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The motivational determinants of human action, their neural bases and functional impact in adolescents with OCD

Iain E. Perkes, Richard W. Morris, Kristi R. Griffiths, Stephanie Quail, Felicity Waters, Margo O’Brien, Philip L. Hazell, Bernard W. Balleine

Biological Psychiatry Global Open Science

December 2022

Abstract

Background
Establishing the motivational influences on human action is essential for understanding choice and decision-making in health and disease. Here we used tests of value-based decision-making, manipulating both predicted and experienced reward values to assess the motivational control of goal-directed action in healthy adolescents and those with obsessive-compulsive disorder (OCD).

Methods
After instrumental training on a two action-two outcome probabilistic task, adolescents (n=21) underwent Pavlovian conditioning using distinct stimuli predicting either the instrumental outcomes, a third outcome or nothing. We then assessed fMRI during choice tests in which we varied predicted value, using specific and general Pavlovian-instrumental transfer (PIT), and experienced value, using outcome devaluation. To establish functional significance, we tested a matched cohort of adolescents with OCD (n=20).

Results
In healthy adolescents both predicted and experienced values influenced the performance of goal-directed actions, mediated by distinct orbitofrontal (OFC)-striatal circuits involving the lateral-OFC and medial-OFC respectively. In adolescents with OCD, however, choice was insensitive to changes in either predicted or experienced values. These impairments were related to hypoactivity in the lateral OFC and hyperactivity in medial OFC during specific PIT and hypoactivity in anterior prefrontal cortex, caudate nucleus and their connectivity in the devaluation test.

Discussion
We found, therefore, that predicted and experienced values exerted a potent influence on the performance of goal-directed actions in adolescents via distinct orbitofrontal- and prefrontal-striatal circuits. Furthermore, the influence of these motivational processes was severely blunted in OCD as was the functional segregation of circuits involving medial and lateral OFC, producing dysregulated action control.

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