CoChat
Sign Up
Cited by 30Obsessive-Compulsive Spectrum DisordersAnxiety, Depression, Psychometrics, Treatment, Cognitive ProcessesNeural and Behavioral Psychology Studies

Task-based fMRI predicts response and remission to exposure therapy in obsessive-compulsive disorder

Open access
Pagliaccio, David, Middleton, Rachel, Hezel, Dianne, Steinman, Shari, Snorrason, Ivar, Gershkovich, Marina, Campeas, Raphael, Pinto, Anthony +3 more·2019·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1909199116PMC PMC6789627
Open this paper in CoChat — free accountOpen PDF

Abstract

Exposure and ritual prevention (EX/RP) is an effective first-line treatment for obsessive-compulsive disorder (OCD), but only some patients achieve minimal symptoms following EX/RP. Herein, we investigate whether task-based neural activity can predict who responds best to EX/RP. Unmedicated adult patients with OCD ( n = 36) and healthy participants ( n = 33) completed the Simon Spatial Incompatibility Task during high-resolution, multiband functional MRI (fMRI); patients were then offered twice-weekly EX/RP (17 sessions). Linear mixed-effects models were used to identify brain regions where conflict-related activity moderated the slope of change in Yale–Brown Obsessive-Compulsive Scale (Y-BOCS) scores across treatment. Conflict-related activity in the left pallidum and 35 cortical parcels/regions significantly predicted symptom improvement with EX/RP for patients with OCD (false discovery rate-corrected P < 0.05). Significant parcels/regions included cingulo-opercular and default mode network regions, specifically the anterior insula and anterior and posterior cingulate. Summarizing across these parcels/regions, greater conflict-related activity predicted greater EX/RP response and which patients achieved remission (Y-BOCS score ≤ 12; Cohen’s d = 1.68) with >80% sensitivity and specificity. The association between brain activity and treatment response was partially mediated by patient EX/RP adherence (b = −2.99; 43.61% of total effect; P = 0.02). Brain activity and adherence together were highly predictive of remission. Together, these findings suggest that cingulo-opercular and default mode regions typically implicated in task control and introspective processes, respectively, may be targets for novel treatments that augment the ability of persons with OCD to resolve cognitive conflict and thereby facilitate adherence to EX/RP, increasing the likelihood of remission.

Integrity signals

Registry

Crossref · 10.1073/pnas.1909199116

Cites

62 of 62 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

0 of 51 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Each 0.13 increase in PC1 activity predicted an additional one-point symptom reduction over treatment.

    “Thus, every 0.13 increase in PC1 activity predicted an additional point reduction in symptoms over the course of treatment.”
    Quote in the paperSubstantial claim
  • Findingown data

    No group difference in conflict-related activity between OCD and healthy participants survived stringent permutation-based correction.

    “No significant group differences in conflictrelated activity between patients with OCD and healthy participants passed stringent permutation-based correction for multiple comparisons.”
    Quote in the paperNot a substantial claim
  • Findingown data

    PC1 significantly interacted with time to predict Y-BOCS scores (b=-0.97, t=-5.07, P<0.001).

    “PC1 significantly interacted with time to predict Y-BOCS scores (b = -0.97,B = -0.07,t = -5.07,P < 0.001; SI Appendix, Fig. S9).”
    Quote in the paperSubstantial claim
  • Findingown data

    Y-BOCS scores fell significantly over treatment, by about 1.50 points per week.

    “Y-BOCS scores declined significantly over time (assessment weeks 0, 4, 8; b = -1.50, t = -8.78, P < 0.001), reflecting a 1.50 point decrease in symptoms per week across treatment”
    Quote in the paperNot a substantial claim
  • Findingown data

    None of the identified regions had significant main effects on pretreatment Y-BOCS scores.

    “None of these regions showed significant main effect associations with pretreatment Y-BOCS scores (all P > 0.05).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 30
  • The quote only partly states this claim. 2
  • Classified as probably not a substantial claim. 35

  • May combine two claims.

