Cortico-cortical Evoked Potentials Research Articles

CARLA: Adjusted common average referencing for cortico-cortical evoked potential data

Human brain connectivity can be mapped by single pulse electrical stimulation during intracranial EEG measurements. The raw cortico-cortical evoked potentials (CCEP) are often contaminated by noise. Common average referencing (CAR) removes common noise and preserves response shapes but can introduce bias from responsive channels. We address this issue with an adjusted, adaptive CAR algorithm termed “CAR by Least Anticorrelation (CARLA)”.CARLA was tested on simulated CCEP data and real CCEP data collected from four human participants. In CARLA, the channels are ordered by increasing mean cross-trial covariance, and iteratively added to the common average until anticorrelation between any single channel and all re-referenced channels reaches a minimum, as a measure of shared noise.We simulated CCEP data with true responses in 0 to 45 of 50 total channels. We quantified CARLA’s error and found that it erroneously included 0 (median) truly responsive channels in the common average with ≤42 responsive channels, and erroneously excluded ≤2.5 (median) unresponsive channels at all responsiveness levels. On real CCEP data, signal quality was quantified with the mean R2 between all pairs of channels, which represents inter-channel dependency and is low for well-referenced data. CARLA re-referencing produced significantly lower mean R2 than standard CAR, CAR using a fixed bottom quartile of channels by covariance, and no re-referencing.CARLA minimizes bias in re-referenced CCEP data by adaptively selecting the optimal subset of non-responsive channels. It showed high specificity and sensitivity on simulated CCEP data and lowered inter-channel dependency compared to CAR on real CCEP data.

243 Intracranial Theta-burst Stimulation Modulates Cortical Excitability in a Dose and Location-dependent Fashion

INTRODUCTION: Direct electrical stimulation is a powerful therapeutic approach to treating a wide range of brain disorders. In particular, theta-burst stimulation (TBS) which delivers electrical pulses in rhythmic bursts of 3-8 Hz to mimic endogenous brain rhythms, has been increasingly used to improve cognitive processes and relieve symptoms of depression. However, how TBS alters underlying neural activity is poorly understood. METHODS: In nine neurosurgical epilepsy subjects undergoing intracranial monitoring, we applied direct cortical TBS at varying stimulation amplitudes and locations (prefrontal, temporal, parietal). We obtained single-pulse corticocortical evoked potentials (CCEPs) prior to stimulation to map functional connectivity. Intracranial EEG (iEEG) was recorded from non-stimulated electrodes before, during and after TBS. RESULTS: We found that TBS evoked consistent responses after each burst. These responses were observed in regions with high amplitude CCEPs and resting spontaneous delta (1-4 Hz) phase-locking to the stimulation site, consistent with our hypothesis that the underlying functional brain architecture guides information flow after stimulation. Furthermore, we observed changes in cortical excitability over time as measured by changes in amplitude of the TBS evoked responses both within stimulation burst trains and across burst trains. The degree of change in cortical excitability was modulated by anatomical location, proximity of the stimulating electrode to white matter, and current amplitude. CONCLUSIONS: These results indicate that direct cortical TBS produces neural effects that can be measured over time and correlate with baseline biophysical parameters. Thus, personalizing stimulation parameters might be critical to predictably maximize our ability to alter disease-relevant brain networks.

