Synergistic Neural Circuits for Novelty and Goal-Directed Behavior

The ability to adapt in a dynamic world relies on detecting, learning, and responding to environmental changes. The detection of novelty serves as a critical indicator of such changes, prompting mechanisms to detect and respond to goal-relevant information. However, neural regions that support novelty detection and learning (hippocampus), salience detection (dopaminergic midbrain [VTA]), and executive function (prefrontal cortex [PFC]) have yet to be described as a sequential process that unfolds over time. Using functional magnetic resonance imaging (fMRI) we explored interactions between the hippocampus, VTA, and PFC in humans performing a novelty-imbued target-detection task. Hippocampal novelty activation predicted subsequent goal-directed VTA activity, enhancing readiness to detect goal-relevant information. Concurrently, goal-directed PFC activation modulated VTA target activation, refining focus on behaviorally significant cues. These circuits function both synergistically and independently, promoting subsequent hippocampal activity. This work provides new insights into how distributed circuits coordinate to optimize adaptive behavior.