Intracranial electrophysiological recordings from the human brain during memory tasks with pupillometry

Data comprise intracranial EEG (iEEG) brain activity represented by stereo EEG (sEEG) signals, recorded from over 100 electrode channels implanted in any one patient across various brain regions. The iEEG signals were recorded in epilepsy patients (N = 10) undergoing invasive monitoring and localization of seizures when they were performing a battery of four memory tasks lasting approx. 1 hour in total. Gaze tracking on the task computer screen with estimating the pupil size was also recorded together with behavioral performance. Each dataset comes from one patient with anatomical localization of each electrode contact. Metadata contains labels for the recording channels with behavioral events marked from all tasks, including timing of correct and incorrect vocalization of the remembered stimuli. The iEEG and the pupillometric signals are saved in BIDS data structure to facilitate efficient data sharing and analysis.

More Than Spikes: On the Added Value of Non-linear Intracranial EEG Analysis for Surgery Planning in Temporal Lobe Epilepsy

Epilepsy surgery can be a very effective therapy in medication refractory patients. During patient evaluation intracranial EEG is analyzed by clinical experts to identify the brain tissue generating epileptiform events. Quantitative EEG analysis increasingly complements this approach in research settings, but not yet in clinical routine. We investigate the correspondence between epileptiform events and a specific quantitative EEG marker. We analyzed 99 preictal epochs of multichannel intracranial EEG of 40 patients with mixed etiologies. Time and channel of occurrence of epileptiform events (spikes, slow waves, sharp waves, fast oscillations) were annotated by a human expert and non-linear excess interrelations were calculated as a quantitative EEG marker. We assessed whether the visually identified preictal events predicted channels that belonged to the seizure onset zone, that were later resected or that showed strong non-linear interrelations. We also investigated whether the seizure onset zone or the resection were predicted by channels with strong non-linear interrelations. In patients with temporal lobe epilepsy (32 of 40), epileptic spikes and the seizure onset zone predicted the resected brain tissue much better in patients with favorable seizure control after surgery than in unfavorable outcomes. Beyond that, our analysis did not reveal any significant associations with epileptiform EEG events. Specifically, none of the epileptiform event types did predict non-linear interrelations. In contrast, channels with strong non-linear excess EEG interrelations predicted the resected channels better in patients with temporal lobe epilepsy and favorable outcome. Also in the small number of patients with seizure onset in the frontal and parietal lobes, no association between epileptiform events and channels with strong non-linear excess EEG interrelations was detectable. In contrast to patients with temporal seizure onset, EEG channels with strong non-linear excess interrelations did neither predict the seizure onset zone nor the resection of these patients or allow separation between patients with favorable and unfavorable seizure control. Our study indicates that non-linear excess EEG interrelations are not strictly associated with epileptiform events, which are one key concept of current clinical EEG assessment. Rather, they may provide information relevant for surgery planning in temporal lobe epilepsy. Our study suggests to incorporate quantitative EEG analysis in the workup of clinical cases. We make the EEG epochs and expert annotations publicly available in anonymized form to foster similar analyses for other quantitative EEG methods.

Region-specific complexity of the intracranial EEG in the sleeping human brain

As the brain is a complex system with occurrence of self-similarity at different levels, a dedicated analysis of the complexity of brain signals is of interest to elucidate the functional role of various brain regions across the various stages of vigilance. We exploited intracranial electroencephalogram data from 38 cortical regions using the Higuchi fractal dimension (HFD) as measure to assess brain complexity, on a dataset of 1772 electrode locations. HFD values depended on sleep stage and topography. HFD increased with higher levels of vigilance, being highest during wakefulness in the frontal lobe. HFD did not change from wake to stage N2 in temporo-occipital regions. The transverse temporal gyrus was the only area in which the HFD did not differ between any two vigilance stages. Interestingly, HFD of wakefulness and stage R were different mainly in the precentral gyrus, possibly reflecting motor inhibition in stage R. The fusiform and parahippocampal gyri were the only areas showing no difference between wakefulness and N2. Stages R and N2 were similar only for the postcentral gyrus. Topographical analysis of brain complexity revealed that sleep stages are clearly differentiated in fronto-central brain regions, but that temporo-occipital regions sleep differently.

Imagined speech can be decoded from low- and cross-frequency intracranial EEG features

Reconstructing intended speech from neural activity using brain-computer interfaces holds great promises for people with severe speech production deficits. While decoding overt speech has progressed, decoding imagined speech has met limited success, mainly because the associated neural signals are weak and variable compared to overt speech, hence difficult to decode by learning algorithms. We obtained three electrocorticography datasets from 13 patients, with electrodes implanted for epilepsy evaluation, who performed overt and imagined speech production tasks. Based on recent theories of speech neural processing, we extracted consistent and specific neural features usable for future brain computer interfaces, and assessed their performance to discriminate speech items in articulatory, phonetic, and vocalic representation spaces. While high-frequency activity provided the best signal for overt speech, both low- and higher-frequency power and local cross-frequency contributed to imagined speech decoding, in particular in phonetic and vocalic, i.e. perceptual, spaces. These findings show that low-frequency power and cross-frequency dynamics contain key information for imagined speech decoding.

