspiratory event. These findings are consistent with the idea that during singing the temporal structure of EPs is under the direct control of forebrain circuits, whereas that of IPs can be strongly influenced by circuits downstream of HVC, likely in the brainstem. An analysis of the temporal jitter of respiratory and vocal structure suggests that IPs may be initiated by HVC at the end of each syllable and terminated by HVC immediately before the onset of the next syllable. PMID:21980466

  4. Musical training heightens auditory brainstem function during sensitive periods in development

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    Erika eSkoe


    Full Text Available Experience has a profound influence on how sound is processed in the brain. Yet little is known about how enriched experiences interact with developmental processes to shape neural processing of sound. We examine this question as part of a large cross-sectional study of auditory brainstem development involving more than 700 participants, 213 of whom were classified as musicians. We hypothesized that experience-dependent processes piggyback on developmental processes, resulting in a waxing-and-waning effect of experience that tracks with the undulating developmental baseline. This hypothesis led to the prediction that experience-dependent plasticity would be amplified during periods when developmental changes are underway (i.e., early and later in life and that the peak in experience-dependent plasticity would coincide with the developmental apex for each subcomponent of the auditory brainstem response. Consistent with our predictions, we reveal that musicians have heightened response features at distinctive times in the life span that coincide with periods of developmental change and climax. The effect of musicianship is also quite specific: we find that only select components of auditory brainstem activity are affected, with musicians having heightened function for onset latency, high frequency phase-locking, and response consistency, and with little effect observed for other measures, including lower frequency phase-locking and non-stimulus-related activity. By showing that musicianship imparts a neural signature that is especially evident during childhood and old age, our findings reinforce the idea that the nervous system’s response to sound is chiseled by how a person interacts with his specific auditory environment, with the effect of the environment wielding its greatest influence during certain privileged windows of development.

  5. Chronic exposure to hypergravity affects thyrotropin-releasing hormone levels in rat brainstem and cerebellum (United States)

    Daunton, N. G.; Tang, F.; Corcoran, M. L.; Fox, R. A.; Man, S. Y.


    In studies to determine the neurochemical mechanisms underlying adaptation to altered gravity we have investigated changes in neuropeptide levels in brainstem, cerebellum, hypothalamus, striatum, hippocampus, and cerebral cortex by radioimmunoassay. Fourteen days of hypergravity (hyperG) exposure resulted in significant increases in thyrotropin-releasing hormone (TRH) content of brainstem and cerebellum, but no changes in levels of other neuropeptides (beta-endorphin, cholecystokinin, met-enkephalin, somatostatin, and substance P) examined in these areas were found, nor were TRH levels significantly changed in any other brain regions investigated. The increase in TRH in brainstem and cerebellum was not seen in animals exposed only to the rotational component of centrifugation, suggesting that this increase was elicited by the alteration in the gravitational environment. The only other neuropeptide affected by chronic hyperG exposure was met-enkephalin, which was significantly decreased in the cerebral cortex. However, this alteration in met-enkephalin was found in both hyperG and rotation control animals and thus may be due to the rotational rather than the hyperG component of centrifugation. Thus it does not appear as if there is a generalized neuropeptide response to chronic hyperG following 2 weeks of exposure. Rather, there is an increase only of TRH and that occurs only in areas of the brain known to be heavily involved with vestibular inputs and motor control (both voluntary and autonomic). These results suggest that TRH may play a role in adaptation to altered gravity as it does in adaptation to altered vestibular input following labyrinthectomy, and in cerebellar and vestibular control of locomotion, as seen in studies of ataxia.

  6. Enterovirus 71 can directly infect the brainstem via cranial nerves and infection can be ameliorated by passive immunization. (United States)

    Tan, Soon Hao; Ong, Kien Chai; Wong, Kum Thong


    Enterovirus 71 (EV71)-associated hand, foot, and mouth disease may be complicated by encephalomyelitis. We investigated EV71 brainstem infection and whether this infection could be ameliorated by passive immunization in a mouse model. Enterovirus 71 was injected into unilateral jaw/facial muscles of 2-week-old mice, and hyperimmune sera were given before or after infection. Harvested tissues were studied by light microscopy, immunohistochemistry, in situ hybridization, and viral titration. In unimmunized mice, viral antigen and RNA were detected within 24 hours after infection only in ipsilateral cranial nerves, motor trigeminal nucleus, reticular formation, and facial nucleus; viral titers were significantly higher in the brainstem than in the spinal cord samples. Mice given preinfection hyperimmune serum showed a marked reduction of ipsilateral viral antigen/RNA and viral titers in the brainstem in a dose-dependent manner. With optimum hyperimmune serum given after infection, brainstem infection was significantly reduced in a time-dependent manner. A delay in disease onset and a reduction of disease severity and mortality were also observed. Thus, EV71 can directly infect the brainstem, including the medulla, via cranial nerves, most likely by retrograde axonal transport. This may explain the sudden cardiorespiratory collapse in human patients with fatal encephalomyelitis. Moreover, our results suggest that passive immunization may still benefit EV71-infected patients who have neurologic complications.

  7. Effect of Alcohol on Diffuse Axonal Injury in Rat Brainstem: Diffusion Tensor Imaging and Aquaporin-4 Expression Study

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    Lingmei Kong


    Full Text Available The aim of this study is to assess the effects of alcohol on traumatic brain injury by using diffusion tensor imaging (DTI and evaluate aquaporin-4(AQP4 expression changes in rat brainstems following acute alcohol intoxication with diffuse axonal injury (DAI. We further investigated the correlation between the AQP4 expression and DTI in the brain edema. Eighty-five rats were imaged before and after injury at various stages. DTI was used to measure brainstem apparent diffusion coefficient (ADC and fractional anisotropy (FA, with immunostaining being used to determine AQP4 expression. After acute alcoholism with DAI, ADC values of the brainstem first decreased within 6 h and then elevated. FA values began to decline by 1 h, reaching a minimum at 24 h after trauma. There was a negative correlation between ADC values and brainstem AQP4 expression at 6 h and positive correlation at 6 h to 24 h. Changes of ADC and FA values in DAI with acute alcoholism indicate the effects of ethanol on brain edema and the severity of axonal injury. The correlations between ADC values and the brainstem AQP4 expression at different time points suggest that AQP4 expression follows an adaptative profile to the severity of brain edema.

  8. Individual differences in brainstem and basal ganglia structure predict postural control and balance loss in young and older adults. (United States)

    Boisgontier, Matthieu P; Cheval, Boris; Chalavi, Sima; van Ruitenbeek, Peter; Leunissen, Inge; Levin, Oron; Nieuwboer, Alice; Swinnen, Stephan P


    It remains unclear which specific brain regions are the most critical for human postural control and balance, and whether they mediate the effect of age. Here, associations between postural performance and corticosubcortical brain regions were examined in young and older adults using multiple structural imaging and linear mixed models. Results showed that of the regions involved in posture, the brainstem was the strongest predictor of postural control and balance: lower brainstem volume predicted larger center of pressure deviation and higher odds of balance loss. Analyses of white and gray matter in the brainstem showed that the pedunculopontine nucleus area appeared to be critical for postural control in both young and older adults. In addition, the brainstem mediated the effect of age on postural control, underscoring the brainstem's fundamental role in aging. Conversely, lower basal ganglia volume predicted better postural performance, suggesting an association between greater neural resources in the basal ganglia and greater movement vigor, resulting in exaggerated postural adjustments. Finally, results showed that practice, shorter height and heavier weight (i.e., higher body mass index), higher total physical activity, and larger ankle active (but not passive) range of motion were predictive of more stable posture, irrespective of age. Copyright © 2016 Elsevier Inc. All rights reserved.


    The paper give results of a characterization of ozone emissions from air cleaners equipped with ozone generators and sensor and feedback control circuitry. Ozone emission rates of several consumer appliances, marketed as indoor air treatment or air purification systems, were det...

  10. Neuroimaging of Infectious and Inflammatory Diseases of the Pediatric Cerebellum and Brainstem. (United States)

    Rossi, Andrea; Martinetti, Carola; Morana, Giovanni; Severino, Mariasavina; Tortora, Domenico


    Cerebellar involvement by infectious-inflammatory conditions is rare in children. Most patients present with acute ataxia, and are typically previously healthy, young (often preschool) children. Viral involvement is the most common cause and ranges from acute postinfectious ataxia to acute cerebellitis MR imaging plays a crucial role in the evaluation of patients suspected of harboring inflammatory-infectious involvement of the cerebellum and brainstem. Knowledge of the imaging features of these disorders and technical competence on pediatric MR imaging are necessary for a correct interpretation of findings, which in turn prompts further management. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Increased brainstem perfusion, but no blood-brain barrier disruption, during attacks of migraine with aura. (United States)

    Hougaard, Anders; Amin, Faisal M; Christensen, Casper E; Younis, Samaira; Wolfram, Frauke; Cramer, Stig P; Larsson, Henrik B W; Ashina, Messoud


    See Moskowitz (doi:10.1093/brain/awx099) for a scientific commentary on this article.The migraine aura is characterized by transient focal cortical disturbances causing dramatic neurological symptoms that are usually followed by migraine headache. It is currently not understood how the aura symptoms are related to the headache phase of migraine. Animal studies suggest that cortical spreading depression, the likely mechanism of migraine aura, causes disruption of the blood-brain barrier and noxious stimulation of trigeminal afferents leading to activation of brainstem nuclei and triggering of migraine headache. We used the sensitive and validated technique of dynamic contrast-enhanced high-field magnetic resonance imaging to simultaneously investigate blood-brain barrier permeability and tissue perfusion in the brainstem (at the level of the lower pons), visual cortex, and brain areas of the anterior, middle and posterior circulation during spontaneous attacks of migraine with aura. Patients reported to our institution to undergo magnetic resonance imaging during the headache phase after presenting with typical visual aura. Nineteen patients were scanned during attacks and on an attack-free day. The mean time from attack onset to scanning was 7.6 h. We found increased brainstem perfusion bilaterally during migraine with aura attacks. Perfusion also increased in the visual cortex and posterior white matter following migraine aura. We found no increase in blood-brain barrier permeability in any of the investigated regions. There was no correlation between blood-brain barrier permeability, brain perfusion, and time from symptom onset to examination or pain intensity. Our findings demonstrate hyperperfusion in brainstem during the headache phase of migraine with aura, while the blood-brain barrier remains intact during attacks of migraine with aura. These data thus contradict the preclinical hypothesis of cortical spreading depression-induced blood-brain barrier

  12. A rare case of acute poster ior reversible encephalopathy syndrome involving brainstem in a child

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    Olfa Chakroun-Walha


    Full Text Available Posterior reversible encephalopathy syndrome (PRES is a rare entity involving brainstem in very rare reported cases. We describe here the case of a boy who presented to the emergency department for headaches and strabismus. Diagnosis of PRES was retained by magnetic resonance imaging. The causes were blood pressure urgency and renal failure. Location of lesions was very rarely reported in literature and neurological troubles were persistent. Emergency physicians should evocate PRES each time there is a clinical context associated with neurological troubles by a normal brain CT scan. Early diagnosis is very important to treat its causes and improve prognosis.

  13. Simultaneous POMC gene transfer to hypothalamus and brainstem increases physical activity, lipolysis and reduces adult-onset obesity. (United States)

    Zhang, Yi; Rodrigues, Enda; Li, Gang; Gao, Yongxin; King, Michael; Carter, Christy S; Tumer, Nihal; Cheng, Kit-Yan; Scarpace, Philip J


    Pro-opiomelanocortin (POMC) neurons are identified in two brain sites, the arcuate nucleus of the hypothalamus and nucleus of the solitary tract (NTS) in brainstem. Earlier pharmacological and POMC gene transfer studies demonstrate that melanocortin activation in either site alone improves insulin sensitivity and reduces obesity. The present study, for the first time, investigated the long-term efficacy of POMC gene transfer concurrently into both sites in the regulation of energy metabolism in aged F344xBN rats bearing adult-onset obesity. Pair feeding was included to reveal food-independent POMC impact on energy expenditure. We introduced adeno-associated virus encoding either POMC or green fluorescence protein to the two brain areas in 22-month-old rats, then recorded food intake and body weight, assessed oxygen consumption, serum leptin, insulin and glucose, tested voluntary wheel running, analysed POMC expression, and examined fat metabolism in brown and white adipose tissues. POMC mRNA was significantly increased in both the hypothalamus and NTS region at termination. Relative to pair feeding, POMC caused sustained weight reduction and additional fat loss, lowered fasting insulin and glucose, and augmented white fat hormone-sensitive lipase activity and brown fat uncoupling protein 1 level. By wheel running assessment, the POMC animals ran twice the distance as the Control or pair-fed rats. Thus, the dual-site POMC treatment ameliorated adult-onset obesity effectively, involving a moderate hypophagia lasting ∼60 days, enhanced lipolysis and thermogenesis, and increased physical activity in the form of voluntary wheel running. The latter finding provides a clue for countering age-related decline in physical activity. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd. No claim to original US government works.

  14. Brainstem neurons survive the identical ischemic stress that kills higher neurons: insight to the persistent vegetative state.

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    C Devin Brisson

    Full Text Available Global ischemia caused by heart attack, pulmonary failure, near-drowning or traumatic brain injury often damages the higher brain but not the brainstem, leading to a 'persistent vegetative state' where the patient is awake but not aware. Approximately 30,000 U.S. patients are held captive in this condition but not a single research study has addressed how the lower brain is preferentially protected in these people. In the higher brain, ischemia elicits a profound anoxic depolarization (AD causing neuronal dysfunction and vasoconstriction within minutes. Might brainstem nuclei generate less damaging AD and so be more resilient? Here we compared resistance to acute injury induced from simulated ischemia by 'higher' hippocampal and striatal neurons versus brainstem neurons in live slices from rat and mouse. Light transmittance (LT imaging in response to 10 minutes of oxygen/glucose deprivation (OGD revealed immediate and acutely damaging AD propagating through gray matter of neocortex, hippocampus, striatum, thalamus and cerebellar cortex. In adjacent brainstem nuclei, OGD-evoked AD caused little tissue injury. Whole-cell patch recordings from hippocampal and striatal neurons under OGD revealed sudden membrane potential loss that did not recover. In contrast brainstem neurons from locus ceruleus and mesencephalic nucleus as well as from sensory and motor nuclei only slowly depolarized and then repolarized post-OGD. Two-photon microscopy confirmed non-recoverable swelling and dendritic beading of hippocampal neurons during OGD, while mesencephalic neurons in midbrain appeared uninjured. All of the above responses were mimicked by bath exposure to 100 µM ouabain which inhibits the Na+/K+ pump or to 1-10 nM palytoxin which converts the pump into an open cationic channel. Therefore during ischemia the Na+/K+ pump of higher neurons fails quickly and extensively compared to naturally resilient hypothalamic and brainstem neurons. The selective survival

  15. Channel-noise-induced stochastic facilitation in an auditory brainstem neuron model (United States)

    Schmerl, Brett A.; McDonnell, Mark D.


    Neuronal membrane potentials fluctuate stochastically due to conductance changes caused by random transitions between the open and closed states of ion channels. Although it has previously been shown that channel noise can nontrivially affect neuronal dynamics, it is unknown whether ion-channel noise is strong enough to act as a noise source for hypothesized noise-enhanced information processing in real neuronal systems, i.e., “stochastic facilitation”. Here we demonstrate that biophysical models of channel noise can give rise to two kinds of recently discovered stochastic facilitation effects in a Hodgkin-Huxley-like model of auditory brainstem neurons. The first, known as slope-based stochastic resonance (SBSR), enables phasic neurons to emit action potentials that can encode the slope of inputs that vary slowly relative to key time constants in the model. The second, known as inverse stochastic resonance (ISR), occurs in tonically firing neurons when small levels of noise inhibit tonic firing and replace it with burstlike dynamics. Consistent with previous work, we conclude that channel noise can provide significant variability in firing dynamics, even for large numbers of channels. Moreover, our results show that possible associated computational benefits may occur due to channel noise in neurons of the auditory brainstem. This holds whether the firing dynamics in the model are phasic (SBSR can occur due to channel noise) or tonic (ISR can occur due to channel noise).

  16. Correlation of augmented startle reflex with brainstem electrophysiological responses in Tay-Sachs disease. (United States)

    Nakamura, Sadao; Saito, Yoshiaki; Ishiyama, Akihiko; Sugai, Kenji; Iso, Takashi; Inagaki, Masumi; Sasaki, Masayuki


    To clarify the evolution of an augmented startle reflex in Tay-Sachs disease and compare the temporal relationship between this reflex and brainstem evoked potentials. Clinical and electrophysiological data from 3 patients with Tay-Sachs disease were retrospectively collected. The augmented startle reflex appeared between the age of 3 and 17 months and disappeared between the age of 4 and 6 years. Analysis of brainstem auditory evoked potentials revealed that poor segregation of peak I, but not peak III, coincided with the disappearance of the augmented startle reflex. A blink reflex with markedly high amplitude was observed in a patient with an augmented startle reflex. The correlation between the augmented startle reflex and the preservation of peak I but not peak III supports the theory that the superior olivary nucleus is dispensable for this reflex. The blink reflex with high amplitudes may represent augmented excitability of reticular formation at the pontine tegmentum in Tay-Sachs disease, where the pattern generators for the augmented startle and blink reflexes may functionally overlap. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  17. The Physiological Basis and Clinical Use of the Binaural Interaction Component of the Auditory Brainstem Response (United States)

    Klump, Georg M.; Tollin, Daniel J.


