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Cited by 165Obsessive-Compulsive Spectrum DisordersNeural and Behavioral Psychology StudiesNeurological disorders and treatments

Developmental alterations of frontal-striatal-thalamic connectivity in obsessive-compulsive disorder

Open access
Fitzgerald, Kate Dimond, Welsh, Robert C., Stern, Emily R., Angstadt, Mike, Hanna, Gregory L., Abelson, James L., Taylor, Stephan F.·2011·Journal of the American Academy of Child & Adolescent Psychiatry
DOI 10.1016/j.jaac.2011.06.011PMC PMC3167379
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Abstract

Objective Pediatric obsessive-compulsive disorder is characterized by abnormalities of frontal-striatal-thalamic circuitry that appear near illness onset and persist over its course. Distinct frontal-striatal-thalamic loops through cortical centers for cognitive control (anterior cingulate cortex) and emotion processing (ventral medial frontal cortex) follow unique maturational trajectories, and altered connectivity within distinct loops may be differentially associated with OCD at specific stages of development.Method Altered development of striatal and thalamic connectivity to medial frontal cortex was tested in 60 OCD patients compared with 61 healthy control subjects at child, adolescent, and adult stages of development, using resting-state functional connectivity MRI.Results OCD in the youngest patients was associated with reduced connectivity of dorsal striatum and medial dorsal thalamus to rostral and dorsal anterior cingulate cortex, respectively. Increased connectivity of dorsal striatum to ventral medial frontal cortex was observed in patients at all developmental stages. In child patients, reduced connectivity between dorsal striatum and rostral anterior cingulate cortex correlated with OCD severity.Conclusions Frontal-striatal-thalamic loops involved in cognitive control are hypoconnected in young patients near illness onset, whereas loops implicated in emotion processing are hyperconnected throughout the illness.

AI snapshot

Written from the paper’s full text.

TL;DR

This cross-sectional resting-state fMRI study compared frontal-striatal-thalamic connectivity in 60 OCD patients and 61 healthy controls from childhood through adulthood. It reports that subcortical–anterior cingulate connectivity is lower in the youngest patients, while dorsal striatum–ventromedial frontal connectivity is higher across development.

Key findings

  • In child OCD patients, connectivity was reduced between left dorsal striatum and rostral anterior cingulate cortex, and between medial dorsal thalamus and dorsal anterior cingulate cortex; these group-by-age effects were driven by the youngest group.
  • Dorsal striatum connectivity to the medial frontal pole/ventral medial frontal cortex was greater in OCD patients than controls across child, adolescent, and adult stages.
  • Among child patients, lower left dorsal striatum–rostral anterior cingulate connectivity was associated with greater OCD severity (r = .66, p = .03).
  • No main group or group-by-age effects emerged for ventral striatal seeds; post-hoc analyses generally retained the main findings after excluding subclinical or medicated patients, with some changes.

Methods

  • Cross-sectional resting-state functional connectivity MRI in 60 OCD outpatients and 61 healthy controls, ages 8–50, grouped as children (8–12), adolescents (13–17), younger adults (18–25), and older adults (26–40); these were the remaining participants after exclusions from 67 OCD and 68 control subjects.
  • Seed regions were ventral striatum, dorsal striatum, and medial dorsal thalamus; low-frequency BOLD time series were correlated with medial frontal cortex, and group and group × age effects were tested with factorial ANOVAs using FDR and AlphaSim correction.
  • OCD severity was assessed with child or adult Yale-Brown Obsessive Compulsive Scale versions, and post-hoc tests examined medication and subclinical symptom effects.

Limitations

  • The authors state that functional interpretations are extrapolated from the imaging literature, that resting-state connectivity’s relationship to underlying structure is unknown, and that structural frontal-striatal-thalamic abnormalities could have contributed; they also note possible normalization inaccuracy from warping younger subjects to an adult template, caution about medial frontal pole localization due to orbitofrontal signal dropout, small child sample size, adolescent group differences in symptom severity and medication use, and the cross-sectional design.
  • Evident from the text: the design cannot establish developmental trajectories or causality; adult patients were relatively young compared with prior studies, possibly limiting power to detect ventral striatum–ventromedial frontal hyperconnectivity; comorbid tic, anxiety, and depressive disorders were allowed, and adolescent patients had higher medication use and lower symptom severity.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.jaac.2011.06.011

Cites

34 of 34 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 48 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    A group by age interaction was found for left medial dorsal thalamus connectivity with left dorsal anterior cingulate cortex, driven by reduced connectivity in child patients and increased connectivity in adolescent patients compared with healthy controls.

