ACNP 55th Annual Meeting: Poster Session IDecember 5, 2016

Abstract

Background: Foraging is experimentally defined as a rewardguided behavior that involves deciding whether to engage with the current environment or leave and search elsewhere. This type of decision is crucial for survival and depends on a widespread circuit in the brain (including the midbrain, striatum, medial prefrontal cortex, and anterior cingulate cortex) that is important for encoding and comparing values of different options in order to appropriately adjust behavior (6,7,8). Furthermore, neuromodulators such as dopamine and norepinephrine have been implicated in foraging behavior due to their role in value coding, through integration of reward prediction errors, as well as by controlling the tradeoff between exploitation of a known reward environment and exploration of other unknown options (1,3,4,11). Abnormalities in this type of decision-making have been found in addiction, Parkinson’s disease, and schizophrenia, all associated with dysfunction of the dopamine system. Although previous studies have identified an important role of the anterior cingulate cortex (ACC) and of neuromodulators in foraging behavior, it is unclear how regional variation in dopamine synthesis and receptors impacts behavior in humans. Here we directly measured dopamine presynaptic synthesis capacity and D1 and D2 receptor binding potential with PET imaging. In these same individuals, we measured foraging behavior using a computer-based task and tested for relationships between dopamine measures and adaptive foraging behaviors. Methods: Fifty-one healthy adults (mean age 33.9 ± 1.3 years; 25 females) were recruited from the local community and screened by a physician to rule out psychiatric, neurological, or major medical illness. Participants were also excluded if they were taking medications that could affect neural function. Foraging behavior was assessed with a computer-based task in which subjects collect apples (later converted to money and added to their compensation) from trees in four different apple orchards (hereafter referred to as reward environments) that differ in how quickly the trees run out of apples with each harvest (depletion rate) and how long it takes to travel from tree to tree, both of which affect the average reward rate (2). With each presented decision, subjects can either harvest apples from the tree they are currently at or leave and move on to a new tree. The behavioral measure of interest is the threshold for leaving a tree (patch-leaving threshold) and how the threshold changes between reward environments that differ in average reward rates. On separate days, subjects completed three PET scans to directly measure presynaptic dopamine synthesis capacity ([18F]-FDOPA, 45 participants) and D1 ([11C]NNC112, 39 participants) and D2-3 ([18F]Fallypride, 39 participants) receptor binding potential (BPnd), while resting with their eyes open. Subjects also completed a T1-weighted MRI scan used for registration and brain segmentation (with Freesurfer and manual adjustments) to generate native-space regions of interest (ROIs) in the basal ganglia (putamen, caudate nucleus, ventral striatum, and dopaminergic midbrain). The FDOPA uptake rate (Ki) was calculated with the Gjedde-Patlak method (5,10) and dopamine D1 and D2 receptor BPnd was calculated with the SRTM method (9) using a cerebellar reference region. We tested for correlations between PET measures and adaptive foraging behavior, measured as the change in patch leaving threshold between the two reward environments with maximally different average reward rates, using statistical thresholds of po0.05 (hypothesis-driven basal ganglia ROIs) and po0.005 (whole-brain voxelwise data), uncorrected. Results: Adaptive foraging behavior was positively correlated with FDOPA Ki in extrastriatal regions including the ACC (r= 0.50, p= 0.00073) and posterior midbrain (r= 0.47, p= 0.0015), with D1 BPnd in the ventral striatum (r= 0.43, p= 0.0071), and with D2-3 BPnd in the dopaminergic midbrain (r= 0.41, p= 0.033). Conclusions: We found PET correlates of decision-making in a patch foraging task that supports previous work in animals and patients with Parkinson’s disease suggesting a role of neuromodulators in tracking the average reward rate of the environment and adjusting the threshold for deciding to leave a particular potentially rewarding environment (3,6). Specifically, the change in patch exit threshold between environments with maximally different average reward rates was correlated with dopamine synthesis capacity in the anterior cingulate cortex and posterior midbrain as well as D1 receptor BPnd in the ventral striatum and D2 receptor BPnd in the midbrain. These data provide direct insights into the roles of dopamine synthesis capacity and receptor availability in frontostriatal and midbrain in modulating adaptive behavior in humans.

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