    Findingown data

    All identified parcels/regions except the left entorhinal cortex had negative interaction effects, meaning greater conflict-related activity accompanied greater symptom decline during treatment.

    “All identified parcels/regions, except the left entorhinal cortex, showed negative interaction effects, with greater conflict-related activity in patients who showed the greatest decline in symptoms during treatment.”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    Conflict-related activity by time interactions survived multiple-comparison correction in 36 parcels/regions (uncorrected P<0.005; FDR-corrected P<0.05).

    “showed conflict-related activity × time interactions passing multiple comparisons correction (all uncorrected P < 0.005, false discovery rate [FDR]-corrected P < 0.05; Fig. 1 and Table 2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In categorical remission analyses, similar effects appeared in all parcels/regions and reached significance in 29 of 36.

    “In follow-up categorical analyses predicting remission, similar effects were observed in all parcels/regions and reached significance in 29 of these 36 parcels/regions (all P < 0.05; Table 2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The identified regions included right pallidum, bilateral visual cortex parcels, right anterior insula, left anterior cingulate, DLPFC, right superior temporal sulcus, right inferior parietal cortex/angular gyrus, and bilateral posterior cingulate cortex.

    “These regions included the right pallidum and cortical parcels within the bilateral visual cortex, right anterior insula, left anterior cingulate, dorsolateral prefrontal cortex (DLPFC), right superior temporal sulcus, right inferior parietal cortex (angular gyrus), and bilateral posterior cingulate cortex (PCC).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Using PCA across the 36 parcels/regions, the authors found a large effect size for conflict-related activity differences between remitters and nonremitters, and this activity predicted remission with >80% sensitivity and specificity.

    “Using principal components analysis to summarize/simplify testing across the 36 identified parcels/regions, we found a large effect size for differences in conflict-related activity between patients who would or would not achieve remission; moreover, this activity predicted remission with >80% sensitivity and specificity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    This alternative interpretation is not supported by the data, because task performance did not predict EX/RP response and reduced, rather than greater, DLPFC and ACC activation predicted better response.

    “Although plausible, this interpretation is not supported by our data, as task performance did not predict EX/ RP response and reduced, rather than greater, DLPFC and ACC activation predicted a better response to EX/RP.”
    Quote in the paperNot a substantial claim

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    Among 374 tested cortical and subcortical parcels/regions, 36 showed a significant interaction between conflict-related activity (incongruent minus congruent trials) and time in predicting Y-BOCS scores in OCD patients receiving EX/RP, and these survived FDR correction.

    “These highlighted cortical parcels and the right pallidum showed significant conflict-related activity × time (assessment week) interactions in LME models predicting Y-BOCS scores and passed FDR correction for multiple comparisons.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [31] source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Neither demographic covariates nor baseline Y-BOCS scores significantly predicted remission.

    “Neither the demographic covariates nor baseline Y-BOCS scores significantly predicted remission (P > 0.05).”
    Quote in the paperSubstantial claim

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

    Findingreasoning

    Patients were not selected by specific obsessions/compulsions or OCD subtypes, so they exhibited a variety of primary symptoms.

    “Fourth, patients were not selected based on specific obsessions/compulsions or subtypes of OCD, and thus exhibited a variety of primary obsessions/compulsions.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    PC1 significantly predicted remission (z=2.64, P=0.008); a 0.10 increase in conflict-related activity was linked to 1.55-fold higher odds of remission (95% CI 1.12-2.15).

    “In a logistic regression, PC1 was also a significant predictor (z = 2.64, P = 0.008) of remission [operationalized as in prior studies (12,26) as a posttreatment Y-BOCS score ≤ 12] such that a 0.10 increase in conflict-related activity was associated with 1.55-fold greater odds of remission (95% confidence interval [CI] = 1.12 to 2.15).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    An unthresholded map showed increased conflict-related activity in OCD in inferior frontal gyrus, anterior insula, ACC, and striatum, with a smaller effect size than seen under rigorous correction.