The effect of propofol on effective brain networks

ObjectiveWe compared the effective networks derived from Single Pulse Electrical Stimulation (SPES) in intracranial electrocorticography (ECoG) of awake epilepsy patients and while under general propofol-anesthesia to investigate the effect of propofol on these brain networks. MethodsWe included nine patients who underwent ECoG for epilepsy surgery evaluation. We performed SPES when the patient was awake (SPES-clinical) and repeated this under propofol-anesthesia during the surgery in which the ECoG grids were removed (SPES-propofol). We detected the cortico-cortical evoked potentials (CCEPs) with an automatic detector. We constructed two effective networks derived from SPES-clinical and SPES-propofol. We compared three network measures (indegree, outdegree and betweenness centrality), the N1-peak-latency and amplitude of CCEPs between the two effective networks. ResultsFewer CCEPs were observed during SPES-propofol (median: 6.0, range: 0–29) compared to SPES-clinical (median: 10.0, range: 0–36). We found a significant correlation for the indegree, outdegree and betweenness centrality between SPES-clinical and SPES-propofol (respectively rs = 0.77, rs = 0.70, rs = 0.55, p < 0.001). The median N1-peak-latency increased from 22.0 ms during SPES-clinical to 26.4 ms during SPES-propofol. ConclusionsOur findings suggest that the number of effective network connections decreases, but network measures are only marginally affected. SignificanceThe primary network topology is preserved under propofol.

Cortico-cortical evoked potentials of language tracts in minimally invasive glioma surgery guided by Penfield stimulation

ObjectiveWe investigated the feasibility of recording cortico-cortical evoked potentials (CCEPs) in patients with low- and high-grade glioma. We compared CCEPs during awake and asleep surgery, as well as those stimulated from the functional Broca area and recorded from the functional Wernicke area (BtW), and vice versa (WtB). We also analyzed CCEP properties according to tumor location, histopathology, and aphasia. MethodsWe included 20 patients who underwent minimally invasive surgery in an asleep-awake-asleep setting. Strip electrode placement was guided by classical Penfield stimulation of positive language sites and fiber tracking of the arcuate fascicle. CCEPs were elicited with alternating monophasic single pulses of 1.1 Hz frequency and recorded as averaged signals. Intraoperatively, there was no post-processing of the signal. ResultsNinety-seven CCEPs from 19 patients were analyzed. There was no significant difference in CCEP properties when comparing awake versus asleep, nor BtW versus WtB. CCEP amplitude and latency were affected by tumor location and histopathology. CCEP features after tumor resection correlated with short- and long-term postoperative aphasia. ConclusionCCEP recordings are feasible during minimally invasive surgery. CCEPs might be surrogate markers for altered connectivity of the language tracts. SignificanceThis study may guide the incorporation of CCEPs into intraoperative neurophysiological monitoring.

Utilizing Excitatory and Inhibitory Activity Derived from Interictal Intracranial Electroencephalography as Potential Biomarkers for Epileptogenicity.

Epileptogenic zones (EZs), where epileptic seizures cease after resection, are localized by assessing the seizure-onset zone using ictal electroencephalography (EEG). Owing to the difficulty in capturing unpredictable seizures, biomarkers capable of identifying EZs from interictal EEG are anticipated. Recent studies using intracranial EEG have identified several potential candidate biomarkers for epileptogenicity. High-frequency oscillation (HFO) was initially expected to be a robust biomarker of abnormal excitatory activity in the ictogenic region. However, HFO-guided resection failed to improve seizure prognosis. Meanwhile, the regularity of low-gamma oscillations (30-80 Hz) indicates inhibitory interneurons' hypersynchronization, which could be used to localize the EZ. Besides resting-state EEG assessments, evoked potentials elicited by single-pulse electrical stimulation, such as corticocortical evoked potentials (CCEP), became valuable tools for assessing epileptogenic regions. CCEP responses recorded in the cortex remote from the stimulation site indicate functional connectivity, revealing increased internal connectivity within the ictogenic region and elevated inhibitory input from the non-involved regions to the ictogenic region. Conversely, large responses close to the stimulation site reflect local excitability, manifesting as an increased N1 amplitude and overriding HFO. Further research is required to establish whether these novel electrophysiological methods, either individually or in combination, can function as robust biomarkers of epileptogenicity and hold promise for improving seizure prognosis.

