Dopamine, Corticostriatal Connectivity, and Intertemporal Choice

Abstract

Value-based decisions optimize behavioral outcomes. Because delayed rewards are discounted, an increased tendency to choose smaller, immediate rewards can lead to suboptimal choice. Steep discounting of delayed rewards (impulsivity) characterizes subjects with frontal lobe damage and behavioral disorders including substance abuse. Correspondingly, animal studies and indirect evidence in humans suggest that lower dopamine in the frontal cortex contributes to steeper discounting by impairing corticostriatal function. To test this hypothesis directly, we performed a randomized, double-blind, counterbalanced, placebo-controlled study in which we administered the brain penetrant catechol-O-methyltransferase inhibitor tolcapone or placebo to healthy subjects performing a delay discounting task. Tolcapone significantly increased choice of delayed monetary rewards, and this tolcapone-induced increase covaried with increased BOLD activity in the left ventral putamen and anterior insula. Tolcapone also changed corticostriatal connectivity: specifically, by inducing a decrease in the coherence between ventral putamen and pregenual cingulate cortex. These results indicate that raising cortical dopamine levels attenuates impulsive choice by changing corticostriatal function.

Dopamine Modulation of Intertemporal Decision-making: Evidence from Parkinson Disease

“…Previous work has causally implicated the lateral pFC in farsighted decisions (Figner et al, 2010), and pFC dopamine levels may influence baseline activity levels underlying individual differences in intertemporal choice (Gianotti, Figner, Ebstein, & Knoch, 2012). It is tempting to speculate that dopaminergic modulation of the lateral pFC could have played a role in biasing the choices of Parkinson's disease patients on medication toward farsightedness, consistent with results reporting increased patience because of selective increases in pFC dopamine (Kayser et al, 2012). Because pFC receives dopaminergic projections from the ventral tegmental area, which is not severely affected in the early stages of Parkinson's disease (relative to the substantia nigra), it is possible that dopaminergic medication enhances dopamine levels in pFC in Parkinson's disease patients to an extent that results in farsightedness even beyond that of healthy controls.…”

Modulation of impulsivity and reward sensitivity in intertemporal choice by striatal and midbrain dopamine synthesis in healthy adults

“…Another recent PET paper examining temporal discounting in pathological gamblers and patients with Parkinson's disease also included a small sample of control subjects, again with a very large age range [coefficient of variation (CV) Ͼ3 times larger than the age CV for our study], finding no significant relationships among control subjects but significant correlations between ventral striatal DA and Now bias among gamblers and between putamen DA and Now bias among Parkinson's patients. Third, the degree to which tolcapone, a COMT inhibitor, increases activity in the putamen during Now/Later choices significantly correlated with decreased Now bias on tolcapone in healthy adults (Kayser et al 2012). In addition, fMRI data collected during intertemporal choice suggests that the dorsal striatum is involved in integrating subjective valuation systems sensitive to reward delay and magnitude, providing an overall value metric to guide choice behavior (Pine et al 2009).…”

“…First, the Val 158 Met polymorphism (rs4680) in the gene encoding the catechol-O-methyltransferase (COMT) enzyme, which regulates tonic frontal DA (Gogos et al 1998;Kaenmaki et al 2010;Karoum et al 1994;Slifstein et al 2008;Wu et al 2012), predicts Now bias, with putatively lower tonic frontal DA being associated with greater Now bias among adults (Boettiger et al 2007;Smith and Boettiger 2012). Moreover, COMT inhibition reduces Now bias (Kayser et al 2012), and COMT genotype predicts the effects of acute changes in DA signaling on Now bias, according to a U-shaped model, with both low and high DA extremes predicting greater Now bias (Kelm and Boettiger 2013;Smith et al 2014).…”

“…Two more recent reports from primarily clinical samples also support a role for lower subcortical DA being associated with increased Now bias (Ballard et al 2015;Joutsa et al 2015), although neither study included substantial numbers of healthy nonsmoking young adults. Notably, the degree to which COMT inhibition decreases synchrony between the putamen and the pregenual anterior cingulate cortex (pgACC) during Now/Later choices predicts how much COMT inhibition decreases Now bias (Kayser et al 2012). COMT inhibition decreases Now bias more among more impulsive people, who in turn have lower DAT availability in the putamen (Costa et al 2013) and both diminished midbrain D 2 /D 3 autoreceptor binding and elevated amphetamine-induced striatal DA release (Buckholtz et al 2010).…”

Meditation-induced bliss viewed as release from conditioned neural (thought) patterns that block reward signals in the brain pleasure center

“…The anterior insula functions in error awareness (Klein, Ullsperger, & Danielmeier, 2013). ''Increased cortical dopamine levels increases BOLD activity in anterior insula and attenuates impulsive choice'' (Kayser, Allen, Navarro-Cebrian, Mitchell, & Fields, 2012). The insular cortex is well positioned to initiate alterations in emotional and self-referential processing, decrease error prediction (thereby increasing certainty), and up-regulate impulse control.…”