Ince, Nuri F.

Understanding motor representation in the human brain requires mapping beyond the primary motor cortex, into the distributed networks that coordinate complex movements. The insular cortex, a multifunctional hub buried within the Sylvian fissure, has been implicated in motor control through clinical observations and neuroimaging. Yet its precise relation to primary sensorimotor processing remains one of the least understood aspects of motor neurophysiology. To address this gap, we quantified electrophysiological changes from implanted depth electrodes in patients performing simple movement tasks combined with single-pulse electrical stimulation (SPES) to map effective connectivity. The movement data reveal somatotopically specific representation bilaterally, as well as intereffector regions that are active for different movement types. Hand representation is centered along the contralateral ventral aspect of the middle and posterior short gyri bilaterally, while tongue/mouth tuned sites cluster in the dorsal posterior short gyrus and the dorsal long gyri. Insular activity temporally follows the primary motor cortex (M1) and precedes movement onset. SPES revealed somatotopically specific connectivity between corresponding sites in M1 and insula (hand-to-hand, tongue-to-tongue) and between bilateral insulae. These observations establish that somatotopy is a conserved property of distributed motor control incorporating the insular representations and connectivity.

ABSTRACT Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) can reduce seizures in patients with drug-resistant epilepsy. However, seizure freedom is rare, and there is no early response biomarker to predict long-term seizure suppression. To evaluate a short-term biomarker of therapeutic response to DBS, we studied 18-minute trials of ANT stimulation in patients with drug-resistant epilepsy undergoing intracranial electroencephalography. We compared a standard high-frequency periodic versus a non-periodic pulse pattern. We found that short-term ANT stimulation within the clinically used amplitude range preferentially altered the first 150 ms of anterograde ANT to anterior cingulate and superior frontal connectivity. Non-periodic ANT stimulation selectively modified early cortico-cortical evoked potentials more than periodic stimulation, and these changes were driven by the response phase. These pattern-specific changes in connectivity between the ANT and spatially restricted cortical areas suggest differing mechanisms and are a promising biomarker for patients being treated with ANT-DBS.

Abstract INTRODUCTION Preserving language during tumor resection is critical but challenged by the time-intensive, complex nature of direct electrical stimulation (DES). High-gamma electrocorticography (ECoG) captures real-time, task-induced cortical responses, yet its spatiotemporal concordance with DES across language tasks remains underexplored. OBJECTIVE To evaluate how early and late high-gamma ECoG responses align with DES across auditory, object, action, and descriptive naming tasks. METHODS Seventeen patients (14 gliomas, 3 metastases) underwent awake craniotomy. ECoG was recorded, and bipolar DES was applied on the same subdural grid across the four tasks using adjacent contacts. Early (100–200 ms) and late (>200 ms) high-gamma activity (30–150 Hz) and DES-positive sites were co-registered with a standard MNI-152 brain. The spatial overlap was quantified using Dice-Sørensen (D-S) coefficients with accuracy assessed by ECoG–DES contact proximity (exact/adjacent, <1 cm) across tumor, peritumoral (<2 cm), and whole-grid ROIs. Patient language outcomes were determined from longitudinal neurologic exams. RESULTS DES-positive sites were identified in 15/17 (88%) patients, primarily during auditory and action naming. Auditory naming elicited gamma activity in all patients, with early and late responses, reflecting sensory and extended semantic processes, observed in 10/17(59%) cases, showing strong concordance with DES (early: D-S= 0.63, 95% CI: 0.51–0.74; early + late: D-S = 0.66, 95% CI: 0.54–0.77). Non-auditory tasks showed predominantly late gamma responses, with modest DES overlap (object: D-S= 0.34; action: D-S= 0.42; descriptive: D-S= 0.37) suggesting border distributed cortical networks. Accuracy in all tasks ranged from 76–95% within the whole grid; auditory naming achieved 83% sensitivity and 82% specificity in peritumoral ROI. At 6 months, 14/17 (82%) patients had no speech deficits; 8/9 with preoperative deficits improved while 2 had a new deficit. CONCLUSION Gamma activity during auditory naming reliably predicts DES-defined language eloquence for safe maximal resection of brain tumors.

