Behavioral Paradigms to Probe Individual Mouse Differences in Value-Based Decision Making

Abstract

Value-based decision making relies on distributed neural systems that weigh the benefits of actions against the cost required to obtain a given outcome. Perturbations of these systems are thought to underlie abnormalities in action selection seen across many neuropsychiatric disorders. Genetic tools in mice provide a promising opportunity to explore the cellular components of these systems and their molecular foundations. However, few tasks have been designed that robustly characterize how individual mice integrate differential reward benefits and cost in their selection of actions. Here we present a forced-choice, two-alternative task in which each option is associated with a specific reward outcome, and unique operant contingency. We employed global and individual trial measures to assess the choice patterns and behavioral flexibility of mice in response to differing "choice benefits" (modeled as varying reward magnitude ratios) and different modalities of "choice cost" (modeled as either increasing repetitive motor output to obtain reward or increased delay to reward delivery). We demonstrate that (1) mouse choice is highly sensitive to the relative benefit of outcomes; (2) choice costs are heavily discounted in environments with large discrepancies in relative reward; (3) divergent cost modalities are differentially integrated into action selection; (4) individual mouse sensitivity to reward benefit is correlated with sensitivity to reward costs. These paradigms reveal stable individual animal differences in value-based action selection, thereby providing a foundation for interrogating the neural circuit and molecular pathophysiology of goal-directed dysfunction.

Disruption of Nrxn1α within excitatory forebrain circuits drives value-based dysfunction

“…To assess whether Nrxn1α KOs show altered influence of reward history on current choice, we employed logistic regression models to generate weighted coefficients representing the relative effect of choice and outcome 5 trials preceding current choice (Lau and Glimcher, 2005; Parker et al, 2016; Tai et al, 2012). Similar to prior work (Alabi et al, 2019), we found that wildtype mice and Nrxn1α KOs heavily discount all but the immediately preceding trial (t-1) (Fig.S1E-H). This suggested a significant portion of variability in choice behavior could be understood by analyzing the results of the t-1 trial.…”

“…To specifically test how Nrxn1α mutant mice use value information to guide future choice, we employed a feedback-based paradigm that samples mouse choice across outcome values (Fig.1A). This task utilizes a block design with dynamically alternating reward contingencies triggered by recent choice biases to maintain outcome sensitivity over hundreds of trials (Fig.1A, see (Alabi et al, 2019) and STAR Methods for details). Mice self-initiated trials in which two lateralized (left/right) choices with contrasting reward volumes were available.…”

“…Performance in this task can be altered by changes in: (1) the integration window for feedback history; (2) sensitivity to outcome feedback; (3) response to the absence of feedback; (4) flexibility to changing contingencies (Alabi et al, 2019). To assess whether Nrxn1α KOs show altered influence of reward history on current choice, we employed logistic regression models to generate weighted coefficients representing the relative effect of choice and outcome 5 trials preceding current choice (Lau and Glimcher, 2005; Parker et al, 2016; Tai et al, 2012).…”

“…We reasoned the efficiency of selecting more beneficial alternatives is driven by comparative sensitivity to reward outcomes of differing magnitudes. Given the steep decay of our logistic regression curves, we calculated the relative reward-stay (RRS), a descriptive measure of the relative reinforcing properties of large and small rewarded t-1 outcomes (previously called relative action value in (Alabi et al, 2019)). We noted smaller gaps between large reward-stay and small reward-stay behavior in Nrxn1α KOs as compared with wildtypes (Fig.1C,D), leading to smaller relative reward-stay values across reward contrasts and feedback environment (Fig.1E).…”

“…Deficits in behavioral adaptability have been observed across neuropsychiatric disorders and can impact performance in our task (Alabi et al, 2019). To explore differences in flexible responding between Nrxn1α mutants and wildtypes, we compared choice patterns immediately before and after un-c ued contingency switches triggered by a fixed directional bias (8/10 selections to the large reward choice).…”