Beyond seizure freedom: Dissecting long-term seizure control after surgical resection for drug-resistant epilepsy.

OBJECTIVE: This study was undertaken to better understand the long-term palliative and disease-modifying effects of surgical resection beyond seizure freedom, including frequency reduction and both late recurrence and remission, in patients with drug-resistant epilepsy. METHODS: This retrospective database-driven cohort study included all patients with >9 years of follow-up at a single high-volume epilepsy center. We included patients who underwent lobectomy, multilobar resection, or lesionectomies for drug-resistant epilepsy; we excluded patients who underwent hemispherectomies. Our main outcomes were (1) reduction in frequency of disabling seizures (at 6 months, each year up to 9 years postoperatively, and at last follow-up), (2) achievement of seizure remission (>6 months, >1 year, and longest duration), and (3) seizure freedom at last follow-up. RESULTS: We included 251 patients; 234 (93.2%) achieved 6 months and 232 (92.4%) experienced 1 year of seizure freedom. Of these, the average period of seizure freedom was 10.3 years. A total of 182 (72.5%) patients were seizure-free at last follow-up (defined as >1 year without seizures), with a median 11.9 years since remission. For patients not completely seizure-free, the mean seizure frequency reduction at each time point was 76.2%, and ranged from 66.6% to 85.0%. Patients decreased their number of antiseizure medications on average by .58, and 53 (21.2%) patients were on no antiseizure medication at last follow-up. Nearly half (47.1%) of those seizure-free at last follow-up were not seizure-free immediately postoperatively. SIGNIFICANCE: Patients who continue to have seizures after resection often have considerable reductions in seizure frequency, and many are able to achieve seizure freedom in a delayed manner.

Cognitive phenotypes in frontal lobe epilepsy.

OBJECTIVE: Neuropsychological profiles are heterogeneous both across and within epilepsy syndromes, but especially in frontal lobe epilepsy (FLE), which has complex semiology and epileptogenicity. This study aimed to characterize the cognitive heterogeneity within FLE by identifying cognitive phenotypes and determining their demographic and clinical characteristics. METHOD: One hundred and six patients (age 16-66; 44% female) with FLE completed comprehensive neuropsychological testing, including measures within five cognitive domains: language, attention, executive function, processing speed, and verbal/visual learning. Patients were categorized into one of four phenotypes based on the number of impaired domains. Patterns of domain impairment and clinical and demographic characteristics were examined across phenotypes. RESULTS: Twenty-five percent of patients met criteria for the Generalized Phenotype (impairment in at least four domains), 20% met criteria for the Tri-Domain Phenotype (impairment in three domains), 36% met criteria for the Domain-Specific Phenotype (impairment in one or two domains), and 19% met criteria for the Intact Phenotype (no impairment). Language was the most common domain-specific impairment, followed by attention, executive function, and processing speed. In contrast, learning was the least impacted cognitive domain. The Generalized Phenotype had fewer years of education compared to the Intact Phenotype, but otherwise, there was no differentiation between phenotypes in demographic and clinical variables. However, qualitative analysis suggested that the Generalized and Tri-Domain Phenotypes had a more widespread area of epileptogenicity, whereas the Intact Phenotype most frequently had seizures limited to the lateral frontal region. SIGNIFICANCE: This study identified four cognitive phenotypes in FLE that were largely indistinguishable in clinical and demographic features, aside from education and extent of epileptogenic zone. These findings enhance our appreciation of the cognitive heterogeneity within FLE and provide additional support for the development and use of cognitive taxonomies in epilepsy.

Subthalamic Nucleus Activity Influences Sensory and Motor Cortex during Force Transduction.

