Optimized Multilayer Perceptron for Sensorimotor Functional Mapping Based on a Few Minutes of Intracranial Electroencephalogram Data.

Using 6-minute free-running intracranial-electroencephalogram (icEEG) during sleep, an optimized multilayer perceptron (MLP) neural network accurately maps the sensorimotor cortex (SM) and identifies the anterior lip of the central sulcus (CS) in intractable epilepsy patients. We calculated 6 performance metrics to evaluate the MLP's efficacy: accuracy, area under the curve (AUC), recall, precision, F1-scores, and specificity. Each layer had 4 neurons with hyperbolic TanH activation function and 4 with Gaussian distribution function. Conventional 10-fold cross-validation was used. Feature extension (ε) and weighted imbalanced data (w) improved MLP performance. ANN NEUROL 2024;96:187-193.

Functional parcellation of the cingulate gyrus by electrical cortical stimulation: a synthetic literature review and future directions.

BACKGROUND: The cingulate gyrus (CG), a brain structure above the corpus callosum, is recognised as part of the limbic system and plays numerous vital roles. However, its full functional capacity is yet to be understood. In recent years, emerging evidence from imaging modalities, supported by electrical cortical stimulation (ECS) findings, has improved our understanding. To our knowledge, there is a limited number of systematic reviews of the cingulate function studied by ECS. We aim to parcellate the CG by reviewing ECS studies. DESIGN/METHODS: We searched PubMed and Embase for studies investigating CG using ECS. A total of 30 studies met the inclusion criteria. We evaluated the ECS responses across the cingulate subregions and summarised the reported findings. RESULTS: We included 30 studies (totalling 887 patients, with a mean age of 31.8±9.8 years). The total number of electrodes implanted within the cingulate was 3028 electrode contacts; positive responses were obtained in 941 (31.1%, median percentages, 32.3%, IQR 22.2%-64.3%). The responses elicited from the CG were as follows. Simple motor (8 studies, 26.7 %), complex motor (10 studies, 33.3%), gelastic with and without mirth (7 studies, 23.3%), somatosensory (9 studies, 30%), autonomic (11 studies, 36.7 %), psychic (8 studies, 26.7%) and vestibular (3 studies, 10%). Visual and speech responses were also reported. Despite some overlap, the results indicate that the anterior cingulate cortex is responsible for most emotional, laughter and autonomic responses, while the middle cingulate cortex controls most complex motor behaviours, and the posterior cingulate cortex (PCC) regulates visual, among various other responses. Consistent null responses have been observed across different regions, emphasising PCC. CONCLUSIONS: Our results provide a segmental mapping of the functional properties of CG, helping to improve precision in the surgical planning of epilepsy.

Age-dependent vestibular cingulate-cerebral network underlying gravitational perception: a cross-sectional multimodal study.

BACKGROUND AND OBJECTIVES: The cingulate gyrus (CG) is a frequently studied yet not wholly understood area of the human cerebrum. Previous studies have implicated CG in different adaptive cognitive-emotional functions and fascinating or debilitating symptoms. We describe an unusual loss of gravity perception/floating sensation in consecutive persons with drug-resistant epilepsy undergoing electrical cortical stimulation (ECS), network analysis, and network robustness mapping. METHODS: Using Intracranial-EEG, Granger causality analysis, cortico-cortical evoked potentials, and fMRI, we explicate the functional networks arising from this phenomenon's anterior, middle, and posterior cingulate cortex. RESULTS: Fifty-four icEEG cases from 2013 to 2019 were screened. In 40.7% of cases, CG was sampled and in 22.2% the sampling was bilateral. ECS mapping was carried out in 18.5% of the entire cohort and 45.4% of the cingulate sampled cases. Five of the ten CG cases experienced symptoms during stimulation. A total of 1942 electrodes were implanted with a median number of 182 electrode contacts per patient (range: 106-274). The electrode contacts sampled all major cortex regions. Sixty-three contacts were within CG. Of those, 26 were electrically stimulated; 53.8% of the stimulated contacts produced positive responses, whereas 46.2% produced no observable responses. Our study reports a unique perceptive phenomenon of a subjective sense of weightlessness/floating sensation triggered by anterior and posterior CG stimulation, in 30% of cases and 21.42% of electrode stimulation sites. Notable findings include functional connections between the insula, the posterior and anterior cingulate cortex, and networks between the middle cingulate and the frontal and temporal lobes and the cerebellum. We also postulate a vestibular-cerebral-cingulate network responsible for the perception of gravity while suggesting that cingulate functional connectivity follows a long-term developmental trajectory as indicated by a robust, positive correlation with age and the extent of Granger connectivity (r = 0.82, p = 0.0035). DISCUSSION: We propose, in conjunction with ECS techniques, that a better understanding of the underlying gravity perception networks can lead to promising neuromodulatory clinical applications. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence for CG's involvement in the higher order processing of gravity perception and related actions.

