Research report Hemispheric dissociation of reward processing in humans: Insights from deep brain stimulation Stefano Palminteri a,b , Giulia Serra b , Anne Buot b , Liane Schmidt a,b , Marie-Laure Welter b and Mathias Pessiglione a,b, * a Motivation, Brain and Behavior (MBB) Team, Institut du Cerveau et de la Moelle Epinie `re (ICM), Ho ˆpital de la Pitie ´-Salpe ˆtrie `re, Paris, France b Inserm UMR 975, CNRS UMR 7225, Universite ´ Pierre et Marie Curie (UPMC e Paris 6), Ho ˆpital de la Pitie ´-Salpe ˆtrie `re, Paris, France article info Article history: Received 21 August 2012 Reviewed 26 November 2012 Revised 10 January 2013 Accepted 5 February 2013 Action editor Marco Catani Published online xxx Keywords: Reinforcement learning Incentive motivation Hemispheric dissociation Deep brain stimulation Parkinson’s disease abstract Rewards have various effects on human behavior and multiple representations in the human brain. Behaviorally, rewards notably enhance response vigor in incentive motiva- tion paradigms and bias subsequent choices in instrumental learning paradigms. Neurally, rewards affect activity in different fronto-striatal regions attached to different motor ef- fectors, for instance in left and right hemispheres for the two hands. Here we address the question of whether manipulating reward-related brain activity has local or general effects, with respect to behavioral paradigms and motor effectors. Neuronal activity was manip- ulated in a single hemisphere using unilateral deep brain stimulation (DBS) in patients with Parkinson’s disease. Results suggest that DBS amplifies the representation of reward magnitude within the targeted hemisphere, so as to affect the behavior of the contralateral hand specifically. These unilateral DBS effects on behavior include both boosting incentive motivation and biasing instrumental choices. Furthermore, using computational modeling we show that DBS effects on incentive motivation can predict DBS effects on instrumental learning (or vice versa). Thus, we demonstrate the feasibility of causally manipulating reward-related neuronal activity in humans, in a manner that is specific to a class of motor effectors but that generalizes to different computational processes. As these findings proved independent from therapeutic effects on parkinsonian motor symptoms, they might provide insight into DBS impact on non-motor disorders, such as apathy or hypomania. ª 2013 Elsevier Ltd. All rights reserved. 1. Introduction Incentive motivation and instrumental learning: these two reward-related processes are often confounded, as they are naturally intermingled in real-life situations. The crucial dif- ference is that the reward is known before engaging the action in incentive motivation and after completing the action in instrumental learning. Incentive motivation is the process through which reward prospects activate particular behaviors (Berridge, 2004; Haggard, 2008). Instrumental learning is the process through which obtained rewards increase the pro- pensity to repeat particular behaviors (Skinner, 1938; Thorndike, 1911). There is ample evidence that reward expectation and obtainment are represented in fronto-striatal * Corresponding author. 47 Bd de l’Ho ˆ pital, 75013 Paris, France. E-mail address: mathias.pessiglione@gmail.com (M. Pessiglione). Available online at www.sciencedirect.com Journal homepage: www.elsevier.com/locate/cortex cortex xxx (2013) 1 e11 Please cite this article in press as: Palminteri S, et al., Hemispheric dissociation of reward processing in humans: Insights from deep brain stimulation, Cortex (2013), http://dx.doi.org/10.1016/j.cortex.2013.02.014 0010-9452/$ e see front matter ª 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.cortex.2013.02.014