Dopamine restores reward prediction errors in old age

Abstract

Senescence affects the ability to utilize information about the likelihood of rewards for optimal decision-making. In a human functional magnetic resonance imaging (fMRI) study, we show that healthy older adults have an abnormal signature of expected value resulting in an incomplete reward prediction error signal in the nucleus accumbens, a brain region receiving rich input projections from substantia nigra/ventral tegmental area (SN/VTA) dopaminergic neurons. Structural connectivity between SN/VTA and striatum measured with diffusion tensor imaging (DTI) was tightly coupled to inter-individual differences in the expression of this expected reward value signal. The dopamine precursor levodopa (L-DOPA) increased the task-based learning rate and task performance in some older adults to a level shown by young adults. Critically this drug-effect was linked to restoration of a canonical neural reward prediction error. Thus we identify a neurochemical signature underlying abnormal reward processing in older adults and show this can be modulated by L-DOPA.

The left hemisphere learns what is right: Hemispatial reward learning depends on reinforcement learning processes in the contralateral hemisphere

“…such learning deficits could have been caused by disruptions of striatal reward-and reinforcement learning processes. Moreover, the degree of rightward-directed hemispatial learning bias was associated with both increased reward processing in the ventral striatum, known to be modulated by DA (Knutson and Gibbs, 2007;van der Vegt et al, 2013), and relatively better neural encoding of PEs in the contralateral left ventral striatum, which is consistent with pharmacological studies showing that the neural encoding of PEs in the ventral striatum is influenced by the level of DA function (Chowdhury et al, 2013;Jocham et al, 2011;Pessiglione et al, 2006). This reasoning may also provide an alternative explanation for the results of a recent study by Palminteri et al (2013), in which unilateral increases in DA function, achieved through deep brain stimulation of the subthalamic nucleus (DBS-STN), enhanced reward learning for stimuli presented in the hemifield contralateral (vs. ipsilateral) to the stimulated hemisphere.…”

“…Because DA levels directly influence the neural encoding of prediction errors (PEs), i.e. the mismatch between actual and predicted outcomes (Chowdhury et al, 2013;Jocham et al, 2011;Pessiglione et al, 2006;Sutton and Barto, 1998) in the striatum (Abler et al, 2006;O'Doherty et al, 2003), here we hypothesized that hemispheric asymmetries in DA function could be associated with hemispheric asymmetries in the neural encoding of PEs. In particular, a relative increase of DA function in one hemisphere would lead to better encoding of PEs related to stimuli presented in the contralateral (vs. ipsilateral) hemispace, and thus also result in hemispatial learning biases.…”

Amphetamine modulates brain signal variability and working memory in younger and older adults

“…Accordingly, we predicted that pharmacological agents that boost systemic DA, such as amphetamine (AMPH), would restore deficient signal variability levels in older adults. Extant studies have examined the effect of DA agonists on average blood oxygen level-dependent (BOLD) signal responses and cognition (13,21,22); however, the effects of DA agonists on BOLD signal variability and cognition, and the moderation of these effects by adult age, have not been investigated thus far.…”

Estradiol and isotype-selective estrogen receptor agonists modulate the mesocortical dopaminergic system in gonadectomized female rats

“…Changes in the synaptic/extracellular content of dopamine [22], or alterations of the dopamine receptorcoupled signal transduction mechanisms [23,24] evoke disturbances in mood [25], learning and memory [26] and processing of reward signals [16]. Dysfunction of the VTA-PFC unit has been implicated in the pathology of schizophrenia [27], bipolar disorder [28,29] attention deficit hyperactivity disorder [30], and in the development of drug addiction [31]. It is noteworthy that effective medication of psychotic diseases partly relies on the selective targeting of dopaminergic neurotransmission [32].…”

“…In addition to the manifest psychotic diseases, an altered, deteriorating dopamine signaling characterizes the aging female brain [29,[33][34][35]. Obvious signs of decline in PFC-associated cognitive functions appear during perimenopause [18] .…”