    “For the left medial dorsal thalamus, a group × age interaction was observed on connectivity with left dorsal ACC (Figure 3b, Table 2), driven by reduced connectivity in child patients and increased connectivity in adolescent patients compared to healthy controls.”
    Quote in the paperSubstantial claim
  • Findingcitation

    The present study also observed a decrease in subcortical connectivity with anterior cingulate cortex from childhood into adolescence in healthy youth.

    “– a pattern that we also observed”
    Quote in the paperSubstantial claim
  • Findingown data

    There were no other significant associations between symptom severity and connectivity measures for any age group or for all obsessive-compulsive disorder patients collapsed across age groups.

    “There were no other significant associations between symptom severity and connectivity measures for any age group, or for all OCD patients collapsed across age groups.”
    Quote in the paperNot a substantial claim
  • Findingcitation

    Functional connectivity patterns for subcortical seed regions showed topographic distinctions in both obsessive-compulsive disorder and healthy groups.

    “Functional connectivity patterns for subcortical seed regions showed topographic distinctions as seen in previous work5,23 in both OCD and healthy groups (Figure 1).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [5] Harrison, 2009, Altered corticostriatal functional connectivity in obsessive-compulsive disorder, Arch Gen Psychiatry source

      Not checked in the free run.

    • cites [23] Welsh, 2010, Low-frequency BOLD fluctuations demonstrate altered thalamocortical connectivity in schizophrenia, Schizophr Bull source

      Not checked in the free run.

  • Findingown data

    A significant group by age interaction was found for right medial dorsal thalamus connectivity with bilateral dorsal anterior cingulate cortex, driven by reduced connectivity in the youngest patients.

    “For the right medial dorsal thalamus, a significant group × age interaction was observed on connectivity with the bilateral dorsal ACC, again driven by reduced connectivity in the youngest patients (Figure 3a, Table 2).”
    Quote in the paperSubstantial claim
  • May combine two claims. 23
  • Classified as probably not a substantial claim. 19

  • May combine two claims.

    Findingown data

    There were no main effects of group or group by age interactions for connectivity with left or right ventral striatal seeds.

    “There were no main effects of group or group × age interactions for connectivity with left or right ventral striatal seeds.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    After excluding medicated patients, increased left dorsal striatum connectivity with rostral anterior cingulate cortex became a trend-level group by age interaction, with reduced connectivity in child patients.

    “In addition, while the primary analysis showed increased left dorsal striatum connectivity with the rostral ACC (6, 39, 4) in patients across all age groups, the exclusion of medicated patients revealed a trend-level group × age interaction (F = 2.5, p = .06) instead, and in the same pattern as the group × age interaction for the left DS connectivity to the neighboring rostral ACC cluster (−6, 51,”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There were no other group effects and no group by age interactions driven by increased connectivity in obsessive-compulsive disorder.

    “There were no other effects of group, and no group × age interactions driven by increased connectivity in OCD.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    A sub-threshold increase of ventral striatum connectivity with ventral medial frontal cortex was observed in obsessive-compulsive disorder compared with healthy controls, and in post-hoc testing it appeared driven by adult patients.

    “We observed a sub-threshold increase of ventral striatum connectivity with vMFC (x = 9, y = 69, z = 9; Z = 3.47, k =9) in OCD compared to healthy control subjects that, in post-hoc testing, appeared to be driven by adult patients”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    A significant increase in dorsal striatum connectivity with medial frontal pole was observed across child, adolescent and adult stages in patients compared with controls, partially replicating prior work showing excessive ventral caudate connectivity with ventral medial frontal cortex in adults.

    “A significant increase in dorsal striatum connectivity with medial frontal pole was observed across child, adolescent and adult stages of development in patients compared to controls, partially replicating prior work showing excessive ventral (rather than dorsal) caudate connectivity with vMFC in adults with OCD5,33.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [5] Harrison, 2009, Altered corticostriatal functional connectivity in obsessive-compulsive disorder, Arch Gen Psychiatry source

      Not checked in the free run.

