Non-invasive Temporal Interference Stimulation of the Hippocampus Suppresses Epileptic Biomarkers in Patients with Epilepsy: Biophysical Differences between Kilohertz and Amplitude Modulated Stimulation.

Medication-refractory focal epilepsy poses a significant challenge, with approximately 30% of patients ineligible for surgery due to the involvement of eloquent cortex in the epileptogenic network. For such patients with limited surgical options, electrical neuromodulation represents a promising alternative therapy. In this study, we investigate the potential of non-invasive temporal interference (TI) electrical stimulation to reduce epileptic biomarkers in patients with epilepsy by comparing intracerebral recordings obtained before, during, and after TI stimulation, and to those recorded during low and high kHz frequency (HF) sham stimulation.

A single-center learning curve for stereotactic laser amygdalohippocampotomy and a surgical framework to manage failures.

Objective: Stereotactic laser amygdalohippocampotomy (SLAH) is a minimally invasive procedure for mesial temporal lobe epilepsy that preserves more tissue than open procedures. As a result, although patients have better functional outcomes, more patients do not achieve seizure freedom. The rate at which this occurs is evolving with improved surgical practices.

An ordinal clinical score predicts seizure freedom after minimally invasive epilepsy surgery.

Objective: To predict one-year seizure freedom, using a combination of relevant clinical variables, following stereotactic laser amygdalohippocampotomy for mesial temporal lobe epilepsy in a series of 101 patients.

Methods: Eight predictors of seizure freedom were selected based on their association with medial temporal lobe epilepsy: (1) MRI evidence of mesial temporal sclerosis (MTS); (2) unitemporal interictal epileptiform discharges; (3) absence of generalized tonic-clonic seizures; (4) history of febrile seizures; (5) onset of epilepsy ≤16 years; (6) absence of an auditory, visual, or vertiginous aura; and (7) unitemporal ictal onset; (8) unitemporal PET hypometabolism. We compared four multivariate models: "MTS," using just evidence of MTS; "FULL," using all eight binary predictors; "AIC" using backwards selection of variables; and "SCORE," using a 0-to-8-point ordinal score awarding one point for each binary predictor.

Bayesian Estimation Improves Prediction of Outcomes after Epilepsy Surgery.

Low power is a problem in many fields, as underpowered studies that find a statistically significant result will exaggerate the magnitude of the observed effect size. We quantified the statistical power and magnitude error of studies of epilepsy surgery outcomes. The median power across all studies was 14%.

Selective Posterior Cerebral Artery Wada Better Predicts Good Memory and Naming Outcomes Following Selective Stereotactic Thermal Ablation for Medial Temporal Lobe Epilepsy Than Internal Carotid Artery Wada.

The conventional intracarotid amobarbital (Wada) test has been used to assess memory function in patients being considered for temporal lobe epilepsy (TLE) surgery. Minimally invasive approaches that target the medial temporal lobe (MTL) and spare neocortex are increasingly used, but a knowledge gap remains in how to assess memory and language risk from these procedures. We retrospectively compared results of two versions of the Wada test, the intracarotid artery (ICA-Wada) and posterior cerebral artery (PCA-Wada) approaches, with respect to predicting subsequent memory and language outcomes, particularly after stereotactic laser amygdalohippocampotomy (SLAH).

Psychiatric changes after stereotactic laser amygdalohippocampotomy for medial temporal lobe epilepsy.

Purpose: Stereotactic laser amygdalohippocampotomy (SLAH) is a minimally invasive surgical treatment for drug-resistant temporal lobe epilepsy (TLE) that has comparable rates of seizure freedom to traditional open resective TLE surgery. The objective of this study was to determine psychiatric outcome (i.e.

Stereoelectroencephalography-guided radiofrequency ablation of the epileptogenic zone as a treatment and predictor of future success of further surgical intervention.

Objective: Stereoelectroencephalography (SEEG)-guided radiofrequency ablation (RFA) is increasingly being used as a treatment for drug-resistant localization-related epilepsy. The aim of this study is to analyze the successes and failures using RFA and how response correlates with surgical epilepsy treatment outcomes.

Methods: We retrospectively reviewed 62 patients who underwent RFA via SEEG electrodes.

Mapping the Central Sulcus Extraoperatively Using Stereoelectroencephalography: A New Application of an Established Method.