The subthalamic nucleus (STN) is proposed to participate in pausing, or alternately, in dynamic scaling of behavioral responses, roles that have conflicting implications for understanding STN function in the context of deep brain stimulation (DBS) therapy. To examine the nature of event-related STN activity and subthalamic-cortical dynamics, we performed primary motor and somatosensory electrocorticography while subjects (n = 10) performed a grip force task during DBS implantation surgery. Phase-locking analyses demonstrated periods of STN-cortical coherence that bracketed force transduction, in both beta and gamma ranges. Event-related causality measures demonstrated that both STN beta and gamma activity predicted motor cortical beta and gamma activity not only during force generation but also prior to movement onset. These findings are consistent with the idea that the STN participates in motor planning, in addition to the modulation of ongoing movement. We also demonstrated bidirectional information flow between the STN and somatosensory cortex in both beta and gamma range frequencies, suggesting robust STN participation in somatosensory integration. In fact, interactions in beta activity between the STN and somatosensory cortex, and not between STN and motor cortex, predicted PD symptom severity. Thus, the STN contributes to multiple aspects of sensorimotor behavior dynamically across time.

Dynamics of human subthalamic neuron phase-locking to motor and sensory cortical oscillations during movement.

Coupled oscillatory activity recorded between sensorimotor regions of the basal ganglia-thalamocortical loop is thought to reflect information transfer relevant to movement. A neuronal firing-rate model of basal ganglia-thalamocortical circuitry, however, has dominated thinking about basal ganglia function for the past three decades, without knowledge of the relationship between basal ganglia single neuron firing and cortical population activity during movement itself. We recorded activity from 34 subthalamic nucleus (STN) neurons, simultaneously with cortical local field potentials and motor output, in 11 subjects with Parkinson's disease (PD) undergoing awake deep brain stimulator lead placement. STN firing demonstrated phase synchronization to both low- and high-beta-frequency cortical oscillations, and to the amplitude envelope of gamma oscillations, in motor cortex. We found that during movement, the magnitude of this synchronization was dynamically modulated in a phase-frequency-specific manner. Importantly, we found that phase synchronization was not correlated with changes in neuronal firing rate. Furthermore, we found that these relationships were not exclusive to motor cortex, because STN firing also demonstrated phase synchronization to both premotor and sensory cortex. The data indicate that models of basal ganglia function ultimately will need to account for the activity of populations of STN neurons that are bound in distinct functional networks with both motor and sensory cortices and code for movement parameters independent of changes in firing rate.NEW & NOTEWORTHY Current models of basal ganglia-thalamocortical networks do not adequately explain simple motor functions, let alone dysfunction in movement disorders. Our findings provide data that inform models of human basal ganglia function by demonstrating how movement is encoded by networks of subthalamic nucleus (STN) neurons via dynamic phase synchronization with cortex. The data also demonstrate, for the first time in humans, a mechanism through which the premotor and sensory cortices are functionally connected to the STN.

Movement-related dynamics of cortical oscillations in Parkinson's disease and essential tremor.

Recent electrocorticography data have demonstrated excessive coupling of beta-phase to gamma-amplitude in primary motor cortex and that deep brain stimulation facilitates motor improvement by decreasing baseline phase-amplitude coupling. However, both the dynamic modulation of phase-amplitude coupling during movement and the general cortical neurophysiology of other movement disorders, such as essential tremor, are relatively unexplored. To clarify the relationship of these interactions in cortical oscillatory activity to movement and disease state, we recorded local field potentials from hand sensorimotor cortex using subdural electrocorticography during a visually cued, incentivized handgrip task in subjects with Parkinson's disease (n = 11), with essential tremor (n = 9) and without a movement disorder (n = 6). We demonstrate that abnormal coupling of the phase of low frequency oscillations to the amplitude of gamma oscillations is not specific to Parkinson's disease, but also occurs in essential tremor, most prominently for the coupling of alpha to gamma oscillations. Movement kinematics were not significantly different between these groups, allowing us to show for the first time that robust alpha and beta desynchronization is a shared feature of sensorimotor cortical activity in Parkinson's disease and essential tremor, with the greatest high-beta desynchronization occurring in Parkinson's disease and the greatest alpha desynchronization occurring in essential tremor. We also show that the spatial extent of cortical phase-amplitude decoupling during movement is much greater in subjects with Parkinson's disease and essential tremor than in subjects without a movement disorder. These findings suggest that subjects with Parkinson's disease and essential tremor can produce movements that are kinematically similar to those of subjects without a movement disorder by reducing excess sensorimotor cortical phase-amplitude coupling that is characteristic of these diseases.

