Search

Central-positive complexes (CPCs) are elicited during electroconvulsive therapy (ECT) as generalized high-amplitude waveforms with maximum positive voltage over the vertex. While these complexes have been qualitatively assessed in previous literature, quantitative analyses are lacking. This study aims to characterize CPCs across temporal, spatial, and spectral domains.High-density 64-electrode electroencephalogram (EEG) recordings during 50 seizures acquired from 11 patients undergoing right unilateral ECT allowed for evaluation of spatiotemporal characteristics of CPCs via source localization and spectral analysis.Peak-amplitude CPC scalp topology was consistent across seizures, showing maximal positive polarity over the midline fronto-central region and maximal negative polarity over the suborbital regions. The sources of these peak potentials were localized to the bilateral medial thalamus and cingulate cortical regions. Delta, beta, and gamma oscillations were correlated with the peak amplitude of CPCs during seizures induced during ketamine, whereas delta and gamma oscillations were associated with CPC peaks during etomidate anesthesia (excluding the dose-charge titration).Our findings demonstrate the consistency of CPC presence across participant, stimulus charge, time, and anesthetic agent, with peaks localized to bilateral medial thalamus and cingulate cortical regions and associated with delta, beta, and gamma band oscillations (depending on the anesthetic condition).The consistency and reproducibility of CPCs offers ECT as a new avenue for studying the dynamics of generalized seizure activity and thalamocortical networks.

Periods of low-amplitude electroencephalographic (EEG) signal (quiescence) are present during both anesthetic-induced burst suppression (BS) and postictal generalized electroencephalographic suppression (PGES). PGES following generalized seizures induced by electroconvulsive therapy (ECT) has been previously linked to antidepressant response. The commonality of quiescence during both BS and PGES motivated trials to recapitulate the antidepressant effects of ECT using high doses of anesthetics. However, there have been no direct electrographic comparisons of these quiescent periods to address whether these are distinct entities.We compared periods of EEG quiescence recorded from two human studies: BS induced in 29 healthy adult volunteers by isoflurane general anesthesia and PGES in 11 patients undergoing right unilateral ECT for treatment-resistant depression. An automated algorithm allowed detection of EEG quiescence based on a 10-microvolt amplitude threshold. Spatial, spectral, and temporal analyses compared quiescent epochs during BS and PGES.The median (interquartile range) voltage for quiescent periods during PGES was greater than during BS (1.81 (0.22) microvolts vs 1.22 (0.33) microvolts, p 0.001). Relative power was greater for quiescence during PGES than BS for the 1-4 Hz delta band (p 0.001), at the expense of power in the theta (4-8 Hz, p 0.001), beta (13-30 Hz, p = 0.04) and gamma (30-70 Hz, p = 0.006) frequency bands. Topographic analyses revealed that amplitude across the scalp was consistently higher for quiescent periods during PGES than BS, whose voltage was within the noise floor.Quiescent epochs during PGES and BS have distinct patterns of EEG signals across voltage, frequency, and spatial domains.Quiescent epochs during PGES and BS, important neurophysiological markers for clinical outcomes, are shown to have distinct voltage and frequency characteristics.

Delirium is an acute syndrome characterized by inattention, disorganized thinking, and an altered level of consciousness. A reliable biomarker for tracking delirium does not exist, but oscillations in the electroencephalogram (EEG) could address this need. We evaluated whether the frequencies of EEG oscillations are associated with delirium onset, severity, and recovery in the postoperative period.Twenty-six adults enrolled in the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES; ClinicalTrials.gov NCT02241655) study underwent major surgery requiring general anesthesia, and provided longitudinal postoperative EEG recordings for this prespecified substudy. The presence and severity of delirium were evaluated with the confusion assessment method (CAM) or the CAM-intensive care unit. EEG data obtained during awake eyes-open and eyes-closed states yielded relative power in the delta (1-4 Hz), theta (4-8 Hz), and alpha (8-13 Hz) bands. Discriminability for delirium presence was evaluated with c-statistics. To account for correlation among repeated measures within patients, mixed-effects models were generated to assess relationships between: (1) delirium severity and EEG relative power (ordinal), and (2) EEG relative power and time (linear). Slopes of ordinal and linear mixed-effects models are reported as the change in delirium severity score/change in EEG relative power, and the change in EEG relative power/time (days), respectively. Bonferroni correction was applied to confidence intervals (CIs) to account for multiple comparisons.Occipital alpha relative power during eyes-closed states offered moderate discriminability (c-statistic, 0.75; 98% CI, 0.58-0.87), varying inversely with delirium severity (slope, -0.67; 98% CI, -1.36 to -0.01; P = .01) and with severity of inattention (slope, -1.44; 98% CI, -2.30 to -0.58; P = .002). Occipital theta relative power during eyes-open states correlated directly with severity of delirium (slope, 1.28; 98% CI, 0.12-2.44; P = .007), inattention (slope, 2.00; 98% CI, 0.48-3.54; P = .01), and disorganized thinking (slope, 3.15; 98% CI, 0.66-5.65; P = .01). Corresponding frontal EEG measures recapitulated these relationships to varying degrees. Severity of altered level of consciousness correlated with frontal theta relative power during eyes-open states (slope, 11.52; 98% CI, 6.33-16.71; P.001). Frontal theta relative power during eyes-open states correlated inversely with time (slope, -0.05; 98% CI, -0.12 to -0.04; P = .002).Presence, severity, and core features of postoperative delirium covary with spectral features of the EEG. The cost and accessibility of EEG facilitate the translation of these findings to future mechanistic and interventional trials.

