Fronto-striatal structures related with model-based control as an endophenotype for obsessive–compulsive disorder

Kasal, Meltem I.; Beşiroğlu, Lütfullah; Zorlu, Nabi; Dikmeer, Nur; Bilge, Aslıhan; Durmaz, Ercan; Polat, Serap; Gelal, Fazıl; Rapp, Michael A.; Heinz, Andreas; Sebold, Miriam

doi:10.1038/s41598-021-91179-2

Cited by 4 publications

(4 citation statements)

References 57 publications

(75 reference statements)

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“…This may support previous findings of a disrupted arbitration mechanism in OCD patients (28,51) and might potentially be responsible for the dominance of habitual behaviours in OCD. In line with our findings, past studies have also found structural and functional alterations within the fronto-striatal circuits, particularly the mPFC, putamen and caudate responsible for the imbalance between model-free and model-based decision-making in OCD (28,52). Additionally, the mPFC is a crucial part of the dorsal cognitive CSTC circuit which contributes to habit formation and compulsivity in OCD (53).…”

Section: Discussionsupporting

confidence: 91%

Altered model-based prediction error signalling in the medial prefrontal cortex in patients with obsessive-compulsive disorder: An fMRI study

Sen,

Koch,

Schmitz-Koep

et al. 2024

Preprint

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BackgroundCompared to healthy individuals, patients with obsessive-compulsive disorder (OCD) are found to rely more on model-free decision-making strategies which may underlie symptom expression. It is, however, unclear whether these behavioural differences are represented in neural alterations of model-free and model-based decision-making when tested simultaneously.MethodsWe investigated the neural signatures of 22 OCD patients and 22 matched controls who completed a two-step Markov decision-making task during functional MRI scanning. We used hierarchical Bayesian modelling and Bayesian statistics to examine model-based and model-free decision-making behaviours. Parametric regressors were employed for model-free and model-based reward prediction errors to inform neural reward presentation, which we analysed using a Bayesian Multilevel Modeling (BML) approach. Associations between significant activations and symptoms as well as cognitive scores were explored using Bayesian linear regression.ResultsWhile controls received significantly more rewards and were significantly less stochastic compared to patients, both groups similarly relied on model-free decision-making strategies. Importantly, our group comparison of neural reward prediction error responses showed greater activation for model-based reward prediction error in the medial prefrontal cortex (mPFC) in OCD patients compared to controls, but no differences for model-free reward prediction error processing. Increased mPFC activity was associated with lower depressive symptoms but not with other clinical or cognitive scores.ConclusionThese findings support the notion that OCD is associated with a bias towards habitual behaviour, which may be expressed through altered mPFC activity underlying goal-directed behaviour. Tackling the hyperactivity on the mPFC may provide a new target for optimised treatment and interventions.

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Section: Discussionsupporting

confidence: 91%

Altered model-based prediction error signalling in the medial prefrontal cortex in patients with obsessive-compulsive disorder: An fMRI study

Sen,

Koch,

Schmitz-Koep

et al. 2024

Preprint

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“…Although they achieved the same nestlet score as the other genotypes by 24 hours, they also used less of the nestlet overall compared to Ptprd WT and HT mice (Fig 4B). Future studies will evaluate Ptprd KO mice in a probabilistic learning task (PLT) which can be used to measure goal-directed versus habitual decision-making strategies in both rodent and humans [79,80], with OCD patients showing a shift towards habitual choices in this paradigm [81,82].…”

Section: Plos Onementioning

confidence: 99%

Mice lacking Ptprd exhibit deficits in goal-directed behavior and female-specific impairments in sensorimotor gating

