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Touchscreen-based assessment of risky-choice in mice.

ABSTRACT: Addictions are characterized by choices made to satisfy the addiction despite the risk it could produce an adverse consequence. Here, we developed a murine version of a 'risky decision-making' task (RDT), in which mice could respond on a touchscreen panel to obtain either a large milkshake reward associated with varying probability of footshock, or a smaller amount of the same reward that was never punished. Results showed that (the following font is incorrectly smaller/subscripted) mice shifted choice from the large to small reward stimulus as shock probability increased. Immunohistochemical analysis revealed more Fos-positive cells in prelimbic cortex (PL) and basal amygdala (BA) after RDT testing, and a strong anti-correlation between infralimbic cortex (IL) activity and choice of the large reward stimulus under likely (75-100 % probability) punishment. These findings establish an assay for risky choice in mice and provide preliminary insight into the underlying neural substrates.

SUBMITTER: Glover LR

PROVIDER: S-EPMC7423716 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Touchscreen-based assessment of risky-choice in mice.

Glover Lucas R LR Postle Abagail F AF Holmes Andrew A

Behavioural brain research 20200610

Addictions are characterized by choices made to satisfy the addiction despite the risk it could produce an adverse consequence. Here, we developed a murine version of a 'risky decision-making' task (RDT), in which mice could respond on a touchscreen panel to obtain either a large milkshake reward associated with varying probability of footshock, or a smaller amount of the same reward that was never punished. Results showed that (the following font is incorrectly smaller/subscripted) mice shifted ...[more]

PMID: 32531231

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Project description:BackgroundRisky decision-making is commonly observed in persons at risk for and infected with HIV and is associated with executive dysfunction. Yet it is currently unknown whether HIV alters brain processing of risk-taking decision-making.MethodsThis study examined the neural substrate of a risky decision-making task in 21 HIV seropositive (HIV+) and 19 seronegative (HIV-) comparison participants. Functional magnetic resonance imaging was conducted while participants performed the risky-gains task, which involves choosing among safe (20 cents) and risky (40/80 cent win or loss) choices. Linear mixed effects analyses examining group and decision type were conducted. Robust regressions were performed to examine the relationship between nadir CD4 count and Kalichman sexual compulsivity and brain activation in the HIV+ group. The overlap between the task effects and robust regressions was explored.ResultsAlthough there were no serostatus effects in behavioral performance on the risky-gains task, HIV+ individuals exhibited greater activation for risky choices in the basal ganglia, i.e. the caudate nucleus, but also in the anterior cingulate, dorsolateral prefrontal cortex, and insula relative to the HIV- group. The HIV+ group also demonstrated reduced functional responses to safe choices in the anterior cingulate and dorsolateral prefrontal cortex relative to the HIV- group. HIV+ individuals with higher nadir CD4 count and greater sexual compulsivity displayed lower differential responses to safe versus risky choices in many of these regions.ConclusionsThis study demonstrated fronto-striatal loop dysfunction associated with HIV infection during risky decision-making. Combined with similar between-group task behavior, this suggests an adaptive functional response in regions critical to reward and behavioral control in the HIV+ group. HIV-infected individuals with higher CD4 nadirs demonstrated activation patterns more similar to seronegative individuals. This suggests that the severity of past immunosuppression (CD4 nadir) may exert a legacy effect on processing of risky choices in the HIV-infected brain.

Project description:Both normative and many descriptive theories of decision making under risk are based on the notion that outcomes are weighted by their probability, with subsequent maximization of the (subjective) expected outcome. Numerous investigations from psychology, economics, and neuroscience have produced evidence consistent with this notion. However, this research has typically investigated choices involving relatively affect-poor, monetary outcomes. We compared choice in relatively affect-poor, monetary lottery problems with choice in relatively affect-rich medical decision problems. Computational modeling of behavioral data and model-based neuroimaging analyses provide converging evidence for substantial differences in the respective decision mechanisms. Relative to affect-poor choices, affect-rich choices yielded a more strongly curved probability weighting function of cumulative prospect theory, thus signaling that the psychological impact of probabilities is strongly diminished for affect-rich outcomes. Examining task-dependent brain activation, we identified a region-by-condition interaction indicating qualitative differences of activation between affect-rich and affect-poor choices. Moreover, brain activation in regions that were more active during affect-poor choices (e.g., the supramarginal gyrus) correlated with individual trial-by-trial decision weights, indicating that these regions reflect processing of probabilities. Formal reverse inference Neurosynth meta-analyses suggested that whereas affect-poor choices seem to be based on brain mechanisms for calculative processes, affect-rich choices are driven by the representation of outcomes' emotional value and autobiographical memories associated with them. These results provide evidence that the traditional notion of expectation maximization may not apply in the context of outcomes laden with affective responses, and that understanding the brain mechanisms of decision making requires the domain of the decision to be taken into account.

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Touchscreen-based assessment of risky-choice in mice.

Publications

Touchscreen-based assessment of risky-choice in mice.

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