New research
Reduced Error-Related Activation of Dorsolateral Prefrontal Cortex Across Pediatric Anxiety Disorders

https://doi.org/10.1016/j.jaac.2013.09.002Get rights and content

Objective

Abnormalities of cognitive control functions, such as conflict and error monitoring, have been theorized to underlie obsessive-compulsive symptoms but only recently have been considered a potentially relevant psychological construct for understanding other forms of anxiety. The authors sought to determine whether these cognitive control processes elicit the same abnormalities of brain function in patients with pediatric obsessive-compulsive disorder (OCD) as in those with non-OCD anxiety disorders.

Method

Functional magnetic resonance imaging of the Multisource Interference Task was used to measure conflict- and error-related activations in youth (8–18 years) with OCD (n = 21) and non-OCD anxiety disorders (generalized anxiety disorder, social phobia, separation anxiety disorder; n = 23) compared with age-matched healthy controls (n = 25).

Results

There were no differences in performance (accuracy, response times) among groups. However, a significant effect of group was observed in the dorsolateral prefrontal cortex (dlPFC) during error processing, driven by decreased activation in patients with OCD and those with non-OCD anxiety compared with healthy youth. Between patient groups, there was no difference in error-related dlPFC activation.

Conclusions

Hypoactive dlPFC response to errors occurs in pediatric patients with OCD and those with non-OCD anxiety. These findings suggest that insufficient error-related engagement of the dlPFC associates with anxiety across traditional diagnostic boundaries and appears during the early stages of illness.

Section snippets

Participants

Subjects were female, ranged in age from 8 to 19 years, and included 21 patients with OCD, 23 patients with non-OCD anxiety disorders, and 25 healthy youth. Anxiety disorders occur more commonly in female than in male youth, suggesting an influence of gender, and leading the authors to include female subjects only. There was no significant difference in age among groups (Table 1). All subjects underwent a structured clinical interview using the Schedule for Affective Disorders and

Behavioral

Subjects were less accurate on incongruent than on congruent trials (Table 2), with a significant effect of condition (F1,65 = 4, p < .05), but no significant effect of group (F2,65 = 0.1, p = .92) or group-by-condition interaction (F2,65 = 0.9, p = .40). For response latencies, there was a significant effect of condition, with slower latencies for incongruent than for congruent trials (F1,65 = 68, p < .05), but no significant effect of group (F2,65 = 2.5, p = .09) or group-by-condition

Discussion

Abnormalities of cognitive control functions, such as conflict and error monitoring, have been theorized to underlie obsessive-compulsive symptoms17 but only recently have been considered potentially relevant for understanding other forms of anxiety.24 To test whether brain-based alterations of these functions mark early illness in OCD and non-OCD anxiety disorders, fMRI was performed during MSIT in pediatric patients with these 2 forms of anxiety. Compared with healthy youth, pediatric

References (48)

  • D.M. Olvet et al.

    The error-related negativity (ERN) and psychopathology: toward an endophenotype

    Clin Psychol Rev

    (2008)
  • K.D. Fitzgerald et al.

    The development of performance-monitoring function in the posterior medial frontal cortex

    Neuroimage

    (2010)
  • J. Kaufman et al.

    Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data

    J Am Acad Child Adolesc Psychiatry

    (1997)
  • L. Scahill et al.

    Children’s Yale-Brown Obsessive Compulsive Scale: reliability and validity

    J Am Acad Child Adolesc Psychiatry

    (1997)
  • J.S. March et al.

    The Multidimensional Anxiety Scale for Children (MASC): factor structure, reliability, and validity

    J Am Acad Child Adolesc Psychiatry

    (1997)
  • D. Geller et al.

    Is juvenile obsessive-compulsive disorder a developmental subtype of the disorder? A review of the pediatric literature

    J Am Acad Child Adolesc Psychiatry

    (1998)
  • G.K. Aguirre et al.

    Empirical analyses of BOLD fMRI statistics. II. Spatially smoothed data collected under null-hypothesis and experimental conditions

    Neuroimage

    (1997)
  • M. Jenkinson et al.