    The auditory brainstem response (ABR) is a sound-evoked non-invasively measured electrical potential representing the sum of neuronal activity in the auditory brainstem and midbrain. ABR peak amplitudes and latencies are widely used in human and animal auditory research and for clinical screening. The binaural interaction component (BIC) of the ABR stands for the difference between the sum of the monaural ABRs and the ABR obtained with binaural stimulation. The BIC comprises a series of distinct waves, the largest of which (DN1) has been used for evaluating binaural hearing in both normal hearing and hearing-impaired listeners. Based on data from animal and human studies, we discuss the possible anatomical and physiological bases of the BIC (DN1 in particular). The effects of electrode placement and stimulus characteristics on the binaurally evoked ABR are evaluated. We review how inter-aural time and intensity differences affect the BIC and, analyzing these dependencies, draw conclusion about the mechanism underlying the generation of the BIC. Finally, the utility of the BIC for clinical diagnoses are summarized. PMID:27232077

  18. Ophthalmoplegia associated with transorbital penetrating brainstem injury by broken fishing pole

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    Kaneko-Ohtaki A


    Full Text Available Aki Kaneko-Ohtaki, Shigeki Machida, Takeshi Sugawara, Daijiro KurosakaDepartment of Ophthalmology, Iwate Medical University School of Medicine, Iwate, JapanAbstract: We report our findings in a case of ophthalmoplegia caused by a transorbital penetrating brainstem injury. An 8-year-old boy was accidentally injured by a broken fishing fiberglass pole which penetrated through the right orbit and entered the brainstem. Magnetic resonance imaging showed a linear wound that entered and passed through the pons obliquely and reached the fourth cerebral ventricle and cerebellar vermis. He had a left-sided hemiplegia and left facial nerve palsy and was diagnosed with “one-and-a-half syndrome”. His hemiplegia and left facial nerve palsy resolved in 2 weeks leaving only a left abducens nerve palsy. The eye position and eye movements fully recovered within 3 months. These findings suggest a good prognosis for this type of trauma unless life-threatening changes develop.Keywords: penetrating orbitocranial trauma, trauma, penetrating orbitocranial injury

  19. English consensus protocol evaluating candidacy for auditory brainstem and cochlear implantation in neurofibromatosis type 2. (United States)

    Tysome, James R; Axon, Patrick R; Donnelly, Neil P; Evans, Dafydd Gareth; Ferner, Rosalie E; O'Connor, Alec F Fitzgerald; Freeman, Simon R; Gleeson, Michael; Halliday, Dorothy; Harris, Frances; Jiang, Dan; Kerr, Richard; King, Andrew; Knight, Richard D; Lloyd, Simon K; Macfarlane, Robert; Mannion, Richard; Mawman, Deborah; O'Driscoll, Martin; Parry, Allyson; Ramsden, James; Ramsden, Richard; Rutherford, Scott A; Saeed, Shakeel R; Thomas, Nick; Vanat, Zebunnisa H


    Hearing loss resulting from bilateral vestibular schwannomas (VSs) has a significant effect on the quality of life of patients with neurofibromatosis Type 2 (NF2). A national consensus protocol was produced in England as a guide for cochlear implantation (CI) and auditory brainstem implantation (ABI) in these patients. Consensus statement. English NF2 Service. Clinicians from all 4 lead NF2 units in England. A protocol for the assessment, insertion and rehabilitation of CI and ABI in NF2 patients. Patients should undergo more detailed hearing assessment once their maximum aided speech discrimination score falls below 50% in the better hearing ear. Bamford-Kowal-Bench sentence testing scores below 50% should trigger assessment for auditory implantation, as recommended by the National Institute for Clinical Excellence guidelines on CI. Where this occurs in patients with bilateral stable VS or a unilateral stable VS where the contralateral cochlear nerve was lost at previous surgery, CI should be considered. Where VS surgery is planned, CI should be considered where cochlear nerve preservation is thought possible, otherwise an ABI should be considered. Intraoperative testing using electrically evoked auditory brainstem responses or cochlear nerve action potentials may be used to determine whether a CI or ABI is inserted. The NF2 centers in England agreed on this protocol. Multisite, prospective assessments of standardized protocols for auditory implantation in NF2 provide an essential model for evaluating candidacy and outcomes in this challenging patient population.

  20. The auditory brainstem response to complex sounds: a potential biomarker for guiding treatment of psychosis

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    Melissa A Tarasenko


    Full Text Available Cognitive deficits limit psychosocial functioning in schizophrenia. For many patients, cognitive remediation approaches have yielded encouraging results. Nevertheless, therapeutic response is variable, and outcome studies consistently identify individuals who respond minimally to these interventions. Biomarkers that can assist in identifying patients likely to benefit from particular forms of cognitive remediation are needed. Here we describe an event-related potential (ERP biomarker – the auditory brainstem response to complex sounds (cABR – that appears to be particularly well-suited for predicting response to at least one form of cognitive remediation that targets auditory information processing. Uniquely, the cABR quantifies the fidelity of sound encoded at the level of the brainstem and midbrain. This ERP biomarker has revealed auditory processing abnormalities in various neurodevelopmental disorders, correlates with functioning across several cognitive domains, and appears to be responsive to targeted auditory training. We present preliminary cABR data from 18 schizophrenia patients and propose further investigation of this biomarker for predicting and tracking response to cognitive interventions.

  1. Neonatal brainstem function and 4-month arousal-modulated attention are jointly associated with autism. (United States)

    Cohen, Ira L; Gardner, Judith M; Karmel, Bernard Z; Phan, Ha T T; Kittler, Phyllis; Gomez, Tina Rovito; Gonzalez, Maripaz G; Lennon, Elizabeth M; Parab, Santosh; Barone, Anthony


    The authors evaluated the contribution of initially abnormal neonatal auditory brainstem responses (ABRs) and 4-month arousal-modulated attention visual preference to later autism spectrum disorder (ASD) behaviors in neonatal intensive care unit (NICU) graduates. A longitudinal study design was used to compare NICU graduates with normal ABRs (n = 28) to those with initially abnormal ABRs (n = 46) that later resolved. At 4 months postterm age, visual preference (measured after feeding) for a random check pattern flashing at 1, 3, or 8 Hz and gestational age (GA) served as additional predictors. Outcome measures were PDD Behavior Inventory (PDDBI) scores at 3.4 years (standard deviation = 1.2), and developmental quotients (DQ) obtained around the same age with the Griffiths Mental Development Scales (GMDS). Preferences for higher rates of stimulation at 4 months were highly correlated with PDDBI scores (all P-values stimulation as infants were linked to nonlinear increases in severity of ASD at 3 years and to an ASD diagnosis. Abnormal ABRs were associated with later reports of repetitive and ritualistic behaviors irrespective of 4-month preference for stimulation. The joint occurrence of initially abnormal neonatal ABRs and preference for more stimulation at 4 months, both indices of early brainstem dysfunction, may be a marker for the development of autism in this cohort. © 2012 International Society for Autism Research, Wiley Periodicals, Inc.

  2. Developmental neuropathology of brainstem respiratory centers in unexplained stillbirth: What's the meaning? (United States)

    Lavezzi, Anna M; Ferrero, Stefano; Matturri, Luigi; Roncati, Luca; Pusiol, Teresa


    Stillbirth is one of the most stressful life events affecting over 3 million pregnancies per year throughout the world. An accurate autopsy of the stillborn fetus, including the placenta and umbilical cord examination, should be performed promptly after delivery. A thorough maternal history also should be taken, including exposures to risk factors. In many cases a death cause, attributable to fetal, maternal, or placental pathology, is clearly identified. However, in 50% or more of cases the cause remains unknown. The purpose of this study is to highlight possible developmental alterations of the autonomic nervous system in unexplained stillbirths to provide an explanation of the pathogenetic mechanism of their death. We conducted a careful neuropathological study of the brainstem, where the main vital centers are located, in 85 unexplained stillbirths and 52 age-matched controls died of known cause. Information on the maternal lifestyle, including the smoking habit, was collected in all cases. Hypodevelopment of neuronal centers involved in breathing control, all connected together in a "respiratory network", precisely hypoplasia of the facial/parafacial complex, Kölliker-Fuse nucleus, pre-Bötzinger nucleus and intermediolateral nucleus, were frequently observed in unexplained deaths, significantly related to maternal cigarette smoking. We support the hypothesis of a strong action of maternal smoking during pregnancy on the development of brainstem respiratory nuclei and suggest an explanation of the high incidence of the respiratory network alterations in unexplained fetal death, when breathing not represents a vital function. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

  3. Brainstem and spinal projections of augmenting expiratory neurons in the rat. (United States)

    Ezure, Kazuhisa; Tanaka, Ikuko; Saito, Yoshiaki


    There are two types of expiratory neurons with augmenting firing patterns (E-AUG neurons), those in the Bötzinger complex (BOT) and those in the caudal ventral respiratory group (cVRG). We studied their axonal projections morphologically using intracellular labeling of single E-AUG neurons with Neurobiotin, in anesthetized, paralyzed and artificially-ventilated rats. BOT E-AUG neurons (n = 11) had extensive axonal projections to the brainstem, but E-AUG neurons (n = 5) of the cVRG sent axons that descended the contralateral spinal cord without medullary collaterals. In addition to these somewhat expected characteristics, the present study revealed a number of new projection patterns of the BOT E-AUG neurons. First, as compared with the dense projections to the ipsilateral brainstem, those to the contralateral side were sparse. Second, several BOT E-AUG neurons sent long ascending collaterals to the pons, which included an axon that reached the ipsilateral parabrachial and Kölliker-Fuse nuclei and distributed boutons. Third, conspicuous projections from branches of these ascending collaterals to the area dorsolateral to the facial nucleus were found. Thus, the present study has shown an anatomical substrate for the extensive inhibitory projections of single BOT E-AUG neurons to the areas spanning the bilateral medulla and the pons. Copyright 2002 Elsevier Science Ireland Ltd and the Japan Neuroscience Society

  4. Brainstem processing of vestibular sensory exafference: implications for motion sickness etiology. (United States)

    Oman, Charles M; Cullen, Kathleen E


    The origin of the internal "sensory conflict" stimulus causing motion sickness has been debated for more than four decades. Recent studies show a subclass of neurons in the vestibular nuclei and deep cerebellar nuclei that respond preferentially to passive head movements. During active movement, the semicircular canal and otolith input ("reafference") to these neurons are canceled by a mechanism comparing the expected consequences of self-generated movement (estimated with an internal model-presumably located in the cerebellum) with the actual sensory feedback. The un-canceled component ("exafference") resulting from passive movement normally helps compensate for unexpected postural disturbances. Notably, the existence of such vestibular "sensory conflict" neurons had been postulated as early as 1982, but their existence and putative role in posture control and motion sickness have been long debated. Here, we review the development of "sensory conflict" theories in relation to recent evidence for brainstem and cerebellar reafference cancelation, and identify some open research questions. We propose that conditions producing persistent activity of these neurons, or their targets, stimulate nearby brainstem emetic centers-via an as yet unidentified mechanism. We discuss how such a mechanism is consistent with the notable difference in motion sickness susceptibility of drivers as opposed to passengers, human immunity to normal self-generated movement and why head restraint or lying horizontal confers relative immunity. Finally, we propose that fuller characterization of these mechanisms and their potential role in motion sickness could lead to more effective, scientifically based prevention and treatment for motion sickness.

  5. Short GSM mobile phone exposure does not alter human auditory brainstem response

    Directory of Open Access Journals (Sweden)

    Thuróczy György


    Full Text Available Abstract Background There are about 1.6 billion GSM cellular phones in use throughout the world today. Numerous papers have reported various biological effects in humans exposed to electromagnetic fields emitted by mobile phones. The aim of the present study was to advance our understanding of potential adverse effects of the GSM mobile phones on the human hearing system. Methods Auditory Brainstem Response (ABR was recorded with three non-polarizing Ag-AgCl scalp electrodes in thirty young and healthy volunteers (age 18–26 years with normal hearing. ABR data were collected before, and immediately after a 10 minute exposure to 900 MHz pulsed electromagnetic field (EMF emitted by a commercial Nokia 6310 mobile phone. Fifteen subjects were exposed to genuine EMF and fifteen to sham EMF in a double blind and counterbalanced order. Possible effects of irradiation was analyzed by comparing the latency of ABR waves I, III and V before and after genuine/sham EMF exposure. Results Paired sample t-test was conducted for statistical analysis. Results revealed no significant differences in the latency of ABR waves I, III and V before and after 10 minutes of genuine/sham EMF exposure. Conclusion The present results suggest that, in our experimental conditions, a single 10 minute exposure of 900 MHz EMF emitted by a commercial mobile phone does not produce measurable immediate effects in the latency of auditory brainstem waves I, III and V.

  6. Comparison of Auditory Brainstem Response in Noise Induced Tinnitus and Non-Tinnitus Control Subjects

    Directory of Open Access Journals (Sweden)

    Ghassem Mohammadkhani


    Full Text Available Background and Aim: Tinnitus is an unpleasant sound which can cause some behavioral disorders. According to evidence the origin of tinnitus is not only in peripheral but also in central auditory system. So evaluation of central auditory system function is necessary. In this study Auditory brainstem responses (ABR were compared in noise induced tinnitus and non-tinnitus control subjects.Materials and Methods: This cross-sectional, descriptive and analytic study is conducted in 60 cases in two groups including of 30 noise induced tinnitus and 30 non-tinnitus control subjects. ABRs were recorded ipsilateraly and contralateraly and their latencies and amplitudes were analyzed.Results: Mean interpeak latencies of III-V (p= 0.022, I-V (p=0.033 in ipsilatral electrode array and mean absolute latencies of IV (p=0.015 and V (p=0.048 in contralatral electrode array were significantly increased in noise induced tinnitus group relative to control group. Conclusion: It can be concluded from that there are some decrease in neural transmission time in brainstem and there are some sign of involvement of medial nuclei in olivery complex in addition to lateral lemniscus.

  7. Speech-evoked auditory brainstem responses in children with hearing loss. (United States)

    Koravand, Amineh; Al Osman, Rida; Rivest, Véronique; Poulin, Catherine


    The main objective of the present study was to investigate subcortical auditory processing in children with sensorineural hearing loss. Auditory Brainstem Responses (ABRs) were recorded using click and speech/da/stimuli. Twenty-five children, aged 6-14 years old, participated in the study: 13 with normal hearing acuity and 12 with sensorineural hearing loss. No significant differences were observed for the click-evoked ABRs between normal hearing and hearing-impaired groups. For the speech-evoked ABRs, no significant differences were found for the latencies of the following responses between the two groups: onset (V and A), transition (C), one of the steady-state wave (F), and offset (O). However, the latency of the steady-state waves (D and E) was significantly longer for the hearing-impaired compared to the normal hearing group. Furthermore, the amplitude of the offset wave O and of the envelope frequency response (EFR) of the speech-evoked ABRs was significantly larger for the hearing-impaired compared to the normal hearing group. Results obtained from the speech-evoked ABRs suggest that children with a mild to moderately-severe sensorineural hearing loss have a specific pattern of subcortical auditory processing. Our results show differences for the speech-evoked ABRs in normal hearing children compared to hearing-impaired children. These results add to the body of the literature on how children with hearing loss process speech at the brainstem level. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Perinatal sulfur dioxide exposure alters brainstem parasympathetic control of heart rate. (United States)

    Woerman, Amanda L; Mendelowitz, David


    Sulfur dioxide (SO₂) is an air pollutant that impedes neonatal development and induces adverse cardiorespiratory health effects, including tachycardia. Here, an animal model was developed that enabled characterization of (i) in vivo alterations in heart rate and (ii) altered activity in brainstem neurons that control heart rate after perinatal SO₂ exposure. Pregnant Sprague-Dawley dams and their pups were exposed to 5 parts per million SO₂ for 1 h daily throughout gestation and 6 days postnatal. Electrocardiograms were recorded from pups at 5 days postnatal to examine changes in basal and diving reflex-evoked changes in heart rate following perinatal SO₂ exposure. In vitro studies employed whole-cell patch-clamp electrophysiology to examine changes in neurotransmission to cardiac vagal neurons within the nucleus ambiguus upon SO₂ exposure using a preparation that maintains fictive inspiratory activity recorded from the hypoglossal rootlet. Perinatal SO₂ exposure increased heart rate and blunted the parasympathetic-mediated diving reflex-evoked changes in heart rate. Neither spontaneous nor inspiratory-related inhibitory GABAergic or glycinergic neurotransmission to cardiac vagal neurons was altered by SO₂ exposure. However, excitatory glutamatergic neurotransmission was decreased by 51.2% upon SO₂ exposure. This diminished excitatory neurotransmission was tetrodotoxin-sensitive, indicating SO₂ exposure impaired the activity of preceding glutamatergic neurons that synapse upon cardiac vagal neurons. Diminished glutamatergic, but unaltered inhibitory neurotransmission to cardiac vagal neurons provides a mechanism for the observed SO₂-induced elevated heart rate via an impairment of brainstem cardioinhibitory parasympathetic activity to the heart.

  9. Abnormal auditory forward masking pattern in the brainstem response of individuals with Asperger syndrome

    Directory of Open Access Journals (Sweden)

    Johan Källstrand


    Full Text Available Johan Källstrand1, Olle Olsson2, Sara Fristedt Nehlstedt1, Mia Ling Sköld1, Sören Nielzén21SensoDetect AB, Lund, Sweden; 2Department of Clinical Neuroscience, Section of Psychiatry, Lund University, Lund, SwedenAbstract: Abnormal auditory information processing has been reported in individuals with autism spectrum disorders (ASD. In the present study auditory processing was investigated by recording auditory brainstem responses (ABRs elicited by forward masking in adults diagnosed with Asperger syndrome (AS. Sixteen AS subjects were included in the forward masking experiment and compared to three control groups consisting of healthy individuals (n = 16, schizophrenic patients (n = 16 and attention deficit hyperactivity disorder patients (n = 16, respectively, of matching age and gender. The results showed that the AS subjects exhibited abnormally low activity in the early part of their ABRs that distinctly separated them from the three control groups. Specifically, wave III amplitudes were significantly lower in the AS group than for all the control groups in the forward masking condition (P < 0.005, which was not the case in the baseline condition. Thus, electrophysiological measurements of ABRs to complex sound stimuli (eg, forward masking may lead to a better understanding of the underlying neurophysiology of AS. Future studies may further point to specific ABR characteristics in AS individuals that separate them from individuals diagnosed with other neurodevelopmental diseases.Keywords: asperger syndrome, auditory brainstem response, forward masking, psychoacoustics

  10. Effects of reverberation on brainstem representation of speech in musicians and non-musicians. (United States)

    Bidelman, Gavin M; Krishnan, Ananthanarayan


    Perceptual and neurophysiological enhancements in linguistic processing in musicians suggest that domain specific experience may enhance neural resources recruited for language specific behaviors. In everyday situations, listeners are faced with extracting speech signals in degraded listening conditions. Here, we examine whether musical training provides resilience to the degradative effects of reverberation on subcortical representations of pitch and formant-related harmonic information of speech. Brainstem frequency-following responses (FFRs) were recorded from musicians and non-musician controls in response to the vowel /i/ in four different levels of reverberation and analyzed based on their spectro-temporal composition. For both groups, reverberation had little effect on the neural encoding of pitch but significantly degraded neural encoding of formant-related harmonics (i.e., vowel quality) suggesting a differential impact on the source-filter components of speech. However, in quiet and across nearly all reverberation conditions, musicians showed more robust responses than non-musicians. Neurophysiologic results were confirmed behaviorally by comparing brainstem spectral magnitudes with perceptual measures of fundamental (F0) and first formant (F1) frequency difference limens (DLs). For both types of discrimination, musicians obtained DLs which were 2-4 times better than non-musicians. Results suggest that musicians' enhanced neural encoding of acoustic features, an experience-dependent effect, is more resistant to reverberation degradation which may explain their enhanced perceptual ability on behaviorally relevant speech and/or music tasks in adverse listening conditions. Copyright © 2010 Elsevier B.V. All rights reserved.

  11. The Usefulness of Diffusion Tensor Imaging and Tractography in Surgery of Brainstem Cavernous Malformations. (United States)

    Januszewski, Jacob; Albert, Lauren; Black, Karen; Dehdashti, Amir R


    Diffusion tensor imaging (DTI) estimates the course and connectivity patterns of white matter tracts. The objective of this study is to evaluate whether findings in the brain stem modify the preoperative surgical trajectory planning or postoperative outcome in patients with brain stem cavernous malformations. Ten patients with symptomatic brainstem cavernous malformation underwent surgical resection. Five patients received preoperative DTI evaluation and the remaining 5 did not. Reconstructed DTI tracts consisted of corticospinal, medial lemnisci, and cerebellar peduncles. The surgical planning and postoperative outcome were evaluated. In 5 patients with no preoperative DTI evaluation, surgical planning was based on anatomic landmark and the 2-point technique. The other 5 patients underwent preoperative DTI, and findings were factored into the selection of the surgical approach. In 3 of the 5 cases with DTI evaluation, the 2-point technique suggested a similar trajectory. In the other 2, the DTI findings suggested a different approach to avoid damage to the white matter tract. Two patients in the group with no DTI had immediate postoperative new or worsened deficit, which improved at long-term follow-up. No patient in the DTI group had a new neurologic deficit. Compared with the standard magnetic resonance imaging, DTI provided improved visualization of cavernous malformation involvement in eloquent fiber tracts of the brainstem. This additional information might help in selecting a more appropriate surgical trajectory in selected lesions. Larger patient cohorts are needed to assess the effect of this modality in patients' outcome. Published by Elsevier Inc.

