Sensory-substitution based sound perception using a spinal computer-brain interface.

Sensory substitution offers a promising approach to restore lost sensory functions. Here we show that spinal cord stimulation (SCS), typically used for chronic pain management, can potentially serve as a novel auditory sensory substitution device. We recruited 13 patients undergoing SCS implantation and translated everyday sound samples into personalized SCS patterns during their trial phase.

Intracortical mechanisms of single pulse electrical stimulation (SPES) evoked excitations and inhibitions in humans.

Cortico-cortical evoked potentials (CCEPs) elicited by single-pulse electric stimulation (SPES) are widely used to assess effective connectivity between cortical areas and are also implemented in the presurgical evaluation of epileptic patients. Nevertheless, the cortical generators underlying the various components of CCEPs in humans have not yet been elucidated. Our aim was to describe the laminar pattern arising under SPES evoked CCEP components (P1, N1, P2, N2, P3) and to evaluate the similarities between N2 and the downstate of sleep slow waves.

The role of superficial and deep layers in the generation of high frequency oscillations and interictal epileptiform discharges in the human cortex.

Describing intracortical laminar organization of interictal epileptiform discharges (IED) and high frequency oscillations (HFOs), also known as ripples. Defining the frequency limits of slow and fast ripples. We recorded potential gradients with laminar multielectrode arrays (LME) for current source density (CSD) and multi-unit activity (MUA) analysis of interictal epileptiform discharges IEDs and HFOs in the neocortex and mesial temporal lobe of focal epilepsy patients.

Limbic and paralimbic respiratory modulation: From inhibition to enhancement.

Objective: Increased understanding of the role of cortical structures in respiratory control may help the understanding of seizure-induced respiratory dysfunction that leads to sudden unexpected death in epilepsy (SUDEP). The aim of this study was to characterize respiratory responses to electrical stimulation (ES), including inhibition and enhancement of respiration.

Methods: We prospectively recruited 19 consecutive patients with intractable epilepsy undergoing stereotactic electroencephalography (EEG) evaluation from June 2015 to June 2018.

Ictal high-frequency activity in limbic thalamic nuclei varies with electrographic seizure-onset patterns in temporal lobe epilepsy.

Objective: To characterize ictal high-frequency activity (HFA, 80-500 Hz) within the limbic thalami and correlate HFA with seizure onset patterns in patients with temporal lobe epilepsy (TLE).

Methods: Patients with TLE undergoing stereoelectroencephalography (SEEG) for presurgical workup were prospectively recruited for electrode implantation in one of the anterior (AN), centromedian (CeM), or mediodorsal (MD) thalamic nuclei. HFA was computed by three complementary methods: (1.

Direct Cortical Stimulation to Probe the Ictogenicity of the Epileptogenic Nodes in Temporal Lobe Epilepsy.

Accurate mapping of the seizure onset zone (SOZ) is critical to the success of epilepsy surgery outcomes. Epileptogenicity index (EI) is a statistical method that delineates hyperexcitable brain regions involved in the generation and early propagation of seizures. However, EI can overestimate the SOZ for particular electrographic seizure onset patterns.

Laminar distribution of electrically evoked hippocampal short latency ripple activity highlights the importance of the subiculum in vivo in human epilepsy, an intraoperative study.

Objective: The goal of this study was to define the pathology and anesthesia dependency of single pulse electrical stimulation (SPES) dependent high-frequency oscillations (HFOs, ripples, fast ripples) in the hippocampal formation.

Methods: Laminar profile of electrically evoked short latency (<100 ms) high-frequency oscillations (80-500 Hz) was examined in the hippocampus of therapy-resistant epileptic patients (6 female, 2 male) in vivo, under general anesthesia.

Results: Parahippocampal SPES evoked HFOs in all recorded hippocampal subregions (Cornu Ammonis 2-3, dentate gyrus, and subiculum) were not uniform, rather the combination of ripples, fast ripples, sharp transients, and multiple unit activities.

Machine learning approach to detect focal-onset seizures in the human anterior nucleus of the thalamus.

There is an unmet need to develop seizure detection algorithms from brain regions outside the epileptogenic cortex. The study aimed to demonstrate the feasibility of classifying seizures and interictal states from local field potentials (LFPs) recorded from the human thalamus-a subcortical region remote to the epileptogenic cortex. We tested the hypothesis that spectral and entropy-based features extracted from LFPs recorded from the anterior nucleus of the thalamus (ANT) can distinguish its state of ictal recruitment from other interictal states (including awake, sleep).

Precision mapping of the epileptogenic network with low- and high-frequency stimulation of anterior nucleus of thalamus.

Objective: The goal of thalamic deep brain stimulation in epilepsy is to engage and modulate the epileptogenic network. We demonstrate how the anterior nucleus of thalamus (ANT) stimulation engages the epileptogenic network using electrophysiological measures (gamma response and post-stimulation excitability).

Methods: Five patients with suspected temporal lobe epilepsy syndrome, undergoing stereo-electroencephalography (SEEG), were enrolled in the IRB approved study to undergo recording and stimulation of the ANT.

Acute modulation of the limbic network with low and high-frequency stimulation of the human fornix.

