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Samanez-Larkin, G. R.

Publications and source records attributed to Samanez-Larkin, G. R..

8 recordsLinked to original sources

A neural signature of reward

Using a neurometric approach, we identify and validate a neural signature of reward encoded in a distributed pattern of brain activity using data collected from 21 different studies (N = 2,691). Our model can discriminate between receiving rewards from punishments in completely independent data with 99% accuracy and includes weights located in regions containing a high density of D2/D3 receptors. The model exhibits strong generalizability across a range of tasks probing reward, and a high degree of specificity for reward compared to non-reward constructs. We demonstrate several applications of how this model can infer psychological states of positive affect in the absence of self report. The model is sensitive to changes in brain activity following causal manipulations of homeostatic states, can uncover individual preferences for loss-aversion, and can be used to identify positive affective experiences when watching a television show. Our results suggest that there is a shared neural signature of reward elicited across these different task contexts.

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Dopamine biases sensitivity to personal goals and social influence in self-control over everyday desires

People regularly give in to daily temptations in spite of conflict with personal goals. To test hypotheses about neuropharmacological influences on self-control, we used positron emission tomography to measure dopamine D2-like receptors (D2R) and experience sampling surveys to naturalistically track daily desires outside the laboratory in everyday life in a sample of 103 adults. Higher D2R availability in the ventral striatum was associated with increased sensitivity to personal goal conflict but not desire strength in deciding whether to attempt to resist a desire. The influence of D2Rs on sensitivity to personal goal conflict depended on whether desires were experienced in a social context. D2R availability in the midbrain (but not the ventral striatum) influenced whether desires were enacted. These findings provide unique evidence that the dopamine system influences decision making and regulatory behavior and provides new insights into how these mechanisms interact with personal goals and social contexts.

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Multivariate associations between dopamine receptor availability and risky investment decision making across adulthood

Pharmacological manipulations have revealed that enhancing dopamine increases financial risk taking across adulthood. However, it is unclear whether baseline individual differences in dopamine function, assessed using PET imaging, are related to performance on risky financial decision making tasks. Here, thirty-five healthy adults completed an incentive-compatible learning-based risky investment decision task and a PET scan at rest using [11C]FLB457 to assess dopamine D2-like receptor availability. In the task, participants made choices between a safe asset (bond) and a risky asset (stock) with either an expected value less than the bond ("bad stock") or expected value greater than the bond ("good stock"). Five measures of behavioral performance (choice inflexibility, risk seeking, suboptimal investment) and beliefs (absolute error, optimism) were extracted from the task data and average non-displaceable dopamine D2-like binding potential was extracted from four brain regions of interest (midbrain, amygdala, anterior cingulate, insula) from the PET imaging data. Given the presence of multiple independent and dependent variables, we used canonical correlation analysis (CCA) to evaluate multivariate associations between learning-based decision making and dopamine function controlling for age. Decomposition of the first dimension (r = .76) revealed that the strongest associations were between measures of choice inflexibility, incorrect choice, optimism, amygdala binding potential, and age. Follow-up univariate analyses revealed that amygdala binding potential and age were both independently associated with choice inflexibility. The findings reveal latent associations between baseline neural and behavioral measures suggesting that individual differences in dopamine function may be associated with learning-based financial risk taking in healthy adults.

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Dopaminergic modulation of reward discounting: a systematic review and meta-analysis

Although numerous studies have suggested that pharmacological alteration of the dopamine (DA) system modulates reward discounting, these studies have produced inconsistent findings. Here, we conducted a systematic review and pre-registered meta-analysis to evaluate DA drug-mediated effects on reward discounting of time, probability, and effort costs in studies of healthy rats. This produced a total of 1,343 articles to screen for inclusion/exclusion. From the literature, we identified 117 effects from approximately 1,549 individual rats. Using random-effects with maximum-likelihood estimation, we meta-analyzed placebo-controlled drug effects for (1) DA D1-like receptor agonists and (2) antagonists, (3) D2-like agonists and (4) antagonists, and (5) DA transporter-modulating drugs. Meta-analytic effects showed that DAT-modulating drugs decreased reward discounting. While D1-like and D2-like antagonists both increased discounting, agonist drugs for those receptors had no significant effect on discounting behavior. A number of these effects appear contingent on study design features like cost type, rat strain, and microinfusion location. These findings suggest a nuanced relationship between DA and discounting behavior and urge caution when drawing generalizations about the effects of pharmacologically manipulating dopamine on reward-based decision making.

