Dopamine, Time, and Impulsivity in Humans

“These results show that the characteristic decrease in activity of these regions as rewards become more delayed (or increase as they become temporally closer) (McClure et al., 2004; Tanaka et al., 2004; Kable and Glimcher, 2007; Pine et al., 2009) (see also supplemental Results for placebo, available at www.”

“However, temporal (or choice) impulsivity— the preference for smaller–sooner over larger–later rewards, due to excessive discounting of future rewards (Ainslie, 1975; Evenden, 1999; Ho et al., 1999; Cardinal et al., 2004)—is much harder to account for in terms of learning, although it remains an…”

“This indicates that, unlike the choice outcome, dopamine manipulation did not influence the amount of time given to weigh a decision, or ability to “hold your horses,” and corroborates the suggestion that impulsivity is not a unitary construct (Evenden, 1999; Ho et al., 1999; Winstanley et al., 2004a; Dalley et al., 2…”

“Subjective effects were analyzed by comparing changes in the three factors identified by Bond and Lader (1974), namely, alertness, contentedness, and calmness, relative to the change in scores observed in the placebo condition.”

“…activity of these regions as rewards become more delayed (or increase as they become temporally closer) (McClure et al., 2004; Tanaka et al., 2004; Kable and Glimcher, 2007; Pine et al., 2009) (see also supplemental Results for placebo, available at www.jneurosci.org as supplemental material) is…”

“D can be thought of as the discount factor—the delay-dependent factor (between 0 and 1) by which the utility is discounted in a standard hyperbolic fashion (Mazur, 1987).”

“…syndrome, addiction, and ADHD, all of which are associated with hyperdopaminergic states caused by striatal dopamine flooding or sensitization (Solanto, 1998, 2002; Seeman and Madras, 2002; Berridge, 2007; Robinson and Berridge, 2008; Dagher and Robbins, 2009; O’Sullivan et al., 2009).”

“DOI:10.1523/JNEUROSCI.6028-09.2010 Copyright © 2010 the authors 0270-6474/10/308888-09$15.00/0 effect on the rate of slowing down engendered by decision– conflict (Frank et al., 2007; Pochon et al., 2008) to distinguish global from discrete influences on impulsivity.”

“…but did not impact on deliberation—“holding your horses” (Frank et al., 2007)—that occurs when options are closely valued, engendering decision– conflict (Botvinick, 2007; Pochon et al., 2008) also related to reflection or preparation impulsiveness (Evenden, 1999; Clark et al., 2006).”

“The characteristic loss of self-control and impulsivity associated with aberrant dopamine function is exemplified by disorders such as addiction, attention-deficit/hyperactivity disorder (ADHD), and dopamine dysregulation syndrome (Winstanley et al., 2006; Dagher and Robbins, 2009; O’Sullivan et al., 2009).”

“We used a sequence designed to optimize functional sensitivity in the orbitofrontal cortex (Deichmann et al., 2003).”

“D can be thought of as the discount factor—the delay-dependent factor (between 0 and 1) by which the utility is discounted in a standard hyperbolic fashion (Mazur, 1987).”

“…via presynaptic effects, which may explain its dose-dependent effects in many previous studies as well as its therapeutic efficacy (in moderate doses) in a putatively hyperdopaminergic ADHD (Seeman and Madras, 1998, 2002; Solanto, 1998, 2002; Solanto et al., 2001; de Wit et al., 2002).”

“, 2008), whereas others demonstrate the opposite, a dosedependent effect, or no effect (Logue et al., 1992; Charrier and Thiébot, 1996; Evenden and Ryan, 1996; Richards et al., 1999; Cardinal et al., 2000; Isles et al., 2003; Helms et al., 2006; Bizot et al., 2007; Floresco et al., 2008).”

“These studies could be confounded by the concomitant release of serotonin (Kuczenski and Segal, 1997), which is also implicated in the modulation of intertemporal choice.”

“…intertemporal choice indicate that addicts and a subgroup of ADHD patients appear to have abnormally high temporal discount rates, strongly preferring smaller–sooner rewards (Sagvolden and Sergeant, 1998; Bickel and Marsch, 2001; Solanto et al., 2001; Winstanley et al., 2006; Bickel et al., 2007).”

“In principle, some of the aforementioned deficits can be related to dopaminergic effects by way of dopamine’s established role in reward learning (Redish, 2004; Frank et al., 2007; Dagher and Robbins, 2009).”

“These include haloperidol’s nonspecific and widespread pharmacological effects or dosage—some studies indicate haloperidol may paradoxically boost dopamine in small doses, due to presynaptic effects on the D2 autoreceptor (Frank and O’Reilly, 2006).”

“…the choice outcome, dopamine manipulation did not influence the amount of time given to weigh a decision, or ability to “hold your horses,” and corroborates the suggestion that impulsivity is not a unitary construct (Evenden, 1999; Ho et al., 1999; Winstanley et al., 2004a; Dalley et al., 2008).”

“Thus our findings reveal a novel mechanism by which dopamine influences human decision-making that can account for behavioral aberrations associated with a hyperfunctioning dopamine system.”

“…et al., 1999; Cardinal et al., 2000; Wade et al., 2000; Isles et al., 2003; Winstanley et al., 2003; van Gaalen et al., 2006; Bizot et al., 2007; Floresco et al., 2008), whereas others demonstrate the opposite, a dosedependent effect, or no effect (Logue et al., 1992; Charrier and Thiébot,…”

“…Pavlovian impulsivity, where responses associated with primary, innate values form a simple, evolutionarily specified action set operating alongside, and sometimes in competition with, other control mechanisms, such as habit-based and goal-directed action (Dayan et al., 2006; Seymour et al., 2009).”

