Information Capacity of a Stochastically Responding Neuron Assembly.

In this work, certain aspects of the structure of the overlapping groups of neurons encoding specific signals are examined. Individual neurons are assumed to respond stochastically to input signal. Identification of a particular signal is assumed to result from the aggregate activity of a group of neurons, which we call information pathway. Conditions for definite response and for non-interference of pathways are derived. These conditions constrain the response properties of individual neurons and the allowed overlap among pathways. Under these constrains, and under the simplifying assumption that all pathways have similar structure, the information capacity of the system is derived. Furthermore, we show that there is a definite advantage in the information capacity if pathway neurons areinterspersed among the neuron assembly.

Visuomotor control in mice and primates.

We conduct a comparative evaluation of the visual systems from the retina to the muscles of the mouse and the macaque monkey noting the differences and similarities between these two species. The topics covered include (1) visual-field overlap, (2) visual spatial resolution, (3) V1 cortical point-image [i.e., V1 tissue dedicated to analyzing a unit receptive field], (4) object versus motion encoding, (5) oculomotor range, (6) eye, head, and body movement coordination, and (7) neocortical and cerebellar function. We also discuss blindsight in rodents and primates which provides insights on how the neocortex mediates conscious vision in these species. This review is timely because the field of visuomotor neurophysiology is expanding beyond the macaque monkey to include the mouse; there is therefore a need for a comparative analysis between these two species on how the brain generates visuomotor responses.

Ventral striatal and septal area hypermetabolism on FDG-PET in herpes simplex viral encephalitis.

A 71-year-old man presented with sudden onset, generalized tonic-clonic seizures and altered mental status. Initial brain magnetic resonance imaging was normal but a brain FDG-PET scan showed hypermetabolism in the left ventral striatum and septal area. Initial cerebrospinal fluid (CSF) examination showed mildly elevated protein but herpes simplex virus (HSV) polymerase chain reaction (PCR) was negative. A repeat CSF examination performed 9 days later showed a positive HSV PCR. Histopathological and immunohistochemical examination of autopsy specimen confirmed the presence of CD45+ lymphocytes and HSV antigen, suggesting the presence of both inflammation and viral infection corresponding to PET abnormality.

Correction to: Ventral striatal and septal area hypermetabolism on FDG-PET in herpes simplex viral encephalitis.

The word "hypermetabolism" needs to be replaced by "hypometabolism" at only ONE place and NOT throughout the article.So the correction could be stated as:"In the case description section, the sentence "A repeat dedicatedbrain FDG-PET scan performed on day 9, under burst suppression,showed diffuse hypermetabolism with persistent relativehypermetabolism in the left ventral striatum and septalarea (Fig. 1b)."should read as"A repeat dedicatedbrain FDG-PET scan performed on day 9, under burst suppression,showed diffuse hypometabolism with persistent relativehypermetabolism in the left ventral striatum and septalarea (Fig. 1b)." At all other places, the word hypermetabolism is appropriate.

Effects of Osmotic Therapy on Pupil Reactivity: Quantification Using Pupillometry in Critically Ill Neurologic Patients.

BACKGROUND: Osmotic therapy is a critical component of medical management for cerebral edema. While up to 90% of neurointensivists report using these treatments, few quantitative clinical measurements guide optimal timing, dose, or administration frequency. Its use is frequently triggered by a qualitative assessment of neurologic deterioration and/or pupil size, and anecdotally appears to improve pupil asymmetry suggestive of uncal herniation. However, subjective pupil assessment has poor reliability, making it difficult to detect or track subtle changes. We hypothesized that osmotic therapy reproducibly improves quantitative pupil metrics. METHODS: We included patients at two centers who had recorded quantitative pupil measurements within 2 h before and after either 20% mannitol or 23.4% hypertonic saline in the neurosciences intensive care unit. The primary outcome was the Neurologic Pupil Index (NPi), a composite metric ranging from 0 to 5 in which > 3 is considered normal. Secondary outcomes included pupil size, percent change, constriction and dilation velocity, and latency. Results were analyzed with Wilcoxon signed-rank tests, Chi-square and multi-level linear regression to control for other edema-reducing interventions. RESULTS: Out of 72 admissions (403 paired pupil observations), NPi significantly differed within 2 h of osmotic therapy when controlling for other commonly used interventions in our whole cohort (ß = 0.08, p = 0.0168). The effect was most pronounced (ß = 0.57) in patients with abnormal NPi prior to intervention (p = 0.0235). CONCLUSIONS: Pupil reactivity significantly improves after osmotic therapy in a heterogenous critically ill population when controlling for various other interventions. Future work is necessary to determine dose-dependent effects and clinical utility.

