Central-positive complexes in ECT-induced seizures: Evidence for thalamocortical mechanisms

Abstract

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.

Correlating electroconvulsive therapy response to electroencephalographic markers: Study protocol

“…Data from Phase 3, with rhythmic 2.5–3.5 Hz spike/polyspike-wave activity, will be utilized for CPC analysis using EEGLAB ( 95 ) in MATLAB. Custom MATLAB scripts will employ an automatic algorithm which will be utilized to detect large amplitude CPCs based on the difference between average suborbital facial electrode signals and Cz electrode ( 82 ). Cumulative duration of CPCs will be computed for each ECT session.…”

“…During ECT-induced seizures, CPCs correlate with bilateral clonic activity, qualitatively decreasing in frequency over time ( 81 ). Peak amplitude of CPCs are localized to the cingulate cortex and medial dorsal thalamus ( 82 )—structures involved in the formation of sleep slow waves and sleep spindles ( 64 , 83 – 85 ). Thus, CPCs could be involved in the alteration of SWA and sleep spindles, but the relationships between CPCs, sleep slow waves, and sleep spindles throughout treatment course requires further elucidation.…”

Seizures induced in electroconvulsive therapy as a human epilepsy model: A comparative case study

“…20,27,30 Both in generalized spontaneous seizures and ECT-induced seizures, stereotypical electroencephalographic (EEG) characteristics include ictal large amplitude rhythmic and hypersynchronous activity along with postictal suppression. [31][32][33][34][35] Ictal hyperperfusion of the brain and postictal hypoperfusion have been established in both epilepsy and ECT patients. 7,15,36,37 Investigating tonic-clonic seizures is of increased value because clinical manifestation (ie, tonic and clonic phase), electroencephalographic characteristics (ie, generalized EEG spike-wave complexes and postictal suppression), and neuroimaging findings (ie, ictal hyperperfusion and postictal hypoperfusion) are similar compared to ECT-induced seizures.…”