  12. Searching for the optimal stimulus eliciting auditory brainstem responses in humans

    DEFF Research Database (Denmark)

    Fobel, Oliver; Dau, Torsten


    This study examines auditory brainstem responses (ABR) elicited by rising frequency chirps. Two chirp stimuli were developed and designed such as to compensate for cochlear travel-time differences across frequency, in order to maximize neural synchrony. One chirp, referred to as the O-chirp, was ......This study examines auditory brainstem responses (ABR) elicited by rising frequency chirps. Two chirp stimuli were developed and designed such as to compensate for cochlear travel-time differences across frequency, in order to maximize neural synchrony. One chirp, referred to as the O...... compared to click responses and to responses obtained with the original chirp as defined in Dau et al. [J. Acoust. Soc. Am. 107(3), 1530–1540 (2000)], referred to here as the M-chirp since it is based on a (linear) cochlea model. The main hypothesis was that, at low and medium stimulation levels, the O......- and A-chirps might produce a larger response than the original M-chirp whose parameters were essentially derived from high-level BM data. The main results of the present study are as follows: (i) All chirps evoked a larger wave-V amplitude than the click stimulus indicating that for the chirps a broader...

  13. Evolution of Sound Source Localization Circuits in the Nonmammalian Vertebrate Brainstem

    DEFF Research Database (Denmark)

    Walton, Peggy L; Christensen-Dalsgaard, Jakob; Carr, Catherine E


    . This directional information is further enhanced by bilateral computations in the medulla and the auditory midbrain. We propose that similar direction-sensitive neurons were present in the early aquatic tetrapods and that selection for sound localization in air acted upon preexisting brain stem circuits like those...... created by external sources. The potential to identify and localize these external sources may have been a major selection force in the evolution of the early vertebrate ear and in the processing of sound in the central nervous system. The intrinsic physiological polarization of sensory hair cells...... to increased sensitivity to a broader frequency range and to modification of the preexisting circuitry for sound source localization....

  14. Central neural circuitry in the jellyfish Aglantha: a model 'simple nervous system'. (United States)

    Mackie, George O


    Like other hydrozoan medusae, Aglantha lacks a brain, but the two marginal nerve rings function together as a central nervous system. Twelve neuronal and two excitable epithelial conduction systems are described and their interactions summarized. Aglantha differs from most medusae in having giant axons. It can swim and contract its tentacles in two distinct ways (escape and slow). Escape responses are mediated primarily by giant axons but conventional interneurons are also involved in transmission of information within the nerve rings during one form of escape behavior. Surprisingly, giant axons provide the motor pathway to the swim muscles in both escape and slow swimming. This is possible because these axons can conduct calcium spikes as well as sodium spikes and do so on an either/or basis without overlap. The synaptic and ionic bases for these responses are reviewed. During feeding, the manubrium performs highly accurate flexions to points at the margin. At the same time, the oral lips flare open. The directional flexions are conducted by FMRFamide immunoreactive nerves, the lip flaring by an excitable epithelium lining the radial canals. Inhibition of swimming during feeding is due to impulses propagated centrifugally in the same epithelium. Aglantha probably evolved from an ancestor possessing a relatively simple wiring plan, as seen in other hydromedusae. Acquisition of giant axons resulted in considerable modification of this basic plan, and required novel solutions to the problems of integrating escape with non-escape circuitry. Copyright 2004 S. Karger AG, Basel

  15. The emotional power of poetry: neural circuitry, psychophysiology and compositional principles. (United States)

    Wassiliwizky, Eugen; Koelsch, Stefan; Wagner, Valentin; Jacobsen, Thomas; Menninghaus, Winfried


    It is a common experience-and well established experimentally-that music can engage us emotionally in a compelling manner. The mechanisms underlying these experiences are receiving increasing scrutiny. However, the extent to which other domains of aesthetic experience can similarly elicit strong emotions is unknown. Using psychophysiology, neuroimaging and behavioral responses, we show that recited poetry can act as a powerful stimulus for eliciting peak emotional responses, including chills and objectively measurable goosebumps that engage the primary reward circuitry. Importantly, while these responses to poetry are largely analogous to those found for music, their neural underpinnings show important differences, specifically with regard to the crucial role of the nucleus accumbens. We also go beyond replicating previous music-related studies by showing that peak aesthetic pleasure can co-occur with physiological markers of negative affect. Finally, the distribution of chills across the trajectory of poems provides insight into compositional principles of poetry. © The Author (2017). Published by Oxford University Press.

  16. Exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson's disease. (United States)

    Petzinger, Giselle M; Fisher, Beth E; McEwen, Sarah; Beeler, Jeff A; Walsh, John P; Jakowec, Michael W


    Exercise interventions in individuals with Parkinson's disease incorporate goal-based motor skill training to engage cognitive circuitry important in motor learning. With this exercise approach, physical therapy helps with learning through instruction and feedback (reinforcement) and encouragement to perform beyond self-perceived capability. Individuals with Parkinson's disease become more cognitively engaged with the practice and learning of movements and skills that were previously automatic and unconscious. Aerobic exercise, regarded as important for improvement of blood flow and facilitation of neuroplasticity in elderly people, might also have a role in improvement of behavioural function in individuals with Parkinson's disease. Exercises that incorporate goal-based training and aerobic activity have the potential to improve both cognitive and automatic components of motor control in individuals with mild to moderate disease through experience-dependent neuroplasticity. Basic research in animal models of Parkinson's disease is beginning to show exercise-induced neuroplastic effects at the level of synaptic connections and circuits. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. The pluripotent regulatory circuitry connecting promoters to their long-range interacting elements. (United States)

    Schoenfelder, Stefan; Furlan-Magaril, Mayra; Mifsud, Borbala; Tavares-Cadete, Filipe; Sugar, Robert; Javierre, Biola-Maria; Nagano, Takashi; Katsman, Yulia; Sakthidevi, Moorthy; Wingett, Steven W; Dimitrova, Emilia; Dimond, Andrew; Edelman, Lucas B; Elderkin, Sarah; Tabbada, Kristina; Darbo, Elodie; Andrews, Simon; Herman, Bram; Higgs, Andy; LeProust, Emily; Osborne, Cameron S; Mitchell, Jennifer A; Luscombe, Nicholas M; Fraser, Peter


    The mammalian genome harbors up to one million regulatory elements often located at great distances from their target genes. Long-range elements control genes through physical contact with promoters and can be recognized by the presence of specific histone modifications and transcription factor binding. Linking regulatory elements to specific promoters genome-wide is currently impeded by the limited resolution of high-throughput chromatin interaction assays. Here we apply a sequence capture approach to enrich Hi-C libraries for >22,000 annotated mouse promoters to identify statistically significant, long-range interactions at restriction fragment resolution, assigning long-range interacting elements to their target genes genome-wide in embryonic stem cells and fetal liver cells. The distal sites contacting active genes are enriched in active histone modifications and transcription factor occupancy, whereas inactive genes contact distal sites with repressive histone marks, demonstrating the regulatory potential of the distal elements identified. Furthermore, we find that coregulated genes cluster nonrandomly in spatial interaction networks correlated with their biological function and expression level. Interestingly, we find the strongest gene clustering in ES cells between transcription factor genes that control key developmental processes in embryogenesis. The results provide the first genome-wide catalog linking gene promoters to their long-range interacting elements and highlight the complex spatial regulatory circuitry controlling mammalian gene expression. © 2015 Schoenfelder et al.; Published by Cold Spring Harbor Laboratory Press.

  18. Differences in brain circuitry for appetitive and reactive aggression as revealed by realistic auditory scripts

    Directory of Open Access Journals (Sweden)

    James Kenneth Moran


    Full Text Available Aggressive behavior is thought to divide into two motivational elements: The first being a self-defensively motivated aggression against threat and a second, hedonically motivated ‘appetitive’ aggression. Appetitive aggression is the less understood of the two, often only researched within abnormal psychology. Our approach is to understand it as a universal and adaptive response, and examine the functional neural activity of ordinary men (N=50 presented with an imaginative listening task involving a murderer describing a kill. We manipulated motivational context in a between-subjects design to evoke appetitive or reactive aggression, against a neutral control, measuring activity with Magnetoencephalography (MEG. Results show differences in left frontal regions in delta (2-5 Hz and alpha band (8-12 Hz for aggressive conditions and right parietal delta activity differentiating appetitive and reactive aggression. These results validate the distinction of reward-driven appetitive aggression from reactive aggression in ordinary populations at the level of functional neural brain circuitry.

  19. Ultrafast all-optical modulation with hyperbolic metamaterial integrated in Si photonic circuitry. (United States)

    Neira, Andres D; Wurtz, Gregory A; Ginzburg, Pavel; Zayats, Anatoly V


    The integration of optical metamaterials within silicon integrated photonic circuitry bears significantly potential in the design of low-power, nanoscale footprint, all-optical functionalities. We propose a novel concept and provide detailed analysis of an on-chip ultrafast all-optical modulator based on an hyperbolic metamaterial integrated in a silicon waveguide. The anisotropic metamaterial based on gold nanorods is placed on top of the silicon waveguide to form a modulator with a 300x440x600 nm(3) footprint. For the operating wavelength of 1.5 μm, the optimized geometry of the device has insertion loss of about 5 dB and a modulation depth of 35% with a sub-ps switching rate. The switching energy estimated from nonlinear transient dynamic numerical simulations is 3.7 pJ/bit when the transmission is controlled optically at a wavelength of 532 nm, resonant with the transverse plasmonic mode of the metamaterial. The switching mechanism is based on the control of the hybridization of eigenmodes in the metamaterial slab and the Si waveguide.

  20. Electric field induced needle-pulsed arc discharge carbon nanotube production apparatus: Circuitry and mechanical design (United States)

    Kia, Kaveh Kazemi; Bonabi, Fahimeh


    A simple and low cost apparatus is reported to produce multiwall carbon nanotubes and carbon nano-onions by a low power short pulsed arc discharge reactor. The electric circuitry and the mechanical design details and a micro-filtering assembly are described. The pulsed-plasma is generated and applied between two graphite electrodes. The pulse width is 0.3 μs. A strong dc electric field is established along side the electrodes. The repetitive discharges occur in less than 1 mm distance between a sharp tip graphite rod as anode, and a tubular graphite as cathode. A hydrocarbon vapor, as carbon source, is introduced through the graphite nozzle in the cathode assembly. The pressure of the chamber is controlled by a vacuum pump. A magnetic field, perpendicular to the plasma path, is provided. The results show that the synergetic use of a pulsed-current and a dc power supply enables us to synthesize carbon nanoparticles with short pulsed plasma. The simplicity and inexpensiveness of this plan is noticeable. Pulsed nature of plasma provides some extra degrees of freedom that make the production more controllable. Effects of some design parameters such as electric field, pulse frequency, and cathode shape are discussed. The products are examined using scanning probe microscopy techniques.

  1. Assessing Ink Transfer Performance of Gravure-Offset Fine-Line Circuitry Printing (United States)

    Cheng, Hsien-Chie; Chen, You-Wei; Chen, Wen-Hwa; Lu, Su-Tsai; Lin, Shih-Ming


    In this study, the printing mechanism and performance of gravure-offset fine-line circuitry printing technology are investigated in terms of key printing parameters through experimental and theoretical analyses. First, the contact angles of the ink deposited on different substrates, blankets, and gravure metal plates are experimentally determined; moreover, their temperature and solvent content dependences are analyzed. Next, the ink solvent absorption and evaporation behaviors of the blankets at different temperatures, times, and numbers of printing repetitions are characterized by conducting experiments. In addition, while printing repeatedly, the surface characteristics of the blankets, such as the contact angle, vary with the amount of absorbed ink solvent, further affecting the ink transfer performance (ratio) and printing quality. Accordingly, the surface effect of the blanket due to ink solvent absorption on the ink contact angle is analyzed. Furthermore, the amount of ink transferred from the gravure plate to the blanket in the "off process" and from the blanket to the substrate in the "set process" is evaluated by conducting a simplified plate-to-plate experiment. The influences of loading rate (printing velocity), temperature, and solvent content on the ink transfer performance are addressed. Finally, the ink transfer mechanism is theoretically analyzed for different solvent contents using Surface Evolver. The calculation results are compared with those of the experiment.

  2. Brain IL-6 elevation causes neuronal circuitry imbalances and mediates autism-like behaviors. (United States)

    Wei, Hongen; Chadman, Kathryn K; McCloskey, Daniel P; Sheikh, Ashfaq M; Malik, Mazhar; Brown, W Ted; Li, Xiaohong


    Abnormal immune responses have been reported to be associated with autism. A number of studies showed that cytokines were increased in the blood, brain, and cerebrospinal fluid of autistic subjects. Elevated IL-6 in autistic brain has been a consistent finding. However, the mechanisms by which IL-6 may be involved in the pathogenesis of autism are not well understood. Here we show that mice with elevated IL-6 in the brain display many autistic features, including impaired cognitive abilities, deficits in learning, abnormal anxiety traits and habituations, as well as decreased social interactions. IL-6 elevation caused alterations in excitatory and inhibitory synaptic formations and disrupted the balance of excitatory/inhibitory synaptic transmissions. IL-6 elevation also resulted in an abnormal change in the shape, length and distributing pattern of dendritic spines. These findings suggest that IL-6 elevation in the brain could mediate autistic-like behaviors, possibly through the imbalances of neural circuitry and impairments of synaptic plasticity. Published by Elsevier B.V.

  3. The circuitry mediating cocaine-induced reinstatement of drug-seeking behavior. (United States)

    McFarland, K; Kalivas, P W


    The role of limbic-striato-pallidal circuitry in cocaine-induced reinstatement was evaluated. The transient inhibition of brain nuclei associated with motor systems [including the ventral tegmental area (VTA), dorsal prefrontal cortex (dPFC), core of the nucleus accumbens (NAcore), and ventral pallidum (VP)] prevented cocaine-induced reinstatement. However, only the VP proved to be necessary for food reinstatement, suggesting that the identified circuit is specific to drug-related reinstatement. Supporting the possibility that the VTA-dPFC-NAcore-VP is a series circuit mediating reinstatement, simultaneous unilateral microinjection of GABA agonists into the dPFC in one hemisphere and into the VP in the contralateral hemisphere abolished cocaine reinstatement. Although dopamine projections from the VTA innervate all three forebrain nuclei, the blockade of dopamine receptors only in the dPFC antagonized cocaine-induced reinstatement. Furthermore, DA administration into the dPFC was sufficient to elicit a reinstatement in drug-related responding. These data demonstrate that dopamine release in the dPFC initiates a dPFC-NAcore-VP series circuit that mediates cocaine-induced drug-seeking behavior.

  4. Integrated plasmonic circuitry on a vertical-cavity surface-emitting semiconductor laser platform. (United States)

    McPolin, Cillian P T; Bouillard, Jean-Sebastien; Vilain, Sebastien; Krasavin, Alexey V; Dickson, Wayne; O'Connor, Daniel; Wurtz, Gregory A; Justice, John; Corbett, Brian; Zayats, Anatoly V


    Integrated plasmonic sources and detectors are imperative in the practical development of plasmonic circuitry for bio- and chemical sensing, nanoscale optical information processing, as well as transducers for high-density optical data storage. Here we show that vertical-cavity surface-emitting lasers (VCSELs) can be employed as an on-chip, electrically pumped source or detector of plasmonic signals, when operated in forward or reverse bias, respectively. To this end, we experimentally demonstrate surface plasmon polariton excitation, waveguiding, frequency conversion and detection on a VCSEL-based plasmonic platform. The coupling efficiency of the VCSEL emission to waveguided surface plasmon polariton modes has been optimized using asymmetric plasmonic nanostructures. The plasmonic VCSEL platform validated here is a viable solution for practical realizations of plasmonic functionalities for various applications, such as those requiring sub-wavelength field confinement, refractive index sensitivity or optical near-field transduction with electrically driven sources, thus enabling the realization of on-chip optical communication and lab-on-a-chip devices.

  5. Congenital prosopagnosia: multistage anatomical and functional deficits in face processing circuitry. (United States)

    Dinkelacker, V; Grüter, M; Klaver, P; Grüter, T; Specht, K; Weis, S; Kennerknecht, I; Elger, C E; Fernandez, G


    Face recognition is a primary social skill which depends on a distributed neural network. A pronounced face recognition deficit in the absence of any lesion is seen in congenital prosopagnosia. This study investigating 24 congenital prosopagnosic subjects and 25 control subjects aims at elucidating its neural basis with fMRI and voxel-based morphometry. We found a comprehensive behavioral pattern, an impairment in visual recognition for faces and buildings that spared long-term memory for faces with negative valence. Anatomical analysis revealed diminished gray matter density in the bilateral lingual gyrus, the right middle temporal gyrus, and the dorsolateral prefrontal cortex. In most of these areas, gray matter density correlated with memory success. Decreased functional activation was found in the left fusiform gyrus, a crucial area for face processing, and in the dorsolateral prefrontal cortex, whereas activation of the medial prefrontal cortex was enhanced. Hence, our data lend strength to the hypothesis that congenital prosopagnosia is explained by network dysfunction and suggest that anatomic curtailing of visual processing in the lingual gyrus plays a substantial role. The dysfunctional circuitry further encompasses the fusiform gyrus and the dorsolateral prefrontal cortex, which may contribute to their difficulties in long-term memory for complex visual information. Despite their deficits in face identity recognition, processing of emotion related information is preserved and possibly mediated by the medial prefrontal cortex. Congenital prosopagnosia may, therefore, be a blueprint of differential curtailing in networks of visual cognition.

  6. Taste Reward Circuitry Related Brain Structures Characterize Ill and Recovered Anorexia Nervosa and Bulimia Nervosa (United States)

    Frank, Guido K.; Shott, Megan E.; Hagman, Jennifer O.; Mittal, Vijay A.


