Separate Prefrontal-Subcortical Circuits Mediate Different Components of Risk-Based Decision Making

Abstract

Choosing between smaller, assured rewards or larger, uncertain ones requires reconciliation of competing biases towards more certain or riskier options. We used disconnection and neuroanatomical techniques to reveal that separate, yet interconnected, neural pathways linking the medial prefrontal cortex (PFC), the basolateral amygdala (BLA) and nucleus accumbens (NAc) contribute to these different decision biases in rats. Disrupting communication between the BLA and NAc revealed that this subcortical circuit biases choice towards larger, uncertain rewards on a probabilistic discounting task. In contrast, disconnections between the BLA and PFC increased choice of the Large/Risky option. PFC-NAc disconnections did not affect choice but did increase choice latencies and trial omissions. Neuroanatomical studies confirmed that projection pathways carrying axons from BLA-to-PFC transverse a distinctly different route relative to PFC-to-BLA pathways (via the ventrolateral amydalofugal pathway and ventromedial internal capsule, respectively). We exploited these dissociable axonal pathways to selectively disrupt bottom-up and top-down communication between the BLA and PFC. Subsequent disconnection studies revealed that disruption of top-down (but not bottom-up) information transfer between the medial PFC and BLA increased choice of the larger, riskier option, suggesting that this circuit facilitates tracking of actions and outcomes to temper urges for riskier rewards as they become less profitable. These findings provide novel insight into the dynamic competition between these cortical/subcortical circuits that shape our decision biases and underlie conflicting urges when evaluating options that vary in terms of potential risks and rewards.

Modulation of risk/reward decision making by dopaminergic transmission within the basolateral amygdala

“…One potential mechanism through which choice bias could be influenced may be in balancing sensory and PFC inputs into the BLA. PFC inputs to the BLA play a critical role in modulating probabilistic discounting (St Onge et al 2012) and D 1 receptor activity can modulate neurophysiological inputs from the PFC a Choice data from the subset of rats tested on the ascending (top) and Descending (bottom) variants of the task. Inset displays baseline choice behavior from risk-averse and risk-prone rats averaged over 4 days prior to the first microinfusion test.…”

“…On the other hand, administration of a large (6 mg/kg) dose of SKF 81297 in vivo has been reported to attenuate prefrontal inputs onto BLA neurons, putatively via presynaptic actions (Rosenkranz and Grace 2001). Thus, more intense stimulation of D 1 receptors within the BLA may blunt incoming signals from the PFC that aid to refine decision biases (St Onge et al 2012), which could potentially counteract the ability of postsynaptic activation of these receptors to optimize decision making.…”

“…Previous studies using this assay have identified a key role for the BLA in biasing choice towards larger, uncertain rewards via interactions with its primary striatal output, the NAc. Bilateral inactivation of either region reduced preference of larger, uncertain rewards (Ghods-Sharifi et al 2009;Stopper and Floresco 2011), as did asymmetrical disconnection inactivations of the BLA and NAc (St Onge et al 2012). In comparison, the prelimbic region of the medial PFC appears to facilitate modification of decision biases in response to changes in reward probabilities (St Onge et al 2011).…”

“…When the probability of obtaining a larger reward was initially high at the start of a session and then decreased (100→12.5 %) PFC inactivation increased risky choice, whereas when the odds were initially poor and improved over a session, rats were slower to shift bias towards the risky option as the odds became more favorable. Furthermore, the ability of the PFC to aid in modifying decision biases appears to be mediated via top-down control of the BLA, as selective disconnection of PFC projections to the BLA altered decision making in a manner similar to bilateral inactivation of the PFC (St Onge et al 2012). This latter finding suggests that the PFC tempers the influence that BLA-NAc circuitry exerts over the direction of choice.…”

Enhancement of Fear Extinction with Deep Brain Stimulation: Evidence for Medial Orbitofrontal Involvement

“…The infralimbic(IL) cortex and prelimbic (PL) cortex project through VS (Berendse et al, 1992;Mailly et al, 2013;McGeorge and Faull, 1989;Sesack et al, 1989;St Onge et al, 2012;Vertes, 2004) and could potentially mediate DBS effects on extinction. It is well established that inhibition of IL impairs fear extinction (Burgos-Robles et al, 2007;Laurent and Westbrook, 2009;Quirk et al, 2000;SierraMercado et al, 2011), whereas stimulation of IL enhances extinction (Kim et al, 2010;Maroun et al, 2012;Milad and Quirk, 2002;Milad et al, 2004).…”