Neuronal current imaging of epileptic activity: An MRI study in patients with a first unprovoked epileptic seizure.

OBJECTIVE: This study evaluates the performance of the novel MRI sequence stimulus-induced rotary saturation (SIRS) to map responses to interictal epileptic activity in the human cortex. Spin-lock pulses have been applied to indirectly detect neuronal activity through magnetic field perturbations. Following initial reports about the feasibility of the method in humans and animals with epilepsy, we aimed to investigate the diagnostic yield of spin-lock MR pulses in comparison with scalp-EEG in first seizure patients. METHODS: We employed a novel method for measurements of neuronal activity through the detection of a resonant oscillating field, stimulus-induced rotary saturation contrast (SIRS) at spin-lock frequencies of 120 and 240 Hz acquired at a single 3T MRI system. Within a prospective observational study, we conducted SIRS experiments in 55 patients within 7 days after a suspected first unprovoked epileptic seizure and 61 healthy control subjects. In this study, we report on the analysis of data from a single 3T MRI system, encompassing 35 first seizure patients and 31 controls. RESULTS: The SIRS method was applicable in all patients and healthy controls at frequencies of 120 and 240 Hz. We did not observe any significant age- or sex-related differences. Specificity of SIRS at 120 Hz was 90.3% and 93.5% at 240 Hz. Sensitivity was 17.1% at 120 Hz and 40.0% at 240 Hz. SIGNIFICANCE: SIRS targets neuronal oscillating magnetic fields in patients with epilepsy. The coupling of presaturated spins to epilepsy-related magnetic field perturbations may serve as a-at this stage experimental-diagnostic test in first seizure patients to complement EEG findings as a standard screening test. PLAIN LANGUAGE SUMMARY: Routine diagnostic tests carry several limitations when applied after a suspected first seizure. SIRS is a noninvasive MRI method to enable time-sensitive diagnosis of image correlates of epileptic activity with increased sensitivity compared to routine EEG.

Feasibility, Safety, and Performance of Full-Head Subscalp EEG Using Minimally Invasive Electrode Implantation.

BACKGROUND AND OBJECTIVES: Current practice in clinical neurophysiology is limited to short recordings with conventional EEG (days) that fail to capture a range of brain (dys)functions at longer timescales (months). The future ability to optimally manage chronic brain disorders, such as epilepsy, hinges upon finding methods to monitor electrical brain activity in daily life. We developed a device for full-head subscalp EEG (Epios) and tested here the feasibility to safely insert the electrode leads beneath the scalp by a minimally invasive technique (primary outcome). As secondary outcome, we verified the noninferiority of subscalp EEG in measuring physiologic brain oscillations and pathologic discharges compared with scalp EEG, the established standard of care. METHODS: Eight participants with pharmacoresistant epilepsy undergoing intracranial EEG received in the same surgery subscalp electrodes tunneled between the scalp and the skull with custom-made tools. Postoperative safety was monitored on an inpatient ward for up to 9 days. Sleep-wake, ictal, and interictal EEG signals from subscalp, scalp, and intracranial electrodes were compared quantitatively using windowed multitaper transforms and spectral coherence. Noninferiority was tested for pairs of neighboring subscalp and scalp electrodes with a Bland-Altman analysis for measurement bias and calculation of the interclass correlation coefficient (ICC). RESULTS: As primary outcome, up to 28 subscalp electrodes could be safely placed over the entire head through 1-cm scalp incisions in a ∼1-hour procedure. Five of 10 observed perioperative adverse events were linked to the investigational procedure, but none were serious, and all resolved. As a secondary outcome, subscalp electrodes advantageously recorded EEG percutaneously without requiring any maintenance and were noninferior to scalp electrodes for measuring (1) variably strong, stage-specific brain oscillations (alpha in wake, delta, sigma, and beta in sleep) and (2) interictal spikes peak-potentials and ictal signals coherent with seizure propagation in different brain regions (ICC >0.8 and absence of bias). DISCUSSION: Recording full-head subscalp EEG for localization and monitoring purposes is feasible up to 9 days in humans using minimally invasive techniques and noninferior to the current standard of care. A longer prospective ambulatory study of the full system will be necessary to establish the safety and utility of this innovative approach. TRIAL REGISTRATION INFORMATION: clinicaltrials.gov/study/NCT04796597.

