Why some people discount more than others: baseline activation in the dorsal PFC mediates the link between COMT genotype and impatient choice

Abstract

Individuals differ widely in how steeply they discount future rewards. The sources of these stable individual differences in delay discounting (DD) are largely unknown. One candidate is the COMT Val158Met polymorphism, known to modulate prefrontal dopamine levels and affect DD. To identify possible neural mechanisms by which this polymorphism may contribute to stable individual DD differences, we measured 73 participants’ neural baseline activation using resting electroencephalogram (EEG). Such neural baseline activation measures are highly heritable and stable over time, thus an ideal endophenotype candidate to explain how genes may influence behavior via individual differences in neural function. After EEG-recording, participants made a series of incentive-compatible intertemporal choices to determine the steepness of their DD. We found that COMT significantly affected DD and that this effect was mediated by baseline activation level in the left dorsal prefrontal cortex (DPFC): (i) COMT had a significant effect on DD such that the number of Val alleles was positively correlated with steeper DD (higher numbers of Val alleles means greater COMT activity and thus lower dopamine levels). (ii) A whole-brain search identified a cluster in left DPFC where baseline activation was correlated with DD; lower activation was associated with steeper DD. (iii) COMT had a significant effect on the baseline activation level in this left DPFC cluster such that a higher number of Val alleles was associated with lower baseline activation. (iv) The effect of COMT on DD was explained by the mediating effect of neural baseline activation in the left DPFC cluster. Our study thus establishes baseline activation level in left DPFC as salient neural signature in the form of an endophenotype that mediates the link between COMT and DD.

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

“…Our results are compatible with both points of view and, together with prior work showing increased impulsivity in young adults administered L-dopa (Pine et al, 2010), suggest that increasing dopamine levels in the striatum may affect young and old adults differentially, with greater benefits for farsighted choice in older adults (as found in the current study). 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).…”

“…Consistent with this idea, some studies found dose-or population-dependent effects (Floresco et al, 2008;Bizot et al, 2007;Cardinal et al, 2000). Such baseline differences (see also Gianotti et al, 2012;Eisenegger et al, 2010) may explain why Pine et al (2010) found that L-dopa increased temporal impulsivity. In healthy young participants, administering L-dopa may result in overdosing of frontostriatal circuits depending on individual differences in baseline dopamine levels (Kayser et al, 2012;Clatworthy et al, 2009;Cools, Sheridan, Jacobs, & D'Esposito, 2007).…”

Mesocorticolimbic dopamine functioning in primary psychopathy: A source of within-group heterogeneity

“…Since both Met-and Val-homozygosity have been related to increased striatal DA activations to reward-feedback or reward-predictive cues (Yacubian et al, 2007;Dreher et al, 2009;Camara et al, 2010;Lancaster et al, 2012;Katz et al, 2014), immediate response bias/delay discounting (Boettiger et al, 2007;Paloyelis et al, 2010;Gianotti et al, 2012;Smith and Boettiger, 2012), impulsivity (Salo et al, 2010;Groleau et al, 2012;Varga et al, 2012;Malloy-Diniz et al, 2013;Soeiro-DeSouza et al, 2013;Guillot et al, 2014), and aggression (Rujescu et al, 2003;Caspi et al, 2008;Albaugh et al, 2010;Wagner et al, 2010;Brennan et al, 2011), the effect of COMT genotypes on disinhibitory traits is likely modulated by other factors such as tonic striatal DA activity and D2-receptor densities. For example, Reuter et al (2006) demonstrated that BAS scores correlate with the relative ratio between PFC DA activity as mediated by COMT and striatal DA activity/D2-receptor functioning as mediated by the TaqIA-ANKK1 SNP.…”

Does Power Increase Self-Control? Episodic Priming May Not Provide the Answer

“…It has successfully been used in pathological (e.g., substance addicts, MacKillop, Amlung, Few, Ray, Sweet, & Munafò, 2011; pathological gamblers, Dixon, Marley, & Jacobs, 2003) as well as in normal populations, in student as well as non-student populations (e.g., Buono, Whiting, & Sprong, 2015), in the USA as well as in Germany and Switzerland (e.g., Gianotti, Figner, Ebstein, & Knoch, 2012;Peters, & Büchel, 2009).…”