Executive control in Obsessive-Compulsive Disorder: A worldwide mega-analysis of task-based functional neuroimaging data of the ENIGMA-OCD consortium

Dzinalija, N.; Veer, I. M.; Simpson, H. B.; Ivanov, I.; Balachander, S.; Benedetti, F.; Calesella, F.; Fitzsimmons, S. M. D. D.; Grutzmann, R.; Hagen, K.; Hansen, B.; Heinzel, S.; Huijser, C.; Ipser, J. C.; Jaspers-Fayer, F.; de Joode, N. T.; Kathmann, N.; Kim, M.; Kwon, J. S.; Liu, W.; Lochner, C.; Martinez-Zalacain, I.; Menchon, J. M.; Narayanaswamy, J. C.; Olivier, I. S.; Postma, T. S.; Reddy, Y. C. J.; Soriano-Mas, C.; Stewart, S. E.; Thomopoulos, S. I.; Thorsen, A. L.; Vai, B.; Veltman, D. J.; Venkatasubramanian, G.; Voon, V.; Waller, L.; van der Werf, Y. D.; Zhao, Y.-J.; ENIGMA-OCD Conso

doi:10.1101/2025.08.20.671231

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bioRxiv · 10.1101/2025.08.20.671231

Executive control in Obsessive-Compulsive Disorder: A worldwide mega-analysis of task-based functional neuroimaging data of the ENIGMA-OCD consortium

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Abstract

ObjectiveObsessive-compulsive disorder (OCD) is associated with impaired executive function and altered activity in associated neural circuits, contributing to reduced goal-directed behavior. To investigate neural activation during executive control, we conducted a mega-analysis in the ENIGMA-OCD consortium pooling individual participant data from 475 individuals with OCD and 345 healthy controls across 15 fMRI tasks collected worldwide. MethodsIndividual participant data was uniformly processed using HALFpipe to construct voxelwise statistical images of executive control and task load contrasts. Parameter estimates extracted from regions of interest were entered into multilevel Bayesian models to examine regional and whole-brain effects of diagnosis, and, within OCD, the influence of medication status, symptom severity, and age of onset on task activation. ResultsWe observed a robust task activation pattern across individuals with OCD and control participants in executive control regions across tasks. Relative to controls, individuals with OCD showed moderate to very strong evidence of weaker activation of the dorsolateral prefrontal cortex, precuneus, frontal eye fields, and inferior parietal lobule during executive control (all positive posterior probabilities [P+]<0.1). Individuals with OCD also showed stronger activation in regions of the default mode network during executive function relative to controls. We found little evidence for differential activation during executive control in task- positive regions related to disease onset, severity and medication status. ConclusionIn the first mega-analysis of fMRI studies of executive function in OCD, we found strong evidence of weaker frontoparietal activation during executive control tasks. Our findings also suggest a failure of default mode network regions to appropriately disengage during task performance in OCD.

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Dzinalija, N., Veer, I. M., Simpson, H. B., Ivanov, I., Balachander, S., Benedetti, F., Calesella, F., Fitzsimmons, S. M. D. D., Grutzmann, R., Hagen, K., Hansen, B., Heinzel, S., Huijser, C., Ipser, J. C., Jaspers-Fayer, F., de Joode, N. T., Kathmann, N., Kim, M., Kwon, J. S., Liu, W., Lochner, C., Martinez-Zalacain, I., Menchon, J. M., Narayanaswamy, J. C., Olivier, I. S., Postma, T. S., Reddy, Y. C. J., Soriano-Mas, C., Stewart, S. E., Thomopoulos, S. I., Thorsen, A. L., Vai, B., Veltman, D. J., Venkatasubramanian, G., Voon, V., Waller, L., van der Werf, Y. D., Zhao, Y.-J., ENIGMA-OCD Conso. 2025-08-21. Executive control in Obsessive-Compulsive Disorder: A worldwide mega-analysis of task-based functional neuroimaging data of the ENIGMA-OCD consortium. https://doi.org/10.1101/2025.08.20.671231

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