Pharmacological modulation of subliminal learning in Parkinson's and Tourette's syndromes

Abstract

Theories of instrumental learning aim to elucidate the mechanisms that integrate success and failure to improve future decisions. One computational solution consists of updating the value of choices in proportion to reward prediction errors, which are potentially encoded in dopamine signals. Accordingly, drugs that modulate dopamine transmission were shown to impact instrumental learning performance. However, whether these drugs act on conscious or subconscious learning processes remains unclear. To address this issue, we examined the effects of dopamine-related medications in a subliminal instrumental learning paradigm. To assess generality of dopamine implication, we tested both dopamine enhancers in Parkinson's disease (PD) and dopamine blockers in Tourette's syndrome (TS). During the task, patients had to learn from monetary outcomes the expected value of a risky choice. The different outcomes (rewards and punishments) were announced by visual cues, which were masked such that patients could not consciously perceive them. Boosting dopamine transmission in PD patients improved reward learning but worsened punishment avoidance. Conversely, blocking dopamine transmission in TS patients favored punishment avoidance but impaired reward seeking. These results thus extend previous findings in PD to subliminal situations and to another pathological condition, TS. More generally, they suggest that pharmacological manipulation of dopamine transmission can subconsciously drive us to either get more rewards or avoid more punishments.dopamine ͉ instrumental learning ͉ subliminal perception ͉ reward ͉ punishment H ow we learn from success and failure is a long-standing question in neuroscience. Instrumental learning theories explain how outcomes can be used to modify the value of choices, such that better decisions are made in the future. A basic learning mechanism consists of updating the value of the chosen option according to a reward prediction error, which is the difference between the actual and the expected reward (1, 2). This learning rule, using prediction error as a teaching signal, has provided a good account of instrumental learning in a variety of species including both human and nonhuman primates (3, 4). Single-cell recordings in monkeys suggest that reward prediction errors are encoded by the phasic discharge of dopamine neurons (5, 6). In humans, dopamine-related drugs have been shown to bias prediction error encoding in the striatum to modulate reward-based learning (7). One of these drugs, levodopa (a metabolic precursor of dopamine), is used to alleviate motor symptoms in idiopathic Parkinson's disease (PD), which is primarily caused by degeneration of nigral dopamine neurons. PD patients were shown to learn better from positive feedback when on levodopa and from negative feedback when off levodopa (8, 9). This double dissociation lead Frank and colleagues to propose a computational model of fronto-striatal circuits where dopamine bursts (encoding positive prediction errors) reinforce approach pathways,...

Neurogenetics and Pharmacology of Learning, Motivation, and Cognition

“…Recent functional imaging data support this notion, showing that medication blunts the normal striatal response to negative prediction errors and also impairs learning in this condition (Voon et al, 2010). Conversely, D2 receptor blockade actually improves NoGo learning from negative prediction errors in patients with Tourette's syndrome (Palminteri et al, 2009). This latter result is also supported by both theoretical and empirical data: D2-blockade and resulting enhancement of striatopallidal excitability and plasticity promotes avoidance learning in both models and rats (Wiecki et al, 2009).…”

“…Recent feats in genetic engineering revealed striking support for these mechanisms, whereby reward and aversive/avoidance learning was impaired in animals with selected targeted disruption of striatonigral and striatopallidal cells, respectively (Hikida et al, 2010). Moreover, the model correctly predicted that human Parkinson's patients would show impairments in learning to make responses associated with positive outcomes but relative enhancements in NoGo learning from negative prediction errorsFand that both these effects would be reversed when patients were taking dopamine medication (Frank et al, 2004(Frank et al, , 2007bMoustafa et al, 2008a;Cools et al, 2006;Bodi et al, 2009;Palminteri et al, 2009;Voon et al, 2010).…”

Gray’s revised Reinforcement Sensitivity Theory in relation to Attention-Deficit/Hyperactivity and Tourette-like behaviors in the general population

“…Studies have found (i) greater amygdala activation for fearful, angry and neutral facial expressions in TS patients (though comorbidity was not controlled; Neuner et al, 2010); (ii) impaired punishment learning in unmedicated TS patients, whereas reward sensitivity and reward learning were only reduced in medicated and OCD-comorbid TS patients (Palminteri et al, 2009; and (iii) no differences in reward learning between pure TS patients and healthy controls (Crawford, Channon & Robertson, 2005). These findings suggest increased sensitivity to aversive and ambiguous cues (overactive FFFS and BIS) but deficits in negative reinforcement learning (dysfunctional FFFS or BIS) in TS, whereas reward processing deficits (underactive BAS) appear to be linked to medication status and presence of OCD symptoms.…”

“…In line with Gomez and Corr (2010), we predicted that BAS-fun seeking would be related to increased hyperactivity/impulsivity whereas BIS-anxiety should relate to increased inattention ADHD-like behaviors. Given the previous findings in clinical TS (e.g., Palminteri et al, 2009Palminteri et al, , 2011, we expected a dysfunctional BIS and/or FFFS to be linked to pure phonic and motor TS-like behaviors and any associations with BAS to be due to 'comorbidity' in TS-like behaviors.…”

Separating the effect of reward from corrective feedback during learning in patients with Parkinson’s disease

“…Shohamy, Myers, Onlaor, et al, 2004;Swainson et al, 2000). Interestingly, despite the feedback-learning deficits exhibited by patients with PD, three recent studies have demonstrated that PD patients are able to learn from reward just as well or better than healthy controls (HCs) when taking their usual antiparkinsonian medication (Bódi et al, 2009;Frank et al, 2004;Palminteri et al, 2009).…”