Electrocorticographic Recordings Research Articles

Primary somatosensory cortex CB1 and 5‑HT1A receptors interaction in the penicillin model of epilepsy.

Cannabinoid and serotonin systems regulate many biological processes. The aim of the present study was to investigate the functional interaction between the cannabinoid and serotonergic systems of the primary somatosensory region (S1) of the brain in epileptiform activity caused by penicillin. The ACEA (an agonist of CB1 receptor), AM‑251 (an antagonist of CB1 receptor), 8‑OH‑DPAT (an agonist of 5‑HT1A receptor) and WAY‑100635 (an antagonist of 5‑HT1A receptor) were administered into the S1 after the same site administration of penicillin in urethane‑anesthetized rats. Electrocorticographic recording was done for a 90‑min period. The spike waves number and amplitude were recorded in 15‑min intervals. Areas under the curve (AUC) of the above‑mentioned spike alterations was calculated in 90 min. Spike waves with frequency of 30/min and amplitude of 1.3 mV were appeared after penicillin microinjection. The ACEA (50 ng), 8‑OH‑DPAT (500 ng) and ACEA (10 ng) plus 8‑OH‑DPAT (100 ng) reduced epileptiform activity. The AM‑251 (50 ng) and WAY‑100365 (500 ng) prevented the reducing effects of ACEA (50 ng) and 8‑OH‑DPAT (500 ng). The AM‑251 alone increased spike waves frequency. The AUC results supported the effects of the above‑mentioned treatments. The results showed that activating CB1 and 5‑HT1A receptors in the S1 may reduce the epileptiform activity caused by penicillin. Therefore, alone and together activation of central CB1 and 5‑HT1A receptors might be considered in the management of epilepsy treatment.

Enhancing Sleep Quantity and Quality with a Novel GABAergic Dietary Supplement

Purpose: The primary objective of this investigation was to evaluate the effects of BH_SLP_01 (Bonafide Health Sleep Product) on sleep quality and brain wave patterns using a caffeine-induced insomnia model, and on sleep duration and latency using a pentobarbital-induced sleep model. Methods: Five male BALB/c mice were allocated per treatment arm (age: 8 weeks, body mass: 180 ± 20 g). Treatment arms included control, caffeine or phenobarbital (active) control, and BH_SLP_01. Caffeine treatment model. To induce sleep disturbance, 7.5 mg/kg caffeine was injected intraperitoneally at the 15th minute (min) of recordings, and second injections (saline or combinations) were performed at the 30th minute. Brain electrical activity was monitored and recorded for a total of two hours using electrocorticography (ECoG) recording. Serum melatonin, serotonin, and dopamine were measured by ELISA. Brain levels of MDA were measured by HPLC, and protein concentrations were determined using Western Blot analysis. Phenobarbital treatment model Groups were administered saline or BH_SLP_01, and then, 45 min later, pentobarbital (42 mg/kg) was injected. After injection, sleep latency and duration were measured. Study treatments were compared using an ANOVA and Student's unpaired t-test. Significance levels were set at p<0.05. Results: Analysis of ECoG recording data revealed notable findings. In the caffeine-pretreated group, a significant increase in amplitude was observed during the 30-45 min interval, compared to control. Caffeine administration also significantly increased frequency at 75-90 and 90-105 min compared to control (p<0.05). Conversely, the group treated with BH_SLP_01 displayed no significant changes in amplitude and frequency, except for a significant change in frequency at 90-105 min compared to control (p<0.05). Both sleep duration and sleep latency were significantly improved for BH_SLP_01 compared to control and phenobarbital control (p<0.05). In addition, serotonin, dopamine, melatonin, GABAA R2, GABAB R1, GABAB R2, 5-HT1A, GluA1, GluN1, GluN2A, Bax, Bcl-2, and Caspase-3 levels were significantly improved by BH_SLP_01 compared to control and caffeine control (p<0.05). Conclusion: The results of these studies provide evidence for the effcacy of BH_SLP_01 to improve impaired sleep, leading to notable enhancements in markers of deep sleep. This conclusion is supported by the significant upregulation of GABA, glutamine receptors, and endogenous melatonin, all of which collectively contribute to the augmentation of both sleep quantity and quality. These findings underscore the potential of BH_SLP_01 as a promising therapeutic intervention for optimizing sleep parameters and promoting overall sleep wellness. This research was supported by Bonafide Health, LLC. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Sudden unexpected death in epilepsy in a patient with a brain‐responsive neurostimulation device

