Links between electroconvulsive therapy responsive and cognitive impairment multimodal brain networks in late-life major depressive disorder

Abstract

Background Although electroconvulsive therapy (ECT) is an effective treatment for depression, ECT cognitive impairment remains a major concern. The neurobiological underpinnings and mechanisms underlying ECT antidepressant and cognitive impairment effects remain unknown. This investigation aims to identify ECT antidepressant-response and cognitive-impairment multimodal brain networks and assesses whether they are associated with the ECT-induced electric field (E-field) with an optimal pulse amplitude estimation. Methods A single site clinical trial focused on amplitude (600, 700, and 800 mA) included longitudinal multimodal imaging and clinical and cognitive assessments completed before and immediately after the ECT series (n = 54) for late-life depression. Another two independent validation cohorts (n = 84, n = 260) were included. Symptom and cognition were used as references to supervise fMRI and sMRI fusion to identify ECT antidepressant-response and cognitive-impairment multimodal brain networks. Correlations between ECT-induced E-field within these two networks and clinical and cognitive outcomes were calculated. An optimal pulse amplitude was estimated based on E-field within antidepressant-response and cognitive-impairment networks. Results Decreased function in the superior orbitofrontal cortex and caudate accompanied with increased volume in medial temporal cortex showed covarying functional and structural alterations in both antidepressant-response and cognitive-impairment networks. Volume increases in the hippocampal complex and thalamus were antidepressant-response specific, and functional decreases in the amygdala and hippocampal complex were cognitive-impairment specific, which were validated in two independent datasets. The E-field within these two networks showed an inverse relationship with HDRS reduction and cognitive impairment. The optimal E-filed range as [92.7–113.9] V/m was estimated to maximize antidepressant outcomes without compromising cognitive safety. Conclusions The large degree of overlap between antidepressant-response and cognitive-impairment networks challenges parameter development focused on precise E-field dosing with new electrode placements. The determination of the optimal individualized ECT amplitude within the antidepressant and cognitive networks may improve the treatment benefit–risk ratio. Trial registration ClinicalTrials.gov Identifier: NCT02999269.

Amplitude-determined seizure-threshold, electric field modeling, and electroconvulsive therapy antidepressant and cognitive outcomes

“…In contrast, ST a was unrelated with cognitive outcomes. The strong association between E brain /I and cognitive outcomes replicates our previous work and adds support for the role of E brain /I in ECT dosing [14,54]. In this sample, an E brain /I of 0.15 V/m/mA was the maximal associated with stable cognitive performance with traditional fixed amplitude 800 mA dosing.…”

The heterogeneity of late-life depression and its pathobiology: a brain network dysfunction disorder

“…Recent studies demonstrated links between ECT therapy response and multimodal brain networks in LLD. Volume increases in the hippocampal complex and thalamus were antidepressant response-specific, while functional decreases in amygdala and hippocampus complex were CI-specific, the overlap between antidepressant-response and CI networks challenges parameters of ECT implicating individualized treatment modules (Qi et al 2022 ).…”

Correction: Links between electroconvulsive therapy responsive and cognitive impairment multimodal brain networks in late-life major depressive disorder

“…The original article [ 1 ] mistakenly omitted panel (g) from Figure 1; the panel has since been re-inserted.…”