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Aberrant cortico-striatal white matter connectivity and associated subregional microstructure of the striatum in obsessive-compulsive disorder

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Abstract

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.

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Fig. 1: Group comparison of cortico-striatal white matter (WM) connectivity.
Fig. 2: Visualization of striatal subregions with strong connections to the caudal-motor (in orange column) and parietal (in navy column) targets.

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Acknowledgements

This research was supported by the Basic Science Research Program and the Bio & Medical Technology Development Program through National Research Foundation of Korea (NRF) funded by the Ministry of Science & ICT (Grant no. 2019R1C1C1002457 and 2021M3A9E4080784).

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  1. These authors contributed equally: Hyungyou Park, Minah Kim.

Authors and Affiliations

  1. Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, Republic of Korea

    Hyungyou Park, Yoo Bin Kwak & Jun Soo Kwon

  2. Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea

    Minah Kim, Sun-Young Moon, Silvia Kyungjin Lho & Jun Soo Kwon

  3. Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea

    Minah Kim, Sun-Young Moon, Silvia Kyungjin Lho & Jun Soo Kwon

  4. Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Kang Ik K. Cho

  5. Institute of Human Behavioral Medicine, SNU-MRC, Seoul, Republic of Korea

    Junhee Lee & Jun Soo Kwon

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Contributions

HP, MK, and JSK conceived and designed the study. MK, YBK, and JSK supervised all the processes. MK, JL, SYM, SKL, and JSK collected clinical information from the participants. HP, KIKC, and YBK performed image processing and data analysis. HP and MK wrote the manuscript. YBK, KIKC, JL, SYM, SKL, and JSK edited the manuscript.

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Correspondence to Jun Soo Kwon.

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Park, H., Kim, M., Kwak, Y.B. et al. Aberrant cortico-striatal white matter connectivity and associated subregional microstructure of the striatum in obsessive-compulsive disorder. Mol Psychiatry 27, 3460–3467 (2022). https://doi.org/10.1038/s41380-022-01588-6

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