Objective Postictal generalized electroencephalographic suppression (PGES) has been defined as electroencephalographic (EEG) activity of less than 10 microvolts following a generalized seizure. PGES is associated with an increased risk of sudden unexplained death in epilepsy, as well as treatment efficacy of electroconvulsive therapy (ECT). We investigated the impact of anesthetic on PGES expression and temporal characteristics. Methods We recorded postictal EEG in 50 ECT sessions in 11 patients with treatment resistant depression (ClinicalTrials.gov NCT02761330). For each participant, repeated sessions included either ketamine or etomidate general anesthesia during ECT. An automated algorithm was employed to detect PGES within 5 minutes after seizure termination. Results PGES was detected in 31/50 recordings, with intermittent epochs recurring up to five minutes after seizure termination. PGES total duration was greater following ketamine than etomidate anesthesia (p = 0.04). PGES expression declined loglinearly as a function of time (r = -0.89, p Conclusions PGES can occur intermittently for several minutes following seizure termination. Anesthetic effects should be considered when correlating PGES duration to clinical outcomes. Significance Prolonged EEG monitoring several minutes following seizure termination may be necessary to fully evaluate the presence and total duration of PGES.

Electroconvulsive therapy (ECT) relies on the electrical induction of generalized seizures to treat major depressive disorder and other psychiatric illnesses. These planned procedures provide a clinically relevant model system for studying neurophysiologic characteristics of generalized seizures. We recently described novel central-positive complexes (CPCs), which were observed during ECT-induced seizures as generalized, high-amplitude waveforms with maximum positive voltage over the vertex. Here, we performed a systematic characterization of 6,928 CPC ictal waveforms recorded in 11 patients undergoing right unilateral (RUL) ECT. Analyses of high-density 65-electrode EEG recordings during these 50 seizures allowed evaluation of these CPCs across temporal, spatial, and spectral domains. Peak-amplitude CPC scalp topology was consistent across seizures, showing maximal positive polarity over the midline fronto-central region and maximal negative polarity over the suborbital regions. Total duration of CPCs positively correlated with the time required for return of responsiveness after ECT treatment (r = 0.39, p = 0.005). The rate of CPCs showed a frequency decline consistent with an exponential decay (median 0.032 (IQR 0.053) complexes/second). Gamma band (30-80 Hz) oscillations correlated with the peak amplitude of CPCs, which was also reproducible across seizures, with band power declining over time (r = −0.32, p < 10−7). The sources of these peak potentials were localized to the bilateral medial thalamus and cingulate cortical regions. Our findings demonstrated CPC characteristics that were invariant to participant, stimulus charge, time, and agent used to induce general anesthesia during the procedure. Consistent with ictal waveforms of other generalized epilepsy syndromes, CPCs showed topographic distribution over the fronto-central regions, predictable intra-seizure frequency decline, and correlation with gamma-range frequencies. Furthermore, source localization to the medial thalamus was consistent with underlying thalamocortical pathophysiology, as established in generalized epilepsy syndromes. The consistency and reproducibility of CPCs offers a new avenue for studying the dynamics of seizure activity and thalamocortical networks.

Objective Postictal generalized electroencephalographic suppression (PGES) is a pattern of low-voltage scalp electroencephalographic (EEG) activity following termination of generalized seizures. PGES has been associated with both sudden unexplained death in patients with epilepsy and therapeutic efficacy of electroconvulsive therapy (ECT). Automated detection of PGES epochs may aid in reliable quantification of this phenomenon. Methods We developed a voltage-based algorithm for detecting PGES. This algorithm applies existing criteria to simulate expert epileptologist readings. Validation relied on postictal EEG recording from patients undergoing ECT (NCT02761330), assessing concordance among the algorithm and four clinical epileptologists. Results We observed low-to-moderate concordance among epileptologist ratings of PGES. Despite this, the algorithm displayed high discriminability in comparison to individual epileptologists (c-statistic range: 0.86-0.92). The algorithm displayed high discrimination (c-statistic: 0.91) and substantial peak agreement (Cohen’s Kappa: 0.65) in comparison to a consensus of clinical ratings. Interrater agreement between the algorithm and individual epileptologists was on par with that among expert epileptologists. Conclusions An automated voltage-based algorithm can be used to detect PGES following ECT, with discriminability nearing that of experts. Significance Algorithmic detection may support clinical readings of PGES and improve precision when correlating this marker with clinical outcomes following generalized seizures.