    Objective The pathophysiology of the eating disorder anorexia nervosa remains obscure, but structural brain alterations could be functionally important biomarkers. Here we assessed taste pleasantness and reward sensitivity in relation to brain structure, which might be related to food avoidance commonly seen in eating disorders. Method We used structural magnetic resonance brain imaging to study gray and white matter volumes in individuals with restricting type currently ill (n = 19) or recovered-anorexia nervosa (n = 24), bulimia nervosa (n= 19) and healthy control women (n=24). Results All eating disorder groups showed increased gray matter volume of the medial orbitofrontal cortex (gyrus rectus). Manually tracing confirmed larger gyrus rectus volume, and predicted taste pleasantness across all groups. The analyses also indicated other morphological differences between diagnostic categories: Ill and recovered-anorexia nervosa had increased right, while bulimia nervosa had increased left antero-ventral insula gray matter volumes compared to controls. Furthermore, dorsal striatum volumes were reduced in recovered-anorexia and bulimia nervosa, and predicted sensitivity to reward in the eating disorder groups. The eating disorder groups also showed reduced white matter in right temporal and parietal areas when compared to healthy controls. Notably, the results held when controlling for a range of covariates (e.g., age, depression, anxiety, medications). Conclusion Brain structure in medial orbitofrontal cortex, insula and striatum is altered in eating disorders and suggests altered brain circuitry that has been associated with taste pleasantness and reward value. PMID:23680873

  7. Closed circuitry operation influence on microbial electrofermentation: Proton/electron effluxes on electro-fuels productivity. (United States)

    Nikhil, G N; Venkata Subhash, G; Yeruva, Dileep Kumar; Venkata Mohan, S


    A novel biocatalyzed electrofermentor (BEF) was designed which uncovers the intricate role of biocatalyst involved in cogeneration of electro-fuels (hydrogen and electricity). The specific role of external resistance (Rext, electrical load) on the performance of BEF was evaluated. Four BEFs were operated separately with different resistances (25, 50, 100 and 200 Ω) at an organic load of 5 g/L. Among the tested conditions, external resistance (R3) with 100 Ω revealed maximum power and cumulative H2 production (148 mW and 450 mL, respectively). The competence of closed circuitry comparatively excelled because it facilitates congenial ambiance for the enriched EAB (electroactive bacteria) resulting high rate of metabolic activity that paves way for higher substrate degradation and electro-fuel productivity. Probing of electron kinetics was studied using voltammetric analyses wherein electron transfer by redox proteins was noticed. The designed BEF is found to be sustainable system for harnessing renewable energy through wastewater treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Kernel Architecture of the Genetic Circuitry of the Arabidopsis Circadian System.

    Directory of Open Access Journals (Sweden)

    Mathias Foo


    Full Text Available A wide range of organisms features molecular machines, circadian clocks, which generate endogenous oscillations with ~24 h periodicity and thereby synchronize biological processes to diurnal environmental fluctuations. Recently, it has become clear that plants harbor more complex gene regulatory circuits within the core circadian clocks than other organisms, inspiring a fundamental question: are all these regulatory interactions between clock genes equally crucial for the establishment and maintenance of circadian rhythms? Our mechanistic simulation for Arabidopsis thaliana demonstrates that at least half of the total regulatory interactions must be present to express the circadian molecular profiles observed in wild-type plants. A set of those essential interactions is called herein a kernel of the circadian system. The kernel structure unbiasedly reveals four interlocked negative feedback loops contributing to circadian rhythms, and three feedback loops among them drive the autonomous oscillation itself. Strikingly, the kernel structure, as well as the whole clock circuitry, is overwhelmingly composed of inhibitory, rather than activating, interactions between genes. We found that this tendency underlies plant circadian molecular profiles which often exhibit sharply-shaped, cuspidate waveforms. Through the generation of these cuspidate profiles, inhibitory interactions may facilitate the global coordination of temporally-distant clock events that are markedly peaked at very specific times of day. Our systematic approach resulting in experimentally-testable predictions provides insights into a design principle of biological clockwork, with implications for synthetic biology.

  9. Thapsigargin-induced activation of Ca(2+)-CaMKII-ERK in brainstem contributes to substance P release and induction of emesis in the least shrew. (United States)

    Zhong, Weixia; Chebolu, Seetha; Darmani, Nissar A


    Cytoplasmic calcium (Ca(2+)) mobilization has been proposed to be an important factor in the induction of emesis. The selective sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA) inhibitor thapsigargin, is known to deplete intracellular Ca(2+) stores, which consequently evokes extracellular Ca(2+) entry through cell membrane-associated channels, accompanied by a prominent rise in cytosolic Ca(2+). A pro-drug form of thapsigargin is currently under clinical trial as a targeted cancer chemotherapeutic. We envisioned that the intracellular effects of thapsigargin could cause emesis and planned to investigate its mechanisms of emetic action. Indeed, thapsigargin did induce vomiting in the least shrew in a dose-dependent and bell-shaped manner, with maximal efficacy (100%) at 0.5 mg/kg (i.p.). Thapsigargin (0.5 mg/kg) also caused increases in c-Fos immunoreactivity in the brainstem emetic nuclei including the area postrema (AP), nucleus tractus solitarius (NTS) and dorsal motor nucleus of the vagus (DMNX), as well as enhancement of substance P (SP) immunoreactivity in DMNX. In addition, thapsigargin (0.5 mg/kg, i.p.) led to vomit-associated and time-dependent increases in phosphorylation of Ca(2+)/calmodulin kinase IIα (CaMKIIα) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) in the brainstem. We then explored the suppressive potential of diverse chemicals against thapsigargin-evoked emesis including antagonists of: i) neurokinin-1 receptors (netupitant), ii) the type 3 serotonin receptors (palonosetron), iii) store-operated Ca(2+) entry (YM-58483), iv) L-type Ca(2+) channels (nifedipine), and v) SER Ca(2+)-release channels inositol trisphosphate (IP3Rs) (2-APB)-, and ryanodine (RyRs) (dantrolene)-receptors. In addition, the antiemetic potential of inhibitors of CaMKII (KN93) and ERK1/2 (PD98059) were investigated. All tested antagonists/blockers attenuated emetic parameters to varying degrees except palonosetron, however a combination of non

  10. Neonate Auditory Brainstem Responses to CE-Chirp and CE-Chirp Octave Band Stimuli II: Versus Adult Auditory Brainstem Responses. (United States)

    Cobb, Kensi M; Stuart, Andrew

    The purpose of the study was to examine the differences in auditory brainstem response (ABR) latency and amplitude indices to the CE-Chirp stimuli in neonates versus young adults as a function of stimulus level, rate, polarity, frequency and gender. Participants were 168 healthy neonates and 20 normal-hearing young adults. ABRs were obtained to air- and bone-conducted CE-Chirps and air-conducted CE-Chirp octave band stimuli. The effects of stimulus level, rate, and polarity were examined with air-conducted CE-Chirps. The effect of stimulus level was also examined with bone-conducted CE-Chirps and CE-Chirp octave band stimuli. The effect of gender was examined across all stimulus manipulations. In general, ABR wave V amplitudes were significantly larger (p 0.05). Significant differences in ABR latencies and amplitudes exist between newborns and young adults using CE-Chirp stimuli. These differences are consistent with differences to traditional click and tone burst stimuli and reflect maturational differences as a function of age. These findings continue to emphasize the importance of interpreting ABR results using age-based normative data.

  11. Regulation of body fat mass by the gut microbiota

    DEFF Research Database (Denmark)

    Schéle, Erik; Grahnemo, Louise; Anesten, Fredrik


    New insight suggests gut microbiota as a component in energy balance. However, the underlying mechanisms by which gut microbiota can impact metabolic regulation is unclear. A recent study from our lab shows, for the first time, a link between gut microbiota and energy balance circuitries...

  12. Prescription dose and fractionation predict improved survival after stereotactic radiotherapy for brainstem metastases

    Directory of Open Access Journals (Sweden)

    Leeman Jonathan E


    Full Text Available Abstract Background Brainstem metastases represent an uncommon clinical presentation that is associated with a poor prognosis. Treatment options are limited given the unacceptable risks associated with surgical resection in this location. However, without local control, symptoms including progressive cranial nerve dysfunction are frequently observed. The objective of this study was to determine the outcomes associated with linear accelerator-based stereotactic radiotherapy or radiosurgery (SRT/SRS of brainstem metastases. Methods We retrospectively reviewed 38 tumors in 36 patients treated with SRT/SRS between February 2003 and December 2011. Treatment was delivered with the Cyberknife™ or Trilogy™ radiosurgical systems. The median age of patients was 62 (range: 28–89. Primary pathologies included 14 lung, 7 breast, 4 colon and 11 others. Sixteen patients (44% had received whole brain radiation therapy (WBRT prior to SRT/SRS; ten had received prior SRT/SRS at a different site (28%. The median tumor volume was 0.94 cm3 (range: 0.01-4.2 with a median prescription dose of 17 Gy (range: 12–24 delivered in 1–5 fractions. Results Median follow-up for the cohort was 3.2 months (range: 0.4-20.6. Nineteen patients (52% had an MRI follow-up available for review. Of these, one patient experienced local failure corresponding to an actuarial 6-month local control of 93%. Fifteen of the patients with available follow-up imaging (79% experienced intracranial failure outside of the treatment volume. The median time to distant intracranial failure was 2.1 months. Six of the 15 patients with distant intracranial failure (40% had received previous WBRT. The actuarial overall survival rates at 6- and 12-months were 27% and 8%, respectively. Predictors of survival included Graded Prognostic Assessment (GPA score, greater number of treatment fractions, and higher prescription dose. Three patients experienced acute treatment-related toxicity consisting of

  13. Comparison of binaural auditory brainstem responses and the binaural difference potential evoked by chirps and clicks. (United States)

    Riedel, Helmut; Kollmeier, Birger


    Rising chirps that compensate for the dispersion of the travelling wave on the basilar membrane evoke larger monaural brainstem responses than clicks. In order to test if a similar effect applies for the early processing stages of binaural information, monaurally and binaurally evoked auditory brainstem responses were recorded for clicks and chirps for levels from 10 to 60 dB nHL in steps of 10 dB. Ten thousand sweeps were collected for every stimulus condition from 10 normal hearing subjects. Wave V amplitudes are significantly larger for chirps than for clicks for all conditions. The amplitude of the binaural difference potential, DP1-DN1, is significantly larger for chirps at the levels 30 and 40 dB nHL. Both the binaurally evoked potential and the binaural difference potential exhibit steeper growth functions for chirps than for clicks for levels up to 40 dB nHL. For higher stimulation levels the chirp responses saturate approaching the click evoked amplitude. For both stimuli the latency of DP1 is shorter than the latency of the binaural wave V, which in turn is shorter than the latency of DN1. The amplitude ratio of the binaural difference potential to the binaural response is independent of stimulus level for clicks and chirps. A possible interpretation is that with click stimulation predominantly binaural interaction from high frequency regions is seen which is compatible with a processing by contralateral inhibitory and ipsilateral excitatory (IE) cells. Contributions from low frequencies are negligible since the responses from low frequencies are not synchronized for clicks. The improved synchronization at lower frequencies using chirp stimuli yields contributions from both low and high frequency neurons enlarging the amplitudes of the binaural responses as well as the binaural difference potential. Since the constant amplitude ratio of the binaural difference potential to the binaural response makes contralateral and ipsilateral excitatory interaction

  14. Objective information-theoretic algorithm for detecting brainstem-evoked responses to complex stimuli. (United States)

    Bidelman, Gavin M


    The scalp-recorded frequency-following response (FFR), an auditory-evoked potential with putative neural generators in the rostral brainstem, provides a robust representation of the neurophysiologic encoding of complex stimuli. The FFR is rapidly becoming a valuable tool for understanding the neural transcription of speech and music, language-related processing disorders, and brain plasticity at initial stages of the auditory pathway. Despite its potential clinical and empirical utility, determining the presence of a response is still dependent on the subjective interpretation by an experimenter/clinician. The purpose of the present work was to develop and validate a fully objective procedure for the automatic detection of FFRs elicited by complex auditory stimuli, including speech. Mutual information (MI) was computed between the spectrographic representation of neural FFRs and their evoking acoustic stimuli to quantify the amount of shared time-frequency information between electrophysiologic responses and stimulus acoustics. To remove human subjectivity associated with typical response evaluation, FFRs were first simulated at known signal-to-noise ratios using a computational model of the auditory periphery. The MI at which model FFRs contained +3 dB Signal-to-noise ratio was taken as the criterion threshold (θMI) for the presence of a response. θMI was then applied as a binary classifier on actual neurophysiologic responses recorded previously in human participants (n = 35). Sham recordings, in which no stimulus was presented to participants, allowed us to determine the receiver operating characteristics of the MI metric and the capabilities of the algorithm to segregate true evoked responses from sham recordings. RESULTS showed high overall accuracy (93%) in the metric's ability to identify true responses from sham recordings. The metric's overall performance was considerably better than trained human observers who, on average, accurately identified only

  15. Sleep-wake disturbances in common neurodegenerative diseases: a closer look at selected aspects of the neural circuitry. (United States)

    Zhong, George; Naismith, Sharon Linda; Rogers, Naomi Louise; Lewis, Simon John Geoffrey


    There is a growing appreciation regarding the relationship between common neurodegenerative diseases, such as Alzheimer's and Parkinson's and sleep-wake disturbances. These clinical features often herald the onset of such conditions and certainly appear to influence disease phenotype and progression. This article reviews some of the pathophysiological processes underlying specific disruptions within the neural circuitry underlying sleep-wake disturbances and explores how clinicopathological relationships commonly manifest. It is proposed that a greater understanding of these relationships should allow insights in to the efficacy of currently available treatments and help in the development of future therapies targeting disruptions within the sleep-wake neural circuitry. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. First realization of a tracking detector for high energy physics experiments based on Josephson digital readout circuitry

    CERN Document Server

    Pagano, S; Esposito, A P; Mukhanov, O; Rylov, S


    We have designed and realized a prototype of a high energy particle microstrip detector with Josephson readout circuits. The key features of this device are: minimum ionizing particle sensitivity, due to the use of semiconductive sensors, fast speed and radiation hardness, due to the use of superconductive circuitry, and current discrimination, which allows the use of several types of semiconductors as detector (Si, GaAs, CVD-diamond) without loss in performances. The Josephson circuitry, made by a combination of RSFQ and latching logic gates, realizes an 8-bit current discriminator and parallel to serial converter and can be directly interfaced to room temperature electronics. This device, which is designed for application as vertex detector for the Compass and LHC-B accelerator experiments, has been tested with small radioactive sources acid will undergo to a test beam at the CERN SPS facility with 24 GeV/c protons. Current results and future perspectives will be reported. (11 refs).

  17. Apollo experience report: Detection and minimization of ignition hazards from water/glycol contamination of silver-clad electrical circuitry (United States)

    Downs, W. R.


    The potential flammability hazard when a water/glycol solution contacts defectively insulated silver-clad copper circuitry or electrical components carrying a direct current is described. The chemical reactions and means for detecting them are explained. Methods for detecting and cleaning contaminated areas and the use of inhibitors to arrest chemical reactivity are also explained. Preventive measures to minimize hazards are given. Photomicrographs of the chemical reactions occurring on silver clad wires are also included.

  18. Analysis of graph invariants in functional neocortical circuitry reveals generalized features common to three areas of sensory cortex.

    Directory of Open Access Journals (Sweden)

    Suchin S Gururangan


    Full Text Available Correlations in local neocortical spiking activity can provide insight into the underlying organization of cortical microcircuitry. However, identifying structure in patterned multi-neuronal spiking remains a daunting task due to the high dimensionality of the activity. Using two-photon imaging, we monitored spontaneous circuit dynamics in large, densely sampled neuronal populations within slices of mouse primary auditory, somatosensory, and visual cortex. Using the lagged correlation of spiking activity between neurons, we generated functional wiring diagrams to gain insight into the underlying neocortical circuitry. By establishing the presence of graph invariants, which are label-independent characteristics common to all circuit topologies, our study revealed organizational features that generalized across functionally distinct cortical regions. Regardless of sensory area, random and k-nearest neighbors null graphs failed to capture the structure of experimentally derived functional circuitry. These null models indicated that despite a bias in the data towards spatially proximal functional connections, functional circuit structure is best described by non-random and occasionally distal connections. Eigenvector centrality, which quantifies the importance of a neuron in the temporal flow of circuit activity, was highly related to feedforwardness in all functional circuits. The number of nodes participating in a functional circuit did not scale with the number of neurons imaged regardless of sensory area, indicating that circuit size is not tied to the sampling of neocortex. Local circuit flow comprehensively covered angular space regardless of the spatial scale that we tested, demonstrating that circuitry itself does not bias activity flow toward pia. Finally, analysis revealed that a minimal numerical sample size of neurons was necessary to capture at least 90 percent of functional circuit topology. These data and analyses indicated that

  19. Implementation of a nation-wide automated auditory brainstem response hearing screening programme in neonatal intensive care units

    NARCIS (Netherlands)

    Straaten, H.L.M. van; Hille, E.T.M.; Kok, J.H.; Verkerk, P.H.; Baerts, W.; Bunkers, C.M.; Smink, E.W.A.; Elburg, R.M. van; Kleine, M.J.K. de; Ilsen, A.; Maingay-Visser, A.P.G.F.; Vries, L.S. de; Weisglas-Kuperus, N.


    Aim: As part of a future national neonatal hearing screening programme in the Netherlands, automated auditory brainstem response (AABR) hearing screening was implemented in seven neonatal intensive care units (NICUs). The objective was to evaluate key outcomes of this programme: participation rate,

  20. Endorphins and the hypotensive response to stimulation of alpha-receptors in the brainstem by alpha-methylnoradrenaline

    NARCIS (Netherlands)

    Jong, Wybren de; Petty, M.A.


    Opioid peptide involvement in the fall in blood pressure resulting from stimulation of alpha-receptors in the brainstem has been investigated in the urethane-anaesthetised rat. Unilateral microinjection of alpha-methylnoradrenaline into the nucleus tractus solitarii (NTS) induced a doserelated fall

  1. The Relationship between Brainstem Temporal Processing and Performance on Tests of Central Auditory Function in Children with Reading Disorders (United States)

    Billiet, Cassandra R.; Bellis, Teri James


    Purpose: Studies using speech stimuli to elicit electrophysiologic responses have found approximately 30% of children with language-based learning problems demonstrate abnormal brainstem timing. Research is needed regarding how these responses relate to performance on behavioral tests of central auditory function. The purpose of the study was to…

  2. Astrocyte-secreted factors modulate a gradient of primary dendritic arbors in nucleus laminaris of the avian auditory brainstem.

    Directory of Open Access Journals (Sweden)

    Matthew J Korn

    Full Text Available Neurons in nucleus laminaris (NL receive binaural, tonotopically matched input from nucleus magnocelluaris (NM onto bitufted dendrites that display a gradient of dendritic arbor size. These features improve computation of interaural time differences, which are used to determine the locations of sound sources. The dendritic gradient emerges following a period of significant reorganization at embryonic day 15 (E15, which coincides with the emergence of astrocytes that express glial fibrillary acidic protein (GFAP in the auditory brainstem. The major changes include a loss of total dendritic length, a systematic loss of primary dendrites along the tonotopic axis, and lengthening of primary dendrites on caudolateral NL neurons. Here we have tested whether astrocyte-derived molecules contribute to these changes in dendritic morphology. We used an organotypic brainstem slice preparation to perform repeated imaging of individual dye-filled NL neurons to determine the effects of astrocyte-conditioned medium (ACM on dendritic morphology. We found that treatment with ACM induced a decrease in the number of primary dendrites in a tonotopically graded manner similar to that observed during normal development. Our data introduce a new interaction between astrocytes and neurons in the auditory brainstem and suggest that these astrocytes influence multiple aspects of auditory brainstem maturation.

