Increased functional connectivity between presupplementary motor area and inferior frontal gyrus associated with the ability of motor response inhibition in obsessive-compulsive disorder.

Recent evidence suggests that presupplementary motor area (pre-SMA) and inferior frontal gyrus (IFG) play an important role in response inhibition. However, no study has investigated the relationship between these brain networks at resting-state and response inhibition in obsessive-compulsive disorder (OCD). We performed resting-state functional magnetic resonance imaging scans and then measured the response inhibition of 41 medication-free OCD patients and 49 healthy control (HC) participants by using the stop-signal task outside the scanner. We explored the differences between OCD and HC groups in the functional connectivity of pre-SMA and IFG associated with the ability of motor response inhibition. OCD patients showed a longer stop-signal reaction time (SSRT). Compared to HC, OCD patients exhibit different associations between the ability of motor response inhibition and the functional connectivity between pre-SMA and IFG, inferior parietal lobule, dorsal anterior cingulate cortex, insula, and anterior prefrontal cortex. Additional analysis to investigate the functional connectivity difference from the seed ROIs to the whole brain voxels revealed that, compared to HC, OCD exhibited greater functional connectivity between pre-SMA and IFG. Also, this functional connectivity was positively correlated with the SSRT score. These results provide additional insight into the characteristics of the resting-state functional connectivity of the regions belonging to the cortico-striato-thalamo-cortical circuit and the cingulo-opercular salience network, underlying the impaired motor response inhibition of OCD. In particular, we emphasize the importance of altered functional connectivity between pre-SMA and IFG for the pathophysiology of motor response inhibition in OCD.

Reduced resting-state functional connectivity between insula and inferior frontal gyrus and superior temporal gyrus in hoarding disorder.

Background: Hoarding disorder (HD) is characterized by cognitive control impairments and abnormal brain activity in the insula and anterior cingulate cortex (ACC) during disposal of personal items or certain executive function tasks. However, whether there are any changes in resting-state functional connectivity of the insula and ACC remains unclear. Methods: A total of 55 subjects, including 24 patients with HD and 31 healthy controls (HCs), participated in the study. We acquired resting-state functional magnetic resonance imaging data and examined group differences in functional connectivity from the insula and ACC in whole-brain voxels. Results: In patients with HD, functional connectivity was significantly lower between the right insula and right inferior frontal gyrus (IFG) and left superior temporal gyrus (STG) compared to HCs. There was no correlation between these connectivities and HD symptoms. Conclusions: Although the clinical implication is uncertain, our results suggest that patients with HD have resting-state functional alterations between the insula and IFG and STG, corresponding with the results of previous fMRI studies. These findings provide new insight into the neurobiological basis of HD.

Posterior cingulate cortex spontaneous activity associated with motor response inhibition in patients with obsessive-compulsive disorder: A resting-state fMRI study.

Recent evidence suggests that broad brain regions, not limited to the fronto-striato-thalamo-cortical circuit, play an important role in motor response inhibition. However, it is still unclear which specific key brain region is responsible for impaired motor response inhibition observed in obsessive-compulsive disorder (OCD). We calculated the fractional amplitude of low-frequency fluctuations (fALFF) and measured response inhibition ability using the stop-signal task in 41 medication-free patients with OCD and 49 healthy control (HC) participants. We explored the brain region that shows different association between the fALFF and the ability of motor response inhibition. Significant differences in fALFF associated with the ability of motor response inhibition were identified in dorsal posterior cingulate cortex (PCC). There was a positive correlation between increased fALFF in the dorsal PCC and impaired motor response inhibition in OCD. In the HC group, there was a negative correlation between the two variables. Our results suggest that the magnitude of resting-state blood oxygen level-dependent oscillation of the dorsal PCC is a key brain region for the underlying mechanisms of impaired motor response inhibition in OCD. Future studies should examine whether this characteristic of dorsal PCC affects other large-scale networks responsible for motor response inhibition of OCD.

Inverse Association Between Resting-State Putamen Activity and Iowa Gambling Task Performance in Patients With Obsessive-Compulsive Disorder and Control Subjects.

Background: Symptoms of obsessive-compulsive disorder (OCD) have been conceptualized as manifestations of decision-making deficits. Patients with OCD exhibit impairment during the decision-making process, as assessed by the Iowa Gambling Task (IGT). This impairment is independent of clinical severity and disease progression. However, the association between the decision-making deficit and resting-state brain activity of patients with OCD has not been examined. Methods: Fifty unmedicated patients with OCD and 55 matched control subjects completed IGT. Resting-state brain activity was examined using the fractional amplitude of low-frequency fluctuations (fALFFs). fALFF analysis focused on the slow-4 and 5 bands. Group comparisons were performed to determine the association between IGT performance and fALFFs. Results: There was a significant group difference in the association between the IGT total net score and slow-4 fALFFs in the left putamen (voxel height threshold of p < 0.001; cluster size threshold of p < 0.05; family wise error-corrected). Higher putamen slow-4 fALFFs were correlated with lower IGT scores for OCD patients (r = -0.485; p < 0.0005) and higher IGT scores for control subjects (r = 0.402; p < 0.005). There was no group difference in the association between the IGT total net score and slow-5 fALFFs. Conclusions: These findings in unmedicated patients demonstrate the importance of resting-state putamen activity for decision-making deficit associated with OCD, as measured by IGT. The inverse correlation may be explained by the hypersensitive response of the putamen in patients with OCD.

