Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy.

Objective: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years.

Methods: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory.

Changes in the electrocorticogram after implantation of intracranial electrodes in humans: The implant effect.

Objective: Subacute and long-term electrocorticographic (ECoG) changes in ambulatory patients with depth and cortical strip electrodes were evaluated in order to determine the length of the implant effect.

Methods: ECoG records were assessed in patients with medically intractable epilepsy who had depth and/or strip leads implanted in order to be treated with brain-responsive stimulation. Changes in total spectral power, band-limited spectral power, and spike rate were assessed.

Brain-responsive neurostimulation in patients with medically intractable mesial temporal lobe epilepsy.

Objective: 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.

Circadian and ultradian patterns of epileptiform discharges differ by seizure-onset location during long-term ambulatory intracranial monitoring.

Objective: Previous studies reporting circadian patterns of epileptiform activity and seizures are limited by (1) short-term recording in an epilepsy monitoring unit (EMU) with altered antiepileptic drugs (AEDs) and sleep, or (2) subjective seizure diary reports. We studied circadian patterns using long-term ambulatory intracranial recordings captured by the NeuroPace RNS System.

Methods: Retrospective study of RNS System trial participants with stable detection parameters over a continuous 84-day period.

Day-Night Patterns of Epileptiform Activity in 65 Patients With Long-Term Ambulatory Electrocorticography.

Purpose: To characterize cyclic day-night patterns of electrocorticographic epileptiform activity (EA) in patients with focal onset seizures.

Methods: Epileptiform events as defined by the physician (also termed more generally as "epileptiform activity" or EA) were recorded in 65 patients with partial onset (also referred to as "focal onset") seizures using the RNS System, which includes a cranially implanted neurostimulator connected to 1 or two 4-contact leads placed at the seizure focus. The neurostimulator is programmed to detect specific patterns of electrocorticographic activity and to provide responsive stimulation.

Lateralization of mesial temporal lobe epilepsy with chronic ambulatory electrocorticography.

Objective: Patients with suspected mesial temporal lobe (MTL) epilepsy typically undergo inpatient video-electroencephalography (EEG) monitoring with scalp and/or intracranial electrodes for 1 to 2 weeks to localize and lateralize the seizure focus or foci. Chronic ambulatory electrocorticography (ECoG) in patients with MTL epilepsy may provide additional information about seizure lateralization. This analysis describes data obtained from chronic ambulatory ECoG in patients with suspected bilateral MTL epilepsy in order to assess the time required to determine the seizure lateralization and whether this information could influence treatment decisions.

Interrater reliability in interpretation of electrocorticographic seizure detections of the responsive neurostimulator.

Objective: Electrocorticographic (ECoG) recordings from patients with medically intractable partial-onset seizures treated with a responsive neurostimulator system (the RNS System) that detects and stores physician-specified ECoG events provide a new data resource. Interpretation of these recordings has not yet been validated. The purpose was to evaluate the interrater interpretation of chronic ambulatory ECoG recordings obtained by the RNS System.

Long-term treatment with responsive brain stimulation in adults with refractory partial seizures.

Objective: The long-term efficacy and safety of responsive direct neurostimulation was assessed in adults with medically refractory partial onset seizures.

Methods: All participants were treated with a cranially implanted responsive neurostimulator that delivers stimulation to 1 or 2 seizure foci via chronically implanted electrodes when specific electrocorticographic patterns are detected (RNS System). Participants had completed a 2-year primarily open-label safety study (n = 65) or a 2-year randomized blinded controlled safety and efficacy study (n = 191); 230 participants transitioned into an ongoing 7-year study to assess safety and efficacy.

The RNS System: responsive cortical stimulation for the treatment of refractory partial epilepsy.

The RNS(®) System is the first commercially available device to provide closed-loop responsive brain stimulation. The system includes a cranially implanted neurostimulator that continually monitors the electrocorticogram through one or two depth and/or subdural cortical strip leads that are placed at the seizure focus. When abnormal electrographic activity is detected, the neurostimulator delivers brief pulses of electrical stimulation to the seizure focus through the implanted leads.

Closed-loop neurostimulation: the clinical experience.

Neurostimulation is now an established therapy for the treatment of movement disorders, pain, and epilepsy. While most neurostimulation systems available today provide stimulation in an open-loop manner (i.e.

Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: final results of the RNS System Pivotal trial.

Objective: To demonstrate the safety and effectiveness of responsive stimulation at the seizure focus as an adjunctive therapy to reduce the frequency of seizures in adults with medically intractable partial onset seizures arising from one or two seizure foci.

Methods: Randomized multicenter double-blinded controlled trial of responsive focal cortical stimulation (RNS System). Subjects with medically intractable partial onset seizures from one or two foci were implanted, and 1 month postimplant were randomized 1:1 to active or sham stimulation.

Responsive neurostimulation suppresses synchronized cortical rhythms in patients with epilepsy.

Deep brain stimulation (DBS) is an established treatment for Parkinson's disease, and is increasingly used for other neuropsychiatric conditions including epilepsy. Nevertheless, neural mechanisms for DBS and other forms of neurostimulation remain elusive. The authors measured effects of responsive neurostimulation on intracranially recorded activity from participants in a clinical investigation to assess the safety of an implantable responsive neurostimulation system in epilepsy (RNS™ System, NeuroPace, Inc.

