Integrated Amygdala, Orbitofrontal and Hippocampal Contributions to Reward and Loss Coding Revealed with Human Intracranial EEG.

Neurophysiological work in primates and rodents have shown the amygdala plays a central role in reward processing through connectivity with the orbitofrontal cortex (OFC) and hippocampus. However, understanding the role of oscillations in each region and their connectivity in different stages of reward processing in humans has been hampered by limitations with noninvasive methods such as poor spatial and temporal resolution. To overcome these limitations, we recorded local field potentials (LFPs) directly from the amygdala, OFC and hippocampus simultaneously in human male and female epilepsy patients performing a monetary incentive delay (MID) task. This allowed us to dissociate electrophysiological activity and connectivity patterns related to the anticipation and receipt of rewards and losses in real time. Anticipation of reward increased high-frequency gamma (HFG; 60-250 Hz) activity in the hippocampus and theta band (4-8 Hz) synchronization between amygdala and OFC, suggesting roles in memory and motivation. During receipt, HFG in the amygdala was involved in outcome value coding, the OFC cue context-specific outcome value comparison and the hippocampus reward coding. Receipt of loss decreased amygdala-hippocampus theta and increased amygdala-OFC HFG amplitude coupling which coincided with subsequent adjustments in behavior. Increased HFG synchronization between the amygdala and hippocampus during reward receipt suggested encoding of reward information into memory for reinstatement during anticipation. These findings extend what is known about the primate brain to humans, showing key spectrotemporal coding and communication dynamics for reward and punishment related processes which could serve as more precise targets for neuromodulation to establish causality and potential therapeutic applications.SIGNIFICANCE STATEMENT Dysfunctional reward processing contributes to many psychiatric disorders. Neurophysiological work in primates has shown the amygdala, orbitofrontal cortex (OFC), and hippocampus play a synergistic role in reward processing. However, because of limitations with noninvasive imaging, it is unclear whether the same interactions occur in humans and what oscillatory mechanisms underpin them. We addressed this issue by recording local field potentials (LFPs) from all three regions in human epilepsy patients during monetary reward processing. There was increased amygdala-OFC high-frequency coupling when losing money which coincided with subsequent adjustments in behavior. In contrast, increased amygdala-hippocampus high-frequency phase-locking suggested a role in reward memory. The findings highlight amygdala networks for reward and punishment processes that could act as more precise neuromodulation targets to treat psychiatric disorders.