Human and mouse subjects tried to anticipate at which of 2 locations a reward would appear. On a randomly scheduled fraction of the trials, it appeared with a short latency at one location; on the complementary fraction, it appeared after a longer latency at the other location. Subjects of both species accurately assessed the exogenous uncertainty (the probability of a short versus a long trial) and the endogenous uncertainty (from the scalar variability in their estimates of an elapsed duration) to compute the optimal target latency for a switch from the short- to the long-latency location. The optimal latency was arrived at so rapidly that there was no reliably discernible improvement over trials. Under these nonverbal conditions, humans and mice accurately assess risks and behave nearly optimally. That this capacity is well-developed in the mouse opens up the possibility of a genetic approach to the neurobiological mechanisms underlying risk assessment.

Time is an essential feature of most decisions, because the reward earned from decisions frequently depends on the temporal statistics of the environment (e.g., on whether decisions must be made under deadlines). Accordingly, evolution appears to have favored a mechanism that predicts intervals in the seconds to minutes range with high accuracy on average, but significant variability from trial to trial. Importantly, the subjective sense of time that results is sufficiently imprecise that maximizing rewards in decision-making can require substantial behavioral adjustments (e.g., accumulating less evidence for a decision in order to beat a deadline). Reward maximization in many daily decisions therefore requires optimal temporal risk assessment. Here, we review the temporal decision-making literature, conduct secondary analyses of relevant published datasets, and analyze the results of a new experiment. The paper is organized in three parts. In the first part, we review literature and analyze existing data suggesting that animals take account of their inherent behavioral variability (their “endogenous timing uncertainty”) in temporal decision-making. In the second part, we review literature that quantitatively demonstrates nearly optimal temporal risk assessment with sub-second and supra-second intervals using perceptual tasks (with humans and mice) and motor timing tasks (with humans). We supplement this section with original research that tested human and rat performance on a task that requires finding the optimal balance between two time-dependent quantities for reward maximization. This optimal balance in turn depends on the level of timing uncertainty. Corroborating the reviewed literature, humans and rats exhibited nearly optimal temporal risk assessment in this task. In the third section, we discuss the role of timing uncertainty in reward maximization in two-choice perceptual decision-making tasks and review literature that implicates timing uncertainty as an important factor in performance quality. Together, these studies strongly support the hypothesis that animals take normative account of their endogenous timing uncertainty. By incorporating the psychophysics of interval timing into the study of reward maximization, our approach bridges empirical and theoretical gaps between the interval timing and decision-making literatures.

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In three experiments with mice (Mus musculus) and rats (Rattus norvigicus), we used a switch paradigm to measure quantitative properties of the interval-timing mechanism. We found that: 1) Rodents adjusted the precision of their timed switches in response to changes in the interval between the short and long feed latencies (the temporal goalposts). 2) The variability in the timing of the switch response was reduced or unchanged in the face of large trial-to-trial random variability in the short and long feed latencies. 3) The adjustment in the distribution of switch latencies in response to changes in the relative frequency of short and long trials was sensitive to the asymmetry in the Kullback-Leibler divergence. The three results suggest that durations are represented with adjustable precision, that they are timed by multiple timers, and that there is a trial-by-trial (episodic) record of feed latencies in memory.

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The analysis of response rates has been highly influential in psychology, giving rise to many prominent theories of learning. There is, however, growing interest in explaining response rates, not as a global response to associations or value, but as a decision about how to space responses in time. Recently, researchers have shown that humans and mice can time a single response optimally, i.e., in a way that maximizes reward. Here, we use the well-established DRL timing task to show that humans and rats come close to optimizing reinforcement rate, but respond systematically faster than they should.

The goals of this research were to describe age-related changes in brain biochemistry and behavior, and the relationships between them. The chronological ages of greatest change are particularly important for targeting interventions. In this experiment, 36 Fischer 344/Brown-Norway rats (3, 12, 20, and 30 months old) were trained in lever boxes on temporal discrimination tasks. The greatest response rate decrease and response pattern change occurred between 12 and 20 months. The biochemical results showed that amyloid-beta peptides (Aβ40 and Aβ42) increased with age. The endothelial expression of the Aβ influx transporter (RAGE) also increased, and the expression of Aβ efflux transporter (LPR-1) decreased, with age. The greatest change in the biochemical measures also were between 12 and 20 months. Twenty additional rats were analyzed for stem cell proliferation, and neurogenesis decreased with age, particularly between about 12 and 20 months. These early changes in brain, biochemistry, and behavior provide opportunity for new therapies or prophylaxis.