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.

Interval timing and working memory are critical components of cognition that are supported by neural oscillations in prefrontal-striatal-hippocampal circuits. In this review, the properties of interval timing and working memory are explored in terms of behavioral, anatomical, pharmacological, and neurophysiological findings. We then describe the various neurobiological theories that have been developed to explain these cognitive processes - largely independent of each other. Following this, a coupled excitatory - inhibitory oscillation (EIO) model of temporal processing is proposed to address the shared oscillatory properties of interval timing and working memory. Using this integrative approach, we describe a hybrid model explaining how interval timing and working memory can originate from the same oscillatory processes, but differ in terms of which dimension of the neural oscillation is utilized for the extraction of item, temporal order, and duration information. This extension of the striatal beat-frequency (SBF) model of interval timing (Matell and Meck, 2000, 2004) is based on prefrontal-striatal-hippocampal circuit dynamics and has direct relevance to the pathophysiological distortions observed in time perception and working memory in a variety of psychiatric and neurological conditions.