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Cited by 13Obsessive-Compulsive Spectrum DisordersNeurotransmitter Receptor Influence on BehaviorMemory and Neural Mechanisms

Evidence for Distinct Forms of Compulsivity in the SAPAP3 Mutant-Mouse Model for Obsessive-Compulsive Disorder

Open access
Ehmer, I., Crown, L., van Leeuwen, W., Feenstra, M., Willuhn, I., Denys, D.·2020·eneuro
DOI 10.1523/eneuro.0245-19.2020PMC PMC7189488
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Abstract

The specific mechanisms underlying compulsive behavior in obsessive-compulsive disorder (OCD) are unknown. It has been suggested that such compulsivity may have its origin in cognitive dysfunction such as impaired processing of feedback information, received after the completion of goal-directed actions. The signal attenuation (SA) task models such a processing deficit in animals by attenuating the association strength between food reward and audiovisual feedback (signal) presented after performance of an operant response. The compulsive-like responding resulting from SA is well characterized in rats, but was so far not established in mice, a species for which powerful genetic OCD models exist. Thus, first, we demonstrate that the SA task can be implemented in mice and show that attenuation of reward-associated response feedback produces similar behavior in C57BL/6 mice as previously reported in rats. Second, we tested the hypothesis that SAPAP3 knock-out mice (SAPAP3-/-), prone to exhibit several OCD-like abnormalities including excessive grooming, show enhanced compulsive-like behavior in the SA task compared with their wild-type (WT) littermates. However, task-related compulsivity measures in SAPAP3-/-and WT did not yield significant differences, neither following SA nor during “regular” extinction of operant behavior. Thus, compulsive-like instrumental behavior following feedback distortion was not potentiated in compulsively grooming mice, implicating specifically that (1) a general deficit in feedback processing is not related to excessive grooming in SAPAP3-/-and (2) different manifestations of compulsivity may be driven by independent mechanisms.

AI snapshot

Written from the paper’s full text.

TL;DR

The signal attenuation (SA) task was successfully implemented in mice, producing increased uncompleted trials (UCTs) and extra nose-pokes in UCT (ENP-UCT) in C57BL/6 SA mice versus regular extinction (RE) controls. In SAPAP3-/- OCD-model mice, SA induced similar compulsivity to wild-type (WT) mice, with no genotype potentiation, suggesting behaviorally and genetically induced compulsivity may be driven by independent mechanisms.

Key findings

  • In C57BL/6 mice, SA was effective: magazine entries declined across SA sessions (Friedman χ²(2)=16.04, p<0.001), and SA mice showed more UCTs than RE mice (U=26.0, p=0.006; SA 4.7±0.97 vs RE 1.2±0.53), more ENPs (U=28.5, p=0.012; SA 46.1±5.6 vs RE 25.0±6.6), and more ENP-UCTs (U=19.0, p=0.001; SA 16.2±3.2 vs RE 2.3±1.3).
  • Within genotypes, SA increased compulsive-like responding: WT-SA vs WT-RE showed more UCTs (U=60.5, p=0.035; 6.4±1.1 vs 3.2±1.1) and more ENP-UCTs (U=56.0, p=0.022; 31.2±6.4 vs 15.8±6.4); SAPAP3-/--SA vs SAPAP3-/--RE also showed more UCTs (U=52.0, p=0.006; 6.9±1.4 vs 2.6±0.56) and more ENP-UCTs (U=53.0, p=0.008; 42.4±14.5 vs 8.2±2.6).
  • SAPAP3-/- did not show enhanced SA-induced compulsivity compared with WT: UCTs were similar between genotypes (χ²(1)=0.111, p=0.739), as were ENP-UCTs (χ²(1)=0.872, p=0.351).
  • SAPAP3-/- groomed more than WT overall during the extinction test (χ²(1)=4.516, p=0.034; 156.9±19.4 s vs 119.9±25.1 s), most clearly in the RE condition (U=45.0, p=0.01; 190.8±33.4 s vs 76.2±12.3 s), but not following SA.

