双相II型障碍中rTMS、tACS及其联合治疗后的认知变化：一项整合度中心性与个体化电场建模的探索性研究

Repetitive transcranial magnetic stimulation (rTMS), transcranial alternating current stimulation (tACS), and combined tACS-rTMS may improve cognition in bipolar disorder (BD), but how individualized stimulation dose relates to neural and cognitive changes remains unclear. This secondary neuroimaging analysis included 52 euthymic participants with bipolar II disorder from a 3-week, randomized, double-blind, sham-controlled trial. Participants received combined tACS-rTMS (n = 16), rTMS (n = 14), tACS (n = 13), and sham (n = 9) conditions, with stimulation delivered to an individualized left dorsolateral prefrontal cortex target. We integrated electric field (EF) modeling with degree centrality (DC) analysis to explore dose–network–cognition relationships. Group × time interaction effects and exploratory associations among EF intensity, changes in DC (ΔDC), and cognitive outcomes were examined using correlation, regression, and mediation analyses. Significant group × time interactions in DC were identified in all three active-versus-sham contrasts, converging in the left rolandic operculum, with additional changes in the parahippocampal and middle occipital gyri in the rTMS contrast. Associations between ΔDC and cognition outcomes were observed but did not survive false discovery rate (FDR) correction. Nominal associations between tACS-related EF intensity and local ΔDC were observed in the tACS and combined tACS-rTMS groups. Importantly, EF intensity was significantly associated with the DC–cognition coupling index in the left caudate nucleus in the tACS group after FDR correction. Exploratory mediation models suggested nominal indirect associations between EF intensity and cognitive change via ΔDC, neither of which survived FDR correction. In conclusion, rTMS, tACS, and combined tACS-rTMS were associated with partially distinct patterns of DC change in euthymic bipolar II disorder. Integrating individualized EF modeling with DC analysis may help characterize dose–network–cognition relationships, but larger prospective studies are needed.

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