Targeted stimulation of white matter has opened newer perspectives in the field of neuromodulation, towards an attempt to improve memory or as a therapy for epilepsy. Stimulation of the fornix, being a part of the Papez circuit, is likely to modulate the limbic network excitability. However, the stimulation-frequency dependent variability in network excitability is unknown.

Robot-assisted stereoelectroencephalography exploration of the limbic thalamus in human focal epilepsy: implantation technique and complications in the first 24 patients.

Objective: Despite numerous imaging studies highlighting the importance of the thalamus in a patient's surgical prognosis, human electrophysiological studies involving the limbic thalamic nuclei are limited. The objective of this study was to evaluate the safety and accuracy of robot-assisted stereotactic electrode placement in the limbic thalamic nuclei of patients with suspected temporal lobe epilepsy (TLE).

Methods: After providing informed consent, 24 adults with drug-resistant, suspected TLE undergoing evaluation with stereoelectroencephalography (SEEG) were enrolled in the prospective study.

Reorganization of Large-Scale Functional Networks During Low-Frequency Electrical Stimulation of the Cortical Surface.

We investigated the functional network reorganization caused by low-frequency electrical stimulation (LFES) of human brain cortical surface. Intracranial EEG data from subdural grid positions were analyzed in 16 pre-surgery epileptic patients. LFES was performed by injecting current pulses (10mA, 0.

Spectral organization of focal seizures within the thalamotemporal network.

Objective: To investigate dynamic changes in neural activity between the anterior nucleus of the thalamus (ANT) and the seizure onset zone (SOZ) in patients with drug-resistant temporal lobe epilepsy (TLE) based on anatomic location, seizure subtype, and state of vigilance (SOV).

Methods: Eleven patients undergoing stereoelectroencephalography for seizure localization were recruited prospectively for local field potential (LFP) recording directly from the ANT. The SOZ was identified using line length and epileptogenicity index.

Practice trends and the outcome of neuromodulation therapies in epilepsy: A single-center study.

Neuromodulation therapies (VNS, RNS, and DBS) can improve seizure control in persons with epilepsy. However, there is a significant service gap in integrating these therapies in clinical care. Our epilepsy center has established an epilepsy neuromodulation clinic to improve access to patients, communication with referring physicians, track outcome and train future providers in programming neuromodulation devices.

Early ictal recruitment of midline thalamus in mesial temporal lobe epilepsy.

The causal role of midline thalamus in the initiation and early organization of mesial temporal lobe seizures is studied. Three patients undergoing stereoelectroencephalography were enrolled for the placement of an additional depth electrode targeting the midline thalamus. The midline thalamus was recruited in all three patients at varying points of seizure initiation (0-13 sec) and propagation (9-60 sec).

Modulation of neural oscillations by vagus nerve stimulation in posttraumatic multifocal epilepsy: case report.

The putative mechanism of vagus nerve stimulation (VNS) for medically refractory epilepsy is desynchronization of hippocampal and thalamocortical circuitry; however, the nature of the dose-response relationship and temporal dynamics is poorly understood. For greater elucidation, a study in a nonepileptic rat model was previously conducted and showed that rapid-cycle (RC) VNS achieved superior desynchrony compared to standard-cycle (SC) VNS. Here, the authors report on the first in-human analysis of the neuromodulatory dose-response effects of VNS in a patient with posttraumatic, independent, bilateral mesial temporal lobe epilepsy refractory to medications and SC-VNS who was referred as a potential candidate for a responsive neurostimulation device.

Auras localized to the temporal lobe disrupt verbal memory and learning - Causal evidence from direct electrical stimulation of the hippocampus.

Auras (focal aware seizure; FAS) are subjective ictal events with retained consciousness. Epileptiform activities can disrupt cognitive tasks, but studies are limited to seizures with impaired awareness. As a proof of concept, we examined the cognitive effects of direct electrical stimulation to the left hippocampus which induced a habitual FAS in a patient with left mesial temporal lobe epilepsy.

Automated detection of mesial temporal and temporoperisylvian seizures in the anterior thalamic nucleus.

Background And Purpose: Focal seizures can arise from coordinated activity across large-scale epileptic networks and propagate to regions that are not functionally altered but are recruited by epileptiform discharges. In preclinical models of focal epilepsy, the thalamus is recruited by cortical onset seizures, but it remains to be demonstrated in clinical studies. In this pilot study, the authors investigate whether seizures with onset within and outside the mesial temporal structures are detected in the anterior thalamus (ATN).

Dynamics of seizure-induced behavioral and autonomic arousal.

Purpose: Arousal is the most primitive, powerful instinct with survival benefit present in all vertebrates. Even though the arousal systems are classically viewed as "ascending" brainstem phenomena, there is a "descending" cortical feedback system that maintains consciousness. In this study, we provide electrophysiological confirmation that seizures localized to the anterior cingulum can behaviorally manifest as paroxysms of arousal from sleep.

Intracranial neuronal ensemble recordings and analysis in epilepsy.

Pathological neuronal firing was demonstrated 50 years ago as the hallmark of epileptically transformed cortex with the use of implanted microelectrodes. Since then, microelectrodes remained only experimental tools in humans to detect unitary neuronal activity to reveal physiological and pathological brain functions. This recording technique has evolved substantially in the past few decades; however, based on recent human data implying their usefulness as diagnostic tools, we expect a substantial increase in the development of microelectrodes in the near future.