Aberrant Structural Connectivity of the Triple Network System in Borderline Personality Disorder Is Associated with Behavioral Dysregulation

Background: Core symptoms of Borderline Personality Disorder (BPD) are associated to aberrant connectivity of the triple network system (salience network [SN], default mode network [DMN], executive control network [ECN]). While functional abnormalities are widely reported, structural connectivity (SC) and anatomical changes have not yet been investigated. Here, we explored the triple network's SC, structure, and its association with BPD clinical features. Methods: A total of 60 BPD and 26 healthy controls (HC) underwent a multidomain neuropsychological and multimodal MRI (diffusion- and T1-weighted imaging) assessment. Metrics (fractional anisotropy [FA], mean diffusivity [MD], cortical thickness) were extracted from SN, DMN, ECN (triple network), and visual network (control network) using established atlases. Multivariate general linear models were conducted to assess group differences in metrics and associations with clinical features. Results: Patients showed increased MD in the anterior SN, dorsal DMN, and right ECN compared to HC. Diffusivity increases were more pronounced in patients with higher behavioral dysregulation, i.e., suicidal attempting, self-harm, and aggressiveness. No differences were detected in network structure. Conclusions: These results indicate that the triple network system is impaired in BPD at the microstructural level. The preferential involvement of anterior and right-lateralized subsystems and their clinical association suggests that these abnormalities could contribute to behavioral dysregulation.