Stabilized carbon coating on microelectrodes for scalable and interoperable neurotransmitter sensing.

Real-time monitoring of neurotransmitters is essential in driving basic neuroscience understandings and creating treatments for various brain disorders. However, current neurotransmitter sensing devices are highly limited in their spatiotemporal resolution and ability to integrate with neuronal recording. Here, we introduce a unique carbon coating approach to achieve high-performance voltammetry electrodes with extraordinary scalability and interoperability.

Solving the enigma of burst suppression.

The neural mechanisms underlying burst suppression during anaesthesia remain poorly understood. A recent study in the British Journal of Anaesthesia used calcium imaging to examine neuronal activity driving burst suppression in both cortical and subcortical structures. The results reveal diverse involvement of cortical excitatory neurones in burst suppression, while distinct interneurone subtypes play varied roles.

Protocol for detecting and analyzing non-oscillatory traveling waves from high-spatiotemporal-resolution human electrophysiological recordings.

Innovations in electrophysiological recordings and computational analytic techniques enable high-resolution analysis of neural traveling waves. Here, we present a protocol for the detection and analysis of traveling waves from multi-day microelectrode array human electrophysiological recordings through a multi-linear regression statistical approach using point estimator data. We describe steps for traveling wave detection, feature characterization, and propagation pattern analysis.

Seizure network characterization by functional connectivity mapping and manipulation.

Significance: Despite the availability of various anti-seizure medications, nearly 1/3 of epilepsy patients experience drug-resistant seizures. These patients are left with invasive surgical options that do not guarantee seizure remission. The development of novel treatment options depends on elucidating the complex biology of seizures and brain networks.

Multifunctional Nanomesh Enables Cellular-Resolution, Elastic Neuroelectronics.

Silicone-based devices have the potential to achieve an ideal interface with nervous tissue but suffer from scalability, primarily due to the mechanical mismatch between established electronic materials and soft elastomer substrates. This study presents a novel approach using conventional electrode materials through multifunctional nanomesh to achieve reliable elastic microelectrodes directly on polydimethylsiloxane (PDMS) silicone with an unprecedented cellular resolution. This engineered nanomesh features an in-plane nanoscale mesh pattern, physically embodied by a stack of three thin-film materials by design, namely Parylene-C for mechanical buffering, gold (Au) for electrical conduction, and Poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) for improved electrochemical interfacing.

Single unit analysis and wide-field imaging reveal alterations in excitatory and inhibitory neurons in glioma.

While several studies have attributed the development of tumour-associated seizures to an excitatory-inhibitory imbalance, we have yet to resolve the spatiotemporal interplay between different types of neuron in glioma-infiltrated cortex. Herein, we combined methods for single unit analysis of microelectrode array recordings with wide-field optical mapping of Thy1-GCaMP pyramidal cells in an ex vivo acute slice model of diffusely infiltrating glioma. This enabled simultaneous tracking of individual neurons from both excitatory and inhibitory populations throughout seizure-like events.

Human interictal epileptiform discharges are bidirectional traveling waves echoing ictal discharges.

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 are less studied, and their relationship to seizures remains unclear. To better understand this relationship, we examined multi-day recordings of microelectrode arrays implanted in human epilepsy patients, allowing us to precisely observe the spatiotemporal propagation of IEDs, spontaneous seizures, and how they relate.

Dual mechanisms of ictal high frequency oscillations in human rhythmic onset seizures.

High frequency oscillations (HFOs) are bursts of neural activity in the range of 80 Hz or higher, recorded from intracranial electrodes during epileptiform discharges. HFOs are a proposed biomarker of epileptic brain tissue and may also be useful for seizure forecasting. Despite such clinical utility of HFOs, the spatial context and neuronal activity underlying these local field potential (LFP) events remains unclear.

A model for focal seizure onset, propagation, evolution, and progression.

We developed a neural network model that can account for major elements common to human focal seizures. These include the tonic-clonic transition, slow advance of clinical semiology and corresponding seizure territory expansion, widespread EEG synchronization, and slowing of the ictal rhythm as the seizure approaches termination. These were reproduced by incorporating usage-dependent exhaustion of inhibition in an adaptive neural network that receives global feedback inhibition in addition to local recurrent projections.

Ex vivo multi-electrode analysis reveals spatiotemporal dynamics of ictal behavior at the infiltrated margin of glioma.

The purpose of this study is to develop a platform in which the cellular and molecular underpinnings of chronic focal neocortical lesional epilepsy can be explored and use it to characterize seizure-like events (SLEs) in an ex vivo model of infiltrating high-grade glioma. Microelectrode arrays were used to study electrophysiologic changes in ex vivo acute brain slices from a PTEN/p53 deleted, PDGF-B driven mouse model of high-grade glioma. Electrode locations were co-registered to the underlying histology to ascertain the influence of the varying histologic landscape on the observed electrophysiologic changes.

