Microelectrode recordings were performed during awake deep brain stimulation surgery for obsessive-compulsive disorder, revealing robust brain oscillations that were plainly visible throughout the ventral striatum. There was an elegant topological correspondence between each oscillation and the underlying brain anatomy, most prominently a ~35-Hz gamma-oscillation specific to the nucleus accumbens. Direct provocation of the patient\'s contamination obsession modulated both firing rate and gamma-oscillation amplitude within the nucleus accumbens. NEW & NOTEWORTHY Surgical implantation of deep brain stimulating electrodes (DBS) to treat obsessive-compulsive disorder (OCD) is an option for patients who have not fully responded to medical intervention or cognitive behavioral therapy. We measured the electrophysiology of a collection of deep brain structures during awake DBS surgery for an OCD patient with an obsession about cleanliness and contamination. The anatomic delineation of these deep brain structures was revealed by distinct brain rhythms, most notably a ~35 Hz oscillation specific to the nucleus accumbens. In the first ever measurement of a human obsessive thought, we found that this ~35-Hz biomarker, as well as the local neuronal action potential rate, were modulated by handing the patient a toothbrush to bring to his face and instructing him to \"imagine brushing your teeth with this dirty toothbrush.\"

Synaptotagmin 1 (SYT1) is a critical mediator of fast, synchronous, calcium-dependent neurotransmitter release and also modulates synaptic vesicle endocytosis. This paper describes 11 patients with de novo heterozygous missense mutations in SYT1. All mutations alter highly conserved residues, and cluster in two regions of the SYT1 C2B domain at positions Met303 (M303K), Asp304 (D304G), Asp366 (D366E), Ile368 (I368T) and Asn371 (N371K). Phenotypic features include infantile hypotonia, congenital ophthalmic abnormalities, childhood-onset hyperkinetic movement disorders, motor stereotypies, and developmental delay varying in severity from moderate to profound. Behavioural characteristics include sleep disturbance and episodic agitation. Absence of epileptic seizures and normal orbitofrontal head circumference are important negative features. Structural MRI is unremarkable but EEG disturbance is universal, characterized by intermittent low frequency high amplitude oscillations. The functional impact of these five de novo SYT1 mutations has been assessed by expressing rat SYT1 protein containing the equivalent human variants in wild-type mouse primary hippocampal cultures. All mutant forms of SYT1 were expressed at levels approximately equal to endogenous wild-type protein, and correctly localized to nerve terminals at rest, except for SYT1M303K, which was expressed at a lower level and failed to localize at nerve terminals. Following stimulation, SYT1I368T and SYT1N371K relocalized to nerve terminals at least as efficiently as wild-type SYT1. However, SYT1D304G and SYT1D366E failed to relocalize to nerve terminals following stimulation, indicative of impairments in endocytic retrieval and trafficking of SYT1. In addition, the presence of SYT1 variants at nerve terminals induced a slowing of exocytic rate following sustained action potential stimulation. The extent of disturbance to synaptic vesicle kinetics is mirrored by the severity of the affected individuals\' phenotypes, suggesting that the efficiency of SYT1-mediated neurotransmitter release is critical to cognitive development. In summary, de novo dominant SYT1 missense mutations are associated with a recognizable neurodevelopmental syndrome, and further cases can now be diagnosed based on clinical features, electrophysiological signature and mutation characteristics. Variation in phenotype severity may reflect mutation-specific impact on the diverse physiological functions of SYT1.

Simultaneous changes in ion concentrations, glutamate, and cell volume together with exchange of matter between cell network and vasculature are ubiquitous in numerous brain pathologies. A complete understanding of pathological conditions as well as normal brain function, therefore, hinges on elucidating the molecular and cellular pathways involved in these mostly interdependent variations. In this paper, we develop the first computational framework that combines the Hodgkin-Huxley type spiking dynamics, dynamic ion concentrations and glutamate homeostasis, neuronal and astroglial volume changes, and ion exchange with vasculature into a comprehensive model to elucidate the role of glutamate uptake in the dynamics of spreading depolarization (SD)-the electrophysiological event underlying numerous pathologies including migraine, ischemic stroke, aneurysmal subarachnoid hemorrhage, intracerebral hematoma, and trauma. We are particularly interested in investigating the role of glutamate in the duration and termination of SD caused by K+ perfusion and oxygen-glucose deprivation. Our results demonstrate that glutamate signaling plays a key role in the dynamics of SD, and that impaired glutamate uptake leads to recovery failure of neurons from SD. We confirm predictions from our model experimentally by showing that inhibiting astrocytic glutamate uptake using TFB-TBOA nearly quadruples the duration of SD in layers 2-3 of visual cortical slices from juvenile rats. The model equations are either derived purely from first physical principles of electroneutrality, osmosis, and conservation of particles or a combination of these principles and known physiological facts. Accordingly, we claim that our approach can be used as a future guide to investigate the role of glutamate, ion concentrations, and dynamics cell volume in other brain pathologies and normal brain function.

