Age-Related Changes in Risky Decision Making and Associated Neural Circuitry in a Rat Model

Abstract

Altered decision making at advanced ages can have a significant impact on an individual’s quality of life and the ability to maintain personal independence. Relative to young adults, older adults make less impulsive and less risky choices; although these changes in decision making could be considered beneficial, they can also lead to choices with potentially negative consequences (e.g., avoidance of medical procedures). Rodent models of decision making have been invaluable for dissecting cognitive and neurobiological mechanisms that contribute to age-related changes in decision making, but they have predominantly used costs related to timing or probability of reward delivery and have not considered other equally important costs, such as risk of adverse consequences. The current study therefore used a rat model of decision making involving risk of explicit punishment to examine age-related changes in this form of choice behavior in male rats, and to identify potential cognitive and neurobiological mechanisms that contribute to these changes. Relative to young rats, aged rats displayed greater risk aversion, which was not attributable to reduced motivation for food, changes in shock sensitivity, or impaired cognitive flexibility. Functional MRI analyses revealed that overall, functional connectivity was greater in aged rats compared with young rats, particularly among brain regions implicated in risky decision making such as basolateral amygdala, orbitofrontal cortex, and ventral tegmental area. Collectively, these findings are consistent with greater risk aversion found in older humans, and reveal age-related changes in brain connectivity.SIGNIFICANCE STATEMENTChanges in cost-benefit decision making at advanced ages can be modeled in rats. Although such models have largely corroborated age changes in some forms of decision making, they have not evaluated decisions involving risks of adverse consequences (i.e., punishment). The current study evaluated young and aged rats in a decision making task involving risk of punishment. As in humans, aged rats were more risk averse than young. This greater risk aversion was accompanied by greater functional connectivity among brain regions implicated in risky decision making. The findings suggest that greater risk aversion in aging is due to inherent (biological) factors, and establish a model in which future work can evaluate neural mechanisms underlying age-related changes in risk taking.

Aging or chronic stress impairs working memory and modulates GABA and glutamate gene expression in prelimbic cortex

“…Fewer trials could reflect reduced motivation to respond for food rewards or greater sensitivity to reward devaluation as rats become sated during each test session. Normal aging is associated with lower motivation to work for food rewards in progressive ratio tasks ( Hernandez et al, 2017 ; Jackson et al, 2021 ; Orsini et al, 2023 ) whereas pre-feeding to induce satiety and devalue food rewards is similar between young adult and aged rats ( Samson et al, 2014 ). To the best of our knowledge, no studies have investigated the effect of CVS on either progressive ratio or outcome devaluation tasks.…”

RECORD: A high-throughput system for complex naturalistic decision-making in rodents

“…RECORD Manual tmazes 5,10,15,25 Automatic tmazes 12,13 Virtual reality tasks 14,59 Operant Chambers (lever pressing and nose pokes) 3,22,23,28,49,60 Wheel Displacement…”

“…Some operant conditioning tasks use touchscreens as an alternative to traditional nose-poke compartments 21 ; others may extend the experimental space so the rodent traverses the chamber when deciding 22 , while some tasks utilize auditory cues to signal the presence of a reward or cost 19 .All the aforementioned methods are excellent tools for studying different facets of DM. Nonetheless, most of these methods are used to analyze one or two levels of rewards and costs at a time 3,5,23 . A task environment that enables the implementation of multiple reward and cost trade-offs within one behavioral session heightens a system's ability to detect individual differences, as well as enabling the comprehensive identification of DM phenotypes that are overrepresented in animal models of psychiatric disorders 11,24 .…”

“…Executing and analyzing numerous trials is greatly facilitated by using an automatic and high-throughput system 26 . Moreover, published DM tasks do not incorporate natural rodent behaviors, which may lead to choices and behaviors that differ from those displayed in a natural environment 27 .A predominant component of published DM tasks is the use of food 3,5,12,18,21,28 or water restriction 14,16,22,23,25 to train and motivate rodents to perform the behavioral protocols. Chronic deprivation may impact DM, along with its associated behaviors, because it is a form of stress that dramatically alters circulating hormones, blood glucose, and other physiological measures that impact appetitive processing 29 .…”

How Does Aging Affect Decision-making? An Integrated Model Based on Neuroscience

“…The greater risk aversion is observed in older humans and highlights age-related alterations in brain connectivity. FMRI analyses demonstrated that, on the whole, aged rats exhibited higher functional connectivity compared to young rats, especially among brain regions associated with risky decisionmaking, such as the basolateral amygdala, orbitofrontal cortex, and ventral tegmental area [22].…”