    • cites [33] Sakai Y, Narumoto J, Nishida S, et al. Corticostriatal functional connectivity in non-medicated patients with obsessive-compulsive disorder [published online ahead of print November 8, 2010]. Eur Psychiatry. doi:10.1016/j.eurpsy.2010.09.005. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Earlier development of emotion-processing areas such as ventral medial frontal cortex may interact with more gradual development of cognitive control centers such as anterior cingulate cortex to support age-related improvements in behavioral flexibility.

    “Earlier development of emotion-processing areas (e.g., vMFC) within this circuitry may interact with more gradual, protracted development of cognitive control centers (e.g., ACC) to support age-related improvements in behavioral flexibility10.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [10] Somerville, 2011, Frontostriatal maturation predicts cognitive control failure to appetitive cues in adolescents, J Cogn Neurosci source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In obsessive-compulsive disorder, enlarged volume and hyperactive function of the anterior cingulate cortex associate with cognitive control deficits, while ventral medial frontal cortex alterations, especially orbitofrontal hyperactivity, link to excessive valuation of action consequences.

    “In OCD, enlarged volume and hyperactive function of the ACC associate with deficits of cognitive control2,3,9, while vMFC alterations – especially hyperactivity in the orbitofrontal cortex – has been linked to excessive valuation of consequences from actions3.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [2] Rosenberg, 1998, A.E. Bennett Research Award, Biol Psychiatry source

      Not checked in the free run.

    • cites [3] Menzies, 2008, Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: the orbitofronto-striatal model revisited, Neurosci Biobehav Rev source

      Not checked in the free run.

    • cites [9] Fitzgerald, 2010, Altered function and connectivity of the medial frontal cortex in pediatric obsessive-compulsive disorder, Biol Psychiatry source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The frontal-striatal-thalamic circuitry consists of parallel, segregated loops connecting distinct cortical, striatal and thalamic regions.

    “The FSTC system is comprised of parallel, segregated “loops” between distinct portions of the cortex, striatum and thalamus6.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [6] Alexander, 1986, Parallel organization of functionally segregated circuits linking basal ganglia and cortex, Annu Rev Neurosci source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In adult obsessive-compulsive disorder, positron emission tomography studies show resting hyperactivity in the caudate, medial dorsal thalamus and medial frontal cortex that increases with symptom provocation.

    “In adult OCD, positron emission tomography studies show hyperactivity in the caudate, medial dorsal thalamus and medial frontal cortex (MFC) occurs at rest and increases with symptom provocation”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [3] Menzies, 2008, Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: the orbitofronto-striatal model revisited, Neurosci Biobehav Rev source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A recent resting-state functional connectivity MRI study found increased connectivity of ventral caudate to medial frontal cortex in adult obsessive-compulsive disorder patients.

    “A recent resting state functional connectivity study using magnetic resonance imaging found increased connectivity of ventral caudate to MFC in adult patients”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [5] Harrison, 2009, Altered corticostriatal functional connectivity in obsessive-compulsive disorder, Arch Gen Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    The frontal-striatal-thalamic circuitry develops dramatically in typically developing youth, with somewhat different trajectories across loops.

    “Dramatic development of FSTC occurs in typically developing youth, with somewhat different trajectories in different loops.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Altered neurodevelopment may contribute to the frontal-striatal-thalamic circuitry abnormalities associated with obsessive-compulsive disorder.

    “leading investigators to suggest that altered neurodevelopment1,2 may contribute to the frontal-striatal-thalamic circuitry (FSTC) abnormalities associated with illness3.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [1] Evans, 2004, The role of the orbitofrontal cortex in normally developing compulsive-like behaviors and obsessive-compulsive disorder, Brain Cogn source

      Not checked in the free run.

    • cites [2] Rosenberg, 1998, A.E. Bennett Research Award, Biol Psychiatry source

      Not checked in the free run.

    • cites [3] Menzies, 2008, Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: the orbitofronto-striatal model revisited, Neurosci Biobehav Rev source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Frontal-striatal-thalamic circuitry maturation supports engagement of cognitive control in response to potential rewards and processing of errors to improve performance on cognitive tasks.

    “FSTC maturation supports the engagement of cognitive control in response to potential rewards10 and the processing of errors to improve performance on cognitive tasks11.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [10] Somerville, 2011, Frontostriatal maturation predicts cognitive control failure to appetitive cues in adolescents, J Cogn Neurosci source

      Not checked in the free run.

