Investigating the impact of electroconvulsive therapy on brain networks and sleep: an observational study protocol.

Introduction: Electroconvulsive therapy (ECT) is a highly effective treatment for refractory depression, but it may also cause cognitive side effects. Despite decades of use, the mechanisms by which ECT exerts both its antidepressant and cognitive effects are still poorly understood, with the latter substantially limiting referral and adherence to therapy. ECT induces changes in correlated neural activity-functional connectivity-across various brain networks, which may underlie both its clinical efficacy and associated cognitive side effects. Electroencephalography (EEG) could address these knowledge gaps by identifying biomarkers that predict therapeutic outcomes or cognitive side effects. Such developments could ultimately improve patient selection and adherence. Such markers likely span large-scale functional brain networks or temporal dynamics of brain activity during sleep. We hypothesise that enhancement in slow wave sleep mediates the relationship between antidepressant effects and changes in functional connectivity throughout the course of ECT.

Methods And Analysis: Disruptions of Brain Networks and Sleep by Electroconvulsive Therapy (DNS-ECT) is an ongoing observational study investigating the impact of ECT on large-scale brain functional networks and their relationships to sleep slow waves, an EEG marker linked to synaptic plasticity. The novelty of this study stems from our focus on the assessment of EEG markers during sleep, wakefulness and ECT-induced seizures over the course of therapy. Graph-based network analyses of high-density EEG signals allow characterisation of functional networks locally in specific subnetworks and globally over large-scale functional networks. Longitudinal assessments of EEG alongside clinical and cognitive outcomes provide a unique opportunity to improve our understanding of the circuit mechanisms underlying the development of cognitive impairments and antidepressant effects incurred during ECT.

Ethics And Dissemination: Recruitment for this 5-year study started in March 2023. Dissemination plans include presentations at scientific conferences and peer-reviewed publications. This study has been registered with ClinicalTrials.gov registry under identifier.

Trial Registration Number: NCT05905705.