Localizing seizure onset zone by a cortico-cortical evoked potentials-based machine learning approach in focal epilepsy

ObjectiveWe aimed to develop a new approach for identifying the localization of the seizure onset zone (SOZ) based on corticocortical evoked potentials (CCEPs) and to compare the connectivity patterns in patients with different clinical phenotypes. MethodsFifty patients who underwent stereoelectroencephalography and CCEP procedures were included. Logistic regression was used in the model, and six CCEP metrics were input as features: root mean square of the first peak (N1RMS) and second peak (N2RMS), peak latency, onset latency, width duration, and area. ResultsThe area under the curve (AUC) for localizing the SOZ ranged from 0.88 to 0.93. The N1RMS values in the hippocampus sclerosis (HS) group were greater than that of the focal cortical dysplasia (FCD) IIa group (p < 0.001), independent of the distance between the recorded and stimulated sites. The sensitivity of localization was higher in the seizure-free group than in the non-seizure-free group (p = 0.036). ConclusionsThis new method can be used to predict the SOZ localization in various focal epilepsy phenotypes. SignificanceThis study proposed a machine-learning approach for localizing the SOZ. Moreover, we examined how clinical phenotypes impact large-scale abnormality of the epileptogenic networks.

Delayed effective connectivity characterizes the epileptogenic zone during stereo-EEG

ObjectiveSingle-pulse electrical stimulations (SPES) can elicit normal and abnormal responses that might characterize the epileptogenic zone, including spikes, high-frequency oscillations and cortico-cortical evoked potentials (CCEPs).In this study, we investigate their association with the epileptogenic zone during stereoelectroencephalography (SEEG) in 28 patients with refractory focal epilepsy. MethodsCharacteristics of CCEPs (distance-corrected or -uncorrected latency, amplitude and the connectivity index) and the occurrence of spikes and ripples were assessed. Responses within the epileptogenic zone and within the non-involved zone were compared using receiver operating characteristics curves and analysis of variance (ANOVA) either in all patients, patients with well-delineated epileptogenic zone, and patients older than 15 years old. ResultsWe found an increase in distance-corrected CCEPs latency after stimulation within the epileptogenic zone (area under the curve = 0.71, 0.72, 0.70, ANOVA significant after false discovery rate correction). ConclusionsThe increased distance-corrected CCEPs latency suggests that neuronal propagation velocity is altered within the epileptogenic network. This association might reflect effective connectivity changes at cortico-cortical or cortico-subcortico-cortical levels. Other responses were not associated with the epileptogenic zone, including the CCEPs amplitude, the connectivity index, the occurrences of induced ripples and spikes. The discrepancy with previous descriptions may be explained by different spatial brain sampling between subdural and depth electrodes. SignificanceIncreased distance-corrected CCEPs latency, indicating delayed effective connectivity, characterizes the epileptogenic zone. This marker could be used to help tailor surgical resection limits after SEEG.

Signatures of Electrical Stimulation Driven Network Interactions in the Human Limbic System.

Stimulation-evoked signals are starting to be used as biomarkers to indicate the state and health of brain networks. The human limbic network, often targeted for brain stimulation therapy, is involved in emotion and memory processing. Previous anatomic, neurophysiological, and functional studies suggest distinct subsystems within the limbic network (Rolls, 2015). Studies using intracranial electrical stimulation, however, have emphasized the similarities of the evoked waveforms across the limbic network. We test whether these subsystems have distinct stimulation-driven signatures. In eight patients (four male, four female) with drug-resistant epilepsy, we stimulated the limbic system with single-pulse electrical stimulation. Reliable corticocortical evoked potentials (CCEPs) were measured between hippocampus and the posterior cingulate cortex (PCC) and between the amygdala and the anterior cingulate cortex (ACC). However, the CCEP waveform in the PCC after hippocampal stimulation showed a unique and reliable morphology, which we term the "limbic Hippocampus-Anterior nucleus of the thalamus-Posterior cingulate, HAP-wave." This limbic HAP-wave was visually distinct and separately decoded from the CCEP waveform in ACC after amygdala stimulation. Diffusion MRI data show that the measured end points in the PCC overlap with the end points of the parolfactory cingulum bundle rather than the parahippocampal cingulum, suggesting that the limbic HAP-wave may travel through fornix, mammillary bodies, and the anterior nucleus of the thalamus (ANT). This was further confirmed by stimulating the ANT, which evoked the same limbic HAP-wave but with an earlier latency. Limbic subsystems have unique stimulation-evoked signatures that may be used in the future to help network pathology diagnosis.SIGNIFICANCE STATEMENT The limbic system is often compromised in diverse clinical conditions, such as epilepsy or Alzheimer's disease, and characterizing its typical circuit responses may provide diagnostic insight. Stimulation-evoked waveforms have been used in the motor system to diagnose circuit pathology. We translate this framework to limbic subsystems using human intracranial stereo EEG (sEEG) recordings that measure deeper brain areas. Our sEEG recordings describe a stimulation-evoked waveform characteristic to the memory and spatial subsystem of the limbic network that we term the "limbic HAP-wave." The limbic HAP-wave follows anatomic white matter pathways from hippocampus to thalamus to the posterior cingulum and shows promise as a distinct biomarker of signaling in the human brain memory and spatial limbic network.