    “An unthresholded map of group differences (SI Appendix, Fig. S5) shows increased conflict-related activity in OCD in the inferior frontal gyrus, anterior insula, ACC, and striatum, albeit of a smaller effect size than observable with the rigorous correction used here.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Adherence predicted posttreatment Y-BOCS scores after adjustment for age, sex, IQ, and baseline Y-BOCS; a one-point higher PEAS score corresponded to an 8-point larger drop in Y-BOCS.

    “As in prior work, treatment adherence significantly predicted posttreatment Y-BOCS scores (b = -8.09,t = -4.66,P < 0.001), controlling for age, sex, IQ, and baseline Y-BOCS score (i.e., a 1-unit increase in the Patient EX/RP Adherence Scale [PEAS] related to an 8-point greater reduction in Y-BOCS scores with treatment).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    All paths in the mediation model were significant: PC1 predicted adherence, and adherence predicted Y-BOCS change.

    “All paths in this medi- ation model were significant: PC1 predicted adherence, and adherence predicted change in Y-BOCS scores.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The number of EX/RP sessions completed is a valid measure of patient treatment adherence.
    • Rests on an assumption: The mediation analysis can be interpreted causally, with no unmeasured confounding of the activity-adherence and adherence-outcome relationships.

  • May combine two claims.

    Findingown data

    Effects were large and predicted remission with relatively high sensitivity and specificity.

    “Effects were large and predicted remission with relatively high sensitivity and specificity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    PC1 activity predicted remission better than baseline symptom severity alone and added prediction over patient adherence.

    “In fact, PC1 activity had more predictive power than baseline symptom severity alone and helped predict remission over and above patient adherence, a known predictor of outcomes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The full model including adherence and PC1 had better fit than the adherence-only model, with AIC 41.11 versus 33.85, Nagelkerke R2 0.50 versus 0.71, and a model-change chi-square P value of 0.002.

    “This full model showed a better fit (model Akaike information criterion = 41.11 vs. 33.85,Nagelkerke R 2 = 0.50 vs. 0.71, model change χ 2 P = 0.002)”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Exposure and ritual prevention is an established first-line therapy for obsessive-compulsive disorder.

    “A first-line treatment for OCD (11), EX/RP involves patients confronting feared situations to trigger obsessions (i.e., intrusive thoughts, images, urges) while abstaining from performing rituals (i.e., repetitive actions aimed at preventing or reducing distress).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11]

      Not checked in the free run.

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

    Premisecitation

    OCD symptoms have been hypothesized to reflect failures to inhibit or control thoughts and behaviors, consistent with neuropsychological deficits in cognitive/executive function including inhibitory control.

    “OCD symptoms have been hypothesized to reflect failures to inhibit/control thoughts and behaviors (18), consistent with neuropsychological findings of deficits in cognitive/executive function, including inhibitory control (19)”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [18] source

      Not checked in the free run.

    • cites [19] source

      Not checked in the free run.

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

    Study design and conductown data

    About 65% of OCD patients completed all 17 EX/RP sessions.

    “Approximately 65% of patients with OCD completed the full course of EX/RP (23 of 36 completed all 17 sessions; median = 17 sessions, M = 14.81,SD = 4.20, range = 2 to 17).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The number of EX/RP sessions completed is a valid measure of patient treatment adherence.

  • Classified as probably not a substantial claim.

    Premisecitation

    EX/RP outcome has been hypothesized to depend on cognitive control.

    “outcome from EX/RP is hypothesized to rely upon cognitive control (20)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [20] source

      Not checked in the free run.

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

    Study design and conductown data

    Only three patients dropped out before week 8.

    “Only 3 patients dropped out from the study before week 8.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    The authors previously found altered conflict-related activity in frontal-striatal and insular cortices in adults with OCD during the Simon task.

