Contributions of medial prefrontal cortex to decision making involving risk of punishment

Abstract

The prefrontal cortex (PFC) plays an important role in several forms of cost-benefit decision making. Its contributions to decision making under risk of explicit punishment, however, are not well understood. A rat model was used to investigate the role of the medial PFC (mPFC) and its monoaminergic innervation in a Risky Decision-making Task (RDT), in which rats chose between a small, "safe" food reward and a large, "risky" food reward accompanied by varying probabilities of mild footshock punishment. Inactivation of mPFC increased choice of the large, risky reward when the punishment probability increased across the session ("ascending RDT"), but decreased choice of the large, risky reward when the punishment probability decreased across the session ("descending RDT"). In contrast, enhancement of monoamine availability via intra-mPFC amphetamine reduced choice of the large, risky reward only in the descending RDT. Systemic administration of amphetamine reduced choice of the large, risky reward in both the ascending and descending RDT; however, this reduction was not attenuated by concurrent mPFC inactivation, indicating that mPFC is not a critical locus of amphetamine's effects on risk taking. These findings suggest that mPFC plays an important role in adapting choice behavior in response to shifting risk contingencies, but not necessarily in risk-taking behavior per se.

Reward/Punishment‐Based Decision Making in Rodents

“…Performance in this task recapitulates individual differences in risk taking observed in the human population, endowing it with high translational validity (Simon et al, 2009;Simon et al, 2011). Further, performance in this task is easily dissociable from measures of anxiety, motivation, and pain and is sensitive to pharmacological manipulations (Blaes et al, 2018;Orsini et al, 2018;Simon et al, 2009;Simon et al, 2011) and chronic drug self-administration (Mitchell et al, 2014). Finally, consistent with human literature (Byrnes, Miller, & Schafer, 1999;Cross, Copping, & Campbell, 2011;Grissom & Reyes, 2019;Killgore, Grugle, Killgore, & Balkin, 2010), there are clear sex differences in choice behavior in the RDT, with females exhibiting greater risk aversion than males (Orsini, Willis, Gilbert, Bizon, & Setlow, 2016).…”

“…Two such brain regions are the orbitofrontal cortex (OFC) and the medial prefrontal cortex (mPFC). Indeed, we have shown that both of these brain areas are necessary for risky choice (Deng, Orsini, Shimp, & Setlow, 2018;Orsini et al, 2018;Orsini et al, 2015), albeit for different aspects of this cognitive process. Based on findings from lesion experiments in the RDT, the OFC seems to be required to match the expected outcomes of a choice with the actual outcomes of said choice and update these expectations for future decisions (Orsini et al, 2015).…”

Punishment history biases corticothalamic responses to motivationally-significant stimuli

“…Medial PFC (mPFC; also referred to as prelimbic cortex) is known to be involved in learning (Holland and Gallagher, 2004; Luk and Wallis, 2009; Alexander and Brown, 2011; Del Arco et al, 2017; Otis et al, 2017; Orsini et al, 2018), stress (Wellman, 2001; Cook and Wellman, 2004; Radley et al, 2004, 2005; Liston et al, 2006; Radley et al, 2006; Cerqueira et al, 2007; Wei et al, 2007; Liu and Aghajanian, 2008; Radley et al, 2008; Goldwater et al, 2009; Yuen et al, 2012; Adhikari et al, 2015), and uncertainty (Ernst and Paulus, 2005; Opris and Bruce, 2005; Sugrue et al, 2005; Bach et al, 2009; Levy et al, 2010; Orsini et al, 2018). These functions are critical for making predictions about previously unobserved stimuli.…”

“…Cognitive processes—appraisals of stimuli, events and situations—play an important role in generating affective states, and vice versa, these affective states influence cognitive functioning by inducing attentional, memory, and judgment biases (Lerner and Keltner, 2000; Haselton et al, 2009; Harding et al, 2004; Enkel et al, 2010; Rygula et al, 2012; Papciak et al, 2013; Rygula et al, 2013; Parker et al, 2014; Rygula et al, 2014). Among brain regions that are engaged in affective processing, the mPFC has long been implicated in adaptive responding by signaling information about expected outcome and by regulating sensitivity to reward and punishment (Holland and Gallagher, 2004; Luk and Wallis, 2009; Alexander and Brown, 2011; Del Arco et al, 2017; Orsini et al, 2018). Here, we found that firing rates in mPFC neurons reflect cue-evoked expectations for aversion- and reward-predictive cues and were enhanced in mice exposed to a mild punishment, which correlates with a reduction in anticipatory responses to the same stimuli.…”

Prefrontal Regulation of Punished Ethanol Self-administration

“…Taken together, these prior studies suggest that the vmPFC, BLA, and NAc are part of an integrated circuit regulating the seeking, consumption, and, in the face of negative outcomes, avoidance of EtOH and other drugs of abuse (31)(32)(33)(34)(35)(36). Nonetheless, understanding of the contributions of the vmPFC and its downstream connections to the BLA and NAcS to the regulation of punished EtOH-SA remains incomplete.…”