Methods

  • The SA task had four stages: magazine training, nose-poke training, SA or RE, and a final extinction test; compulsivity was measured as UCTs and ENP-UCTs, with food reward and an audiovisual feedback signal in operant boxes.
  • Experiment 1 used 24 male C57BL/6JRccHsd mice (SA n=12, RE n=12); experiment 2 used SAPAP3-/- and WT littermates, with final analysis of 31 SAPAP3-/- and 30 WT after exclusions for learning performance or equipment failure.
  • Grooming was scored in the extinction test, open field, and elevated plus maze; statistical analysis used non-parametric tests (Friedman, Wilcoxon, Kruskal–Wallis, Mann–Whitney) and ANOVA when data were normally distributed, with p<0.05.

Limitations

  • Stated: the study did not investigate internal feedback specifically related to compulsive behavior, so it cannot exclude effects of different task conditions on potential internal-feedback processing deficits related to compulsive grooming in SAPAP3-/-.
  • Stated: only positive response feedback in an appetitive learning condition was tested; future work on aversive feedback or feedback valence in avoidance behavior is indicated.
  • Evident: the final analysis excluded three SAPAP3-/- and five WT mice due to decreased learning performance or equipment failure, and the task used food restriction and sucrose reward, which may limit generalization to other motivational contexts.

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

Integrity signals

Registry

Crossref · 10.1523/eneuro.0245-19.2020

Cites

43 of 43 references verified0 citation errors · 0 not checkable

Statistics

23 tests recomputed · 0 with the reported and recomputed p on opposite sides of .05

Claims the paper makes

0 of 28 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    The SA procedure was effective in attenuating the signal in C57BL/6 mice, as marked by a significant reduction of entries into the food magazine following signal presentation.

    “A Friedman test confirmed that the SA procedure was effective in attenuating the signal as marked by a significant reduction of entries into the food magazine following presentation of the signal (χ2(2) = 16.04, p < 0.001; Fig. 2B).”
    Quote in the paperNot a substantial claim
  • Findingown data

    WT-SA mice showed significantly more UCT compared with WT-RE mice.

    “Analysis of compulsive responses of WT-SA (n = 17) and WT-RE (n = 13) revealed that the SA procedure induced significantly more UCT compared with RE (U = 60.5, p = 0.035; WT-SA: 6.4 ± 1.1, WT-RE: 3.2 ± 1.1; Fig. 4A)”
    Quote in the paperSubstantial claim
  • Findingown data

    The SA procedure significantly increases the number of extra nose-pokes (ENP) in C57BL/6 mice.

    “Similar to prior studies with rats, our results with mice confirmed that the SA procedure significantly increases the number of ENP (U = 28.5, p = 0.012; C57BL/6-SA: 46.1 ± 5.6, C57BL/6-RE: 25.0 ± 6.6; Fig. 2E).”
    Quote in the paperSubstantial claim
  • Findingown data

    In SAPAP3-/--SA mice, effective attenuation of the feedback signal was demonstrated by decreasing magazine entries across SA training sessions.

    “In SAPAP3-/--SA, effective attenuation of the feedback signal was also demonstrated by decreasing magazine entries across SA training sessions (F(2,28) = 7.09, p = 0.003; first session SA 21.8 ± 1.4; second session 18.5 ± 1.4; third session 16.1 ± 1.4; Fig. 3D).”
    Quote in the paperSubstantial claim
  • Findingown data

    WT-SA mice showed more ENP-UCT compared with WT-RE mice.

    “analysis revealed more ENP-UCT of WT-SA compared with WT-RE (U = 56.0, p = 0.022; WT-SA: 31.2 ± 6.4, WT-RE: 15.8 ± 6.4; Fig. 4B).”
    Quote in the paperSubstantial claim
  • May combine two claims. 20
  • Classified as probably not a substantial claim. 13

  • May combine two claims.

    Findingown data

    The signal attenuation (SA) task can be implemented and validated in mice, with C57BL/6 mice acquiring the task and completing the final extinction test.

    “first, we demonstrate that the SA task can be implemented in mice”
    • Also stated in: § C57BL/6 mice readily acquired the response requirements in the SA task · plain
      “All C57BL/6 acquired the SA task and completed the final extinction test (Fig. 2A).”
    • Also stated in: § Compulsive-like behavior is increased in C57BL/6 in the signal-attenuation condition · boosted
      “From these results we conclude that we successfully implemented the SA task for mice.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Task-related compulsivity measures in SAPAP3-/- and wild-type (WT) mice did not yield significant differences, neither following SA nor during regular extinction of operant behavior.