BACKGROUND: Peripheral nerve system (PNS) involvement is common in Fabry\'s disease (FD), predominantly affecting the small nerve fibers that are difficult to investigate with conventional electrophysiological methods.
METHODS: Eighteen patients followed for Fabry\'s disease underwent a prospective series of electroneurophysiological explorations, including a study of the cardiac parasympathetic autonomic nervous system (ANS) and electrochemical skin conductance (ESC) tests. Data were compared with those obtained in 18 matched healthy controls.
RESULTS: All patients had at least one clinical sign suggestive of neuropathy: 16 reported an acrosyndrome and 12 had dyshidrosis. Cold hypoesthesia was found in 15 patients and heat hypoesthesia in 13. Electroneurophysiological investigations and study of the cardiac parasympathetic ANS were normal in all patients. The ESC was significantly lower in FD patients compared with controls.
CONCLUSIONS: PNS involvement is common in FD and should be suspected in patients exhibiting an acrosyndrome, dyshidrosis and/or cold hypoesthesia. Conventional electrophysiological investigations are normal. New techniques, such as ESC, provide early diagnosis of small fiber involvement that currently requires more sophisticated tests difficult to apply in routine practice.

Claustrum, a gray matter structure that underlies the neocortex, is reciprocally connected with many neocortical and limbic cortical areas. This connectivity positions claustrum ideally for the integration or coordination of widespread cortical activity. In anatomical studies using multiple planes of section, claustrum has distinct subregions based on latexin immunohistochemistry, and an approximately rostro-caudal alignment of fusiform cells supporting a laminar intrinsic organization. Physiological studies of claustral connectivity in disinhibited brain slices demonstrate (1) intrinsic connectivity sufficient to generate spontaneous synchronized burst discharges, (2) activity spread within the oblique laminae that contained the principal cellular axis, and (3) segregation of activity as evidenced by the absence of spread within coronal planes. Activity spread depended on glutamatergic synaptic transmission, and activity restrictions did not depend on inhibitory circuits. We conclude that the claustrum has an intrinsic excitatory connectivity that is constrained in approximately rostro-caudal laminae, with minimal cross-communication between laminae. Further, claustrum has the intrinsic capability of generating synchronized population activity and facilitating its spread within laminae, a feature that may contribute to seizure generation and spread.

OBJECTIVE: This study aims to investigate characteristics of visual snow accompanied by migraine and special interest on occipital bending, electrophysiological properties, and response to treatment.
BACKGROUND: Visual snow is characterized by continuous dynamically flickering dots in the visual field. Most patients also have comorbid migraine. Cortical hyperexcitability is a feature of migraine. Recent studies indicate an association between occipital bending with psychiatric disorders such as depression. Here, we demonstrate a patient with visual snow, migraine with aura, left occipital bending, and cortical hyperexcitability. Treatment response to lamotrigine was objectively assessed by repetitive pattern reversal visual evoked potentials (rVEP).
METHODS: A 25-year-old woman with a 10-year history of migraine with aura (2-3 attacks/week) admitted for 1-year history of visual snow. She reported continuous bright and colorful lights, palinopsia, floaters, nyctalopsia, and photopsia. Brain magnetic resonance imaging (MRI) was performed. Visual habituation response was assessed before and after lamotrigine treatment by rVEP.
RESULTS: Brain MRI revealed left occipital bending. On rVEP study, there was potentiation response. After lamotrigine treatment, the patient had no more complaints of visual snow, was able to sleep, and the frequency of migraine decreased to 2 attacks/month. Electrophysiologically, the cortical hyperexcitability was improved.
CONCLUSIONS: The visual snow and loss of habituation ability in migraine associated with occipital bending can be improved with lamotrigine treatment. This report may provide new insights on \"visual snow\" pathophysiology in migraine.

Acute motor axonal neuropathy (AMAN) is a variant of Guillain-Barre syndrome. It has been reported to have no sensory symptoms and is diagnosed by typical electrophysiological findings of low-amplitude or unobtainable compound muscle action potentials with normal sensory nerve action potentials. However, the authors experienced atypical case of general electrophysiological findings of AMAN with pain and paresthesia and presented it. This case implies that clinician should be on the alert to atypical sensory symptoms from the classical presentation of AMAN even if the patient is diagnosed with AMAN electrophysiologically and should consider proper treatment options based on clinical presentations.

The creation of biological pathway knowledge bases is largely driven by manual effort to curate based on evidences from the scientific literature. It is highly challenging for the curators to keep up with the literature. Text mining applications have been developed in the last decade to assist human curators to speed up the curation pace where majority of them aim to identify the most relevant papers for curation with little attempt to directly extract the pathway information from text. In this paper, we describe a rule-based literature mining system to extract pathway information from text. We evaluated the system using curated pharmacokinetic (PK) and pharmacodynamic (PD) pathways in PharmGKB. The system achieved an F-measure of 63.11% and 34.99% for entity extraction and event extraction respectively against all PubMed abstracts cited in PharmGKB. It may be possible to improve the system performance by incorporating using statistical machine learning approaches. This study also helped us gain insights into the barriers towards automated event extraction from text for pathway curation.

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common acquired immune-mediated inflammatory disorder of the peripheral nervous system. The diagnosis is based mainly on the clinical presentation and electrophysiological detection of demyelination.
METHODS: Several MRI studies have demonstrated hypertrophy and abnormal enhancement of spinal nerve roots or brachial plexus in CIDP, but there have been only anecdotal reports of similar sonographic findings.
RESULTS: This article reports the sonographic findings of a CIDP case and includes a review of the literature and previously reported cases.
CONCLUSIONS: This case report highlights the importance of sonography in the localization and recognition of focal nerve enlargements in patients with CIDP. This method could be a helpful tool in the diagnosis of conduction block in CIDP, especially in cases where a nerve segment cannot be explored easily with the inching technique. Systematic data are needed to confirm this observation.

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