The Effect of Ambient Light Conditions on Quantitative Pupillometry.

BACKGROUND: Automated devices collecting quantitative measurements of pupil size and reactivity are increasingly used for critically ill patients with neurological disease. However, there are limited data on the effect of ambient light conditions on pupil metrics in these patients. To address this issue, we tested the range of pupil reactivity in healthy volunteers and critically ill patients in both bright and dark conditions. METHODS: We measured quantitative pupil size and reactivity in seven healthy volunteers and seven critically ill patients with the Neuroptics-200 pupillometer in both bright and dark ambient lighting conditions. Bright conditions were created by overhead LED lighting in a room with ample natural light. Dark conditions consisted of a windowless room with no overhead light source. The primary outcome was the Neurological Pupil Index (NPi), a composite metric ranging from 0 to 5 in which > 3 is considered normal. Secondary outcomes included resting and constricted pupil size, change in pupil size, constriction velocity, dilation velocity, and latency. Results were analyzed with multi-level linear regression to account for both inter- and intra-subject variability. RESULTS: Fourteen subjects underwent ten pupil readings each in bright and dark conditions, yielding 280 total measurements. In healthy subjects, median NPi in bright and dark conditions was 4.2 and 4.3, respectively. In critically ill subjects, median NPi was 2.85 and 3.3, respectively. Multi-level linear regression demonstrated significant differences in pupil size, pupil size change, constriction velocity, and dilation velocity in various light levels in healthy patients, but not NPi. In the critically ill, NPi and pupil size change were significantly affected. CONCLUSION: Ambient light levels impact pupil parameters in both healthy and critically ill subjects. Changes in NPi under different light conditions are small and more consistent in healthy subjects, but significantly differ in the critically ill. Practitioners should standardize lighting conditions to maximize measurement reliability.

The neurocritical care research network: NCRN.

Neurocritical care diseases carry a high morbidity and mortality. Therapeutic and technological advances in neurocritical care have greatly improved the outcome of a variety of life-threatening disorders including traumatic brain injury, acute ischemic stroke, intracerebral and subarachnoid hemorrhage, and anoxic injury following cardiac arrest. These advances have stemmed from a better understanding of the physiology of neurocritical care illnesses, improved neuromonitoring techniques, and the introduction of more efficacious treatments. Despite all the advances in neuromonitoring, diagnostic imaging, and emerging treatments, much research needs to be undertaken in neurocritical care. Many of the clinical trials carried out in the general critical care population have excluded neurocritical care patients. For instance, the landmark ARDSNET trial that demonstrated the beneficial effects of low tidal volume ventilation in patients with ARDS cannot be directly applied to neurocritical care patients who frequently may experience this pulmonary complication. There is a need for a more cohesive and integrated research system or network to establish a track record for high-quality, investigator-initiated clinical research in neurocritical care. Such a system may help us overcome potential impediments to the future advancement of neurocritical care research. We propose the creation of the neurocritical care research network. The mission of the Network is to facilitate multicenter and multidisciplinary collaboration and patient enrollment in clinical trials of specific neurocritical care diseases.

Research and technology in neurocritical care.

The daily practice of neurointensivists focuses on the recognition of subtle changes in the neurological examination, interactions between the brain and systemic derangements, and brain physiology. Common alterations such as fever, hyperglycemia, and hypotension have different consequences in patients with brain insults compared with patients of general medical illness. Various technologies have become available or are currently being developed. The session on "research and technology" of the first neurocritical care research conference held in Houston in September of 2009 was devoted to the discussion of the current status, and the research role of state-of-the art technologies in neurocritical patients including multi-modality neuromonitoring, biomarkers, neuroimaging, and "omics" research (proteomix, genomics, and metabolomics). We have summarized the topics discussed in this session. We have provided a brief overview of the current status of these technologies, and put forward recommendations for future research applications in the field of neurocritical care.

Vagus nerve stimulation modulates cortical synchrony and excitability through the activation of muscarinic receptors.