    “we previously identified altered conflictrelated activity (incongruent > congruent) in frontal-striatal and insular cortices in adults with OCD performing this task (21)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [21] source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Earlier MRI work found that anterior cingulate thickness and resting-state connectivity patterns predict CBT/EX/RP response in OCD.

    “Anterior cingulate thickness (3) and various patterns of resting state connectivity have been shown to predict response to cognitive behavioral therapy, specifically exposure and ritual prevention (EX/RP) (4)(5)(6)(7)(8).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [3] source

      Not checked in the free run.

    • cites (4)(5)(6)(7)(8)

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    OCD patients and healthy participants did not differ significantly in demographics, Simon task performance, or head motion.

    “There were no significant group differences in demographic characteristics, Simon task performance (including accuracy, average reaction time, and incongruent-congruent trial reaction time; Table 1), or head motion during the task (mean frame-wise displacement and percentage of frames censored for motion).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The Y-BOCS ≤12 cutoff indicates minimal symptoms and predicts good quality of life and adaptive functioning.

    “this cutoff not only reflects minimal symptoms after treatment but also predicts good quality of life and adaptive functioning (12,26,30).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [12] source

      Not checked in the free run.

    • cites [26] source

      Not checked in the free run.

    • cites [30] source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    Those prior task-based fMRI studies did not report effect size or sensitivity/specificity of neural predictors.

    “Furthermore, these studies have not addressed effect size or the sensitivity/specificity of these neural predictors, both clinically relevant questions.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    The number of EX/RP sessions was unrelated to Simon task performance, demographic, or clinical variables.

    “The number of EX/RP sessions was not associated with any measures of Simon task performance, demographic, or clinical variables of interest (all P > 0.05).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The number of EX/RP sessions completed is a valid measure of patient treatment adherence.

  • May combine two claims.

    Premisecitation

    The Simon Spatial Incompatibility Task demands cognitive control to resolve conflict and ignore spatial information, and it increases activity in frontostriatal control circuitry in healthy people.

    “This task requires the engagement of cognitive control to resolve cognitive conflict and ignore this task-irrelevant spatial information, which elicits increased activity in frontostriatal control circuitry in healthy individuals (14)(15)(16)(17).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites (14)(15)(16)(17)

      Not checked in the free run.

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

    Premisecitation

    Prior data suggest altered visual-area activation during symptom provocation and resting-state visual-network connectivity predict EX/RP response in OCD.

    “Prior data suggest that altered activation of visual areas during symptom provocation (9) and resting state functional connectivity within the visual network (6) predict EX/RP response in OCD.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [9] source

      Not checked in the free run.

    • cites [6] source

      Not checked in the free run.

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

    Premisecitation

    DMN suppression increases with task difficulty, likely helping prioritize task-relevant over task-irrelevant processes.

    “Suppression of the DMN increases as a function of task difficulty (40), likely representing a way to prioritize task-relevant over task-irrelevant cognitive processes (e.g., mind-wandering).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40] source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductreasoning

    The OCD sample was free of psychotropic medications and comorbidity, which allowed identification of regions where brain activity specifically predicted obsessive-compulsive symptom change.

    “First, the OCD sample was free of psychotropic medications and comorbidity, allowing us to identify regions in which brain activity specifically predicted changes in obsessive-compulsive symptoms.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Recent reports suggest standard multiple-comparison corrections may not fully control false positives.

    “Recent reports suggest that standard multiple comparisons corrections may not have been stringent enough to fully control for false-positive results (36).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] 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 conductnone given

    Runs with >35% outlier frames were excluded, and participants with fewer than two usable runs were excluded.

    “Runs with >35% of frames flagged as outliers were excluded.Participants with <2 runs of usable data were excluded.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    The percentage of frames regressed out on included runs was included as a covariate in all second-level analyses.

    “The percentage of frames regressed out (motion or timeseries outliers) on runs included in analysis for each participant were included as a covariate in all secondlevel analyses.”
    Quote in the paperNot a substantial claim

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

    Interpretationreasoning

    Focusing on parcel-wise analyses could limit identification of clusters smaller than or outside atlas-defined parcels/regions.