    “However, task-related compulsivity measures in SAPAP3-/- and WT did not yield significant differences, neither following SA nor during “regular” extinction of operant behavior.”
    • Also stated in: § Significance Statement · plain
      “However, we found no enhancement of feedback-induced compulsivity in SAPAP3 mutants.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The number of completed trials (CT) was significantly higher in C57BL/6-RE mice, whereas C57BL/6-SA mice had more no-poke trials.

    “The number of CT was significantly higher in C57BL/6-RE mice (χ2(1) = 17.35, p < 0.001), whereas C57BL/6-SA mice had more no-poke trials (χ2(1) = 17.44, p < 0.001).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the SA procedure, there was a significant effect of session on magazine entries, but no session-genotype interaction or genotype effect.

    “Results show a significant effect of session (F(2,60) = 32.267, p < 0.001), but no session-genotype interaction or genotype effect.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    C57BL/6-SA mice showed a significant increase in UCT from the last nose-poke training to the final extinction test, which was not observed in C57BL/6-RE mice.

    “Further analysis revealed a significant increase of UCT in C57BL/6-SA mice from the last nose-poke training [to the final extinction test (Z = −2.810, p = 0.005: last: 0.17 ± 0.17; test: 4.7 ± 0.97)] that was not observed in C57BL/6-RE mice (Z = −1.473, p = 0.141).”
    Quote in the paperSubstantial claim

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

    Findingnone given

    Mice required more training sessions than rats to acquire responding for food.

    “We noticed that mice required more training sessions than rats to acquire responding for food”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Grooming during feedback signal presentation occurred only incidentally and was not different between genotypes.

    “Grooming during feedback signal presentation occurred only incidentally and was not different between genotypes.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    A trained experimenter, blinded to the genetic background of the animals, manually analyzed levels of self-grooming during the final extinction test.

    “A trained experimenter, who was blinded for genetic background of the animals, manually analyzed levels of self-grooming during the final extinction test.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    Overall genotype comparison in SA and RE condition did not reveal significant differences, confirming that both genotypes acquired the task equally.

    “While SAPAP3-/- required a few more sessions of Mag and NP 30 training than WT, overall genotype comparison in SA and RE condition did not reveal significant differences, confirming that both genotypes acquired the task equally.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Genotypes were matched on task performance, resulting in exclusion of three SAPAP3-/- and five WT mice from the final analysis due to decreased learning performance or equipment failure.

    “To compare compulsivity of SAPAP3-/- and WT, genotypes were matched on task performance, resulting in exclusion of three SAPAP3-/- (two SA, one RE) and five WT (one SA, four RE) from the final analysis due to decreased learning performance or equipment failure.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Both markers of compulsive-like behavior, UCT and ENP-UCT, are increased following the SA procedure.

    “This suggests that both markers of compulsive-like behavior, UCT and ENP-UCT, are increased following the SA procedure.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Impaired feedback processing has been modeled in the signal attenuation (SA) task, developed for rats by Joel and colleagues.

    “Impaired feedback processing has been modeled in the signal attenuation (SA) task, developed for rats by Joel and colleagues (Joel and Avisar, 2001; Joel, 2006; Albelda and Joel, 2012).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Joel and Avisar, 2001

      Not checked in the free run.

    • cites Joel, 2006

      Not checked in the free run.

    • cites Albelda and Joel, 2012

      Not checked in the free run.

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

    Premisecitation

    Similar to OCD patients, compulsive grooming in SAPAP3-/- mice can be normalized by administration of selective serotonin reuptake inhibitors (SSRIs) or deep-brain stimulation.

    “Similar to OCD patients, compulsive grooming can be normalized by administration of selective serotonin reuptake inhibitors (SSRIs) or deep-brain stimulation (Welch et al., 2007; Pinhal et al., 2018).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Welch et al., 2007

      Not checked in the free run.

    • cites Pinhal et al., 2018

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    SAPAP3-/- in comparison to WT controls do not show excessive, compulsive-like behavior in the SA paradigm, neither under conditions of RE nor when general feedback processing is diminished by SA.