  3. Characteristics of multiple sclerosis patient stance control disorders, measured by means of posturography and related to brainstem lesions. (United States)

    Alpini, Dario; Berardino, Federica Di; Mattei, Valentina; Caputo, Domenico; Schalek, Peter; Cesarani, Antonio


    Balance disorders are commonly observed during the course of multiple sclerosis (MS). The aim of this study is to report characteristics of MS patient stance control disorders, measured by means of posturography and related to the brainstem lesions. Thirty-eight patients affected by MS, mildly to moderately disable according to Kurtzke's Expanded Disability Status Scale, underwent a complete clinical neurological and vestibular evaluation and brain MRI scanning. All patients were then tested on a static posturography platform (Tetrax, Israel) in four conditions: eyes open and eyes closed standing on a firm surface and on a foam pad. Clinical and/or magnetic resonance imaging evidence of brainstem involvement was observed in 55.3% of patients. When brainstem lesion was detected, Fourier analysis showed a typical pattern characterized by inversion of the 0-0.1 Hz and 0.1-0.25 Hz frequency bands. In conclusion, MS leads to pervasive postural disturbances in the majority of subjects, including the visuo-vestibular loops and proprioception involving vestibulo-spinal pathways in at least 55.3% of patients. Our results may also suggest the presence of Fourier inversion in patients with brainstem lesions.

  4. The analgesic agent tapentadol inhibits calcitonin gene-related peptide release from isolated rat brainstem via a serotonergic mechanism. (United States)

    Greco, Maria Cristina; Navarra, Pierluigi; Tringali, Giuseppe


    In this study we tested the hypothesis that tapentadol inhibits GGRP release from the rat brainstem through a mechanism mediated by the inhibition of NA reuptake; as a second alternative hypothesis, we investigated whether tapentadol inhibits GGRP release via the inhibition of 5-HT reuptake. Rat brainstems were explanted and incubated in short-term experiments. CGRP released in the incubation medium was taken as a marker of CGRP release from the central terminals of trigeminal neurons within the brainstem. CGRP levels were measured by radioimmunoassay under basal conditions or in the presence of tapentadol; NA, 5-HT, clonidine, yohimbine and ondansetron were used as pharmacological tools to investigate the action mechanism of tapentadol. The α2-antagonist yohimbine failed to counteract the effects of tapentadol. Moreover, neither NA nor the α2-agonist clonidine per se inhibited K(+)-stimulated CGRP release, thereby indicating that the effects of tapentadol are nor mediated through the block of NA reuptake. Further experiments showed that 5-HT and tramadol, which inhibits both NA and 5-HT reuptake, significantly reduced K(+)-stimulated CGRP release. Moreover, the 5-HT3 antagonist ondansetron was able to counteract the effects of tapentadol in this system. This study provided pharmacological evidence that tapentadol inhibits stimulated CGRP release from the rat brainstem in vitro through a mechanism involving an increase in 5-HT levels in the system and the subsequent activation of 5-HT3 receptors. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Study of the correlation of brainstem auditory evoked potentials and magnetic resonance imaging in children with spastic cerebral palsy

    Energy Technology Data Exchange (ETDEWEB)

    Fobe, Lisete Pessoa de Oliveira [Sao Paulo Univ., SP (Brazil). Faculdade de Medicina]. E-mail:


    Central auditory evaluation in 21 children with cerebral palsy was done with brainstem auditory evoked potentials (BAEP) and correlated with brain magnetic resonance imaging findings (MRI); 12 boys and 9 girls between 5 and 12 years old were studied. All children had follow-up at the Institute of Orthopedics and Traumatology of Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo. The control group was done with 17 children, 10 boys and 7 girls (mean age 8.06 years, SD 2.27 years). The BAEP abnormalities were: decrease of latency of wave V; decrease of latency III-V and I-IV intervals at the right side. All patients has MRI supratentorial abnormalities and 11 had brainstem atrophy. The MRI pathologic findings were: ventricular enlargement (n=17 or 80.95%), cortical/subcortical atrophy (n=15 or 71.42%), left brainstem atrophy (n=11 or 52.38%), periventricular leukomalacia (n=10 or 47.61%), infarction in the left middle cerebral artery territory (n=6 or 28.57%), and malformations such as schizencephaly and colpocephaly (n=5 or 23.80%). The findings of the decrease latencies in children with cerebral palsy suggest the contribution of decussating auditory fibers at the lower and upper pons and midbrain, the lack of homogeneity of the surrounding volume of the conductor fibres and the presence of several concurrently active potential generators sources, should be facilitating mechanisms for the nervous input to brainstem. (author)

  6. Organization of the auditory brainstem in a lizard, Gekko gecko. I. Auditory nerve, cochlear nuclei, and superior olivary nuclei

    DEFF Research Database (Denmark)

    Tang, Y. Z.; Christensen-Dalsgaard, J.; Carr, C. E.


    We used tract tracing to reveal the connections of the auditory brainstem in the Tokay gecko (Gekko gecko). The auditory nerve has two divisions, a rostroventrally directed projection of mid- to high best-frequency fibers to the nucleus angularis (NA) and a more dorsal and caudal projection of lo...

  7. Axonal sprouting of a brainstem-spinal pathway after estrogen administration in the adult female rhesus monkey

    NARCIS (Netherlands)

    Vanderhorst, VGJM; Terasawa, E; Ralston, HJ


    The nucleus retroambiguus (NRA) is located in the caudal medulla oblongata and contains premotor neurons that project to motoneuronal cell groups in the brainstem and spinal cord. NRA projections to the lumbosacral cord are species specific and might be involved in mating behavior. In the female

  8. Characteristics of multiple sclerosis patient stance control disorders, measured by means of posturography and related to brainstem lesions

    Directory of Open Access Journals (Sweden)

    Dario Alpini


    Full Text Available Balance disorders are commonly observed during the course of multiple sclerosis (MS. The aim of this study is to report characteristics of MS patient stance control disorders, measured by means of posturography and related to the brainstem lesions. Thirty-eight patients affected by MS, mildly to moderately disable according to Kurtzke’s Expanded Disability Status Scale, underwent a complete clinical neurological and vestibular evaluation and brain MRI scanning. All patients were then tested on a static posturography platform (Tetrax, Israel in four conditions: eyes open and eyes closed standing on a firm surface and on a foam pad. Clinical and/or magnetic resonance imaging evidence of brainstem involvement was observed in 55.3% of patients. When brainstem lesion was detected, Fourier analysis showed a typical pattern characterized by inversion of the 0- 0.1 Hz and 0.1-0.25 Hz frequency bands. In conclusion, MS leads to pervasive postural disturbances in the majority of subjects, including the visuo-vestibular loops and proprioception involving vestibulospinal pathways in at least 55.3% of patients. Our results may also suggest the presence of Fourier inversion in patients with brainstem lesions.

  9. Therapeutic hypothermia with the use of intracranial pressure monitoring for acute disseminated encephalomyelitis with brainstem lesion: a case report. (United States)

    Miyamoto, Kenji; Kozu, Seiki; Arakawa, Akiko; Tsuboi, Tatsuo; Hirao, Jun-Ichi; Ono, Kazuyuki; Arisaka, Osamu


    Acute disseminated encephalomyelitis confined to the brainstem is associated with poor prognosis. We describe a case of a 10-year-old boy with acute disseminated encephalomyelitis in the brainstem that developed after influenza A infection. A 10-year-old boy presented with fever and prolonged disturbance of consciousness and was admitted to our hospital. Magnetic resonance imaging (MRI) of the midbrain, with T2-weighted and fluid-attenuated inversion recovery images, suggested acute disseminated encephalomyelitis accompanied by a brainstem lesion. Lumbar puncture showed pleocytosis and increased protein content, including myelin basic protein, interleukin-6, and immunoglobulin G, all suggestive of acute disseminated encephalomyelitis. Treatments such as methylprednisolone pulse therapy, intravenous immunoglobulin, and therapeutic hypothermia were performed. Although the patient presented with anisocoria with increased intracranial pressure monitoring during hypothermia, prompt therapy with d-mannitol and dopamine was effective. Our case results suggest that hypothermia could be included in the choice of therapy for acute disseminated encephalomyelitis with brainstem lesions. © The Author(s) 2013.

  10. Musicians and Tone-Language Speakers Share Enhanced Brainstem Encoding but Not Perceptual Benefits for Musical Pitch (United States)

    Bidelman, Gavin M.; Gandour, Jackson T.; Krishnan, Ananthanarayan


    Behavioral and neurophysiological transfer effects from music experience to language processing are well-established but it is currently unclear whether or not linguistic expertise (e.g., speaking a tone language) benefits music-related processing and its perception. Here, we compare brainstem responses of English-speaking musicians/non-musicians…

  11. A glycinergic projection from the ventromedial lower brainstem to spinal motoneurons. An ultrastructural double labeling study in rat

    NARCIS (Netherlands)

    J.C. Holstege (Jan); C.M.H. Bongers (C. M H)


    markdownabstract__Abstract__ In the present study it was determined whether glycine was present in the descending brainstem projections to spinal motoneurons in the rat. For this purpose injections of wheatgerm agglutinin-horseradish peroxidase (WGA-HRP) were made in the ventromedial part of the

  12. Aerial low-frequency hearing in captive and free-ranging harbour seals (Phoca vitulina) measured using auditory brainstem responses

    NARCIS (Netherlands)

    Lucke, K.; Hastie, Gordon D.; Ternes, Kerstin; McConnell, Bernie; Moss, Simon; Russell, Deborah J.F.; Weber, Heike; Janik, Vincent M.


    The hearing sensitivity of 18 free-ranging and 10 captive harbour seals (Phoca vitulina) to aerial sounds was measured in the presence of typical environmental noise through auditory brainstem response measurements. A focus was put on the comparative hearing sensitivity at low frequencies. Low-

  13. Perceptual alternation in obsessive compulsive disorder--implications for a role of the cortico-striatal circuitry in mediating awareness. (United States)

    Li, C S; Chen, M C; Yang, Y Y; Chang, H L; Liu, C Y; Shen, S; Chen, C Y


    Mounting evidence suggests that obsessive compulsive disorder (OCD) results from functional aberrations of the fronto-striatal circuitry. However, empirical studies of the behavioral manifestations of OCD have been relatively lacking. The present study employs a behavioral task that allows a quantitative measure of how alternative percepts are formed from one moment to another, a process mimicking the brain state in which different thoughts and imageries compete for access to awareness. Eighteen patients with OCD, 12 with generalized anxiety disorder, and 18 normal subjects participated in the experiment, in which they viewed one of the three Schröder staircases and responded by pressing a key to each perceptual reversal. The results demonstrate that the patients with OCD have a higher perceptual alternation rate than the normal controls. Moreover, the frequency of perceptual alternation is significantly correlated with the Yale-Brown obsessive compulsive and the Hamilton anxiety scores. The increase in the frequency of perceptual reversals cannot easily be accounted for by learning or by different patterns of eye fixations on the task. These results provide further evidence that an impairment of the inhibitory function of the cortico-striatal circuitry might underlie the etiology of OCD. The implications of the results for a general role of the cortico-striatal circuitry in mediating awareness are discussed.

  14. Survey of the Knowledge of Brainstem Death and Attitude Toward Organ Donation Among Relations of Neurosurgical Patients in Nigeria. (United States)

    Rabiu, T B; Oshola, H A; Adebayo, B O


    Organ transplantation is a developing field in Nigeria, and availability of organs for donation would be a determining factor of the success of the transplant programs. Patients with brainstem death (BSD) are a major source of organs for transplantation. The level of knowledge of BSD as well as attitudes toward organ donation are very important determinants of people's willingness or otherwise to donate organs. We conducted a survey of relations of our in-service neurosurgical patients to assess their knowledge of brainstem death and attitude toward organ donation. To our knowledge, this is the first study of its kind among the growing Nigerian neurosurgery patient and patient-relations population. Convenience sampling of randomly selected relations of neurosurgical patients on admission using interviewer-administered questionnaires was performed. Demographic information and information about brainstem death, attitude toward brainstem death, knowledge of organ donation, and attitude toward organ donation were obtained. The study comprised 127 respondents with a mean age of 36 years (range, 19-72). The majority of the respondents (87, 62.4%) were Christians, 122 (96.1%) were Yorubas, and 66 (52.0%) were women. Eighty-five (66.9%) of the respondents had at least a secondary level of education, and 77 (60.6%) were of low socioeconomic status. Twenty-eight (22.2%) of the respondents had heard of brainstem death. Twenty-six (92.9%) of those who had heard of brainstem death believed that the brain could die long before life finally ceases. One hundred twenty-five (98.4%) of the respondents believed that death only occurs when both breathing and heartbeat stop, and 107 (83.6%) would agree with the physician on a diagnosis of brainstem death in the relation. Sixty-five (51.2%) would want such patients put on a ventilator, and, of these, 43 (66.2%) would want such patients on the ventilator in hope that he or she may recover. One hundred twelve (88.2%) of the relations were

  15. Brainstem auditory evoked responses in man. 1: Effect of stimulus rise-fall time and duration (United States)

    Hecox, K.; Squires, N.; Galambos, R.


    Short latency (under 10 msec) responses elicited by bursts of white noise were recorded from the scalps of human subjects. Response alterations produced by changes in the noise burst duration (on-time), inter-burst interval (off-time), and onset and offset shapes were analyzed. The latency of the most prominent response component, wave V, was markedly delayed with increases in stimulus rise time but was unaffected by changes in fall time. Increases in stimulus duration, and therefore in loudness, resulted in a systematic increase in latency. This was probably due to response recovery processes, since the effect was eliminated with increases in stimulus off-time. The amplitude of wave V was insensitive to changes in signal rise and fall times, while increasing signal on-time produced smaller amplitude responses only for sufficiently short off-times. It was concluded that wave V of the human auditory brainstem evoked response is solely an onset response.

  16. Modular organization of the brainstem noradrenaline system coordinates opposing learning states. (United States)

    Uematsu, Akira; Tan, Bao Zhen; Ycu, Edgar A; Cuevas, Jessica Sulkes; Koivumaa, Jenny; Junyent, Felix; Kremer, Eric J; Witten, Ilana B; Deisseroth, Karl; Johansen, Joshua P


    Noradrenaline modulates global brain states and diverse behaviors through what is traditionally believed to be a homogeneous cell population in the brainstem locus coeruleus (LC). However, it is unclear how LC coordinates disparate behavioral functions. We report a modular LC organization in rats, endowed with distinct neural projection patterns and coding properties for flexible specification of opposing behavioral learning states. LC projection mapping revealed functionally distinct cell modules with specific anatomical connectivity. An amygdala-projecting ensemble promoted aversive learning, while an independent medial prefrontal cortex-projecting ensemble extinguished aversive responses to enable flexible behavior. LC neurons displayed context-dependent inter-relationships, with moderate, discrete activation of distinct cell populations by fear or safety cues and robust, global recruitment of most cells by strong aversive stimuli. These results demonstrate a modular organization in LC in which combinatorial activation modes are coordinated with projection- and behavior-specific cell populations, enabling adaptive tuning of emotional responding and behavioral flexibility.

  17. On the synthesis of multiple frequency tone burst stimuli for efficient high frequency auditory brainstem response. (United States)

    Ellingson, Roger M; Dille, Marilyn L; Leek, Marjorie R; Fausti, Stephen A


    The development and digital waveform synthesis of a multiple-frequency tone-burst (MFTB) stimulus is presented. The stimulus is designed to improve the efficiency of monitoring high-frequency auditory-brainstem-response (ABR) hearing thresholds. The pure-tone-based, fractional-octave-bandwidth MFTB supports frequency selective ABR audiometry with a bandwidth that falls between the conventional click and single-frequency tone-burst stimuli. The MFTB is being used to identify high frequency hearing threshold change due to ototoxic medication which most generally starts at the ultra-highest hearing frequencies and progresses downwards but could be useful in general limited-bandwidth testing applications. Included is a Mathcad implementation and analysis of our MFTB synthesis technique and sample performance measurements of the MFTB stimulus configuration used in a clinical research ABR system.

  18. Concentrated pitch discrimination modulates auditory brainstem responses during contralateral noise exposure. (United States)

    Ikeda, Kazunari; Sekiguchi, Takahiro; Hayashi, Akiko


    This study examined a notion that auditory discrimination is a requisite for attention-related modulation of the auditory brainstem response (ABR) during contralateral noise exposure. Given that the right ear was exposed continuously with white noise at an intensity of 60-80 dB sound pressure level, tone pips at 80 dB sound pressure level were delivered to the left ear through either single-stimulus or oddball procedures. Participants conducted reading (ignoring task) and counting target tones (attentive task) during stimulation. The oddball but not the single-stimulus procedures elicited task-related modulations in both early (ABR) and late (processing negativity) event-related potentials simultaneously. The elicitation of the attention-related ABR modulation during contralateral noise exposure is thus considered to require auditory discrimination and have the corticofugal nature evidently.

  19. Attention-related modulation of auditory brainstem responses during contralateral noise exposure. (United States)

    Ikeda, Kazunari; Sekiguchi, Takahiro; Hayashi, Akiko


    As determinants facilitating attention-related modulation of the auditory brainstem response (ABR), two experimental factors were examined: (i) auditory discrimination; and (ii) contralateral masking intensity. Tone pips at 80 dB sound pressure level were presented to the left ear via either single-tone exposures or oddball exposures, whereas white noise was delivered continuously to the right ear at variable intensities (none--80 dB sound pressure level). Participants each conducted two tasks during stimulation, either reading a book (ignoring task) or detecting target tones (attentive task). Task-related modulation within the ABR range was found only during oddball exposures at contralateral masking intensities greater than or equal to 60 dB. Attention-related modulation of ABR can thus be detected reliably during auditory discrimination under contralateral masking of sufficient intensity.

  20. 'Compassionate use' protocol for auditory brainstem implantation in neurofibromatosis type 2: Early House Ear Institute experience. (United States)

    Roberts, Daniel S; Slattery, William H; Chen, Brian S; Otto, Steve R; Schwartz, Marc S; Lekovic, Gregory P


    To report the preliminary outcomes of auditory brainstem implantation (ABI) under a compassionate use protocol for two ABI devices that are not approved by the US Food and Drug Administration. A retrospective review was performed of neurofibromatosis type 2 (NF2) patients who underwent microsurgery for vestibular schwannoma (VS) and placement of either the Cochlear ABI541 or Med-El Synchrony ABIs. Peri-operative and device- related complications were reviewed. Audiometric performance was also evaluated. Seven patients received either the Cochlear ABI541 (6) or the Med-El Synchrony ABI (1) after the resection of VS. No device or patient-related complications occurred to date. Surgical times and early audiological performance are similar to our previous experience with the Cochlear ABI24 device. Early experience with the Cochlear ABI541 and Med-El Synchrony ABI devices under a compassionate use protocol suggest that both devices are safe with comparable utility to the Cochlear ABI24 device.