    “Second, given current software and multiple comparisons correction constraints, we focused on parcel-wise analyses; this could limit identification of clusters smaller than or not falling within atlas-defined parcels/regions.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    The authors previously found increased conflict-related activity in right insula, putamen, and inferior frontal gyrus in a similar OCD sample using the Simon task.

    “Using the Simon task, we previously detected increased conflict-related activity in the right insula, putamen, and inferior frontal gyrus in a demographically and clinically similar sample of participants with OCD (21).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    OCD diagnoses were confirmed by clinical interview using the SCID for DSM-IV-TR Axis I Disorders, administered by trained raters.

    “OCD diagnoses were determined by clinical interview and confirmed using the Structured Clinical Interview for Diagnostic and Statistical Manual-IV-TR Axis I Disorders (50), administered by trained raters”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [50]

      Not checked in the free run.

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

    Premisecitation

    Meta-analytic findings suggest reduced dorsal ACC, medial prefrontal cortex, DLPFC, and angular gyrus activity during control engagement on inhibitory/cognitive control tasks.

    “In addition, meta-analytic findings suggest reduced dorsal ACC, medial prefrontal cortex, DLPFC, and angular gyrus activity during the engagement of control on inhibitory/cognitive control tasks (44,45).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [44] source

      Not checked in the free run.

    • cites [45] source

      Not checked in the free run.

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

    Interpretationcitation

    One interpretation is that patients with less DMN suppression need fewer resources or less effort to resolve cognitive conflict during the Simon task and possibly during EX/RP.

    “Thus, one way to interpret our data is that patients showing less DMN suppression may require fewer resources/less effort to resolve cognitive conflict during the Simon task and potentially during EX/RP (20).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] source

      Not checked in the free run.

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

    Premisecitation

    The PCC contributes to visual-spatial attention.

    “The PCC is also involved in a number of other functions, including having contributions to visual-spatial attention (43).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationcitation

    The results suggest that improving cognitive conflict resolution may be a target for novel treatments to augment EX/RP efficacy.

    “while suggesting that improving the capacity to resolve cognitive conflict may be a target for novel treatments (e.g., ref. 49) to augment the efficacy of EX/RP.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [49] source

      Not checked in the free run.

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

    Interpretationreasoning

    The sample size was relatively modest, perhaps contributing to nonsignificant group differences.

    “First, while larger than many prior studies, our sample size was still relatively modest, perhaps contributing to nonsignificant group differences.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    EX/RP normalizes hypoconnectivity between cognitive control and DMN regions.

    “In addition, EX/RP normalizes hypoconnectivity between cognitive control and DMN regions (42)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] 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 conductnone given

    The study used up-to-date HCP-aligned methods, including CIFTI space analyses, permitting greater spatial precision.

    “Second, this OCD study used up-to-date methods in line with the HCP, including CIFTI space analyses, permitting greater spatial precision.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    An alternative interpretation is that OCD patients with more efficient control and visual-spatial attention respond better to EX/RP.

    “Thus, our findings might alternatively suggest that patients with OCD who have more efficient control and visual-spatial attention respond better to EX/RP.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Prior work suggests overactivation of typical DMN regions during nonaffective cognitive tasks in adults with OCD and weaker anticorrelation between DMN and salience network than in healthy adults.

    “Prior findings from adults with OCD suggest overactivation of typical DMN regions during nonaffective cognitive tasks (33) and weakened anticorrelation between the DMN and salience network compared with healthy adults (34,35).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [33] source

      Not checked in the free run.

    • cites [34] source

      Not checked in the free run.

    • cites [35] source

      Not checked in the free run.

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

    Study design and conductnone given

    Head motion was controlled by regressing out successive TR pairs with sum frame-wise displacement >0.2 mm and TRs with >10% voxel timeseries outliers.