    “Taken together, these results suggest that SAPAP3-/- in comparison to WT controls do not show excessive, compulsive-like behavior in the SA paradigm, neither under conditions of RE nor when general feedback processing is diminished by SA.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    In the SA task, attenuation of the incentive salience of the feedback signal leads to compulsive-like responding in a subsequent extinction test that is absent in animals not exposed to SA treatment.

    “To simulate feedback deficiency experimentally, the incentive salience of this signal is attenuated by presenting it in absence of food delivery. This leads to compulsive-like responding (in a subsequent extinction test) that is absent in animals not exposed to this SA treatment”
    • Also stated in: § Significance Statement · boosted
      “The signal attenuation (SA) task is a well-established behavioral paradigm for rats that promotes compulsivity.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Joel, 2006

      Not checked in the free run.

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

    Study design and conductnone given

    All animal procedures were performed in accordance with Dutch law and the Royal Netherlands Academy of Arts and Sciences animal care committee's regulations.

    “All animal procedures were performed in accordance with the Dutch law and the Royal Netherlands Academy of Arts and Sciences animal care committee’s regulations.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Such dysfunction seems to be restricted to cortico-striatal circuits and not extend to thalamo-cortical circuits.

    “Notably, such dysfunction seems to be restricted to cortico-striatal circuits, and not extend to thalamo-cortical circuits (Wan et al., 2014).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Wan et al., 2014

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    SAPAP3-/- mice self-groom excessively and display increased anxiety and decreased behavioral flexibility.

    “SAPAP3-/- self-groom excessively and display increased anxiety and decreased behavioral flexibility (Welch et al., 2007; Manning et al., 2019; van den Boom et al., 2019).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Welch et al., 2007

      Not checked in the free run.

    • cites Manning et al., 2019

      Not checked in the free run.

    • cites van den Boom et al., 2019

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Striatal input from the secondary motor cortex is strengthened in SAPAP3-/- mice.

    “For example, striatal input from the secondary motor cortex, which is strengthened in SAPAP3-/- (Corbit et al., 2019), has not yet been tested in SA.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Corbit et al., 2019

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The reduced ENP in CT in SAPAP3-/- during RE is indicative of rapid extinction learning or altered vigor for obtaining rewards.

    “During RE, SAPAP3-/- showed reduced numbers of ENP in CT, indicative of rapid extinction learning or altered vigor for obtaining rewards.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    SAPAP3-/- mice show abnormalities in lOFC neuronal activity and perturbed cortico-striatal network activation.

    “whereas SAPAP3-/- show abnormalities in lOFC neuronal activity and perturbed cortico-striatal network activation (Lei et al., 2019).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Lei et al., 2019

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    SAPAP3-/- do not show a general deficit in feedback processing, as compulsive responding during the extinction test of the SA paradigm was similar to that of WT controls.

    “SAPAP3-/- do not show a general deficit in feedback processing, as compulsive responding during the extinction test (stage 4) of the SA paradigm was similar to that of normal WT controls.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Stimulation of the lOFC-striatal pathway alleviates excessive grooming.

    “Moreover, stimulation of the lOFC-striatal pathway alleviates excessive grooming (Burguière et al., 2013).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Burguière et al., 2013

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The genetic defect may result in excessive grooming, impaired reversal learning, and deficient habit formation (in appetitive learning), but these effects are not obviously linked to one another.

    “Taken together, this implies that the genetic defect may result in excessive grooming, impaired reversal learning, and deficient habit formation (in appetitive learning), but that these effects are not obviously linked to one another and possibly involve more complex or different neurobiological mechanisms.”
    Quote in the paperSubstantial claim

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

    Interpretationcitation

    Potentially decreased employment of external feedback signals might cause only transient learning deficits.

    “Thus, potentially decreased employment of external feedback signals might cause only transient learning deficits, that are less important for behavioral outcomes than OCD-related compulsive symptoms and could reflect decreased task engagement caused by altered processing of appetitive rewards, a condition that was also reported for human OCD patients (Figee et al., 2011; Marsh et al., 2015).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Cognitive inflexibility and an imbalance between goal-directed and habitual behavior may be present in the SAPAP3-/- model for OCD.