AbstractBackgroundSudden unexpected death in epilepsy (SUDEP) is the most common cause of epilepsy‐related mortality. Although most witnessed SUDEPs follow seizures, mechanisms are uncertain. Investigations into the pathophysiology of SUDEP have relied on models and rare recordings of brain function at the time of the event. The brain‐responsive neurostimulation (RNS) device from Neuropace offers a therapeutic option for drug‐refractory epilepsy (DRE), enabling the recording of brain activity and the preemptive termination of seizures. Therefore, patients who experience SUDEP while being treated with an RNS device can provide insights into neural activity at the moment of this event.ObjectiveWe report the history and electrocorticographic (ECoG) recordings of a patient with DRE who experienced SUDEP years after RNS placement.Patient HistoryA girl with Phelan–McDermid syndrome and Lennox–Gastaut syndrome had an RNS device implanted at the age of 14 to treat DRE. Initially, electrodes were positioned in the right orbitofrontal (OF) and right premotor frontal regions, with the OF lead later changed to the centromedian thalamic nucleus. At age 19, the patient was found unconscious and in cardiac arrest by her parents. Although spontaneous circulation returned en route to the hospital, the patient did not regain consciousness and died. Subsequent analysis of ECoGs from RNS recordings at the time of death indicated seizure onset in the right premotor frontal cortex, which persisted despite seizure termination attempts by the RNS.ConclusionsWe present a patient with SUDEP associated with the onset of RNS‐refractory seizures. The significance of this report is highlighted by the rarity of literature on neuronal function at the time of SUDEP. Moreover, it underscores the potential for devices capable of monitoring ECoG activity to shed light on the mechanisms underlying SUDEP and to inform interventions.

Neuroligin-2 shapes individual slow waves during slow-wave sleep and the response to sleep deprivation in mice

BackgroundSleep disturbances are a common comorbidity to most neurodevelopmental disorders and tend to worsen disease symptomatology. It is thus crucial to understand mechanisms underlying sleep disturbances to improve patients’ quality of life. Neuroligin-2 (NLGN2) is a synaptic adhesion protein regulating GABAergic transmission. It has been linked to autism spectrum disorders and schizophrenia in humans, and deregulations of its expression were shown to cause epileptic-like hypersynchronized cerebral activity in rodents. Importantly, the absence of Nlgn2 (knockout: KO) was previously shown to alter sleep-wake duration and quality in mice, notably increasing slow-wave sleep (SWS) delta activity (1–4 Hz) and altering its 24-h dynamics. This type of brain oscillation is involved in memory consolidation, and is also a marker of homeostatic sleep pressure. Sleep deprivation (SD) is notably known to impair cognition and the physiological response to sleep loss involves GABAergic transmission.MethodsUsing electrocorticographic (ECoG) recordings, we here first aimed to verify how individual slow wave (SW; 0.5-4 Hz) density and properties (e.g., amplitude, slope, frequency) contribute to the higher SWS delta activity and altered 24-h dynamics observed in Nlgn2 KO mice. We further investigated the response of these animals to SD. Finally, we tested whether sleep loss affects the gene expression of Nlgn2 and related GABAergic transcripts in the cerebral cortex of wild-type mice using RNA sequencing.ResultsOur results show that Nlgn2 KO mice have both greater SW amplitude and density, and that SW density is the main property contributing to the altered 24-h dynamics. We also found the absence of Nlgn2 to accelerate paradoxical sleep recovery following SD, together with profound alterations in ECoG activity across vigilance states. Sleep loss, however, did not modify the 24-h distribution of the hypersynchronized ECoG events observed in these mice. Finally, RNA sequencing confirmed an overall decrease in cortical expression of Nlgn2 and related GABAergic transcripts following SD in wild-type mice.ConclusionsThis work brings further insight into potential mechanisms of sleep duration and quality deregulation in neurodevelopmental disorders, notably involving NLGN2 and GABAergic neurotransmission.