Three-dimensional localization of cortical electrodes in deep brain stimulation surgery from intraoperative fluoroscopy.

Electrophysiological recordings from subdural electrocorticography (ECoG) electrodes implanted temporarily during deep brain stimulation (DBS) surgeries offer a unique opportunity to record cortical activity for research purposes. The optimal utilization of this important research method relies on accurate and robust localization of ECoG electrodes, and intraoperative fluoroscopy is often the only imaging modality available to visualize electrode locations. However, the localization of a three-dimensional electrode position using a two-dimensional fluoroscopic image is problematic due to the lost dimension orthogonal to the fluoroscopic image, a parallax distortion implicit to fluoroscopy, and variability of visible skull contour among fluoroscopic images. Here, we present a method to project electrodes visible on the fluoroscopic image onto a reconstructed cortical surface by leveraging numerous common landmarks to translate, rotate, and scale coregistered computed tomography (CT) and magnetic resonance imaging (MRI) reconstructed surfaces in order to recreate the coordinate framework in which the fluoroscopic image was acquired, while accounting for parallax distortion. Validation of this approach demonstrated high precision with an average total Euclidian distance between three independent reviewers of 1.65±0.68mm across 8 patients and 82 electrodes. Spatial accuracy was confirmed by correspondence between recorded neural activity over sensorimotor cortex during hand movement. This semi-automated interface reliably estimates the location of temporarily implanted subdural ECoG electrodes visible on intraoperative fluoroscopy to a cortical surface.

Network effects of deep brain stimulation.

The ability to differentially alter specific brain functions via deep brain stimulation (DBS) represents a monumental advance in clinical neuroscience, as well as within medicine as a whole. Despite the efficacy of DBS in the treatment of movement disorders, for which it is often the gold-standard therapy when medical management becomes inadequate, the mechanisms through which DBS in various brain targets produces therapeutic effects is still not well understood. This limited knowledge is a barrier to improving efficacy and reducing side effects in clinical brain stimulation. A field of study related to assessing the network effects of DBS is gradually emerging that promises to reveal aspects of the underlying pathophysiology of various brain disorders and their response to DBS that will be critical to advancing the field. This review summarizes the nascent literature related to network effects of DBS measured by cerebral blood flow and metabolic imaging, functional imaging, and electrophysiology (scalp and intracranial electroencephalography and magnetoencephalography) in order to establish a framework for future studies.

Disconnective hemispherotomy: technique and operative highlights.

Hemispherectomy is an effective procedure used in the treatment of drug-resistant hemispheric epilepsy, especially in the pediatric population. A number of resective and disconnective techniques are used, and selection of surgical strategy is paramount to achieving successful results. Notably, disconnective (or functional) hemispherotomy maximizes the benefits of safe, surgical disconnection while minimizing hemispheric tissue resection, thereby avoiding some of the perioperative factors contributing to morbidity in traditional anatomical hemispherectomy procedures. In this video, the authors outline the principal surgical steps of disconnective hemispherotomy and highlight important technical factors leading to optimal outcomes in patients with refractory, oftentimes catastrophic, hemispheric epilepsy. The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID2436.

Refractory inflammatory hydrocephalus: A case report of a rare and complicated delayed sequelae following cerebral hemispherectomy surgery for epilepsy.

Hydrocephalus is a known complication following surgical resection of a cerebral hemisphere for refractory epilepsy, yet the pathological mechanism remains poorly understood. We present a case of refractory aseptic inflammatory hydrocephalus following cerebral hemispherectomy surgery for refractory epilepsy treated with a combination of cerebral spinal fluid (CSF) diversion and immunosuppression via IL-1 receptor agonist, Anakinra. At 6 month follow up, the patient had returned to neurologic baseline, with improvement in school and physical therapy performance. Further investigation into the beneficial role of immunosuppressive therapy is needed to better understand the relationship between neuro-inflammation and improving outcomes following epilepsy surgery.

