We acknowledge that, as the colleagues point out, targeted temperature management (TTM) and concomitant sedation may alter the electroencephalogram (EEG) in comatose patients after cardiac arrest. In particular, sedation can diminish the EEG amplitude and modify the EEG component frequencies.1Drohan C.M. Cardi A.I. et al.Effect of sedation on quantitative electroencephalography after cardiac arrest.Resuscitation. 2018; 124: 132-137Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar In addition, TTM and sedation may of course interfere with patients' neurological examination, especially so during neuromuscular blocker agents regime. Yet, we feel it is important to point out that these considerations do not affect the reliability of EEG-based prognostic prediction during TTM and sedation. First, in our study the average spectral power in theta and alpha frequency was highly specific in patients with persistent unfavorable outcome, irrespective of the sedative medication dosage (table 2 in2Kustermann T. Nguepnjo Nguissi N.A. Pfeiffer C. et al.Electroencephalography-based power spectra allow coma outcome prediction within 24 h of cardiac arrest.Resuscitation. 2019; 142: 162-167Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar). Second, our work adds to previous evidence that early EEG during TTM and sedation is a robust predictor of patients' outcome, with possibly even higher accuracy than at later stages,3Rossetti A.O. Tovar Quiroga D.F. Juan E. et al.Electroencephalography predicts poor and good outcomes after cardiac arrest: a two-center study.Crit Care Med. 2017; 45: e674-e682Crossref PubMed Scopus (93) Google Scholar, 4Ruijter B.J. Tjepkema-Cloostermans M.C. Tromp S.C. et al.Early electroencephalography for outcome prediction of postanoxic coma: a prospective cohort study.Ann Neurol. 2019; 86: 203-214Crossref PubMed Scopus (83) Google Scholar, 5Tzovara A. Rossetti A. Juan E. et al.Prediction of awakening from hypothermic post anoxic coma based on auditory discrimination.Ann Neurol. 2016; 79: 748-757Crossref PubMed Scopus (36) Google Scholar and that sedative medications do not adversely affect the EEG's predictive value.1Drohan C.M. Cardi A.I. et al.Effect of sedation on quantitative electroencephalography after cardiac arrest.Resuscitation. 2018; 124: 132-137Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar, 6Ruijter B.J. van Putten M. van den Bergh W.M. Tromp S.C. Hofmeijer J. Propofol does not affect the reliability of early EEG for outcome prediction of comatose patients after cardiac arrest.Clin Neurophysiol. 2019; 130: 1263-1270Crossref PubMed Scopus (37) Google Scholar In addition, to our knowledge neuromuscular blockade does not exert any meaningful effect on the EEG signal and – if anything – would decrease the impact of muscle-related artifacts and thus increase the signal-to-noise ratio. An in-depth neurophysiological explanation of these experimental findings requires further research aimed at disentangling the effect of time from that of the medical intervention during the first day of coma, and at uncovering the degree of interaction between effect of sedation and patients' outcome. In the context of our study, the inclusion of patients from multiple hospitals with potentially different treatment protocols reduces the risk of confounding factors modulating the alpha band activity in relation to one specific regimen. One possible neurophysiological explanation for the high specificity of low power spectra values for unfavorable outcome could be based on the sedative effect on neural activity of corticothalamic networks underlying the generation of EEG in the alpha band. If this interpretation would prove correct, the sedative medication would act as a probe of this network, whose preservation may represent a possible minimal condition for patients to survive. In clinical practice, implementation of early quantitative prognostic markers can be highly relevant, as they may guide and encourage timely and personalized clinical interventions to increase chances of awakening and early recovery. The authors declare no conflict of interest. This research was funded by EUREKA-Eurostars, Grant Number E!9361 Com-Alert to Marzia De Lucia.

