Amphetamine reduces utility encoding and stabilizes neural dynamics in rat anterior cingulate cortex

The anterior cingulate cortex (ACC) appears to support decisions by encoding the effort-reward utility of choice options. We show here that d-amphetamine (AMPH) has dose-dependent effects on this encoding and on neural dynamics in rat ACC that are concordant with its behavioral effects. Low-dose AMPH increased task engagement and had mild effects on neural encoding, whereas high doses disrupted utility signaling and decreased task engagement. The disruption involved reduced reward signaling and compressed effort-reward encoding of utility cells, which corresponded with reduced reward consumption behaviors. Furthermore, low-dose AMPH stabilized and accelerated trajectories of neural activity in state-space, whereas high-dose AMPH destabilized trajectories. We propose that low-dose AMPH increases both excitability and stability, which preserves information and accelerates evolution of a neural script for task execution. Excessive excitability at high doses overcomes stability enhancement to suppress weakly encoded features (e.g. reward) and cause deviation from the script, which interrupts task performance. Significance StatementAmphetamine reduced reward signaling by individual neurons in rat prefrontal cortex, but increased the stability of ensemble dynamics. These effects account for animals increased task engagement, despite reduced reward intake.