489 Increase in Broadband Power Is an Electrophysiologic Marker of Focal Thalamic Activity During Movement

INTRODUCTION: The architecture of the human thalamus is currently indirectly inferred from human histopathologic and non-human animal studies. Given that movement-related increases in broadband power from electrocorticography recording have been previously shown to identify specific motor cortical subregions involved with a particular movement, we explored whether this phenomenon can also be used to localize motor subregions of thalamus. METHODS: We performed serial human thalamic local field potentials recordings using an electrode moved through the lateral thalamusduring deep brain stimulation surgery in 10 subjects. During the recording at each location, subjects alternated between 5 second epochs of rest and 5 second periods of contralateral hand movement. Power spectra were generated for each epoch using Welch’s overlapping periodogram method (1 second window, 50% overlap). Spectra from all movement and rest epochs were separately averaged. The difference between the power in the 65 to 95 Hz band during movement versus rest was used as a proxy for task-related change in broadband activity. Task-related differences in prominent low-frequency oscillations (patient-specific sub-ranges within 5 to 30 Hz) were analyzed per individual oscillation and in aggregate. Significance was determined using unpaired T tests at a threshold of p = 0.05. RESULTS: We find that recording sites showing statistically significant increases in broadband power during movement tend to tightly cluster in areas predicted to represent motor thalamus, whereas sites showing statistically significant reduction in the power (desynchronization) of low frequency oscillations are more diffusely distributed. This finding is replicated across all subjects. CONCLUSIONS: These results suggest that a task-dependent increase in broadband power is an electrophysiologic marker of focal thalamic activity and may be useful to delineate specific thalamic subregions on an individual subject basis.

253 Tissue Partial Pressure of Oxygen During Spreading Depolarization in Malignant Stroke is Associated With Outcome

INTRODUCTION: Spreading depolarization (SD) describes a propagating neuronal mass depolarization within the cerebral cortex that likely represents a relevant mechanism of secondary lesion progression. METHODS: This prospective observational study included 25 patients with MHS that underwent decompressive hemicraniectomy (DC) followed by subdural placement of an electrocorticography (ECoG) strip electrode and cortical implantation of a PtiO2 probe within in the periinfarct tissue. Continuous ECoG and PtiO2 recordings were obtained at bedside for five days and analyzed for the occurrence of SD and SD-associated PtiO2 changes, as well as their association with clinical outcome at 6 months. RESULTS: The overall simultaneous ECoG and PtiO2 recording time was 2603 hours, during which 796 SDs were detected. The overall SD duration and SD frequency did not correlate with outcome. During the observation period, the overall PtiO2baseline changed significantly with an almost linear increase that reached a peak around 100 hours (*p=0.0055), followed by a PtiO2 drop until the end of the monitoring period (*p = 0.0048). Accordingly, low baseline PtiO2 (<15 mmHg) was mainly noted during the first 24 hours but did not correlate with outcome (p = 0.916). Conversely, 20 out of 25 patients showed SD-associated PtiO2 changes in 363 out of 796 SDs (45.6%), which were categorized as biphasic (222), hypoxic (119) and hyperoxic (22). Among these SD-associated PtiO2 responses, a high occurrence rate, biphasic response pattern and high amplitude correlated significantly with favorable outcome (mRS 1-3) at 6 months. CONCLUSIONS: SD-associated PtiO2 coupling in patients suffering hemispheric stroke appears to be associated with clinical outcome and could reflect the presence of viable and metabolically less impaired peri-infarct tissue.

Canonical Wnt activator Chir99021 prevents epileptogenesis in the intrahippocampal kainate mouse model of temporal lobe epilepsy

