Reduced orbitofrontal-striatal activity on a reversal learning task in obsessive-compulsive disorder

CONTEXT: The orbitofrontal cortex (OFC)-striatal circuit, which is important for motivational behavior, is assumed to be involved in the pathophysiology of obsessive-compulsive disorder (OCD) according to current neurobiological models of this disorder. However, the engagement of this neural loop in OCD has not been tested directly in a cognitive activation imaging paradigm so far. OBJECTIVE: To determine whether the OFC and the ventral striatum show abnormal neural activity in OCD during cognitive challenge. DESIGN: A reversal learning task was employed in 20 patients with OCD who were not receiving medication and 27 healthy controls during an event-related functional magnetic resonance imaging experiment using a scanning sequence sensitive to OFC signal. This design allowed investigation of the neural correlates of reward and punishment receipt as well as of "affective switching," ie, altering behavior on reversing reinforcement contingencies. RESULTS: Patients with OCD exhibited an impaired task end result reflected by a reduced number of correct responses relative to control subjects but showed adequate behavior on receipt of punishment and with regard to affective switching. On reward outcome, patients showed decreased responsiveness in right medial and lateral OFC as well as in the right caudate nucleus (border zone ventral striatum) when compared with controls. During affective switching, patients recruited the left posterior OFC, bilateral insular cortex, bilateral dorsolateral, and bilateral anterior prefrontal cortex to a lesser extent than control subjects. No areas were found for which patients exhibited increased activity relative to controls, and no differential activations were observed for punishment in a direct group comparison. CONCLUSIONS: These data show behavioral impairments accompanied by aberrant OFC-striatal and dorsal prefrontal activity in OCD on a reversal learning task that addresses this circuit's function. These findings not only confirm previous reports of dorsal prefrontal dysfunction in OCD but also provide evidence for the involvement of the OFC-striatal loop in the pathophysiology of OC

Reduced orbitofrontal-striatal activity on a reversal learning task in obsessive-compulsive disorder

CONTEXT: The orbitofrontal cortex (OFC)-striatal circuit, which is important for motivational behavior, is assumed to be involved in the pathophysiology of obsessive-compulsive disorder (OCD) according to current neurobiological models of this disorder. However, the engagement of this neural loop in OCD has not been tested directly in a cognitive activation imaging paradigm so far. OBJECTIVE: To determine whether the OFC and the ventral striatum show abnormal neural activity in OCD during cognitive challenge. DESIGN: A reversal learning task was employed in 20 patients with OCD who were not receiving medication and 27 healthy controls during an event-related functional magnetic resonance imaging experiment using a scanning sequence sensitive to OFC signal. This design allowed investigation of the neural correlates of reward and punishment receipt as well as of "affective switching," ie, altering behavior on reversing reinforcement contingencies. RESULTS: Patients with OCD exhibited an impaired task end result reflected by a reduced number of correct responses relative to control subjects but showed adequate behavior on receipt of punishment and with regard to affective switching. On reward outcome, patients showed decreased responsiveness in right medial and lateral OFC as well as in the right caudate nucleus (border zone ventral striatum) when compared with controls. During affective switching, patients recruited the left posterior OFC, bilateral insular cortex, bilateral dorsolateral, and bilateral anterior prefrontal cortex to a lesser extent than control subjects. No areas were found for which patients exhibited increased activity relative to controls, and no differential activations were observed for punishment in a direct group comparison. CONCLUSIONS: These data show behavioral impairments accompanied by aberrant OFC-striatal and dorsal prefrontal activity in OCD on a reversal learning task that addresses this circuit's function. These findings not only confirm previous reports of dorsal prefrontal dysfunction in OCD but also provide evidence for the involvement of the OFC-striatal loop in the pathophysiology of OC

Cognitive inflexibility in obsessive-compulsive disorder and major depression is associated with distinct neural correlates

Contains fulltext : 118166.pdf (publisher's version ) (Open Access)Obsessive-compulsive disorder (OCD) and major depressive disorder (MDD) are frequently co-morbid, and dysfunctional frontal-striatal circuits have been implicated in both disorders. Neurobiological distinctions between OCD and MDD are insufficiently clear, and comparative neuroimaging studies are extremely scarce. OCD and MDD may be characterized by cognitive rigidity at the phenotype level, and frontal-striatal brain circuits constitute the neural substrate of intact cognitive flexibility. In the present study, 18 non-medicated MDD-free patients with OCD, 19 non-medicated OCD-free patients with MDD, and 29 matched healthy controls underwent functional magnetic resonance imaging during performance of a self-paced letter/digit task switching paradigm. Results showed that both patient groups responded slower relative to controls during repeat events, but only in OCD patients slowing was associated with decreased error rates. During switching, patients with OCD showed increased activation of the putamen, anterior cingulate and insula, whereas MDD patients recruited inferior parietal cortex and precuneus to a lesser extent. Patients with OCD and MDD commonly failed to reveal anterior prefrontal cortex activation during switching. This study shows subtle behavioral abnormalities on a measure of cognitive flexibility in MDD and OCD, associated with differential frontal-striatal brain dysfunction in both disorders. These findings may add to the development of biological markers that more precisely characterize frequently co-morbid neuropsychiatric disorders such as OCD and MDD

Demographic and clinical data for patients with obsessive-compulsive disorder (OCD), patients with major depressive disorder (MDD), and healthy controls.

<p># chi-square ‡ One-way ANOVA * Tukey and Scheffe post-hoc tests.</p

Behavioral data on the task switching paradigm for patients with obsessive-compulsive disorder (OCD), patients with major depressive disorder (MDD), and healthy controls.

<p>Behavioral data on the task switching paradigm for patients with obsessive-compulsive disorder (OCD), patients with major depressive disorder (MDD), and healthy controls.</p

The letter/digit task switching paradigm.

<p>In this example (consecutive trials are running from top-left to bottom-right) the events-of-interest are displayed. Subjects are presented two stimuli on each trial, i.e. a letter and a digit, for 4000 ms maximally. Subjects select either stimulus by pressing the left or right button on a button box, after which a fixation cross is presented for 500 ms. Each letter/digit pair is presented in either blue or red color. The trial color cues the task to be performed. In the letter task, subjects indicate whether the letter presented is a vowel or a consonant. In the digit task, subjects indicate whether the digit presented is odd or even. Two consecutive trials never contain the same letter or digit. Trial color changes, and therefore task switching, occurs randomly after 4–6 trials to avoid predictability. The first trials immediately after task switching are defined ‘switch events’ (SEs), all other trials as ‘repeat events’ (REs). Color-task and stimulus-response associations were counterbalanced across participants.</p

Group x task interaction effects on the task switching paradigm for the group of patients with obsessive-compulsive disorder (OCD), patients with major depressive disorder (MDD), and healthy controls. All activations at p<.001 uncorrected.

<p>Group x task interaction effects on the task switching paradigm for the group of patients with obsessive-compulsive disorder (OCD), patients with major depressive disorder (MDD), and healthy controls. All activations at p<.001 uncorrected.</p

Group by condition (SE vs. RE) differences.

<p>(A) enhanced BOLD response in left anterior PFC (controls vs. OCD), (B) in dorsal ACC (OCD vs. controls), (C) in right inferior parietal cortex (controls vs. MDD) and (D) in left insula (OCD vs. MDD).</p