Impulsive Personality Predicts Dopamine-Dependent Changes in Frontostriatal Activity during Component Processes of Working Memory

Abstract

Dopaminergic drugs affect a variety of cognitive processes, but the direction and extent of effects vary across individuals and tasks.Paradoxical effects are observed, by which the same drug causes cognitive enhancing as well as adverse effects. Here, we demonstrate that individual differences in impulsive personality account for the contrasting effects of dopaminergic drugs on working memory and associated frontostriatal activity. We observed that the dopamine D 2 receptor agonist bromocriptine improved the flexible updating (switching) of relevant information in working memory in high-impulsive subjects, but not in low-impulsive subjects. These behavioral effects in high-impulsive subjects accompanied dissociable effects on frontostriatal activity. Bromocriptine modulated the striatum during switching but not during distraction from relevant information in working memory. Conversely, the lateral frontal cortex was modulated by bromocriptine during distraction but not during switching. The present results provide a key link between dopamine D 2 receptor function, impulsivity, and frontostriatal activity during component processes of working memory.Key words: dopamine; working memory; prefrontal cortex; basal ganglia; fMRI; impulsivity IntroductionThe mesocorticolimbic dopamine (DA) system is implicated in working memory (Brozoski et al., 1979;Sawaguchi and Goldman-Rakic, 1991). However, the effects of dopaminergic drugs are complex and depend on task demands and associated neural systems . Recent work suggests that DA may have opposite effects depending on the neural site of modulation [prefrontal cortex (PFC) vs striatum] (Crofts et al., 2001;Frank et al., 2001;Gruber et al., 2006). DA in the PFC is thought to stabilize representations by reducing susceptibility to distraction (Durstewitz et al., 2000;Seamans and Yang, 2004). Conversely, DA in the striatum may rapidly update representations in a task-relevant manner (Frank et al., 2001;Gruber et al., 2006). In the current study, we aimed to test the hypothesis that DA modulates the striatum and frontal cortex during the flexible updating and stable maintenance of representations, respectively, by examining the effects of the D 2 receptor agonist bromocriptine with functional magnetic resonance imaging (fMRI). Dopaminergic drug effects vary not only across task demands but also across individuals . Paradoxical effects are observed, by which drugs improve performance in individuals with suboptimal DA and poor performance but impair performance in individuals with already optimized DA and good performance (Kimberg et al., 1997;Arnsten, 1998;Mattay et al., 2003;Phillips et al., 2004). Here, we demonstrate that dopaminergic drug effects can also be predicted from trait impulsivity. We observed differential effects of bromocriptine in highand low-impulsive subjects, who were preselected based on selfreport trait impulsivity. The rationale for impulsivity-based subject selection was threefold. First, impulsivity is the primary trait thought to mediate vulnerability ...

A close relationship between verbal memory and SN/VTA integrity in young and older adults

“…Although this close functional relationship between SN/VTA integrity and CVLT performance was hypothesized it should be noted, that working memory span also seems to be influenced by integrity of the SN/VTA, hippocampus and frontal WM (as apparent from our multiple regression analyses). This is compatible with data indicating that dopaminergic neuromodulation is also related to memory span (Aalto, Bruck, Laine, Nagren, & Rinne, 2005;Cools, Sheridan, Jacobs, & D'Esposito, 2007). In our data, memory span was most strongly predicted by age and hippocampal MTR, and adding SN/VTA integrity explained 3% additional variance of working memory span performance.…”

Neurogenetics and Pharmacology of Learning, Motivation, and Cognition

“…It is noteworthy that DAT1 genotype is predictive of brain and behavioral responses to cognitive flexibility (GarciaGarcia et al, 2010) and, in particular, a recent study showed that DAT1 modulates striatal (caudate) activation as a function of working memory load in an updating task (Stollstorff et al, 2010). A role for striatal dopamine in cognitive flexibility and working memory updating is consistent with multiple behavioral pharmacological and imaging studies (Cools et al, 2007;Clatworthy et al, 2009;Frank and O'Reilly, 2006;Moustafa et al, 2008b). Thus, given the evidence that striatal activation predicts the extent to which cognitive training can be achieved with updating tasks (Dahlin et al, 2008a), future research should analyze the degree to which these training effects are modulated by variations with striatal dopaminergic genes such as DARPP-32, DAT1 and DRD2.…”

“…Indeed, dopamine-releasing stimulants are well known to improve cognitive function in both participants with ADHD and healthy individuals (Klorman et al, 1984;Elliott et al, 1997). However, multiple studies have shown that whether dopaminergic agents (particularly D2 receptor agonists), improve or impair cognitive function strongly depends on baseline measures (Kimberg et al, 1998;Mehta et al, 2004;Roesch-Ely et al, 2005;Frank and O'Reilly, 2006;Cools et al, 2009Cools et al, , 2007Clatworthy et al, 2009). For example, D2 stimulation generally improves performance in individuals with low working memory span (Kimberg et al, 1998;Frank and O'Reilly, 2006), or high impulsivity (Cools et al, 2007), or low baseline DA synthesis (Cools et al, 2009), whereas it impairs performance in those in the opposite groups.…”

Dopamine, Corticostriatal Connectivity, and Intertemporal Choice

“…This finding is also consistent with previous reports that the effects of other dopaminergic agents, such as the D 2 receptor agonist bromocriptine, depend on baseline impulsivity levels. In a working memory paradigm, Cools et al (2007) demonstrated that bromocriptine improved the updating of working memory in high-impulsive but not low-impulsive subjects. In keeping with that result, we find that tolcapone reduced impulsivity more in high-impulsive subjects.…”