Ultra-Long-Term-EEG Monitoring (ULTEEM) Systems: Towards User-Friendly Out-of-Hospital Recordings of Electrical Brain Signals in Epilepsy.

Epilepsy is characterized by the occurrence of epileptic events, ranging from brief bursts of interictal epileptiform brain activity to their most dramatic manifestation as clinically overt bilateral tonic-clonic seizures. Epileptic events are often modulated in a patient-specific way, for example by sleep. But they also reveal temporal patterns not only on ultra- and circadian, but also on multidien scales. Thus, to accurately track the dynamics of epilepsy and to thereby enable and improve personalized diagnostics and therapies, user-friendly systems for long-term out-of-hospital recordings of electrical brain signals are needed. Here, we present two wearable devices, namely ULTEEM and ULTEEMNite, to address this unmet need. We demonstrate how the usability concerns of the patients and the signal quality requirements of the clinicians have been incorporated in the design. Upon testbench verification of the devices, ULTEEM was successfully benchmarked against a reference EEG device in a pilot clinical study. ULTEEMNite was shown to record typical macro- and micro-sleep EEG characteristics in a proof-of-concept study. We conclude by discussing how these devices can be further improved and become particularly useful for a better understanding of the relationships between sleep, epilepsy, and neurodegeneration.

Triggered Seizures for Ictal SPECT Imaging: A Case Series and Feasibility Study.

Ictal SPECT is an informative seizure imaging technique to tailor epilepsy surgery. However, capturing the onset of unpredictable seizures is a medical and logistic challenge. Here, we sought to image planned seizures triggered by direct stimulation of epileptic networks via stereotactic electroencephalography (sEEG) electrodes. Methods: In this case series of 3 adult participants with left temporal epilepsy, we identified and stimulated sEEG contacts able to trigger patient-typical seizures. We administered 99mTc-HMPAO within 12 s of ictal onset and acquired SPECT images within 40 min without any adverse events. Results: Ictal hyperperfusion maps partially overlapped concomitant sEEG seizure activity. In both participants known for periictal aphasia, SPECT imaging revealed hyperperfusion in the speech cortex lacking sEEG coverage. Conclusion: Triggering of seizures for ictal SPECT complements discrete sEEG sampling with spatially complete images of early seizure propagation. This readily implementable method revives interest in seizure imaging to guide resective epilepsy surgery.

Neural complexity and the spectral slope characterise auditory processing in wakefulness and sleep.

Auditory processing and the complexity of neural activity can both indicate residual consciousness levels and differentiate states of arousal. However, how measures of neural signal complexity manifest in neural activity following environmental stimulation and, more generally, how the electrophysiological characteristics of auditory responses change in states of reduced consciousness remain under-explored. Here, we tested the hypothesis that measures of neural complexity and the spectral slope would discriminate stages of sleep and wakefulness not only in baseline electroencephalography (EEG) activity but also in EEG signals following auditory stimulation. High-density EEG was recorded in 21 participants to determine the spatial relationship between these measures and between EEG recorded pre- and post-auditory stimulation. Results showed that the complexity and the spectral slope in the 2-20 Hz range discriminated between sleep stages and had a high correlation in sleep. In wakefulness, complexity was strongly correlated to the 20-40 Hz spectral slope. Auditory stimulation resulted in reduced complexity in sleep compared to the pre-stimulation EEG activity and modulated the spectral slope in wakefulness. These findings confirm our hypothesis that electrophysiological markers of arousal are sensitive to sleep/wake states in EEG activity during baseline and following auditory stimulation. Our results have direct applications to studies using auditory stimulation to probe neural functions in states of reduced consciousness.

