(PI: Jean-Claude Dreher)
Our laboratory investigates the neural mechanisms underlying decision making, motivation and reward processing in humans, using concepts from cognitive neuroscience, psychology and behavioral economics. We use experimental tools such as model-based functional Magnetic Resonance Imaging, intracranial electrophysiological recordings and pharmacological manipulations to understand the computational processes involved when making a choice. Our goals are to understand the functional organization of the prefrontal cortex in humans, the various functions that the reward dopaminergic system exerts on cognition and motivation and the neural mechanisms underlying dysfunctions of these two systems in patients with neurological or psychiatric illnesses (Parkinson’s disease, patients with focal prefrontal cortex lesions, schizophrenia and pathological gambling). In parallel, we are also studying how individual variations in hormones and genes influence reward processing and decision-making.
Social decision making and Neuroeconomics
We have contributed to understanding the neurocomputational mechanisms engaged in social decision making. In particular, the fact that complex social decision making relies on probabilistic knowledge about the possible outcomes of choices and on the intentions and cooperativeness of other individuals has been underappreciated. We have established a mechanistic foundation for understanding group decision making, combining Bayesian models of social interactions and model-based fMRI (Khalvati et al., Science Advances, 2019; Park et al., Nature Communications, 2019). For example, in collective decisions, both the size of the groups and the confidence that each member has in their own judgment determine how much a given individual will adapt to the judgment of the group. We showed that judgment adaptation during collective decisions can be accounted for by Bayesian inference computations. At the time of judgment adaptation, individuals trade off the credibility inferred from their own confidence levels against the credibility of social information. The dorsal anterior cingulate cortex represented belief updates, while the lateral frontopolar cortex monitored the changes in credibility assigned to social information (Park et al., Plos Biology, 2017).
We have demonstrated that activity in the rostromedial prefrontal cortex represents social dominance relationships as learned from competitive interactions, whereas the ventromedial prefrontal cortex and the ventral striatum encode social victories and defeats, respectively (Ligneul et al., Current Biology, 2016). Electrical stimulation of the rmPFC modulates learning and updating of social dominance representations. These results, together with recent reviews, elucidate the role of the computations that govern the emergence and maintenance of social dominance relationships (Qu el al., TICS, 2017). We have also investigated the neural representations of moral decisions, investigating tradeoffs between moral and monetary costs/benefits. We showed the existence of two distinct brain networks for decisions in the moral and immoral contexts (Qu et al., Plos Biology, 2019), and provided evidence of a causal role of the right Temporo-Parietal Junction in altruism (Obeso et al., eLife, 2018).
We have described new functional divisions in the lateral orbitofrontal cortex (OFC) according to reward value coding (primary/secondary rewards) (Sescousse et al., J. Neurosci., 2010; Li et al., J. Neurosci., 2015). The anterior lateral OFC, a phylogenetically recent structure, processes monetary gains, the posterior lateral OFC, phylogenetically and ontogenetically older, processes more basic stimuli such as erotic stimuli. We have also made significant progress on understanding the neural mechanisms engaged in reward processing and value based-decision making. For example, we showed that the orbitofrontal cortex responds to different theoretical signals such as expected value and uncertainty, as demonstrated by intracranial recordings in patients with epilepsy (Li et al., Brain, 2016). We demonstrated that drift-diffusion models can be extended to account for value-based decision making when choosing between different primary rewards (Domenech et al., Cerebral Cortex, 2018).
Hormonal influences on reward and decision making
We have investigated how gonadal steroid hormones and genes involved in dopaminergic transmission modulate reward-related mechanisms and value-based decision making. Although popular discussion of testosterone's influence on males often centers on aggression and antisocial behavior, contemporary theorists have proposed that it instead enhances behaviors involved in obtaining and maintaining a high social status. Using injection of testosterone enanthate or a placebo in a double-blind, between-subjects, randomized design in young men, we have provided causal evidence for a role of testosterone in driving status-enhancing behaviors in males (Dreher et al., PNAS, 2016). In young women, we have investigated how the menstrual cycle modulates reward-related neural function (Dreher et al., PNAS, 2007). We observed a neurofunctional modulation of the reward system by gonadal steroid hormones in women. In addition, we studied how hormone therapy (HT) modulates brain reward processing (Thomas et al., Psychoneuroendocrinology, 2014). The results showed that HT enhanced ventral striatum activity during reward processing. These findings demonstrate that HT can prevent the appearance of reduced activity of the valuation brain system, a neurophysiological measure observed in early dementia. Moreover, we showed that genetically influenced variations in dopamine transmission modulate the response of brain regions involved in anticipation and reception of rewards, suggesting that these responses may contribute to individual differences in reward-seeking behavior and in predisposition to neuropsychiatric disorders (Dreher et al., PNAS, 2009)
Neurobiology of impulse control disorders
Impulse control disorders include a wide spectrum of behaviors, such as hypersexuality, pathological gambling or compulsive shopping. We have studied impulse control disorders in a number of domains, including money (in pathological gambling) and erotic stimuli (in specific Parkinson’s disease patients with hypersexuality disorders). We have compared how different types of primary vs secondary rewards (erotic stimuli vs money) are processed in brain disorders which are more specific to one reward domain (eg. money in pathological gambling, erotic stimuli in PD with hypersexuality). For example, we found that the posterior lateral orbitofrontal cortex, normally recruited by primary rewards in healthy subjects is in fact recruited by secondary rewards (money) in pathological gamblers, as if money had become a primary reward for these patients (Sescousse et al., Brain, 2013; Sescousse et al., Neuroscience and Biobehavioral reviews, 2013). More recently, we studied patients with Parkinson's disease and hypersexuality, we found that they discount erotic stimuli less than other PD patients and controls and the brain regions responsible for this effect engage the classical valuation brain system, including the ventral striatum and the ventromedial prefrontal cortex (Girard et al., Brain, 2019). We have also studied the link between midbrain dopamine and reward-related neural response and the alterations of this relationship in older humans (Dreher et al., PNAS, 2008).