    “Evidence is accumulating that cognitive inflexibility and an imbalance between goal-directed and habitual behavior may be present in the SAPAP3-/- model for OCD (Manning et al., 2019; van den Boom et al., 2019; Ehmer et al., 2020).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Manning et al., 2019

      Not checked in the free run.

    • cites van den Boom et al., 2019

      Not checked in the free run.

    • cites Ehmer et al., 2020

      Not checked in the free run.

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

    Interpretationreasoning

    The difference in training sessions may reflect differences in species' learning abilities or effects of different response manipulanda.

    “possibly reflecting differences in the species’ learning abilities or effects of different response manipulanda (i.e., we used nose-poke holes whereas rats are usually trained with levers).”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    During initial trial-and-error learning, OCD patients exhibit response deficits.

    “During initial trial-and-error learning, in which behavioral responses needed to be updated by external feedback, OCD patients were observed to exhibit response deficits (Nielen et al., 2009).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Nielen et al., 2009

      Not checked in the free run.

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

    Interpretationreasoning

    The difference in ENP in CT between genotypes may reflect a difference in extinction learning or reduced response vigor of SAPAP3-/-.

    “As numbers of CT and no-poke trials were similar between genotypes, this result may reflect a difference in extinction learning or reduced response vigor of SAPAP3-/- (Fig. 4C).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premiseown data

    Neither cognitive inflexibility nor deficient habit formation were correlated to compulsive grooming.

    “The relation between the dysfunction, compulsive grooming, and the genetic deletion, however, seems to be complex: neither cognitive inflexibility nor deficient habit formation were correlated to compulsive grooming.”
    Quote in the paperSubstantial claim
30 of 30

  • The authors state this as an assumption.

    Compulsive behavior can be caused by deficient processing of environmental cues that signal the completion of goal-directed behavior.

    “This task is based on the assumption that compulsive behavior can be caused by deficient processing of environmental cues that signal the completion of goal-directed behavior.”

  • The authors state this as an assumption.

    A general deficit in feedback processing is a major source of compulsive behavior, via a shared underlying neuronal pathology.

    “Under the assumptions that a general deficit in feedback processing is a major source of compulsive behavior (via a shared underlying neuronal pathology) and that compulsivity is a unitary and uniform phenomenon”

  • The authors state this as an assumption.

    Compulsivity is a unitary and uniform phenomenon.

    “Under the assumptions that a general deficit in feedback processing is a major source of compulsive behavior (via a shared underlying neuronal pathology) and that compulsivity is a unitary and uniform phenomenon”

  • The authors state this as an assumption.

    In the SA stage, presenting the signal without reward and making nose-poke holes inaccessible reduces the association between signal and reward without affecting response-outcome associations.

    “In the SA stage (stage 3), the signal is presented without reward and nose-poke holes are inaccessible, thereby reducing the association between signal and reward, presumably without affecting response-outcome associations.”

  • The authors state this as an assumption.

    The SA task simulates feedback deficiency, which is hypothesized to contribute to compulsive symptoms in psychiatric disorders such as OCD.

    “In summary, the SA task simulates feedback deficiency, which is hypothesized to contribute to compulsive symptoms in psychiatric disorders such as OCD.”
5 of 5

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?

  • Excessive grooming in Sapap3-KO mice has been consistently observed across experimental conditions, including testing during light cycle and during the dark period.

    “In contrast, excessive grooming in Sapap3-KO mice has been consistently observed across experimental conditions, including testing during light cycle [9,12,13] and during the dark period [9,10,17,33], which shows the robustness of the phenotype.”

    From Projection-specific deficits in synaptic transmission in adult Sapap3-knockout mice (2020) · cites this paper as [33]

Statistics that don’t add up

Each reported p-value recomputed from its test statistic and degrees of freedom.

  • Inconsistent p-value: χ2(1) = 0.17, p = .60

    Minor

    The paper reports p = .6 here; recomputing from the test statistic and its degrees of freedom gives p = .680. The check cannot tell whether the statistic or the p-value is the misprint.

    Reported p = .6 · recomputed p = .680

1 of 1

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.