Vagus nerve stimulation (VNS) is an FDA approved treatment for drug-resistant epilepsy and depression. Recently, we demonstrated the capacity for repeatedly pairing sensory input with brief pulses of VNS to induce input specific reorganization in rat auditory cortex. This was subsequently used to reverse the pathological neural and perceptual correlates of hearing loss induced tinnitus. Despite its therapeutic potential, VNS mechanisms of action remain speculative. In this study, we report the acute effects of VNS on intra-cortical synchrony, excitability, and sensory processing in anesthetized rat auditory cortex. VNS significantly increased and decorrelated spontaneous multi-unit activity, and suppressed entrainment to repetitive noise burst stimulation at 6-8 Hz but not after application of the muscarinic antagonist scopolamine. Collectively, these experiments demonstrate the capacity for VNS to acutely influence cortical synchrony and excitability and strengthen the hypothesis that acetylcholine and muscarinic receptors are involved in VNS mechanisms of action. These results are discussed with respect to their possible implications for sensory processing, neural plasticity, and epilepsy.

Adult acute disseminated encephalomyelitis associated with poststreptococcal infection.

Acute disseminated encephalomyelitis (ADEM) is a monophasic illness that is thought to develop from antigenic mimicry with antibodies having cross-reactivity to host epitopes in the nervous system. The disorder typically follows an exanthematous or recent viral infection. In contrast, complications from bacterial poststreptococcal infections more commonly give rise to disorders in the pediatric population including Sydenham's chorea, pediatric autoimmune neuropsychiatric disorders, and ADEM. We present the novel case of documented streptococcal pharyngitis and elevated antideoxyribonuclease B (ADNB) titers in an adult giving rise to ADEM. Furthermore, the absence of basal ganglia abnormalities on MRI and the degree of leukocytosis in the CSF distinguish the adult form of ADEM from childhood ADEM and adult viral demyelinating diseases.

Motion processing in the macaque: revisited with functional magnetic resonance imaging.

A great deal is known about the response properties of single neurons processing sensory information. In contrast, less is understood about the collective characteristics of networks of neurons that may underlie sensory capacities of animals. We used functional magnetic resonance imaging to study the emergent properties of populations of neurons processing motion across different brain areas. Using a visual adaptation paradigm, we localized a distributed network of visual areas that process information about the direction of motion as expected from single-cell recording studies. However, we found an apparent discrepancy between the directional signals in certain visual areas as measured with blood oxygenation level-dependent imaging compared with an estimate based on the spiking of single neurons. We propose a hypothesis that may account for this difference based on the postulate that neuronal selectivity is a function of the state of adaptation. Consequently, neurons classically thought to lack information about certain attributes of the visual scene may nevertheless receive and process this information. We further hypothesize that this adaptation-dependent selectivity may arise from intra- or inter-area cellular connections, such as feedback from higher areas. This network property may be a universal principle the computational goal of which is to enhance the ability of neurons in earlier visual areas to adapt to statistical regularities of the input and therefore increase their sensitivity to detect changes along these stimulus dimensions.

Eye movements modulate visual receptive fields of V4 neurons.

The receptive field, defined as the spatiotemporal selectivity of neurons to sensory stimuli, is central to our understanding of the neuronal mechanisms of perception. However, despite the fact that eye movements are critical during normal vision, the influence of eye movements on the structure of receptive fields has never been characterized. Here, we map the receptive fields of macaque area V4 neurons during saccadic eye movements and find that receptive fields are remarkably dynamic. Specifically, before the initiation of a saccadic eye movement, receptive fields shrink and shift towards the saccade target. These spatiotemporal dynamics may enhance information processing of relevant stimuli during the scanning of a visual scene, thereby assisting the selection of saccade targets and accelerating the analysis of the visual scene during free viewing.

Adaptation of retinal processing to image contrast and spatial scale.

Owing to the limited dynamic range of a neuron's output, neural circuits are faced with a trade-off between encoding the full range of their inputs and resolving gradations among those inputs. For example, the ambient light level varies daily over more than nine orders of magnitude, whereas the firing rate of optic nerve fibres spans less than two. This discrepancy is alleviated by light adaptation: as the mean intensity increases, the retina becomes proportionately less sensitive. However, image statistics other than the mean intensity also vary drastically during routine visual processing. Theory predicts that an efficient visual encoder should adapt its strategy not only to the mean, but to the full shape of the intensity distribution. Here we report that retinal ganglion cells, the output neurons of the retina, adapt to both image contrast-the range of light intensities-and to spatial correlations within the scene, even at constant mean intensity. The adaptation occurs on a scale of seconds, one hundred times more slowly than the immediate light response, and involves 2-5-fold changes in the firing rate. It is mediated within the retinal network: two independent sites of modulation after the photoreceptor cells appear to be involved. Our results demonstrate a remarkable plasticity in retinal processing that may contribute to the contrast adaptation of human vision.