Article

Subjective uncertainty and limbic hyperactivation in obsessive-compulsive disorder

Department of Psychiatry, University of Michigan, Ann Arbor, Michigan. .
Human Brain Mapping (Impact Factor: 5.97). 08/2013; 34(8). DOI: 10.1002/hbm.22038
Source: PubMed

ABSTRACT

Obsessive-compulsive disorder (OCD) is often associated with pathological uncertainty regarding whether an action has been performed correctly or whether a bad outcome will occur, leading to compulsive "evidence gathering" behaviors aimed at reducing uncertainty. The current study used event-related functional magnetic resonance imaging to investigate neural functioning in OCD patients and controls as subjective certainty was rated in response to sequential pieces of evidence for a decision. Uncertainty was experimentally manipulated so that some decisions were associated with no "objective" uncertainty (all observed evidence pointed to one correct choice), whereas other decisions contained calculable but varying levels of objective uncertainty based on displayed probabilities. Results indicated that OCD patients differed from controls on decisions that contained no objective uncertainty, such that patients rated themselves as more uncertain. Patients also showed greater activation in a network of brain regions previously associated with internally-focused thought and valuation including ventromedial prefrontal cortex, parahippocampus, middle temporal cortex, as well as amygdala and orbitofrontal cortex/ventral anterior insula. In the patient group, a significantly greater number of positive intersubject correlations were found among several of these brain regions, suggesting that this network is more interconnected in patients. OCD patients did not differ from controls on decisions where task parameters led to uncertainty. These results indicate that OCD is associated with hyperactivation in a network of limbic/paralimbic brain regions when making decisions, which may contribute to the greater subjective experience of doubt that characterizes the disorder. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.