Objective: In patients with disorders of consciousness (DOC), properties of functional brain networks at rest are informative of the degree of consciousness impairment and of long-term outcome. Here we investigate whether connectivity differences between patients with favorable and unfavorable outcome are already present within 24 h of coma onset. Methods: We prospectively recorded 63-channel electroencephalography (EEG) at rest during the first day of coma after cardiac arrest. We analyzed 98 adults, of whom 57 survived beyond unresponsive wakefulness. Functional connectivity was estimated by computing the 'debiased weighted phase lag index' over epochs of five seconds duration. We evaluated the network's topological features, including clustering coefficient, path length, modularity and participation coefficient and computed their variance over time. Finally, we estimated the predictive value of these topological features for patients' outcomes by splitting the patient sample in training and test datasets. Results: Group-level analysis revealed lower clustering coefficient, higher modularity and path length variance in patients with favorable compared to those with unfavorable outcomes (p < 0.01). Within all features, the path length variance in the network provided the best positive predictive value (PPV) for favorable outcome and specificity for unfavorable outcome in the test dataset (PPV: 0.83, p < 0.01; specificity: 0.86, p < 0.01) with above-chance negative predictive value and accuracy. Of note, the exclusion of patients with epileptiform activity (20 in total) eliminates all false positive predictions (n = 6) for path length variance. Interpretation: Topological features of functional connectivity differ as a function of long-term outcome in patients on the first day of coma. These differences are not interpretable in terms of consciousness levels as all patients were in a deep unconscious state. The time variance of path length is informative of comatose patients' outcome, as patients with favorable outcome exhibit a richer repertoire of path length than those with unfavorable outcomes.

Aim: To assess whether stimulus-induced modifications of electromyographic activity observed on scalp EEG have a prognostic value in comatose patients after cardiac arrest. Methods: 184 adult patients from a multi-centric prospective register who underwent an early EEG after cardiac arrest were included. Auditory and somatosensory stimulation was performed during EEG-recording. EEG reactivity (EEG-R) and EMG reactivity (EMG-R) were retrospectively assessed visually by board-certified electroencephalographers, and compared with clinical outcome (cerebral performance category, CPC) at three months. A favorable functional outcome was defined as CPC 1-2, an unfavorable outcome as CPC 3-5. Results: Both EEG-R and EMG-R were predictors for good outcome (EEG-R accuracy 72% (95%-CI 66-79), sensitivity 86% (78-93), specificity 60% (50-69), EMG-R accuracy 65% (58-72), sensitivity 61% (51-75), specificity 69% (60-78)). When reactivity was defined as EEG-R and/or EMG-R, the accuracy was 73% (67-70), the sensitivity 94% (90-99), and the specificity 53% (43-63). Conclusion: Taking EMG into account when assessing reactivity of EEG seems to reduce false negative predictions for identifying patients with favorable outcome after cardiac arrest.

Background: Outcome prediction in comatose patients following cardiac arrest remains challenging. Here, we assess the predictive performance of electroencephalography-based power spectra within 24 h from coma onset. Methods: We acquired electroencephalography (EEG) from comatose patients (n = 138) on the first day of coma in four hospital sites in Switzerland. Outcome was categorised as favourable or unfavourable based on the best state within three months. Data were split in training and test sets. We evaluated the predictive performance of EEG power spectra for long term outcome and its added value to standard clinical tests. Results: Out of 138 patients, 80 had a favourable outcome. Power spectra comparison between favourable and unfavourable outcome in the training set yielded significant differences at 5.2-13.2 Hz and above 21 Hz. Outcome prediction based on power at 5.2-13.2 Hz was accurate in training and test sets. Overall, power spectra predicted patients' outcome with maximum specificity and positive predictive value: 1.00 (95% with CI: 0.94-1.00 and 0.89-1.00, respectively). The combination of power spectra and reactivity yielded better accuracy and sensitivity (0.81, 95% CI: 0.71-0.89) than prediction based on power spectra alone. Conclusions: On the first day of coma following cardiac arrest, low power spectra values around 10 Hz, typically linked to impaired cortico-thalamic structural connections, are highly specific of unfavourable outcome. Peaks in this frequency range can predict long-term outcome.