    Improved optimization for the robust and accurate linear registration and motion correction of brain images

    Neuroimage

    (2002)
  • E. Kang et al.

    Age-associated changes of cerebral glucose metabolic activity in both male and female deaf children: parametric analysis using objective volume of interest and voxel-based mapping

    Neuroimage

    (2004)
  • K.J. Worsley et al.

    Characterizing the response of PET and fMRI data using multivariate linear models

    Neuroimage

    (1997)
  • K.D. Fitzgerald et al.

    Error-related hyperactivity of the anterior cingulate cortex in obsessive compulsive disorder

    Biol Psychiatry

    (2005)
  • E.R. Stern et al.

    Hyperactive error responses and altered connectivity in ventromedial and frontoinsular cortices in obsessive-compulsive disorder

    Biol Psychiatry

    (2011)
  • R.C. Kessler et al.

    The role of latent internalizing and externalizing predispositions in accounting for the development of comorbidity among common mental disorders

    Curr Opin Psychiatry

    (2011)
  • S. Ursu et al.

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

    Psychol Sci

    (2003)
  • Cited by (45)

    • Risk Factors for Pediatric Anxiety Disorders

      2023, Child and Adolescent Psychiatric Clinics of North America
    • Cross-sectional and Longitudinal Associations of Anxiety and Irritability With Adolescents’ Neural Responses to Cognitive Conflict

      2023, Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
      Citation Excerpt :

      Anxiety has been linked to larger error-related negativity (43) reflecting activation in the anterior cingulate cortex and medial PFC (44,45). Furthermore, associations between anxiety and reduced BOLD response to error have been found in the dorsolateral PFC (46). Contrary to these prior findings, we found no significant associations between anxiety and neural response to error.

    • Inhibitory control in obsessive compulsive disorder: A systematic review and activation likelihood estimation meta-analysis of functional magnetic resonance imaging studies

      2022, NeuroImage: Clinical
      Citation Excerpt :

      We included 21 articles (Britton et al., 2010; de Wit et al., 2012; Fitzgerald et al., 2010; Fitzgerald et al., 2005; Gu et al., 2008; Han et al., 2011; Huyser et al., 2011; Kang et al., 2013; Marsh et al., 2014; Morein-Zamir et al., 2016; Nabeyama et al., 2008; Nakao et al., 2009; Nakao et al., 2005; Page et al., 2009; Remijnse et al., 2013; Roth et al., 2007; Schlösser et al., 2010; Theiss et al., 2019; Thorsen et al., 2020; van den Heuvel et al., 2005; Yücel et al., 2007) that compared activation related to inhibitory control in 394 OCD patients and 410 HC subjects in 35 experiments in the review (Table 1). Thirty-four articles were excluded based on our pre-defined criteria, of which 9 articles were excluded solely because they did not find significant case-control differences for the appropriate task contrast (Fitzgerald et al., 2018; Fitzgerald et al., 2013; Gooskens et al., 2019; Hollestein et al., 2021; Hough et al., 2016; Pagliaccio et al., 2019; Stern et al., 2011; Suñol et al., 2020; Viard et al., 2005). Furthermore, one article (Tolin et al., 2014) was excluded post-hoc because the OCD and HC groups differed substantially in their respective mean ages (33.5 years and 51.3 years) and gender distributions (25 % females and 83 % females).

    View all citing articles on Scopus

    This work was funded by National Institute of Mental Health grants K23MH082176 (K.D.F.), 1R01MH086517-01A2 (K.L.P., C.S.M.), R01 MH071821 (S.F.T.), and F32 MH082573 (E.R.S.); the National Alliance for Research on Schizophrenia and Depression Young Investigator Awards (K.D.F., E.R.S.); and the Dana Foundation (K.D.F.).

    The authors thank Georgia Stamatopoulos, M.S.W., Joanna Ingebritsen, B.A., and Keith Newhham of the University of Michigan for assistance with data collection.

    Disclosure: Dr. Taylor has received financial support for unrelated research from St. Jude Medical and Neuronetics. Drs. Fitzgerald, Liu, Stern, Welsh, Hanna, Monk, and Phan report no biomedical financial interests or potential conflicts of interest.

    View full text