Cross-metric convergence reveals altered white matter microstructural-functional correspondence in bipolar ii disorder

White matter (WM) microstructural abnormalities are increasingly recognized in bipolar II disorder (BD-II), but it remains unclear how tract-wise microstructural organization corresponds to WM functional connectivity.

Diffusion MRI and resting-state fMRI data were acquired from 86 patients with BD-II and 84 healthy controls (HCs). Microstructural profile similarity (MPS) and functional connectivity (FC) matrices were constructed across 48 WM tracts. Following participant-wise, modality-specific standardization of the MPS and FC matrices, tract-wise correspondence was quantified using Spearman correlation and Euclidean profile distance, with self-connections excluded. Group differences were assessed using covariate-adjusted linear models with false discovery rate correction. Sensitivity analyses assessed robustness to clinical sample restrictions and methodological choices.

BD-II showed altered MPS-FC correspondence in a restricted set of WM tracts, with 4 tracts identified by Spearman correlation and 6 by Euclidean distance. The left posterior corona radiata (PCR_L) and left external capsule (EC_L) showed convergent abnormalities across both metrics, characterized by higher rank-order correspondence and lower profile distance in BD-II. These convergent findings were stable across several sensitivity analyses but were sensitive to the diffusion-feature normalization reference and Euclidean profile scaling. Neither tract was significantly associated with symptom severity after multiple-comparison correction, whereas exploratory analyses implicated the left uncinate fasciculus in depressive symptom variation.

BD-II is associated with altered correspondence between WM microstructural and functional organization. These findings provide multimodal evidence for atypical WM organization and extend current understanding of the neurobiological alterations associated with BD-II.