The Wnt signaling pathway mediates the development of dentate granule cell neurons in the hippocampus. These neurons are central to the development of temporal lobe epilepsy and undergo structural and physiological remodeling during epileptogenesis, which results in the formation of epileptic circuits. The pathways responsible for granule cell remodeling during epileptogenesis have yet to be well defined, and represent therapeutic targets for the prevention of epilepsy. The current study explores Wnt signaling during epileptogenesis and for the first time describes the effect of Wnt activation using Wnt activator Chir99021 as a novel anti-epileptogenic therapeutic approach.Focal mesial temporal lobe epilepsy was induced by intrahippocampal kainate (IHK) injection in wild-type and POMC-eGFP transgenic mice. Wnt activator Chir99021 was administered daily, beginning 3 h after seizure induction, and continued up to 21-days. Immature granule cell morphology was quantified in the ipsilateral epileptogenic zone and the contralateral peri-ictal zone 14 days after IHK, targeting the end of the latent period. Bilateral hippocampal electrocorticographic recordings were performed for 28-days, 7-days beyond treatment cessation. Hippocampal behavioral tests were performed after completion of Chir99021 treatment.Consistent with previous studies, IHK resulted in the development of epilepsy after a 14 day latent period in this well-described mouse model. Activation of the canonical Wnt pathway with Chir99021 significantly reduced bilateral hippocampal seizure number and duration. Critically, this effect was retained after treatment cessation, suggesting a durable antiepileptogenic change in epileptic circuitry. Morphological analyses demonstrated that Wnt activation prevented pathological remodeling of the primary dendrite in both the epileptogenic zone and peri-ictal zone, changes in which may serve as a biomarker of epileptogenesis and anti-epileptogenic treatment response in pre-clinical studies. These findings were associated with improved object location memory with Chir99021 treatment after IHK.This study provides novel evidence that canonical Wnt activation prevents epileptogenesis in the IHK mouse model of mesial temporal lobe epilepsy, preventing pathological remodeling of dentate granule cells. Wnt signaling may therefore play a key role in mesial temporal lobe epileptogenesis, and Wnt modulation may represent a novel therapeutic strategy in the prevention of epilepsy.

Irregularity of instantaneous gamma frequency in the motor control network characterize visuomotor and proprioceptive information processing

Objective. The study aims to characterize movements with different sensory goals, by contrasting the neural activity involved in processing proprioceptive and visuo-motor information. To accomplish this, we have developed a new methodology that utilizes the irregularity of the instantaneous gamma frequency parameter for characterization. Approach. In this study, eight essential tremor patients undergoing an awake deep brain stimulation implantation surgery repetitively touched the clinician’s finger (forward visually-guided/FV movement) and then one’s own chin (backward proprioceptively-guided/BP movement). Neural electrocorticographic recordings from the motor (M1), somatosensory (S1), and posterior parietal cortex (PPC) were obtained and band-pass filtered in the gamma range (30–80 Hz). The irregularity of the inter-event intervals (IEI; inverse of instantaneous gamma frequency) were examined as: (1) auto-information of the IEI time series and (2) correlation between the amplitude and its proceeding IEI. We further explored the network connectivity after segmenting the FV and BP movements by periods of accelerating and decelerating forces, and applying the IEI parameter to transfer entropy methods. Main results. Conceptualizing that the irregularity in IEI reflects active new information processing, we found the highest irregularity in M1 during BP movement, highest in PPC during FV movement, and the lowest during rest at all sites. Also, connectivity was the strongest from S1 to M1 and from S1 to PPC during FV movement with accelerating force and weakest during rest. Significance. We introduce a novel methodology that utilize the instantaneous gamma frequency (i.e. IEI) parameter in characterizing goal-oriented movements with different sensory goals, and demonstrate its use to inform the directional connectivity within the motor cortical network. This method successfully characterizes different movement types, while providing interpretations to the sensory-motor integration processes.

Intraoperative ECoG in bottom-of-the-sulcus syndrome using a novel flexible strip electrode.

The recording of epileptiform discharges from bottom-of-sulcus focal cortical dysplasia (BOSD) is often difficult during intraoperative electrocorticography (ECoG) due to the deep localization. We describe the use in this scenario of a new-generation electrode strip with high flexibility, easily adapted to cortical gyri and sulci. A right-handed 20-year-old male with drug-resistant focal epilepsy due to BOSD of the inferior frontal gyrus and daily focal aware seizures was evaluated for epilepsy surgery. Based on electroclinical and neuroimaging results, a focal cortectomy guided by ECoG was proposed. ECoG recordings were performed with new-generation cortical strips (Wise Cortical Strip; WCS®) and standard cortical strips. ECoG, performed on the convexity of the frontal cortical surface, recorded only sporadic spikes with both types of strips. Then, after microsurgical trans-sulcal dissection, WCS was molded along the sulcal surface of the suspected BOSD based on 3D-imaging reconstruction, showing continuous/subcontinuous 3-4-Hz rhythmic spike activity from the deepest electrode. Registration after resection of the BOSD did not show any epileptiform activity. Pathology showed dysmorphic neurons and gliosis. No surgical complications occurred. The patient is seizure-free after 12 months. This single case experience shows that highly flexible electrode strips with adaptability to cortical gyrations can identify IEDs originating from deep location and could therefore be useful in cases of bottom of the sulcus dysplasia.