Neural representations of self-perception of voice: An intracortical evoked potential analysis based on an adolescent with right temporal lobe epilepsy

IntroductionThe neural bases for language perception have been studied elsewhere using Transcranial Magnetic Stimulation, functional Magnetic Resonance Imaging and Direct Cortical Stimulation. However, to our knowledge, there is no previous report about a patient identifying the change in his voice tone, speed, and prosody because of right temporal cortical stimulation. Nor has there been a cortico-cortical evoked potential (CCEP) assessment of the network underlying this process. Case reportWe present CCEP from a patient with right focal refractory temporal lobe epilepsy of tumoral etiology who reported changes in the perception of his own speech prosody during stimulation. This report will serve as a complement to the understanding of the neural networks of language and prosody. ConclusionThe present report shows that right superior temporal gyrus, transverse temporal gyrus, right amygdala, hippocampus, and fusiform gyrus (FG) are part of the neural network subjacent to own human voice perception.

Towards optimizing single pulse electrical stimulation: High current intensity, short pulse width stimulation most effectively elicits evoked potentials

BackgroundWhile single pulse electrical stimulation (SPES) is increasingly used to study effective connectivity, the effects of varying stimulation parameters on the resulting cortico-cortical evoked potentials (CCEPs) have not been systematically explored. ObjectiveWe sought to understand the interacting effects of stimulation pulse width, current intensity, and charge on CCEPs through an extensive testing of this parameter space and analysis of several response metrics. MethodsWe conducted SPES in 11 patients undergoing intracranial EEG monitoring using five combinations of current intensity (1.5, 2.0, 3.0, 5.0, and 7.5 mA) and pulse width at each of three charges (0.750, 1.125, and 1.500 μC/phase) to study how CCEP amplitude, distribution, latency, morphology, and stimulus artifact amplitude vary with each parameter. ResultsStimulations with a greater charge or a greater current intensity and shorter pulse width at a given charge generally resulted in greater CCEP amplitudes and spatial distributions, shorter latencies, and increased waveform correlation. These effects interacted such that stimulations with the lowest charge and highest current intensities resulted in greater response amplitudes and spatial distributions than stimulations with the highest charge and lowest current intensities. Stimulus artifact amplitude increased with charge, but this could be mitigated by using shorter pulse widths. ConclusionsOur results indicate that individual combinations of current intensity and pulse width, in addition to charge, are important determinants of CCEP magnitude, morphology, and spatial extent. Together, these findings suggest that high current intensity, short pulse width stimulations are optimal SPES settings for eliciting strong and consistent responses while minimizing charge.

[Intraoperative Cortico-Cortical Evoked Potential].

