Aberrant default mode network in patients with obsessive-compulsive disorder: an fMRI study

Abstract

Objective: Resting state functional connectivity is a relatively novel functional magnetic resonance imaging (fMRI) approach that analyzes the temporal correlation of blood oxygen leveldependent (BOLD) signal fluctuations in different brain areas that is not attributable to specific inputs and outputs. It represents neuronal activity that is intrinsically generated by the brain. Many researchers have been emphasized the functional connectivity across distributed brain areas during resting state. In the neuropsychiatric field, abnormal functional connectivity was reported in disorders such as Alzheimer's dementia, schizophrenia, or depression. However, there have been no studies regarding functional connectivity during resting state in the patients with obsessive-compulsive disorder (OCD). The aim of the current study was to determine whether functional connectivity in default mode network was altered in patients with OCD during resting state. It was hypothesized that OCD patients would show abnormal spatial and/or temporal patterns in default mode network. We also hypothesized altered activation of regions would include anterior cingulate cortex and prefrontal cortex, which have been shown to have altered activation in previous studies of OCD. Method: Twenty-two patients with OCD (16 drug-naive, and 6 drug-free at least 4 weeks), and 22 age-, and sex-matched healthy comparison subjects were included in this study. All subjects underwent 4.68-min resting state functional scanning runs (120 volumes) in eyes closed conditions. The posterior cingulate cortex (pCC) region was chosen as the seed region for the connectivity analysis. Correlations between temporal connectivity with the PCC seed region in each regions of interest and clinical measures were also assessed. Results: At the time of the study, the patients had a mean duration of illness of 7.61 (SD=5.33) years. The mean scores for obsessive and compulsive symptoms measured by the YaleBrown Obsessive Compulsive Scale were 11.50 (SD = 4.42) and 9.86 (SD = 4.99), respectively. The mean scores for the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI) were 16.09 (SD= 10.93) and 17.77 (SD= 15.12) for OCD patients, and 3.65 (SD =4.93) and 4.05 (SD = 5.20) for comparison subjects, respectively. The patients with OCD demonstrated lesser default mode activity compared to the comparison subjects in the anterior cingulate cortex, putamen, insula and superior frontal gyrus. OCD patients had greater default mode activity in the posterior cingulate cortex. The BAI score was negatively correlated with connectivity between the PCC seed region and the putamen. Conclusions: The current study is the first resting state fMRI study demonstrating disruption of functional connectivity in the default mode network in drug-free OCD patients. We detected decreases in default mode activity in the anterior cingulate cortex, putamen, insula and prefrontal cortex, which are components of the fronto-subcortical circuitry in OCD patients. These data provide evidence for fronto-subcortical dysfunction in patients with OCD. Further research to clarify the functional connectivity change after treatment should increase our understanding of the pathophysiology of OCD.