    • cites [11] Rubia, 2006, Progressive increase of frontostriatal brain activation from childhood to adulthood during event-related tasks of cognitive control, Hum Brain Mapp source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Earlier onset obsessive-compulsive disorder may define a unique subtype associated with higher rates of comorbid tic disorders, male predominance, increased familiality, and particular genetic polymorphisms.

    “Earlier onset illness may define a unique subtype of OCD associated with higher rates of comorbid tic disorders, male predominance, increased familiality, and particular genetic polymorphisms29.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [29] Dickel, 2006, Association testing of the positional and functional candidate gene SLC1A1/EAAC1 in early-onset obsessive-compulsive disorder, Arch Gen Psychiatry source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    There were no significant age or gender differences between diagnostic groups within any developmental subgroup.

    “There were no significant differences in age or gender for any subgroup.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Resting-state functional connectivity MRI measures correlations of low-frequency blood oxygen level-dependent signal fluctuations between brain regions and is thought to reflect functional connections that evolve over development.

    “This technique measures correlations of low-frequency blood oxygen level-dependent signal fluctuations between brain regions, and is thought to reflect functional connections that evolve over the course of development12,13.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [12] Supekar, 2009, Development of large-scale functional brain networks in children, PLoS Biol source

      Not checked in the free run.

    • cites [13] Fair, 2007, Development of distinct control networks through segregation and integration, Proc Natl Acad Sci U S A source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Development of anterior cingulate cortex cognitive control function depends not only on maturation of its connections within frontal-striatal-thalamic circuitry but also on its role within other brain networks such as the cingulopercular network.

    “However, the development of ACC cognitive control function depends not only on the maturation of its connections within FSTC, but also on its role within other brain networks (e.g., cingulopercular network for task control13) implicated in both pediatric9 and adult28 OCD.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [13] Fair, 2007, Development of distinct control networks through segregation and integration, Proc Natl Acad Sci U S A source

      Not checked in the free run.

    • cites [9] Fitzgerald, 2010, Altered function and connectivity of the medial frontal cortex in pediatric obsessive-compulsive disorder, Biol Psychiatry source

      Not checked in the free run.

    • cites [28] Stern, 2011, Hyperactive error responses and altered connectivity in ventromedial and frontoinsular cortices in obsessive-compulsive disorder, Biol Psychiatry source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    The imaging analysis initially used an uncorrected threshold of p = 0.005, then tested medial frontal cortex clusters at p < 0.05 with false-discovery-rate correction within seed-specific search volumes, using AlphaSim to determine cluster-size thresholds.

    “results were initially evaluated at a threshold of p = 0.005, uncorrected. MFC clusters showing group or group × age effects were tested for significance at p < 0.05, correcting for false discovery rate (FDR)24 within seed-specific MFC search volumes”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [24] Genovese, 2002, Thresholding of statistical maps in functional neuroimaging using the false discovery rate, Neuroimage source

      Not checked in the free run.

    • cites [25] Ward

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    Primary findings generally survived post-hoc testing that excluded obsessive-compulsive disorder patients with subclinical symptoms or medication, including the right dorsal striatum-ventral medial frontal cortex hyperconnectivity group effect and the group by age interactions for left dorsal striatum-rostral anterior cingulate cortex and right medial dorsal thalamus-dorsal anterior cingulate cort

    “In general, findings from the primary analysis survived post-hoc testing, including 1) the group effect for right dorsal striatum – ventral MFC hyperconnectivity in patients across all age groups, and 2) the group × age interactions for left dorsal striatum – rostral ACC and right medial dorsal thalamus – dorsal ACC connectivity showing reduced connectivity in child patients.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Recent work showed increased ventral striatum connectivity to anterior cingulate cortex in adult obsessive-compulsive disorder patients.

    “Our finding of reduced connectivity of dorsal striatum with rostral ACC and medial dorsal thalamus with dorsal ACC in children with OCD stands in partial contrast to recent work showing increased ventral striatum connectivity to the ACC in adult patients5.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [5] Harrison, 2009, Altered corticostriatal functional connectivity in obsessive-compulsive disorder, Arch Gen Psychiatry source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    From the original sample, 14 subjects were excluded because of technical image-collection difficulties or excessive movement, leaving 60 obsessive-compulsive disorder patients and 61 healthy controls.