  1. The superior fovea triangle approach: a novel safe entry zone to the brainstem. (United States)

    Yagmurlu, Kaan; Kalani, M Yashar S; Preul, Mark C; Spetzler, Robert F


    The authors describe a safe entry zone, the superior fovea triangle, on the floor of the fourth ventricle for resection of deep dorsal pontine lesions at the level of the facial colliculus. Clinical data from a patient undergoing a suboccipital telovelar transsuperior fovea triangle approach to a deep pontine cavernous malformation were reviewed and supplemented with 6 formalin-fixed adult human brainstem and 2 silicone-injected adult human cadaveric heads using the fiber dissection technique to illustrate the utility of this novel safe entry zone. The superior fovea has a triangular shape that is an important landmark for the motor nucleus of the trigeminal, abducens, and facial nerves. The inferior half of the superior fovea triangle may be incised to remove deep dorsal pontine lesions through the floor of the fourth ventricle. The superior fovea triangle may be used as a safe entry zone for dorsally located lesions at the level of the facial colliculus.

  2. Increased brainstem perfusion, but no blood-brain barrier disruption, during attacks of migraine with aura

    DEFF Research Database (Denmark)

    Hougaard, Anders; Amin, Faisal M; Christensen, Casper E


    See Moskowitz (doi:10.1093/brain/awx099) for a scientific commentary on this article.The migraine aura is characterized by transient focal cortical disturbances causing dramatic neurological symptoms that are usually followed by migraine headache. It is currently not understood how the aura...... symptoms are related to the headache phase of migraine. Animal studies suggest that cortical spreading depression, the likely mechanism of migraine aura, causes disruption of the blood-brain barrier and noxious stimulation of trigeminal afferents leading to activation of brainstem nuclei and triggering...... of the anterior, middle and posterior circulation during spontaneous attacks of migraine with aura. Patients reported to our institution to undergo magnetic resonance imaging during the headache phase after presenting with typical visual aura. Nineteen patients were scanned during attacks and on an attack...

  3. Guillain-Barré Syndrome with Absent Brainstem Reflexes: a Case Report

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    Susana Gordon Chaves


    Full Text Available A 41-year-old man was admitted to an intensive care unit following respiratory arrest. One day prior to admission, he had complaints of nausea and pain involving lower limbs. On the night of admission he developed diplopia, dysphagia, and rapidly progressive quadriparesis. He developed respiratory failure requiring mechanical lung ventilation 24 hours later. On the fifth day of hospital stay the patient became comatose with absent brainstem reflexes and appeared to be brain dead. The cerebrospinal fluid showed albuminocytological dissociation. The electroencephalogram revealed an alpha rhythmical activity. The electrophysiological evaluation revealed an inexcitability of all nerves. Guillain-Barré syndrome was suspected. With supportive treatment the patient had a remarkable recovery and now is able to independently conduct his daily activities.

  4. Brainstem Monitoring in the Neurocritical Care Unit: A Rationale for Real-Time, Automated Neurophysiological Monitoring. (United States)

    Stone, James L; Bailes, Julian E; Hassan, Ahmed N; Sindelar, Brian; Patel, Vimal; Fino, John


    Patients with severe traumatic brain injury or large intracranial space-occupying lesions (spontaneous cerebral hemorrhage, infarction, or tumor) commonly present to the neurocritical care unit with an altered mental status. Many experience progressive stupor and coma from mass effects and transtentorial brain herniation compromising the ascending arousal (reticular activating) system. Yet, little progress has been made in the practicality of bedside, noninvasive, real-time, automated, neurophysiological brainstem, or cerebral hemispheric monitoring. In this critical review, we discuss the ascending arousal system, brain herniation, and shortcomings of our current management including the neurological exam, intracranial pressure monitoring, and neuroimaging. We present a rationale for the development of nurse-friendly-continuous, automated, and alarmed-evoked potential monitoring, based upon the clinical and experimental literature, advances in the prognostication of cerebral anoxia, and intraoperative neurophysiological monitoring.

  5. An Examination of Executive Dysfunction Associated with Frontostriatal Circuitry in Parkinson’s Disease (United States)



    Parkinson’s disease (PD) is a neurodegenerative movement disorder presenting with subcortical pathology and characterized by motor deficits. However, as is frequently reported in the literature, patients with PD can also exhibit cognitive and behavioral (i.e., nonmotor) impairments, cognitive executive deficits and depression being the most prominent. Considerable attention has addressed the role that disruption to frontostriatal circuitry can play in mediating nonmotor dysfunction in PD. The three nonmotor frontostriatal circuits, which connect frontal cortical regions to the basal ganglia, originate from the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and orbitofrontal cortex (OFC). The objective of the current study was to use our understanding of frontostriatal circuit function (via literature review) to categorize neuropsychological measures of cognitive and behavioral executive functions by circuit. To our knowledge, such an approach has not been previously attempted in the study of executive dysfunction in PD. Neuropsychological measures of executive functions and self-report behavioral inventories, categorized by circuit function, were administered to 32 nondemented patients with Parkinson’s disease (NDPD) and to 29 demographically matched, healthy normal control participants (NC). Our findings revealed significant group differences for each circuit, with the PD group performing worse than the NC group. Among the patients with PD, indices of impairment were greater for tasks associated with DLPFC function than with OFC function. Further, only an index of DLPFC test performance was demonstrated to significantly discriminate individuals with and without PD. In conclusion, our findings suggest that nondemented patients with PD exhibit greater impairment on neuropsychological measures associated with DLPFC than with ACC or OFC circuit function. PMID:16840240

  6. The banana code – Natural blend processing in the olfactory circuitry of Drosophila melanogaster

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    Marco eSchubert


    Full Text Available Odor information is predominantly perceived as complex odor blends. For Drosophila melanogaster one of the most attractive blends is emitted by an over-ripe banana. To analyze how the fly’s olfactory system processes natural blends we combined the experimental advantages of gas chromatography and functional imaging (GC-I. In this way, natural banana compounds were presented successively to the fly antenna in close to natural occurring concentrations. This technique allowed us to identify the active odor components, use these compounds as stimuli and measure odor-induced Ca2+ signals in input and output neurons of the Drosophila antennal lobe (AL, the first olfactory neuropil. We demonstrate that mixture interactions of a natural blend are very rare and occur only at the AL output level resulting in a surprisingly linear blend representation. However, the information regarding single components is strongly modulated by the olfactory circuitry within the AL leading to a higher similarity between the representation of individual components and the banana blend. This observed modulation might tune the olfactory system in a way to distinctively categorize odor components and improve the detection of suitable food sources. Functional GC-I thus enables analysis of virtually any unknown natural odorant blend and its components in their relative occurring concentrations and allows characterization of neuronal responses of complete neural assemblies. This technique can be seen as a valuable complementary method to classical GC/electrophysiology techniques, and will be a highly useful tool in future investigations of insect-insect and insect-plant chemical interactions.

  7. Dopamine elevates and lowers astroglial Ca2+ through distinct pathways depending on local synaptic circuitry. (United States)

    Jennings, Alistair; Tyurikova, Olga; Bard, Lucie; Zheng, Kaiyu; Semyanov, Alexey; Henneberger, Christian; Rusakov, Dmitri A


    Whilst astrocytes in culture invariably respond to dopamine with cytosolic Ca2+ rises, the dopamine sensitivity of astroglia in situ and its physiological roles remain unknown. To minimize effects of experimental manipulations on astroglial physiology, here we monitored Ca2+ in cells connected via gap junctions to astrocytes loaded whole-cell with cytosolic indicators in area CA1 of acute hippocampal slices. Aiming at high sensitivity of [Ca2+ ] measurements, we also employed life-time imaging of the Ca2+ indicator Oregon Green BAPTA-1. We found that dopamine triggered a dose-dependent, bidirectional Ca2+ response in stratum radiatum astroglia, a jagged elevation accompanied and followed by below-baseline decreases. The elevation depended on D1/D2 receptors and engaged intracellular Ca2+ storage and removal whereas the dopamine-induced [Ca2+ ] decrease involved D2 receptors only and was sensitive to Ca2+ channel blockade. In contrast, the stratum lacunosum moleculare astroglia generated higher-threshold dopamine-induced Ca2+ responses which did not depend on dopamine receptors and were uncoupled from the prominent inhibitory action of dopamine on local perforant path synapses. Our findings thus suggest that a single neurotransmitter-dopamine-could either elevate or decrease astrocyte [Ca2+ ] depending on the receptors involved, that such actions are specific to the regional neural circuitry and that they may be causally uncoupled from dopamine actions on local synapses. The results also indicate that [Ca2+ ] elevations commonly detected in astroglia can represent the variety of distinct mechanisms acting on the microscopic scale. GLIA 2017;65:447-459. © 2016 The Authors Glia Published by Wiley Periodicals, Inc.

  8. Invasive circuitry-based neurotherapeutics: stereotactic ablation and deep brain stimulation for OCD. (United States)

    Greenberg, Benjamin D; Rauch, Scott L; Haber, Suzanne N


    patterns of potential benefits and burdens. Translational research to elucidate how targeting specific nodes in putative OCD circuitry might lead to therapeutic gains is accelerating in tandem with clinical use.

  9. Effects of direct social experience on trust decisions and neural reward circuitry

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    Dominic S. Fareri


    Full Text Available The human striatum is integral for reward-processing and supports learning by linking experienced outcomes with prior expectations. Recent endeavors implicate the striatum in processing outcomes of social interactions, such as social approval/rejection, as well as in learning reputations of others. Interestingly, social impressions often influence our behavior with others during interactions. Information about an interaction partner’s moral character acquired from biographical information hinders updating of expectations after interactions via top down modulation of reward circuitry. An outstanding question is whether initial impressions formed through experience similarly modulate the ability to update social impressions at the behavioral and neural level. We investigated the role of experienced social information on trust behavior and reward-related BOLD activity. Participants played a computerized ball tossing game with three fictional partners manipulated to be perceived as good, bad or neutral. Participants then played an iterated trust game as investors with these same partners while undergoing fMRI. Unbeknownst to participants, partner behavior in the trust game was random and unrelated to their ball-tossing behavior. Participants’ trust decisions were influenced by their prior experience in the ball tossing game, investing less often with the bad partner compared to the good and neutral. Reinforcement learning models revealed that participants were more sensitive to updating their beliefs about good and bad partners when experiencing outcomes consistent with initial experience. Increased striatal and anterior cingulate BOLD activity for positive versus negative trust game outcomes emerged, which further correlated with model-derived prediction-error (PE learning signals. These results suggest that initial impressions formed from direct social experience can be continually shaped by consistent information through reward learning

  10. Hyperleptinemia in Neonatally Overfed Female Rats Does Not Dysregulate Feeding Circuitry

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    Ilvana Ziko


    Full Text Available Neonatal overfeeding during the first weeks of life in male rats is associated with a disruption in the peripheral and central leptin systems. Neonatally overfed male rats have increased circulating leptin in the first 2 weeks of life, which corresponds to an increase in body weight compared to normally fed counterparts. These effects are associated with a short-term disruption in the connectivity of neuropeptide Y (NPY, agouti-related peptide (AgRP, and pro-opiomelanocortin (POMC neurons within the regions of the hypothalamus responsible for control of energy balance and food intake. Female rats that are overfed during the first weeks of their life experience similar changes in circulating leptin levels as well as in their body weight. However, it has not yet been studied whether these metabolic changes are associated with the same central effects as observed in males. Here, we hypothesized that hyperleptinemia associated with neonatal overfeeding would lead to changes in central feeding circuitry in females as it does in males. We assessed hypothalamic NPY, AgRP, and POMC gene expression and immunoreactivity at 7, 12, or 14 days of age, as well as neuronal activation in response to exogenous leptin in neonatally overfed and control female rats. Neonatally overfed female rats were hyperleptinemic and were heavier than controls. However, these metabolic changes were not mirrored centrally by changes in hypothalamic NPY, AGRP, and POMC fiber density. These findings are suggestive of sex differences in the effects of neonatal overfeeding and of differences in the ability of the female and male central systems to respond to changes in the early life nutritional environment.

  11. Disrupted brain circuitry for pain-related reward/punishment in fibromyalgia. (United States)

    Loggia, Marco L; Berna, Chantal; Kim, Jieun; Cahalan, Christine M; Gollub, Randy L; Wasan, Ajay D; Harris, Richard E; Edwards, Robert R; Napadow, Vitaly


    While patients with fibromyalgia (FM) are known to exhibit hyperalgesia, the central mechanisms contributing to this altered pain processing are not fully understood. This study was undertaken to investigate potential dysregulation of the neural circuitry underlying cognitive and hedonic aspects of the subjective experience of pain, such as anticipation of pain and anticipation of pain relief. Thirty-one FM patients and 14 controls underwent functional magnetic resonance imaging, while receiving cuff pressure pain stimuli on the leg calibrated to elicit a pain rating of ~50 on a 100-point scale. During the scan, subjects also received visual cues informing them of the impending onset of pain (pain anticipation) and the impending offset of pain (relief anticipation). Patients exhibited less robust activation during both anticipation of pain and anticipation of relief within regions of the brain commonly thought to be involved in sensory, affective, cognitive, and pain-modulatory processes. In healthy controls, direct searches and region-of-interest analyses of the ventral tegmental area revealed a pattern of activity compatible with the encoding of punishment signals: activation during anticipation of pain and pain stimulation, but deactivation during anticipation of pain relief. In FM patients, however, activity in the ventral tegmental area during periods of pain and periods of anticipation (of both pain and relief) was dramatically reduced or abolished. FM patients exhibit disrupted brain responses to reward/punishment. The ventral tegmental area is a source of reward-linked dopaminergic/γ-aminobutyric acid-releasing (GABAergic) neurotransmission in the brain, and our observations are compatible with reports of altered dopaminergic/GABAergic neurotransmission in FM. Reduced reward/punishment signaling in FM may be related to the augmented central processing of pain and reduced efficacy of opioid treatments in these patients. Copyright © 2014 by the American

  12. Changes in brainstem auditory evoked potentials among North Indian females with Type 2 diabetes mellitus

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    Pooja Baweja


    Full Text Available Background: Diabetes mellitus is a complex metabolic disorder whose detrimental effects on various organ systems, including the nervous system are well known. Aim: This study was conducted to determine the changes in the brainstem auditory evoked potentials (BAEP in patients with type 2 diabetes mellitus. Materials and Methods: In this case-control study, 116 females with type 2 diabetes and 100 age matched, healthy female volunteers were selected. The brainstem auditory evoked potentials (BAEP were recorded with RMS EMG EP Marc-II Channel machine. The measures included latencies of waves I, II, III, IV, V and Interpeak latencies (IPL I-III, III-V and I-V separately for both ears. Data was analysed statistically with SPSS software v13.0. Results: It was found that IPL I-III was significantly delayed (P = 0.028 only in the right ear, while the latency of wave V and IPL I-V showed a significant delay bilaterally (P values for right ear being 0.021 and 0.0381 respectively while those for left ear being 0.028 and 0.016 respectively, in diabetic females. However, no significant difference (P > 0.05 was found between diabetic and control subjects as regards to the latencies of waves I, II, III, IV and IPL III-V bilaterally and IPL I-III unilaterally in the left ear. Also, none of the BAEP latencies were significantly correlated with either the duration of disease or with fasting blood glucose levels in diabetics. Conclusions: Therefore, it could be concluded that diabetes patients have an early involvement of central auditory pathway, which can be detected quite accurately with the help of auditory evoked potential studies.

  13. Gap prepulse inhibition and auditory brainstem evoked potentials as objective measures for tinnitus in guinea pigs.

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    Susanne eDehmel


    Full Text Available Tinnitus or ringing of the ears is a subjective phantom sensation necessitating behavioral models that objectively demonstrate the existence and quality of the tinnitus sensation. The gap detection test uses the acoustic startle response elicited by loud noise pulses and its gating or suppression by preceding sub-startling prepulses. Gaps in noise bands serve as prepulses, assuming that ongoing tinnitus masks the gap and results in impaired gap detection. This test has shown its reliability in rats, mice, and gerbils. No data exists for the guinea pig so far, although gap detection is similar across mammals and the acoustic startle response is a well-established tool in guinea pig studies of psychiatric disorders and in pharmacological studies. Here we investigated the startle behavior and prepulse inhibition (PPI of the guinea pig and showed that guinea pigs have a reliable startle response that can be suppressed by 15 ms gaps embedded in narrow noise bands preceding the startle noise pulse. After recovery of auditory brainstem response (ABR thresholds from a unilateral noise over-exposure centered at 7 kHz, guinea pigs showed diminished gap-induced reduction of the startle response in frequency bands between 8 and 18 kHz. This suggests the development of tinnitus in frequency regions that showed a temporary threshold shift (TTS after noise over-exposure. Changes in discharge rate and synchrony, two neuronal correlates of tinnitus, should be reflected in altered ABR waveforms, which would be useful to objectively detect tinnitus and its localization to auditory brainstem structures. Therefore we analyzed latencies and amplitudes of the first five ABR waves at suprathreshold sound intensities and correlated ABR abnormalities with the results of the behavioral tinnitus testing. Early ABR wave amplitudes up to N3 were increased for animals with tinnitus possibly stemming from hyperactivity and hypersynchrony underlying the tinnitus percept.

  14. The role of the auditory brainstem in processing musically-relevant pitch

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    Gavin M. Bidelman


    Full Text Available Neuroimaging work has shed light on the cerebral architecture involved in processing the melodic and harmonic aspects of music. Here, recent evidence is reviewed illustrating that subcortical auditory structures contribute to the early formation and processing of musically-relevant pitch. Electrophysiological recordings from the human brainstem and population responses from the auditory nerve reveal that nascent features of tonal music (e.g., consonance/dissonance, pitch salience, harmonic sonority are evident at early, subcortical levels of the auditory pathway. The salience and harmonicity of brainstem activity is strongly correlated with listeners’ perceptual preferences and perceived consonance for the tonal relationships of music. Moreover, the hierarchical ordering of pitch intervals/chords described by the Western music practice and their perceptual consonance is well-predicted by the salience with which pitch combinations are encoded in subcortical auditory structures. While the neural correlates of consonance can be tuned and exaggerated with musical training, they persist even in the absence of musicianship or long-term enculturation. As such, it is posited that the structural foundations of musical pitch might result from innate processing performed by the central auditory system. A neurobiological predisposition for consonant, pleasant sounding pitch relationships may be one reason why these pitch combinations have been favored by composers and listeners for centuries. It is suggested that important perceptual dimensions of music emerge well before the auditory signal reaches cerebral cortex and prior to attentional engagement. While cortical mechanisms are no doubt critical to the perception, production, and enjoyment of music, the contribution of subcortical structures implicates a more integrated, hierarchically organized network underlying music processing within the brain.

  15. The Role of the Auditory Brainstem in Processing Musically Relevant Pitch (United States)

    Bidelman, Gavin M.