Loss of Efficacy in Ventral Intermediate Nucleus Stimulation for Essential Tremor.

OBJECTIVE: The primary aim of this study is to report long-term outcomes associated with deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) performed at our institution. We further aimed to elicit the factors associated with loss of efficacy and to discuss the need for exploring and establishing reliable rescue targets. METHODS: To study long-term outcomes, we performed a retrospective chart review and extracted tremor scores of 43 patients who underwent VIM DBS lead implantation for essential tremor at our center. We further evaluated factors that could influence outcomes over time, including demographics, body mass index, duration of follow-up, degree of parenchymal atrophy indexed by the global cortical atrophy scale, and third ventricular width. RESULTS: In this cohort, tremor scores on the latest follow-up (median 52.7 months) were noted to be worse than initial postoperative scores in 56% of DBS leads. Furthermore, 14% of leads were associated with clinically significant loss of benefit. Factors including the length of time since the lead implantation, age at the time of surgery, sex, body mass index, preoperative atrophy, and third ventricular width were not predictive of long-term outcomes. CONCLUSIONS: Our study identified a substantial subgroup of VIM-DBS patient who experienced a gradual decline in treatment efficacy over time. We propose that this phenomenon can be attributed primarily to habituation and disease progression. Furthermore, we discuss the need to establish reliable and effective rescue targets for this subpopulation of patients, with ventral-oralis complex and dentate nucleus emerging as potential candidates.

The Rate and Risk Factors of Deep Brain Stimulation-Associated Complications: A Single-Center Experience.

BACKGROUND AND OBJECTIVES: Deep brain stimulation (DBS) is an established neurosurgical treatment of a variety of neurological disorders. DBS is considered a safe and effective neurosurgical procedure; however, surgical complications are inevitable, and clinical outcomes may vary. The aim of this study was to describe DBS complications at a large clinical center in the United States and to investigate the relationship between patients' baseline characteristics, surgical technique, and operative complications. METHODS: We identified all patients who underwent DBS lead implantation at our center between 1st January 2012 and 1st January 2020. We extracted relevant information regarding patient demographics, surgical details, clinical complications, and clinical outcomes from the electronic medical records. RESULTS: A total of 859 leads were implanted in 481 patients (153 men, 328 women). The mean patient age at the time of the surgery was 65 years, with the mean disease duration of 13.3 years. There were no mortalities and 57 readmissions within 30 days (mean = 14.2 days). The most common complications included pneumocephalus (n = 661), edema (n = 78), altered mental state (n = 35), implantable pulse generator discomfort (n = 34), hemorrhage (n = 26), and infection (n = 23). Most notably, the use of general anesthesia, hypertension, heart disease, and depression were associated with significantly longer postoperative stay. High preoperative body mass index was associated with higher rates of surgery-related infections and lead revision/explantation. The intraoperative mean arterial pressure, anesthesia type, and frame apparatus were all important predictors of postoperative pneumocephalus. CONCLUSION: In this report, we described the rates and types of complications associated with DBS surgery at a large neurosurgical center in the United States. The novel insights highlighted in this study present an opportunity to further improve the clinical outcomes and patient selection in DBS surgery.

The impact of skull thickness on pediatric stereoencephalography electrode implantation and technical considerations.

OBJECTIVE: One consideration in pediatric stereoencephalography (SEEG) is decreased skull thicknesses compared with adults, which may limit traditional bolt-based anchoring of electrodes. The authors aimed to investigate the safety profile, complication rates, and technical adaptations of placing SEEG electrodes in pediatric patients. METHODS: The authors retrospectively reviewed all patients aged 12 years or younger at the time of SEEG implantation at their institution. Postimplantation CT scans were used to measure skull thickness at the entry point of each SEEG lead. Postimplantation lead accuracy was also assessed. RESULTS: Fifty-three patients were reviewed. The median skull thickness was 4.1 (interquartile range [IQR] 3.15-5.2) mm. There were 5 total complications: 1 retained bolt fragment, 3 asymptomatic subdural hematomas, and 1 asymptomatic intracranial hemorrhage. Median radial error from the lead target was 3.5 (IQR 2.24-5.25) mm. Linear regression analysis revealed that increasing skull thickness decreased the deviation from the intended target, implying an improved accuracy to target at thicker skull entry points; this trended towards improved accuracy, but did not achieve statistical significance (p = 0.54). CONCLUSIONS: This study found a 1.9% hardware complication rate and a 9.4% asymptomatic hemorrhage rate. Suturing electrodes to the scalp may represent a reasonable option if there are concerns of young age or a thin skull. These data indicate that invasive SEEG evaluation is safe among patients 12 years old or younger.

