There is active debate regarding how GABAergic function changes during seizure initiation and propagation, and whether interneuronal activity drives or impedes the pathophysiology. Here, we track cell-type specific firing during spontaneous human seizures to identify neocortical mechanisms of inhibitory failure. Fast-spiking interneuron activity was maximal over 1 second before equivalent excitatory increases, and showed transitions to out-of-phase firing prior to local tissue becoming incorporated into the seizure-driving territory.
View Article and Find Full Text PDFCalcifying pseudoneoplasm of the neuraxis are rare fibro-osseous lesions that can occur throughout the central nervous system. This paper reports one case of this lesion within the posterior fossa and contains a literature review of all cases documented within the posterior fossa to date. A 53-year-old female patient with a history of epiphora, facial irritation, and headaches was found to have a mass centered in the posterior fossa.
View Article and Find Full Text PDFCorpus callosotomy is among the oldest surgeries performed for drug-resistant epilepsy. Since it was first performed in 1940, numerous studies have assessed its outcomes in various patient populations in addition to describing different extents of sectioning and emerging technologies (i.e.
View Article and Find Full Text PDFAnalyzing neuronal activity during human seizures is pivotal to understanding mechanisms of seizure onset and propagation. These analyses, however, invariably using extracellular recordings, are greatly hindered by various phenomena that are well established in animal studies: changes in local ionic concentration, changes in ionic conductance, and intense, hypersynchronous firing. The first two alter the action potential waveform, whereas the third increases the "noise"; all three factors confound attempts to detect and classify single neurons.
View Article and Find Full Text PDFHigh 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.
View Article and Find Full Text PDFWe 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.
View Article and Find Full Text PDFWe analyze the role of inhibition in sustaining focal epileptic seizure activity. We review ongoing seizure activity at the mesoscopic scale that can be observed with microelectrode arrays as well as at the macroscale of standard clinical EEG. We provide clinical, experimental, and modeling data to support the hypothesis that paroxysmal depolarization (PD) is a critical component of the ictal machinery.
View Article and Find Full Text PDFDuring neocortical seizures in patients with epilepsy, microelectrode array recordings from the ictal core show a strong correlation between the fast, cellular spiking activities and the low-frequency component of the potential field, reflected in the electrocorticogram (ECoG). Here, we model the relationship between the cellular spike activity and this low-frequency component as the input and output signals of a linear time invariant system. Our approach is based on the observation that this relationship can be characterized by a so-called sinc function, the unit impulse response of an ideal (brick-wall) filter.
View Article and Find Full Text PDFSmall-scale neuronal networks may impose widespread effects on large network dynamics. To unravel this relationship, we analyzed eight multiscale recordings of spontaneous seizures from four patients with epilepsy. During seizures, multiunit spike activity organizes into a submillimeter-sized wavefront, and this activity correlates significantly with low-frequency rhythms from electrocorticographic recordings across a 10-cm-sized neocortical network.
View Article and Find Full Text PDFObjective: Evaluate the seizure-reduction response and safety of mesial temporal lobe (MTL) brain-responsive stimulation in adults with medically intractable partial-onset seizures of mesial temporal lobe origin.
Methods: Subjects with mesial temporal lobe epilepsy (MTLE) were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline.
Objective: Evaluate the seizure-reduction response and safety of brain-responsive stimulation in adults with medically intractable partial-onset seizures of neocortical origin.
Methods: Patients with partial seizures of neocortical origin were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline.
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.
View Article and Find Full Text PDFObjective: To explore the feasibility of eliciting the brainstem H reflex in the masseter muscle in patients under general anesthesia.
Methods: We electrically stimulated the masseteric nerve, a branch of the trigeminal nerve, and recorded ipsilateral masseteric and temporalis muscle responses. We tested eight patients who presented with trigeminal neuralgia; one patient had a temporal bone tumor and one patient had a brainstem arteriovenous malformation.
