PMID: 40468342 https://pubmed.ncbi.nlm.nih.gov/40468342/

Abstract

BACKGROUND: Traditional neuromodulation strategies show promise in enhancing cognitive abilities in bipolar disorder (BD) but remain suboptimal. This study introduces a novel multimodal neurostimulation (MNS) protocol to improve therapeutic outcomes.

METHODS: The novel MNS protocol used individualized diffusion tensor imaging (DTI) data to identify fiber tracts between the dorsolateral prefrontal cortex and dorsal anterior cingulate cortex. The highest structural connectivity point is selected as the individualized stimulation site, which is then targeted using a combination of optimized transcranial alternating current stimulation (tACS) and robot-assisted navigated repetitive transcranial magnetic stimulation (rTMS). A double-blind randomized controlled trial was conducted to investigate the clinical efficacy of this innovative neuromodulation approach on cognitive abilities in stable-phase BD patients. One hundred BD patients were randomly assigned to four groups: group A (active tACS-active rTMS (MNS protocol)), group B (sham tACS-active rTMS), group C (active tACS-sham rTMS), and group D (sham tACS-sham rTMS). Participants underwent 15 sessions over 3 weeks. Cognitive assessments (THINC integrated tool) were conducted at baseline (week 0) and post-treatment (week 3).

RESULTS: Sixty-six participants completed all 15 sessions. Group A (MNS protocol) showed superior improvements in Spotter CRT, TMT, and DSST scores compared to other groups at week 3. Only group A exhibited significant activation in the left frontal region post-MNS intervention. The novel MNS protocol was well tolerated, with no significant side effects observed.

CONCLUSIONS: The study indicates that DTI-guided multimodal neurostimulation mode significantly improves cognitive impairments and is safe for stable-phase BD patients.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05964777.