High expectations on phase locking: Better quantifying the concentration of circular data.

The degree to which unimodal circular data are concentrated around the mean direction can be quantified using the mean resultant length, a measure known under many alternative names, such as the phase locking value or the Kuramoto order parameter. For maximal concentration, achieved when all of the data take the same value, the mean resultant length attains its upper bound of one. However, for a random sample drawn from the circular uniform distribution, the expected value of the mean resultant length achieves its lower bound of zero only as the sample size tends to infinity. Moreover, as the expected value of the mean resultant length depends on the sample size, bias is induced when comparing the mean resultant lengths of samples of different sizes. In order to ameliorate this problem, here, we introduce a re-normalized version of the mean resultant length. Regardless of the sample size, the re-normalized measure has an expected value that is essentially zero for a random sample from the circular uniform distribution, takes intermediate values for partially concentrated unimodal data, and attains its upper bound of one for maximal concentration. The re-normalized measure retains the simplicity of the original mean resultant length and is, therefore, easy to implement and compute. We illustrate the relevance and effectiveness of the proposed re-normalized measure for mathematical models and electroencephalographic recordings of an epileptic seizure.

Clinical Evaluation of a Quantitative Imaging Biomarker Supporting Radiological Assessment of Hippocampal Sclerosis.

OBJECTIVE: To evaluate the influence of quantitative reports (QReports) on the radiological assessment of hippocampal sclerosis (HS) from MRI of patients with epilepsy in a setting mimicking clinical reality. METHODS: The study included 40 patients with epilepsy, among them 20 with structural abnormalities in the mesial temporal lobe (13 with HS). Six raters blinded to the diagnosis assessed the 3T MRI in two rounds, first using MRI only and later with both MRI and the QReport. Results were evaluated using inter-rater agreement (Fleiss' kappa [Formula: see text]) and comparison with a consensus of two radiological experts derived from clinical and imaging data, including 7T MRI. RESULTS: For the primary outcome, diagnosis of HS, the mean accuracy of the raters improved from 77.5% with MRI only to 86.3% with the additional QReport (effect size [Formula: see text]). Inter-rater agreement increased from [Formula: see text] to [Formula: see text]. Five of the six raters reached higher accuracies, and all reported higher confidence when using the QReports. CONCLUSION: In this pre-use clinical evaluation study, we demonstrated clinical feasibility and usefulness as well as the potential impact of a previously suggested imaging biomarker for radiological assessment of HS.

Intrinsic Neural Timescales in the Temporal Lobe Support an Auditory Processing Hierarchy.

During rest, intrinsic neural dynamics manifest at multiple timescales, which progressively increase along visual and somatosensory hierarchies. Theoretically, intrinsic timescales are thought to facilitate processing of external stimuli at multiple stages. However, direct links between timescales at rest and sensory processing, as well as translation to the auditory system are lacking. Here, we measured intracranial EEG in 11 human patients with epilepsy (4 women), while listening to pure tones. We show that, in the auditory network, intrinsic neural timescales progressively increase, while the spectral exponent flattens, from temporal to entorhinal cortex, hippocampus, and amygdala. Within the neocortex, intrinsic timescales exhibit spatial gradients that follow the temporal lobe anatomy. Crucially, intrinsic timescales at baseline can explain the latency of auditory responses: as intrinsic timescales increase, so do the single-electrode response onset and peak latencies. Our results suggest that the human auditory network exhibits a repertoire of intrinsic neural dynamics, which manifest in cortical gradients with millimeter resolution and may provide a variety of temporal windows to support auditory processing.SIGNIFICANCE STATEMENT Endogenous neural dynamics are often characterized by their intrinsic timescales. These are thought to facilitate processing of external stimuli. However, a direct link between intrinsic timing at rest and sensory processing is missing. Here, with intracranial EEG, we show that intrinsic timescales progressively increase from temporal to entorhinal cortex, hippocampus, and amygdala. Intrinsic timescales at baseline can explain the variability in the timing of intracranial EEG responses to sounds: cortical electrodes with fast timescales also show fast- and short-lasting responses to auditory stimuli, which progressively increase in the hippocampus and amygdala. Our results suggest that a hierarchy of neural dynamics in the temporal lobe manifests across cortical and limbic structures and can explain the temporal richness of auditory responses.

