Cognitive flexibility in obsessive-compulsive disorder and major depression: Functional neuroimaging studies on reversal learning and task switching

Veltman, D.J. [Promotor]Uylings, H.B.M. [Promotor]Nielen, M.M.A. [Copromotor

Electrophysiological correlates of reinforcement learning in young people with Tourette syndrome with and without co-occurring ADHD symptoms

Altered reinforcement learning is implicated in the causes of Tourette syndrome (TS) and attention-deficit/hyperactivity disorder (ADHD). TS and ADHD frequently co-occur but how this affects reinforcement learning has not been investigated. We examined the ability of young people with TS (n = 18), TS+ADHD (N = 17), ADHD (n = 13) and typically developing controls (n = 20) to learn and reverse stimulus-response (S-R) associations based on positive and negative reinforcement feedback. We used a 2 (TS-yes, TS-no) x 2 (ADHD-yes, ADHD-no) factorial design to assess the effects of TS, ADHD, and their interaction on behavioural (accuracy, RT) and event-related potential (stimulus-locked P3, feedback-locked P2, feedback-related negativity, FRN) indices of learning and reversing the S-R associations. TS was associated with intact learning and reversal performance and largely typical ERP amplitudes. ADHD was associated with lower accuracy during S-R learning and impaired reversal learning (significantly reduced accuracy and a trend for smaller P3 amplitude). The results indicate that co-occurring ADHD symptoms impair reversal learning in TS+ADHD. The implications of these findings for behavioural tic therapies are discussed

Neural correlates of a reversal learning task with an affectively neutral baseline: an event-related fMRI study

Reversal learning may conceptually be dissected into acquiring stimulus-reinforcement associations and subsequently altering behavior by switching to new associations as stimulus-reinforcement contingencies reverse (i.e., affective switching). Previous imaging studies have found regions of the ventrolateral and orbitofrontal cortex (OFC) to be involved in both subprocesses. However, these studies did not contain an affectively neutral baseline, which precluded adequate assessment of main effects of reward, punishment, and affective switching. We aimed to determine the neural substrate of these main effects, and of common and dissociable regions for reward and punishment. Furthermore, we aimed to discriminate between stimulus-punishment association and affective switching, i.e., to assess affective switching proper. To this end, we implemented a reversal learning task with an affectively neutral baseline condition that matched the experimental task in visual complexity and motor demands. Interestingly, we found dorsolateral prefrontal cortex (DLPFC) and anterior PFC to be engaged in affective switching, a finding that has not been reported before to our knowledge. Enhanced responses in these areas may represent their involvement in cognitive set shifting per se unrelated to the affective context in a reversal learning design. In addition, OFC, insular and medial prefrontal cortex regions were involved in affective switching. Left medial and lateral OFC were shown to be common areas for feedback processing, whereas left ventral striatum and left lateral OFC were specifically activated by reward and punishment, respectively. These results extend our understanding of the neural substrate of reversal learning in human

Differential neural correlates underlie cognitive inflexibility in obsessive-compulsive disorder and major depression.

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Switch the itch: A naturalistic follow-up study on the neural correlates of cognitive flexibility in obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is a relatively common psychiatric disorder characterized by intrusive thoughts and behaviors that dominate daily living, like an itch patients cannot ignore. Deficits in executive functioning are common in OCD and are thought to be related to dysfunctional frontal-striatal systems. One of those executive functions is cognitive flexibility, defined as the ability to rapidly switch response strategies following changes in task-relevant information. The temporal stability of cognitive flexibility impairments in OCD has been incompletely investigated since previous studies have suggested both state and trait dependency. In this study, 16 OCD patients performed a functional magnetic resonance imaging version of a task-switching paradigm twice, intervened by a follow-up period of on average 6 months. Results show that functional abnormalities in the dorsal frontal-striatal circuit and anterior cingulate cortex at baseline normalized at follow-up. This change in the recruitment of task-related brain circuits correlated with change in disease severity. These results support the view that the imbalance between the dorsal and ventral frontal-striatal circuits is at least partly state-dependent, and is associated with a reduction in symptom severit

The course of the neural correlates of reversal learning in obsessive-compulsive disorder and major depression: A naturalistic follow-up fMRI study

Objectives Reversal learning (RL) is impaired in obsessive–compulsive disorder (OCD) as well as in major depressive disorder (MDD). It is yet unknown to what extent pathophysiological mechanisms are state-dependent. Methods Neural activation patterns during RL were measured using event-related functional magnetic resonance imaging (fMRI) reversal learning in patients with OCD (N=18) and MDD (N=15). A naturalistic follow-up design enabled investigation of the relationship between changes in clinical state, task performance and task-related neural activation over time. Results During follow-up, disease severity decreased significantly in both groups. Whereas task speed improved trend-significantly, task accuracy was unchanged. Task-related dorsal frontal-striatal activation decreased at follow-up in MDD, but increased in OCD. In both groups, symptom improvement was associated with reward-related changes in neural activation in the putamen and the orbitofrontal cortex. Conclusions In both OCD and MDD, symptom reduction over time was associated with partial normalization of task-related activation patterns in brain regions. Whereas in OCD this normalization was characterized by increased recruitment of previously hypoactive frontal-striatal brain regions (i.e. dorsal frontal-striatal failure), in MDD previously hyperactive brain regions (frontal-striatal inefficiency), were recruited less after recovery. These results show that in both disorders frontal-striatal dysfunction is at least partly state-dependent