Leveraging individual differences in cue-reward learning to investigate the psychological and neural basis of shared psychiatric symptomatology: The sign-tracker/goal-tracker model

Abstract

In our modern environment, we are bombarded with stimuli or cues that exert significant influence over our actions. The extent to which such cues attain control over or disrupt goal-directed behavior is dependent on several factors, including one's inherent tendencies. Using a rodent model, we have shown that individuals vary in the value they place on stimuli associated with reward. Some individuals, termed "goal-trackers," primarily attribute predictive value to reward cues, whereas others, termed "sign-trackers," attribute predictive and incentive value. Thus, for sign-trackers, the reward cue is transformed into an incentive stimulus that is capable of eliciting maladaptive behaviors. The sign-tracker/goal-tracker animal model has allowed us to refine our understanding of behavioral and computational theories related to reward learning and to parse the underlying neural processes. Further, the neurobehavioral profile of sign-trackers is relevant to several psychiatric disorders, including substance use disorder, impulse control disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, and posttraumatic stress disorder. This model, therefore, can advance our understanding of the psychological and neurobiological mechanisms that contribute to individual differences in vulnerability to psychopathology. Notably, initial attempts at translation-capturing individual variability in the propensity to sign-track in humans-have been promising and in line with what we have learned from the animal model. In this review, we highlight the pivotal role played by the sign-tracker/goal-tracker animal model in enriching our understanding of the psychological and neural basis of motivated behavior and psychiatric symptomatology. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Figure 1. Neural circuits underlying sign-tracking and goal-tracking.

This graphic illustrates brain areas as well as the afferent and efferent connections thought to underlie (A) goal-tracking and (B) sign-tracking. (A) Goal-trackers (GTs) attribute predictive value to the lever-cue (conditioned stimulus, CS) that precedes the delivery of food reward (unconditional stimulus, US) and approach the location of the reward upon presentation of the lever-cue (CS). (B) Sign-trackers (STs) attribute both predictive and incentive value to the lever-cue (CS) and approach and manipulate it upon presentation. Brain regions believed to contribute to the respective behaviors are presented in color, while regions that do not appear to play significant role are in gray. Projections that are depicted as dotted black lines indicate the presence of neuronal connections but their influence on sign- or goal-tracking have not yet been elucidated. Neuronal projections that have been shown to play a role are depicted by the axonal schematic. (A) Goal-tracking behavior appears to depend largely on cortical systems, while (B) sign-tracking behavior relies on sub-cortical systems. The paraventricular nucleus of the thalamus (PVT; orange neuron) and nucleus accumbens (NAc; neuron) have been implicated in both behaviors, but likely with different “weights” of inputs from cortical and subcortical structures in goal-trackers versus sign-trackers. (A) The green neuron represents the dense glutamatergic (Glu) innervation from the prelimbic cortex (PrL)-PVT. (B) The purple neuron represents orexinergic (OX) innervation from the lateral hypothalamus (LH)-PVT. The orange neuron is illustrating glutamatergic (Glu) innervation from the PVT- NAc. The turquoise neuron represents dopaminergic (DA) innervation from the ventral tegmental area (VTA)-NAc. Abbreviations: Amy, amygdala; Hipp, hippocampus; LH, lateral hypothalamus; NAc, nucleus accumbens; PrL, prelimbic cortex; PVT, paraventricular thalamic nucleus; VTA, ventral tegmental area; DA, dopamine; Glu, glutamate; OX, orexin.

Figure 2. Distribution of the sign-tracker/goal-tracker phenotypes in a large rat population and associated behaviors of relevance to psychiatric disorders.

This histogram represents a frequency distribution of the propensity to attribute incentive salience to a reward cue in 6182 Sprague-Dawley rats. The Pavlovian conditioned approach (PavCA) Index, is a composite score used to assess the propensity of an individual rat to approach the lever-CS (sign-tracking) vs. the food cup (goal-tracking) across five conditioning sessions. An index of −0.5 to −1.0 indicates that the rat is a goal-tracker (GT). An index of 0.5 to 1.0 indicates that the rat is a sign-tracker (ST). An index between −0.5 to 0.5 indicates that the rat is an intermediate responder (IR). The large population of rats came from a database of rats that have been screened for Pavlovian conditioned approach behavior in the labs of Drs. Shelly Flagel, Jonathan Morrow, Terry Robinson, and Martin Sarter at the University of Michigan. The behavioral characteristics of each phenotype (described in the main text) are indicated below the goal-trackers (orange) and sign-trackers (blue). Abbreviations: ICD, Impulse Control Disorders; ADHD, Attention Deficit Hyperactivity Disorder; PTSD, Post-traumatic Stress Disorder; SUD, Substance Use Disorder; OCD, Obsessive-Compulsive Disorder