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The Neural Correlates of Probabilistic Classification Learning in Obsessive-Compulsive Disorder: A Pilot Study.

ABSTRACT: Individuals suffering from obsessive-compulsive disorder (OCD) have been found to show deficits in implicitly learning probabilistic associations between events. Neuroimaging studies have associated these implicit learning deficits in OCD individuals with aberrant activation of the striatal system. Recent behavioral studies have highlighted that probabilistic classification learning (PCL) deficits in OCD individuals only occur in a disorder-specific context, while PCL remains intact in a neutral context. The neural correlates of implicit learning in an OCD-specific context, however, have not yet been investigated. Using functional magnetic resonance imaging during a neutral (prediction of weather) and an OCD-specific variant (prediction of a virus epidemic) of a PCL paradigm, we assessed brain activity associated with implicit learning processes in 10 participants with OCD and 10 matched healthy controls. Regions of interest (ROIs) were the striatum and the medial temporal lobe. ROI analyses revealed a significantly higher activity in the bilateral putamen and the left hippocampus of OCD participants as compared to healthy controls during both PCL tasks. The group differences could partly be subsumed under a group × task interaction effect with OCD participants showing a significantly higher activity than healthy controls in the left putamen and the left hippocampus in the OCD-specific task variant only. These results suggest a compensation of aberrant striatal activity by an augmented engagement of the explicit memory system particularly in a disorder-relevant context in OCD participants.

SUBMITTER: Hansmeier J

PROVIDER: S-EPMC5863501 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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The Neural Correlates of Probabilistic Classification Learning in Obsessive-Compulsive Disorder: A Pilot Study.

Hansmeier Jana J Exner Cornelia C Zetsche Ulrike U Jansen Andreas A

Frontiers in psychiatry 20180228

Individuals suffering from obsessive-compulsive disorder (OCD) have been found to show deficits in implicitly learning probabilistic associations between events. Neuroimaging studies have associated these implicit learning deficits in OCD individuals with aberrant activation of the striatal system. Recent behavioral studies have highlighted that probabilistic classification learning (PCL) deficits in OCD individuals only occur in a disorder-specific context, while PCL remains intact in a neutral ...[more]

PMID: 29599726

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Project description:Background: Many children and adults with Obsessive-Compulsive Disorder (OCD) fail to respond to first-line pharmacological and behavioral treatments. Glutamate dysfunction may contribute to the development of OCD. N-acetylcysteine (NAC), a glutamate modulating drug, has shown to be a promising agent in adults with OCD. Methods: We conducted a double-blind, placebo-controlled clinical trial from July 2012 to January 2017. Children ages 8 to 17 years with OCD were assigned to receive NAC (up to 2700 mg/day) or the matching placebo for a period of 12 weeks. Children were required to be on stable psychiatric treatment (both medication and therapy) but were not required to be treatment-refractory. The primary outcome was OCD symptom severity as measured by the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). We used linear mixed models to analyze the effect of NAC compared to placebo. Results: Due to poor recruitment and eventual expiration of the study medication, enrollment was stopped at 11 children out of a planned sample size of 40. Nonetheless, NAC was associated with significant reduction in CY-BOCS total score compared to placebo (Satterthwaite's test: t (37) = 2.36, p = 0.024) with effects separating from placebo beginning at week 8. Mean CY-BOCS total score decreased in the NAC group from 21.4 ± 4.65 at baseline to 14.4 ± 5.55 at week 12. In the placebo group, mean CY-BOCS total score remained unchanged (21.3 ± 4.65). In the NAC group, 1 out of 5 participants achieved >35% improvement in CY-BOCS total score, while none of the six patients in placebo group reached this improvement level. NAC and placebo were well tolerated. One mild adverse event was reported in each group. Conclusions: Our trial suggests that there may be some initial improvement in OCD symptom severity with NAC treatment. NAC was well tolerated in the study population. Future trials should employ multiple sites and have a larger study population to further confirm any benefits of NAC.

Dataset Information

The Neural Correlates of Probabilistic Classification Learning in Obsessive-Compulsive Disorder: A Pilot Study.

Publications

The Neural Correlates of Probabilistic Classification Learning in Obsessive-Compulsive Disorder: A Pilot Study.

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