The neural networks underlying the illusion of time dilation: case study and literature survey.

This is the first known case report of a profound illusionary time dilation produced by direct electrical cortical stimulation. The patient with drug-resistant epilepsy was undergoing invasive EEG evaluation for the localization of the focus prior to resection. Stimulation of the non-dominant claustrum/insula and inferior right frontal gyrus correlated with the equivalent of a pacemaker of an internal clock in the brain. The site exhibited strong outflow connectivity with a wide region of the right fronto-parietal executive network and pre-motor system. The patient described the experience as unique and fascinating, and underwent resection involving the face motor area where seizures arose from, with a substantial decrease in seizure burden >90%. Extensive brain networks are employed in evaluation/assessment of time, which may be modulated via electrical stimulation. This is the first of such an incident. Further studies may investigate the potential benefit of neuromodulation of these brain regions in the management of conditions in which time-perception may be impaired.

EEG Findings in Coronavirus Disease.

PURPOSE: Neurologic manifestations of coronavirus disease (COVID-19) such as encephalopathy and seizures have been described. To our knowledge, detailed EEG findings in COVID-19 have not yet been reported. This report adds to the scarce body of evidence. METHODS: We identified eight COVID-19 positive patients who underwent EEG monitoring in our hospital system. RESULTS: EEGs were most commonly ordered for an altered level of consciousness, a nonspecific neurologic manifestation. We observed generalized background slowing in all patients and generalized epileptiform discharges with triphasic morphology in three patients. Focal electrographic seizures were observed in one patient with a history of focal epilepsy and in another patient with no such history. Five of eight patients had a previous diagnosis of epilepsy, suggesting that pre-existing epilepsy can be a potential risk factor for COVID-19-associated neurological manifestations. Five of eight patients who underwent EEG experienced a fatal outcome of infection. CONCLUSIONS: Our findings underscore previous observations that neurologic manifestations are common in severe cases. COVID-19 patients with epilepsy may have an increased risk of neurological manifestations and abnormal EEG.

Tongue as a Wire? Glossokinetic Artifact and Insights From Intracranial EEG.

BACKGROUND: Glossokinetic artifact (GKA) is a well-known scalp EEG artifact characterized by deflections within the delta to low-theta frequency bands and dynamic polarity typically attributed to the direction of tongue movement. This study aims to investigate intracranial EEG correlations of scalp-GKA. If the tongue is a dipole, per the conventional view, then volume-conducted deflections are expected in the nearest frontal intracranial EEG contacts. MATERIALS AND METHODS: Simultaneous scalp and intracranial EEG recordings were evaluated in five consecutive medically resistant epilepsy patients at Yale Epilepsy Center in 2017 and 2018, who had classic GKA deflections on scalp EEG. The EEG was sampled at 2,048 to 4,096 Hz and analyzed visually, using a reference placed in the diploic space or over the convexity, and confirmed quantitatively by a statistical framework. Ten GKA deflections were analyzed per case. RESULTS: The medians of age at the time of recording, contacts per case, and amplitude of scalp GKA deflections were 35 years (range: 20-41 years), 171 contacts (range: 165-241 contacts), and 56 µV (range: 51-72 µV), respectively. There were no slow discharges in the frontal intracranial EEG contacts synchronized with the scalp GKA, either in the delta (1-3 Hz) or in the sub-delta (0.1-1 Hz) bands. However, the expected physiologic attenuation of alpha and beta rhythms and the emergence of high-gamma activity were observed over the peri-Rolandic regions in the invasive recordings. CONCLUSIONS: The traditional view of the tongue as a dipole generator of scalp GKA is simplistic and does not account for the findings reported herein. The tongue most probably shunts other scalp and soft-tissue currents. Knowledge of tongue potentials is of interest in the education and the design of tongue-computer interfaces.

