Symptom-specific functional and structural connectivity of the fronto-striatal circuitry in obsessive-compulsive disorder

强迫症(OCD)是一种严重的精神疾病，具有高度的症状异质性。虽然一些患者主要受到污染恐惧或洗涤强迫的影响，但另一些患者主要受到检查强迫等强迫性行为的影响。最近的研究表明，现有的治疗方法在不同的精神病理亚组中并不是同样有效。此外，越来越多的证据表明，不同的症状维度可能由部分不同的神经系统介导，并可能与相关网络(主要是额纹状体)内功能和结构连通性的特定症状变化有关。因此，从诊断和病因学的角度以及治疗方面的原因，对强迫症的精神病理亚群或症状维度进行更具体的表征是明智和重要的。到目前为止，还没有在强迫症中进行关于症状特定改变的特定功能系统(功能连通性)和辅助白质纤维束(结构连通性)的多模式研究。在此背景下，拟议的项目旨在调查强迫症患者在功能和结构连接方面的特定症状变化。这项研究将重点关注以检查为主的患者以及以害怕污染和洗涤为主的患者。这些症状维度被证明是相对独立的，并具有高结构效度的特点，从而允许对群体进行可靠的区分。为此，该项目将使用神经认知范式来研究不确定性、奖励加工和认知控制下的决策，即主要涉及额纹状体网络的过程，这些网络已知在障碍的背景下发生改变。结构连接性将通过扩散张量成像(DTI)来确定。将使用基于纤维束的空间统计和概率纤维跟踪来检查特定的纤维束。将使用动态因果建模(DCM)研究功能连接性的假定改变，并将使用相关和基于体素的方法将其与相应的白质改变相关联。这种多模式程序应该提供有关强迫症患者功能和结构连接性改变潜在的病理生理基础的具体信息，从而允许不同症状维度或患者亚组之间的神经生物学区分。从前瞻性的角度来看，识别特定症状的神经功能改变可能为个性化的药物和心理治疗策略提供基础。

Obsessive-compulsive disorder (OCD) is a severe psychiatric illness that is characterized by high symptom heterogeneity. Whereas some patients suffer mainly from contamination fears or washing compulsions, others are affected predominantly by obsessive behaviors such as checking compulsions. Recent studies indicated that established therapies are not equally effective in the different psychopathological subgroups. Moreover, there is increasing evidence showing that the different symptom dimensions may be mediated by partially distinct neural systems and may be associated with symptom-specific alterations in functional and structural connectivity within relevant, mainly fronto-striatal, networks.Thus, a more specific characterization of psychopathological subgroups or symptom dimensions in OCD is sensible and important, both from a diagnostic and etiologic perspective, as well as for therapeutic reasons. Multimodal studies investigating specific functional systems (functional connectivity) and subserving white matter fiber tracts (structural connectivity) with regard to symptom-specific alterations have not been performed in OCD so far. Against this background, the proposed project aims at investigating symptom-specific alterations in functional and structural connectivity in patients with OCD. The study will be focusing on patients with predominantly checking compulsions as well as patients with predominantly contamination fears and washing compulsions. These symptom dimensions have been shown to be relatively independent from each other and to be characterized by high construct validity thus allowing for a reliable discrimination of groups. To this aim, the project will employ neurocognitive paradigms examining decision making under uncertainty, reward processing and cognitive control, i.e. processes involving mainly fronto-striatal networks which are known to be altered in the context of the disorder. Structural connectivity will be determined by means of diffusion tensor imaging (DTI). Specific fiber tracts will be examined using tract-based spatial statistics and probabilistic fiber tracking. Postulated alterations in functional connectivity will be studied with ¿Dynamic Causal Modeling¿ (DCM) and will be related to respective white matter alterations using correlational and voxel-based methods. This multimodal procedure should provide specific information about the pathophysiological substrates underlying alterations in functional and structural connectivity in patients with OCD that allow for a neurobiological differentiation between different symptom dimensions or patient subgroups. Perspectively, the identification of symptom-specific neurofunctional alterations may provide the basis for personalized pharmacological and psychotherapeutic treatment strategies.