    Neuroimaging work has shed light on the cerebral architecture involved in processing the melodic and harmonic aspects of music. Here, recent evidence is reviewed illustrating that subcortical auditory structures contribute to the early formation and processing of musically relevant pitch. Electrophysiological recordings from the human brainstem and population responses from the auditory nerve reveal that nascent features of tonal music (e.g., consonance/dissonance, pitch salience, harmonic sonority) are evident at early, subcortical levels of the auditory pathway. The salience and harmonicity of brainstem activity is strongly correlated with listeners’ perceptual preferences and perceived consonance for the tonal relationships of music. Moreover, the hierarchical ordering of pitch intervals/chords described by the Western music practice and their perceptual consonance is well-predicted by the salience with which pitch combinations are encoded in subcortical auditory structures. While the neural correlates of consonance can be tuned and exaggerated with musical training, they persist even in the absence of musicianship or long-term enculturation. As such, it is posited that the structural foundations of musical pitch might result from innate processing performed by the central auditory system. A neurobiological predisposition for consonant, pleasant sounding pitch relationships may be one reason why these pitch combinations have been favored by composers and listeners for centuries. It is suggested that important perceptual dimensions of music emerge well before the auditory signal reaches cerebral cortex and prior to attentional engagement. While cortical mechanisms are no doubt critical to the perception, production, and enjoyment of music, the contribution of subcortical structures implicates a more integrated, hierarchically organized network underlying music processing within the brain. PMID:23717294

  16. Visualization of oxytocin release that mediates paired pulse facilitation in hypothalamic pathways to brainstem autonomic neurons.

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    Ramón A Piñol

    Full Text Available Recent work has shown that oxytocin is involved in more than lactation and uterine contraction. The paraventricular nucleus of the hypothalamus (PVN contains neuroendocrine neurons that control the release of hormones, including vasopressin and oxytocin. Other populations of PVN neurons do not release hormones, but rather project to and release neurotransmitters onto other neurons in the CNS involved in fluid retention, thermoregulation, sexual behavior and responses to stress. Activation of oxytocin receptors can be cardioprotective and reduces the adverse cardiovascular consequences of anxiety and stress, yet how oxytocin can affect heart rate and cardiac function is unknown. While anatomical work has shown the presence of peptides, including oxytocin, in the projections from the PVN to parasympathetic nuclei, electrophysiological studies to date have only demonstrated release of glutamate and activation of fast ligand gated receptors in these pathways. In this study, using rats, we directly show, using sniffer CHO cells that express oxytocin receptors and the Ca2+ indicator R-GECO, that optogenetic activation of channelrhodopsin-2 (ChR2 expressing PVN fibers in the brainstem activates oxytocin receptors in the dorsomotor nucleus of the vagus (DMNV. We also demonstrate that while a single photoactivation of PVN terminals only activates glutamatergic receptors in brainstem cardiac vagal neurons (CVNs, neurons that dominate the neural control of heart rate, both the paired pulse facilitation, and sustained enhancement of glutamate release in this pathway is mediated by activation of oxytocin receptors. Our results provide direct evidence that a pathway from the PVN likely releases oxytocin and enhances short-term plasticity of this critical autonomic connection.

  17. Influence of sucrose ingestion on brainstem and hypothalamic intrinsic oscillations in lean and obese women. (United States)

    Kilpatrick, Lisa A; Coveleskie, Kristen; Connolly, Lynn; Labus, Jennifer S; Ebrat, Bahar; Stains, Jean; Jiang, Zhiguo; Suyenobu, Brandall Y; Raybould, Helen E; Tillisch, Kirsten; Mayer, Emeran A


    The study of intrinsic fluctuations in the blood oxygen level-dependent signal of functional magnetic resonance imaging can provide insight into the effect of physiologic states on brain processes. In an effort to better understand the brain-gut communication induced by the absorption and metabolism of nutrients in healthy lean and obese individuals, we investigated whether ingestion of nutritive and non-nutritive sweetened beverages differentially engages the hypothalamus and brainstem vagal pathways in lean and obese women. In a 2-day, double-blind crossover study, 11 lean and 11 obese healthy women underwent functional magnetic resonance imaging scans after ingestion of 2 beverages of different sucrose content, but identical sweetness. During scans, subjects rested with eyes closed. Blood oxygen level-dependent fluctuations demonstrated significantly greater power in the highest frequency band (slow-3: 0.073-0.198 Hz) after ingestion of high-sucrose compared with low-sucrose beverages in the nucleus tractus solitarius for both groups. Obese women had greater connectivity between the right lateral hypothalamus and a reward-related brain region and weaker connectivity with homeostasis and gustatory-related brain regions than lean women. In a functional magnetic resonance imaging study, we observed sucrose-related changes in oscillatory dynamics of blood oxygen level-dependent fluctuations in brainstem and hypothalamus in lean and obese women. The observed frequency changes are consistent with a rapid vagally mediated mechanism due to nutrient absorption, rather than sweet taste receptor activation. These findings provide support for altered interaction between homeostatic and reward networks in obese individuals. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  18. Activation of Brainstem Pro-opiomelanocortin Neurons Produces Opioidergic Analgesia, Bradycardia and Bradypnoea.

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    Serena Cerritelli

    Full Text Available Opioids are widely used medicinally as analgesics and abused for hedonic effects, actions that are each complicated by substantial risks such as cardiorespiratory depression. These drugs mimic peptides such as β-endorphin, which has a key role in endogenous analgesia. The β-endorphin in the central nervous system originates from pro-opiomelanocortin (POMC neurons in the arcuate nucleus and nucleus of the solitary tract (NTS. Relatively little is known about the NTSPOMC neurons but their position within the sensory nucleus of the vagus led us to test the hypothesis that they play a role in modulation of cardiorespiratory and nociceptive control. The NTSPOMC neurons were targeted using viral vectors in a POMC-Cre mouse line to express either opto-genetic (channelrhodopsin-2 or chemo-genetic (Pharmacologically Selective Actuator Modules. Opto-genetic activation of the NTSPOMC neurons in the working heart brainstem preparation (n = 21 evoked a reliable, titratable and time-locked respiratory inhibition (120% increase in inter-breath interval with a bradycardia (125±26 beats per minute and augmented respiratory sinus arrhythmia (58% increase. Chemo-genetic activation of NTSPOMC neurons in vivo was anti-nociceptive in the tail flick assay (latency increased by 126±65%, p<0.001; n = 8. All effects of NTSPOMC activation were blocked by systemic naloxone (opioid antagonist but not by SHU9119 (melanocortin receptor antagonist. The NTSPOMC neurons were found to project to key brainstem structures involved in cardiorespiratory control (nucleus ambiguus and ventral respiratory group and endogenous analgesia (periaqueductal gray and midline raphe. Thus the NTSPOMC neurons may be capable of tuning behaviour by an opioidergic modulation of nociceptive, respiratory and cardiac control.

  19. Relationship between age and brainstem allometry in the African grasscutter (Thryonomys swinderianus Temminck, 1827

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    Chikera S. Ibe


    Full Text Available Allometric values of brainstem structures were evaluated in African grasscutters Thryonomys swinderianus (n = 27. Brain samples were extracted from 9 animals each of 3 days (neonates, 72 days (juveniles and 450 days of age (adults. The midbrain, pons and medulla oblongata were separated from each brain sample and dimensions and weights obtained. The weights of the midbrain in the neonate, juvenile and adult African grasscutters were 0.33 g ± 0.01 g, 0.47 g ± 0.01 g and 0.93 g ± 0.02 g, respectively. The increase from neonate to juvenile (p = 0.002 and adult (p = 0.003 was significant. The pons lengths in the neonate, juvenile and adult were 2.05 mm ± 0.05 mm, 3.86 mm ± 0.05 mm and 4.16 mm ± 0.22 mm, respectively. There was a significant increase in the length of the pons from the neonate to the juvenile (p = 0.002, but the increase from the juvenile to the adult period was not significant (p = 0.263. There was also a significant (p < 0.05 increase in the weights and lengths of the medulla oblongata from neonate to juvenile and adult periods. In adults, the nose-rump length and the length of the medulla were significantly negatively correlated (r² = 0.47; p = 0.043. The present study concluded that the postnatal development of some brainstem structures in the African grasscutter varies with age.

  20. Maturation of canal-related brainstem neurons in the detection of horizontal angular acceleration in rats. (United States)

    Lai, Chun-Hong; Yiu, Christina N S; Lai, Suk-King; Ng, Ka-Pak; Yung, Ken K L; Shum, Daisy K Y; Chan, Ying-Shing


    We examined the functional maturation of canal-related brainstem neurons in Sprague-Dawley rats at postnatal day (P)1 to adult. Conscious animals were subjected to cycles of angular acceleration and deceleration so as to selectively activate hair cells of the horizontal semicircular canals. Brainstem neurons were monitored for c-fos expression by immuno-hybridization histochemistry as an indicator of neuronal activation. Fos-immunoreactive canal-related neurons were identifiable from P4 onwards in the vestibular nucleus and downstream vestibular relay stations, prepositus hypoglossal nucleus, and inferior olive. In the vestibular nucleus and prepositus hypoglossal nucleus, the number of canal-related neurons increased progressively with age, reaching the adult level by P21. Those in the inferior olive increased in number from P4 to P14 but decreased significantly afterwards until adulthood. The topography was not clear in the vestibular nucleus and prepositus hypoglossal nucleus. Canal-related neurons in P4-7 rats were spread throughout the rostrocaudal length of each subnucleus but clusters of canal-related neurons tended to form within specific subnuclei by P21. These were concentrated in the caudal halves of medial and spinal vestibular nuclei and the rostral parts of superior vestibular nucleus and prepositus hypoglossal nucleus. In the inferior olive, the topography was evident early in the course of development. Canal-related neurons were exclusively located in four subnuclei: dorsal medial cell column, dorsal cap, subnucleus A, and subnucleus C, but not in other subnuclei. Taken together, our data revealed the developmental profile of neuronal subpopulations within the horizontal canal system, thus providing an internal neural representation for postnatal coding of horizontal head rotations in spatial perception. (c) 2009 Wiley-Liss, Inc.

  1. Population calcium imaging of spontaneous respiratory and novel motor activity in the facial nucleus and ventral brainstem in newborn mice (United States)

    Persson, Karin; Rekling, Jens C


    Abstract The brainstem contains rhythm and pattern forming circuits, which drive cranial and spinal motor pools to produce respiratory and other motor patterns. Here we used calcium imaging combined with nerve recordings in newborn mice to reveal spontaneous population activity in the ventral brainstem and in the facial nucleus. In Fluo-8 AM loaded brainstem–spinal cord preparations, respiratory activity on cervical nerves was synchronized with calcium signals at the ventrolateral brainstem surface. Individual ventrolateral neurons at the level of the parafacial respiratory group showed perfect or partial synchrony with respiratory nerve bursts. In brainstem–spinal cord preparations, cut at the level of the mid-facial nucleus, calcium signals were recorded in the dorsal, lateral and medial facial subnuclei during respiratory activity. Strong activity initiated in the dorsal subnucleus, followed by activity in lateral and medial subnuclei. Whole-cell recordings from facial motoneurons showed weak respiratory drives, and electrical field potential recordings confirmed respiratory drive to particularly the dorsal and lateral subnuclei. Putative facial premotoneurons showed respiratory-related calcium signals, and were predominantly located dorsomedial to the facial nucleus. A novel motor activity on facial, cervical and thoracic nerves was synchronized with calcium signals at the ventromedial brainstem extending from the level of the facial nucleus to the medulla–spinal cord border. Cervical dorsal root stimulation induced similar ventromedial activity. The medial facial subnucleus showed calcium signals synchronized with this novel motor activity on cervical nerves, and cervical dorsal root stimulation induced similar medial facial subnucleus activity. In conclusion, the dorsal and lateral facial subnuclei are strongly respiratory-modulated, and the brainstem contains a novel pattern forming circuit that drives the medial facial subnucleus and cervical motor

  2. MRI and associated clinical characteristics of EV71-induced brainstem encephalitis in children with hand-foot-mouth disease

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    Zeng, Hongwu; Gan, Yungen [Shenzhen Children' s Hospital, Department of Radiology, Shenzhen (China); Wen, Feiqiu [Shenzhen Children' s Hospital, Department of Neurology, Shenzhen (China); Huang, Wenxian [Shenzhen Children' s Hospital, Department of Respiratory, Shenzhen (China)


    This study was conducted to investigate MRI and associated clinical characteristics of brainstem encephalitis induced by enterovirus 71 (EV71) in children with hand-foot-mouth disease (HFMD). We analyzed clinical and imaging data from 42 HFMD cases with EV71-induced brainstem encephalitis. All patients underwent plain and enhanced MRI cranial scans and were placed into one of two groups according to MRI enhancement results, an enhanced group or a nonenhanced group. Thirty-two cases were positive on MRI exam. The primary location of the lesion for brainstem encephalitis was the dorsal pons and medulla oblongata (32 cases), followed by the cerebellar dentate nucleus (8 cases), midbrain (5 cases), and thalamus (2 cases). Plain T1-weighted images showed isointense or hypointense signals, and T2-weighted images showed isointense and hyperintense signals. Enhanced MRI scans showed that 12 cases had slight to moderate enhancement; 4 of these were normal on plain scan. The time from MRI examination to disease onset was statistically different between the enhanced (n = 12) and nonenhanced (n = 21) groups with a mean of 7.67 days (SD = 1.07) vs 11.95 days (SD = 5.33), respectively. The most common neurological symptoms for brainstem encephalitis were myoclonus and tremor. The greater the area of affected brain, the more severe the clinical symptoms were. The locations of EV71-induced HFMD-associated brainstem encephalitis lesions are relatively specific. Enhanced MRI scans could also identify the lesions missed by early plain scans. MRI scans can provide important information for clinical evaluation and treatment. (orig.)

  3. Computational simulation of convection-enhanced drug delivery in the non-human primate brainstem: a simple model predicting the drug distribution. (United States)

    Sugiyama, Shin-Ichiro; Saito, Ryuta; Funamoto, Kenichi; Nakayama, Toshio; Sonoda, Yukihiko; Yamashita, Yoji; Inoue, Tomoo; Kumabe, Toshihiro; Hayase, Toshiyuki; Tominaga, Teiji


    Convection-enhanced delivery (CED) is a technique that delivers therapeutic agents directly and effectively into the brain parenchyma. Application of CED is now under investigation as a new treatment for various diseases. Diffuse brainstem glioma is one of the important candidates that could be targeted with CED. Especially when targeting brainstem lesions, prediction of drug distribution prior to CED will be necessary. This study evaluated the computational simulation of CED in the primate brainstem using a simplified model. Three in vivo experiments infusing gadolinium solution into the non-human primate brainstem were analyzed. T1-weighted magnetic resonance (MR) images were acquired during infusion of a total of 300 μl gadolinium solution. Computational simulation reconstructed the surface geometry of the brainstem from the MR images. The volume of the whole structure was meshed by grid generating software. Under the assumptions that the brainstem surface was rigid and the interior was filled with cerebrospinal fluid, the equations of continuity and Darcy's law were solved within a computational fluid dynamics package using a finite volume method. The results of computational simulations were compared with those of the in vivo experiments. The distribution volume (Vd) in the simulations corresponded well with the in vivo experiments. Under the condition without massive 'catheter back flow', computational simulations predicted almost 70% of the Vd of the in vivo experiments. The simplified computational simulations were consistent with the experiments in vivo. The methodology used in this study can be applied to predict convective drug distribution in the primate brainstem.

  4. Abnormal structure of fear circuitry in pediatric post-traumatic stress disorder. (United States)

    Keding, Taylor J; Herringa, Ryan J


    Structural brain studies of adult post-traumatic stress disorder (PTSD) show reduced gray matter volume (GMV) in fear regulatory areas including the ventromedial prefrontal cortex (vmPFC) and hippocampus. Surprisingly, neither finding has been reported in pediatric PTSD. One possibility is that they represent age-dependent effects that are not fully apparent until adulthood. In addition, lower-resolution MRI and image processing in prior studies may have limited detection of such differences. Here we examine fear circuitry GMV, including age-related differences, using higher-resolution MRI in pediatric PTSD vs healthy youth. In a cross-sectional design, 3 T anatomical brain MRI was acquired in 27 medication-free youth with PTSD and 27 healthy non-traumatized youth of comparable age, sex, and IQ. Voxel-based morphometry was used to compare GMV in a priori regions including the medial prefrontal cortex and amygdala/hippocampus. Compared with healthy youth, PTSD youth had reduced GMV but no age-related differences in anterior vmPFC (BA 10/11, Z=4.5), which inversely correlated with PTSD duration. In contrast, although there was no overall group difference in hippocampal volume, a group × age interaction (Z=3.6) was present in the right anterior hippocampus. Here, age positively predicted hippocampal volume in healthy youth but negatively predicted volume in PTSD youth. Within the PTSD group, re-experiencing symptoms inversely correlated with subgenual anterior cingulate cortex (sgACC, Z=3.7) and right anterior hippocampus (Z=3.5) GMV. Pediatric PTSD is associated with abnormal structure of the vmPFC and age-related differences in the hippocampus, regions important in the extinction and contextual gating of fear. Reduced anterior vmPFC volume may confer impaired recovery from illness, consistent with its role in the allocation of attentional resources. In contrast, individual differences in sgACC volume were associated with re-experiencing symptoms, consistent with

  5. Radiation-Hardened Circuitry Using Mask-Programmable Analog Arrays. Report 3

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    Britton, Jr, Charles L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Shelton, Jacob H. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Ericson, Milton Nance [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Blalock, Benjamin [Univ. of Tennessee, Knoxville, TN (United States)


    As the recent accident at Fukushima Daiichi so vividly demonstrated, telerobotic technologies capable of withstanding high radiation environments need to be readily available to enable operations, repair, and recovery under severe accident scenarios when human entry is extremely dangerous or not possible. Telerobotic technologies that enable remote operation in high dose rate environments have undergone revolutionary improvement over the past few decades. However, much of this technology cannot be employed in nuclear power environments because of the radiation sensitivity of the electronics and the organic insulator materials currently in use. This is a report of the activities involving Task 3 of the Nuclear Energy Enabling Technologies (NEET) 2 project Radiation Hardened Circuitry Using Mask-Programmable Analog Arrays [1]. Evaluation of the performance of the system for both pre- and post-irradiation as well as operation at elevated temperature will be performed. Detailed performance of the system will be documented to ensure the design meets requirements prior to any extended evaluation. A suite of tests will be developed which will allow evaluation before and after irradiation and during temperature. Selection of the radiation exposure facilities will be determined in the early phase of the project. Radiation exposure will consist of total integrated dose (TID) up to 200 kRad or above with several intermediate doses during test. Dose rates will be in various ranges determined by the facility that will be used with a target of 30 kRad/hr. Many samples of the pre-commercial devices to be used will have been tested in previous projects to doses of at least 300 kRad and temperatures up to 125C. The complete systems will therefore be tested for performance at intermediate doses. Extended temperature testing will be performed up to the limit of the commercial sensors. The test suite performed at each test point will consist of operational testing of the three basic

