Pathological conditions such as amyotrophic lateral sclerosis or damage to the brainstem can leave patients severely paralyzed but fully aware, in a condition known 'locked-in syndrome'. Communication this state is often reduced selecting individual letters words by arduous residual movements. More intuitive and rapid communication may be restored directly interfacing with language areas of cerebral cortex. We used grid closely spaced, nonpenetrating micro-electrodes record local field...

Abstract Central nervous system infection can induce epilepsy that is often refractory to established antiseizure drugs. Previous studies in the Theiler’s murine encephalomyelitis virus (TMEV)-induced mouse model of limbic have demonstrated importance inflammation, especially mediated by tumor necrosis factor-α (TNFα), development acute seizures. TNFα modulates glutamate receptor trafficking via TNF 1 (TNFR1) cause increased excitatory synaptic transmission. Therefore, we hypothesized an...

Interictal epileptiform discharges (IEDs), also known as interictal spikes, are large intermittent electrophysiological events observed between seizures in patients with epilepsy. Although they occur far more often than seizures, IEDs less studied, and their relationship to remains unclear. To better understand this relationship, we examined multi-day recordings of microelectrode arrays implanted human epilepsy patients, allowing us precisely observe the spatiotemporal propagation IEDs,...

This paper describes an area and power-efficient VLSI approach for implementing the discrete wavelet transform on streaming multielectrode neurophysiological data in real time. The implementation is based lifting scheme computation using symmlet4 basis with quantized coefficients integer fixed-point precision to minimize hardware demands. proposed design driven by need compress neural signals recorded high-density microelectrode arrays implanted cortex prior telemetry. Our results indicate...

The mouse 6 Hz model of psychomotor seizures is a well-established and commonly used preclinical for antiseizure drug (ASD) discovery. Despite its widespread use both in the identification differentiation novel ASDs mice, corresponding assay rats has not been developed. We established method seizure induction rats, with behaviors similar to those observed mice including head nod, jaw clonus, forelimb clonus.A convulsive current that elicits these 97% (CC97 ) was determined using Probit...

Treatment With Hydroxychloroquine or Azithromycin and In-Hospital Mortality in Patients COVID-19

Object The goal of this study was to determine whether a nonpenetrating, high-density microwire array could provide sufficient information serve as the interface for decoding motor cortical signals. Methods Arrays nonpenetrating microwires were implanted over human cortex in 2 patients. patients performed directed stereotypical reaching movements directions. resulting data used reach direction be distinguished through frequency power analysis. Results Correlation analysis revealed decreasing...

Astrocytes have emerged as active participants of synaptic transmission and are increasingly implicated in neurologic disorders including epilepsy. Adult glial fibrillary acidic protein (GFAP)-positive hippocampal astrocytes not known for ionotropic glutamate receptor expression under basal conditions. Using a chemoconvulsive status epilepticus (SE) model temporal lobe epilepsy, we show by immunohistochemistry colocalization analysis that reactive express kainate (KAR) subunits after SE. In...

Electrographic status epilepticus (ESE) is a medical emergency consisting of repetitive seizures and may result in death or severe brain damage. Epilepsy can develop following ESE. The properties ESE (e.g., duration intensity) are variable, as the effects putative therapeutic treatments. Therefore straightforward method to quantify different components would be beneficial for both researchers clinicians. A frequency range close gamma band was selected extraction seizure-related activity from...

The lamotrigine-resistant amygdala kindling model uses repeated administration of a low dose lamotrigine during the process to produce resistance lamotrigine, which also extends some other antiseizure drugs (ASDs). This pharmacoresistant epilepsy has been incorporated into testing scheme utilized by Epilepsy Therapy Screening Program (ETSP). Although ASDs have evaluated in this model, comprehensive evaluation ASD prototypes not reported.Following depth electrode implantation and recovery,...