Passive localization of the central sulcus during sleep based on intracranial EEG.

We test the performance of a novel operator-independent EEG-based method for passive identification of the central sulcus (CS) and sensorimotor (SM) cortex. We studied seven patients with intractable epilepsy undergoing intracranial EEG (icEEG) monitoring, in whom CS localization was accomplished by standard methods. Our innovative approach takes advantage of intrinsic properties of the primary motor cortex (MC), which exhibits enhanced icEEG band-power and coherence across the CS. For each contact, we computed a composite power, coherence, and entropy values for activity in the high gamma band (80-115) Hz of 6-10 min of NREM sleep. Statistically transformed EEG data values that did not reach a threshold (th) were set to 0. We computed a metric M based on the transformed values and the mean Euclidian distance of each contact from contacts with Z-scores higher than 0. The last step was implemented to accentuate local network activity. The SM cortex exhibited higher EEG-band-power than non-SM cortex (P < 0.0002). There was no significant difference between the motor/premotor and sensory cortices (P < 0.47). CS was localized in all patients with 0.4 < th < 0.6. The primary hand and leg motor areas showed the highest metric values followed by the tongue motor area. Higher threshold values were specific (94%) for the anterior bank of the CS but not sensitive (42%). Intermediate threshold values achieved an acceptable trade-off (0.4: 89% specific and 70% sensitive).

Effect of anesthesia on electrocorticography for localization of epileptic focus: Literature review and future directions.

Intraoperative electrocorticography (ECoG) is a useful technique to guide resections in epilepsy surgery and is mostly performed under general anesthesia. In this systematic literature review, we seek to investigate the effect of anesthetic agents on the quality and reliability of ECoG for localization of the epileptic focus. We conducted a systematic search using PubMed and EMBASE until January 2019, aiming to review the effects of anesthesia on ECoG yield. Fifty-eight studies were included from 1016 reviewed. There are favorable reports for dexmedetomidine and remifentanil during ECoG recording. There is inadequate, or sometimes conflicting, evidence to support using enflurane, isoflurane, sevoflurane, and propofol. There is evidence to avoid halothane, nitrous oxide, etomidate, ketamine, thiopental, methohexital, midazolam, fentanyl, and alfentanil due to undesired effects. Depth of anesthesia, intraoperative awareness, and surgical outcomes were not consistently evaluated. Available studies provide helpful information about the effect of anesthesia on ECoG to localize the epileptic focus. The proper use of anesthetic agents and careful dose titration, and effective communication between the neurophysiologist and anesthesiologist based on ECoG activity are essential in optimizing recordings. Anesthesia is a crucial variate to consider in the design of studies investigating ECoG and related biomarkers.

Brief history of electrical cortical stimulation: A journey in time from Volta to Penfield.