    “Of the original sample, 14 patients were excluded: 2 adults due to technical difficulties with image collection (1 OCD, 1 healthy) and 12 youth due to excessive movement (6 OCD, 6 healthy). The remaining 60 patients and 61 healthy control subjects were categorized”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    If decreased subcortical-medial frontal cortex connectivity specifically characterizes children with obsessive-compulsive disorder, prior work limited to adult samples could not have detected it.

    “If decreased subcortical-MFC connectivity specifically characterizes children with OCD, then prior work limited to adult samples could not have detected it.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Age-related decreases in subcortical connectivity to anterior cingulate cortex and ventral medial frontal cortex parallel functional changes and may reflect synaptic pruning supporting information flow in frontal-striatal-thalamic circuitry.

    “These functional changes are paralleled by age-related decreases in subcortical connectivity to areas of cortex, including the ACC and vMFC12, that could reflect synaptic pruning to support information flow in FSTC12.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [12] Supekar, 2009, Development of large-scale functional brain networks in children, PLoS Biol source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Dorsal anterior cingulate cortex detects conflict between competing response options, while rostral anterior cingulate cortex activates to errors and to conflict between emotionally salient stimuli.

    “The dorsal ACC detects conflict between competing response options7, while the rostral ACC has been shown to activate to errors26 and conflict between emotionally salient stimuli27.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [7] Ridderinkhof, 2004, The role of the medial frontal cortex in cognitive control, Science source

      Not checked in the free run.

    • cites [26] Taylor, 2006, Medial frontal cortex activity and loss-related responses to errors, J Neurosci source

      Not checked in the free run.

    • cites [27] Etkin, 2006, Resolving emotional conflict: a role for the rostral anterior cingulate cortex in modulating activity in the amygdala, Neuron source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    Adolescent patients had significantly more medication use and more subclinical obsessive-compulsive disorder symptoms than patients in other age groups.

    “However, significantly more adolescent patients were medicated (χ2=13.3, p = .004), and experiencing only subclinical OCD symptoms (YBOCS < 15; χ2=13.2, p = .004) compared to patients in other age groups.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    There were no group differences in head movement at any age.

    “there were no group differences in movement at any age.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A continuum of function has been ascribed to ventral medial frontal cortex, from discerning value in orbitofrontal cortex to value-based decision-making in medial frontal pole.

    “A continuum of function has been ascribed to vMFC – from discerning value in orbitofrontal cortex to value-based decision-making in the medial frontal pole34.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [34] Grabenhorst, 2011, Value, pleasure and choice in the ventral prefrontal cortex, Trends Cogn Sci source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    Type II error may have contributed to the failure to show increased dorsal striatum or medial thalamus connectivity with anterior cingulate cortex in adult obsessive-compulsive disorder.

    “Alternatively, Type II error may have contributed to our failure to show a pattern of increased dorsal striatum or medial thalamus connectivity with ACC in adult OCD”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In obsessive-compulsive disorder, baseline hyperactivity of dorsal caudate and ventral medial frontal cortex associates with symptom severity and increases with symptom provocation.

    “In OCD, baseline hyperactivity of the dorsal caudate and ventral MFC associates with symptom severity and increases with symptom provocation3”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [3] Menzies, 2008, Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: the orbitofronto-striatal model revisited, Neurosci Biobehav Rev source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Hyperactivity of medial and lateral orbitofrontal cortex has been among the most consistently reported findings in obsessive-compulsive disorder and has been linked to altered reward processing and reversal learning in adult patients.

    “Hyperactivity of medial and lateral orbitofrontal cortex have been among the most consistently reported findings in OCD, and have been linked to altered functional processing of reward and reversal learning, respectively, in adult patients3.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3] Menzies, 2008, Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: the orbitofronto-striatal model revisited, Neurosci Biobehav Rev source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    If ventral striatum-ventral medial frontal cortex hyperconnectivity in obsessive-compulsive disorder is unique to older patients, the relatively younger age of adult patients in the present sample may have reduced power to detect this effect.

    “If ventral striatum – vMFC hyperconnectivity in OCD is unique to older patients, then the relatively younger age of the adult patients in our sample (25 +/− 7 years) compared to those in previous work (29 +/− 6 years5; 31 +/− 9 years33) may have reduced our power to detect this effect.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [5] Harrison, 2009, Altered corticostriatal functional connectivity in obsessive-compulsive disorder, Arch Gen Psychiatry source

      Not checked in the free run.

