Neural basis of reward anticipation and its genetic determinants

Abstract

Dysfunctional reward processing is implicated in various mental disorders, including attention deficit hyperactivity disorder (ADHD) and addictions. Such impairments might involve different components of the reward process, including brain activity during reward anticipation. We examined brain nodes engaged by reward anticipation in 1,544 adolescents and identified a network containing a core striatal node and cortical nodes facilitating outcome prediction and response preparation. Distinct nodes and functional connections were preferentially associated with either adolescent hyperactivity or alcohol consumption, thus conveying specificity of reward processing to clinically relevant behavior. We observed associations between the striatal node, hyperactivity, and the vacuolar protein sorting-associated protein 4A (VPS4A) gene in humans, and the causal role of Vps4 for hyperactivity was validated in Drosophila. Our data provide a neurobehavioral model explaining the heterogeneity of rewardrelated behaviors and generate a hypothesis accounting for their enduring nature.uccessful behavioral adaptation requires effective reward processing that determines whether a desired goal is approached and maintained. Reward processing can be separated into behavioral anticipation or reward expectancy as a consequence of learning and behavioral and subjective responses to rewarding outcomes (1). In humans, dysfunctional reward processing (in particular, dysfunctional reward anticipation) has been implicated in various externalizing disorders, including attention-deficit hyperactivity disorder (ADHD) (2) and addiction (3). Brain regions involved in reward anticipation include the ventral tegmental area, the medial forebrain bundle, and the nucleus accumbens/ventral striatum (VS; including the ventral caudate-putamen) as well as the ventromedial and insular cortices (4). More recently, observations have been reported to link reward processing in humans with cortical activation (5), including the primary somatosensory (6), primary visual (V1) (7), and auditory (8) cortices. Dopamine is the principal neurotransmitter regulating reward processing, particularly through the mesocorticolimbic pathway (9), the neuronal projection from the ventral tegmental area to the VS and prefrontal cortex. A general feature of striatal information processing is the control by rewardrelated dopamine signals of direct and indirect cortical inputs from different neurotransmitter systems, including noradrenaline, glutamate, and GABA as well as acetylcholine, endogenous opioids, and cannabinoids (10). As a consequence, striatal dopaminergic activity integrates cortical and subcortical inputs with reward response. In addition to direct and indirect regulation by heteroceptors, dopamine release is regulated by presynaptic autoreceptors of the D2 family, in particular D2 dopamine receptors (DRD2) that Author contributions: T.J., S.D., C.P.M., J.F., A.R., H.F., and G.S. designed research; T.J., C.M., S.D., D.A.G., C.T., B.R., F.N., T.B., G.J.B., A.L.W.B., U.B...

The cerebellum in drug craving

“…Furthermore, this working hypothesis might explain the specific cFos expression found in the cerebellum of rodents expressing a preference for a cocaine-paired odor cue that was not observed when the animal did not acquire this conditioned response (Carbo-Gas et al, 2014ab). A recent neuroimaging study that monitored brain activity during reward anticipation showed 4 active nodes encompassing broad cerebellar areas including the vermis (Jia et al, 2016). Nevertheless, the authors of the study did not propose a specific hypothesis for the cerebellar activity, as no correlation with performance in neuropsychological tests was found.…”

Lack of anticipatory behavior in Gpr88 knockout mice showed by automatized home cage phenotyping

“…Reward anticipation neural networks involve both the striatum and cortical regions including visual association cortex and the somatosensory cortex and the fact that Gpr88 −/− mice did not anticipate the water access suggests a possible alteration of this neural network. This is consistent with the prominent expression of GPR88 in both striatum and cortex .…”

“…This interpretation is based on the fact that, although the 24 hours water deprivation step does not produce robust physiological changes, 35 mice are subjected to 19-hour water deprivation for 9 consecutive days and that, under these conditions, drinking water is considered an innately rewarding behavior. 36 Reward anticipation neural networks involve both the striatum and cortical regions including visual association cortex and the somatosensory cortex 37 and the fact that Gpr88 −/− mice did not anticipate the water access suggests a possible alteration of this neural network. This is consistent with the prominent expression of GPR88 in both striatum and cortex.…”

Mapping adolescent reward anticipation, receipt, and prediction error during the monetary incentive delay task

“…Furthermore, adolescents at a more advanced pubertal stage exhibited less striatal and more medial prefrontal cortex (mPFC) activation during reward processing than those at a less advanced pubertal stage (Forbes et al, 2010). Typically, the effects of gender and puberty have not been analyzed or have been controlled for statistically in previous reward processing studies (Bjork et al, 2004(Bjork et al, , 2010Jia et al, 2016;Peters et al, 2011;Stringaris et al, 2015), which make their specific contribution in reward processing unclear. Typically, the effects of gender and puberty have not been analyzed or have been controlled for statistically in previous reward processing studies (Bjork et al, 2004(Bjork et al, , 2010Jia et al, 2016;Peters et al, 2011;Stringaris et al, 2015), which make their specific contribution in reward processing unclear.…”