  • Doesn’t add upχ²(1) = 0.17reported p = .6 · recomputed p = .680

    “χ2(1) = 0.17, p = .60”

  • Not confirmedr(59) = 0.32reported p = .014 · recomputed p = .012

    “r(59) = 0.320, p = .014”

  • Consistentχ²(1) = 3.07reported p = .08 · recomputed p = .080

    “χ2(1) = 3.07, p = .08”

  • Consistentχ²(1) = 0.04reported p = .84 · recomputed p = .841

    “χ2(1) = 0.04, p = .84”

  • Consistentχ²(2) = 16.04reported p < .001 · recomputed p < .001

    “χ2(2) = 16.04, p < .001”

  • Consistentz = -2.81reported p = .005 · recomputed p = .005

    “(Z = −2.810, p = .005”

  • Consistentz = -1.473reported p = .141 · recomputed p = .141

    “(Z = −1.473, p = .141”

  • Consistentχ²(1) = 17.35reported p < .001 · recomputed p < .001

    “χ2(1) = 17.35, p < .001”

  • Consistentχ²(1) = 17.44reported p < .001 · recomputed p < .001

    “χ2(1) = 17.44, p < .001”

  • ConsistentF(2, 60) = 32.267reported p < .001 · recomputed p < .001

    “F(2,60) = 32.267, p < .001”

  • ConsistentF(2, 32) = 38.6reported p < .001 · recomputed p < .001

    “F(2,32) = 38.6, p < .001”

  • ConsistentF(2, 28) = 7.09reported p = .003 · recomputed p = .003

    “F(2,28) = 7.09, p = .003”

  • Consistentχ²(1) = 12.109reported p = .001 · recomputed p < .001

    “χ2(1) = 12.109, p = .001”

  • Consistentχ²(1) = 4.498reported p = .034 · recomputed p = .034

    “χ2(1) = 4.498, p = .034”

  • Consistentχ²(1) = 6.691reported p = .01 · recomputed p = .010

    “χ2(1) = 6.691, p = .010”

  • Consistentχ²(1) = 0.111reported p = .739 · recomputed p = .739

    “χ2(1) = 0.111, p = .739”

  • Consistentχ²(1) = 0.872reported p = .351 · recomputed p = .350

    “χ2(1) = 0.872, p = .351”

  • Consistentχ²(1) = 11.49reported p < .001 · recomputed p < .001

    “χ2(1) = 11.490, p < .001”

  • Consistentχ²(1) = 4.516reported p = .034 · recomputed p = .034

    “χ2(1) = 4.516, p = .034”

  • Consistentχ²(1) = 6.694reported p = .01 · recomputed p = .010

    “χ2(1) = 6.694, p = .01”

  • Consistentχ²(1) = 6.923reported p = .009 · recomputed p = .009

    “χ2(1) = 6.923, p = .009”

  • Consistentχ²(1) = 5.57reported p = .018 · recomputed p = .018

    “χ2(1) = 5.570, p = .018”

  • Consistentχ²(1) = 5.402reported p = .02 · recomputed p = .020

    “χ2(1) = 5.402, p = .020”

23 of 23

Self-check

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

Self-check results appear here once an independent check has confirmed them.

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Related

Authors
Ehmer, I., Crown, L., van Leeuwen, W., Feenstra, M., Willuhn, I., & Denys, D.
Affiliations
Netherlands Institute for Neuroscience (NL)
Corresponding author
Willuhn, I.
ORCID
Venue
eneuro
Publisher
Society for Neuroscience
Published
2020-03
Volume
7
Issue
2
Pages
ENEURO.0245-19.2020
ISSN
2373-2822 (ISSN-L)
DOI
10.1523/eneuro.0245-19.2020
PMC
PMC7189488
OpenAlex
W3014877521
Cited by
13
References
43
Citations by year
2026: 1 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 1 · 2019: 1
FWCI
0.80
Type
journal article
Language
en
Open access
Licence
Locations
  • eNeuro (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion, cc-by)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion, other-oa)
Funders
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek (864.14.010, 2015/06367/ALW)
  • EC | European Research Council (ERC-2014-STG 638013)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
obsessive-compulsive disorder, compulsivity, feedback processing, reward feedback, excessive grooming, compulsive grooming, extinction, instrumental behavior, genetic animal models
MeSH terms
Animals, Compulsive Behavior, Mice, Inbred C57BL, Nerve Tissue Proteins, Obsessive-Compulsive Disorder, Mice, Knockout, Mice

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 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

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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