Work

Decreased within-default mode network connectivity with accelerated intermittent theta burst stimulation across unipolar and bipolar depression: Candidate transdiagnostic circuit marker for treatment response

Year: 2026

Type: article

Abstract: ABSTRACT Background An accelerated schedule of intermittent theta burst stimulation (aiTBS) has been shown to improve clinical efficacy of transcranial magnetic stimulation for bipolar disorder (BD) and major depressive disorder (MDD). We investigated the functional connectivity changes underpinning clinical effects of aiTBS on transdiagnostic treatment-resistant depression (TRD). Methods Data were collected from two studies: an open-label active aiTBS study for MDD and a double-blind, randomized control aiTBS study for BD. Thirty-four participants (18 female/16 male) with transdiagnostic TRD currently experiencing moderate to severe depressive episodes (Montgomery-Åsberg Rating Scale [MADRS] score ≥ 20). Participants received active (22 total; 12 BD/10MDD) or sham (12 BD) aiTBS delivered to personalized left dorsolateral prefrontal cortical targets. Participants completed MRI scans before and after ten sessions of active or sham aiTBS per day for five days. Within each aiTBS group (active/sham), connectivity changes within the default mode network (DMN) following aiTBS and their correlations with MADRS scores were evaluated. Results Immediately following aiTBS, active group members had lower within-DMN connectivity ( p = .01, d = –0.62) and lower MADRS scores ( p < .0001) than at baseline; these changes were correlated ( r = .47, p = .03). They also reported decreased insomnia ( p < .0001) and suicidality ( p < .0001). These changes were not present in the sham BD group ( p s = .29– .92). Conclusions aiTBS was associated with decreased within-DMN connectivity among people with transdiagnostic TRD, which could underlie depression improvement. The study is registered on ClinicalTrials.gov (study identifier NCT05228457 ). https://clinicaltrials.gov/study/NCT05228457

Source: Transcranial magnetic stimulation .

DOI: 10.1016/j.transm.2026.100205