Neurobiology and Psychophysiology of Impaired Fear Learning and Extinction Processes in Obsessive-Compulsive Disorder
Final Report Abstract
Obsessive-compulsive disorder (OCD) is characterized by recurrent, persistent thoughts and repetitive behaviors. These characteristic symptoms are usually causing considerably stress and anxiety. Previous studies showed altered activation in core regions of the fear circuitry in OCD, and fear learning as well as fear extinction can be assumed to constitute central mechanisms of the disorder. Given that cognitive behavioral therapies used to treat obsessions and compulsions in OCD are typically extinction-based we assumed that exploring fear conditioning (i.e., fear learning and extinction) in OCD might help to enhance therapeutic efficacy. Against this background, the planned project was designed to investigate the neural and psychophysiological correlates of fear conditioning and extinction and extinction recall in OCD using refined psychophysiological readouts (i.e., startle electromyography, pupillometry, SCR) and fMRI fear conditioning to investigate which mechanisms may be altered in association with these processes in patients with OCD. Against expectation, our findings did not show any differences between groups in any of the task phases or parameters, except for a trend towards higher startle amplitudes during extinction for OCD. We also did not detect any differences in brain activation between patients and healthy controls. Overall, our results did not provide evidence for differences in psychophysiology or brain activity using classical fear conditioning, challenging the assumption of generically impaired extinction learning and memory in OCD. Results of the project are not economically feasible but provide a relevant contribution to the field of OCD research.
Publications
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Association between hippocampus volume and symptom profiles in obsessive-compulsive disorder. Neuroimage Clin. 2017 Nov 8;17:474-480
Reess TJ, Rus OG, Gürsel DA, Schmitz-Koep B, Wagner G, Berberich G, Koch K
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Frontoparietal areas link impairments of large-scale intrinsic brain networks with aberrant fronto-striatal interactions in OCD: a meta analysis of resting-state functional connectivity. Neurosci Biobehav Rev. 2018 Apr;87:151-160
Gürsel DA, Avram M, Sorg C, Brandl F, Koch K
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Increased Default Mode Network Connectivity in Obsessive-Compulsive Disorder During Reward Processing. Front Psychiatry. 2018 Jun 12;9:254
Koch K, Reeß TJ, Rus OG, Gürsel DA, Wagner G, Berberich G, Zimmer C
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Network based decoupling of local gyrification in obsessive-compulsive disorder. Hum Brain Mapp. 2018 Aug;39(8):3216-3226
Reess TJ, Rus OG, Gürsel DA, Schmitz-Koep B, Wagner G, Berberich G, Koch K
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Shared vulnerability for connectome alterations across psychiatric and neurological brain disorders. Nat Hum Behav. 2019 Sep;3(9):988-998
de Lange SC, Scholtens LH; Alzheimer’s Disease Neuroimaging Initiative, van den Berg LH, Boks MP, Bozzali M, Cahn W, Dannlowski U, Durston S, Geuze E, van Haren NEM, Hillegers MHJ, Koch K, Jurado MÁ, Mancini M, Marqués-Iturria I, Meinert S, Ophoff RA, Reess TJ, Repple J, Kahn RS, van den Heuvel MP
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Frontoparietal and salience network alterations in obsessive–compulsive disorder: insights from independent component and sliding time window analyses. J Psychiatry Neurosci. 2020 May 1;45(3):214-221
Gürsel DA, Reinholz L, Bremer B, Schmitz-Koep B, Franzmeier N, Avram M, Koch K
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Mapping Cortical and Subcortical Asymmetry in Obsessive-Compulsive Disorder: Findings From the ENIGMA Consortium. Biol Psychiatry. 2020 Jun 15;87(12):1022-1034
Kong XZ, ..., Yun JY; ENIGMA OCD Working Group, Thompson PM, Stein DJ, van den Heuvel OA, Francks C
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Homogeneous grey matter patterns in patients with obsessive-compulsive disorder. Neuroimage Clin. 2021 Jun 13;31:102727
Koch K, Rodriguez-Manrique D, Rus-Oswald OG, Gürsel DA, Berberich G, Kunz M, Zimmer C
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An overview of the first 5 years of the ENIGMA obsessive-compulsive disorder working group: The power of worldwide collaboration. Hum Brain Mapp. 2022 Jan;43(1):23-36
van den Heuvel OA, Boedhoe PSW, Bertolin S, Bruin WB, Francks C, Ivanov I, Jahanshad N, Kong XZ, Kwon JS, O'Neill J, Paus T, Patel Y, Piras F, Schmaal L, Soriano-Mas C, Spalletta G, van Wingen GA, Yun JY, Vriend C, Simpson HB, van Rooij D, Hoexter MQ, Hoogman M, Buitelaar JK, Arnold P, Beucke JC, Benedetti F, Bollettini I, Bose A, Brennan BP, De Nadai AS, Fitzgerald K, Gruner P, Grünblatt E, Hirano Y, Huyser C, James A, Koch K, Kvale G, Lazaro L, Lochner C, Marsh R, Mataix-Cols D, Morgado P, Nakamae T, Nakao T, Narayanaswamy JC, Nurmi E, Pittenger C, Reddy YCJ, Sato JR, Soreni N, Stewart SE, Taylor SF, Tolin D, Thomopoulos SI, Veltman DJ, Venkatasubramanian G, Walitza S, Wang Z, Thompson PM, Stein DJ; ENIGMA-OCD working group