Large-scale transient peri-ictal perfusion magnetic resonance imaging abnormalities detected by quantitative image analysis.

Epileptic seizures require a rapid and safe diagnosis to minimize the time from onset to adequate treatment. Some epileptic seizures can be diagnosed clinically with the respective expertise. For more subtle seizures, imaging is mandatory to rule out treatable structural lesions and potentially life-threatening conditions. MRI perfusion abnormalities associated with epileptic seizures have been reported in CT and MRI studies. However, the interpretation of transient peri-ictal MRI abnormalities is routinely based on qualitative visual analysis and therefore reader dependent. In this retrospective study, we investigated the diagnostic yield of visual analysis of perfusion MRI during ictal and postictal states based on comparative expert ratings in 51 patients. We further propose an automated semi-quantitative method for perfusion analysis to determine perfusion abnormalities observed during ictal and postictal MRI using dynamic susceptibility contrast MRI, which we validated on a subcohort of 27 patients. The semi-quantitative method provides a parcellation of 3D T1-weighted images into 32 standardized cortical regions of interests and subcortical grey matter structures based on a recently proposed method, direct cortical thickness estimation using deep learning-based anatomy segmentation and cortex parcellation for brain anatomy segmentation. Standard perfusion maps from a Food and Drug Administration-approved image analysis tool (Olea Sphere 3.0) were co-registered and investigated for region-wise differences between ictal and postictal states. These results were compared against the visual analysis of two readers experienced in functional image analysis in epilepsy. In the ictal group, cortical hyperperfusion was present in 17/18 patients (94% sensitivity), whereas in the postictal cohort, cortical hypoperfusion was present only in 9/33 (27%) patients while 24/33 (73%) showed normal perfusion. The (semi-)quantitative dynamic susceptibility contrast MRI perfusion analysis indicated increased thalamic perfusion in the ictal cohort and hypoperfusion in the postictal cohort. Visual ratings between expert readers performed well on the patient level, but visual rating agreement was low for analysis of subregions of the brain. The asymmetry of the automated image analysis correlated significantly with the visual consensus ratings of both readers. We conclude that expert analysis of dynamic susceptibility contrast MRI effectively discriminates ictal versus postictal perfusion patterns. Automated perfusion evaluation revealed favourable interpretability and correlated well with the classification of the visual ratings. It may therefore be employed for high-throughput, large-scale perfusion analysis in extended cohorts, especially for research questions with limited expert rater capacity.

From basic sciences and engineering to epileptology: A translational approach.

Collaborative efforts between basic scientists, engineers, and clinicians are enabling translational epileptology. In this article, we summarize the recent advances presented at the International Conference for Technology and Analysis of Seizures (ICTALS 2022): (1) novel developments of structural magnetic resonance imaging; (2) latest electroencephalography signal-processing applications; (3) big data for the development of clinical tools; (4) the emerging field of hyperdimensional computing; (5) the new generation of artificial intelligence (AI)-enabled neuroprostheses; and (6) the use of collaborative platforms to facilitate epilepsy research translation. We highlight the promise of AI reported in recent investigations and the need for multicenter data-sharing initiatives.

Development of an Open-source and Lightweight Sensor Recording Software System for Conducting Biomedical Research: Technical Report.