Abstract BACKGROUND Intraoperative electrocorticography (ECoG) may aid localization of language function and help guide eloquent brain tumor resection. However, relevance of ECoG findings to language outcomes remains unclear. METHODS Fifteen patients with brain tumors (Mdn age=60; 67% high-grade glioma) underwent awake craniotomy and intraoperative language mapping. Time-frequency ECoG gamma activity was visualized in real-time followed by direct electrical stimulation (DES) across 3 paradigms (NeuroMapper Tasks: Object, Action, Auditory). Early and late ECoG gamma modulations and positive DES sites were co-registered with postoperative MRI. A subset (N=11) completed expressive language testing (Phonemic and Semantic Fluency, Confrontation Naming) prior to and <2 months following surgery. Correlational analyses and Mann-Whitney U tests examined relationships between test results and surgical impact upon expressive task-elicited gamma activity (Object and Action Naming). RESULTS Across tasks, positive DES sites were identified in 93% of cases (Auditory, 73%; Action, 71%, Object, 57%). No positive DES sites were resected. Early and/or late gamma activations were elicited in all patients, resected in 40%, and within 1 cm of surgical impact in 90%. Four patients (36%) showed reliable decline on at least 1 outcome, which was associated with Action Naming activity <1 cm of surgical impact (phi=.67, p=.035). On individual tests, Confrontation Naming and Phonemic Fluency decline were rare (9% and 18%), though Semantic Fluency declined in 36% of patients. Change in Semantic Fluency was associated with resection of Object Naming gamma sites (Z=-1.83, p=.044) and presence of Action Naming gamma features near surgical impact (Z=-2.25, p=.014). CONCLUSIONS Despite preservation DES sites and sparing of basic confrontation naming ability, verbal fluency declined in a substantial group of patients. Decline was associated with gamma features resected or near surgical impact. While preliminary, findings suggest task-based ECoG can augment DES in informing risk of surgically-acquired language decline.

This study reveals how EEG burst activity changes with progressive hypoxia, offering insights into its neural correlates. Increased burst features in specific frequency bands correlate strongly with physiological, such as decreasing peripheral oxygen, task performance, such as declining accuracy, and symptom measures, such as increasing report rate. Our findings characterize a neural signature with potential use for real-time EEG monitoring to enhance hypoxia detection in aviation, potentially improving flight safety.

Abstract Deep brain stimulation (DBS) is a targeted manipulation of brain circuitry to treat neurological and neuropsychiatric conditions. Optimal DBS lead placement is essential for treatment efficacy. Current targeting practice is based on preoperative and intraoperative brain imaging, intraoperative electrophysiology, and stimulation mapping. Electrophysiological mapping using extracellular microelectrode recordings aids in identifying functional subdomains, anatomical boundaries, and disease-correlated physiology. The shape of single-unit action potentials may differ due to different biophysical properties between cell-types and brain regions. Here, we describe a technique to parameterize the structure and duration of sorted spike units using a novel algorithmic approach based on canonical response parameterization, and illustrate how it may be used on DBS microelectrode recordings. Isolated spike shapes are parameterized then compared using a spike similarity metric and grouped by hierarchical clustering. When spike morphology is associated with anatomy, we find regional clustering in the human globus pallidus. This method is widely applicable for spike removal and single-unit characterization and could be integrated into intraoperative array-based technologies to enhance targeting and clinical outcomes in DBS lead placement. Author summary We developed a new algorithmic approach to capture the structure of single neuron electrophysiology from microelectrode recordings during deep brain stimulation surgery. This method has broad applications for spike characterization, clustering, removal from the background field potential, and comparison across recording sites. Using this technique, we illustrate regional clustering of spike morphologies in the human globus pallidus.

Abstract BACKGROUND As an adjunct to direct electrical stimulation (DES), intraoperative electrocorticography (ECoG) can aid detection of language-eloquent cortex. However, it is unclear how surgical impact upon mapping findings relates to cognitive-linguistic outcomes. METHODS Ten patients underwent awake craniotomy for tumor resection with ECoG and DES language mapping. Mapping utilized iPad stimulus presentation coupled to an electrode array capable of both recording ECoG activity and delivering DES. Time-frequency gamma band activations were visualized (Early, Long, Late, Double Peak) for 3 naming paradigms (Object, Action, Auditory). DES was also conducted for each task. Mapping results were overlayed on postoperative MRI to examine proximity to parenchymal trauma (cavity, sulcal displacement). Patients completed cognitive-linguistic testing [WAB-R (N=3) or Neuropsychological Assessment (N=7)] prior to surgery and <2 months postoperatively. Patients with persisting aphasia at 6-month follow-up were also identified. RESULTS Postoperative language decline was found in 50% of patients, with 30% showing worsening (>1SD) in Naming and Phonemic Fluency, and 60% in Semantic Fluency. Surgery impacted ECoG features in 60% of patients and DES arrest sites in 30%. A trend was observed where Early and Late Object naming ECoG features were associated with Semantic Fluency decline [rpb(5)=-.69, p=.067]. Arrest during Auditory naming DES <1 cm of surgical effect was associated with decline in Abstraction [rpb(5)=-.83, p=.042; FET, p=.029] and Semantic Fluency [rpb(5)=-.87, p=.012; FET, p=.024]. Excluding the 3 transsulcal surgeries, arrest during Auditory naming DES <1 cm of resection was associated with general language decline [FET, p=.047]. All 3 patients with persisting aphasia had Auditory naming arrest <1 cm of resection and 2/3 patients had Object naming ECoG features resected. CONCLUSIONS While preliminary, results suggest that surgical proximity to ECoG and DES mapping results may inform risk of surgically-acquired cognitive-linguistic decline. Findings support the potential of multimethod-multitask intraoperative language mapping.