TMS for Improving Cognitive Function in Bipolar Disorder

Sponsor
First Affiliated Hospital of Zhejiang University
Study ID
NCT07414147
Status
Not Yet Recruiting

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Conditions

  • Bipolar Disorder (BD)
  • Cognitive Impairment

Eligibility Criteria

Sex
ALL
Age
18 Years - 45 Years
Healthy Volunteers
Not accepted

Interventions

  • Active Intermittent Theta Burst Stimulation — DEVICE
    Active iTBS will be delivered using MRI-guided neuronavigation system. Participants will receive two sessions per day for 5 consecutive days. The iTBS pattern consists of bursts of three pulses at 50 Hz, repeated at 5 Hz. Each train lasts 2 s and is followed by an 8-s inter-train interval. Stimulation will be administered at 90% of the resting motor threshold (RMT), with a total of 1,800 pulses per session. Each session will last approximately 10 minutes. For each participant, the individual stimulation target will be defined within the left V1 as the subregion showing the strongest functional connectivity with the hippocampus. Target coordinates will be mapped onto each participant's native anatomical space and implemented using robot-assisted, MRI-guided neuronavigation based on the participant's T1-weighted structural MRI to ensure accurate and reproducible coil positioning across sessions.
  • Online Cognitive Training — BEHAVIORAL
    Participants in both arms will complete the same computerized pattern recall training paired with each stimulation session (twice daily) throughout the 5-day iTBS intervention period. In each block, one abstract, difficult-to-verbalize target figure is presented centrally for 5 seconds for encoding. Following target offset, participants complete 15 consecutive match/non-match judgments: a sequence of visually similar probe figures is presented one at a time (each for 1500 ms with a 500-ms inter-stimulus interval), and participants indicate whether each probe is identical to the target figure. Upon completion of the 15 judgments, a new target figure is introduced and the next block begins. Task progression is self-paced; therefore, the number of blocks completed within a session may vary across participants depending on response speed. Ten parallel task versions will be used and kept consistent across sessions to align training content with each iTBS visit.
  • Sham Intermittent Theta Burst Stimulation — DEVICE
    Sham iTBS will be delivered over the individualized V1-HPC target using MRI-guided neuronavigation. The coil will be held perpendicular to the target scalp site and kept in contact throughout stimulation. Intensity will be set at 20% RMT, with all other iTBS parameters identical to the active group.

Study Details

Bipolar disorder is a highly disabling psychiatric illness, and cognitive impairment is common in patients with bipolar depression as well as during remission, contributing substantially to functional disability and poorer prognosis. Currently, effective interventions specifically targeting cognitive deficits remain limited, highlighting the need for novel treatment strategies. Transcranial magnetic stimulation, a noninvasive neuromodulation technique, has shown potential benefits for depressive symptoms and cognitive functioning. Based on structural and functional neuroimaging evidence, this study proposes an individualized intermittent theta burst stimulation (iTBS) protocol targeting the primary visual cortex (V1) and its functional pathway to the hippocampus, combined with online cognitive training. This randomized, double-blind, parallel-group, sham-controlled trial will enroll 88 patients with bipolar disorder in remission phase and allocate them to active or sham stimulation. The intervention will be delivered over 5 days, with follow-up assessments through 6 weeks. The primary outcome is change in cognitive performance as measured by the Cambridge Neuropsychological Test Automated Battery (CANTAB). Secondary outcomes include changes in clinical symptom ratings, magnetic resonance imaging (MRI) biomarkers, and the incidence of adverse events. This study aims to evaluate the efficacy and safety of this targeted intervention and to provide evidence for precision treatment approaches to cognitive impairment in bipolar disorder.

Key Dates

First listed
Feb 17, 2026
Start date
Mar 1, 2026
Status verified
Feb 2026
Primary completion
Mar 1, 2027
Completion
Apr 30, 2027

Study Design

Enrollment
88 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Active iTBS + Online Cognitive Training
    Participants will receive active iTBS over the individualized left V1-HPC target using MRI-guided neuronavigation, delivered twice daily for 5 consecutive days (90% RMT; 1,800 pulses per session; \~10 minutes). Each stimulation session will be paired with the same online computerized pattern recall training.
  • Sham Comparator: Sham iTBS + Online Cognitive Training
    Participants will receive sham iTBS over the individualized left V1-HPC target using MRI-guided neuronavigation, delivered twice daily for 5 consecutive days (20% RMT; all other iTBS parameters identical to the active group). Each stimulation session will be paired with the same online computerized pattern recall training.

Primary Outcome Measure

Cognitive performance will be assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB) Spatial Span (SSP) [ Time Frame: Time Frame: Assessments will be conducted at baseline prior to randomization (T0), immediately after completion of the intervention (T1), and at 6 weeks (T2) post-intervention follow-up. ]

Central Contacts

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