EEG functional connectivity contributes to outcome prediction of postanoxic coma

ObjectiveTo investigate the additional value of EEG functional connectivity features, in addition to non-coupling EEG features, for outcome prediction of comatose patients after cardiac arrest.MethodsProspective, multicenter cohort study. Coherence, phase locking value, and mutual information were calculated in 19-channel EEGs at 12 h, 24 h and 48 h after cardiac arrest. Three sets of machine learning classification models were trained and validated with functional connectivity, EEG non-coupling features, and a combination of these. Neurological outcome was assessed at six months and categorized as “good” (Cerebral Performance Category [CPC] 1–2) or “poor” (CPC 3–5).ResultsWe included 594 patients (46% good outcome). A sensitivity of 51% (95% CI: 34–56%) at 100% specificity in predicting poor outcome was achieved by the best functional connectivity-based classifier at 12 h after cardiac arrest, while the best non-coupling-based model reached a sensitivity of 32% (0–54%) at 100% specificity using data at 12 h and 48 h. Combination of both sets of features achieved a sensitivity of 73% (50–77%) at 100% specificity.ConclusionFunctional connectivity measures improve EEG based prediction models for poor outcome of postanoxic coma.SignificanceFunctional connectivity features derived from early EEG hold potential to improve outcome prediction of coma after cardiac arrest.     

Differentiating ictal/subclinical spikes and waves in childhood absence epilepsy by spectral and network analyses: A pilot study

ObjectiveChildhood absence epilepsy (CAE) is a disease with distinct seizure semiology and electroencephalographic (EEG) features. Differentiating ictal and subclinical generalized spikes and waves discharges (GSWDs) in the EEG is challenging, since they appear to be identical upon visual inspection. Here, spectral and functional connectivity (FC) analyses were applied to routine EEG data of CAE patients, to differentiate ictal and subclinical GSWDs.MethodsTwelve CAE patients with both ictal and subclinical GSWDs were retrospectively selected for this study. The selected EEG epochs were subjected to frequency analysis in the range of 1–30 Hz. Further, FC analysis based on the imaginary part of coherency was used to determine sensor level networks.ResultsDelta, alpha and beta band frequencies during ictal GSWDs showed significantly higher power compared to subclinical GSWDs. FC showed significant network differences for all frequency bands, demonstrating weaker connectivity between channels during ictal GSWDs.ConclusionUsing spectral and FC analyses significant differences between ictal and subclinical GSWDs in CAE patients were detected, suggesting that these features could be used for machine learning classification purposes to improve EEG monitoring.SignificanceIdentifying differences between ictal and subclinical GSWDs using routine EEG, may improve understanding of this syndrome and the management of patients with CAE.     

Continuous electroencephalography characteristics and acute symptomatic seizures in COVID-19 patients

ObjectiveAs concerns regarding neurological manifestations in COVID-19 (coronavirus disease 2019) patients increase, limited data exists on continuous electroencephalography (cEEG) findings in these patients. We present a retrospective cohort study of cEEG monitoring in COVID-19 patients to better explore this knowledge gap.MethodsAmong 22 COVID-19 patients, 19 underwent cEEGs, and 3 underwent routine EEGs (<1 h). Demographic and clinical variables, including comorbid conditions, discharge disposition, survival and cEEG findings, were collected.ResultscEEG was performed for evaluation of altered mental status (n = 17) or seizure-like events (n = 5). Five patients, including 2 with epilepsy, had epileptiform abnormalities on cEEG. Two patients had electrographic seizures without a prior epilepsy history. There were no acute neuroimaging findings. Periodic discharges were noted in one-third of patients and encephalopathic EEG findings were not associated with IV anesthetic use.ConclusionsInterictal epileptiform abnormalities in the absence of prior epilepsy history were rare. However, the discovery of asymptomatic seizures in two of twenty-two patients was higher than previously reported and is therefore of concern.SignificancecEEG monitoring in COVID-19 patients may aid in better understanding an epileptogenic potential of SARS-CoV2 infection. Nevertheless, larger studies utilizing cEEG are required to better examine acute epileptic risk in COVID-19 patients.     

