Journal of Neuroscience: Prefrontal Default Mode Network Interactions with Posterior Hippocampus During Exploration

In uncertain environments, organisms must decide whether to stick with a known, rewarding choice (exploit) or search for something potentially better (explore). Early on, behavior leans toward exploration, but once good options are identified, it shifts toward exploitation. When only a few choices are available, subcortical regions such as the striatum and amygdala can arbitrate between exploration and exploitation. In more complex environments, however, the brain relies on richer internal maps of where rewards tend to be, constructed by the hippocampus, and on flexible representations of goals and value in the ventral prefrontal cortex.

Value‑related information resides in different parts of the ventral prefrontal cortex which participates in three major brain networks: limbic, default mode, and frontoparietal control. In a recent Journal of Neuroscience study, Alex Dombrovski, MD (Pittsburgh Foundation Endowed Professor in Brain and Mind Research and Professor of Psychiatry and Psychology)—with colleagues, including first author Andrew Paple, PhD (postdoctoral scholar); Angela Ianni, MD, DPhil (postdoctoral scholar); and Beatriz Luna, PhD (Distinguished Professor of Psychiatry, Bioengineering, Psychology, and Radiology, and Staunton Professor of Pediatrics and Psychiatry)—examined how “value landscapes” (spatial patterns of expected reward) shape activity in the ventral prefrontal cortex. Using functional magnetic resonance imaging (fMRI) and reinforcement‑learning models, the team measured how the ventral prefrontal cortex and hippocampus responded as participants explored and exploited options. 

Value landscapes modulated activity in the hippocampus and default network prefrontal subregions. While default network and hippocampus displayed higher activity in less complex, easy-to-exploit value landscapes, they synchronized in uncertain landscapes requiring exploration. 

“The brain’s decision‑making systems behave very differently depending on whether a person is exploiting a clearly rewarding option or exploring new possibilities. In the good-enough, exploitation mode, activity increases in both the ventral prefrontal cortex and the hippocampus. But the discovery mode depends on synchronization between the hippocampus and ventral prefrontal regions. This coordinated activity allows us to update maps of the environment and find targets for exploration. As failures of exploration are linked to clinical problems such as suicidal behavior, our findings may provide insight into how hippocampal–prefrontal interactions shape high‑stakes decisions,” said Dr. Dombrovski, senior author of the study.

Prefrontal Default Mode Network Interactions with Posterior Hippocampus During Exploration
Papale AE, Brown VM, Ianni AM, Hallquist MN, Luna B, Dombrovski AY.
Journal of Neuroscience 10 December 2025, 45 (50) e0399252025; https://doi.org/10.1523/JNEUROSCI.0399-25.2025