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
Parallel
Transcranial Magnetic Stimulation (TMS)
DeviceTranscranial magnetic stimulation (TMS) is a non-invasive tool for modulating patterns of brain activation and circuit connectivity. It uses electromagnetic pulses to induce electric currents over the cortex that serve to depolarize or hyperpolarize neurons, thereby changing patterns of synaptic activity. This study uses intermittent theta burst stimulation (iTBS), an efficient TMS protocol that uses high frequency (50Hz) triplets of TMS given every 200 milliseconds (i.e. at 5 Hz).
Sham (placebo) TMS
DeviceSham stimulation works by blocking the magnetic field with an internal spacer on the sham side of the TMS coil, allowing the operator to place the coil surface against the scalp. A brief electric pulse calibrated to the stimulator output is delivered to the scalp simultaneous to the TMS pulse to mimic the scalp sensation during the sham condition. 75 Importantly, the electric pulse is calibrated to the stimulator output to ensure a realistic sham condition.
Correlated functional magnetic resonance imaging (fMRI) time series (functional connectivity)
Primary outcome will be changes in the correlated time series between brain regions (inferior parietal lobule and anterior insula) from baseline to post intervention
Affective Multisource Interference Task
Secondary outcome will be changes in reaction time responses to an affective interference task
Balloon Analogue Risk Task
Secondary outcome will be changes in number of button presses in response to a risk versus reward task
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Massachusetts General Hospital
Lead sponsor
University of Pennsylvania
Collaborator
