Immediate Reward Bias in Humans: Fronto-Parietal Networks and a Role for the Catechol-O-Methyltransferase 158^Val/ValGenotype

Abstract

The tendency to choose lesser immediate benefits over greater long-term benefits characterizes alcoholism and other addictive disorders. However, despite its medical and socioeconomic importance, little is known about its neurobiological mechanisms. . These studies assume "hot" and "cool" response selection systems, with the hot system proposed to generate impulsive choices in the presence of a proximate reward. However, to date, brain regions in which the magnitude of activity during decision making reliably predicts intertemporal choice behavior have not been identified. Here we address this question in sober alcoholics and non-substance-abusing control subjects and show that immediate reward bias directly scales with the magnitude of functional magnetic resonance imaging bold oxygen leveldependent (BOLD) signal during decision making at sites within the posterior parietal cortex (PPC), dorsal prefrontal cortex (dPFC), and rostral parahippocampal gyrus regions. Conversely, the tendency of an individual to wait for a larger, delayed reward correlates directly with BOLD signal in the lateral orbitofrontal cortex. In addition, genotype at the Val158Met polymorphism of the catechol-Omethyltransferase gene predicts both impulsive choice behavior and activity levels in the dPFC and PPC during decision making. These genotype effects remained significant after controlling for alcohol abuse history. These results shed new light on the neurobiological underpinnings of temporal discounting behavior and identify novel behavioral and neural consequences of genetic variation in dopamine metabolism.

Anorexia Nervosa and Obesity are Associated with Opposite Brain Reward Response

“…This area was less responsive to food receipt in OB individuals (Gearhardt et al, 2011), and it was hypothesized that lower response in that region could be associated with reduced behavior control and suppression of reward response (Boettiger et al, 2007;Elliott et al, 2000;Goldstein et al, 2007). Reduced lateral orbitofrontal cortex activation in OB may then be associated with reduced, and increased activation in AN could be associated with increased impulse control to reward presentation.…”

Dopamine, Corticostriatal Connectivity, and Intertemporal Choice

“…Conversely, Pine et al (2010) demonstrated that relative to placebo, control subjects given the dopamine precursor L-dopa showed consistent increases in delay discounting. In addition, the genotype for the dopamine-degrading enzyme catechol-Omethyltransferase (COMT) correlates with levels of impulsivity: subjects tend to be more impulsive if they have alleles encoding the more enzymatically active form of COMT (Boettiger et al, 2007). Because COMT represents the primary route for dopamine degradation in frontal cortex (Gogos et al, 1998), lower dopamine tone in frontal cortex may therefore predispose some individuals to greater impulsivity.…”

Ethanol Reduces Neuronal Excitability of Lateral Orbitofrontal Cortex Neurons Via a Glycine Receptor Dependent Mechanism

“…The orbitofrontal cortex (OFC), a region within the prefrontal cortex (PFC), mediates several aspects of learning, including choice behavior (Boettiger et al, 2007;Bokura et al, 2001;Ramus and Eichenbaum, 2000;Roesch et al, 2007a;Schoenbaum et al, 1998), reversal learning (Dalley et al, 2004;McGaughy et al, 2008;Roesch et al, 2007b;Thorpe et al, 1983) and the development of expectancies/predictions (Ito et al, 2001;Tremblay and Schultz, 1999) about appetitive and aversive stimuli. Current thinking suggests that the OFC, with its extensive array of sensory and limbic derived inputs, mediates learning processes and specifically choice behavior by providing a place for incoming information to be integrated and by attributing salience to relevant environmental cues.…”