Postictal clinical and electroencephalographic activity following intracranially recorded bilateral tonic-clonic seizures.

Objective: The dynamics of the postictal period, which may demonstrate such dramatic clinical phenomena as focal neurological deficits, prolonged coma and immobility, and even sudden death, are poorly understood. We sought to classify and characterize postictal phases of bilateral tonic-clonic seizures based on electroencephalographic (EEG) criteria and associated clinical features.

Methods: We performed a detailed electroclinical evaluation of the postictal period in a series of 31 bilateral tonic-clonic seizures in 16 patients undergoing epilepsy surgery evaluations for focal pharmacoresistant epilepsy with intracranial electrodes and time-locked video.

Role of inhibitory control in modulating focal seizure spread.

Focal seizure propagation is classically thought to be spatially contiguous. However, distribution of seizures through a large-scale epileptic network has been theorized. Here, we used a multielectrode array, wide field calcium imaging, and two-photon calcium imaging to study focal seizure propagation pathways in an acute rodent neocortical 4-aminopyridine model.

Glial Calcium Waves are Triggered by Seizure Activity and Not Essential for Initiating Ictal Onset or Neurovascular Coupling.

It has been postulated that glia play a critical role in modifying neuronal activity, mediating neurovascular coupling, and in seizure initiation. We investigated the role of glia in ictogenesis and neurovascular coupling through wide-field multicell and 2-photon single cell imaging of calcium and intrinsic signal imaging of cerebral blood volume in an in vivo rat model of focal neocortical seizures. Ictal events triggered a slowly propagating glial calcium wave that was markedly delayed after both neuronal and hemodynamic onset.

Multivariate regression methods for estimating velocity of ictal discharges from human microelectrode recordings.

Objective: Epileptiform discharges, an electrophysiological hallmark of seizures, can propagate across cortical tissue in a manner similar to traveling waves. Recent work has focused attention on the origination and propagation patterns of these discharges, yielding important clues to their source location and mechanism of travel. However, systematic studies of methods for measuring propagation are lacking.

Neuronal firing patterns outweigh circuitry oscillations in parkinsonian motor control.

Neuronal oscillations at beta frequencies (20-50 Hz) in the cortico-basal ganglia circuits have long been the leading theory for bradykinesia, the slow movements that are cardinal symptoms in Parkinson's disease (PD). The beta oscillation theory helped to drive a frequency-based design in the development of deep brain stimulation therapy for PD. However, in contrast to this theory, here we have found that bradykinesia can be completely dissociated from beta oscillations in rodent models.

Climbing fiber-Purkinje cell synaptic pathology in tremor and cerebellar degenerative diseases.

Changes in climbing fiber-Purkinje cell (CF-PC) synaptic connections have been found in the essential tremor (ET) cerebellum, and these changes are correlated with tremor severity. Whether these postmortem changes are specific to ET remains to be investigated. We assessed CF-PC synaptic pathology in the postmortem cerebellum across a range of degenerative movement disorders [10 Parkinson's disease (PD) cases, 10 multiple system atrophy (MSA) cases, 10 spinocerebellar ataxia type 1 (SCA1) cases, and 20 ET cases] and 25 controls.

Deep brain stimulation and climbing fiber synaptic pathology in essential tremor.

Essential tremor (ET) patients have abnormal climbing fiber (CF) synapses in the parallel fiber territory in the cerebellum, and these abnormal CF synapses are inversely correlated with tremor severity. We therefore examined CF synaptic pathology in ET cases with and without thalamic deep brain stimulation (DBS) and assessed the association with tremor severity. We found that CF synaptic pathology was inversely correlated with tremor severity in ET cases without DBS, and this correlation disappeared in ET cases with DBS.

Risk Factors for Extubation Failure in Extremely Low Birth Weight Infants.

Background: Although antenatal steroids and early use nasal continuous positive airway pressure (NCPAP) have significantly improved outcomes of neonatal respiratory distress syndrome, intubation with ventilator support is still commonly required in extremely low birth weight (ELBW) infants. The optimal timing of extubation in ELBW infants remains unclear.

Methods: We retrospectively analyzed all ELBW preterm infants who were admitted to our neonatal intensive care unit (NICU) from January 2009 to December 2013.

The ictal wavefront is the spatiotemporal source of discharges during spontaneous human seizures.

The extensive distribution and simultaneous termination of seizures across cortical areas has led to the hypothesis that seizures are caused by large-scale coordinated networks spanning these areas. This view, however, is difficult to reconcile with most proposed mechanisms of seizure spread and termination, which operate on a cellular scale. We hypothesize that seizures evolve into self-organized structures wherein a small seizing territory projects high-intensity electrical signals over a broad cortical area.