强迫症患者突显网络神经功能和谷氨酸的关联研究

The salience network is mainly composed of anterior cingulate cortex and insular. It has the effects of integrating sensations, generating stimulus-independent thoughts and internally representing goals and plans. We previously found that patients with obsessive and compulsive disorders (OCD) had abnormal cortical thickness and white matter microstructure in insular. However, whether the neural functional abnormalities of salience network exit in OCD is unclear. Glutamate is the excitatory neurotransmitter in human brain, which has been found to be directly related with the resting-state function in anterior cingulate cortex in healthy subjects. Decreased level of glutamate in anterior cingulate cortex was also reported in OCD patients. However, the relationship between salience network and glutamate in OCD is still unclear. The project combines the techniques of resting-state functional magnetic resonance imaging and magnetic resonance spectroscopy and uses case control method, in order to compare the neural functions of salience network and glutamate level in anterior cingulate cortex and insular between drug-na?ve OCD patients and healthy controls. On this basis, we further plan to study the relationship between salience network and glutamate level in OCD patients. We want to prove that the neural functions of salience network are abnormal; the glutamate levels in anterior cingulate cortex and insular are abnormal; the neural functions of salience network significantly correlate with the glutamate levels. If the hypotheses are to be confirmed, the study will provide new idea for the research of the pathogenesis and early identification of OCD in the future.

突显网络主要由前扣带回和岛叶构成，有整合感知觉，产生刺激不相关的思维以及内在形成目标和计划的作用。我们前期研究发现强迫症患者岛叶的皮质厚度和白质微细结构异常。而强迫症是否存在突显网络功能异常尚不明确。谷氨酸是人脑内兴奋性神经递质，已被发现与健康人群的前扣带回静息态功能直接相关以及在强迫症患者的前扣带回浓度下降。但谷氨酸与强迫症患者突显网络神经功能的关系尚不明确。本项目结合静息态功能磁共振成像和磁共振波谱技术，采用病例对照方法，比较从未用药强迫症患者与健康对照的突显网络神经功能以及前扣带回、岛叶的谷氨酸浓度，在此基础上，进一步研究强迫症患者突显网络神经功能与谷氨酸浓度的关系，尝试证明强迫症患者突显网络神经功能异常，前扣带回和岛叶的谷氨酸水平异常，突显网络神经功能与谷氨酸水平具有相关性。若假设被初步证实，该研究将为今后强迫症的发病机制和早期识别提供新的研究思路和防治手段。

本研究结合静息态功能磁共振成像（fMRI）和磁共振波谱技术（MRS），采用病例对照方法，比较未用药强迫症（OCD）患者与健康对照的突显网络神经功能以及前扣带回、岛叶的谷氨酸浓度，在此基础上，进一步研究强迫症患者突显网络神经功能与谷氨酸浓度的关系，尝试证明强迫症患者突显网络神经功能异常，前扣带回和岛叶的谷氨酸水平异常，突显网络神经功能与谷氨酸水平具有相关性。MRS结果显示OCD患者突显网络中背侧前扣带回谷氨酸复合物绝对浓度较健康对照组显著增加（6.27±2.41vs5.26±2.18，p=0.031）。前后岛叶的谷氨酸浓度未见明显异常。fMRI研究以背侧前扣带回为种子点，结果显示OCD患者背侧前扣带回与左侧小脑、眶额回、额中回及右侧额上回、右前岛等脑区的功能连接下降，与左侧尾状核的功能连接程度增强（p corrected=0.0009 with FDR）；背侧前扣带回与左后岛叶异常的FC值与背侧前扣带回的Glu，Glx浓度正相关；Granger因果分析结果显示dACC的信号更多的流向突显网络中的其他脑区。结果显示强迫症患者突显网络存在谷氨酸水平异常，异常的谷氨酸与突显网络的神经功能也存在相关性，前扣带回脑区在突显网络中作用较突出，为今后强迫症的发病机制和早期识别提供新的研究思路和防治手段。