Parsing the Network Mechanisms of Electroconvulsive Therapy

Amber M. Leaver*, Randall Espinoza, Benjamin Wade, Katherine L. Narr

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

17 Scopus citations


Electroconvulsive therapy (ECT) is one of the oldest and most effective forms of neurostimulation, wherein electrical current is used to elicit brief, generalized seizures under general anesthesia. When electrodes are positioned to target frontotemporal cortex, ECT is arguably the most effective treatment for severe major depression, with response rates and times superior to other available antidepressant therapies. Neuroimaging research has been pivotal in improving the field's mechanistic understanding of ECT, with a growing number of magnetic resonance imaging studies demonstrating hippocampal plasticity after ECT, in line with evidence of upregulated neurotrophic processes in the hippocampus in animal models. However, the precise roles of the hippocampus and other brain regions in antidepressant response to ECT remain unclear. Seizure physiology may also play a role in antidepressant response to ECT, as indicated by early positron emission tomography, single-photon emission computed tomography, and electroencephalography research and corroborated by recent magnetic resonance imaging studies. In this review, we discuss the evidence supporting neuroplasticity in the hippocampus and other brain regions during and after ECT, and their associations with antidepressant response. We also offer a mechanistic, circuit-level model that proposes that core mechanisms of antidepressant response to ECT involve thalamocortical and cerebellar networks that are active during seizure generalization and termination over repeated ECT sessions, and their interactions with corticolimbic circuits that are dysfunctional prior to treatment and targeted with the electrical stimulus.

Original languageEnglish (US)
Pages (from-to)193-203
Number of pages11
JournalBiological psychiatry
Issue number3
StatePublished - Aug 1 2022


  • Antidepressant
  • Depression
  • Electroconvulsive therapy
  • MRI
  • Neuroimaging
  • Seizure

ASJC Scopus subject areas

  • Biological Psychiatry


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