High-gamma (HG; 80-150 Hz) activity in macroscopic clinical records is considered a marker for critical brain regions involved in seizure initiation; it is correlated with pathological multiunit firing during neocortical seizures in the seizure core, an area identified by correlated multiunit spiking and low frequency seizure activity. However, the effects of the spatiotemporal dynamics of seizure on HG power generation are not well understood. Here, we studied HG generation and propagation, using a three-step, multiscale signal analysis and modeling approach.
View Article and Find Full Text PDFThe 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.
View Article and Find Full Text PDFPurpose: The purpose of this study was to assess the safety and outcomes of the clinical use of LINAC (linear accelerator)-based flattening-filter-free beams for delivering ablative stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN).
Methods And Materials: Thirty-six consecutive patients (34 unique patients) followed up by a single neurosurgeon and diagnosed with medically refractory unilateral TN were treated with SRS. There were 14 left-sided cases (41%) and 20 right-sided cases (59%).
Spike-sorting algorithms have been used to identify the firing patterns of isolated neurons ('single units') from implanted electrode recordings in patients undergoing assessment for epilepsy surgery, but we do not know their potential for providing helpful clinical information. It is important therefore to characterize both the stability of these recordings and also their context. A critical consideration is where the units are located with respect to the focus of the pathology.
View Article and Find Full Text PDFDespite an extensive body of work, it is still not clear how short term maintenance of information is implemented in the human brain. Most prior research has focused on "working memory"-typically involving the storage of a number of items, requiring the use of a phonological loop and focused attention during the delay period between encoding and retrieval. These studies largely support a model of enhanced activity in the delay interval as the central mechanism underlying working memory.
View Article and Find Full Text PDFObjective: To determine whether resection of areas with evidence of intense, synchronized neural firing during seizures is an accurate indicator of postoperative outcome.
Methods: Channels meeting phase-locked high gamma (PLHG) criteria were identified retrospectively from intracranial EEG recordings (102 seizures, 46 implantations, 45 patients). Extent of removal of both the seizure onset zone (SOZ) and PLHG was correlated with seizure outcome, classified as good (Engel class I or II, n = 32) or poor (Engel class III or IV, n = 13).
Unlabelled: Measurements of neuronal signals during human seizure activity and evoked epileptic activity in experimental models suggest that, in these pathological states, the individual nerve cells experience an activity driven depolarization block, i.e. they saturate.
View Article and Find Full Text PDFObjective: To report long-term efficacy and safety results of the SANTE trial investigating deep brain stimulation of the anterior nucleus of the thalamus (ANT) for treatment of localization-related epilepsy.
Methods: This long-term follow-up is a continuation of a previously reported trial of 5- vs 0-V ANT stimulation. Long-term follow-up began 13 months after device implantation with stimulation parameters adjusted at the investigators' discretion.
Unlabelled: OBJECT.: The risk of developing epilepsy after perinatal stroke, hypoxic/ischemic injury, and intracerebral hemorrhage is significant, and seizures may become medically refractory in approximately 25% of these patients. Surgical management can be difficult due to multilobar or bilateral cortical injury, nonfocal or poorly lateralizing video electroencephalography (EEG) findings, and limited functional reserve.
View Article and Find Full Text PDFHigh frequency oscillations have been proposed as a clinically useful biomarker of seizure generating sites. We used a unique set of human microelectrode array recordings (four patients, 10 seizures), in which propagating seizure wavefronts could be readily identified, to investigate the basis of ictal high frequency activity at the cortical (subdural) surface. Sustained, repetitive transient increases in high gamma (80-150 Hz) amplitude, phase-locked to the low-frequency (1-25 Hz) ictal rhythm, correlated with strong multi-unit firing bursts synchronized across the core territory of the seizure.
View Article and Find Full Text PDFSubstantia nigra neurons are known to play a key role in normal cognitive processes and disease states. While animal models and neuroimaging studies link dopamine neurons to novelty detection, this has not been demonstrated electrophysiologically in humans. We used single neuron extracellular recordings in awake human subjects undergoing surgery for Parkinson disease to characterize the features and timing of this response in the substantia nigra.
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