Neuroimaging Characteristics In Patients With Obsessive-compulsive Disorder

Objective: Obsessive-compulsive disorder(OCD)is a common and chronic disabling mental disorder.Over the past two decades,numerous studies have investigated the neuroimaging profiles of OCD patients,suggesting extensive abnormality in brain structure and function.However,the relationship between theses abnormalities and disease states of OCD remains unclear.Therefore,the present study aims to address this research gap by adopting a longitudinal research design across disease states to investigate whether and in which brain abnormalities improve among OCD patients from symptomatic to remitted phases.This study will contribute to identify and distinguish state-independent and state-dependent neuroimaging characteristics of OCD,and further elucidate the underlying mechanisms of its development course.Methods: The present study consists of two parts:(1)In study 1,the study sample consisted of 120 OCD patients during the symptomatic phase and 100 matched healthy controls(HCs).Participants underwent cognitive function assessments,including the Dysexecutive Questionnaire(DEX),the verbal fluency Test,the Sustained Attention to Response Task,the Letter-Number Span Test,and the logical and visual memory tests.Participants also underwent magnetic resonance imaging scans,including T1-weighted structural imaging,resting-state functional imaging,and diffusion tensor imaging.The gray matter(GM)volumes and amplitude of low-frequency fluctuations(ALFF)were compared among subjects.Regions of abnormal GM and ALFF in OCD patients were identified and entered as seeds in functional connectivity(FC)analysis.The probabilistic fiber tracking method was further applied to investigate the underlying structural connectivity(SC)between regions that showed abnormal FC in OCD patients.In addition,the relationships between the neuroimaging abnormality and cognitive deficits in OCD patients were also examined.(2)In study 2,the study sample consisted of 40 patients during remitted phase who participated in the test-retest procedure of cognitive function assessments and magnetic resonance imaging scans.All of these patients were followed up from the enrolled OCD patients in Study 1 using a natural observation method.Firstly,the changes of neuroimaging measures were evaluated in OCD patients before and after remission.Then,the relationships between changes of neuroimaging measures and both improvement of clinical symptoms and changes in cognitive performances were examined in OCD patients transitioning from symptomatic to remitted phases.Results:(1)The study 1 revealed that compared to HCs,OCD patients during the symptomatic phase exhibited significantly decreased ALFF in the thalamus and bilateral posterior insula regions,as well as reduced GM volume in the left frontal middle gyrus(MFG),left inferior frontal gyrus(IFG),precuneus(PCUN),and right inferior temporal gyrus(ITG).Functional connectivity analysis showed that OCD patients exhibited reduced left insula FC with bilateral middle cingulate gyrus and right MFG/IFG regions,weakened right insula FC with precentral gyrus/postcentral gyrus,decreased thalamus FC with bilateral PCUN,reduced left MFG FC with the left inferior parietal lobule(IPL),the left middle temporal gyrus,and the cerebellum region,decreased right ITG FC with the medial prefrontal cortex(MPFC),dorsomedial prefrontal cortex(DMPFC),PCUN,left putamen and cerebellum,as well as increased left IFG FC with posterior cingulate gyrus.All of the above results survived voxel-level p < 0.001 and cluster-level p < 0.05 with GRF correction.Structural connectivity analysis showed that OCD patients exhibited weakened SC between right insula and right postcentral gyrus,left MFG and left middle temporal gyrus,right ITG and DMPFC,as well as increased radial diffusivity and mean diffusivity of SC between right ITG and cerebellum(all p < 0.05).The correlation analysis revealed that in OCD patients,the left MFG GM volume and the left MFG-IPL FC were negatively correlated with the total score and most subscale scores of the DEX scale,the GM volume of PCUN and the right ITG FC with the MPFC and PCUN were positively correlated with immediate and delayed recall scores of the logical memory test(all p < 0.05).(2)The study 2 showed that compared to the symptomatic phase,the GM volumes of the left MFG,left IFG,and PCUN,as well as the FC of the left MFG-IPL,right ITG-MPFC,right ITG-PCUN,and THA-PCUN significantly increased after symptom remission in OCD patients.There were no significant changes in other abnormal brain imaging measures before and after remission in patients.In addition,the whole-brain exploratory analysis showed significant changes in the GM of the DMPFC and left MFG,in the ALFF of left MFG/IFG region,and in the FC of left MFG-IPL among OCD patients from symptomatic to remitted phases.All of the above results were statistically significant at voxel-level p<0.05 with FWE correction.From symptomatic to remitted phase,the changes in the GM volume of the left MFG and FC of left MFG-IPL were significantly correlated with the degrees of anxiety reduction,the changes in the GM volume of the PCUN,the FC of THA-PCUN,right ITG-PCUN,and right ITG-MPFC were significantly correlated with the degree of obsession reduction in OCD patients(both p<0.05).Before and after remission,the changes in the GM volume of the left MFG and the FC of left MFG-IPL were significantly correlated with the changes in the DEX scores,the changes in FC of right ITG-PCUN and right ITG-MPFC were significantly correlated with the changes in the scores of logical memory tests in OCD patients.Conclusions:(1)OCD patients during symptomatic phase showed abnormalities in brain structure and brain function both within and outside the cortico-striato-thalamo-cortical circuit,and also exhibited widespread alterations in brain connectivity related to these abnormal brain regions.(2)There are state-dependent abnormalities of brain structure and function exhibited in OCD patients.Specifically,these abnormalities are manifested by decreased gray matter volume and functional connectivity within brain regions associated with the frontal-parietal system and the default mode network.(3)OCD patients exhibit trait-related abnormalities in brain structure and function.These abnormalities are characterized by reduced gray matter volume,decreased resting-state functional activity,and abnormal functional and structural connectivity within brain regions associated with the sensory-motor network,as well as reduced functional and structural connectivity between brain regions associated with sensory and motor function and the prefrontal regions involved in cognitive control.(4)There were not only significant cross-sectional but also longitudinal correlations between the abnormality of the frontal-parietal system and executive function deficits,as well as between the dysfunction of the default model network-related brain regions and verbal memory impairment among OCD patients.