A deficit in cognitive flexibility is acknowledged as a cognitive trait for obsessive-compulsive disorder (OCD). However, no investigations to date have used a cognitive activation paradigm to specify the neural correlates of this deficit in OCD. The objective of this study was to clarify how abnormal brain activities relate to cognitive inflexibility in OCD, using a task-switching paradigm. A task-switching paradigm which has two kinds of task-set was applied to 21 patients with OCD and 21 healthy subjects of matching age, IQ and sex, during an event-related functional magnetic resonance imaging experiment. Compared with the healthy subjects, patients with OCD exhibited a significantly higher error rate in task-switch trials (P < 0.05). Healthy controls showed significant activation in various areas, including dorsal frontal-striatal regions, during task-switching, whereas patients with OCD showed no activation in these areas. Significant differences were also observed in the dorsal frontal-striatal regions and ventromedial prefrontal and right orbitofrontal cortexes between patients with OCD and healthy controls. Correlation analysis indicated that the activations of orbitofrontal cortex were related with the performance in both groups and also with the activation of anterior cingulate cortex in the OCD group. These findings replicate previous studies of cognitive inflexibility in OCD and provide neural correlates related to a task-switching deficit in OCD. The results suggest that impaired task-switching ability in OCD patients might be associated with an imbalance in brain activation between dorsal and ventral frontal-striatal circuits.

Spatial working memory (WM) processing has 3 distinct phases: encoding, maintenance, and retrieval and its dysfunction is a core feature in schizophrenia. We examined phase-specific brain activations associated with spatial WM in first-degree relatives of schizophrenia (genetic high risk, GHR), ultra-high risk (UHR) subjects, patients with schizophrenia, and healthy controls. We used an event-related functional magnetic resonance imaging in 17 GHR subjects, 21 UHR subjects, 15 clinically stable patients with schizophrenia and 16 healthy controls, while subjects were performing a spatial delayed-response task. During the encoding phase, the GHR group showed increased activation in the fronto-parietal regions, whereas the UHR and schizophrenia groups showed significantly less activation in these regions than did the healthy control group. Especially, frontal activation was strongest in GHR subjects, followed by healthy controls, and occurred to a lesser degree in the UHR group, with the least activation occurring in the schizophrenia group. During the maintenance phase, the thalamus showed a differential activation, similar to frontal activation pattern during the encoding phase. During the retrieval phase, no prominent differential activations were found. Increased activations were observed in the superior temporal gyrus during the encoding and maintenance phases in the GHR, UHR, and schizophrenia groups relative to healthy controls. Our findings suggest that functional deficits associated with spatial WM processing emerge in the UHR before the onset of schizophrenia and compensatory neural processes exist in the GHR with genetic liability to schizophrenia.