A comparison of Granger causality and coherency in fMRI-based analysis of the motor system.

The ability of functional MRI to acquire data from multiple brain areas has spurred developments not only in voxel-by-voxel analyses, but also in multivariate techniques critical to quantifying the interactions between brain areas. As the number of multivariate techniques multiplies, however, few studies in any modality have directly compared different connectivity measures, and fewer still have done so in the context of well-characterized neural systems. To focus specifically on the temporal dimension of interactions between brain regions, we compared Granger causality and coherency (Sun et al.

Automated seizure onset detection for accurate onset time determination in intracranial EEG.

Objective: A novel algorithm for automated seizure onset detection is presented. The method allows for precise identification of electrographic seizure onset times within large databases of electrographic data.

Methods: The patient-specific algorithm extracts salient spectral and temporal features in five frequency bands within a sliding window of an electrographic recording.

Transient and sustained brain activity during anticipatory visuospatial attention.

In this study, we determined whether the visuospatial attention network of frontal, parietal, and occipital cortex can be parsed into two different subsets of active regions associated with transient and sustained processes within the same cue-to-target delay period of an endogenously cued visuospatial attention task. We identified regions with early transient activity and regions with later sustained activity during the same trials using a general linear model analysis of event-related BOLD functional MRI data with two timecourse covariates for the same cue-to-target delay period. During the delay between the cue and target, we observed significant transient activity in right frontal eye field and right occipital-parietal junction, and significant sustained activity in right ventral intraparietal sulcus and right dorsolateral and anterior prefrontal cortex.

Responsive cortical stimulation for the treatment of epilepsy.

Epilepsy is a common chronic neurological disorder affecting approximately 1-2% of the population. Despite the available treatment options (pharmacotherapy, surgery, and vagus nerve stimulation), a large percentage of patients continue to have seizures. With the success of deep brain stimulation for treatment of movement disorders, brain stimulation has received renewed attention as a potential treatment option for epilepsy.

Functional connectivity of the hippocampus in elderly with mild memory dysfunction carrying the APOE epsilon4 allele.

The purpose of the present study was to evaluate functional connectivity of the hippocampus during a fMRI face-name learning task in a group of elders with mild memory impairment on the basis of the presence or absence of the APOE epsilon4 allele. Twelve epsilon4 carriers and 20 non-carriers with mild memory dysfunction and exhibiting equivalent performance in clinical evaluations of global cognitive function and memory were studied. Subjects underwent a fMRI session consisting of a face-name encoding memory task.

Automated template-based PET region of interest analyses in the aging brain.

The definition of regions of interest for PET data analysis poses a number of complex problems. While studies have shown that regions drawn on a template can be appropriate for extracting data for normal healthy subjects, it is unclear how these results can be applied to different populations. In this study, we focused on the aging population and examined how different parameters in the template data-extraction process may affect the accuracy of the results.

Functional connectivity of cortical networks involved in bimanual motor sequence learning.

Motor skill learning requires the involvement and integration of several cortical and subcortical regions. In this study, we focus on how the functional connectivity of cortical networks changes with the acquisition of a novel motor skill. Using functional magnetic resonance imaging, we measured the localized blood oxygenation level-dependent (BOLD) signal in cortical regions while subjects performed a bimanual serial reaction time task under 2 conditions: 1) explicitly learning a novel sequence (NOVEL) and 2) playing a previously learned sequence (LEARNED).

Brain imaging evidence of preclinical Alzheimer's disease in normal aging.

Objective: This study was designed to test the hypothesis that baseline glucose metabolism and medial temporal lobe brain volumes are predictive of cognitive decline in normal older people.

Methods: We performed positron emission tomography using [18F]fluorodeoxyglucose and structural magnetic resonance imaging at baseline in 60 cognitively normal community-dwelling older subjects who were part of a longitudinal cohort study. Subjects were followed for a mean of 3.

Measuring temporal dynamics of functional networks using phase spectrum of fMRI data.

We present a novel method to measure relative latencies between functionally connected regions using phase-delay of functional magnetic resonance imaging data. Derived from the phase component of coherency, this quantity estimates the linear delay between two time-series. In conjunction with coherence, derived from the magnitude component of coherency, phase-delay can be used to examine the temporal properties of functional networks.

Functional interactions between oculomotor regions during prosaccades and antisaccades.

Human behavior reflects a continual negotiation of automatic and directed actions. The oculomotor network is a well-characterized neural system in which to study this balance of behavioral control. For instance, saccades made toward and away from a flashed visual stimulus (prosaccades and antisaccades, respectively) are known to engage different cognitive processes.

Coherence between fMRI time-series distinguishes two spatial working memory networks.

Widespread and distributed brain regions are thought to form networks that together support working memory. We recently demonstrated that different cortical areas maintain relatively different codes across a memory delay (Curtis et. al.

Measuring interregional functional connectivity using coherence and partial coherence analyses of fMRI data.

Understanding functional connectivity within the brain is crucial to understanding neural function; even the simplest cognitive operations are supported by highly distributed neural circuits. We developed a novel method to measure task-related functional interactions between neural regions by applying coherence and partial coherence analyses to functional magnetic resonance imaging (fMRI) data. Coherence and partial coherence are spectral measures that estimate the linear time-invariant (LTI) relationship between time series.