BACKGROUND: Digital sensing devices have become an increasingly important component of modern biomedical research, as they help provide objective insights into individuals' everyday behavior in terms of changes in motor and nonmotor symptoms. However, there are significant barriers to the adoption of sensor-enhanced biomedical solutions in terms of both technical expertise and associated costs. The currently available solutions neither allow easy integration of custom sensing devices nor offer a practicable methodology in cases of limited resources. This has become particularly relevant, given the need for real-time sensor data that could help lower health care costs by reducing the frequency of clinical assessments performed by specialists and improve access to health assessments (eg, for people living in remote areas or older adults living at home). OBJECTIVE: The objective of this paper is to detail the end-to-end development of a novel sensor recording software system that supports the integration of heterogeneous sensor technologies, runs as an on-demand service on consumer-grade hardware to build sensor systems, and can be easily used to reliably record longitudinal sensor measurements in research settings. METHODS: The proposed software system is based on a server-client architecture, consisting of multiple self-contained microservices that communicated with each other (eg, the web server transfers data to a database instance) and were implemented as Docker containers. The design of the software is based on state-of-the-art open-source technologies (eg, Node.js or MongoDB), which fulfill nonfunctional requirements and reduce associated costs. A series of programs to facilitate the use of the software were documented. To demonstrate performance, the software was tested in 3 studies (2 gait studies and 1 behavioral study assessing activities of daily living) that ran between 2 and 225 days, with a total of 114 participants. We used descriptive statistics to evaluate longitudinal measurements for reliability, error rates, throughput rates, latency, and usability (with the System Usability Scale [SUS] and the Post-Study System Usability Questionnaire [PSSUQ]). RESULTS: Three qualitative features (event annotation program, sample delay analysis program, and monitoring dashboard) were elaborated and realized as integrated programs. Our quantitative findings demonstrate that the system operates reliably on consumer-grade hardware, even across multiple months (>420 days), providing high throughput (2000 requests per second) with a low latency and error rate (<0.002%). In addition, the results of the usability tests indicate that the system is effective, efficient, and satisfactory to use (mean usability ratings for the SUS and PSSUQ were 89.5 and 1.62, respectively). CONCLUSIONS: Overall, this sensor recording software could be leveraged to test sensor devices, as well as to develop and validate algorithms that are able to extract digital measures (eg, gait parameters or actigraphy). The proposed software could help significantly reduce barriers related to sensor-enhanced biomedical research and allow researchers to focus on the research questions at hand rather than on developing recording technologies.

Diagnostic and prognostic EEG analysis of critically ill patients: A deep learning study.

Visual interpretation of electroencephalography (EEG) is time consuming, may lack objectivity, and is restricted to features detectable by a human. Computer-based approaches, especially deep learning, could potentially overcome these limitations. However, most deep learning studies focus on a specific question or a single pathology. Here we explore the potential of deep learning for EEG-based diagnostic and prognostic assessment of patients with acute consciousness impairment (ACI) of various etiologies. EEGs from 358 adults from a randomized controlled trial (CERTA, NCT03129438) were retrospectively analyzed. A convolutional neural network was used to predict the clinical outcome (based either on survival or on best cerebral performance category) and to determine the etiology (four diagnostic categories). The largest probability output served as marker for the confidence of the network in its prediction ("certainty factor"); we also systematically compared the predictions with raw EEG data, and used a visualization algorithm (Grad-CAM) to highlight discriminative patterns. When all patients were considered, the area under the receiver operating characteristic curve (AUC) was 0.721 for predicting survival and 0.703 for predicting the outcome based on best CPC; for patients with certainty factor ≥ 60 % the AUCs increased to 0.776 and 0.755 respectively; and for certainty factor ≥ 75 % to 0.852 and 0.879. The accuracy for predicting the etiology was 54.5 %; the accuracy increased to 67.7 %, 70.3 % and 84.1 % for patients with certainty factor of 50 %, 60 % and 75 % respectively. Visual analysis showed that the network learnt EEG patterns typically recognized by human experts, and suggested new criteria. This work demonstrates for the first time the potential of deep learning-based EEG analysis in critically ill patients with various etiologies of ACI. Certainty factor and post-hoc correlation of input data with prediction help to better characterize the method and pave the route for future implementations in clinical routine.

