The neuroscience of cognitive-motivational styles: Sign- and goal-trackers as animal models

Abstract

Cognitive-motivational styles describe predominant patterns of processing or biases that broadly influence human cognition and performance. Here we focus on the impact of cognitive-motivational styles on the response to cues predicting the availability of food or addictive drugs. An individual may preferably conduct an analysis of the motivational significance of reward cues, with the result that such cues per se are perceived as rewarding and worth approaching and working for. Alternatively, a propensity for a "cold" analysis of the behavioral utility of a reward cue may yield search behavior for food or drugs but not involve cue approach. Animal models for studying the neuronal mechanisms mediating such styles have originated from research concerning behavioral indices that predict differential vulnerability to addiction-like behaviors. Rats classified as sign- or goal-trackers (STs, GTs) were found to have opposed attentional biases (bottom-up or cue-driven attention vs. top-down or goal-driven attentional control) that are mediated primarily via relatively unresponsive versus elevated levels of cholinergic neuromodulation in the cortex. The capacity for cholinergic neuromodulation in STs is limited by a neuronal choline transporter (CHT) that fails to support increases in cholinergic activity. Moreover, in contrast to STs, the frontal dopamine system in GTs does not respond to the presence of drug cues and, thus, biases against cue-oriented behavior. The opponent cognitive-motivational styles that are indexed by sign- and goal-tracking bestow different cognitive-behavioral vulnerabilities that may contribute to the manifestation of a wide range of neuropsychiatric disorders. (PsycINFO Database Record

Figure 1

Sustained Attention Task (SAT) performance-associated increases in extracellular acetylcholine (ACh) levels in the medial prefrontal cortex of goal-trackers (GTs) and sign-trackers (STs; B1-B3, pretask baseline; T1-T8: during SAT; PT1-PT5: posttask levels). Absolute basal ACh release levels did not differ between the groups. The relatively poor and unstable attentional performance of STs was associated with strikingly attenuated right prefrontal extracellular ACh levels when compared with GTs (from Paolone et al., 2013, reprinted with permission). See the online article for the color version of this figure.

Figure 2

In synaptosomes from sham-stimulated (unstimulated) animals, the density of choline transporters (CHTs) in the synaptosomal plasma membrane (indicated by red protein symbols in membrane) did not differ between sign-trackers (STs) and goal-trackers (GTs), consistent with the absence of differences in basal, absolute levels of acetylcholine (ACh) release as measured by microdialysis. However, while total synaptosomal CHT protein did not differ between the phenotypes, the density of CHTs in the intracellular LP2 fraction (blue protein symbols) was lower in STs than in GTs, suggesting that a portion of CHTs in STs are on domains not captured by our fractionation methods. Following basal forebrain electrical stimulation (BF-ES), in GTs, CHT density in the synaptosomal plasma membrane increased and this was reciprocated by losses in the LP2 fraction, consistent with an upregulation of the capacity of cholinergic neurons of GTs to increase levels of neuromodulation. In STs, BF-ES failed to increase synaptosomal plasma CHT density. Moreover, intracellular CHT density also decreased in STs following BF-ES, suggesting again that CHT trafficking in STs involves additional subcellular domains hosting CHTs. The absence of increases in CHT density in synaptosomal plasma membrane in STs is hypothesized to be the primary mechanism responsible for the limited capacity of cholinergic neurons of STs to support increases in levels of cholinergic neuromodulation (for details see Koshy Cherian et al., 2017). See the online article for the color version of this figure.

Figure 3

Number of approaches to the Pavlovian drug cue and extracellular dopamine (DA) and acetylcholine (ACh) levels in sign-trackers (STs) and goal-trackers (GTs) during 4-min blocks during which the cue was presented eight times for 5 s every 30 s (cocaine was unavailable). STs significantly approached the cue more frequently than GTs, exhibited increased prefrontal DA levels and, in contrast to GTs, did not exhibit increases in ACh release. Unpaired rats did not approach the cue and did not exhibit significant changes in DA or ACh levels. In STs, the number of approaches and DA levels were significantly correlated (Pitchers, Kane, et al., 2017). See the online article for the color version of this figure.

Figure 4

Number of responses previously yielding cocaine infusions in the presence of the DS+ by sham-operated goal-trackers (GTs) and sign-trackers (STs) and rats with 192 IgG saporin-induced (SAP) losses of the BF cholinergic system. Sham-operated GTs generated significantly more nose-pokes than STs. Loss of about 50% of the cholinergic neurons in the basal forebrain reduced cocaine-seeking behavior in GTs to the level seen in sham-operated STs. The lesions had no effects on cocaine-seeking in STs (reproduced with permission from Pitchers, Phillips, et al., 2017). See the online article for the color version of this figure.