Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, Republic of Korea.
Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.
Mol Psychiatry. 2022 Aug;27(8):3460-3467. doi: 10.1038/s41380-022-01588-6. Epub 2022 May 26.
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.
纹状体及其皮质回路在强迫症(OCD)的病理生理学中起着核心作用。纹状体通过皮质连接和功能进行细分;然而,OCD 患者不同皮质-纹状体连接中的解剖异常以及纹状体亚区共存的微观结构异常知之甚少。因此,我们旨在阐明 OCD 患者皮质-纹状体白质(WM)连接的异常以及纹状体的相关亚区微观结构。从 107 名未经药物治疗的 OCD 患者和 110 名匹配的健康对照者(HCs)的弥散张量/峰度成像中,我们计算了皮质-纹状体 WM 连接,并使用概率追踪术对纹状体进行分割。对于分割的纹状体亚区,我们测量了表示微观结构复杂性的平均扩散峰度值。比较了两组之间每个皮质靶区和相关纹状体亚区的连接和平均峰度值。与 HCs 相比,OCD 患者的眶额 WM 连接及其相关的纹状体亚区明显减少。然而,OCD 患者与相关的纹状体亚区的尾状核-运动和顶叶连接明显增加。与尾状核-运动和顶叶皮质相连的纹状体亚区的平均峰度值在 OCD 患者中明显降低。我们的结果突出了与眶额和尾状核-运动/顶叶皮质的纹状体 WM 连接的对比模式,从而支持 OCD 的皮质-纹状体回路失衡模型。我们认为,WM 连接及其下游区域的微观结构在尾状核-/顶叶-纹状体回路中的异常可能是 OCD 病理生理学的基础,并进一步为 OCD 的治疗提供潜在的神经调节靶点。