Continuous versus routine EEG in patients after cardiac arrest: Analysis of a randomized controlled trial (CERTA).

BACKGROUND: Electroencephalography (EEG) is essential to assess prognosis in patients after cardiac arrest (CA). Use of continuous EEG (cEEG) is increasing in critically-ill patients, but it is more resource-consuming than routine EEG (rEEG). Observational studies did not show a major impact of cEEG versus rEEG on outcome, but randomized studies are lacking. METHODS: We analyzed data of the CERTA trial (NCT03129438), including comatose adults after CA undergoing cEEG (30-48 hours) or two rEEG (20-30 minutes each). We explored correlations between recording EEG type and mortality (primary outcome), or Cerebral Performance Categories (CPC, secondary outcome), assessed blindly at 6 months, using uni- and multivariable analyses (adjusting for other prognostic variables showing some imbalance across groups). RESULTS: We analyzed 112 adults (52 underwent rEEG, 60 cEEG,); 31 (27.7%) were women; 68 (60.7%) patients died. In univariate analysis, mortality (rEEG 59%, cEEG 65%, p = 0.318) and good outcome (CPC 1-2; rEEG 33%, cEEG 27%, p = 0.247) were comparable across EEG groups. This did not change after multiple logistic regressions, adjusting for shockable rhythm, time to return of spontaneous circulation, serum neuron-specific enolase, EEG background reactivity, regarding mortality (cEEG vs rEEG: OR 1.60, 95% CI 0.43-5.83, p = 0.477), and good outcome (OR 0.51, 95% CI 0.14-1.90, p = 0.318). CONCLUSION: This analysis suggests that cEEG or repeated rEEG are related to comparable outcomes of comatose patients after CA. Pending a prospective, large randomized trial, this finding does not support the routine use of cEEG for prognostication in this setting. TRIAL REGISTRATION: Continuous EEG Randomized Trial in Adults (CERTA); NCT03129438; July 25, 2019.

EEG recording latency in critically ill patients: Impact on outcome. An analysis of a randomized controlled trial (CERTA).

OBJECTIVE: To assess, in adults with acute consciousness impairment, the impact of latency between hospital admission and EEG recording start, and their outcome. METHODS: We reviewed data of the CERTA trial (NCT03129438) and explored correlations between EEG recording latency and mortality, Cerebral Performance Categories (CPC), and modified Rankin Scale (mRS) at 6 months, considering other variables, using uni- and multivariable analyses. RESULTS: In univariable analysis of 364 adults, median latency between admission and EEG recordings was comparable between surviving (61.1 h; IQR: 24.3-137.7) and deceased patients (57.5 h; IQR: 22.3-141.1); p = 0.727. This did not change after adjusting for potential confounders, such as lower Glasgow Coma Score on enrolment (p < 0.001) and seizure or status epilepticus detection (p < 0.001). There was neither any correlation between EEG latency and mRS (rho 0.087, p 0.236), nor with CPC (rho = 0.027, p = 0.603). CONCLUSION: This analysis shows no correlation between delays of EEG recordings and mortality or functional outcomes at 6 months in critically ill adults. SIGNIFICANCE: These findings might suggest that in critically ill adults mortality correlates with underlying brain injury rather than EEG delay.

An Instrumented Apartment to Monitor Human Behavior: A Pilot Case Study in the NeuroTec Loft.

