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Electroconvulsive therapy treatment responsive multimodal brain networks.

ABSTRACT: Electroconvulsive therapy is regarded as the most effective antidepressant treatment for severe and treatment-resistant depressive episodes. Despite the efficacy of electroconvulsive therapy, the neurobiological underpinnings and mechanisms underlying electroconvulsive therapy induced antidepressant effects remain unclear. The objective of this investigation was to identify electroconvulsive therapy treatment responsive multimodal biomarkers with the 17-item Hamilton Depression Rating Scale guided brain structure-function fusion in 118 patients with depressive episodes and 60 healthy controls. Results show that reduced fractional amplitude of low frequency fluctuations in the prefrontal cortex, insula and hippocampus, linked with increased gray matter volume in anterior cingulate, medial temporal cortex, insula, thalamus, caudate and hippocampus represent electroconvulsive therapy responsive covarying functional and structural brain networks. In addition, relative to nonresponders, responder-specific electroconvulsive therapy related brain networks occur in frontal-limbic network and are associated with successful therapeutic outcomes. Finally, electroconvulsive therapy responsive brain networks were unrelated to verbal declarative memory. Using a data-driven, supervised-learning method, we demonstrated that electroconvulsive therapy produces a remodeling of brain functional and structural covariance that was unique to antidepressant symptom response, but not linked to memory impairment.

SUBMITTER: Qi S

PROVIDER: S-EPMC7267951 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAlthough 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.MethodsA 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.ResultsDecreased 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.ConclusionsThe 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 registrationClinicalTrials.gov Identifier: NCT02999269.

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Electroconvulsive therapy treatment responsive multimodal brain networks.

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