Welch

Thompson

et al. 2023

PLoS ONE

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Protein Tyrosine Phosphatase receptor type D (PTPRD) is a member of the protein tyrosine phosphatase family that mediates cell adhesion and synaptic specification. Genetic studies have linked Ptprd to several neuropsychiatric phenotypes, including Restless Leg Syndrome (RLS), opioid abuse disorder, and antipsychotic-induced weight gain. Genome-wide association studies (GWAS) of either pediatric obsessive-compulsive traits, or Obsessive-Compulsive Disorder (OCD), have identified loci near PTPRD as genome-wide significant, or strongly suggestive for this trait. We assessed Ptprd wild-type (WT), heterozygous (HT), and knockout (KO) mice for behavioral dimensions that are altered in OCD, including anxiety and exploration (open field test, dig test), perseverative behavior (splash-induced grooming, spatial d), sensorimotor gating (prepulse inhibition), and home cage goal-directed behavior (nest building). No effect of genotype was observed in any measure of the open field test, dig test, or splash test. However, Ptprd KO mice of both sexes showed impairments in nest building behavior. Finally, female, but not male, Ptprd KO mice showed deficits in prepulse inhibition, an operational measure of sensorimotor gating that is reduced in female, but not male, OCD patients. Our results indicate that constitutive lack of Ptprd may contribute to the development of certain domains that are altered OCD, including goal-directed behavior, and reduced sensorimotor gating specifically in females.

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“…The DLPFC is involved in executive functions and emotion regulation ( 69 ). It is a key node in the FPN involved in cognitive control and the fronto-striatal loop in habitual behavior ( 70 , 71 ). The decreased FC in the bilateral DLPFC may indicate a top-down disruption between these networks and underlie the pathophysiology and clinical symptoms of OCD ( 72 ).…”

Section: Discussionmentioning

confidence: 99%

Convergent functional change of frontoparietal network in obsessive-compulsive disorder: a voxel-based meta-analysis

Yu,

Xu,

et al. 2024

Front. Psychiatry

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BackgroundObsessive-compulsive disorder (OCD) is a chronic psychiatric illness with complex clinical manifestations. Cognitive dysfunction may underlie OC symptoms. The frontoparietal network (FPN) is a key region involved in cognitive control. However, the findings of impaired FPN regions have been inconsistent. We employed meta-analysis to identify the fMRI-specific abnormalities of the FPN in OCD.MethodsPubMed, Web of Science, Scopus, and EBSCOhost were searched to screen resting-state functional magnetic resonance imaging (rs-fMRI) studies exploring dysfunction in the FPN of OCD patients using three indicators: the amplitude of low-frequency fluctuation/fractional amplitude of low-frequency fluctuation (ALFF/fALFF), regional homogeneity (ReHo) and functional connectivity (FC). We compared all patients with OCD and control group in a primary analysis, and divided the studies by medication in secondary meta-analyses with the activation likelihood estimation (ALE) algorithm.ResultsA total of 31 eligible studies with 1359 OCD patients (756 men) and 1360 healthy controls (733 men) were included in the primary meta-analysis. We concluded specific changes in brain regions of FPN, mainly in the left dorsolateral prefrontal cortex (DLPFC, BA9), left inferior frontal gyrus (IFG, BA47), left superior temporal gyrus (STG, BA38), right posterior cingulate cortex (PCC, BA29), right inferior parietal lobule (IPL, BA40) and bilateral caudate. Additionally, altered connectivity within- and between-FPN were observed in the bilateral DLPFC, right cingulate gyrus and right thalamus. The secondary analyses showed improved convergence relative to the primary analysis.ConclusionOCD patients showed dysfunction FPN, including impaired local important nodal brain regions and hypoconnectivity within the FPN (mainly in the bilateral DLPFC), during the resting state. Moreover, FPN appears to interact with the salience network (SN) and default mode network (DMN) through pivotal brain regions. Consistent with the hypothesis of fronto-striatal circuit dysfunction, especially in the dorsal cognitive circuit, these findings provide strong evidence for integrating two pathophysiological models of OCD.

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Fronto-striatal structures related with model-based control as an endophenotype for obsessive–compulsive disorder

Cited by 4 publications

References 57 publications

Altered model-based prediction error signalling in the medial prefrontal cortex in patients with obsessive-compulsive disorder: An fMRI study

Altered model-based prediction error signalling in the medial prefrontal cortex in patients with obsessive-compulsive disorder: An fMRI study

Mice lacking Ptprd exhibit deficits in goal-directed behavior and female-specific impairments in sensorimotor gating

Convergent functional change of frontoparietal network in obsessive-compulsive disorder: a voxel-based meta-analysis

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