Elsevier

Biological Psychiatry

Volume 69, Issue 6, 15 March 2011, Pages 583-591
Biological Psychiatry

Archival Report
Hyperactive Error Responses and Altered Connectivity in Ventromedial and Frontoinsular Cortices in Obsessive-Compulsive Disorder

https://doi.org/10.1016/j.biopsych.2010.09.048Get rights and content

Background

Patients with obsessive-compulsive disorder (OCD) show abnormal functioning in ventral frontal brain regions involved in emotional/motivational processes, including anterior insula/frontal operculum (aI/fO) and ventromedial frontal cortex (VMPFC). While OCD has been associated with an increased neural response to errors, the influence of motivational factors on this effect remains poorly understood.

Methods

To investigate the contribution of motivational factors to error processing in OCD and to examine functional connectivity between regions involved in the error response, functional magnetic resonance imaging data were measured in 39 OCD patients (20 unmedicated, 19 medicated) and 38 control subjects (20 unmedicated, 18 medicated) during an error-eliciting interference task where motivational context was varied using monetary incentives (null, loss, and gain).

Results

Across all errors, OCD patients showed reduced deactivation of VMPFC and greater activation in left aI/FO compared with control subjects. For errors specifically resulting in a loss, patients further hyperactivated VMPFC, as well as right aI/FO. Independent of activity associated with task events, OCD patients showed greater functional connectivity between VMPFC and regions of bilateral aI/FO and right thalamus.

Conclusions

Obsessive-compulsive disorder patients show greater activation in neural regions associated with emotion and valuation when making errors, which could be related to altered intrinsic functional connectivity between brain networks. These results highlight the importance of emotional/motivational responses to mistakes in OCD and point to the need for further study of network interactions in the disorder.

Section snippets

Subjects

Data were analyzed from 39 OCD patients and 38 control subjects. Twenty OCD patients were unmedicated (uOCD) and 19 were medicated (mOCD), primarily with serotonin reuptake inhibitors (SRIs). All met DSM-IV criteria for primary OCD (see Methods and Materials in Supplement 1 for exclusion criteria). The control group included 20 unmedicated healthy control (uHC) subjects without psychiatric diagnoses and 18 medicated patient control subjects (mPC) who were on SRIs for major depression (in

Behavioral

Error rates and reaction times are shown in Results and Table S3 in Supplement 1. Groups did not differ in number of errors or perception of error frequency (p > .1 for all effects), but OCD patients were more flustered by mistakes [F(1,73) = 5.8, p = .02] and marginally more frustrated with their performance [F(1,73) = 3.3, p = .075].

Errors Versus Corrects

Control and OCD groups exhibited similar patterns of activations for errors > corrects, averaged across incentive value, within the FST area (Figure 2A, Table 1;

Discussion

Using a task that varied the monetary consequences of mistakes to examine how motivational factors modulate error-related neural processing, we have shown that OCD patients exhibit greater activity in VMPFC due to a failure to deactivate this DMN region to the same extent as control subjects, both across all error types and specifically for errors associated with loss. Patients also showed more activation in aI/fO and altered functional connectivity between aI/fO and VMPFC, independent of

References (66)

  • N.U. Dosenbach et al.

    A core system for the implementation of task sets

    Neuron

    (2006)
  • M.P. Paulus et al.

    An insular view of anxiety

    Biol Psychiatry

    (2006)
  • D.F. Cechetto et al.

    Functional neuroanatomy of autonomic regulation

    Neuroimage

    (2009)
  • M.L. Kringelbach et al.

    The functional neuroanatomy of the human orbitofrontal cortex: Evidence from neuroimaging and neuropsychology

    Prog Neurobiol

    (2004)
  • M. Lebreton et al.

    An automatic valuation system in the human brain: Evidence from functional neuroimaging

    Neuron

    (2009)
  • T. Endrass et al.

    Performance monitoring and error significance in patients with obsessive-compulsive disorder

    Biol Psychol

    (2010)
  • D.A. Fair et al.

    A method for using blocked and event-related fMRI data to study “resting state” functional connectivity

    Neuroimage

    (2007)
  • R.W. Cox

    AFNI: Software for analysis and visualization of functional magnetic resonance neuroimages

    Comput Biomed Res

    (1996)
  • A. Simmons et al.

