Study Of Neural Circuits In Obsessive-compulsive Disorder Using Multimodal Magnetic Resonance Imaging

Previous neuroimaging studies have indicated that the dysfunction in cortico-striato-thalamo-cortical(CSTC)circuit contributed to the etiology of obsessive-compulsive disorder(OCD).Moreover,emerging work has shown that the pathophysiology of OCD might be related to more widely distributed large-scale brain systems including limbic system and the salience network.The aim of this study is to investigate the metabolic alterations,particularly glutamatergic signal,and its correlation with functional connectivity within CSTC circuit,as well as aberrant spontaneous neuronal activity within the whole brain of OCD patients.We combined single voxel magnetic resonance spectroscopy(MRS)and resting-state functional magnetic resonance imaging(rs-fMRI)approaches to investigate the functional activity of twenty-eight unmedicated OCD adults and twenty-eight matched healthy controls.The medial prefrontal cortex(mPFC)and bilateral thalamus were chosen as the regions-of-interest(ROIs).Quantitative evaluation and multivariate analysis were performed to identify critical metabolic biomarkers for patient and healthy control groups'differentiation.The right thalamus was set as the seed region,and its functional connectivity(FC)with whole brain voxels was calculated.Pearson's correlation analysis was performed to investigate the relationship between altered FC and glutamatergic signal level in right thalamus.The amplitude of low-frequency fluctuation(ALFF)analysis over whole brain was performed to examine the intrinsic cerebral activity of subjects.In addition,we conducted correlation analysis to probe into the association between metabolite concentrations,functional connectivity,ALFF values and symptom severity for OCD patients.Our results showed that OCD patients had significantly reduced glutamate level in mPFC(p=0.021)and right thalamus(p=0.039),as well as increased choline concentration in left thalamus(p=0.044).And multivariate analysis showed that the right thalamic glutamate was the most important metabolite for distinguishing OCD patients from healthy controls(Q~2=0.134).Decreased glutamate in right thalamus was negatively correlated with the compulsion scores of OCD patients(Spearman r=-0.674,p=0.016)and the resting state FC between right thalamus and left dorsal anterior cingulate cortex(dACC)(Pearson r=-0.505,p=0.008)for all the subjects.Our results showed that OCD patients had increased ALFF measures in the left frontopolar cortex and left orbital frontal cortex(OFC),with decreased ALFF values in the right insula.Moreover,the right insular intrinsic neuronal activity was significantly correlated with compulsion score(r=0.640,p=0.001)for OCD patients.The results consolidate the hypothesis that OCD patients exhibit abnormal glutamatergic signal within CSTC circuit.To our knowledge,it is the first finding about a reduced glutamate level in right thalamus of unmedicated OCD adults.The dysregulation of right thalamic glutamatergic signal and its close association with functional connectivity with dACC area provide a potential target for the OCD pharmacotherapy.Moreover,we found abnormal intrinsic neuronal activity within CSTC circuit and salience network in OCD patients.The altered insular spontaneous brain activity was associated with patients'symptom severity and served as an informative biomarker for OCD pathophysiology.