Iterative Pseudo-Sparse Partial Least Square and Its Higher Order Variant: Application to Inference From High-Dimensional Biosignals

Partial Least Square (PLS) regression and its (L1 or L2 norm) regularized versions have been proposed to handle the high-dimensionality aspects of the problem at hand and select relevant features. Addressing these issues improves the generalizability of decoding the unseen data, with the severe challenge of high computational complexity. In order to avoid directly solving the L1 norm optimization problem or performing matrix inversion, this paper proposes two PLS-based algorithms, Pseudo-Sparse PLS (PS-PLS) and iterative Pseudo-Sparse Higher-Order PLS (iPS-HOPLS). In these proposed methods, we add the Pseudo-Sparsity term to reduce the L1 norm of the regression coefficient vector in a selective scheme for better importance interpretation while keeping the algorithm as simple as possible. Regarding the evaluation of the proposed methods, we investigate three critical high-dimensionality regression problems of 1) the prediction of 3D trajectory from Electrocorticography (ECoG) recordings, 2) decoding continuous fluctuation of the Electromyography (EMG) powers from recorded Magnetoencephalography (MEG) signals, and 3) continuous decoding of the finger forces from the High-Density surface Electromyogram (HD-sEMG) signals. As well as providing cognitive-relevant interpretations, the experimental results show significant improvements over the generic methods and competitive performance compared to the state-of-the-art regularized PLS approaches.

The CB1 cannabinoid receptors involvement in anti-epileptic effect of safranal on penicillin-induced epileptiform activity in rats.

Neuroprotective effects for natural products are supported by several studies. In this regard, safranal, a constitute of saffron, has the potential to exert beneficial effects in neuro-logical disorders such as Parkinson's disease, epilepsy, stroke, multiple sclerosis and Alzheimer's disease. Here, we investigated the effect of safranal on penicillin-induced epileptiform activity. Also, the effects of intracerebroventricular (ICV) microinjection of AM251 as a CB1-cannabinoid receptors antagonist to clarify the possible mechanism of safranal were evaluated. Epileptiform activity was induced by intra-cortical administration of penicillin (300 IU, 1.50 μL) in urethane-anesthetized rats. Electrocorticographic recordings were used to analyze the frequency and amplitude of spike waves. Intraperitoneal injections of safranal at doses of 1.00 and 4.00 mg kg-1 significantly reduced both the number and amplitude of spike waves. The ICV microinjection of AM251 (0.50 μg 2.00 μL-1) significantly increased the frequency and amplitude of spike waves. In addition, the anti-epileptic effect induced by administration of safranal at a dose of 4.00 mg kg-1 was partially prevented by ICV microinjection of 0.50 μg 2.00 μL-1 of AM251. The results showed anti-epileptiform activities for safranal. Central CB1 cannabinergic receptors might be involved in the anti-epileptiform activity of safranal.

KRM–II–81 suppresses epileptifom activity across the neural network of cortical tissue from a patient with pharmacoresistant epilepsy

A clinical case of a 19-year-old male patient with pharmacoresistant seizures occurring following parieto-occipital tumor-resection at age 6 is described. Seizure surgery work-up included prolonged video EEG monitoring and head CT without contrast. Seizure focus was localized to the left temporal lobe, and we felt that the patient was an excellent candidate for seizure surgery. The patient underwent a left frontotemporal craniotomy for removal of the seizure focus with intraoperative electrocorticography (ECoG) conducted pre and post resection. ECoG recordings pre- and post-resection confirmed resolution of seizure generation. Imaging obtained immediately postoperatively showed complete resection of the residual tumor with no evidence of recurrence in follow-ups. A year after the surgery the patient is seizure-free but remains on seizure medication. With the patient's consent the excised epileptogenic tissue was used for ex-vivo research studies. The microelectrode recordings confirmed epileptiform activity in the excised tissue incubated in excitatory artificial cerebrospinal fluid. The epileptiform activity in the epileptogenic tissue was suppressed by addition of KRM–II–81, a novel α2/3 subtype preferring GABAA receptor (GABAAR) potentiator with previously demonstrated antiepileptic efficacy in multiple animal models of epilepsy and with reduced potential for CNS side-effects compared to classical benzodiazepine GABAAR potentiators. These findings support the proposition that KRM–II–81 might reduce seizure burden in pharmacoresistant patients.

