Preliminary Experience with a Four-Lead Implantable Pulse Generator for Deep Brain Stimulation.

BACKGROUND: Implantable pulse generators (IPGs) store energy and deliver electrical impulses for deep brain stimulation (DBS) to treat neurological and psychiatric disorders. IPGs have evolved over time to meet the demands of expanding clinical indications and more nuanced therapeutic approaches. OBJECTIVES: The aim of this study was to examine the workflow of the first 4-lead IPG for DBS in patients with complex disease. METHOD: The engineering capabilities, clinical use cases, and surgical technique are described in a cohort of 12 patients with epilepsy, essential tremor, Parkinson's disease, mixed tremor, and Tourette's syndrome with comorbid obsessive-compulsive disorder between July 2021 and July 2022. RESULTS: This system is a rechargeable 32-channel, 4-port system with independent current control that can be connected to 8 contact linear or directionally segmented leads. The system is ideal for patients with mixed disease or those with multiple severe symptoms amenable to >2 lead implantations. A multidisciplinary team including neurologists, radiologists, and neurosurgeons is necessary to safely plan the procedure. There were no serious intraoperative or postoperative adverse events. One patient required revision surgery for bowstringing. CONCLUSIONS: This new 4-lead IPG represents an important new tool for DBS surgery with the ability to expand lead implantation paradigms for patients with complex disease.

Canonical Response Parameterization: Quantifying the structure of responses to single-pulse intracranial electrical brain stimulation.

Single-pulse electrical stimulation in the nervous system, often called cortico-cortical evoked potential (CCEP) measurement, is an important technique to understand how brain regions interact with one another. Voltages are measured from implanted electrodes in one brain area while stimulating another with brief current impulses separated by several seconds. Historically, researchers have tried to understand the significance of evoked voltage polyphasic deflections by visual inspection, but no general-purpose tool has emerged to understand their shapes or describe them mathematically. We describe and illustrate a new technique to parameterize brain stimulation data, where voltage response traces are projected into one another using a semi-normalized dot product. The length of timepoints from stimulation included in the dot product is varied to obtain a temporal profile of structural significance, and the peak of the profile uniquely identifies the duration of the response. Using linear kernel PCA, a canonical response shape is obtained over this duration, and then single-trial traces are parameterized as a projection of this canonical shape with a residual term. Such parameterization allows for dissimilar trace shapes from different brain areas to be directly compared by quantifying cross-projection magnitudes, response duration, canonical shape projection amplitudes, signal-to-noise ratios, explained variance, and statistical significance. Artifactual trials are automatically identified by outliers in sub-distributions of cross-projection magnitude, and rejected. This technique, which we call "Canonical Response Parameterization" (CRP) dramatically simplifies the study of CCEP shapes, and may also be applied in a wide range of other settings involving event-triggered data.

Electrical Stimulation of Temporal and Limbic Circuitry Produces Distinct Responses in Human Ventral Temporal Cortex.

The human ventral temporal cortex (VTC) is highly connected to integrate visual perceptual inputs with feedback from cognitive and emotional networks. In this study, we used electrical brain stimulation to understand how different inputs from multiple brain regions drive unique electrophysiological responses in the VTC. We recorded intracranial EEG data in 5 patients (3 female) implanted with intracranial electrodes for epilepsy surgery evaluation. Pairs of electrodes were stimulated with single-pulse electrical stimulation, and corticocortical evoked potential responses were measured at electrodes in the collateral sulcus and lateral occipitotemporal sulcus of the VTC. Using a novel unsupervised machine learning method, we uncovered 2-4 distinct response shapes, termed basis profile curves (BPCs), at each measurement electrode in the 11-500 ms after stimulation interval. Corticocortical evoked potentials of unique shape and high amplitude were elicited following stimulation of several regions and classified into a set of four consensus BPCs across subjects. One of the consensus BPCs was primarily elicited by stimulation of the hippocampus; another by stimulation of the amygdala; a third by stimulation of lateral cortical sites, such as the middle temporal gyrus; and the final one by stimulation of multiple distributed sites. Stimulation also produced sustained high-frequency power decreases and low-frequency power increases that spanned multiple BPC categories. Characterizing distinct shapes in stimulation responses provides a novel description of connectivity to the VTC and reveals significant differences in input from cortical and limbic structures.SIGNIFICANCE STATEMENT Disentangling the numerous input influences on highly connected areas in the brain is a critical step toward understanding how brain networks work together to coordinate human behavior. Single-pulse electrical stimulation is an effective tool to accomplish this goal because the shapes and amplitudes of signals recorded from electrodes are informative of the synaptic physiology of the stimulation-driven inputs. We focused on targets in the ventral temporal cortex, an area strongly implicated in visual object perception. By using a data-driven clustering algorithm, we identified anatomic regions with distinct input connectivity profiles to the ventral temporal cortex. Examining high-frequency power changes revealed possible modulation of excitability at the recording site induced by electrical stimulation of connected regions.

Multimodal approach leads to seizure-freedom in a case of highly refractory drug-resistant focal epilepsy.