In the surgery management of lesions in areas of the eloquent cortices the preservation of brain functions is required. Intraoperative electrophysiological methods are necessary to preserve the integrity of the functional network, such as motor or language areas. Cortico-cortical evoked potentials(CCEPs)have recently developed as a new intraoperative monitoring method because of advantages of a recording time of approximately 1-2 min, no requirement of patient cooperation, and high reproducibility and reliability of the data. The recent intraoperative CCEP studies have shown that CCEP can map the eloquent areas and white matter pathway, such as the dorsal language pathway, frontal aslant tract, supplementary motor area, and optic radiation. To establish intraoperative electrophysiological monitoring even under general anesthesia, further studies are required.

Neocortical and medial temporal seizures have distinct impacts on brain responsiveness.

Focal epileptic seizures are characterized by abnormal neuronal discharges that can spread to other cortical areas and interfere with brain activity, thereby altering the patient's experience and behavior. The origin of these pathological neuronal discharges encompasses various mechanisms that converge toward similar clinical manifestations. Recent studies have suggested that medial temporal lobe (MTL) and neocortical (NC) seizures are often underpinned by two characteristic onset patterns, which, respectively, affect and spare synaptic transmission in cortical slices. However, these synaptic alterations and their effects have never been confirmed or studied in intact human brains. To fill this gap, we here evaluate whether responsiveness of MTL and NC are differentially affected by focal seizures, using a unique data set of cortico-cortical evoked potentials (CCEPs) collected during seizures triggered by single-pulse electrical stimulation (SPES). We find that responsiveness is abruptly reduced by the onset of MTL seizures, despite increased spontaneous activity, whereas it is preserved in the case of NC seizures. The present results provide an extreme example of dissociation between responsiveness and activity and show that brain networks are diversely affected by the onset of MTL and NC seizures, thus extending at the whole brain level the evidence of synaptic alteration found in vitro.

Quantifying trial-by-trial variability during cortico-cortical evoked potential mapping of epileptogenic tissue.

Measuring cortico-cortical evoked potentials (CCEPs) is a promising tool for mapping epileptic networks, but it is not known how variability in brain state and stimulation technique might impact the use of CCEPs for epilepsy localization. We test the hypotheses that (1) CCEPs demonstrate systematic variability across trials and (2) CCEP amplitudes depend on the timing of stimulation with respect to endogenous, low-frequency oscillations. We studied 11 patients who underwent CCEP mapping after stereo-electroencephalography electrode implantation for surgical evaluation of drug-resistant epilepsy. Evoked potentials were measured from all electrodes after each pulse of a 30 s, 1Hz bipolar stimulation train. We quantified monotonic trends, phase dependence, and standard deviation (SD) of N1 (15-50 ms post-stimulation) and N2 (50-300 ms post-stimulation) amplitudes across the 30 stimulation trials for each patient. We used linear regression to quantify the relationship between measures of CCEP variability and the clinical seizure-onset zone (SOZ) or interictal spike rates. We found that N1 and N2 waveforms exhibited both positive and negative monotonic trends in amplitude across trials. SOZ electrodes and electrodes with high interictal spike rates had lower N1 and N2 amplitudes with higher SD across trials. Monotonic trends of N1 and N2 amplitude were more positive when stimulating from an area with higher interictal spike rate. We also found intermittent synchronization of trial-level N1 amplitude with low-frequency phase in the hippocampus, which did not localize the SOZ. These findings suggest that standard approaches for CCEP mapping, which involve computing a trial-averaged response over a .2-1Hz stimulation train, may be masking inter-trial variability that localizes to epileptogenic tissue. We also found that CCEP N1 amplitudes synchronize with ongoing low-frequency oscillations in the hippocampus. Further targeted experiments are needed to determine whether phase-locked stimulation could have a role in localizing epileptogenic tissue.

Intraoperative Cortico-Cortical Evoked Potentials for Monitoring Language Function during Brain Tumor Resection in Anesthetized Patients.