Enhanced sensitivity of electrocorticography during awake craniotomy using a novel circular grid electrode.

Awake craniotomy with intraoperative functional brain mapping (FBM) bedside neurological testing is an important technique used to optimize resective brain surgeries near eloquent cortex. Awake craniotomy performed with electrocorticography (ECoG) and direct electrical stimulation (DES) for FBM can delineate eloquent cortex from lesions and epileptogenic regions. However, current electrode technology demonstrates spatial limitations. Our group has developed a novel circular grid with the goal of improving spatial recording of ECoG to enhance detection of ictal and interictal activity. This retrospective study was approved by the institutional review board at Mayo Clinic Florida. We analyzed patients undergoing awake craniotomy with ECoG and DES and compared ECoG data obtained using the 22 contact circular grid to standard 6 contact strip electrode. We included 144 cases of awake craniotomy with ECoG, 73 using circular grid and 71 with strip electrode. No significant differences were seen regarding preoperative clinical and demographic data, duration of ECoG recording (p = 0.676) and use of DES (p = 0.926). Circular grid was more sensitive in detecting periodic focal epileptiform discharges (PFEDs) (p = 0.004), PFEDs plus (p = 0.032), afterdischarges (ADs) per case (p = 0.022) at lower minimum (p = 0.012) and maximum (p < 0.0012) intensity stimulation, and seizures (p = 0.048). PFEDs (p < 0.001), PFEDs plus (p < 0.001), and HFOs (p < 0.001) but not ADs (p = 0.255) predicted electrographic seizures. We demonstrate higher sensitivity in detecting ictal and interictal activity on ECoG during awake craniotomy with a novel circular grid compared to strip electrode, likely due to better spatial sampling during ECoG. We also found association between PFEDs and intraoperative seizures.

Enhanced behavioral performance through interareal gamma and beta synchronization

Cognitive functioning requires coordination between brain areas. Between visual areas, feedforward gamma synchronization improves behavioral performance. Here, we investigate whether similar principles hold across brain regions and frequency bands, using simultaneous electrocorticographic recordings from 15 areas of two macaque monkeys during performance of a selective attention task. Short behavioral reaction times (RTs), suggesting efficient interareal communication, occurred when occipital areas V1, V2, V4, and DP showed gamma synchronization, and fronto-central areas S1, 5, F1, F2, and F4 showed beta synchronization. For both area clusters and corresponding frequency bands, deviations from the typically observed phase relations increased RTs. Across clusters and frequency bands, good phase relations occurred in a correlated manner specifically when they processed the behaviorally relevant stimulus. Furthermore, the fronto-central cluster exerted a beta-band influence onto the occipital cluster whose strength predicted short RTs. These results suggest that local gamma and beta synchronization and their inter-regional coordination jointly improve behavioral performance.

Lateralization and Time-Course of Cortical Phonological Representations during Syllable Production.

Spoken language contains information at a broad range of timescales, from phonetic distinctions on the order of milliseconds to semantic contexts which shift over seconds to minutes. It is not well understood how the brain's speech production systems combine features at these timescales into a coherent vocal output. We investigated the spatial and temporal representations in cerebral cortex of three phonological units with different durations: consonants, vowels, and syllables. Electrocorticography (ECoG) recordings were obtained from five participants while speaking single syllables. We developed a novel clustering and Kalman filter-based trend analysis procedure to sort electrodes into temporal response profiles. A linear discriminant classifier was used to determine how strongly each electrode's response encoded phonological features. We found distinct time-courses of encoding phonological units depending on their duration: consonants were represented more during speech preparation, vowels were represented evenly throughout trials, and syllables during production. Locations of strongly speech-encoding electrodes (the top 30% of electrodes) likewise depended on phonological element duration, with consonant-encoding electrodes left-lateralized, vowel-encoding hemispherically balanced, and syllable-encoding right-lateralized. The lateralization of speech-encoding electrodes depended on onset time, with electrodes active before or after speech production favoring left hemisphere and those active during speech favoring the right. Single-electrode speech classification revealed cortical areas with preferential encoding of particular phonemic elements, including consonant encoding in the left precentral and postcentral gyri and syllable encoding in the right middle frontal gyrus. Our findings support neurolinguistic theories of left hemisphere specialization for processing short-timescale linguistic units and right hemisphere processing of longer-duration units.