Novel Use of the Aurora Surgiscope System for Minimally Invasive Resection of Intraparenchymal Lesions: A Case Series.

BACKGROUND: Minimally invasive surgery (MIS) for intracranial pathology minimizes surgical morbidity but can come at the cost of operator ergonomics and technical surgical success. Here, the authors present a case series to report the first use of a novel 15-mm tubular retraction system with integrated lighting and visualization capabilities for MIS access to intracranial lesions. OBJECTIVE: To demonstrate feasibility and effectiveness of the 15-mm Aurora Surgiscope (Integra Lifesciences) for intracranial MIS approaches. METHODS: The 15-mm Aurora Surgiscope facilitated MIS approach to gain access to intraparenchymal pathologies. The device consists of a tubular access system with integrated light source and a reusable control unit that modifies video parameters. The port was inserted along a preplanned trajectory through a mini-craniotomy. Bimanual access allowed the surgeon to comfortably dissect/resect lesional tissue using high-quality video. RESULTS: Four patients are presented. In cases 1 and 2, the authors evacuated acute intracerebral hemorrhages. Both had <15 cc hemorrhage with improved or stable neurological examination. In case 3, the authors performed gross total resection of a cerebellar pilocytic astrocytoma. In case 4, the authors resected a mesial posterior temporal cavernoma. No perioperative/technical complications were noted. CONCLUSION: The Aurora Surgiscope system is a novel integrated tubular retraction, lighting, and visualization system that allows access to a wide variety of pathologies using a MIS approach. The Surgiscope allows the surgeon to use bimanual dexterity through a small access port while limiting the need for additional equipment such as microscope, exoscope, or endoscope.

Seizure Outcomes and Reoperation in Surgical Rasmussen Encephalitis Patients.

BACKGROUND: Rasmussen encephalitis (RE) is a rare inflammatory disease affecting one hemisphere, causing progressive neurological deficits and intractable seizures. OBJECTIVE: To report long-term seizure outcomes, reoperations, and functional outcomes in patients with RE who underwent hemispherectomy at our institution. METHODS: Retrospective review was performed for all patients with RE who had surgery between 1998 and 2020. We collected seizure history, postoperative outcomes, and functional data. Imaging was independently reviewed in a blinded fashion by 2 neurosurgeons and a neuroradiologist. RESULTS: We analyzed 30 patients with RE who underwent 35 hemispherectomies (5 reoperations). Using Kaplan-Meier analysis, seizure-freedom rate was 81.5%, 63.6%, and 55.6% at 1, 5, and 10 years after surgery, respectively. Patients with shorter duration of hemiparesis preoperatively were less likely to be seizure-free at follow-up (P = .011) and more likely to undergo reoperation (P = .004). Shorter duration of epilepsy (P = .026) and preoperative bilateral MRI abnormalities (P = .011) were associated with increased risk of reoperation. Complete disconnection of diseased hemisphere on postoperative MRI after the first operation improved seizure-freedom (P = .021) and resulted in fewer reoperations (P = .034), and reoperation resulted in seizure freedom in every case. CONCLUSION: Obtaining complete disconnection is critical for favorable seizure outcomes from hemispherectomy, and neurosurgeons should have a low threshold to reoperate in patients with RE with recurrent seizures. Rapid progression of motor deficits and bilateral MRI abnormalities may indicate a subpopulation of patients with RE with increased risk of needing reoperation. Overall, we believe that hemispherectomy is a curative surgery for the majority of patients with RE, with excellent long-term seizure outcome.