Implementation of amplitude-integrated electroencephalography in tertiary Canadian Neonatal Intensive Care Units—a longitudinal study

AimTo investigate the implementation of amplitude-integrated electroencephalography (aEEG) as bedside monitoring tool of cerebral function in tertiary Canadian Neonatal Intensive Care Units (NICU) over the past decade.MethodsLongitudinal study consisting of online surveys of neonatologists on the use of aEEG in 2009 and 2018.ResultsThe response rate to the survey was 72 of 149 (49%) in 2009 and 18 of 30 (60%) in 2018, respectively. aEEG has been implemented in almost all (2009: 62.5%; 2018: 94%) tertiary Canadian NICUs. Two-thirds (2009: 67%; 2018: 71%) of the respondents considered information from aEEG tracing helpful in clinical practice. The main indications for aEEG were term neonates with hypoxic ischemic encephalopathy (2009 and 2018: 76%) and seizure detection/surveillance (2009: 88%; 2018: 94%). Teaching on aEEG has been implemented for neonatologists (2018: 100%) and health care providers (2018: 50%) in tertiary Canadian NICUs but there is a lack of standardization of training. Use of aEEG in preterm neonates (2009: 37%, 2018: 33%) and application of aEEG in research (18% reported occasional use) is less common.ConclusionaEEG is well established in tertiary Canadian NICUs to monitor cerebral function and detect seizure activity. There is a need to develop formalized aEEG training programs and methods to assess competence. Further implementation of aEEG in preterm neonates and research is desirable.     

Toward the establishment of neurophysiological indicators for neuropsychiatric disorders using transcranial magnetic stimulation‐evoked potentials: A systematic review

Transcranial magnetic stimulation (TMS) can depolarize the neurons directly under the coil when applied to the cerebral cortex, and modulate the neural circuit associated with the stimulation site, which makes it possible to measure the neurophysiological index to evaluate excitability and inhibitory functions. Concurrent TMS and electroencephalography (TMS‐EEG) has been developed to assess the neurophysiological characteristics of cortical regions other than the motor cortical region noninvasively. The aim of this review is to comprehensively discuss TMS‐EEG research in the healthy brain focused on excitability, inhibition, and plasticity following neuromodulatory TMS paradigms from a neurophysiological perspective. A search was conducted in PubMed to identify articles that examined humans and that were written in English and published by September 2018. The search terms were as follows: (TMS OR ‘transcranial magnetic stimulation’) AND (EEG OR electroencephalog*) NOT (rTMS OR ‘repetitive transcranial magnetic stimulation’ OR TBS OR ‘theta burst stimulation’) AND (healthy). The study presents an overview of TMS‐EEG methodology and neurophysiological indices and reviews previous findings from TMS‐EEG in healthy individuals. Furthermore, this review discusses the potential application of TMS‐EEG neurophysiology in the clinical setting to study healthy and diseased brain conditions in the future. Combined TMS‐EEG is a powerful tool to probe and map neural circuits in the human brain noninvasively and represents a promising approach for determining the underlying pathophysiology of neuropsychiatric disorders.     

Sensory evoked potentials in patients with Rett syndrome through the lens of animal studies: Systematic review

ObjectiveSystematically review the abnormalities in event related potential (ERP) recorded in Rett Syndrome (RTT) patients and animals in search of translational biomarkers of deficits related to the particular neurophysiological processes of known genetic origin (MECP2 mutations).MethodsPubmed, ISI Web of Knowledge and BIORXIV were searched for the relevant articles according to PRISMA standards.ResultsERP components are generally delayed across all sensory modalities both in RTT patients and its animal model, while findings on ERPs amplitude strongly depend on stimulus properties and presentation rate. Studies on RTT animal models uncovered the abnormalities in the excitatory and inhibitory transmission as critical mechanisms underlying the ERPs changes, but showed that even similar ERP alterations in auditory and visual domains have a diverse neural basis. A range of novel approaches has been developed in animal studies bringing along the meaningful neurophysiological interpretation of ERP measures in RTT patients.ConclusionsWhile there is a clear evidence for sensory ERPs abnormalities in RTT, to further advance the field there is a need in a large-scale ERP studies with the functionally-relevant experimental paradigms.SignificanceThe review provides insights into domain-specific neural basis of the ERP abnormalities and promotes clinical application of the ERP measures as the non-invasive functional biomarkers of RTT pathophysiology.     