OBJECTIVE: To recount the evolution of Electrical Cortical Stimulation (ECS) in localizing brain functions with an emphasis on epilepsy, and a discussion of related instruments and personnel. DESIGN/METHODS: Literature review through historical archives implementing chain-referral sampling. RESULTS: There were important milestones leading to the incorporation of ECS into practice: 1. Aldini's (1802) first known stimulation of exposed brain to defend Galvani's views on excitability in the frog-leg experiment against Volta's, ironically by employing the Voltaic pile. 2. Animal experiments in the 19th-century to study the brain and to optimize the procedure: Rolando (1809) reported on motor induction, Fritsch and Hitzig (ca. 1870) introduced the concepts of bipolar and threshold stimulation, and Ferrier (1873) generated reproducible homunculi in animals. 3. Parallel to 2, advances were made based on clinical observations by Bravais, Todd, Jackson, and Broca among others. 4. First known stimulation in conscious humans by Bartholow (1874) led to catastrophic outcomes. Horsley (1886) performed first intraoperative stimulation on Jackson's epileptic patient. 5. Advances accelerated in the first-half of the 20th century with Cushing (1909) performing first awake-craniotomy eliciting sensory responses to Penfield's work culminating in standardization of clinical use and generation of detailed maps including the famous sensory-motor homunculi. Parallel advances in instrumentation were made from the Leyden jar (1745) to present customizable current-controlled stimulators. CONCLUSIONS: ECS is commonly used in neurosurgery for localization of brain functions and is the benchmark for research studies. Significant leaps have been made since ECS first used in the 19th century. It evolved to remain the gold standard for localization of human brain functions in the 21st century.

The connectivity index: an effective metric for grading epileptogenicity.

OBJECTIVE: The aim of this study was to investigate the performance of a metric of functional connectivity to classify and grade the excitability of brain regions based on evoked potentials in response to single-pulse electrical stimulation (SPES). METHODS: Patients who underwent 1-Hz frequency stimulation at prospectively selected contacts between 2003 and 2014 at the Yale Comprehensive Epilepsy Center were included. The stimulated contacts were classified as the seizure onset zone (SOZ), highly irritative zone (possibly epileptogenic irritative zone [IZp]), and control contacts not involved in the epileptic activity. Response contacts were classified as SOZ, active interictal irritative zone (IZ), quiet, or other. The normalized number of responses was defined as the number of contacts with any evoked responses divided by the total number of recorded contacts, and the normalized distance is the ratio of the average distance between the site of stimulation and sites of evoked responses to the average distances between the site of stimulation and all other recording contacts. A new metric that the authors labeled the connectivity index (CI) is defined as the product of the 2 values. RESULTS: A total of 57 stimulation sessions in 22 patients were analyzed. The CI of the SOZ was higher than for control contacts (median CI of 0.74 vs 0.16, p = 0.0002). The evoked responses after stimulation of SOZ were seen at further distances compared to control (median normalized distance 0.96 vs 0.62, p = 0.0005). It was 1.8 times more likely that a response would be recorded at the SOZ than in nonepileptic contacts after stimulation of a control site. Habitual seizures were triggered in 27% of patients and 35% of SOZ contacts (median stimulation intensity 4 mA) but in none of the control or IZp contacts. Non-SOZ contacts in multifocal or poor surgical outcome cases had a higher CI than non-SOZ contacts in patients with localizable onsets (median CI of 0.5 vs 0.12, p = 0.04). There was a correlation between the stimulation current intensity and the normalized number of evoked responses (r = + 0.49, p = 0.01) but not with distance (r = + 0.1, p = 0.64). CONCLUSIONS: The authors found enhanced connectivity when stimulating the SOZ compared to stimulating control contacts; responses were more distant as well. Habitual auras and seizures provoked by SPES were highly predictive of brain sites involved in seizure generation.

Brain-Computer Interface (BCI) Applications in Mapping of Epileptic Brain Networks Based on Intracranial-EEG: An Update.

