Dopamine, time perception, and future time perspective

Abstract

Rationale Impairment in time perception, a critical component of decision-making, represents a risk factor for psychiatric conditions including substance abuse. A therapeutic that ameliorates this impairment could be advantageous in the treatment of impulsivity and decision-making disorders. Objectives Here we hypothesize that the catechol-O-methyltransferase (COMT) inhibitor tolcapone, which increases dopamine tone in frontal cortex (Ceravolo et al Synapse 43:201-207, 2002), improves time perception, with predictive behavioral, genetic, and neurobiological components. Methods Subjects (n = 66) completed a duration estimation task and other behavioral testing in each of two sessions after receiving a single oral dose of tolcapone (200 mg) or placebo in randomized, double-blind, counterbalanced, crossover fashion. Resting state fMRI data were obtained in a subset of subjects (n = 40). Subjects were also genotyped for the COMT (rs4680) polymorphism. Results Time perception was significantly improved across four proximal time points ranging from 5 to 60 s (T(524) = 2.04, p = 0.042). The degree of this improvement positively correlated with subjective measures of stress, depression, and alcohol consumption and was most robust in carriers of the COMT Val158 allele. Using seed regions defined by a previous metaanalysis (Wiener et al Neuroimage 49:1728-1740, 2010), we found not only that a connection from right inferior frontal gyrus (RIFG) to right putamen decreases in strength on tolcapone versus placebo (p < 0.05, corrected), but also that the strength of this decrease correlates inversely with the increase in duration estimation on tolcapone versus placebo (r = − 0.37, p = 0.02). Conclusions Compressed time perception can be ameliorated by administration of tolcapone. Additional studies should be conducted to determine whether COMT inhibitors may be effective in treating decision-making disorders and addictive behaviors.

Dopamine and Gambling Disorder: Prospects for Personalized Treatment

“…In controls, tolcapone reduced impulsivity in a fashion that varied inversely with an independent measure of baseline impulsivity, the Barratt Impulsiveness Scale (BIS) (66). Consistent with this influence, tolcapone also impacts other cognitive processes contributing to impulsivity: it improved the accuracy of time perception, specifically by ameliorating the tendency to consider specific time intervals to be longer than they actually are (88); and in keeping with influences on prospection, it increased exploratory over exploitative behaviors in subjects with the Met/Met COMT allele (89). In a pilot study of 17 subjects with gambling use disorder, tolcapone also decreased delay discounting in direct proportion to the cognitive subscale of the BIS, suggestive in combination with our previous data of an inverted Ushaped dopamine response (82).…”

The complexity of an artwork affects the subjective perception of time and bimanual motor activity performed in the presence and absence of music of the patients with Parkinson\'s disease

“…Consistent with the significant role of the BG and the dopaminergic system for the time perception Mitchell et al, 2018), our findings, showed an effect of dopaminergic medication on the duration judgment. PD patients on OFF medication underestimated the reproduction of the MCA manipulation time less than the LCA manipulation time.…”

Dopamine and Risky Decision-Making in Gambling Disorder

“…Tolcapone also reduced compulsivity in gamblers in proportion to its effect on fronto-parietal activity (Grant et al, 2013) and reduced temporal discounting in gamblers in proportion to its effect on fronto-striatal connectivity (Kayser et al, 2017). Further effects of tolcapone relate to improvements in decision-making and executive control (Farrell et al, 2012;Kayser et al, 2012Kayser et al, , 2015Mitchell et al, 2018).…”