Functional connectivity between pre-supplementary motor area and inferior parietal lobule associated with impaired motor response inhibition in first-degree relatives of patients with obsessive-compulsive disorder.

Previous studies have suggested that specific fronto-striatal circuits are associated with impaired motor response inhibition in patients with obsessive-compulsive disorder (OCD) and their relatives. However, no study has investigated the underlying resting-state network associated with motor response inhibition in the unaffected first-degree relatives of patients with OCD. We measured motor response inhibition using stop-signal task, and obtained resting-state fMRI in 23 first-degree relatives and 52 healthy control participants. We explored the group differences in the functional network from seed regions-of-interest (ROIs) associated with motor response inhibition abilities. We used the inferior frontal gyrus (IFG) and pre-supplementary motor area (pre-SMA) as seed-ROIs. A significant group difference was observed in functional connectivity between the pre-SMA and inferior parietal lobule. In the relative group, reduced functional connectivity between these areas was associated with a longer stop-signal reaction time. Additionally, relatives showed significantly greater functional connectivity between the IFG and SMA, precentral, and postcentral areas. Our results could provide new insights into the resting-state neural activity of the pre-SMA underlying impaired motor response inhibition of unaffected first-degree relatives. In addition, our results suggested that relatives have an altered connectivity of the sensorimotor region, similar to that of patients with OCD shown in previous literature.

Gyrification of the medial and lateral orbitofrontal cortex in first-degree relatives of patients with obsessive-compulsive disorder.

Gyrification patterns reflect early neurodevelopment and could be highly heritable. While some discrepant results have been reported, the most consistent finding was that patients with obsessive-compulsive disorder showed altered gyrification patterns in the orbitofrontal cortex. Nevertheless, no study has investigated the alterations in gyrification in unaffected first-degree relatives of patients with obsessive-compulsive disorder. We measured local gyrification by the FreeSurfer software in 23 unaffected first-degree relatives of patients with obsessive-compulsive disorder and 52 healthy control participants. We explored differences in the local gyrification index using vertex-wise whole-brain analysis and a region of interest-based approach in the medial and lateral orbitofrontal cortex. There was no significant difference in the local gyrification index between the 2 groups in the vertex-wise whole-brain analysis. Region of interest analyses showed that, compared with healthy controls, first-degree relatives showed significantly reduced local gyrification index in the left medial and lateral orbitofrontal cortex. A negative correlation was observed between the reduced local gyrification index in lateral orbitofrontal cortex and the subclinical anxiety scores of first-degree relatives. Our results showed that first-degree relatives of patients with obsessive-compulsive disorder had an altered local gyrification index in the orbitofrontal cortex. Especially, reduced local gyrification index in lateral orbitofrontal cortex associated with subclinical anxiety symptom could be a potential neurodevelopmental marker for the illness onset.

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.

Decision-making deficits in obsessive-compulsive disorder are associated with abnormality of recency and response consistency parameter in prospect valence learning model.

Background: Patients with obsessive-compulsive disorder (OCD) have deficits in decision-making in the Iowa Gambling Task (IGT). However, no study has investigated the parameters of the prospect valence learning (PVL) model in the IGT for OCD. Aims: This study aimed to investigate deficits in decision-making in OCD using the PVL model and identify whether the parameters of the PVL model were associated with obsessive-compulsive severity. Methods: Forty-seven medication-free patients with OCD were compared with 47 healthy controls (HCs). Decision-making was measured using the total net and block net scores of the IGT. A PVL model with a decay-reinforcement learning rule (PVL-DecayRI) was used to investigate the parameters of the model. Correlation analysis was conducted between each parameter of the PVL-DecayRL and obsessive-compulsive symptoms. Results: The total net score of patients with OCD was significantly lower than that of the HCs. The block net scores of the OCD group did not differ across the five blocks, whereas in the HCs, the fifth block net score was significantly higher than the block net scores of the first and second blocks. The values of the recency and response consistency parameters of the PVL-DecayRI in patients with OCD were significantly lower than those in HCs. The recency parameter positively correlated with the Y-BOCS obsessive score. Meanwhile, there was no correlation between consistency parameter values and symptom severity in OCD. Conclusion: Our detailed analysis of the decision-making deficit in OCD suggests that the most recent outcome has a small influence on the expectancy of prospect valence, as indicated by the lower recency parameter, and is characterized by more impulsive choices, as indicated by the lower consistency parameter.

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.

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.

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.