The main applications of the Brain-Computer Interface (BCI) have been in the domain of rehabilitation, control of prosthetics, and in neuro-feedback. Only a few clinical applications presently exist for the management of drug-resistant epilepsy. Epilepsy surgery can be a life-changing procedure in the subset of millions of patients who are medically intractable. Recording of seizures and localization of the Seizure Onset Zone (SOZ) in the subgroup of "surgical" patients, who require intracranial-EEG (icEEG) evaluations, remain to date the best available surrogate marker of the epileptogenic tissue. icEEG presents certain risks and challenges making it a frontier that will benefit from optimization. Despite the presentation of several novel biomarkers for the localization of epileptic brain regions (HFOs-spikes vs. Spikes for instance), integration of most in practices is not at the prime time as it requires a degree of knowledge about signal and computation. The clinical care remains inspired by the original practices of recording the seizures and expert visual analysis of rhythms at onset. It is becoming increasingly evident, however, that there is more to infer from the large amount of EEG data sampled at rates in the order of less than 1 ms and collected over several days of invasive EEG recordings than commonly done in practice. This opens the door for interesting areas at the intersection of neuroscience, computation, engineering and clinical care. Brain-Computer interface (BCI) has the potential of enabling the processing of a large amount of data in a short period of time and providing insights that are not possible otherwise by human expert readers. Our practices suggest that implementation of BCI and Real-Time processing of EEG data is possible and suitable for most standard clinical applications, in fact, often the performance is comparable to a highly qualified human readers with the advantage of producing the results in real-time reliably and tirelessly. This is of utmost importance in specific environments such as in the operating room (OR) among other applications. In this review, we will present the readers with potential targets for BCI in caring for patients with surgical epilepsy.

Restoration of brain circulation and cellular functions hours post-mortem.

The brains of humans and other mammals are highly vulnerable to interruptions in blood flow and decreases in oxygen levels. Here we describe the restoration and maintenance of microcirculation and molecular and cellular functions of the intact pig brain under ex vivo normothermic conditions up to four hours post-mortem. We have developed an extracorporeal pulsatile-perfusion system and a haemoglobin-based, acellular, non-coagulative, echogenic, and cytoprotective perfusate that promotes recovery from anoxia, reduces reperfusion injury, prevents oedema, and metabolically supports the energy requirements of the brain. With this system, we observed preservation of cytoarchitecture; attenuation of cell death; and restoration of vascular dilatory and glial inflammatory responses, spontaneous synaptic activity, and active cerebral metabolism in the absence of global electrocorticographic activity. These findings demonstrate that under appropriate conditions the isolated, intact large mammalian brain possesses an underappreciated capacity for restoration of microcirculation and molecular and cellular activity after a prolonged post-mortem interval.

A Switch and Wave of Neuronal Activity in the Cerebral Cortex During the First Second of Conscious Perception.

Conscious perception occurs within less than 1 s. To study events on this time scale we used direct electrical recordings from the human cerebral cortex during a conscious visual perception task. Faces were presented at individually titrated visual threshold for 9 subjects while measuring broadband 40-115 Hz gamma power in a total of 1621 intracranial electrodes widely distributed in both hemispheres. Surface maps and k-means clustering analysis showed initial activation of visual cortex for both perceived and non-perceived stimuli. However, only stimuli reported as perceived then elicited a forward-sweeping wave of activity throughout the cerebral cortex accompanied by large-scale network switching. Specifically, a monophasic wave of broadband gamma activation moves through bilateral association cortex at a rate of approximately 150 mm/s and eventually reenters visual cortex for perceived but not for non-perceived stimuli. Meanwhile, the default mode network and the initial visual cortex and higher association cortex networks are switched off for the duration of conscious stimulus processing. Based on these findings, we propose a new "switch-and-wave" model for the processing of consciously perceived stimuli. These findings are important for understanding normal conscious perception and may also shed light on its vulnerability to disruption by brain disorders.

Presurgical language fMRI: Technical practices in epilepsy surgical planning.

Little is known about how language functional MRI (fMRI) is executed in clinical practice in spite of its widespread use. Here we comprehensively documented its execution in surgical planning in epilepsy. A questionnaire focusing on cognitive design, image acquisition, analysis and interpretation, and practical considerations was developed. Individuals responsible for collecting, analyzing, and interpreting clinical language fMRI data at 63 epilepsy surgical programs responded. The central finding was of marked heterogeneity in all aspects of fMRI. Most programs use multiple tasks, with a fifth routinely using 2, 3, 4, or 5 tasks with a modal run duration of 5 min. Variants of over 15 protocols are in routine use with forms of noun-verb generation, verbal fluency, and semantic decision-making used most often. Nearly all aspects of data acquisition and analysis vary markedly. Neither of the two best-validated protocols was used by more than 10% of respondents. Preprocessing steps are broadly consistent across sites, language-related blood flow is most often identified using general linear modeling (76% of respondents), and statistical thresholding typically varies by patient (79%). The software SPM is most often used. fMRI programs inconsistently include input from experts with all required skills (imaging, cognitive assessment, MR physics, statistical analysis, and brain-behavior relationships). These data highlight marked gaps between the evidence supporting fMRI and its clinical application. Teams performing language fMRI may benefit from evaluating practice with reference to the best-validated protocols to date and ensuring individuals trained in all aspects of fMRI are involved to optimize patient care.

