Brain Connectivity In Checking And Washing Symptom Subtypes Of Obsessive-Compulsive Disorder

Objective: Obsessive-compulsive disorder(OCD)is one highly heterogeneous psychiatric disorder.According to the main symptom dimensions in OCD,checking and washing are the two most typical,most common,and most widely investigated symptom subtypes.Previous findings have suggested that checking OCD and washing OCD might be mediated by distinct neural circuits involved in response inhibition and emotional processing,respectively.However,the underlying pathological mechanisms remain unclear.This study aims to investigate whether there are specific behavioral deficits and abnormal brain connectivity of response inhibition and emotional processing in patients with checking OCD and those with washing OCD,elucidate the neurological mechanism of checking OCD and washing OCD subtypes,and then provide further evidences for understanding the psychopathological mechanisms of OCD.Methods: This study adopted a between-subject experimental design,the independent variable was group(checking OCD,washing OCD and HCs),and the dependent variables were behavioral performances as well as neuroimaging indicators.Four sub-studies have been conducted:(1)In study 1,a total of 40 patients with checking OCD,35 patients with washing OCD and 80 healthy controls(HCs)were recruited.The Dimensional Yale-Brown Obsessive-Compulsive Scale was used to assess the severity of obsessive and compulsive symptoms,the Center for Epidemiologic Studies Depression Scale and State Anxiety Inventory were used to assess the severity of depression and anxiety.Also,the Color Trails Test,Stroop Color Word Test,Go/No-go task and Hariri task were used to assess subjects’ function of response inhibition and emotional processing.The one-way analysis of variance(ANOVA)and independent sample t-test were used to investigate group differences in behavioral indicators of psychological tests and experimental tasks among participants.(2)In study 2,functional neuroimaging data were collected from 35 patients with checking OCD,33 patients with washing OCD and 60 healthy controls(HCs)when they were performing Go/No-go task and Hariri task.Focusing on the prefrontal-striatum-thalamus circuit and the prefrontallimbic system,brain activation of response inhibition and emotion processing were analyzed with regions of interest analysis,and effective connectivity of response inhibition and emotion processing were analyzed with dynamic causal modeling analysis.The one-way ANOVA and Bayesian Model Comparison was separately used to investigate group differences in the brain activation and effective connectivity in response inhibition and emotional processing among the checking OCD,washing OCD and HC groups.(3)In study 3,the brain regions with significant group differences in activation of response inhibition and emotion processing were selected as regions of interest,then based on a seed-based method,the one-way ANOVA was applied to investigate group differences in resting-state functional connectivity related to response inhibition and emotion processing among the checking OCD,washing OCD and HC groups.(4)In study 4,the brain regions with significant group differences in brain activation and in functional connectivity were selected as regions of interest,then based on the probabilistic tractography,the one-way ANOVA was applied to investigate the structural connectivity related to response inhibition and emotion processing among the checking OCD,washing OCD and HC groups.Results:(1)Compared with HC group,both checking OCD group and washing OCD group had significantly longer response time in CTT B(p < 0.05).Compared with HC group,checking group had less correct items in SCWT “color” and “color word” condition(ps < 0.05).Additionally,the behavioral results of Go/No-go task showed that checking group had lower accuracy than HC group in No-go task(p < 0.05),and the behavioral results of the Hariri task showed that washing group had lower accuracy than HC group in negative face matching task(p < 0.05).(2)The brain activation results in Go/No-go task showed that checking group had significantly increased activation in bilateral inferior frontal gyrus(IFG)and right putamen than washing group and HC group(both pFWE < 0.05),and both checking group and washing group had significantly increased activation in supplementary motor area(SMA)compared with HC group(both pFWE < 0.05).The effective connectivity results in Go/No-go task further showed that checking group had significantly increased effective connectivity from right putamen to right IFG than washing group and HC group(posterior probability > 0.95).Additionally,the brain activation results in Hariri task showed that washing OCD group had significantly less deactivation in ventromedial prefrontal cortex(vm PFC)and increased activation in bilateral amygdala,bilateral hippocampus and bilateral parahippocampal gyrus compared with checking group and HC group(both pFWE < 0.05).The effective connectivity results in Hariri task further showed that washing group had significantly increased effective connectivity from right amygdala to right vm PFC,from left hippocampus to left parahippocampal gyrus compared with checking group and HC group(posterior probability > 0.95).(3)Resting state functional connectivity results showed that checking group had significantly increased functional connectivity(FC)between left putamen and right IFG than washing group and HC group(both pFWE < 0.05),and increased FC value was significantly positively correlated with the response time in CTT B(p < 0.05)and significantly negatively correlated with the correct items in “color word” condition of SCWT(p < 0.05).Compared with checking group and HC group,washing group had significantly decreased FC between left amygdala and bilateral dorsomedial prefrontal cortex(dm PFC),left hippocampus and right dm PFC,right amygdala and right vm PFC(pFWE < 0.05).(4)Structural connectivity results showed that checking group had significantly decreased fractional anisotropy(FA)between left putamen and right IFG fiber tract than HC group(p < 0.05),checking had significantly increased radial diffusivity(RD)between right IFG and right SMA fiber tract than washing group and HC group(ps < 0.05);both checking group and washing group had significantly increased axial diffusivity(AD)between right IFG and right SMA fiber tract than HC group(ps < 0.05).Compared with checking group and HC group,washing group had significantly decreased FA between left amygdala and right dm PFC fiber tract(p < 0.05),decreased FA and RD between left hippocampus and right dm PFC fiber tract(p < 0.05),decreased FA between right amygdala and right vm PFC fiber tract(p < 0.05).Conclusions:(1)Patients with checking OCD are mainly characterized by impaired response inhibition,and have more severe abnormalities in functional and structural connectivity of the specific brain regions in prefrontal-striatum-thalamus circuit(inferior frontal gyrus,putamen and supplementary motor area),implying the abnormal prefrontal-striatum-thalamus circuit might be the neurological mechanism of impaired response inhibition in checking OCD.(2)Patients with washing OCD are mainly characterized by impaired emotion processing,and have more severe abnormalities in functional and structural connectivity of the specific brain regions in prefrontal-limbic system(medial prefrontal cortex,amygdala,hippocampus and parahippocampal gyrus),implying the abnormal prefrontal-limbic system might be the neurological mechanism of impaired emotion processing in washing OCD.(3)Both checking OCD and washing OCD have some crosssymptom-subtype consistent alterations in brain connectivity in prefrontalstriatum-thalamus circuit,indicating that different symptom subtypes of OCD might have common brain neuropathological abnormalities.