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    • "Other studies have also shown impairments in OCD as a function of uncertainty; using a delayed matching-to-sample task with unrestricted choice verification, poor insight triggered greater checking behaviours in OCD patients, which indexed uncertainty (Jaafari et al, 2011; Rotge et al, 2008). OCD subjects have also shown greater explicit subjective ratings of uncertainty for low but not higher uncertainty evidence in a probabilistic reasoning task (Stern et al, 2013). "
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    ABSTRACT: Objective The compulsive behaviour underlying Obsessive-Compulsive Disorder (OCD) may be related to abnormalities in decision-making. The inability to commit to ultimate decisions, e.g. patients unable to decide whether their hands are sufficiently clean, may reflect failures in accumulating sufficient evidence prior to a decision. Here we investigate the process of evidence accumulation in OCD in perceptual discrimination, hypothesizing enhanced evidence accumulation relative to healthy volunteers. Method Twenty-eight OCD patients and 35 healthy control subjects were tested with a low-level visual perceptual task (random dot motion task), whereby different coherent levels for motion were defined to measure high and low uncertainty, and two response conflict tasks as control tasks (flanker task and probabilistic selection task). Logistic regression analysis across all coherence levels (which accounted for visual detection threshold) and hierarchical drift diffusion modelling (HDDM) were used to characterize response strategies between patients with OCD and healthy controls in the random dot motion task. Results Patients required more evidence under high uncertainty perceptual contexts, as indexed by longer response time and higher decision boundaries. HDDM, which defines a decision when accumulated noisy evidence reaches a decision boundary, further showed slower drift rate towards the decision boundary reflecting poorer quality of evidence entering the decision process in patients under low uncertainty. With monetary incentives emphasizing speed, patients decreased the decision thresholds relative to controls, accumulating less evidence in low uncertainty. These findings were unrelated to visual perceptual deficits and response conflict. Conclusion This study provides evidence for impaired decision-formation processes in OCD, with a differential influence of high and low uncertainty contexts on evidence accumulation (decision threshold) and on the quality of evidence gathered (drift rates). It further emphasizes that OCD patients are sensitive to monetary incentives heightening speed in the speed-accuracy tradeoff, improving evidence accumulation and shifting away from pathological internal monitoring. These findings may have relevance for therapeutic approaches.
    Full-text · Article · Sep 2015 · Journal of Neurology Neurosurgery & Psychiatry
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    • "Furthermore, no difference was observed in response to neutral words, suggesting that this abnormality is specific to emotionally salient stimuli. Consistent with our current finding, prior studies of OCD patients have demonstrated hyperactivity (primarily a failure to deactivate) among DMN brain regions, particularly ventromedial prefrontal cortex (vmPFC) and rACC, in response to cognitive paradigms examining uncertainty (Stern et al, 2013) and response to errors (Fitzgerald et al, 2005Fitzgerald et al, , 2010 Stern et al, 2011). In addition, connectivity analyses in OCD patients have shown reduced positive connectivity within DMN brain regions (Fitzgerald et al, 2010; Jang et al, 2010; Stern et al, 2012) as well as reduced negative connectivity between DMN and the frontoparietal network—a network of brain regions involved in directing attention toward externally focused tasks (Stern et al, 2012). "
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    ABSTRACT: The anterior cingulate cortex is implicated in the neurobiology of obsessive-compulsive disorder (OCD). However, few studies have examined functional and neurochemical abnormalities specifically in the rostral subdivision of the ACC (rACC) in OCD patients. We used functional magnetic resonance imaging (fMRI) during an emotional counting Stroop task and single-voxel J-resolved proton magnetic resonance spectroscopy ((1)H-MRS) in the rACC to examine the function and neurochemistry of the rACC in individuals with OCD and comparison individuals without OCD. Between-group differences in rACC activation and glutamine/glutamate ratio (Gln/Glu), Glu, and Gln levels as well as associations between rACC activation, Gln/Glu, Glu, Gln, behavioral, and clinical measures were examined using linear regression. In a sample of 30 participants with OCD and 29 age- and sex-matched participants without OCD, participants with OCD displayed significantly reduced rACC deactivation compared to those without OCD in response to OCD-specific words versus neutral words on the emotional counting Stroop task. However, Gln/Glu, Glu, and Gln in the rACC did not differ between groups nor was there an association between reduced rACC deactivation and Gln/Glu, Glu, or Gln in the OCD group. Taken together, these findings strengthen the evidence for rACC dysfunction in OCD, but weigh against an underlying association with abnormal rACC glutamatergic neurotransmission.Neuropsychopharmacology accepted article preview online, 09 February 2015. doi:10.1038/npp.2015.36.
    Full-text · Article · Feb 2015 · Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology
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    • "In the repetitive act of washing or checking, the available sensoryperceptual evidence appears insufficient to commit to a solid decision: patients appear unable to decide whether their hands are sufficiently clean or the door is properly locked (Sachdev and Malhi, 2005). Instead, the compulsive behaviour itself appears to reflect the need for continuous 'evidence gathering', possibly to reduce uncertainty (Rotge et al, 2008; Stern et al, 2013). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The compulsive behaviour underlying Obsessive-Compulsive Disorder (OCD) may be related to abnormalities in decision-making. The inability to commit to ultimate decisions, e.g. patients unable to decide whether their hands are sufficiently clean, may reflect failures in accumulating sufficient evidence prior to a decision. Here we investigate the process of evidence accumulation in OCD in perceptual discrimination, hypothesizing enhanced evidence accumulation relative to healthy volunteers. Twenty-eight OCD patients and 35 controls were tested with a low-level visual perceptual task (random-dot-motion task, RDMT) and two response conflict control tasks. Regression analysis across different motion coherence levels and hierarchical drift diffusion modelling (HDDM) were used to characterize response strategies between groups in the RDMT. Patients required more evidence under high uncertainty perceptual contexts, as indexed by longer response time and higher decision boundaries. HDDM, which defines a decision when accumulated noisy evidence reaches a decision boundary, further showed slower drift rate towards the decision boundary reflecting poorer quality of evidence entering the decision process in patients under low uncertainty. With monetary incentives emphasizing speed, patients decreased the decision thresholds relative to controls, accumulating less evidence in low uncertainty. These findings were unrelated to visual perceptual deficits and response conflict. This study provides evidence for impaired decision-formation processes in OCD, with a differential influence of high and low uncertainty contexts on evidence accumulation (decision threshold) and on the quality of evidence gathered (drift rates). It further emphasizes that OCD patients are sensitive to monetary incentives heightening speed in the speed-accuracy tradeoff, improving evidence accumulation.Neuropsychopharmacology accepted article preview online, 26 November 2014. doi:10.1038/npp.2014.303.
    Full-text · Article · Nov 2014 · Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology
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