Orbitofrontal dysfunction in patients with obsessive-compulsive disorder and their unaffected relatives.
ABSTRACT Obsessive-compulsive disorder (OCD) is characterized by repetitive thoughts and behaviors associated with underlying dysregulation of frontostriatal circuitry. Central to neurobiological models of OCD is the orbitofrontal cortex, a neural region that facilitates behavioral flexibility after negative feedback (reversal learning). We identified abnormally reduced activation of several cortical regions, including the lateral orbitofrontal cortex, during reversal learning in OCD patients and their clinically unaffected close relatives, supporting the existence of an underlying previously undiscovered endophenotype for this disorder.
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ABSTRACT: Ample evidence indicates that inhibitory control (IC), a key executive component referring to the ability to suppress cognitive or motor processes, relies on a right-lateralized fronto-basal brain network. However, whether and how IC can be improved with training and the underlying neuroplastic mechanisms remains largely unresolved. We used functional and structural magnetic resonance imaging to measure the effects of 2 weeks of training with a Go/NoGo task specifically designed to improve frontal top-down IC mechanisms. The training-induced behavioral improvements were accompanied by a decrease in neural activity to inhibition trials within the right pars opercularis and triangularis, and in the left pars orbitalis of the inferior frontal gyri. Analyses of changes in brain anatomy induced by the IC training revealed increases in grey matter volume in the right pars orbitalis and modulations of white matter microstructure in the right pars triangularis. The task-specificity of the effects of training was confirmed by an absence of change in neural activity to a control working memory task. Our combined anatomical and functional findings indicate that differential patterns of functional and structural plasticity between and within inferior frontal gyri enhanced the speed of top-down inhibition processes and in turn IC proficiency. The results suggest that training-based interventions might help overcoming the anatomic and functional deficits of inferior frontal gyri manifesting in inhibition-related clinical conditions. More generally, we demonstrate how multimodal neuroimaging investigations of training-induced neuroplasticity enable revealing novel anatomo-functional dissociations within frontal executive brain networks. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.Human Brain Mapping 03/2015; DOI:10.1002/hbm.22789 · 6.92 Impact Factor
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ABSTRACT: Behavioral flexibility is an important aspect of self-regulation and involves effectively learning, unlearning, and relearning associations between actions and outcome. Using a probabilistic reversal learning paradigm (PRL), the neural correlates of flexibility have previously been associated with brain regions implicated in cognitive control, including the anterior cingulate cortex (ACC) and lateral prefrontal cortex, and with the nucleus accumbens (Nacc) implicated in reward. The current study on healthy young males (n = 40) extends this previously published work in 3 ways. First we corroborate the involvement of ACC, VLPFC, and DLPFC at the exact moment of behavioral switches. Second, we report increased activation of the dACC and caudate head with increasing number of perseverating errors preceding a behavioral switch. Third, better performance on the task is associated with increased activation of rACC and VLPFC during switching, suggesting that these regions contribute to individual differences in behavioral flexibility. These findings cannot be extended to individual differences in a self-reported measure of self-regulation. (PsycINFO Database Record (c) 2014 APA, all rights reserved)Journal of Neuroscience Psychology and Economics 01/2014; 7(4):203-218. DOI:10.1037/npe0000026
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ABSTRACT: For over a quarter century, a substantial body of literature investigating neuropsychological test performance in obsessive-compulsive disorder (OCD) has yielded inconsistent results. Thus, it has been continuously challenging to draw conclusions regarding an OCD-specific neuropsychological profile. In this comprehensive review of the neuropsychological literature in OCD, we critically review neuropsychological test performance by domain, as well as potential moderators of neuropsychological functions, proposed endophenotypes, neuropsychological predictors of treatment response, and contemporary controversies in the field. Previous qualitative/systematic reviews of this body of literature have repeatedly noted its inconsistency, concluding that more research is needed. Unfortunately, the accumulation of neuropsychological research is OCD has not yet promoted our ability to draw conclusions about a distinct neuropsychological profile of OCD. Thus, we conclude this review with novel suggestions for future investigations.Journal of Obsessive-Compulsive and Related Disorders 02/2015; 5. DOI:10.1016/j.jocrd.2015.01.002 · 0.81 Impact Factor