Robot-Assisted Stereoelectroencephalography: 2-Dimensional Operative Video.

Invasive neuromonitoring is an important component of presurgical workup and seizure onset zone localization in patients with epilepsy being considered for surgical resection. In the United States, intraparenchymal stereoelectroencephalography (SEEG) electrodes have been replacing subdural grid electrodes for most cases, following a trend that has already matured in Europe. The use of robotic assistance has been shown to improve operative times and accuracy in SEEG electrode placement, as users benefit from the embedded planning software as well as the efficiency and accuracy of the robotic arm. The greatest barriers to implementation of this technology are the upfront cost and learning curve. This case-based surgeon's perspective operative video could benefit those considering incorporating robotic assistance for SEEG electrode placement. Those considering robotic assistance for pedicle screw placement and other budding applications may also benefit, as well as innovators looking for new applications. The patient consented for the procedure, video recording, and inclusion in subsequent publications.

Neuropsychological outcomes after thalamic deep brain stimulation for essential tremor.

INTRODUCTION: Non-motor DBS outcomes have received little attention in ET relative to PD. This study examines neuropsychological outcomes in ET following thalamic VIM DBS. METHODS: Fifty patients completed neuropsychological evaluations preoperatively and approximately seven months postoperatively. Cognition and mood changes were analyzed at the group level and individual level. Additional associations with treatment, disease, and demographic characteristics were assessed. RESULTS: Significant cognitive decline was not observed at the group level. At the individual level, 46% of patients demonstrated at least subtle overall cognitive decline (≥1SD on at least one test within at least two domains). Mild decline (≥1SD) was seen in 10%-29.17% of patients on individual tests across all cognitive domains, with highest rates in verbal memory. Substantial cognitive decline (≥2SD) occurred in less than 9% of the sample across all tests. Factors related to cognitive decline included higher DBS parameter settings, older age of ET onset, intracranial complications, and inability to reduce ET medications postoperatively. Depression and anxiety did not change when accounting for questionnaire items that could be falsely elevated by tremor. CONCLUSION: Substantial cognitive decline after VIM DBS is rare in patients with ET. However, subtle decrements can occur across cognitive domains and particularly in verbal memory. DBS parameter settings may relate to cognitive decline. Further research is needed to better understand possible associations with electrode lateralization and other variables that could also relate to disease progression and test-retest effects. Symptoms of depression and anxiety remain stable.

ResectVol: A tool to automatically segment and characterize lacunas in brain images.

OBJECTIVE: To assess and validate the performance of a new tool developed for segmenting and characterizing lacunas in postoperative MR images of epilepsy patients. METHODS: A MATLAB-based pipeline was implemented using SPM12 to produce the 3D mask of the surgical lacuna and estimate its volume. To validate its performance, we compared the manual and automatic lacuna segmentations obtained from 51 MRI scans of epilepsy patients who underwent temporal lobe resections. RESULTS: The code is consolidated as a tool named ResectVol, which can be run via a graphical user interface or command line. The automatic and manual segmentation comparison resulted in a median Dice similarity coefficient of 0.77 (interquartile range: 0.71-0.81). SIGNIFICANCE: Epilepsy surgery is the treatment of choice for pharmacoresistant focal epilepsies, and despite the extensive literature on the subject, we still cannot predict surgical outcomes accurately. As the volume and location of the resected tissue are fundamentally relevant to this prediction, researchers commonly perform a manual segmentation of the lacuna, which presents human bias and does not provide detailed information about the structures removed. In this study, we introduce ResectVol, a user-friendly, fully automatic tool to accomplish these tasks. This capability enables more advanced analytical techniques applied to surgical outcomes prediction, such as machine-learning algorithms, by facilitating coregistration of the resected area and preoperative findings with other imaging modalities such as PET, SPECT, and functional MRI ResectVol is freely available at https://www.lniunicamp.com/resectvol.

