Hyungyou Park^1,6, Minah Kim^2,3,6, Yoo Bin Kwak¹, Kang Ik K. Cho⁴, Junhee Lee⁵, Sun-Young Moon^2,3, Silvia Kyungjin Lho^2,3 and Jun Soo Kwon^1,2,3,5,*

¹Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, Republic of Korea. ²Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea. ³Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea. ⁴Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA. ⁵Institute of Human Behavioral Medicine, SNU-MRC, Seoul, Republic of Korea. ⁶These authors contributed equally: Hyungyou Park, Minah Kim.

^*Corresponding author.

The striatum and its cortical circuits play central roles in the pathophysiology of obsessive-compulsive disorder (OCD). The striatum is subdivided by cortical connections and functions; however, the anatomical aberrations in different cortico-striatal connections and coexisting microstructural anomalies in striatal subregions of OCD patients are poorly understood. Thus, we aimed to elucidate the aberrations in cortico-striatal white matter (WM) connectivity and the associated subregional microstructure of the striatum in patients with OCD. From diffusion tensor/kurtosis imaging of 107 unmedicated OCD patients and 110 matched healthy controls (HCs), we calculated the cortico-striatal WM connectivity and segmented the striatum using probabilistic tractography. For the segmented striatal subregions, we measured average diffusion kurtosis values, which represent microstructural complexity. Connectivity and mean kurtosis values in each cortical target and associated striatal subregions were compared between groups. We identified significantly reduced orbitofrontal WM connectivity with its associated striatal subregion in patients with OCD compared to that in HCs. However, OCD patients exhibited significantly increased caudal-motor and parietal connectivity with the associated striatal subregions. The mean kurtosis values of the striatal subregions connected to the caudal-motor and parietal cortex were significantly decreased in OCD patients. Our results highlighted contrasting patterns of striatal WM connections with the orbitofrontal and caudal-motor/parietal cortices, thus supporting the cortico-striatal circuitry imbalance model of OCD. We suggest that aberrations in WM connections and the microstructure of their downstream regions in the caudal-motor-/parietal-striatal circuits may underlie OCD pathophysiology and further provide potential neuromodulation targets for the treatment of OCD.