Extrasynaptic GABAA receptors: form, pharmacology, and function.

GABA is the principal inhibitory neurotransmitter in the CNS and acts via GABA(A) and GABA(B) receptors. Recently, a novel form of GABA(A) receptor-mediated inhibition, termed "tonic" inhibition, has been described. Whereas synaptic GABA(A) receptors underlie classical "phasic" GABA(A) receptor-mediated inhibition (inhibitory postsynaptic currents), tonic GABA(A) receptor-mediated inhibition results from the activation of extrasynaptic receptors by low concentrations of ambient GABA.

Pathologic cardiac repolarization in pharmacoresistant epilepsy and its potential role in sudden unexpected death in epilepsy: a case-control study.

Purpose: To determine whether abnormal cardiac repolarization and other electrocardiography (ECG) predictors for cardiac mortality occur in epilepsy patients and whether they are associated with an increased risk for sudden unexpected death in epilepsy (SUDEP).

Methods: In a matched-pair case-control study, recordings of adult patients with pharmacoresistant focal epilepsies who died from SUDEP and who had previously had presurgical video-EEG (electroencephalography) telemetry were reviewed. Living controls were matched for age, gender, and date of admission for video-EEG telemetry.

Implications of using hierarchical and six degree-of-freedom models for normal gait analyses.

Hierarchical biomechanical models (conventional gait model, CGM) are attractive because of simple data collection demands, yet they are susceptible to errors that are theoretically better controlled using six degree-of-freedom models that track body segments independently (OPT1). We wished to compare gait variables obtained with these models. Twenty-five normal children walked while wearing a hybrid marker configuration, permitting identical strides to be analyzed using CGM and OPT1.

Computational sophistication at a single GABAergic connection.

Diverse computational roles of GABAergic inhibition are often assumed to reflect heterogeneity in the sources of GABA and in the receptors sensing the neurotransmitter. New data suggest that distinct effects on integration of excitatory inputs by cerebellar granule cells might result from different modes of signaling by individual interneurons.

Do subclinical electrographic seizure patterns affect heart rate and its variability?

Purpose: Autonomic symptoms during seizures may provide information on seizure onset zone. We investigated whether changes in heart rate (HR) and HR variability (HRV) occur during subclinical electrographic seizure patterns, and whether these have a localising/lateralising value.

Methods: EEG and ECG recordings of pharmacoresistant epilepsy patients who underwent intracranial video-EEG telemetry were reviewed.

Loss of dendritic HCN1 subunits enhances cortical excitability and epileptogenesis.

Hyperpolarization-activated cation nonselective 1 (HCN1) plasticity in entorhinal cortical (EC) and hippocampal pyramidal cell dendrites is a salient feature of temporal lobe epilepsy. However, the significance remains undetermined. We demonstrate that adult HCN1 null mice are more susceptible to kainic acid-induced seizures.

Vascular smooth muscle cell durotaxis depends on substrate stiffness gradient strength.

Mechanical compliance is emerging as an important environmental cue that can influence certain cell behaviors, such as morphology and motility. Recent in vitro studies have shown that cells preferentially migrate from less stiff to more stiff substrates; however, much of this phenomenon, termed durotaxis, remains ill-defined. To address this problem, we studied the morphology and motility of vascular smooth muscle cells on well-defined stiffness gradients.

The unrested resting brain: sleep deprivation alters activity within the default-mode network.

The sleep-deprived brain has principally been characterized by examining dysfunction during cognitive task performance. However, far less attention has been afforded the possibility that sleep deprivation may be as, if not more, accurately characterized on the basis of abnormal resting-state brain activity. Here we report that one night of sleep deprivation significantly disrupts the canonical signature of task-related deactivation, resulting in a double dissociation within anterior as well as posterior midline regions of the default network.

Overnight therapy? The role of sleep in emotional brain processing.