“, 2008) also related to reflection or preparation impulsiveness (Evenden, 1999; Clark et al., 2006).”

“, 2008), whereas others demonstrate the opposite, a dosedependent effect, or no effect (Logue et al., 1992; Charrier and Thiébot, 1996; Evenden and Ryan, 1996; Richards et al., 1999; Cardinal et al., 2000; Isles et al., 2003; Helms et al., 2006; Bizot et al., 2007; Floresco et al., 2008).”

“The characteristic loss of self-control and impulsivity associated with aberrant dopamine function is exemplified by disorders such as addiction, attention-deficit/hyperactivity disorder (ADHD), and dopamine dysregulation syndrome (Winstanley et al., 2006; Dagher and Robbins, 2009; O’Sullivan et al., 2009).”

“…attenuation leads to an increase (Richards et al., 1999; Cardinal et al., 2000; Wade et al., 2000; Isles et al., 2003; Winstanley et al., 2003; van Gaalen et al., 2006; Bizot et al., 2007; Floresco et al., 2008), whereas others demonstrate the opposite, a dosedependent effect, or no effect…”

“…enhancement leads to a decrease in impulsive choice or that dopamine attenuation leads to an increase (Richards et al., 1999; Cardinal et al., 2000; Wade et al., 2000; Isles et al., 2003; Winstanley et al., 2003; van Gaalen et al., 2006; Bizot et al., 2007; Floresco et al., 2008), whereas others…”

“…(PIT), a phenomenon dependent on connectivity between amygdala and striatum (Cardinal et al., 2002; Seymour and Dolan, 2008), and whose expression is known to be modulated by dopamine (Dickinson et al., 2000; Lex and Hauber, 2008), appetitive Pavlovian values increase responding for rewards.”

“Notably, individual susceptibility to this influence correlates with amygdala activity (Talmi et al., 2008), suggesting that the amygdala might modulate the extent to which primary conditioned and unconditioned reward values influence instrumental (habitbased and goal-directed) choice.”

“Dopamine is known to have a dominant effect on primitive reward behaviors such as approach and consummation (Parkinson et al., 2002).”

“…preference for smaller–sooner over larger–later rewards, due to excessive discounting of future rewards (Ainslie, 1975; Evenden, 1999; Ho et al., 1999; Cardinal et al., 2004)—is much harder to account for in terms of learning, although it remains an important feature of putative dopaminergic…”

“, 2000) and that destruction of serotonergic neurons can block the effects of amphetamine (Winstanley et al., 2003).”

“…via presynaptic effects, which may explain its dose-dependent effects in many previous studies as well as its therapeutic efficacy (in moderate doses) in a putatively hyperdopaminergic ADHD (Seeman and Madras, 1998, 2002; Solanto, 1998, 2002; Solanto et al., 2001; de Wit et al., 2002).”

“The greater K or r, the more the individual is likely to choose the sooner option and therefore the more impulsive is the individual (Ho et al., 1999; Pine et al., 2009).”

“The greater K or r, the more the individual is likely to choose the sooner option and therefore the more impulsive is the individual (Ho et al., 1999; Pine et al., 2009).”

“…et al., 2008), whereas others demonstrate the opposite, a dosedependent effect, or no effect (Logue et al., 1992; Charrier and Thiébot, 1996; Evenden and Ryan, 1996; Richards et al., 1999; Cardinal et al., 2000; Isles et al., 2003; Helms et al., 2006; Bizot et al., 2007; Floresco et al., 2008).”

“effect on the rate of slowing down engendered by decision– conflict (Frank et al., 2007; Pochon et al., 2008) to distinguish global from discrete influences on impulsivity.”

“, 2002) or no effect (Acheson and de Wit, 2008; Hamidovic et al., 2008) when enhancing dopamine function.”

“…et al., 2008), whereas others demonstrate the opposite, a dosedependent effect, or no effect (Logue et al., 1992; Charrier and Thiébot, 1996; Evenden and Ryan, 1996; Richards et al., 1999; Cardinal et al., 2000; Isles et al., 2003; Helms et al., 2006; Bizot et al., 2007; Floresco et al., 2008).”

“…et al., 2008), whereas others demonstrate the opposite, a dosedependent effect, or no effect (Logue et al., 1992; Charrier and Thiébot, 1996; Evenden and Ryan, 1996; Richards et al., 1999; Cardinal et al., 2000; Isles et al., 2003; Helms et al., 2006; Bizot et al., 2007; Floresco et al., 2008).”

“, 2008), whereas others demonstrate the opposite, a dosedependent effect, or no effect (Logue et al., 1992; Charrier and Thiébot, 1996; Evenden and Ryan, 1996; Richards et al., 1999; Cardinal et al., 2000; Isles et al., 2003; Helms et al., 2006; Bizot et al., 2007; Floresco et al., 2008).”

“Anatomical localization was performed by overlaying the t maps on a normalized structural image averaged across subjects and with reference to the anatomical atlas of Mai et al. (2003).”

“located) [90,91] and of the PFC, including OFC [92], and is sensitive to DA manipulations [93].”

“Interestingly, delay discounting seems to depend on the function of the ventral striatum (104) and of the PFC, including OFC (105) and its connections to the NAc (106), and is sensitive to DA manipulations (107).”