Purpose: Central sulcus localization is undertaken intraoperatively with subdural electrodes through a phase reversal technique using somatosensory evoked potentials from sensorimotor cortices. Extraoperative central sulcus localization using stereoelectroencephalography has not been described previously.

Methods: Six pediatric patients (aged 12-18 years, 50% females) were investigated with stereoelectroencephalography.

Anterior nucleus of the thalamus deep brain stimulation vs temporal lobe responsive neurostimulation for temporal lobe epilepsy.

Objective: Based on the promising results of randomized controlled trials, deep brain stimulation (DBS) and responsive neurostimulation (RNS) are used increasingly in the treatment of patients with drug-resistant epilepsy. Drug-resistant temporal lobe epilepsy (TLE) is an indication for either DBS of the anterior nucleus of the thalamus (ANT) or temporal lobe (TL) RNS, but there are no studies that directly compare the seizure benefits and adverse effects associated with these therapies in this patient population. We, therefore, examined all patients who underwent ANT-DBS or TL-RNS for drug-resistant TLE at our center.

Ordinal regression increases statistical power to predict epilepsy surgical outcomes.

Studies of epilepsy surgery outcomes are often small and thus underpowered to reach statistically valid conclusions. We hypothesized that ordinal logistic regression would have greater statistical power than binary logistic regression when analyzing epilepsy surgery outcomes. We reviewed 10 manuscripts included in a recent meta-analysis which found that mesial temporal sclerosis (MTS) predicted better surgical outcomes after a stereotactic laser amygdalohippocampectomy (SLAH).

Cognitive and Emotional Mapping With SEEG.

Mapping of cortical functions is critical for the best clinical care of patients undergoing epilepsy and tumor surgery, but also to better understand human brain function and connectivity. The purpose of this review is to explore existing and potential means of mapping higher cortical functions, including stimulation mapping, passive mapping, and connectivity analyses. We examine the history of mapping, differences between subdural and stereoelectroencephalographic approaches, and some risks and safety aspects, before examining different types of functional mapping.

The Referential Montage Inadequately Localizes Corticocortical Evoked Potentials in Stereoelectroencephalography.

Purpose: Corticocortical evoked potentials (CCEPs) resulting from single pulse electrical stimulation are increasingly used to understand seizure networks, as well as normal brain connectivity. However, we observed that when using depth electrodes, traditional measures of CCEPs amplitude using a referential montage can be falsely localizing, often to white matter.

Methods: We pooled 27 linear electrode arrays targeting the amygdala, hippocampus, or cingulate cortex from eight participants.

Robot Assisted MRI-Guided LITT of the Anterior, Lateral, and Medial Temporal Lobe for Temporal Lobe Epilepsy.

Robotic systems have fundamentally altered the landscape of functional neurosurgery. These allow automated stereotaxy with high accuracy and reliability, and are rapidly becoming a mainstay in stereotactic surgeries such as deep brain stimulation (DBS), stereoelectroencephalography (SEEG), and stereotactic laser ablation/MRI guided laser interstitial thermal therapy (MRgLITT). Robotic systems have been effectively applied to create a minimally invasive approach for diagnostics and therapeutics in the treatment of epilepsy, utilizing robots for expeditious and accurate stereotaxy for SEEG and MRgLITT.

The Prognostic Value of Quantitative EEG in Patients Undergoing Mechanical Thrombectomy for Acute Ischemic Stroke.

Purpose: Previous work has shown that quantitative EEG measures correlate with the severity of ischemic stroke. This has not been systematically validated in patients with acute ischemic stroke who have undergone mechanical thrombectomy.

Methods: Data were collected from 73 patients who underwent mechanical thrombectomy and had a standard head set EEG performed during their hospital admission.

Ultra-long term stability of single units using chronically implanted multielectrode arrays.

Recordings from chronically implanted multielectrode arrays have become prevalent in both neuroscience and neural engineering experiments. To date, however, the extent to which populations of single-units remain stable over long periods of time has not been well characterized. In this study, neural activity was recorded from a Utah multielectrode array implanted in the primary motor cortex of a rhesus macaque during 18 recording sessions spanning nine months.

Heterogeneous neural coding of corrective movements in motor cortex.