  6. More tryptophan hydroxylase in the brainstem dorsal raphe nucleus in depressed suicides. (United States)

    Boldrini, Maura; Underwood, Mark D; Mann, J John; Arango, Victoria


    Deficient serotonin neurotransmission in suicide is indicated by reduced brainstem serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), fewer 5-HT(1A) autoreceptors and reduced cortical serotonin transporter binding in suicide victims. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of 5-HT, and alterations in TPH could explain some of these findings. We sought to determine the amount of TPH immunoreactivity (TPH-IR) in the dorsal (DRN) and median (MRN) raphe nuclei in suicides and controls. Brainstems of suicide victims and controls (n = 11 pairs) were collected at autopsy, matched for age, sex and postmortem interval, frozen and sectioned (20 microm). Immunoautoradiography, using an antibody to label TPH, was performed, slides exposed to film and autoradiograms quantified by a computer-based image analysis system. We examined sections every 1000 microm throughout the whole length of the nucleus, performing statistical analysis only on those subjects for whom the raphe was complete (n = 8 pairs). TPH-IR (microCi/g) was higher in suicides than controls (S: 300.8 +/- 70.8 vs. C: 259.6 +/- 40.7, t = 2.57, df = 7, P = 0.04) in the dorsal raphe nucleus (DRN), and not different between suicides and controls (S: 251.3 +/- 44.2 vs. C: 235.9 +/- 27.4, t = 1.49, df = 7, P = 0.18) in the MRN. DRN TPH-IR was higher in male suicide victims (MS) compared to male controls (MC; MS: 318.4 +/- 54.4 vs. MC: 271.9 +/- 22.5, t = 2.66, df = 6, P = 0.03). The analysis of TPH-IR area and density at each DRN rostrocaudal levels showed higher area and density in suicides compared to controls in the rostral DRN and lower area and density in the caudal DRN. TPH-IR, an index of the amount of TPH enzyme, in the DRN is higher in depressed suicides. More TPH may be an upregulatory homeostatic response to impaired serotonin release or less autoreceptor activation. Alternatively, the serotonin impairment in suicide may be due to hypofunctional serotonin

  7. Neurophysiological anomalies in brainstem responses of mercury-exposed children of Andean gold miners. (United States)

    Counter, S Allen


    The health hazards of occupational exposure to Mercury (Hg) in adult gold miners are well known, but little attention has been given to the effects of Hg exposure in the children of gold miners. Children who assist their parents in gold mining operations or live in mining enclaves may be exposed to elemental Hg vapors or methylmercury-contaminated food, both of which may induce neurodevelopmental disabilities. Brainstem auditory-evoked responses (BAER) were measured as biomarkers of subtle mercury-induced neurological impairment in Andean children of gold miners living in the Ecuadorian gold mining settlement of Nambija, where Hg exposure is prevalent. Thirty-one children (19 boys and 12 girls, aged 4-14 years, mean age: 10 years) in the study group were found to have a mean blood mercury (HgB) level of 23.0 micrograms/L (SD: 19, range: 2.0-89.0 micrograms/L; median: 20 micrograms/L), which was significantly higher than the mean HgB level of a reference group of 21 Ecuadorian children (4.5 micrograms/L, SD: 2.3; t = 4.39, P = 0.0001), and in excess of the health-based biological limits for the U.S. (10 micrograms/L). The BAER measures indicated statistically significant differences in interpeak III-V (P = 0.03) and I-V (P = 0.008) neural conduction times for children with HgB levels above the median. BAERs at the conventional click stimulus rate of 10/second showed statistically significant positive correlations between HgB level and the absolute latency of wave V (P = 0.03), and the neural conduction times of the eighth nerve to midbrain I-V interval (P = 0.02). BAER at 50/second revealed statistically significant relationships between HgB and the latency of wave VI (P = 0.03), and the I-VI interpeak interval (P = 0.02). Brainstem neural conduction times suggested that some of the Hg-intoxicated children in the study group have subtle neurophysiological anomalies that may be more manifest at higher BAER stimulus rates, and that the Hg-exposed children of gold

  8. Enhanced auditory brainstem response and parental bonding style in children with gastrointestinal symptoms.

    Directory of Open Access Journals (Sweden)

    Shizuka Seino

    Full Text Available BACKGROUND: The electrophysiological properties of the brain and influence of parental bonding in childhood irritable bowel syndrome (IBS are unclear. We hypothesized that children with chronic gastrointestinal (GI symptoms like IBS may show exaggerated brainstem auditory evoked potential (BAEP responses and receive more inadequate parental bonding. METHODOLOGY/PRINCIPAL FINDINGS: Children aged seven and their mothers (141 pairs participated. BAEP was measured by summation of 1,000 waves of the electroencephalogram triggered by 75 dB click sounds. The mothers completed their Children's Somatization Inventory (CSI and Parental Bonding Instrument (PBI. CSI results revealed 66 (42% children without GI symptoms (controls and 75 (58% children with one or more GI symptoms (GI group. The III wave in the GI group (median 4.10 interquartile range [3.95-4.24] ms right, 4.04 [3.90-4.18] ms left had a significantly shorter peak latency than controls (4.18 [4.06-4.34] ms right, p = 0.032, 4.13 [4.02-4.24] ms left, p = 0.018. The female GI group showed a significantly shorter peak latency of the III wave (4.00 [3.90-4.18] ms than controls (4.18 [3.97-4.31] ms, p = 0.034 in the right side. BAEP in the male GI group did not significantly differ from that in controls. GI scores showed a significant correlation with the peak latency of the III wave in the left side (rho = -0.192, p = 0.025. The maternal care PBI scores in the GI group (29 [26]-[33] were significantly lower than controls (31 [28.5-33], p = 0.010, while the maternal over-protection PBI scores were significantly higher in the GI group (16 [12]-[17] than controls (13 [10.5-16], p = 0.024. Multiple regression analysis in females also supported these findings. CONCLUSIONS: It is suggested that children with chronic GI symptoms have exaggerated brainstem responses to environmental stimuli and inadequate parental behaviors aggravate these symptoms.

  9. Age and gender modulate the neural circuitry supporting facial emotion processing in adults with major depressive disorder. (United States)

    Briceño, Emily M; Rapport, Lisa J; Kassel, Michelle T; Bieliauskas, Linas A; Zubieta, Jon-Kar; Weisenbach, Sara L; Langenecker, Scott A


    Emotion processing, supported by frontolimbic circuitry known to be sensitive to the effects of aging, is a relatively understudied cognitive-emotional domain in geriatric depression. Some evidence suggests that the neurophysiological disruption observed in emotion processing among adults with major depressive disorder (MDD) may be modulated by both gender and age. Therefore, the present study investigated the effects of gender and age on the neural circuitry supporting emotion processing in MDD. Cross-sectional comparison of fMRI signal during performance of an emotion processing task. Outpatient university setting. One hundred adults recruited by MDD status, gender, and age. Participants underwent fMRI while completing the Facial Emotion Perception Test. They viewed photographs of faces and categorized the emotion perceived. Contrast for fMRI was of face perception minus animal identification blocks. Effects of depression were observed in precuneus and effects of age in a number of frontolimbic regions. Three-way interactions were present between MDD status, gender, and age in regions pertinent to emotion processing, including frontal, limbic, and basal ganglia. Young women with MDD and older men with MDD exhibited hyperactivation in these regions compared with their respective same-gender healthy comparison (HC) counterparts. In contrast, older women and younger men with MDD exhibited hypoactivation compared to their respective same-gender HC counterparts. This the first study to report gender- and age-specific differences in emotion processing circuitry in MDD. Gender-differential mechanisms may underlie cognitive-emotional disruption in older adults with MDD. The present findings have implications for improved probes into the heterogeneity of the MDD syndrome. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  10. Initiation and modulation of locomotor circuitry output with multisite transcutaneous electrical stimulation of the spinal cord in noninjured humans. (United States)

    Gerasimenko, Yury; Gorodnichev, Ruslan; Puhov, Aleksandr; Moshonkina, Tatiana; Savochin, Aleksandr; Selionov, Victor; Roy, Roland R; Lu, Daniel C; Edgerton, V Reggie


    The mammalian lumbar spinal cord has the capability to generate locomotor activity in the absence of input from the brain. Previously, we reported that transcutaneous electrical stimulation of the spinal cord at vertebral level T11 can activate the locomotor circuitry in noninjured subjects when their legs are placed in a gravity-neutral position (Gorodnichev RM, Pivovarova EA, Pukhov A, Moiseev SA, Savokhin AA, Moshonkina TR, Shcherbakova NA, Kilimnik VA, Selionov VA, Kozlovskaia IB, Edgerton VR, Gerasimenko IU. Fiziol Cheloveka 38: 46-56, 2012). In the present study we hypothesized that stimulating multiple spinal sites and therefore unique combinations of networks converging on postural and locomotor lumbosacral networks would be more effective in inducing more robust locomotor behavior and more selective control than stimulation of more restricted networks. We demonstrate that simultaneous stimulation at the cervical, thoracic, and lumbar levels induced coordinated stepping movements with a greater range of motion at multiple joints in five of six noninjured subjects. We show that the addition of stimulation at L1 and/or at C5 to stimulation at T11 immediately resulted in enhancing the kinematics and interlimb coordination as well as the EMG patterns in proximal and distal leg muscles. Sequential cessation of stimulation at C5 and then at L1 resulted in a progressive degradation of the stepping pattern. The synergistic and interactive effects of transcutaneous stimulation suggest a multisegmental convergence of descending and ascending, and most likely propriospinal, influences on the spinal neuronal circuitries associated with locomotor activity. The potential impact of using multisite spinal cord stimulation as a strategy to neuromodulate the spinal circuitry has significant implications in furthering our understanding of the mechanisms controlling posture and locomotion and for regaining significant sensorimotor function even after a severe spinal cord

  11. Reduced wave amplitudes of brainstem auditory response in high-risk babies born at 28-32week gestation. (United States)

    Jiang, Ze Dong; Ping, Li Li


    To examine brainstem auditory electrophysiology in high-risk babies born at 28-32week gestation by analysing the amplitudes of wave components in maximum length sequence brainstem auditory evoked response (MLS BAER). 94 preterm babies, ranging in gestation 28-32weeks, with perinatal problems (high-risk) were recruited. The amplitudes of MLS BAER wave components were studied at term age (37-42weeks postconceptional age). Compared with normal term controls, the amplitude in the high-risk preterm babies was significantly smaller at the highest click rate 910/s for wave I (pauditory neuron in such babies is depressed, mainly attributed to or related to the associated perinatal problems. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  12. The Dipeptides Ile-Tyr and Ser-Tyr Exert Distinct Effects on Catecholamine Metabolism in the Mouse Brainstem. (United States)

    Moriyasu, Kazuki; Ichinose, Takashi; Nakahata, Akane; Tanaka, Mitsuru; Matsui, Toshiro; Furuya, Shigeki


    Catecholamine synthesis and transmission in the brain are influenced by the availability of Tyr in the body. In this study, we compared the effects of oral administration of Tyr-containing dipeptides Ile-Tyr, Ser-Tyr, and Tyr-Pro with Tyr alone on catecholamine metabolism in the mouse brainstem. Among these dipeptides, Ile-Tyr administration led to increases in dopamine, the dopamine metabolites homovanillic acid, and 3,4-dihydroxyphenylacetic acid, compared to administration of Ser-Tyr, Tyr-Pro, or Tyr alone. In comparison, administration of Ser-Tyr induced significantly increasing noradrenaline turnover, while Tyr-Pro administration suppressed dopamine turnover. Therefore, oral administration of Ile-Tyr, Ser-Tyr, and Tyr-Pro differentially affected metabolism of dopamine and noradrenaline. These observations strongly suggest that Tyr-containing dipeptides exert distinct effects on catecholamine metabolism in the brainstem when ingested orally.

  13. Variant Type of Posterior Reversible Encephalopathy Syndrome with Diffuse Cerebral White Matter and Brainstem Involvement Associated with Intracranial Hemorrhage. (United States)

    Zhang, Yin-Xi; Zheng, Yang; Zhang, Bi-Jun; Zhang, Yun; Ding, Mei-Ping; Zhang, Bao-Rong


    Posterior reversible encephalopathy syndrome (PRES) is a clinical-radiological syndrome characterized by reversible vasogenic edema typically at a posterior location of the cerebrum. PRES with prominent brainstem or basal ganglia involvement is defined as central-variant, which is rare. We herein report an atypical case of a 35-year-old man with a 2-year history of untreated hypertension who complained of recurrent dizziness. The patient presented with brainstem and diffuse white matter involvement associated with intracranial hemorrhage and recovered fully after therapy. Recognition of this uncommon benign syndrome as a potentially treatable disorder can be of great importance. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  14. A neonate with hand, foot, and mouth disease complicated with brainstem encephalitis and pulmonary edema:A complete recovery. (United States)

    Guo, Shi-Jie; Wang, Dong-Xuan; Dai, Chun-Lai; Wu, Hui


    Hand, foot, and mouth disease (HFMD) with serious complications and fatal cases have been reported over the last decade worldwide. The authors report a rare case of HFMD in a neonate complicated with brainstem encephalitis and pulmonary edema. She had fever, lethargy, dyspnea. Physical examination revealed shock signs, fine rales on both lungs, absent Moro reflex. The patient had a rapidly progressive course with seizures, coma, no spontaneous breathing, chemosis. There were some vesicles on left sole and red maculopapular rashes on perianal skin. She had a history of exposure to HFMD. Fecal sample was positive for EV71 RNA by real-time PCR. Chest X-rays showed bilateral pulmonary infiltrates. MRI of the brain showed significant hypointensity in the brainstem on T1WI and hyperintensity on T2WI. She recovered well. This case highlights severe HFMD in neonates is rare. Medical history and physical examination are important in making diagnosis.

  15. EEG and brainstem auditory evoked response potentials in adult male drug abusers with self-reported histories of aggressive behavior. (United States)

    Fishbein, D H; Herning, R I; Pickworth, W B; Haertzen, C A; Hickey, J E; Jaffe, J H


    Auditory brainstem evoked response (BAER) and spontaneous electroencephalogram (EEG) were measured in 124 adult male drug abusers. We examined the relationships among psychiatric diagnoses, paper and pencil measures of aggression and hostility, and electrophysiological features. Subjects meeting criteria for antisocial personality disorder (ASP), as defined by DSM-III, were not significantly different from non-ASP subjects for either BAER or spontaneous EEG measures. The more overtly aggressive subjects had significant delays in BAER latency. Aggressive subjects also had more delta activity and less alpha activity in the spontaneous EEG, as have been observed in "psychopaths" and "criminals." Although ASP and aggression are related, these data indicate that aggressiveness may be a separate, albeit overlapping, trait. As both early aggression and a diagnosis of ASP are predictors of later drug use, the findings that only aggression was associated with EEG slowing and brainstem delays may indicate that ASP and aggression make independent contributions to vulnerability to the development of drug abuse.

  16. Effects of cigarette smoke exposure on nicotinic acetylcholine receptor subunits {alpha}7 and {beta}2 in the sudden infant death syndrome (SIDS) brainstem

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    Machaalani, Rita, E-mail: [Department of Medicine, The University of Sydney, NSW 2006 (Australia); Bosch Institute, The University of Sydney, NSW 2006 (Australia); The Children' s Hospital at Westmead, NSW 2145 (Australia); Say, Meichien [Department of Medicine, The University of Sydney, NSW 2006 (Australia); Bosch Institute, The University of Sydney, NSW 2006 (Australia); Waters, Karen A. [Department of Medicine, The University of Sydney, NSW 2006 (Australia); Bosch Institute, The University of Sydney, NSW 2006 (Australia); The Children' s Hospital at Westmead, NSW 2145 (Australia)


    It is postulated that nicotine, as the main neurotoxic constituent of cigarette smoke, influences SIDS risk through effects on nicotinic acetylcholine receptors (nAChRs) in brainstem nuclei that control respiration and arousal. This study compared {alpha}7 and {beta}2 nAChR subunit expression in eight nuclei of the caudal and rostral medulla and seven nuclei of the pons between SIDS (n = 46) and non-SIDS infants (n = 14). Evaluation for associations with known SIDS risk factors included comparison according to whether infants had a history of exposure to cigarette smoke in the home, and stratification for sleep position and gender. Compared to non-SIDS infants, SIDS infants had significantly decreased {alpha}7 in the caudal nucleus of the solitary tract (cNTS), gracile and cuneate nuclei, with decreased {beta}2 in the cNTS and increased {beta}2 in the facial. When considering only the SIDS cohort: 1-cigarette smoke exposure was associated with increased {alpha}7 in the vestibular nucleus and increased {beta}2 in the rostral dorsal motor nucleus of the vagus, rNTS and Cuneate, 2-there was a gender interaction for {alpha}7 in the gracile and cuneate, and {beta}2 in the cNTS and rostral arcuate nucleus, and 3-there was no effect of sleep position on {alpha}7, but prone sleep was associated with decreased {beta}2 in three nuclei of the pons. In conclusion, SIDS infants demonstrate differences in expression of {alpha}7 and {beta}2 nAChRs within brainstem nuclei that control respiration and arousal, which is independent on prior history of cigarette smoke exposure, especially for the NTS, with additional differences for smoke exposure ({beta}2), gender ({alpha}7 and {beta}2) and sleep position ({beta}2) evident. -- Highlights: Black-Right-Pointing-Pointer The 'normal' response to smoke exposure is decreased {alpha}7 and {beta}2 in certain nuclei. Black-Right-Pointing-Pointer SIDS infants have decreased {alpha}7 in cNTS, Grac and Cun. Black

  17. Noise-Induced “Toughening” Effect in Wistar Rats: Enhanced Auditory Brainstem Responses Are Related to Calretinin and Nitric Oxide Synthase Upregulation (United States)

    Alvarado, Juan C.; Fuentes-Santamaría, Verónica; Gabaldón-Ull, María C.; Jareño-Flores, Tania; Miller, Josef M.; Juiz, José M.


    An appropriate conditioning noise exposure may reduce a subsequent noise-induced threshold shift. Although this “toughening” effect helps to protect the auditory system from a subsequent traumatic noise exposure, the mechanisms that regulate this protective process are not fully understood yet. Accordingly, the goal of the present study was to characterize physiological processes associated with “toughening” and to determine their relationship to metabolic changes in the cochlea and cochlear nucleus (CN). Auditory brainstem responses (ABR) were evaluated in Wistar rats before and after exposures to a sound conditioning protocol consisting of a broad-band white noise of 118 dB SPL for 1 h every 72 h, four times. After the last ABR evaluation, animals were perfused and their cochleae and brains removed and processed for the activity markers calretinin (CR) and neuronal nitric oxide synthase (nNOS). Toughening was demonstrated by a progressively faster recovery of the threshold shift, as well as wave amplitudes and latencies over time. Immunostaining revealed an increase in CR and nNOS levels in the spiral ganglion, spiral ligament, and CN in noise-conditioned rats. Overall, these results suggest that the protective mechanisms of the auditory toughening effect initiate in the cochlea and extend to the central auditory system. Such phenomenon might be in part related to an interplay between CR and nitric oxide signaling pathways, and involve an increased cytosolic calcium buffering capacity induced by the noise conditioning protocol. PMID:27065815



    Ranganadh Narayanam


    In this research as a first step we have concentrated on collecting non-intra cortical EEG data of Brainstem Speech Evoked Potentials from human subjects in an Audiology Lab in University of Ottawa. The problems we have considered are the most advanced and most essential problems of interest in Auditory Neural Signal Processing area in the world: The first problem is the Voice Activity Detection (VAD) in Speech Auditory Brainstem Responses (ABR); The second problem is to identify the best De-...



    Ranganadh Narayanam


    In speech signals two activities - voiced & unvoiced - are prominently observed, in both the cases of “production speech” from mouth, and “hearing speech” passed through ears-brainstem-and brain. These speech signals are broadly categorized into these two regions: Voiced- nearly periodic in nature; Unvoiced – random noise lik