Abnormal white matter structure in hoarding disorder.

Although preliminary neuroimaging research suggests that patients with hoarding disorder (HD) show widespread abnormal task-related activity in the brain, there has been no research on alterations in the white matter tracts in these patients. The aim of this study was to investigate the characteristics of the major white matter tracts in patients with HD. Tract-based spatial statistics were used to search for white matter tract abnormalities throughout the brain in 25 patients with HD and 36 healthy controls. Post hoc analysis of regions of interest was performed to detect correlations with clinical features. Compared with the controls, patients with HD showed decreased fractional anisotropy and increased radial diffusivity in anatomically widespread white matter tracts. Post hoc analysis of regions of interest revealed a significant negative correlation between the severity of hoarding symptoms and fractional anisotropy in the left anterior limb of the internal capsule and a positive correlation between the severity of these symptoms and radial diffusivity in the right anterior thalamic radiation. Patients with HD showed a broad range of alterations in the frontal white matter tracts, including the frontothalamic circuit, frontoparietal network, and frontolimbic pathway. The findings of this study indicate associations between frontal white matter abnormalities related to the severity of hoarding symptoms in HD and the cortical regions involved in cognitive dysfunction. The insights provided would be useful for understanding the neurobiological basis of HD.

Alterations of default mode and cingulo-opercular salience network and frontostriatal circuit: A candidate endophenotype of obsessive-compulsive disorder.

Background It is gradually becoming clear that obsessive-compulsive disorder (OCD) patients have aberrant resting-state large-scale intrinsic networks of cingulo-opercular salience (SN), default mode (DMN), and front-parietal network (FPN). However, it remains unknown whether unaffected first-degree relatives of OCD patients have these alterations as a vulnerability marker to the disorder. Methods We performed resting-state functional magnetic resonance imaging (rsfMRI) scans of 47 medication-free OCD patients, 21 unaffected healthy first-degree relatives of OCD patients, and 62 healthy control (HC) participants. We explored differences between the three groups in the functional connectivity from SN (seeds: anterior-insula (AI) and dorsal anterior cingulate cortex (dACC)), DMN (seeds: medial prefrontal cortex (MPFC) and posterior parietal cortex (PCC)), and FPN (seeds: dorsolateral prefrontal cortex (DLPFC)). Results Compared to HC, both OCD patients and first-degree relatives showed significantly greater functional connectivity between AI and PCC and between DLPFC and the thalamus. Compared to first-degree relatives and HC, OCD patients showed reduced functional connectivity between PCC and DLPFC, and this altered functional connectivity was negatively correlated with anxiety and depressive symptom within OCD group. Conclusions OCD patients and unaffected first-degree relatives of OCD patients showed overlapping alterations in resting state functional connectivity between the regions of SN and DMN and between DLPFC and the thalamus. Our results suggested that alterations between large-scale intrinsic networks and within the dorsal cognitive cortico-striato-thalamo-cortical (CSTC) circuit could represent endophenotype markers of OCD.

Aberrant Resting-State Cerebellar-Cerebral Functional Connectivity in Unmedicated Patients With Obsessive-Compulsive Disorder.

Background: Although abnormality of cerebellar-cerebral functional connectivity at rest in obsessive-compulsive disorder (OCD) has been hypothesized, only a few studies have investigated the neural mechanism. To verify the findings of previous studies, a large sample of patients with OCD was studied because OCD shows possible heterogeneity. Methods: Forty-seven medication-free patients with OCD and 62 healthy controls (HCs) underwent resting-state functional magnetic imaging scans. Seed-based connectivity was examined to investigate differences in cerebellar-cerebral functional connectivity in OCD patients compared with HCs. Correlations between functional connectivity and the severity of obsessive-compulsive symptoms were analyzed. Results: In OCD, we found significantly increased functional connectivity between the right lobule VI and the left precuneus, which is a component of the default mode network (DMN), compared to HCs. However, there was no correlation between the connectivity of the right lobule VI-left precuneus and obsessive-compulsive severity. Conclusions: These findings suggest that altered functional connectivity between the cerebellum and DMN might cause changes in intrinsic large-scale brain networks related to the traits of OCD.

Impacts of Stressful Life Events and Traumatic Experiences on Onset of Obsessive-Compulsive Disorder.

Not a few patients with obsessive-compulsive disorder (OCD) have experienced events that affected the onset. The onset of OCD is not limited to the original meaning of trauma; rather, traumatic experiences such as unexpected exposure to contaminants or various stressful life events often cause the onset of OCD. It would be useful to understand the experiences surrounding the onset, including stressful life events and traumatic experiences, for comprehension of the pathophysiology of OCD. In the present study, we investigated the onset conditions of 281 patients with OCD and compared clinical characteristics among groups with or without stressful life events including traumatic experiences. As a result, 172 (61.2%) participants had experienced various stressful life events, and 98 (34%) participants had had traumatic experiences before the onset. Furthermore, the participants who had had stressful life events showed more contamination/fear symptoms compared with those without such life events. Meanwhile, the patients who had had specific traumatic experiences showed a tendency toward hoarding obsessions. To comprehend the pathophysiology of OCD, it is important to understand the stressful life events that precede its onset.