Direct speech reconstruction from sensorimotor brain activity with optimized deep learning models.

Objective.Development of brain-computer interface (BCI) technology is key for enabling communication in individuals who have lost the faculty of speech due to severe motor paralysis. A BCI control strategy that is gaining attention employs speech decoding from neural data. Recent studies have shown that a combination of direct neural recordings and advanced computational models can provide promising results. Understanding which decoding strategies deliver best and directly applicable results is crucial for advancing the field.Approach.In this paper, we optimized and validated a decoding approach based on speech reconstruction directly from high-density electrocorticography recordings from sensorimotor cortex during a speech production task.Main results.We show that (1) dedicated machine learning optimization of reconstruction models is key for achieving the best reconstruction performance; (2) individual word decoding in reconstructed speech achieves 92%-100% accuracy (chance level is 8%); (3) direct reconstruction from sensorimotor brain activity produces intelligible speech.Significance.These results underline the need for model optimization in achieving best speech decoding results and highlight the potential that reconstruction-based speech decoding from sensorimotor cortex can offer for development of next-generation BCI technology for communication.

Flexible Thin‐Film Neural Electrodes with Improved Conformability for ECoG Measurements and Electrical Stimulation

Neural electrodes for electrocorticography (ECoG) recording and electrical stimulation are used for diagnosis and treatment of epilepsy, which are temporarily attached to the surface of cerebral cortex within the subdural space. However, conventional electrodes have a mechanical mismatch with the surface curvature of the brain cortex. Thus, it is necessary to develop a thin and flexible ECoG electrode to overcome the mechanical mismatch with cortex tissue and achieve long‐term ECoG measurement. Herein, a flexible thin‐film electrode is reported with a thickness of ≈8 µm by exploiting printed electronics. A simple fabrication method of conductive wiring is proposed by inkjet printing Au nanoink on a flexible elastomeric thin film consisting of polystyrene‐block‐polybutadiene‐block‐polystyrene (SBS). The conductive wiring printed on the SBS thin film is encapsulated by another SBS thin film as an insulation layer, with laser‐processed micropatterns. The flexible thin‐film electrode is implanted on the cortical surface of rats and used for in vivo ECoG recording and electrical stimulation without the occurrence of severe inflammatory reactions after 6 weeks of implantation. The flexible electrode with 35 ECoG channels visualized the epileptiform activity in a drug‐induced epilepsy rat model, which demonstrates the potential application for the management of intractable epilepsy.

Intracranial intraoperative radiotherapy (IORT): evaluation of electrocorticography and peri-operative seizure risk.

Intra-operative radiotherapy (IORT) for brain metastases (BMs) and primary brain tumors has emerged as an adjuvant radiation modality that allows for consolidation of care into a single anesthetic episode with surgical resection. Yet, there is a paucity of data regarding the impact that IORT may have on peri-operative and long-term seizure risk. A retrospective analysis of patients receiving IORT during tumor resection was performed via registry including data regarding peri-operative anti-seizure medications and anesthetic agents. Intra-operative neuromonitoring was performed using electrocorticography (ECoG) captured before-, during-, and after-IORT then analyzed for evidence of seizure or significant baseline changes. Kaplan-Meir estimations were used for overall survival analysis relative to documented clinical seizure incidence post-IORT. Of the 24 consecutive patients treated with IORT during tumor resection included, 18 (75%) patients were diagnosed with BMs while 6 (25%) had newly-diagnosed glioblastoma. Mean and median survival times were 487 and 372 days, respectively. Clinical seizures occurred in 3 patients post-IORT, 2 BMs patients within 9 months and 1 glioblastoma patient at 14 months. IORT time represented 9.5% of anesthetic time. ECoG recordings were available for 5 patients (4 BMs; 1 glioblastoma), with mean recording durations of 13% of the total anesthetic time and no evidence of high-frequency oscillations or seizure activity. IORT is an option for delivery of definitive radiation in surgically resected brain tumors without increasing the peri-operative or long-term risk of seizure. ECoG data during the delivery of radiation fail to demonstrate any electrophysiological changes in response to ionizing radiation.