Assessment of the Utility of Ictal Magnetoencephalography in the Localization of the Epileptic Seizure Onset Zone.

Importance: Literature on ictal magnetoencephalography (MEG) in clinical practice and the relationship to other modalities is limited because of the brevity of routine studies. Objective: To investigate the utility and reliability of ictal MEG in the localization of the epileptogenic zone. Design, Setting, and Participants: A retrospective medical record review and prospective analysis of a novel ictal rhythm analysis method was conducted at a tertiary epilepsy center with a wide base of referrals for epilepsy surgery evaluation and included consecutive cases of patients who experienced epileptic seizures during routine MEG studies from March 2008 to February 2012. A total of 377 studies screened. Data were analyzed from November 2011 to October 2015. Main Outcomes and Measures: Presurgical workup and interictal and ictal MEG data were reviewed. The localizing value of using extended-source localization of a narrow band identified visually at onset was analyzed. Results: Of the 44 included patients, the mean (SD) age at the time of recording was 19.3 (14.9) years, and 25 (57%) were male. The mean duration of recording was 51.2 minutes. Seizures were provoked by known triggers in 3 patients and were spontaneous otherwise. Twenty-five patients (57%) had 1 seizure, 6 (14%) had 2, and 13 (30%) had 3 or more. Magnetoencephalography single equivalent current dipole analysis was possible in 29 patients (66%), of whom 8 (28%) had no clear interictal discharges. Sublobar concordance between ictal and interictal dipoles was seen in 18 of 21 patients (86%). Three patients (7%) showed clear ictal MEG patterns without electroencephalography changes. Ictal MEG dipoles correlated with the lobe of onset in 7 of 8 patients (88%) who underwent intracranial electroencephalography evaluations. Reasons for failure to identify ictal dipoles included diffuse or poor dipolar ictal patterns, no MEG changes, and movement artifact. Resection of areas containing a minimum-norm estimate of a narrow band at onset, not single equivalent current dipole, was associated with sustained seizure freedom. Conclusions and Significance: Ictal MEG data can provide reliable localization, including in cases that are difficult to localize by other modalities. These findings support the use of extended-source localization for seizures recorded during MEG.

Averaging in time-frequency domain reveals the temporal and spatial extent of seizures recorded by scalp EEG.

To demonstrate the importance of averaging in time-frequency space and the added localizing value in time and space in a case of cortical myoclonus. One hundred myoclonic jerks were averaged in time series and in spectral domain. For the latter, we chose 100 (10-second) segments from interictal background and used the unpaired t-test for the jerk-related and control spectral data to obtain the t value and corresponding p value at each pixel. We corrected for multiple comparisons using false discovery rate procedure. We generated maps of spectral significance per electrode. All insignificant t-values were converted to 0 for easier visual analysis. Standard back-averaging of 100 jerks disclosed a single spike preceding EMG activity by 19-27 milliseconds. No other definite ictal patterns were discernible in the time domain. Statistical analysis of the same 100 epochs in the time-frequency domain disclosed a greater temporal extent of the seizure, as well as a more detailed rendering of rhythms and frequencies involved. Valproate was added and led to substantial improvement. Averaging in the spectral domain may reveal frequency-specific changes that may not be otherwise appreciated in the time domain. Future studies may elucidate the effect on the sensitivity of diagnosis of simple partial seizures and auras.