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Mesolimbic dopamine D2 receptors and neural representations of subjective value

The process by which the value of delayed rewards is discounted varies from person to person. It has been suggested that these individual differences in subjective valuation of delayed rewards are supported by mesolimbic dopamine D2-like receptors (D2Rs) in the ventral striatum. However, no study to date has documented an association between direct measures of dopamine receptors and neural representations of subjective value in humans. Here, we examined whether individual differences in D2R availability were related to neural subjective value signals during decision making. Human participants completed a monetary delay discounting task during an fMRI scan and on a separate visit completed a PET scan with the high affinity D2R tracer [18F]fallypride. Region-of-interest analyses revealed that D2R availability in the ventral striatum was positively correlated with subjective value-related activity in the ventromedial prefrontal cortex and midbrain but not with choice behavior. Whole-brain analyses revealed a positive correlation between ventral striatum D2R availability and subjective value-related activity in the left inferior frontal gyrus. These findings are the first to identify a link between directly-measured mesolimbic dopamine function and subjective value representation in humans and suggest a mechanism by which individuals vary in neural representation of discounted subjective value.

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Reliability of the correlative triad among aging, dopamine D2-like receptor availability, and cognition

The evidence that dopamine function mediates the association between aging and cognition is one of the most cited findings in the cognitive neuroscience of aging. However, few and relatively small studies have directly examined these associations. Here we examined correlations among adult age, dopamine D2-like receptor (D2R) availability, and cognition in two cross-sectional studies of healthy human adults. Participants completed a short cognitive test battery and, on a separate day, a PET scan with either the high-affinity D2R tracer [18F]Fallypride (Study 1) or [11C]FLB457 (Study 2). Digit span, a measure of short-term memory maintenance and working memory, was the only cognitive test for which dopamine D2R availability partially mediated the age effect on cognition. In Study 1, age was negatively correlated with digit span. Striatal D2R availability was positively correlated with digit span controlling for age. The age effect on digit span was smaller when controlling for striatal D2R availability. Although other cognitive measures used here have individually been associated with age and D2R availability in prior studies, we found no consistent evidence for significant associations between low D2R availability and low cognitive performance on these measures. These results at best only partially supported the correlative triad of age, dopamine D2R availability, and cognition. While a wealth of other research in human and non-human animals demonstrates that dopamine makes critical contributions to cognition, the present studies suggest caution in interpreting PET findings as evidence that dopamine D2R loss is a primary cause of broad age-related declines in fluid cognition.

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Reduced serotonin receptors and transporters in normal aging adults: a meta-analysis of PET and SPECT imaging studies

Age-related alterations in serotonin (5-HT) function have been hypothesized to underlie a range of physiological, emotional, and cognitive changes in older age. Here, we conducted a quantitative synthesis and comparison of the effects of age on 5-HT receptors and transporters from cross-sectional PET and SPECT imaging studies. Random-effects meta-analyses of 31 studies including 1087 healthy adults yielded large negative age effects in 5-HT-2A receptors, moderate negative age effects in 5-HT transporters, and small negative age effects in 5-HT-1A receptors. Age differences were significantly larger in 5-HT-2A receptors compared to 5-HT-1A receptors. A meta-regression showed that 5-HT target, brain region, tracer kinetic measure, radionuclide, and publication year significantly moderated the age effect. The findings overall identify reduced serotonergic signal transmission in age. The evidence for a relative preservation of 5-HT-1A compared to 5-HT-2A receptors may partially explain differential psychological changes with age, such as why older people use more emotion-focused rather than problem-focused coping strategies.

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Individual differences in dopamine are associated with reward discounting in clinical groups but not in healthy adults

Some people are more willing to make immediate, risky, or costly reward-focused choices than others, which has been hypothesized to be associated with individual differences in dopamine (DA) function. In two studies using PET imaging, one empirical (Study 1: N=144 males and females across 3 samples) and one meta-analytic (Study 2: N=307 across 12 samples), we sought to characterize associations between individual differences in DA and time, probability, and physical effort discounting in human adults. Study 1 demonstrated that individual differences in DA D2-like receptors were not associated with time or probability discounting of monetary rewards in healthy humans, and associations with physical effort discounting were inconsistent across adults of different ages. Meta-analytic results for temporal discounting corroborated our empirical finding for minimal effect of DA measures on discounting in healthy individuals, but suggested that associations between individual differences in DA and reward discounting depend on clinical features. Addictions were characterized by negative correlations between DA and discounting but other clinical conditions like Parkinsons Disease, obesity, and ADHD were characterized by positive correlations between DA and discounting. Together the results suggest that trait differences in discounting in healthy adults do not appear to be strongly associated with individual differences in D2-like receptors. The difference in meta-analytic correlation effects between healthy controls and individuals with psychopathology suggests that individual difference findings related to DA and reward discounting in clinical samples may not be reliably generalized to healthy controls, and vice-versa.\n\nSignificance StatementDecisions to forgo large rewards for smaller ones due to increasing time delays, uncertainty, or physical effort have been linked to differences in dopamine (DA) function, which is disrupted in some forms of psychopathology. It remains unclear whether alterations in DA function associated with psychopathology also extend to explaining associations between DA function and decision making in healthy individuals. We show that individual differences in dopamine D2 receptor availability are not consistently related to monetary discounting of time, probability, or physical effort in healthy individuals across a broad age range. By contrast, we suggest that psychopathology accounts for observed inconsistencies in the relationship between measures of dopamine function and reward discounting behavior.

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