Modulatory effects of ketamine on EEG source-based resting state connectivity in treatment resistant depression.
Ty Lees, Jason N Scott, Brian W Boyle, Shiba M Esfand, Samantha R Linton, Courtney Miller, Mohan Li, Sarah E Woronko, Rebecca Dunayev, Mario Bogdanov, Paula Bolton, Shuang Li, Robert C Meisner, Diego A Pizzagalli
Translational psychiatry March 6, 2026 Peer reviewed DOI: 10.1038/s41398-026-03928-4 via PubMed
Summary
A single subanesthetic dose of racemic ketamine (0.5 mg/kg) significantly reduced depressive, anhedonic, and ruminative symptoms in 24 participants with treatment-resistant depression (TRD) 24 hours after infusion. While there were broad increases in resting state functional connectivity (rsFC) within the Default Mode Network (DMN) and Frontoparietal Network (FPN), these changes did not correlate with symptom improvement. Initial pre-ketamine rsFC was associated with symptom reduction, suggesting that ketamine's effects may be linked to its impact on brain connectivity.
Study at a glance
| Sample size | 24 |
|---|---|
| Population | participants with treatment-resistant depression |
| Key finding | Twenty-four hours post-infusion, depressive, anhedonic, and ruminative symptoms for the TRD sample were significantly reduced. |
Abstract
Treatment-resistant depression (TRD) accounts for approximately 30% of major depressive disorder cases and has been characterized by altered functional connectivity within and between the Default Mode (DMN) and Frontoparietal networks (FPN). Ketamine can be an effective treatment for TRD, and its antidepressant response has been associated with alterations in resting state functional connectivity (rsFC). Here, we evaluated the effect of a single subanesthetic dose of racemic ketamine (0.5 mg/kg) on electroencephalogram (EEG) derived source-based measures of rsFC from 24 participants with TRD (16 women; aged 44.35 ± 15.86 years). Ninety-six channel resting state EEG data were collected 24 h before and after ketamine infusion. Exact low-resolution electromagnetic tomography (eLORETA) was used to estimate theta and beta-band rsFC within and between the DMN and FPN. Ruminative symptoms were assessed using the Ruminative Response Scale. Analogous data were collected from 34 healthy control participants (25 women, aged 32.49 ± 14.07 years) who did not receive any intervention. Twenty-four hours post-infusion, depressive, anhedonic, and ruminative symptoms for the TRD sample were significantly reduced. Interestingly, symptom reduction was not correlated with any changes in rsFC but was associated with initial pre-ketamine rsFC. Moreover, individuals with TRD displayed broad increases in rsFC within the DMN and FPN as well as between these two networks. Based on preclinical findings, we posit that ketamine's synaptogenic effects may be driving this general increase in connectivity. However, these synaptogenic effects can be short lived, and future work probing the full time-course of rsFC via EEG pre- and post-ketamine administration is warranted.