Thalamic Functional Connectivity In Early-and Late-onset Obsessive-compulsive Disorder

Objective: Obsessive-compulsive disorder(OCD)is a heterogeneous disorder with phenotypical differences between earlyonset and late-onset subtypes.Differences in age at OCD symptom onset are linked to gender,symptom subtypes,comorbidity patterns,and treatment response.These findings indicate that early-and late-onset OCD are distinct subtypes with potentially distinct underlying pathophysiology.Previous studies have shown that the characteristics of thalamic impairment are related to the age of OCD onset,the current study aimed to explore the characterictics of the thalamic connectivity in early-and late-onset OCD to further clarify the neuropathology.Methods: A total of 120 subjects were recruited for this study,but 5subjects(1 early-onset OCD and 4 HCs)were excluded from analysis due to excessive head motion.Thirty patients with early-onset OCD(EOOCD),49 late-onset OCD(LO-OCD),and 36 matched health controls(HCs)were included in the final analysis.All participants were scanned for head magnetic resonance imaging(MRI)to obtain the resting-state f MRI images.Seed-based functional connectivity and the Oxford-FSL thalamus probabilistic Atlas were adopted to identify the thalamic dysconnectivity in early-and late-onset OCD and corresponding thalamic location.We used Pearson correlation analysis to determine whether the thalamic subregional resting state-functional connectivity abnormalities were associated with clinical characteristics.Results:(1)We found significantly decreased posterior parietal thalamus —posterior cingulate cortex/pre-frontal thalamus —cerebellum connectivity in EO-OCD patients and also in LO-OCD patients(p<0.05,FWE).(2)EO-OCD patients exhibited decreased primary motor thalamus/pre-motor thalamus — left orbitofrontal cortex connectivity(p<0.05,FWE)when compared with both HCs and LO-OCD patients.(3)There was a significant positive correlation between the duration of illness and functional connectivity of pre-frontal thalamus and left parahippocampal gyrus in EO-OCD patients(r=0.530,p=0.003);a significant negative correlation between BABS scores and functional connectivity of pre-frontal thalamus and right inferior semi-lunar lobule in LO-OCD patients(r=-0.308,p=0.042);a marginal significant negative correlation between age of onset and functional connectivity of pre-motor thalamus—left orbitofrontal cortex and a significant negative correlation between BABS scores and functional connectivity of pre-motor thalamus— left precuneus in LO-OCD patients(r=-0.281,p=0.051;r=-0.339,p=0.017).However,there was no significant correlation between thalamocortical connection and clinical symptoms.Conclusion: We found that EO-OCD and LO-OCD patients matched and differed in patterns of thalamic connectivity alterations.EO-OCD patients showed abnormal decreased thalamic resting functional connectivity with cerebrum/posterior cingulate cortex as well as LO-OCD.Deficiencies in thalamic — orbitofrontal cortex connectivity might underlie the neural mechanism in EO-OCD.