The Stroop color-word interference task, prompting slower response to color-incongruent than to congruent items, is often used to study neural mechanisms of inhibitory control and dysfunction in schizophrenia-spectrum disorders. Inconsistent findings of an augmented Stroop effect limit identification of relevant dysfunctional mechanism(s) in schizophrenia. The present study sought to advance understanding of normal and impaired neural oscillatory dynamics by distinguishing interference detection and response preparation during the Stroop task in schizophrenia-spectrum disorders via analysis of behavioral performance and 4-7 Hz (theta) and 10-30 Hz (alpha/beta) EEG oscillations in 40 patients (SZ) and 27 healthy comparison participants (HC). SZ responded more slowly and showed less dorsal anterior cingulate (dACC) theta enhancement during INC trials, less enhancement of dACC-sensorimotor cortex connectivity (theta phase synchrony) during INC trials, more alpha/beta suppression though less enhancement of that suppression during INC trials, and slower post-response alpha/beta rebound than did HC Reaction time distributions showed larger group and Stroop effects during the 25% of trials with the slowest responses. Poorer theta phase coherence in patients indicates impaired communication between regions associated with interference processing (dACC) and response preparation (sensorimotor cortex). Results suggest a failure cascade in which compromised behavioral Stroop effects are driven at least in part by dysfunctional interference processing (less theta power increase) prompting dysfunctional motor response preparation (less alpha/beta power suppression). Inconsistent Stroop effects in past studies of schizophrenia may result from differing task parameters sampling different degrees of Stroop task difficulty. (C) 2018 Published by Elsevier B.V.

Impaired working memory (WM) in schizophrenia is associated with reduced hemo-dynamic and electromagnetic activity and altered network connectivity within and between memory-associated neural networks. The present study sought to determine whether schizophrenia involves disruption of a frontal-parietal network normally supporting WM and/or involvement of another brain network. Nineteen schizophrenia patients (SZ) and 19 healthy comparison subjects (HC) participated in a cued visual-verbal Sternberg task while dense-array EEG was recorded. A pair of item arrays each consisting of 2-4 consonants was presented bilaterally for 200 ms with a prior cue signaling the hemifield of the task-relevant WM set. A central probe letter 2,000 ms later prompted a choice reaction time decision about match/mismatch with the target WM set. Group and WM load effects on time domain and time-frequency domain 11-15 Hz alpha power were assessed for the cue-to-probe time window, and posterior 11-1.5 Hz alpha power and frontal 4-8 Hz theta power were assessed during the retention period. Directional connectivity was estimated via Granger causality, evaluating group differences in communication. SZ showed slower responding, lower accuracy, smaller overall time-domain alpha power increase, and less load-dependent alpha power increase. Midline frontal theta power increases did not vary by group or load. Network communication in SZ was characterized by temporal-to-posterior information flow, in contrast to bidirectional temporal-posterior communication in HC. Results indicate aberrant WM network activity supporting WM in SZ that might facilitate normal load-dependent and only marginally less accurate task performance, despite generally slower responding.

Oscillatory brain activity in the theta, alpha, and gamma frequency ranges has been associated with working memory (WM). In addition to alpha and theta activity associated with WM retention, and gamma band activity with item encoding, activity in the alpha band is related to the deployment of attention resources and information. The present study sought to specify distinct roles of neuromagnetic 4-7 Hz theta, 9-13 Hz alpha, and 50-70 Hz gamma power modulation and communication in fronto-parietal networks during cued, hemifield-specific item presentation in a modified Sternberg verbal WM task in 14 student volunteers. Lateralized posterior alpha and gamma power during encoding suggest a preparatory role of alpha oscillations. Bilateral alpha power increases during maintenance reflect information retention for the non-lateralized probe response. Lateralized alpha power increase during encoding was apparently driven by a monotonic increase in fronto-parietal 6 Hz phase, suggesting a mechanism facilitating WM encoding and successful performance.

Modulation of 8-14 Hz (alpha) activity in posterior brain regions is associated with covert attention deployment in visuospatial tasks. Alpha power decrease contralateral to to-be-attended stimuli is believed to foster subsequent processing, such as retention of task-relevant input. Degradation of this alpha-regulation mechanism may reflect an early stage of disturbed attention regulation contributing to impaired attention and working memory commonly found in schizophrenia. The present study tested this hypothesis of early disturbed attention regulation by examining alpha power modulation in a lateralized cued delayed response task in 14 schizophrenia patients (SZ) and 25 healthy controls (HC). Participants were instructed to remember the location of a 100-ms saccade-target cue in the left or right visual hemifield in order to perform a delayed saccade to that location after a retention interval. As expected, alpha power decrease during the retention interval was larger in contralateral than ipsilateral posterior regions, and SZ showed less of this lateralization than did HC. In particular, SZ failed to show hemifield-specific alpha modulation in posterior right hemisphere. Results suggest less efficient modulation of alpha oscillations that are considered critical for attention deployment and item encoding and, hence, may affect subsequent spatial working memory performance.