Cognitive neuroscience continues to build meaningful connections between affective behavior and human brain function. Within the biological sciences, a similar renaissance has taken place, focusing on the role of sleep in various neurocognitive processes and, most recently, on the interaction between sleep and emotional regulation. This review surveys an array of diverse findings across basic and clinical research domains, resulting in a convergent view of sleep-dependent emotional brain processing.

Peri-ictal atrioventricular conduction block in a patient with a lesion in the left insula: case report and review of the literature.

Seizure-induced syncope is uncommon and is usually due to peri-ictal bradycardia and asystole. In contrast, peri-ictal atrioventricular conduction block (AV block) has been reported only rarely. Here, we review the literature on peri-ictal AV block and describe a patient with recurrent episodes of epigastric auras that were occasionally followed by a sensation of dizziness and syncope because of transient third-degree AV block.

Optimization of the injected activity in dynamic 3D PET: a generalized approach using patient-specific NECs as demonstrated by a series of 15O-H2O scans.

Unlabelled: The magnitude of the injected activity (A(0)) has a direct impact on the statistical quality of PET images. This study aimed to develop a generalized method for maximizing the statistical quality of dynamic PET images by optimizing A(0).

Methods: Patient-specific noise-equivalent counts (PS-NECs) were used as a metric of the statistical quality of each time frame of a dynamic PET image.

Bing-Neel syndrome: an illustrative case and a comprehensive review of the published literature.

Waldenstrom's macroglobulinemia (WM) is a chronic lymphoproliferative disorder within the spectrum of lymphoplasmacytic lymphoma characterized by proliferation of plasma cells, small lymphocytes, and plasmacytoid lymphocytes. Central nervous system involvement is very rare (Bing-Neel [BN] syndrome). We present the case of a 62-year-old woman previously diagnosed with WM who presented with Bing-Neel syndrome and review the published literature which consists of only case reports.

Characterisation of cortical activity in response to deep brain stimulation of ventral-lateral nucleus: modelling and experiment.

Motivated by its success as a therapeutic treatment in other neurological disorders, most notably Parkinson's disease, Deep Brain Stimulation (DBS) is currently being trialled in a number of patients with drug unresponsive epilepsies. However, the mechanisms by which DBS interferes with neuronal activity linked to the disorder are not well understood. Furthermore, there is a need to identify optimized values of parameters (for example in amplitude/frequency space) of the stimulation protocol with which one aims to achieve the desired outcome.

Quantitative right and left ventricular functional analysis during gated whole-chest MDCT: a feasibility study comparing automatic segmentation to semi-manual contouring.

Purpose: To evaluate the feasibility of an automatic, whole-heart segmentation algorithm for measuring global heart function from gated, whole-chest MDCT images.

Material And Methods: 15 patients with suspicion of PE underwent whole-chest contrast-enhanced MDCT with retrospective ECG synchronization. Two observers computed right and left ventricular functional indices using a semi-manual and an automatic whole-heart segmentation algorithm.

Novel inhibitors complexed with glutamate dehydrogenase: allosteric regulation by control of protein dynamics.

Mammalian glutamate dehydrogenase (GDH) is a homohexameric enzyme that catalyzes the reversible oxidative deamination of l-glutamate to 2-oxoglutarate using NAD(P)(+) as coenzyme. Unlike its counterparts from other animal kingdoms, mammalian GDH is regulated by a host of ligands. The recently discovered hyperinsulinism/hyperammonemia disorder showed that the loss of allosteric inhibition of GDH by GTP causes excessive secretion of insulin.

Response of an adult patient with pineoblastoma to vorinostat and retinoic acid.

We report the case of an adult patient with pineoblastoma (PBL) who had a complete radiographic response following treatment with vorinostat and retinoic acid. This regimen was used to treat bulky residual tumor that persisted despite radiation therapy (RT) and two cycles of cytotoxic chemotherapy. Vorinostat and retinoic acid were chosen as an alternative to cytotoxic chemotherapy, which our patient was unable to tolerate, based on preclinical data suggesting efficacy of this combination.