A novel method for multi-scale recording of intracranial EEG through dynamic alteration of electrode surface area

Intracranial EEG (iEEG) plays a critical role in the treatment of neurological diseases, such as epilepsy and Parkinson's disease, as well as the development of neural prostheses and brain computer interfaces. While electrode geometries vary widely across these applications, the impact of electrode size on iEEG features and morphology is not well understood. Some insight has been gained from computer simulation studies and experiments in which signals are recorded using electrodes of different sizes concurrently in different brain regions. Here, we introduce a novel method to record from electrodes of different sizes in the exact same location by changing the size of iEEG electrodes after implantation in the brain. We first present a theoretical model and an in vitro validation of the method. We then report the results of an in vivo implementation in three human subjects with refractory epilepsy. We recorded iEEG data from three different electrode sizes and compared the amplitudes, power spectra, interchannel correlations, and signal-to-noise ratio (SNR) of interictal epileptiform discharges, i.e., epileptic spikes. We found that iEEG amplitude and power decreased as electrode size increased, while inter-channel correlation increased with electrode size. The SNR of epileptic spikes was generally highest in the smallest electrodes, but 39% of spikes had maximal SNR in medium or large electrodes. This likely depends on the precise location and spatial spread of each spike. Overall, this new method enables multi-scale measurements of electrical activity in the human brain that facilitate our understanding of neurophysiology, treatment of neurological disease, and development of novel technologies.

Engineering Nonlinear Epileptic Biomarkers Using Deep Learning and Benford’s Law

In this study we designed two deep neural networks to encode 16 feature latent spaces for early seizure detection in intracranial EEG and compared them to 16 widely used engineered metrics: Epileptogenicity Index (EI), Phase Locked High Gamma (PLHG), Time and Frequency Domain Cho Gaines Distance (TDCG, FDCG), relative band powers, and log absolute band powers (from alpha, beta, theta, delta, gamma, and high gamma bands. The deep learning models were pretrained for seizure identification on the time and frequency domains of one second single channel clips of 127 seizures (from 25 different subjects) using “leave-one-out” (LOO) cross validation. Each neural network extracted unique feature spaces that were used to train a Random Forest Classifier (RFC) for seizure identification and latency tasks. The Gini Importance of each feature was calculated from the pretrained RFC, enabling the most significant features (MSFs) for each task to be identified. The MSFs were extracted from the UPenn and Mayo Clinic's Seizure Detection Challenge to train another RFC for the contest. They obtained an AUC score of 0.93, demonstrating a transferable method to identify interpretable biomarkers for seizure detection.

Thalamic deep brain stimulation modulates cycles of seizure risk in epilepsy

Chronic brain recordings suggest that seizure risk is not uniform, but rather varies systematically relative to daily (circadian) and multiday (multidien) cycles. Here, one human and seven dogs with naturally occurring epilepsy had continuous intracranial EEG (median 298 days) using novel implantable sensing and stimulation devices. Two pet dogs and the human subject received concurrent thalamic deep brain stimulation (DBS) over multiple months. All subjects had circadian and multiday cycles in the rate of interictal epileptiform spikes (IES). There was seizure phase locking to circadian and multiday IES cycles in five and seven out of eight subjects, respectively. Thalamic DBS modified circadian (all 3 subjects) and multiday (analysis limited to the human participant) IES cycles. DBS modified seizure clustering and circadian phase locking in the human subject. Multiscale cycles in brain excitability and seizure risk are features of human and canine epilepsy and are modifiable by thalamic DBS.

Theta rhythmicity governs human behavior and hippocampal signals during memory-dependent tasks

Memory formation and reinstatement are thought to lock to the hippocampal theta rhythm, predicting that encoding and retrieval processes appear rhythmic themselves. Here, we show that rhythmicity can be observed in behavioral responses from memory tasks, where participants indicate, using button presses, the timing of encoding and recall of cue-object associative memories. We find no evidence for rhythmicity in button presses for visual tasks using the same stimuli, or for questions about already retrieved objects. The oscillations for correctly remembered trials center in the slow theta frequency range (1-5 Hz). Using intracranial EEG recordings, we show that the memory task induces temporally extended phase consistency in hippocampal local field potentials at slow theta frequencies, but significantly more for remembered than forgotten trials, providing a potential mechanistic underpinning for the theta oscillations found in behavioral responses.