Though there is a paucity of human research linking endogenous measures of dopamine function with reinforcement learning, dopaminergic drugs modulate RPE-like fMRI signals . Beyond reinforcement learning, dopamine has been linked to a multitude of cognitive processes thought to support complex, goal-directed decision-making such as episodic memory , working memory , flexibility , and valuation . Therefore, it would be reasonable to expect that deficits in dopamine function would negatively impact decision-making, and possibly through multiple paths. Aging is accompanied by alterations in multiple components of the dopamine system, including loss of dopamine-producing neurons in the substantia nigra , and losses in dopamine receptors and transporters . However, there is accumulating evidence from in vivo PET imaging in humans indicating that dopamine changes in aging are more heterogenous than previously thought. In this review, we focus on three aspects of intra and inter individual variability and consider how they may obscure evidence of systematic changes in decision-making with age. First, declines in the dopamine system vary substantially across individuals . Second, pre and post synaptic components of the dopamine system may decline at different rates and in different directions . Third, declines in the dopamine system may be spatially heterogeneous . We provide examples for how these factors may affect decision-making processes relying on reinforcement learning as well as goal-directed processes thought to rely on working memory . We posit that incorporating in vivo imaging to account for intraindividual and inter individual variability in dopamine function may explain some of the null or conflicting age effects in the decision sciences.Perhaps reflecting the complex relationship between dopamine function and aging, black plastic plant pots wholesale there is surprisingly little consensus on the nature of age-related changes in value-based decision making using laboratory-based tasks.

For example, studies in animal models strongly implicate dopamine in risk-taking . However, meta-analyses of tasks assessing risk-taking in young and older adults found no effect of age , or small effects indicating greater risk aversion in older adults when potential financial gains are at stake . Previous discussions of the mixed effects in the decision making literature have emphasized how variability in task framing and difficulty have profound effects on performance in older adults and can potentially alter the direction of observed age differences . For example, a recent meta-analysis of the Iowa gambling task suggests risk aversion in aging may develop progressively over the course of a single experimental session . Therefore, older adults may appear more risk seeking or more risk averse depending on a given task’s demands on learning. While previous discussions have brought to light the importance of between-study task differences in interpreting inconsistencies in the direction of reported age-group differences, here we emphasize the ways in which inter individual variability in older adults preclude the identification of systematic age-group differences within a single study. One limitation of previous studies is the absence of in vivo assessment of dopamine function using methods such as PET. PET imaging has been critical for clarifying essential questions in cognitive aging. For example, relevant to the field of Alzheimer’s disease research, PET imaging is being used to resolve conflicting accounts of the pathological mechanisms affecting memory. Recent PET findings have demonstrated preferential relationships between the accumulation of tau and memory . Similarly, dopamine PET imaging has been central for resolving controversies regarding the neural basis of cognitive training gains and mechanisms of transfer.

Backman and colleagues have demonstrated 5 weeks of working memory training increases striatal dopamine release during performance of the training task as well during performance on untrained working memory tasks . Incorporation of neurochemical and neuropathological quantitation allows for unique insights into the mechanisms underlying cognitive decline or enhancement in humans that are not possible using fMRI, electroencephalography, or structural imaging alone. Here, we discuss how the addition of in vivo dopamine measures to behavioral and structural and functional imaging studies will be useful for organizing the range of age effects reported in the decision sciences. We first provide background on in vivo dopamine imaging, and describe the strengths and limitations of these methods. We next identify three sources of inter individual and intra individual variability in age-related changes in brain dopamine, which have been revealed through PET imaging. Using specific examples to illustrate how these sources of variability can produce inconsistent age group effects, we propose ways in which in vivo imaging can clarify the neural basis for these findings. Finally, we address the possibility that changes in dopamine function join with age-related alterations in affective attention to increase inter individual variability in decision-making performance. We suggest that age-related changes in affective attention influence decision-making, and may, at times, oppose the effects of altered dopamine function on performance. We propose that accounting for interactions between dopamine and affective attention will be useful for explaining apparent noise in decision-making performance between individuals and between tasks.In this section, we briefly review methods for in vivo dopamine imaging in humans, which we hope provides useful background information for our discussion of how these methods can bolster our understanding of decision-making in aging.

