Association between cortical dopamine receptor patterns and valuative network functional responses

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Abstract Submission 

Niall Duncan¹, Melanie Sun²

¹Taipei Medical University, Taiwan, Taipei, ²Taipei Medical University, Taipei, Taipei City

Niall Duncan  
Taipei Medical University
Taiwan, Taipei

Melanie Sun  
Taipei Medical University
Taipei, Taipei City

The dopamine system is integral to how we learn from experiences in the world. It appears to respond to events that provide positive or negative consequences to update internal models that then inform future behavioural decisions. Studying this system in humans is challenging though, as there are limited non-invasive options available for characterising it (Sands et al., 2023). One technique that can give insight is PET imaging using ligands that bind to dopamine receptors. A limitation of this approach is that it primarily gives static estimates of receptor distributions. Integration of these with functional imaging techniques is therefore required. In this work we aimed to relate dopamine receptor (D1 and D2) distributions with fMRI responses from a task in which participants had to make choices that resulted in them either winning or losing money.

Openly available maps of D1 and D2 receptor distributions were used (Hansen et al., 2022), with D1 receptors being the primary target. D1 receptors were imaged with SCH23390. A group map was made by averaging across the 13 participants. D2 receptors were imaged with FLB457, with a group map being made in the same manner (n = 55). Serotonin receptor maps (5-HT1A and 5-HT2A) were also analysed as controls. Task fMRI data was also taken from an open dataset (Botvinik-Nezer et al., 2019). In this, participants did a gambling task where they could either win or lose a certain amount of money. In one group (n = 54), the win and loss amounts were the same ("equal range") whilst in the other potential winnings were larger than losses ("equal indifference"). Task data were analysed with a standard GLM approach to produce activation maps for gains and losses. These activation maps were then correlated with receptor maps through spin permutation.

The fMRI task produced distinct activation maps for the two groups (Figure 1A). Gain activation in the "equal indifference" group was centred around the vmPFC whilst activations in the "equal range" group were seen in more lateral prefrontal regions. Loss trials showed responses centred more around the midcingulate in both groups. D1 receptors alone were correlated with task responses during winning trials in the "equal indifference" group (Figure 1B). No associations were found with responses in the "equal gain" group. Taking the "equal indifference" gain maps, the specificity of the relationship with D1 receptors was then investigated. No relationship was found with the D2 receptor distribution. A potential correlation with 5-HT2A receptors was identified but this did not survive correction for multiple comparisons (Figure 1C).

These results suggest that cortical D1 receptors specifically are involved in modulating local responses to positive valuations. This appears only to be true, though, when there is a difference in valuation to be attached to two options as there was no relationship with activity patterns in response to equal win/loss outcome values. This points to a role for cortical D1 receptors in modulating local neural network dynamics to facilitate decision making in contexts where a choice for potentially advantageous outcomes are present and when that predicted outcome is delivered. This may fit with the more general view of the dopamine system's involvement in outcome prediction and the updating of internal models based upon mismatch signals (Dabney et al., 2020). This would provide useful additional information from humans in vivo that builds upon that obtained from non-human primates.

Reward and Punishment ¹

Transmitter Receptors ²

Dopamine

FUNCTIONAL MRI

Neurotransmitter

Open Data

Positron Emission Tomography (PET)

RECEPTORS