    • cites [33] Sakai Y, Narumoto J, Nishida S, et al. Corticostriatal functional connectivity in non-medicated patients with obsessive-compulsive disorder [published online ahead of print November 8, 2010]. Eur Psychiatry. doi:10.1016/j.eurpsy.2010.09.005. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Ventral medial frontal cortex typically projects to ventral striatum and dorsal striatum is more often associated with anterior cingulate cortex, but converging evidence suggests these regions interact through overlapping projections in dorsal and ventral striatum.

    “The vMFC is typically characterized by projections to the ventral striatum, particularly nucleus accumbens, whereas the dorsal striatum is more often associated with projections to the ACC. However, converging lines of evidence from animal-tracing and human neuroimaging research suggests these regions may interact through overlapping projections in dorsal and ventral striatum8.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [8] Haber, 2010, The reward circuit: linking primate anatomy and human imaging, Neuropsychopharmacology source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Alterations of anterior cingulate cortex-based frontal-striatal-thalamic circuitry for cognitive control and ventral medial frontal cortex-based circuitry for emotion processing during development may increase vulnerability for obsessive-compulsive disorder and other psychopathologies including Tourette's syndrome, eating disorders, and attention deficit hyperactivity disorder.

    “Alterations of ACC-based FSTC for cognitive control and vMFC-based FSTC for emotion processing during development may increase vulnerability for OCD, but also other forms of psychopathology, including Tourette's syndrome, eating disorders, and attention deficit hyperactivity disorder35.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [35] Marsh, 2009, Functional disturbances within frontostriatal circuits across multiple childhood psychopathologies, Am J Psychiatry source

      Not checked in the free run.

33 of 33

  • The paper relies on this without support.

    Obsessive-compulsive disorder commonly emerges during childhood or adolescence.

    “Obsessive compulsive disorder (OCD) commonly emerges during childhood or adolescence”

  • The paper relies on this without support.

    Age-related differences observed cross-sectionally in connectivity reflect developmental trajectories.

    “We studied resting state functional connectivity of striatum and thalamus with medial frontal cortex in OCD patients and healthy controls at successive stages of development to test for differences in frontal-striatal-thalamic circuit (FSTC) maturation.”
2 of 2

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  • Excluded participants are incorrectly described as patients

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    The text calls all 14 excluded participants patients, but its breakdown includes seven healthy controls.

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Authors
Fitzgerald, K. D., Welsh, R. C., Stern, E. R., Angstadt, M., Hanna, G. L., Abelson, J. L., & Taylor, S. F.
Affiliations
University of Michigan (US)
Corresponding author
Fitzgerald, Kate Dimond
ORCID
Venue
Journal of the American Academy of Child & Adolescent Psychiatry
Publisher
Elsevier BV
Published
2011-09
Volume
50
Issue
9
Pages
938-948.e3
ISSN
0890-8567 (ISSN-L)
DOI
10.1016/j.jaac.2011.06.011
PMC
PMC3167379
OpenAlex
W2010992646
Cited by
165
References
36
Citations by year
2026: 6 · 2025: 4 · 2024: 8 · 2023: 7 · 2022: 9 · 2021: 14 · 2020: 13 · 2019: 10 · 2018: 9 · 2017: 12 · 2016: 18 · 2015: 15 · 2014: 15 · 2013: 12 · 2012: 10
FWCI
12.78
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Journal of the American Academy of Child & Adolescent Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (5r01ns052514-04)
  • National Institute of Mental Health (R01MH071821, K23MH082176, F32MH082573)
  • National Institute of Neurological Disorders and Stroke (R01-NS052514)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
  • Health Sciences › Medicine › Neurology › Neurological disorders and treatments
Keywords
pediatric obsessive-compulsive disorder, anterior cingulate cortex, dorsal striatum, mediodorsal thalamus, resting-state functional connectivity, developmental trajectories, cognitive control, emotional processing, disease onset, OCD severity
MeSH terms
Adolescent, Adult, Child, Female, Frontal Lobe, Humans, Magnetic Resonance Imaging, Male, Neural Pathways, Obsessive-Compulsive Disorder, Oxygen, Thalamus, Neostriatum, Young Adult

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-04.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-04.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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