Wagner, B. J. | bioRxiv Science

bioRxiv2020

Temporal discounting in adolescents and adults with Tourette syndrome

BackgroundTourette syndrome is a neurodevelopmental disorder with the clinical hallmarks of motor and phonic tics which are associated with hyperactivity in dopaminergic networks. Dopaminergic hyperactivity in the basal ganglia has previously been linked to increased sensitivity to positive reinforcement and increases in choice impulsivity. ObjectiveWe address whether this extends to changes in temporal discounting, where impulsivity is operationalized as an increased preference to choose smaller-but-sooner over larger-but-later rewards. Results are discussed with respect to neural models of temporal discounting, dopaminergic alterations in Tourette syndrome and the developmental trajectory of temporal discounting. MethodsIn the first study we included nineteen adolescent patients with Tourette syndrome and nineteen age- and education matched controls. In the second study, we compared twenty-five adult patients with Tourette syndrome and twenty-five age- and education-matched controls. ResultsIn the light of the dopaminergic hyperactivity model, we predicted differences in temporal discounting in patients with Tourette syndrome. However, computational modeling of choice behavior using hierarchical Bayesian parameter estimation revealed reduced impulsive choice in adolescent patients, and no group differences in adults. ConclusionWe speculate that adolescents might show reduced discounting due to improved inhibitory functions that also affect choice impulsivity and/or the developmental trajectory of executive control functions. The absence of an effect in adults might be due to differences in the clinical population (e.g. patients who acquired successful tic inhibition during adolescence might have gone into remission). Future studies would benefit from adopting longitudinal approaches to further elucidate the developmental trajectory of these effects.

neuroscience↗

bioRxiv2020

Dopaminergic modulation of human inter-temporal choice: a diffusion model analysis using the D2-receptor-antagonist haloperidol.

The neurotransmitter dopamine is implicated in diverse functions, including reward processing, reinforcement learning and cognitive control. The tendency to discount future rewards in value over time has long been discussed in the context of potential dopaminergic modulation. Here we examined the effect of a single dose of the D2 receptor antagonist Haloperidol (2mg) on temporal discounting. Our approach extends previous human pharmacological studies in two ways. First, we applied state-of-the-art computational modeling based on the drift diffusion model to comprehensively examine choice dynamics. Second, we examined dopaminergic modulation of reward magnitude effects on temporal discounting. Drift diffusion modeling revealed reduced temporal discounting and substantially faster non-decision times under Haloperidol. Temporal discounting was substantially increased for low vs. high reward magnitudes, but this magnitude effect was largely unaffected by Haloperidol. These results were corroborated by model-free analyses as well as modeling via more standard approaches using softmax action selection. We previously reported elevated caudate activation under Haloperidol in this sample of participants, supporting the idea that Haloperidol elevated dopamine neurotransmission, e.g. by blocking inhibitory feedback via presynaptic D2 autoreceptors. The present modeling results show that during inter-temporal choice, this leads to attenuated temporal discounting and increased response vigor (shorter non-decision times).

neuroscience↗