Cortico-cortical evoked potentials (CCEPs) have been used to map the frontal (FLA) and parietal (PLA) cortical regions related to language function. However, they have usually been employed as a complementary method during sleep-awake surgery. Five male and two female patients received surgery for tumors located near language areas. Six patients received general anesthesia and the sleep-awake method was used for patients with tumors located near the cortical language areas. We performed motor and somatosensory mapping with CCEPs to identify language areas and we monitored responses during surgery based on the mapping results. Electrocorticography was performed throughout the surgery. Single pulses of 1 ms duration at 5-20 mA were delivered by direct cortical stimulation using one grid at one region (e.g., FLA) and then recording using a second gird at another area (i.e., PLA). Next, reversed stimulation (from PLA to FLA) was performed. The charge density for electrical stimulation was computed. Sensibility, specificity, predictive positive values, and predicted negative values were also computed for warning alterations of CCEPs. Gross tumor resection was achieved in four cases. The first postsurgical day showed language alterations in three patients, but one year later six patients remained asymptomatic and one patient showed the same symptomatology as previously. Seizures were observed in two patients that were easily jugulated. CCEPs predicted warning events with high sensibility and specificity. Postsurgical language deficits were mostly transitory. Although the latency between frontal and parietal regions showed symmetry, the amplitude and the relationship between amplitude and latency were different for FLA than for PLA. The charge density elicited by CCEPs ranged from 442 to 1768 μC/cm2. CCEPs have proven to be a reliable neurophysiological technique for mapping and monitoring the regions associated with language function in a small group of anesthetized patients. The high correlation between warning events and postsurgical outcomes suggested a high sensitivity and specificity and CCEPs can be used systematically in patients under general anesthesia. Nevertheless, the small number of studied patients suggests considering these results cautiously.

Functional Magnetic Resonance Imaging and Diffusion Tensor Imaging for Language Mapping in Brain Tumor Surgery: Validation With Direct Cortical Stimulation and Cortico-Cortical Evoked Potential.

Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging-derived tractography (DTI-t) contribute to the localization of language areas, but their accuracy remains controversial. This study aimed to investigate the diagnostic performance of preoperative fMRI and DTI-t obtained with a simultaneous multi-slice technique using intraoperative direct cortical stimulation (DCS) or corticocortical evoked potential (CCEP) as reference standards. This prospective study included 26 patients (23-74 years; male:female, 13:13) with tumors in the vicinity of Broca's area who underwent preoperative fMRI and DTI-t. A site-by-site comparison between preoperative (fMRI and DTI-t) and intraoperative language mapping (DCS or CCEP) was performed for 226 cortical sites to calculate the sensitivity and specificity of fMRI and DTI-t for mapping Broca's areas. For sites with positive signals on fMRI or DTI-t, the true-positive rate (TPR) was calculated based on the concordance and discordance between fMRI and DTI-t. Among 226 cortical sites, DCS was performed in 100 sites and CCEP was performed in 166 sites. The specificities of fMRI and DTI-t ranged from 72.4% (63/87) to 96.8% (122/126), respectively. The sensitivities of fMRI (except for verb generation) and DTI-t were 69.2% (9/13) to 92.3% (12/13) with DCS as the reference standard, and 40.0% (16/40) or lower with CCEP as the reference standard. For sites with preoperative fMRI or DTI-t positivity (n = 82), the TPR was high when fMRI and DTI-t were concordant (81.2% and 100% using DCS and CCEP, respectively, as the reference standards) and low when fMRI and DTI-t were discordant (≤ 24.2%). fMRI and DTI-t are sensitive and specific for mapping Broca's area compared with DCS and specific but insensitive compared with CCEP. A site with a positive signal on both fMRI and DTI-t represents a high probability of being an essential language area.

Preservation of language function by mapping the arcuate fasciculus using intraoperative corticocortical evoked potential under general anesthesia in glioma surgery.