    “To control for head motion in the first-level models, we regressed out successive TR pairs with sum frame-wise displacement between them exceeding 0.2 mm and TRs where >10% of voxels contained timeseries outliers.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    The analyses used an intent-to-treat framework rather than excluding non-completers and predicted EX/RP outcomes.

    “Third, our analyses used an intent-to-treat framework rather than excluding participants who do not finish treatment and predicted EX/RP outcomes.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Meta-analytic findings suggest functional hypoconnectivity between DMN and task-positive networks in OCD.

    “Interestingly, meta-analytic findings suggest functional hypoconnectivity between the DMN and task-positive networks in OCD (41).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41] source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The interaction between activity and time was adjusted for multiple comparisons across brain regions using FDR.

    “This interaction effect was corrected for multiple comparisons across brain parcels/regions using FDR.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Group differences in conflict-related activity were tested with stringent permutation testing and threshold-free cluster enhancement.

    “Thus, we tested group differences in conflict-related activity (difference between incongruent and congruent trials [I-C] contrast) using stringent permutation testing (https:// fsl.fmrib.ox.ac.uk/fsl/fslwiki/PALM) (60) and threshold-free cluster enhancement (61).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [60] source

      Not checked in the free run.

    • cites [61] source

      Not checked in the free run.

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

    Study design and conductown data

    An intent-to-treat linear mixed-effects model was used for treatment outcomes, permitting missing data and using every available Y-BOCS score at weeks 0, 4, and 8.

    “First, in a LME model [R lme4 package (59)] taking an intent-to-treat approach allowing for missing data, all available Y-BOCS data (repeated measure at weeks 0, 4, and 8) were examined continuously as the dependent variable with a random effect for participant and fixed effects for time (i.e., week of assessment), age, sex, and IQ.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [59] source

      Not checked in the free run.

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

    Premisecitation

    A posttreatment Y-BOCS score of 12 or less indicates meaningful symptom reduction and is linked to better quality of life and daily functioning.

    “operationalized as a posttreatment Y-BOCS score ≤ 12, given that this cutoff reflects symptom reduction and predicts good quality of life and adaptive functioning (12,26,30).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [12] source

      Not checked in the free run.

    • cites [26] source

      Not checked in the free run.

    • cites [30] source

      Not checked in the free run.

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

    Study design and conductown data

    Missing Y-BOCS data were minimal: only 7 of 108 possible scores were absent.

    “There were minimal missing data (missing 7 of 108 potential Y-BOCS scores).”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    The study was registered as a clinical trial under NCT02221518.

    “This study has been registered as a clinical trial (Control and Reward Circuits in Obsessive Compulsive Disorder, NCT02221518)”
    Quote in the paperNot a substantial claim
55 of 55

  • The paper relies on this without support.

    The number of EX/RP sessions completed is a valid measure of patient treatment adherence.

    “Approximately 65% of patients with OCD completed the full course of EX/RP (23 of 36 completed all 17 sessions; median = 17 sessions, M = 14.81,SD = 4.20, range = 2 to 17).”
    “as patient treatment adherence is a known predictor of EX/RP response (27)”

  • The paper relies on this without support.

    The mediation analysis can be interpreted causally, with no unmeasured confounding of the activity-adherence and adherence-outcome relationships.

    “the association between PC1 and change in Y-BOCS scores (posttreatment Y-BOCS scores controlling for pretreatment Y-BOCS scores) was partially mediated by patient EX/RP adherence (indirect effect: b = -2.99,95% CI = -7.95 to -0.36, P = 0.02; 43.61% of total effect mediated; SI Appendix, Fig. S10).”
    “All paths in this medi- ation model were significant: PC1 predicted adherence, and adherence predicted change in Y-BOCS scores.”

  • The paper relies on this without support.

    Adhering to EX/RP, which involves confronting anxiety-provoking stimuli while refraining from rituals, likely requires cognitive control.