Drug-resistant, nonlesional, extratemporal lobe focal epilepsy can be difficult to treat and may require a high degree of multidisciplinary teamwork to localize the seizure onset zone for resective surgery. Here, we describe a patient with longstanding drug-resistant, nonlesional, extratemporal focal epilepsy with a high seizure burden who became seizure-free after prolonged evaluation and eventual left frontal cortical resection. Prior evaluations included magnetoencephalography, invasive video-EEG monitoring, and implantation of a responsive neurostimulation (RNS) device for ongoing intracranial stimulation. Highly sophisticated techniques were utilized including stereotactic localization of prior evaluations to guide repeat stereo-EEG (SEEG), electrical stimulation mapping, SEEG-guided radiofrequency ablation, and awake resection with language and motor mapping using a cognitive testing platform . Incorporating a wide array of data from multiple centers and evaluation time periods was necessary to optimize seizure control and minimize the risk of neurological deficits from surgery.

Invasive neuromodulation for epilepsy: Comparison of multiple approaches from a single center.

BACKGROUND: Drug-resistant epilepsy (DRE) patients not amenable to epilepsy surgery can benefit from neurostimulation. Few data compare different neuromodulation strategies. OBJECTIVE: Compare five invasive neuromodulation strategies for the treatment of DRE: anterior thalamic nuclei deep brain stimulation (ANT-DBS), centromedian thalamic nuclei DBS (CM-DBS), responsive neurostimulation (RNS), chronic subthreshold stimulation (CSS), and vagus nerve stimulation (VNS). METHODS: Single center retrospective review and phone survey for patients implanted with invasive neuromodulation for 2004-2021. RESULTS: N = 159 (ANT-DBS = 38, CM-DBS = 19, RNS = 30, CSS = 32, VNS = 40). Total median seizure reduction (MSR) was 61 % for the entire cohort (IQR 5-90) and in descending order: CSS (85 %), CM-DBS (63 %), ANT-DBS (52 %), RNS (50 %), and VNS (50 %); p = 0.07. The responder rate was 60 % after a median follow-up time of 26 months. Seizure severity, life satisfaction, and quality of sleep were improved. Cortical stimulation (RNS and CSS) was associated with improved seizure reduction compared to subcortical stimulation (ANT-DBS, CM-DBS, and VNS) (67 % vs. 52 %). Effectiveness was similar for focal epilepsy vs. generalized epilepsy, closed-loop vs. open-loop stimulation, pediatric vs. adult cases, and high frequency (>100 Hz) vs. low frequency (<100 Hz) stimulation settings. Delivered charge per hour varied widely across approaches but was not correlated with improved seizure reduction. CONCLUSIONS: Multiple invasive neuromodulation approaches are available to treat DRE, but little evidence compares the approaches. This study used a uniform approach for single-center results and represents an effort to compare neuromodulation approaches.

Safety and Management of Implanted Epilepsy Devices for Imaging and Surgery.

Permanently implanted devices that deliver electrical stimulation are increasingly used to treat patients with drug-resistant epilepsy. Primary care physicians, neurologists, and epilepsy clinicians may encounter patients with a variety of implanted neuromodulation devices in the course of clinical care. Due to the rapidly changing landscape of available epilepsy-related neurostimulators, there may be uncertainty related to how these devices should be handled during imaging procedures and perioperative care. We review the safety and management of epilepsy-related implanted neurostimulators that may be encountered during imaging and surgery. We provide a summary of approved device labeling and recommendations for the practical management of these devices to help guide clinicians as they care for patients treated with bioelectronic medicine.

Case Report: Prolonged Effects of Short-Term Transcranial Magnetic Stimulation on EEG Biomarkers, Spectral Power, and Seizure Frequency.

Transcranial magnetic stimulation (TMS) is a non-invasive modality of focal brain stimulation in which a fluctuating magnetic field induces electrical currents within the cortex. It remains unclear to what extent TMS alters EEG biomarkers and how EEG biomarkers may guide treatment of focal epilepsy. We present a case of a 48-year-old man with focal epilepsy, refractory to multiple medication trials, who experienced a dramatic reduction in seizures after targeting the area of seizure onset within the left parietal-occipital region with low-frequency repetitive TMS (rTMS). Prior to treatment, he experienced focal seizures that impacted cognition including apraxia at least 50-60 times daily. MRI of the brain showed a large focal cortical dysplasia with contrast enhancement involving the left occipital-parietal junction. Stimulation for 5 consecutive days was well-tolerated and associated with a day-by-day reduction in seizure frequency. In addition, he was monitored with continuous video EEG, which showed continued and progressive changes in spectral power (decreased broadband power and increased infraslow delta activity) and a gradual reduction in seizure frequency and duration. One month after initial treatment, 2-day ambulatory EEG demonstrated seizure-freedom and MRI showed resolution of focal contrast enhancement. He continues to receive 2-3 days of rTMS every 2-4 months. He was seizure-free for 6 months, and at last follow-up of 17 months was experiencing auras approximately every 2 weeks without progression to disabling seizures. This case demonstrates that rTMS can be a well-tolerated and effective means of controlling medication-refractory seizures, and that EEG biomarkers change gradually in a fashion in association with seizure frequency. TMS influences cortical excitability, is a promising non-invasive means of treating focal epilepsy, and has measurable electrophysiologic effects.