The Turner Institute for Brain and Mental Health, School of Psychological Sciences, and Monash Biomedical Imaging, Monash University, Victoria, Australia.
The Turner Institute for Brain and Mental Health, School of Psychological Sciences, and Monash Biomedical Imaging, Monash University, Victoria, Australia.
Neuroimage. 2019 Nov 15;202:116070. doi: 10.1016/j.neuroimage.2019.116070. Epub 2019 Aug 2.
Individual differences in impulsivity and compulsivity is thought to underlie vulnerability to a broad range of disorders and are closely tied to cortical-striatal-thalamic-cortical function. However, whether impulsivity and compulsivity in clinical disorders is continuous with the healthy population and explains cortical-striatal-thalamic-cortical dysfunction across different disorders remains unclear. Here, we characterized the relationship between cortical-striatal-thalamic-cortical effective connectivity, estimated using dynamic causal modelling of resting-state functional magnetic resonance imaging data, and dimensional phenotypes of impulsivity and compulsivity in two symptomatically distinct but phenotypically related disorders, obsessive-compulsive disorder and gambling disorder. 487 online participants provided data for modelling of dimensional phenotypes. These data were combined with 34 obsessive-compulsive disorder patients, 22 gambling disorder patients, and 39 healthy controls, who underwent functional magnetic resonance imaging. Three core dimensions were identified: disinhibition, impulsivity, and compulsivity. Patients' scores on these dimensions were continuously distributed with the healthy participants, supporting a continuum model of psychopathology. Across all participants, higher disinhibition correlated with lower bottom-up connectivity in the dorsal circuit and greater bottom-up connectivity in the ventral circuit, and higher compulsivity correlated with lower bottom-up connectivity in the dorsal circuit. In patients, higher clinical severity was also linked to lower bottom-up connectivity in the dorsal circuit, but these findings were independent of phenotypic variation, demonstrating convergence towards behaviourally and clinically relevant changes in brain dynamics. Effective connectivity did not differ as a function of traditional diagnostic labels and only weak associations were observed for functional connectivity measures. Together, our results demonstrate that cortical-striatal-thalamic-cortical dysfunction across obsessive-compulsive disorder and gambling disorder may be better characterized by dimensional phenotypes than diagnostic comparisons, supporting investigation of quantitative liability phenotypes.
个体冲动性和强迫性的差异被认为是易患广泛障碍的基础，并且与皮质-纹状体-丘脑-皮质功能密切相关。然而，临床障碍中的冲动性和强迫性是否与健康人群连续，并解释不同障碍中的皮质-纹状体-丘脑-皮质功能障碍仍不清楚。在这里，我们描述了使用静息态功能磁共振成像数据的动态因果建模来估计皮质-纹状体-丘脑-皮质有效连接与冲动性和强迫性两个症状不同但表型相关的障碍（强迫症和赌博障碍）的维度表型之间的关系。487 名在线参与者提供了建模维度表型的数据。这些数据与 34 名强迫症患者、22 名赌博障碍患者和 39 名健康对照者结合，这些患者接受了功能磁共振成像检查。确定了三个核心维度：抑制解除、冲动性和强迫性。这些维度上患者的得分与健康参与者连续分布，支持精神病理学的连续模型。在所有参与者中，抑制解除程度越高，背侧回路中的自上而下连接越低，腹侧回路中的自上而下连接越高，而强迫性程度越高，背侧回路中的自上而下连接越低。在患者中，更高的临床严重程度也与背侧回路中的自上而下连接降低有关，但这些发现与表型变化无关，表明大脑动力学的行为和临床相关变化趋于一致。有效连接不随传统诊断标签而变化，仅观察到功能连接测量值的弱相关性。总的来说，我们的结果表明，强迫症和赌博障碍的皮质-纹状体-丘脑-皮质功能障碍可能通过维度表型更好地描述，而不是通过诊断比较，这支持对定量易感性表型的研究。