    “Treatment adherence is among the strongest known predictors of EX/RP response (27), and adhering to EX/RP (i.e., confronting anxiety-provoking stimuli while refraining from rituals) likely requires the engagement of cognitive control.”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Other studies have attempted to identify predictors of therapeutic response in OCD patients, but the wide diversity of methodologies and outcomes makes it difficult to identify precise and reproducible markers of resistance.

    “Other studies have attempted to identify predictors of therapeutic response in OCD patients, but the wide diversity of methodologies and outcomes makes it difficult to identify precise and reproducible markers of resistance [47–53].”

    From Error-Related Brain Potentials as Biomarkers of Pathology Severity and Treatment Resistance in Patients With Obsessive-Compulsive Disorder (2026) · cites this paper as [51]

    The introductory section (page not available) describes prior OCD treatment-prediction studies using different MRI approaches and notes that task-based studies had small samples or nonsignificant predictions. It does not say that diversity of methods and outcomes makes precise, reproducible markers of treatment resistance difficult to identify. The Discussion calls for replication of this paper’s findings, but does not establish that broader explanation. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

Statistics recomputed

Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.

  • Consistentz = 2.64reported p = .008 · recomputed p = .008

    “(z = 2.64, p = .008”

  • Consistentz = 2.49reported p = .013 · recomputed p = .013

    “(z = 2.49, p = .013”

  • Consistentz = 2.23reported p = .025 · recomputed p = .026

    “(z = 2.23, p = .025”

3 of 3

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Discussion reverses the reported direction of frontal activity effects

    Major

    The discussion says reduced DLPFC and ACC activation predicted better response. The results instead say greater conflict-related activity predicted a greater symptom decline in all identified regions except the left entorhinal cortex, which includes the listed DLPFC and anterior cingulate regions.

  • Figure description attributes the pallidum to a cortical atlas

    Minor

    The figure description calls all 36 findings parcels from the Glasser atlas, but another figure description distinguishes the cortical parcels from the right pallidum. The methods assign subcortical regions to the Harvard-Oxford atlas.

  • Pallidum predictor is assigned to opposite hemispheres

    Minor

    The opening summary identifies the left pallidum, whereas the results and Table 2 identify the right pallidum.

3 of 3

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. M. First, R. Spitzer, M. Gibbon, J. Williams, Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition (SCID-I/P) (Biometrics Research, New York State Psychiatric Institute, New York, 2002).

Cited by

Sorted by citations

Related

Authors
Pagliaccio, D., Middleton, R., Hezel, D., Steinman, S., Snorrason, I., Gershkovich, M., Campeas, R., Pinto, A., Van Meter, P., Simpson, H. B., & Marsh, R.
Affiliations
  • New York State Psychiatric Institute (US)
  • Center for OCD and Related Disorders, New York State Psychiatric Institute, New York, NY 10032;
  • Donald & Barbara Zucker School of Medicine at Hofstra/Northwell (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2019-09-23
Volume
116
Issue
41
Pages
20346-20353
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1909199116
PMC
PMC6789627
OpenAlex
W2975889270
Cited by
30
References
62
Citations by year
2026: 5 · 2025: 2 · 2024: 3 · 2023: 5 · 2022: 6 · 2021: 6 · 2020: 2 · 2019: 1
FWCI
4.38
Type
journal article
Language
en
Open access
Licence
www.pnas.org/site/aboutpnas/licenses.xhtml (vor, 182 d)
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
HHS | NIH | National Institute of Mental Health (R01MH104648)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords
obsessive-compulsive disorder, exposure and response prevention, treatment response prediction, remission, cognitive conflict, globus pallidus, cingulo-opercular network, default mode network, anterior insula, anterior cingulate cortex, medication adherence, neural markers
MeSH terms
Adult, Female, Humans, Implosive Therapy, Magnetic Resonance Imaging, Male, Obsessive-Compulsive Disorder, Case-Control Studies, 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 2026-10-05.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-05.

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 ›

Are you an author, or do you see a problem with this page? Request a review