Associations among mediodorsal thalamic-ventrolateral prefrontal cortical white matter fiber dispersion and...

Recent studies link microstructural properties of thalamocortical connections to obsessive-compulsive disorder (OCD) symptom dimensions such as harm avoidance and incompleteness. However, the contribution of specific thalamic nuclei remains unclear. The mediodorsal nucleus (MD), implicated in OCD, includes magnocellular (MDMC) and parvocellular (MDPC) subdivisions, thought to support affective and cognitive processes, respectively. Nucleus-specific connectivity profiles may improve neurobiological models of OCD by clarifying symptom-linked neural mechanisms. In a sample of 51 individuals with OCD and 49 controls, we applied whole-brain tractography to identify pathways connecting MD subdivisions (MDMC and MDPC) with four prefrontal cortex (PFC) regions: Ventrolateral, Ventromedial, Dorsolateral, and Dorsomedial. Neurite Orientation Dispersion and Density Imaging (NODDI) was used to quantify neurite density (NDI) and orientation dispersion (ODI). Harm avoidance and incompleteness dimensions were assessed using the Obsessive-Compulsive Trait Core Dimensions Questionnaire. False discovery rate (FDR) correction was applied for multiple comparisons (Q values). Higher ODI (reflecting greater dispersion/complexity) in MD-Ventrolateral PFC connections (Left MDPC-VLPFC: β = 0.35; Right MDPC-VLPFC: β = 0.31; Left MDMC-VLPFC: β = 0.37; Right MDMC-VLPFC: β = 0.30; all P values < 0.029; all Q values < 0.043) was significantly associated with greater incompleteness symptoms in the combined sample. No associations were found with harm avoidance or for other thalamic nuclei (P > 0.05). These findings suggest that incompleteness is associated with the microstructural complexity of connections involving both MD subdivisions, highlighting their joint contribution to this dimension. Additionally, the specific involvement of the Ventrolateral PFC points to a circuit implicated in cognitive-affective control. Together, these results move toward more precise neurobiological models of incompleteness, which may inform future targeted OCD interventions.