Abstract Objective Approximately 30% of patients with epilepsy do not experience full seizure control on their antiseizure drug (ASD) regimen. Historically, screening for novel ASDs has relied evaluating efficacy following a single administration test compound in either acute electrical or chemical induction. However, the use animal models spontaneous seizures and repeated compounds may better differentiate compounds. Therefore, this approach been instituted as part National Institute...

Summary Objective Nonadherence to prescribed dosing regimens is a significant problem in the treatment of pediatric and adult chronic epilepsy, can result severe consequences patient outcomes. In this first‐of‐kind preclinical study, impact nonadherence on seizure control was studied by simulating human patterns an animal epilepsy model. Methods study 1, three different were modeled newly diagnosed epileptic rats treated with carbamazepine: perfect adherence (100% pellets contained...

The discovery and development of novel antiseizure drugs (ASDs) that are effective in controlling pharmacoresistant spontaneous recurrent seizures (SRSs) continues to represent a significant unmet clinical need. Epilepsy Therapy Screening Program (ETSP) has undertaken efforts address this need by adopting animal models the salient features human epilepsy employing these for preclinical testing investigational ASDs. One such model garnered increased interest recent years is mouse variant...

Summary Objective Medication nonadherence directly contributes to poor seizure control. A lack of emphasis on correcting adherence and failures in patient can result unwarranted alterations a patient's drug regimen. We have modeled nonadherent patients an animal model epilepsy study how pharmacotherapy, made without consideration adherence, changes Methods Newly diagnosed rats with were treated carbamazepine ( CBZ ) during 4‐week baseline period establish their rate the presence 50%...

Regulatory approaches to COVID-19 vaccine authorizations varied substantially across countries. Facing a common public health threat, what accounts for regulatory variation? This study focuses on emergency pharmaceutical and procedures whether how regulators' going into the pandemic shaped processes decisions during pandemic.The authors conducted an analysis of seven high-impact national international regulators with case studies from Brazil, China, India, Russia, United Kingdom, States,...

Neuroprosthetics can benefit greatly from area and power efficient signal processing circuitry suitable for implanting alongside miniature neural probes that interface to the nervous system. This work identifies an optimal VLSI architecture computing a 1-dimensional multilevel discrete wavelet transform multiple electrode channels simultaneously. The is based on lifting-scheme computation integer fixed-point precision real-time under constraints imposed by implantability requirements. Two...

Developments in microfabrication of high-density electronic interfaces to the central nervous system rapidly evolved recent years. Nonetheless, there is a lack higher digital signal processing capability cope with larger data throughput. Multiresolution analysis by means wavelet transform has shown yield substantial and compression capabilities high volumes neural signals while preserving necessary information needed understand coding mechanism. We describe systems approach for reducing...

Abstract Objective Seizure detection is a major facet of electroencephalography (EEG) analysis in neurocritical care, epilepsy diagnosis and management, the instantiation novel therapies such as closed‐loop stimulation or optogenetic control seizures. It also increased importance high‐throughput, robust, reproducible pre‐clinical research. However, seizure detectors are not widely relied upon either clinical research settings due to limited validation. In this study, we create...

Two hardware architectures for implementing lifting-based discrete wavelet transform (DWT) suitable implantable, real-time operation of high-density sensor array neuroprosthetic devices. A core computational node (CN) is designed use in both to yield maximum processor usage. The first uses multiple pipelined replicas the CN, requiring fewer clock cycles. second architecture reuses a single thus requires less chip area but longer time delay. By utilizing difference between data sampling rate...

Abstract Background Patients with drug-resistant epilepsy, including Dravet syndrome (DS), are frequently prescribed multiple antiseizure medications (ASMs). Nevertheless, people DS often have inadequate seizure control, and there is an ongoing unmet clinical need to identify novel therapeutics. As a proof-of-principle study further validate characterize the Scn1a A1783V/WT mouse model drug screening paradigm face, construct, predictive value, we assessed efficacy of subchronic...