The role of sleep in false memory formation.

Memories are not stored as exact copies of our experiences. As a result, remembering is subject not only to memory failure, but to inaccuracies and distortions as well. Although such distortions are often retained or even enhanced over time, sleep's contribution to the development of false memories is unknown.

The role of sleep in cognition and emotion.

As critical as waking brain function is to cognition, an extensive literature now indicates that sleep supports equally important, different yet complementary operations. This review will consider recent and emerging findings implicating sleep and specific sleep-stage physiologies in the modulation, regulation, and even preparation of cognitive and emotional brain processes. First, evidence for the role of sleep in memory processing will be discussed, principally focusing on declarative memory.

A FERM domain autoregulates Drosophila myosin 7a activity.

Full-length Drosophila myosin 7a (myosin 7a-FL) has a complex tail containing a short predicted coiled coil followed by a MyTH4-FERM domain, an SH3 domain, and a C-terminal MyTH4-FERM domain. Myosin 7a-FL expressed in Sf9 cells is monomeric despite the predicted coiled coil. We showed previously that Subfragment-1 (S1) from this myosin has MgATPase of V(max) approximately 1 s(-1) and K(ATPase) approximately 1 microM actin.

Segmentation of arterial vessel wall motion to sub-pixel resolution using M-mode ultrasound.

We describe a method for segmenting arterial vessel wall motion to sub-pixel resolution, using the returns from M-mode ultrasound. The technique involves measuring the spatial offset between all pairs of scans from their cross-correlation, converting the spatial offsets to relative wall motion through a global optimization, and finally translating from relative to absolute wall motion by interpolation over the M-mode image. The resulting detailed wall distension waveform has the potential to enhance existing vascular biomarkers, such as strain and compliance, as well as enable new ones.

A novel 3-dimensional micro-ultrasound approach to automated measurement of carotid arterial plaque volume as a biomarker for experimental atherosclerosis.

Improved methods for non-invasive in vivo assessment are needed to guide development of animal models of atherosclerosis and to evaluate target engagement and in vivo efficacy of new drugs. Using novel 3D-micro-ultrasound technology, we developed and validated a novel protocol for 3D acquisition and analysis of imaging to follow lesion progression in atherosclerotic mice. The carotid arteries of ApoE receptor knockout mice and normal control mice were imaged within the proximal 2mm from the aortic branch point.

Advanced noninvasive imaging of spinal vascular malformations.

Spinal vascular malformations (SVMs) are an uncommon, heterogeneous group of vascular anomalies that can render devastating neurological consequences if they are not diagnosed and treated in a timely fashion. Imaging SVMs has always presented a formidable challenge because their clinical and imaging presentations resemble those of neoplasms, demyelination diseases, and infection. Advancements in noninvasive imaging modalities (MR and CT angiography) have increased during the last decade and have improved the ability to accurately diagnose spinal vascular anomalies.

Repetitive transcranial magnetic stimulation-associated neurobehavioral gains during coma recovery.

Background: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive method to induce changes in cortical neural excitability. This report presents findings from the first participant of a safety and efficacy study that examined a therapeutic rTMS protocol for persons with severe traumatic brain injury (TBI).

Objective: The primary hypothesis was that there will be no adverse events related to the provision of a 6-week rTMS protocol for persons with severe TBI who remain, at best, in a minimally conscious state for longer than 3 months.

Cognitive consequences of sleep and sleep loss.

Although we still lack any consensus function(s) for sleep, accumulating evidence suggests it plays an important role in homeostatic restoration, thermoregulation, tissue repair, immune control and memory processing. In the last decade an increasing number of reports continue to support a bidirectional and symbiotic relationship between sleep and memory. Studies using procedural and declarative learning tasks have demonstrated the need for sleep after learning in the offline consolidation of new memories.