Prior novelty invigorates future mesolimbic target detection.

The ability to adapt to a dynamic world relies on detecting, learning, and responding to environmental changes. The detection of novelty serves as a critical indicator of such changes, priming mechanisms to detect and respond to goal-relevant information. However, neural regions that support novelty detection (hippocampus) and goal-directed behavior [dopaminergic midbrain (VTA) and prefrontal cortex (PFC)] have yet to be described as a sequential process that unfolds over time. Using a forward-prediction functional MRI model, we explored interactions between the hippocampus, VTA, and PFC in humans performing a novelty-imbued target-detection task. Hippocampal novelty activation predicted subsequent VTA target activation, 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 during target trials. This work provides insights into how distributed circuits coordinate to optimize adaptive behavior.