    Intolerance of uncertainty correlates with insula activation during affective ambiguity

    Neurosci Lett

    (2008)
  • K.L. Phan et al.

    Functional neuroanatomy of emotion: A meta-analysis of emotion activation studies in PET and fMRI

    Neuroimage

    (2002)
  • K.L. Phan et al.

    Neural correlates of individual ratings of emotional salience: A trial-related fMRI study

    Neuroimage

    (2004)
  • J.R. Andrews-Hanna et al.

    Functional-anatomic fractionation of the brain's default network

    Neuron

    (2010)
  • S.L. Bressler et al.

    Large-scale brain networks in cognition: Emerging methods and principles

    Trends Cogn Sci

    (2010)
  • S.J. Broyd et al.

    Default-mode brain dysfunction in mental disorders: A systematic review

    Neurosci Biobehav Rev

    (2009)
  • S.F. Taylor et al.

    Neural systems for error monitoring: Recent findings and theoretical perspectives

    Neuroscientist

    (2007)
  • J.Y. Rotge et al.

    Provocation of obsessive-compulsive symptoms: A quantitative voxel-based meta-analysis of functional neuroimaging studies

    J Psychiatry Neurosci

    (2008)
  • S. Ursu et al.

    Overactive action monitoring in obsessive-compulsive disorder: Evidence from functional magnetic resonance imaging

    Psychol Sci

    (2003)
  • E.R. Stern et al.

    Chronic medication does not affect hyperactive error responses in obsessive-compulsive disorder

    Psychophysiology

    (2010)
  • W.J. Gehring et al.

    Action-monitoring dysfunction in obsessive-compulsive disorder

    Psychol Sci

    (2000)
  • J. Woolley et al.

    Brain activation in paediatric obsessive compulsive disorder during tasks of inhibitory control

    Br J Psychiatry

    (2008)
  • S.L. Rauch et al.

    Probing striatal function in obsessive-compulsive disorder: A PET study of implicit sequence learning

    J Neuropsychiatry Clin Neurosci

    (1997)
  • D. Sridharan et al.

    A critical role for the right fronto-insular cortex in switching between central-executive and default-mode networks

    Proc Natl Acad Sci U S A

    (2008)
  • W.W. Seeley et al.

    Dissociable intrinsic connectivity networks for salience processing and executive control

    J Neurosci

    (2007)
  • Cited by (107)

    • Cognitive Neuroscience of Obsessive-Compulsive Disorder

      2023, Psychiatric Clinics of North America
      Citation Excerpt :

      In a recent meta-analysis of functional magnetic resonance imaging (fMRI) studies of error processing in adults with OCD, patients showed significantly greater activation of dorsal MFC regions (dACC, SMA, and pre-SMA), right aI/fO, and anterior lateral prefrontal cortex in response to errors compared with HCs.14 Although not found in the meta-analytic results, two earlier studies found greater activation (or reduced deactivation) of the ventromedial prefrontal cortex (vmPFC) in response to errors in OCD children15 and adults16 compared with control subjects. The vmPFC is a key area of the default mode network (DMN) that typically deactivates during externally focused cognitive tasks,17,18 including the detection of errors,16 but activates more (or deactivates less) during tasks of internally focused cognition such as event imagination, episodic memory, and self-processing.17,19

    • Error-related activity of the sensorimotor network contributes to the prediction of response to cognitive-behavioral therapy in obsessive–compulsive disorder

      2022, NeuroImage: Clinical
      Citation Excerpt :

      Although the flanker task successfully activated the cingulo-opercular salience network in OCD patients and healthy control participants, the group differences for the postcentral gyrus and precuneus are located outside these regions. In line with this, some previous studies have shown that error monitoring alterations in OCD might not only be characterized by an increased activity of the cingulo-opercular network, but also by broader activation within this network and the recruitment of additional brain regions (Fitzgerald et al., 2010; Grutzmann et al., 2016; Grützmann et al., 2021; Stern et al., 2011). In a combined EEG-FMRI study we observed that the increased ERN amplitude in OCD was related to an altered generator configuration: while the MCC contributed to ERN amplitude in both groups, an additional generator within the SMA was selectively present in the patient group (Grutzmann et al., 2016).

    View all citing articles on Scopus
    View full text