Intraoperative language mapping under general anesthesia is imperative for brain tumor surgery because awake surgery is not always feasible. Monitoring corticocortical evoked potential (CCEP) is known to be a useful method for tracking neuronal connectivity and localizing functional areas. The authors evaluated the clinical benefit of intraoperative CCEP monitoring for language function preservation in patients undergoing glioma surgery. Between January 2019 and June 2021, the authors performed a total of 29 consecutive glioma surgeries using CCEP monitoring under general anesthesia because of a risk of speech impairment; these were analyzed. Language area mapping was implemented by the anterior language area to posterior language area CCEP method for arcuate fasciculus mapping, and tumor resection was performed while avoiding the localized language areas. Language function before and after surgery was evaluated by the Controlled Oral Word Association Test (COWAT). Intraoperative CCEP was successfully monitored in 25 patients (86.2%), and a valid signal was undetectable in the other 4 patients. Language function evaluation was possible before and after surgery in a total of 20 patients. Overall, the preservation rate of language function was 65.0%, and the deterioration rate was 35.0% after tumor resection with CCEP monitoring. Among those 8 patients with preoperative COWAT scores ≥ 18, 5 patients (62.5%) successfully preserved their language function, with COWAT scores > 18 after tumor resection. Among the 12 patients with preoperative deteriorated language function (COWAT score < 18), 8 patients (66.7%) showed improvement or preserved language function after surgery. Intraoperative CCEP monitoring of the arcuate fasciculus is an acceptable technology for the preservation of language function under general anesthesia in glioma surgery in patients in whom awake surgery is not feasible.

Distinct connectivity patterns in human medial parietal cortices: Evidence from standardized connectivity map using cortico-cortical evoked potential

The medial parietal cortices are components of the default mode network (DMN), which are active in the resting state. The medial parietal cortices include the precuneus and the dorsal posterior cingulate cortex (dPCC). Few studies have mentioned differences in the connectivity in the medial parietal cortices, and these differences have not yet been precisely elucidated. Electrophysiological connectivity is essential for understanding cortical function or functional differences. Since little is known about electrophysiological connections from the medial parietal cortices in humans, we evaluated distinct connectivity patterns in the medial parietal cortices by constructing a standardized connectivity map using cortico-cortical evoked potential (CCEP). This study included nine patients with partial epilepsy or a brain tumor who underwent chronic intracranial electrode placement covering the medial parietal cortices. Single-pulse electrical stimuli were delivered to the medial parietal cortices (38 pairs of electrodes). Responses were standardized using the z-score of the baseline activity, and a response density map was constructed in the Montreal Neurological Institutes (MNI) space. The precuneus tended to connect with the inferior parietal lobule (IPL), the occipital cortex, superior parietal lobule (SPL), and the dorsal premotor area (PMd) (the four most active regions, in descending order), while the dPCC tended to connect to the middle cingulate cortex, SPL, precuneus, and IPL. The connectivity pattern differs significantly between the precuneus and dPCC stimulation (p<0.05). Regarding each part of the medial parietal cortices, the distributions of parts of CCEP responses resembled those of the functional connectivity database. Based on how the dPCC was connected to the medial frontal area, SPL, and IPL, its connectivity pattern could not be explained by DMN alone, but suggested a mixture of DMN and the frontoparietal cognitive network. These findings improve our understanding of the connectivity profile within the medial parietal cortices. The electrophysiological connectivity is the basis of propagation of electrical activities in patients with epilepsy. In addition, it helps us to better understand the epileptic network arising from the medial parietal cortices.

Anatomical features decide the atypical seizure manifestation of parahypothalamic hamartomas.

