Altered model-based prediction error signaling in the lateral orbitofrontal cortex in patients with obsessive-compulsive disorder: An fMRI study

Background: Compared 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 behavioral differences are represented in neural alterations of...

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Main Authors: Pritha Sen, Kathrin Koch, Benita Schmitz-Koep, Deniz Gürsel, Franziska Knolle
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:NeuroImage
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Online Access:http://www.sciencedirect.com/science/article/pii/S1053811925003611
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author Pritha Sen
Kathrin Koch
Benita Schmitz-Koep
Deniz Gürsel
Franziska Knolle
author_facet Pritha Sen
Kathrin Koch
Benita Schmitz-Koep
Deniz Gürsel
Franziska Knolle
author_sort Pritha Sen
collection DOAJ
description Background: Compared 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 behavioral differences are represented in neural alterations of model-free and model-based decision-making when tested simultaneously. Methods: We 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 behaviors. Parametric regressors were employed for model-free and model-based reward prediction errors to inform neural reward presentation, which we analyzed using a Bayesian Multilevel Modeling (BML) approach. Associations between significant activations and symptoms as well as cognitive scores were explored using Bayesian linear regression. Results: While 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 lateral orbitofrontal cortex (lateral OFC) in OCD patients compared to controls, but no differences for model-free reward prediction error processing. Increased lateral OFC activity was associated with lower obsessive symptoms and better cognitive functioning. Conclusion: These findings support the notion that OCD is associated with an altered goal-directed system, which may be expressed through increased activation in the lateral OFC activity underlying goal-directed behavior. Importantly, the hyperactivity observed in this region was linked to reduced obsessive symptoms and improved cognitive functioning, potentially indicating compensatory mechanisms and highlighting the lateral OFC as a potential target for future interventions.
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spelling doaj-art-240fbc4d9a7240f1ba531ce5870d694c2025-08-20T03:50:01ZengElsevierNeuroImage1095-95722025-08-0131712135810.1016/j.neuroimage.2025.121358Altered model-based prediction error signaling in the lateral orbitofrontal cortex in patients with obsessive-compulsive disorder: An fMRI studyPritha Sen0Kathrin Koch1Benita Schmitz-Koep2Deniz Gürsel3Franziska Knolle4School of Medicine and Health, Department of Diagnostic and Interventional Neuroradiology, Technical University of Munich, Munich, Germany; School of Medicine and Health, TUM-NIC Neuroimaging Center, Technical University of Munich, Munich, Germany; Graduate School of Systemic Neurosciences, Ludwig Maximilian University, Munich, GermanySchool of Medicine and Health, Department of Diagnostic and Interventional Neuroradiology, Technical University of Munich, Munich, Germany; School of Medicine and Health, TUM-NIC Neuroimaging Center, Technical University of Munich, Munich, GermanySchool of Medicine and Health, Department of Diagnostic and Interventional Neuroradiology, Technical University of Munich, Munich, Germany; School of Medicine and Health, TUM-NIC Neuroimaging Center, Technical University of Munich, Munich, GermanySchool of Medicine and Health, Department of Diagnostic and Interventional Neuroradiology, Technical University of Munich, Munich, Germany; School of Medicine and Health, TUM-NIC Neuroimaging Center, Technical University of Munich, Munich, GermanySchool of Medicine and Health, Department of Diagnostic and Interventional Neuroradiology, Technical University of Munich, Munich, Germany; School of Medicine and Health, TUM-NIC Neuroimaging Center, Technical University of Munich, Munich, Germany; Corresponding author at: Department of Diagnostic and Interventional Neuroradiology, School of Medicine and Health, Klinikum rechts der Isar, Technical University Munich, 81675 Munich, Germany.Background: Compared 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 behavioral differences are represented in neural alterations of model-free and model-based decision-making when tested simultaneously. Methods: We 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 behaviors. Parametric regressors were employed for model-free and model-based reward prediction errors to inform neural reward presentation, which we analyzed using a Bayesian Multilevel Modeling (BML) approach. Associations between significant activations and symptoms as well as cognitive scores were explored using Bayesian linear regression. Results: While 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 lateral orbitofrontal cortex (lateral OFC) in OCD patients compared to controls, but no differences for model-free reward prediction error processing. Increased lateral OFC activity was associated with lower obsessive symptoms and better cognitive functioning. Conclusion: These findings support the notion that OCD is associated with an altered goal-directed system, which may be expressed through increased activation in the lateral OFC activity underlying goal-directed behavior. Importantly, the hyperactivity observed in this region was linked to reduced obsessive symptoms and improved cognitive functioning, potentially indicating compensatory mechanisms and highlighting the lateral OFC as a potential target for future interventions.http://www.sciencedirect.com/science/article/pii/S1053811925003611Two-step taskLateral orbitofrontal cortexGoal-directed decisionsComputational psychiatryNeuropsychiatric disorders
spellingShingle Pritha Sen
Kathrin Koch
Benita Schmitz-Koep
Deniz Gürsel
Franziska Knolle
Altered model-based prediction error signaling in the lateral orbitofrontal cortex in patients with obsessive-compulsive disorder: An fMRI study
NeuroImage
Two-step task
Lateral orbitofrontal cortex
Goal-directed decisions
Computational psychiatry
Neuropsychiatric disorders
title Altered model-based prediction error signaling in the lateral orbitofrontal cortex in patients with obsessive-compulsive disorder: An fMRI study
title_full Altered model-based prediction error signaling in the lateral orbitofrontal cortex in patients with obsessive-compulsive disorder: An fMRI study
title_fullStr Altered model-based prediction error signaling in the lateral orbitofrontal cortex in patients with obsessive-compulsive disorder: An fMRI study
title_full_unstemmed Altered model-based prediction error signaling in the lateral orbitofrontal cortex in patients with obsessive-compulsive disorder: An fMRI study
title_short Altered model-based prediction error signaling in the lateral orbitofrontal cortex in patients with obsessive-compulsive disorder: An fMRI study
title_sort altered model based prediction error signaling in the lateral orbitofrontal cortex in patients with obsessive compulsive disorder an fmri study
topic Two-step task
Lateral orbitofrontal cortex
Goal-directed decisions
Computational psychiatry
Neuropsychiatric disorders
url http://www.sciencedirect.com/science/article/pii/S1053811925003611
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