A mechanistic account of striatal dopamine function in human cognition: Psychopharmacological studies with cabergoline and haloperidol.

Abstract

The authors test a neurocomputational model of dopamine function in cognition by administering to healthy participants low doses of D 2 agents cabergoline and haloperidol. The model suggests that DA dynamically modulates the balance of Go and No-Go basal ganglia pathways during cognitive learning and performance. Cabergoline impaired, while haloperidol enhanced, Go learning from positive reinforcement, consistent with presynaptic drug effects. Cabergoline also caused an overall bias toward Go responding, consistent with postsynaptic action. These same effects extended to working memory and attentional domains, supporting the idea that the basal ganglia/dopamine system modulates the updating of prefrontal representations. Drug effects interacted with baseline working memory span in all tasks. Taken together, the results support a unified account of the role of dopamine in modulating cognitive processes that depend on the basal ganglia.Keywords: basal ganglia, dopamine, cognition, computational, psychopharmacologyThe basal ganglia (BG) participate in various aspects of cognition and behavior by interacting with and modulating multiple areas of frontal cortex (Alexander, DeLong, & Strick, 1986). Similarly, the neurotransmitter dopamine (DA) plays a modulatory role in cognition through extensive diffuse projections from midbrain DA nuclei to the BG and frontal cortical areas (Fallon & Moore, 1978;Gerfen, 1992;Joel & Weiner, 2000). Several neurological conditions implicate DA dysfunction, including Parkinson's disease, attention deficit/hyperactivity disorder (ADHD), and schizophrenia (Abi-Dargham et al., 2000;Dougherty et al., 1999;Ilgin et al., 2001;Kish, Shannak, & Hornykiewicz, 1988;McGowan, Lawrence, Sales, Quested, & Graby, 2004;Nieoullon, 2002;Seeman, 1987;Weiner & Joel, 2002;Weinberger, 1987). Notably, the cognitive deficits observed in all of these conditions are qualitatively similar to those observed in patients with damage to prefrontal cortex (PFC; Barch et al., 2001;Brown & Marsden, 1990;Cools, Barker, Sahakian, & Robbins, 2001;Perlstein, Dixit, Carter, Noll, & Cohen, 2003;Willcutt et al., 2005). Consequently, the overwhelming tendency in the literature is to attribute patient cognitive deficits to dopaminergic dysfunction within PFC. This is a potentially valid attribution, given that selective disruption to prefrontal DA in monkeys gives rise to cognitive deficits that are similar to those observed under full excitotoxic PFC lesions (Sawaguchi & Goldman-Rakic, 1991; Williams & GoldmanRakic, 1995). However, there is growing evidence in both animals and humans that DA dysfunction within the BG alone can lead to frontal-like cognitive deficits (Collins, Wilkinson, Everitt, Robbins, & Roberts, 2000;Crofts et al., 2001;Frank, 2005;J. O. Rinne et al., 2000).Psychopharmacological studies that transiently manipulate the DA system in healthy individuals can potentially inform the cause of DA-related cognitive deficits. In particular, drugs that target the D 2 receptor, which is predominantly expressed in BG re...

Stress and Alcohol Cues Exert Conjoint Effects on Go and Stop Signal Responding in Male Problem Drinkers

“…Drugs that preferentially reduce tonic DA transmission at D2 receptors (haloperidol) reduce Stroop interference to drug-related words in heroin-dependent subjects (Franken et al, 2004). A previous account on DA and distraction (Frank and O'Reilly R, 2006) noted that 'a presynaptic increase in DA bursting by [the selective D2 antagonist] sulpiride could explain recent observations from the same group (Mehta et al, 2004) that the drug increased distractibility in a working memory task when distractors were task relevant (and could therefore elicit DA bursts and cause working memory updating) but not when distractors were irrelevant' (pp 511-512). In the present study, the Go task entailed a rapid and flexible key press response.…”

The anterior medial temporal lobes: Their role in food intake and body weight regulation

“…Obese individuals preferred the cue associated with a 10% possibility of receiving food ( [20], Experiment 1). This result might be explained by a difficulty of learning to avoid negative outcomes in obese individuals [39], as this result was not specific to food reward but also replicated with monetary reward ( [20]; Experiment 2).…”

Opponent actor learning (OpAL): Modeling interactive effects of striatal dopamine on reinforcement learning and choice incentive.

“…However, higher tonic levels can also prevent D2 receptors from detecting phasic dips, thereby reducing sensitivity to negative prediction errors (Frank, 2005). Conversely, low dopamine levels may reduce phasic burst signaling but actually increase the sensitivity to dips (Frank & O'Reilly, 2006). In the OpAL framework, this modulation can be modeled by asymmetries in the actor learning rate parameters ␣ G and ␣ N , capturing the sensitivity of D1 and D2 MSNs to dopaminergic signals and resultant effects on plasticity.…”