For patients suffering from neurodegenerative disorders, the behavior and activities of daily living are an indicator of a change in health status, and home-monitoring over a prolonged period of time by unobtrusive sensors is a promising technology to foster independent living and maintain quality of life. The aim of this pilot case study was the development of a multi-sensor system in an apartment to unobtrusively monitor patients at home during the day and night. The developed system is based on unobtrusive sensors using basic technologies and gold-standard medical devices measuring physiological (e.g., mobile electrocardiogram), movement (e.g., motion tracking system), and environmental parameters (e.g., temperature). The system was evaluated during one session by a healthy 32-year-old male, and results showed that the sensor system measured accurately during the participant's stay. Furthermore, the participant did not report any negative experiences. Overall, the multi-sensor system has great potential to bridge the gap between laboratories and older adults' homes and thus for a deep and novel understanding of human behavioral and neurological disorders. Finally, this new understanding could be utilized to develop new algorithms and sensor systems to address problems and increase the quality of life of our aging society and patients with neurological disorders.

On the relationships between epilepsy, sleep, and Alzheimer's disease: A narrative review.

Epilepsy, sleep, and Alzheimer's disease (AD) are tightly and potentially causally interconnected. The aim of our review was to investigate current research directions on these relationships. Our hope is that they may indicate preventive measures and new treatment options for early neurodegeneration. We included articles that assessed all three topics and were published during the last ten years. We found that this literature corroborates connections on various pathophysiological levels, including sleep-stage-related epileptiform activity in AD, the negative consequences of different sleep disorders on epilepsy and cognition, common biochemical pathways as well as network dysfunctions. Here we provide a detailed overview of these topics and we discuss promising diagnostic and therapeutic consequences.

Stationary EEG pattern relates to large-scale resting state networks - An EEG-fMRI study connecting brain networks across time-scales.

Relating brain dynamics acting on time scales that differ by at least an order of magnitude is a fundamental issue in brain research. The same is true for the observation of stable dynamical structures in otherwise highly non-stationary signals. The present study addresses both problems by the analysis of simultaneous resting state EEG-fMRI recordings of 53 patients with epilepsy. Confirming previous findings, we observe a generic and temporally stable average correlation pattern in EEG recordings. We design a predictor for the General Linear Model describing fluctuations around the stationary EEG correlation pattern and detect resting state networks in fMRI data. The acquired statistical maps are contrasted to several surrogate tests and compared with maps derived by spatial Independent Component Analysis of the fMRI data. By means of the proposed EEG-predictor we observe core nodes of known fMRI resting state networks with high specificity in the default mode, the executive control and the salience network. Our results suggest that both, the stationary EEG pattern as well as resting state fMRI networks are different expressions of the same brain activity. This activity is interpreted as the dynamics on (or close to) a stable attractor in phase space that is necessary to maintain the brain in an efficient operational mode. We discuss that this interpretation is congruent with the theoretical framework of complex systems as well as with the brain's energy balance.

Continuous Versus Routine Standardized Electroencephalogram for Outcome Prediction in Critically Ill Adults: Analysis From a Randomized Trial.

OBJECTIVES: To investigate electroencephalogram (EEG) features' relation with mortality or functional outcome after disorder of consciousness, stratifying patients between continuous EEG and routine EEG. DESIGN: Retrospective analysis of data from a randomized controlled trial. SETTING: Multiple adult ICUs. PATIENTS: Data from 364 adults with acute disorder of consciousness, randomized to continuous EEG (30-48 hr; n = 182) or repeated 20-minute routine electroencephalogram (n = 182). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Correlations between electrographic features and mortality and modified Rankin scale at 6 months (good 0-2) were assessed. Background continuity, higher frequency, and reactivity correlated with survival and good modified Rankin scale. Rhythmic and periodic patterns carried dual prognostic information: lateralized periodic discharges were associated with mortality and bad modified Rankin scale. Generalized rhythmic delta activity correlated with survival, good modified Rankin scale, and lower occurrence of status epilepticus. Presence of sleep-spindles and continuous EEG background was associated with good outcome in the continuous EEG subgroup. In the routine EEG group, a model combining background frequency, continuity, reactivity, sleep-spindles, and lateralized periodic discharges was associated with mortality at 70.91% (95% CI, 59.62-80.10%) positive predictive value and 63.93% (95% CI, 58.67-68.89%) negative predictive value. In the continuous EEG group, a model combining background continuity, reactivity, generalized rhythmic delta activity, and lateralized periodic discharges was associated with mortality at 84.62% (95%CI, 75.02-90.97) positive predictive value and 74.77% (95% CI, 68.50-80.16) negative predictive value. CONCLUSIONS: Standardized EEG interpretation provides reliable prognostic information. Continuous EEG provides more information than routine EEG.