BackgroundThe intrahypothalamic phenotype of hypothalamic hamartomas (HH) is associated with epilepsy, and the parahypothalamic phenotype usually leads to central precocious puberty but not neurological comorbidities or seizures. No study has confirmed the pathological role of parahypothalamic hamartomas in epileptogenesis, and the underlying mechanism is yet to be elucidated.ObjectiveWe aimed to investigate whether parahypothalamic hamartomas are intrinsically epileptogenic and elucidate the underlying pathway of epileptogenesis.MethodsWe reviewed 92 patients with HH-related epilepsy, categorized them by the classification system of Delalande and Fohlen, and further classified Type I (corresponding to parahypothalamic HH) into the following three groups based on the relationship between the lesion and mammillary bodies (MB): entirely invaded (Group 1), partially connected (Group 2), and not connected at all (Group 3). We examined different anatomical features with their relationship to clinical manifestations. Stereoelectroencephalography (SEEG) was implanted in both HH and extra-HH cortices in different groups to identify the epileptogenic zone. Corticocortical evoked potentials (CCEPs) were also used to determine the pathological correlation among different regions to determine the related epileptogenic network.ResultsA total of 13 patients presented with parahypothalamic HH and 10 (76.9%) presented with non-GS only, with late-onset age and normal cognitive development, which is different from classical clinical features. SEEG showed that HH is intrinsically epileptogenic in MB-involved parahypothalamic groups. No statistical difference was found in onset age (p = 0.213), and lesions horizontally oriented from the tuber cinereum without connection to MB were not involved in seizure genesis. CCEP indicated a pathological connection among HH, middle cingulate cortex, and insular cortex.ConclusionThe parahypothalamic HH can also cause epilepsy and is different from classic HH-related seizures, by non-GS only with the late-onset age and normal cognitive development. MB is proven to be related to non-GS by the mamillo-cingulate-cortex pathway.

Cortico-cortical evoked potentials in response to varying stimulation intensity improves seizure localization

ObjectiveAs single pulse electrical stimulation (SPES) is increasingly utilized to help localize the seizure onset zone (SOZ), it is important to understand how stimulation intensity can affect the ability to use cortico-cortical evoked potentials (CCEPs) to delineate epileptogenic regions. MethodsWe studied 15 drug-resistant epilepsy patients undergoing intracranial EEG monitoring and SPES with titrations of stimulation intensity. The N1 amplitude and distribution of CCEPs elicited in the SOZ and non-seizure onset zone (nSOZ) were quantified at each intensity. The separability of the SOZ and nSOZ using N1 amplitudes was compared between models using responses to titrations, responses to one maximal intensity, or both. ResultsAt 2 mA and above, the increase in N1 amplitude with current intensity was greater for responses within the SOZ, and SOZ response distribution was maximized by 4–6 mA. Models incorporating titrations achieved better separability of SOZ and nSOZ compared to those using one maximal intensity. ConclusionsWe demonstrated that differences in CCEP amplitude over a range of current intensities can improve discriminability of SOZ regions. SignificanceThis study provides insight into the underlying excitability of the SOZ and how differences in current-dependent amplitudes of CCEPs may be used to help localize epileptogenic sites.

Monitoring Cortico-cortical Evoked Potentials Using Only Two 6-strand Strip Electrodes for Gliomas Extending to the Dominant Side of Frontal Operculum During One-step Tumor Removal Surgery

Resection of the dominant side of gliomas extending to the frontal operculum has high risk of severe language dysfunction. Here, we report recording cortico-cortical evoked potentials (CCEP) using only two 6-strand strip electrodes to monitor language-related fibers intraoperatively. We examined whether this simple procedure is useful for removing gliomas extending to the dominant side of frontal operculum. This study included 7 cases of glioma extending to the left frontal operculum. The frontal language area (FLA) was first identified by functional mapping during awake craniotomy. Next, a 6-strand strip electrode was placed on the FLA, while on the temporal side, an electrode was placed so as to slide parallel to the sylvian fissure toward the posterior language area. Electrical stimulation was performed using the electrode on the frontal side, and CCEPs were measured from the electrode on the temporal side. CCEPs were detected in all cases. Immediately after surgery, all patients demonstrated language dysfunction to varying degree. CCEP decreased to 10% in 1 patient, who recovered language function after 24 months. CCEP decreased slightly 80% in 1, and, in the 5 other cases, CCEPs did not change. These 5 patients soon recovered language function within 2 weeks to 1 month. This study confirmed the utility of CCEP monitoring using only two 6-strand strip electrodes during one-step surgery. We believe this simple method helped in monitoring intraoperative language function and predicting its postoperative recovery in patients with gliomas extending to the dominant side of frontal operculum.