The objective of this study protocol is to test whether intermittent theta-burst transcranial magnetic stimulation (iTBS-TMS) to the inferior parietal lobule (IPL) can strengthen functional connectivity with a key region in emotion regulation (ER) neurocircuitry (anterior insula, AI) and improve performance on ER-related tasks in patients with bipolar disorder. Individual IPL sites for stimulation will be identified through baseline, pre-TMS functional magnetic resonance imaging (fMRI) scans. Patient-specific IPL subregions showing positive functional connectivity with the anterior insula and falling within the patient-specific frontoparietal control network will be used as individualized target sites for TMS stimulation. Patients will be randomized to receive 24 sessions of active versus sham iTBS to patient-specific IPL targets (6 sessions/day, 4 days, 43,200 pulses total). Post-iTBS resting-state and task-based fMRI scans will be acquired 3 days after the final day of iTBS administration (Day 4) following identical procedures as baseline. Effects of iTBS-TMS on ER will be evaluated by comparing pre-TMS versus post-TMS functional connectivity and behavior during performance on ER tasks.
Individuals of all genders
ages 24-65
Diagnostic Statistical Manual (DSM-5) defined diagnosis of bipolar I or II disorder (BD); assessed using the Mini-International Neuropsychiatric Interview (M.I.N.I.) version 7.0.2.
Current depressive episode, assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) score ≥20,
current mania/hypomania assessed by the Young Mania Rating Scale (YMRS > 12)
rapid-cycling bipolar illness, defined as >4 episodes per year, indicating increased risk of switch to mania
current active suicidality (suicidal ideation with intent or plan), as assessed by a score >4 on the MADRS item #10
current substance use disorder for the past 6 months; substance use disorder in remission permitted
Massachusetts General Hospital
Lead sponsor
University of Pennsylvania
Collaborator