Biology subjects

Dang, L. C.

Publications and source records attributed to Dang, L. C..

5 recordsLinked to original sources

bioRxiv2021

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.

neuroscience↗

bioRxiv2019

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.

neuroscience↗

bioRxiv2018

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.

neuroscience↗

bioRxiv2018

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.

neuroscience↗

bioRxiv2018

Differential regional decline in dopamine receptor availability across adulthood: Linear and nonlinear effects of age

Theories of adult brain development, based on neuropsychological test results and structural neuroimaging, suggest differential rates of age-related change in function across cortical and subcortical sub-regions. However, it remains unclear if these trends also extend to the aging dopamine system. Here we examined cross-sectional adult age differences in estimates of D2-like receptor binding potential across several cortical and subcortical brain regions using PET imaging and the radiotracer [18F]fallypride in two samples of healthy human adults (combined N = 132). After accounting for regional differences in overall radioligand binding, estimated percent difference in receptor binding potential by decade (linear effects) were highest in most temporal and frontal cortical regions ([~]6-16% per decade), moderate in parahippocampal gyrus, pregenual frontal cortex, fusiform gyrus, caudate, putamen, thalamus, and amygdala ([~]3-5%), and weakest in subcallosal frontal cortex, ventral striatum, pallidum, and hippocampus ([~]0-2%). Some regions showed linear effects of age while many showed curvilinear effects such that binding potential declined from young adulthood to middle age and then was relatively stable until old age. Overall, these data indicate that the rate and pattern of decline in D2 receptor availability is regionally heterogeneous. However, the differences across regions were challenging to organize within existing theories of brain development and did not show the same pattern of regional change that has been observed in gray matter volume, white matter integrity, or cognitive performance. This variation suggests that existing theories of adult brain development may need to be modified to better account for the spatial dynamics of dopaminergic system aging.

neuroscience↗