Delayed Development of Spinal Subdural Hematoma Following Cranial Trauma: A Case Report and Review of the Literature.

BACKGROUND: Spinal subdural hematomas (SDHs) have been reported secondary to direct trauma or iatrogenic causes associated with coagulopathies. Spinal SDHs found after the development of acute intracranial SDHs, without any evidence of trauma to the spine, are extremely rare. In addition to this rare presentation, there is a lack of consensus regarding whether surgical decompression is the ideal treatment strategy. Depending on the extent of SDH within the spinal canal, surgical decompression may be difficult where diffuse hematoma within the intradural space requires multilevel decompression for treatment. CASE DESCRIPTION: A 46-year-old man initially presented with an acute cranial SDH following isolated head trauma. After a period of full recovery, he developed delayed lower extremity paraparesis secondary to the formation of a thoracolumbar SDH. This hematoma coincided with resolution of the cranial SDH and likely was due to redistribution of blood from the cranial subdural space into the spinal canal. Given the diffuse multilevel nature of the spread of hematoma and lack of a focal area of compression, he was managed conservatively. He demonstrated small signs of neurologic improvement over several days and regained considerable strength over the following several weeks. CONCLUSIONS: This report demonstrates a very rare occurrence of a traumatic intracranial SDH migrating into the thoracic and lumbar spine. This case also highlights that despite acute neurologic deficits, conservative management may be a feasible strategy that can result in recovery of neurologic function.

Effects of hippocampal low-frequency stimulation in idiopathic non-human primate epilepsy assessed via a remote-sensing-enabled neurostimulator.

Individuals with pharmacoresistant epilepsy remain a large and under-treated patient population. Continued technologic advancements in implantable neurostimulators have spurred considerable research efforts directed towards the development of novel antiepileptic stimulation therapies. However, the lack of adequate preclinical experimental platforms has precluded a detailed understanding of the differential effects of stimulation parameters on neuronal activity within seizure networks. In order to chronically monitor seizures and the effects of stimulation in a freely-behaving non-human primate with idiopathic epilepsy, we employed a novel simultaneous video-intracranial EEG recording platform using a state-of-the-art sensing-enabled, rechargeable clinical neurostimulator with real-time seizure detection and wireless data streaming capabilities. Using this platform, we were able to characterize the electrographic and semiologic features of the focal-onset, secondarily generalizing tonic-clonic seizures stably expressed in this animal. A series of acute experiments exploring low-frequency (2Hz) hippocampal stimulation identified a pulse width (150µs) and current amplitude (4mA) combination which maximally suppressed local hippocampal activity. These optimized stimulation parameters were then delivered to the seizure onset-side hippocampus in a series of chronic experiments. This long-term testing revealed that the suppressive effects of low-frequency hippocampal stimulation 1) diminish when delivered continuously but are maintained when stimulation is cycled on and off, 2) are dependent on circadian rhythms, and 3) do not necessarily confer seizure protective effects.

High frequency activation data used to validate localization of cortical electrodes during surgery for deep brain stimulation.

Movement related synchronization of high frequency activity (HFA, 76-100 Hz) is a somatotopic process with spectral power changes occurring during movement in the sensorimotor cortex (Miller et al., 2007) [1]. These features allowed movement-related changes in HFA to be used to functionally validate the estimations of subdural electrode locations, which may be placed temporarily for research in deep brain stimulation surgery, using the novel tool described in Randazzo et al. (2015) [2]. We recorded electrocorticography (ECoG) signals and localized electrodes in the region of the sensorimotor cortex during an externally cued hand grip task in 8 subjects. Movement related HFA was determined for each trial by comparing HFA spectral power during movement epochs to pre-movement baseline epochs. Significant movement related HFA was found to be focal in time and space, occurring only during movement and only in a subset of electrodes localized to the pre- and post-central gyri near the hand knob. To further demonstrate the use of movement related HFA to aid electrode localization, we provide a sample of the electrode localization tool, with data loaded to allow readers to map movement related HFA onto the cortical surface of a sample patient.