Patient-derived SLC6A1 variant S295L results in an epileptic phenotype similar to haploinsufficient mice.

The solute carrier family 6 member 1 (SLC6A1) gene encodes GAT-1, a γ-aminobutyric acid transporter expressed on astrocytes and inhibitory neurons. Mutations in SLC6A1 are associated with epilepsy and developmental disorders, including motor and social impairments, but variant-specific animal models are needed to elucidate mechanisms. Here, we report electrocorticographic (ECoG) recordings and clinical data from a patient with a variant in SLC6A1 that encodes GAT-1 with a serine-to-leucine substitution at amino acid 295 (S295L), who was diagnosed with childhood absence epilepsy. Next, we show that mice bearing the S295L mutation (GAT-1S295L/+ ) have spike-and-wave discharges with motor arrest consistent with absence-type seizures, similar to GAT-1+/- mice. GAT-1S295L/+ and GAT-1+/- mice follow the same pattern of pharmacosensitivity, being bidirectionally modulated by ethosuximide (200 mg/kg ip) and the GAT-1 antagonist NO-711 (10 mg/kg ip). By contrast, GAT-1-/- mice were insensitive to both ethosuximide and NO-711 at the doses tested. In conclusion, ECoG findings in GAT-1S295L/+ mice phenocopy GAT-1 haploinsufficiency and provide a useful preclinical model for drug screening and gene therapy investigations.

A brain cytokine-independent switch in cortical activity marks the onset of sickness behavior triggered by acute peripheral inflammation

Systemic inflammation triggers protective as well as pro-inflammatory responses in the brain based on neuronal and/or cytokine signaling, and it associates with acutely and protractedly disrupted cognition. However, the multiple mechanisms underlying the peripheral–central inflammatory signaling are still not fully characterized. We used intraperitoneal (i.p.) injection of lipopolysaccharide (LPS) in freely moving mice with chronically implanted electrodes for recording of local field potentials (LFP) and electrocorticography (ECoG) in the hippocampus and neocortex, respectively. We show here that a sudden switch in the mode of network activity occurred in both areas starting at 10–15 min after the LPS injection, simultaneously with a robust change from exploration to sickness behavior. This switch in cortical mode commenced before any elevations in pro-inflammatory cytokines IL-1β, TNFα, CCL2 or IL-6 were detected in brain tissue. Thereafter, this mode dominated cortical activity for the recording period of 3 h, except for a partial and transient recovery around 40 min post-LPS. These effects were closely paralleled by changes in ECoG spectral entropy. Continuous recordings for up to 72 h showed a protracted attenuation in hippocampal activity, while neocortical activity recovered after 48 h. The acute sickness behavior recovered by 72 h post-LPS. Notably, urethane (1.3 mg/kg) administered prior to LPS blocked the early effect of LPS on cortical activity. However, experiments under urethane anesthesia which were started 24 h post-LPS (with neuroinflammation fully developed before application of urethane) showed that both theta–supratheta and fast gamma CA1 activity were reduced, DG delta activity was increased, and sharp-wave ripples were abolished. Finally, we observed that experimental compensation of inflammation-induced hypothermia 24–48 h post-LPS promoted seizures and status epilepticus; and that LPS decreased the threshold of kainate-provoked seizures beyond the duration of acute sickness behavior indicating post-acute inflammatory hyperexcitability. Taken together, the strikingly fast development and initial independence of brain cytokines of the LPS-induced cortical mode, its spectral characteristics and simultaneity in hippocampus and neocortex, as well as inhibition by pre-applied urethane, strongly suggest that the underlying mechanisms are based on activation of the afferent vagus nerve and its mainly cholinergic ascending projections to higher brain areas.