Immediate reward bias in humans: fronto-parietal networks and a role for the catechol-O-methyltransferase 158(Val/Val) genotype

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. Brain regions that are activated when deciding between immediate or delayed rewards have been identified (McClure et al., 2004, 2007), as have areas in which responses to reward stimuli predict a paper-and-pencil measure of temporal discounting (Hariri et al., 2006). 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 level-dependent (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-O-methyltransferase 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.

Figure 1.

Illustration of behavioral paradigm. A, The temporal sequence of events are shown for one example W trial. Illumination of a fixation point (Ready) indicated the initiation of each trial. The instruction cue was then displayed for 4.4 s, alerting the subject to the upcoming trial type. The two options (Now and Later) were then presented while the instruction cue remained on the screen. The specific dollar amounts (from $1 to $100) and the time of availability (from the day of the experiment to 6 months later) varied across trials, as did the differences between each option. The choices remained on the screen for 4.4 s; however, subjects had a total of 6.6 s to indicate their choice after the appearance of the two options. ITI, Intertrial interval. B, Depiction of the four trial types. The appearance of each option pair was preceded by a cue that indicated trial type, instructing the subject how to select between the Now and Later options. For W trials, subjects were to select the option they preferred. The SOONER (S) and LARGER (L) trials served to control for activity that reflected objective comparison of the two options, rather than subjective preference; these are considered together as CON trials. To assess the ability of the subjects to control unintended motor responses, we included trial type DW, in which subjects were instructed to choose the option they preferred and then press the button corresponding to the opposite choice.

Figure 2.

Behavioral results. A, Ratio of impulsive (Now) choices as a function of subject group. The AA group made significantly more impulsive choices (0.74 > 0.26; *p = 0.002; t₍₁₇₎ = 3.56) than the CS group. Error bars denote SEM. A value of 0 represents always choosing Later over Now, whereas a value of 1 represents the converse. B, Standardized ICR for each subject in rank order. Units are in SDs, with mean equal to 0. ◇, AA; ◆, CS.

Figure 3.

Selection of impulsive choice across subjects: fMRI correlation analysis. Brain regions showing a significant positive correlation between activity during subjective Now versus Later decision making and ICR. Brain activity indices derived from the subjective choice contrast (W − CON); see Materials and Methods for greater detail. A, MNI space coordinates (x, y, z) and t values for the PPC (top; 66, −42, 44; t = 5.03), dPFC (middle; −22, 50, 44; t = 3.79), and PHG (bottom; 18, −4, −28; t = 4). Criterion threshold was p < 0.001 (uncorrected), with a minimum cluster size of five contiguous voxels; results are shown at p < 0.005 for display purposes. These data also survived permutation-based voxelwise correction of familywise error (p < 0.05). L, Left. B, Corresponding correlation plots for each subject's contrast parameter estimate (an index of relative activity) versus ICR for the peak of each region identified at left; the peak regression statistic is displayed in each plot.

Figure 4.

Suppression of impulsive choice across subjects: fMRI correlation analysis. The sole brain region showing a significant negative correlation between activity during subjective Now versus Later decision making and ICR. Methods and conventions are as for Figure 3. A, Right lateral OFC (8, 36, −10; t = 4.13). L, Left. B, Plot of each subject's OFC Now versus Later subjective decision-making parameter estimate as a function of ICR for the peak of the region displayed at left; the peak regression statistic displayed in plot.

Figure 5.

Genotype at the COMT 158 locus predicts impulsive choice behavior. The ratio of impulsive choices as a function of genotype is shown. There was a significant main effect of genotype at the COMT 158 locus on impulsive choice probability, even after controlling for the effects attributable to group (AA vs CS; ANCOVA, F_(2,21) = 5.181, p = 0.015). The 158^Val/Val genotype was associated with significantly more frequent selections of Now over Later than were the other two genotypes (p = 0.012), which did not significantly differ from one another (p = 0.144). Error bars denote SEM. m/m, 158^Met/Met; v/m, 158^Val/Met; v/v, 158^Val/Val.

Figure 6.

COMT 158^Val/Val genotype predicts hyperactivation in the dPFC and PPC during decision making. Parameter estimates indexing brain activity during Now versus Later subjective decision making as a function of the COMT Val158Met genotype within the dPFC and PPC ROI (averaged across voxels). There was a significant main effect of genotype at the COMT 158 locus on BOLD signal in both regions, even after controlling for subject group effects (ANCOVA; dPFC, F_(2,15) = 3.834, p = 0.045; PPC: F_(2,15) = 5.911, p = 0.013). The 158^Val/Val (v/v) genotype was associated with significantly greater activation in the dPFC and PPC during subjective decision making (dPFC, p = 0.026; PPC, p = 0.005). Error bars denote SEM. m/m, 158^Met/Met; v/m, 158^Val/Met; v/v, 158^Val/Val.