During a reach, neural activity recorded from motor cortex is typically thought to linearly encode the observed movement. However, it has also been reported that during a double-step reaching paradigm, neural coding of the original movement is replaced by that of the corrective movement. Here, we use neural data recorded from multi-electrode arrays implanted in the motor and premotor cortices of rhesus macaques to directly compare these two hypotheses.

Electrical activity and exocytotic correlates of biphasic insulin secretion from beta-cells of canine islets of Langerhans: contribution of tuning two modes of Ca2+ entry-dependent exocytosis to two modes of glucose-induced electrical activity.

Biphasic insulin secretion in response to glucose, consisting of a transient first phase followed by a progressive second phase, is well described in pancreatic islets. Using single canine beta-cells we have compared the time courses of electrical activity and insulin granule exocytosis to biphasic insulin secretion. Short trains of action potentials, similar those found during first phase insulin secretion, trigger phasic exocytosis from a small pool of insulin granules, likely an immediately releasable pool docked near voltage activated Ca(2+) channels.

Single-unit stability using chronically implanted multielectrode arrays.

The use of chronic intracortical multielectrode arrays has become increasingly prevalent in neurophysiological experiments. However, it is not obvious whether neuronal signals obtained over multiple recording sessions come from the same or different neurons. Here, we develop a criterion to assess single-unit stability by measuring the similarity of 1) average spike waveforms and 2) interspike interval histograms (ISIHs).

Ion channels underlying stimulus-exocytosis coupling and its cell-to-cell heterogeneity in beta-cells of transplantable porcine islets of Langerhans.

Given the growing interest in porcine islets as model tissue for studying the pathogenesis of human diabetes mellitus and its treatment by transplantation, we investigated stimulus-exocytosis coupling in single porcine beta-cells using patch clamp electrophysiology, Ca2+ imaging, capacitance tracking and amperometry. We establish that porcine beta-cells display several features prominently seen in beta-cells from human islets of Langerhans. These include: (i) wide heterogeneity of electrical responsiveness to glucose; (ii) dependence of action potential activity on voltage-dependent Na(+) as well as high voltage activated Ca2+ current; (iii) heterogeneity of time course of depolarization-evoked insulin granule exocytosis; and (iv) the dependence of vigorous single cell electrical activity and insulin granule exocytosis on the presence of agents that enhance cytosolic cAMP concentration.

Phasic and tonic modes of depolarization-exocytosis coupling in beta-cells of porcine islets of Langerhans.

In response to depolarizations that open voltage dependent Ca2+ channels single porcine beta-cells display heterogeneous time courses of exocytosis. Some cells display phasic exocytosis that is triggered by individual or short burst of action potentials typically characteristic of glucose-induced electrical activity or brief voltage clamp depolarization. Other cells, singularly or additionally, display tonic exocytosis that (i) is triggered during prolonged (up to seconds-long) depolarizations to voltages (-30 to -20 mV), and (ii) coincides with rises in global cytosolic [Ca2+] >500 nM.

Maintenance of stimulus-secretion coupling and single beta-cell function in cryopreserved-thawed human islets of Langerhans.

Studies of stimulus-secretion coupling in human beta-cells have been hampered by poor availability of tissue due to variability of the supply of cadaver pancreati and in the adequacy of enzymatic liberation of islets as well as by the shunting of isolates into transplant trials. Here we establish that aliquots of islets, several from high-quality but low-yield islet isolates (50,000-100,000 islets), cryopreserved and then thawed as needed, respond to glucose in a calcium- and metabolic-dependent fashion. Insulin secretion is modulated by blockers of voltage-dependent Na+ and Ca2+ channels, and paracrine hormones (glucagon and somatostatin) in manners indistinguishable from fresh tissue preparations.

alpha-Latrotoxin increases spontaneous and depolarization-evoked exocytosis from pancreatic islet beta-cells.

alpha-Latrotoxin (alpha-LT), a potent excitatory neurotoxin, increases spontaneous, as well as action potential-evoked, quantal release at nerve terminals and increases hormone release from excitable endocrine cells. We have investigated the effects of alpha-LT on single human, mouse and canine beta-cells. In isolated and combined measurements, alpha-LT, at nanomolar concentrations, induces: (i) rises in cytosolic Ca(2+), into the micromolar range, that are dependent on extracellular Ca(2+); (ii) large conductance non-selective cation channels; and (iii) Ca(2+)-dependent insulin granule exocytosis, measured as increases in membrane capacitance and quantal release of preloaded serotonin.