A Primer on Hyperdimensional Computing for iEEG Seizure Detection.

A central challenge in today's care of epilepsy patients is that the disease dynamics are severely under-sampled in the currently typical setting with appointment-based clinical and electroencephalographic examinations. Implantable devices to monitor electrical brain signals and to detect epileptic seizures may significantly improve this situation and may inform personalized treatment on an unprecedented scale. These implantable devices should be optimized for energy efficiency and compact design. Energy efficiency will ease their maintenance by reducing the time of recharging, or by increasing the lifetime of their batteries. Biological nervous systems use an extremely small amount of energy for information processing. In recent years, a number of methods, often collectively referred to as brain-inspired computing, have also been developed to improve computation in non-biological hardware. Here, we give an overview of one of these methods, which has in particular been inspired by the very size of brains' circuits and termed hyperdimensional computing. Using a tutorial style, we set out to explain the key concepts of hyperdimensional computing including very high-dimensional binary vectors, the operations used to combine and manipulate these vectors, and the crucial characteristics of the mathematical space they inhabit. We then demonstrate step-by-step how hyperdimensional computing can be used to detect epileptic seizures from intracranial electroencephalogram (EEG) recordings with high energy efficiency, high specificity, and high sensitivity. We conclude by describing potential future clinical applications of hyperdimensional computing for the analysis of EEG and non-EEG digital biomarkers.

EEG spindles integrity in critical care adults. Analysis of a randomized trial.

OBJECTIVES: Occurrence of EEG spindles has been recently associated with favorable outcome in ICU patients. Available data mostly rely on relatively small patients' samples, particular etiologies, and limited variables ascertainment. We aimed to expand previous findings on a larger dataset, to identify clinical and EEG patterns correlated with spindle occurrence, and explore its prognostic implications. METHODS: Retrospective observational study of prospectively collected data from a randomized trial (CERTA, NCT03129438) assessing the relationship of continuous (cEEG) versus repeated routine EEG (rEEG) with outcome in adults with acute consciousness impairment. Spindles were prospectively assessed visually as 12-16Hz activity on fronto-central midline regions, at any time during EEG interventions. Uni- and multivariable analyses explored correlations between spindles occurrence, clinical and EEG variables, and outcome (modified Rankin Scale, mRS; mortality) at 6 months. RESULTS: Among the analyzed 364 patients, spindles were independently associated with EEG background reactivity (OR 13.2, 95% CI: 3.11-56.26), and cEEG recording (OR 4.35, 95% CI: 2.5 - 7.69). In the cEEG subgroup (n=182), 33.5% had spindles. They had better FOUR scores (p=0.004), fewer seizures or status epilepticus (p=0.02), and lower mRS (p=0.02). Mortality was reduced (p=0.002), and independently inversely associated with spindle occurrence (OR 0.50, CI 95% 0.25-0.99) and increased EEG background continuity (OR 0.16, 95% CI: 0.07 - 0.41). CONCLUSIONS: Besides confirming that spindle activity occurs in up to one third of acutely ill patients and is associated with better outcome, this study shows that cEEG has a higher yield than rEEG in identifying them. Furthermore, it unravels associations with several clinical and EEG features in this clinical setting.