Epileptogenic modulation index and synchronization in hypsarrhythmia of West syndrome secondary to perinatal arterial ischemic stroke

ObjectivePerinatal arterial ischemic stroke (PAIS) is associated with epileptic spasms of West syndrome (WS) and long term Focal epilepsy (FE). The mechanism of epileptogenic network generation causing hypsarrhythmia of WS is unknown. We hypothesized that Modulation index (MI) [strength of phase-amplitude coupling] and Synchronization likelihood (SL) [degree of connectivity] could interrogate the epileptogenic network in hypsarrhythmia of WS secondary to PAIS.MethodsWe analyzed interictal scalp electroencephalography (EEG) in 10 WS and 11 FE patients with unilateral PAIS. MI between gamma (30–70 Hz) and slow waves (3–4 Hz) was calculated to measure phase-amplitude coupling. SL between electrode pairs was analyzed in 9-frequency bands (5-delta, theta, alpha, beta, gamma) to examine inter- and intra-hemispheric connectivity.ResultsMI was higher in affected hemispheres in WS (p = 0.006); no differences observed in FE. Inter-hemispheric SL of 3-delta, theta, alpha, beta, gamma bands was significantly higher in WS (p < 0.001). In WS, modified Z-Score of intra-hemispheric SL values in 3-delta, theta, alpha, beta and gamma in the affected hemispheres were significantly higher than those in the unaffected hemispheres (p < 0.001) as well as 0.5–4 Hz (p = 0.004).ConclusionsThe significantly higher modulation in affected hemisphere and stronger inter- and intra-hemispheric connectivity generate hypsarrhythmia of WS secondary to PAIS.SignificanceEpileptogenic cortical-subcortical transcallosal networks from affected hemisphere post-PAIS provokes infantile spasms.     

Acute and subsequent continuation electroconvulsive therapy elevates serum BDNF levels in patients with major depression

IntroductionThe induction of brain-derived neurotrophic factor (BDNF) release and subsequent restoration of neuroplastic homeostasis may underlie the effects of electroconvulsive therapy (ECT).ObjectivesWe aimed to assess serum and plasma BDNF levels during the course of acute ECT, as well as before and after subsequent continuation ECT, in patients with depression.MethodsWe included 24 patients with major depressive disorder (mean age ± SD: 54.5 ± 13.7; f/m: 17/7; baseline 17-item Hamilton Depression Rating Scale score of 26.79 ± 4.01). Serum and plasma BDNF (sBDNF, pBDNF) levels were assessed at nine time-points before, during, and after acute ECT series. Data were analysed using linear regression and linear mixed models, which were adjusted for multiple comparisons via Bonferroni correction. Five patients received continuation ECT subsequent to the acute ECT series. In these patients, BDNF levels were assessed before and after each two continuation ECT sessions using Wilcoxon signed-rank tests.ResultsRelative to baseline (mean ng/ml ±SD: 24.68 ± 14.40), sBDNF levels were significantly higher 1 day (33.04 ± 14.11, p = 0.013, corrected), 1 week (37.03 ± 10.29, p < 0.001, corrected), and 1 month (41.05 ± 10.67, p = 0.008, corrected) after the final ECT session, while pBDNF levels did not significantly differ (p > 0.1). Furthermore, our results indicated that sBDNF levels increased after each continuation ECT session. There was no significant association between sBDNF levels and clinical parameters or treatment response.ConclusionThe absence of an association between changes in sBDNF levels and depressive symptoms challenges the proposed concept of sBDNF/pBDNF as key markers of the effects of ECT.     

Spike‐associated networks and intracranial electrographic findings

Aims. Functional connectivity is providing new insights into the network nature of epilepsy with growing clinical applications. Our objective was to validate a novel magnetoencephalography‐based method to non‐invasively measure the epileptic network. Methods. We retrospectively identified pediatric and adult patients with refractory focal epilepsy who underwent pre‐surgical magnetoencephalography with subsequent intracranial electrographic monitoring. Magnetoencephalography tracings were visually reviewed, and interictal epileptiform discharges (“spikes”) were individually marked. We then evaluated differences in whole‐brain connectivity during brief epochs preceding the spikes and during the spikes using the Network‐Based Statistic to test differences at the network level. Results. In six patients with statistically‐significant network differences, we observed substantial overlap between the spike‐associated networks and electrographically active areas identified during intracranial monitoring (the spike‐associated network was 78% and 83% sensitive for intracranial electroencephalography‐defined regions in the irritative and seizure onset zones, respectively). Conclusion. These findings support the neurobiological validity of the spike‐associated network method. Assessment of spike‐associated networks has the potential to improve surgical planning in epilepsy surgery patients by identifying components of the epileptic network prior to implantation.