PET imaging allows for the assessment of multiple components of dopamine function in vivo in animal models and humans. Here, we focus our review on PET imaging methods, though similar principles apply to SPECT imaging. Radiotracers have been developed that target dopamine receptors, transporters, and enzymes involved in dopamine synthesis . Commonly, PET imaging is conducted while subjects are not cognitively engaged in a specific task, but are in baseline resting conditions. Examples of how dopamine PET is paired with simultaneous cognitive task performance is described below. In a typical experiment, a subject is injected with a single bolus of the radiotracer and undergoes imaging over the course of 60–90 minutes. Kinetic modeling is applied to the data to provide a single whole-brain image . This image provides a static snapshot of the occupancy of specific dopamine receptors or transporters, or enzymatic function underlying dopamine synthesis capacity within an individual . Similarly, neuromelanin-sensitive MR approaches provide a static snapshot of the health of the nigral dopamine system , though relationships between MR and PET measures have not yet been established . Region of interest analyses can test how these measures vary across individuals and correlate with specific behaviors or other neural measures. For imaging receptors and transporters, radiotracers that act as competitive agonists or antagonists are used. It is worth noting that while most tracers give good quantitation in the striatum where the concentration of dopamine targets is high, fewer tracers allow for measurement in regions such as thalamus, amygdala, hippocampus, and cortex, where concentrations may be 10-fold less. Therefore, higher affinity tracers for D1 and D2/3 receptors must be used for research aimed at delineating contributions of cortical dopamine in decision-making. Tracers targeting receptors and transporters are characterized as “reversible,” meaning they bind to their target but can also dissociate until they reach a steady state during which the flux of tracer tissue binding equals the flux of dissociation back into blood. Calculations of non-displaceable binding potential are common for assessing individual difference in the availability of dopamine receptors and transporters . In a given region of interest, BPND reflects the density and affinity of the targeted receptor or transporter. However, as the tracer is in competition with endogenous dopamine to bind to its target, BPND is also sensitive to individual differences in the concentration of endogenous dopamine. Therefore,BPND comprises both the density/affinity of the receptor/transporter of interest as well as the concentration of competing dopamine particularly for lower affinity tracers. Thus, there is no “pure” PET measure of dopamine receptor density or transporter density. There are established PET methods for assessing dopamine release within individual subjects, which capitalize on the competitive displacement of radiotracers by endogenous dopamine . Specifically, decreases in receptor BPND accompany increases in extracellular dopamine concentration, which has been validated by simultaneous microdialysis . Due to slow tracer kinetics, black plastic plant pots bulk current PET imaging methods do not allow for event-related measurement of dopamine release for single trials. Therefore, direct comparison with phasic dopamine release afforded by fast scan cyclic voltammetry in animal models is untenable. In humans, PET measures of dopamine release reflect changes in extracellular dopamine across 10–60 minutes, depending on study design.

One approach is to collect two PET scans per subject and compare baseline BPND with BPND during task performance , or following administration of a drug that increases synaptic dopamine concentration by blocking dopamine reuptake or stimulating release . A second approach is to measure alteration in dopamine release across a single session. These protocols are somewhat more onerous and usually require constant infusion of the radiotracer, but have demonstrated increases in dopamine release associated with cognitive task performance . In addition to PET imaging, it is possible to assess dopaminergic function in vivo using neuromelanin-sensitive MR. This approach enables the visualization of monoaminergic nuclei in the substantia nigra pars compacta and locus ceruleus . Neuromelanin’s binding to iron and copper facilitates the visualization of neuromelanin-rich regions in using MR approaches . Its sequestration of heavy metals is likely neuroprotective, though after neuronal death, the release of toxins into extracellular space may be detrimental . Supporting the validity of this measure for assessing individual differences in the integrity of substantia nigra dopaminergic function, there is evidence that neuromelanin MR signal is reduced in Parkinson’s disease and distinguishes healthy controls from people with schizophrenia and depression . Consistent with PET dopamine synthesis findings, healthy aging is associated with elevation of neuromelanin . Individual differences in neuromelanin MR signal in healthy aging have been linked to variability in reward learning , memory performance , and fMRI activation during encoding . To date, there has been little investigation characterizing relationships between neuromelanin MR signal and dopamine PET measures within subject in young or older adults. One study reported a positive relationship between neuromelanin signal and D2/3 BPND in VTA/substantia nigra, but failed to find a relationship with dopaminesynthesis capacity . However, this study may have been underpowered , and used L-[β− 11C]DOPA to measure dopamine synthesis capacity, which complicates data analysis compared to the fluoro-l-mtyrosine PET measure of dopamine synthesis capacity . While the neuromelanin MR imaging approach is still under active development , it represents a low-cost and easily implemented way to approximate individual differences in the integrity of neurochemical systems relevant to cognition.In vivo imaging has the advantage of providing a within-subject, continuous measure of dopamine function that can be used to assess individual differences and offers a perspective of which brain regions may be preferentially associated with specific aspects of cognitive performance. What has emerged in the study of aging is the observation that changes are not monotonic. Different components of the dopamine system appear to change at different rates, in different directions, or not at all. Further, age-related changes in dopamine receptors may be spatially nonuniform. Below, we summarize these findings, which together speak to the limitations of experimental approaches that do not seek to account for such heterogeneity in the effects of aging on the neural systems supporting decision-making. A recent meta-analysis examining age-related changes in dopamine PET measures found consistent evidence that D1 and D2/3 BPND decline with aging . Though the studies examined in this meta-analysis were cross-sectional rather than longitudinal, the magnitude of age-related reductions was illustrated by the estimation of the percent reduction per decade of life. D1 receptors declined at a rate of ~14% per decade while D2/3 receptors and the dopamine transporter declined at a rate of 8%–9% per decade. These estimations derived from human PET imaging studies are generally consistent with, though in some cases are slightly higher than quantitation from postmortem human tissue and nonhuman animal studies . While receptor BPND is lower in older adults relative to young, studies consistently reveal substantial inter-individual variability in D1 and D2/3 BPND in older adults. For example, D2/3 BPND is relatively preserved in people who are more physically active . Such interindividual variability appears to be relevant to cognition, as it correlated with differences in psychomotor function , executive function , and memory in older adults. While dopamine receptor BPND declines in aging, there is accumulating evidence that dopamine synthesis capacity is elevated in older adults .