When facing new situations or problems, humans typically rely on knowledge they acquired in the past. Specifically, neuroscience studies suggest that the brain reorganizes past experiences and previously acquired knowledge, creating mental frameworks that can help humans to solve the problems they are facing. The recombination of past knowledge into new mental structures also allows humans to flexibly plan future actions in changing environments. Past studies suggest that two key brain regions contribute to this process, the hippocampus and the medial prefrontal cortex (mPFC).
The hippocampus is a brain structure that plays a key role in the formation of memories and spatial navigation. The mPFC, on the other hand, is known to support decision-making, planning, reasoning and the integration of information.
Researchers at Beijing Normal University, the Chinese Academy of Medical Sciences, University College London (UCL) and other institutes recently set out to investigate how the hippocampus and mPFC work together to combine past knowledge into new configurations. Their findings, published in Nature Neuroscience, suggest that this process is supported by brief bursts of high-frequency neural activity in the hippocampus, called hippocampal ripples, and the replay (i.e., re-activation) of past experiences in the brain.
“The human brain excels at solving novel problems by flexibly recombining a limited set of familiar elements, often through the internal planning of sequences that assemble these elements into new configurations,” wrote li He, Xiongfei Wang and their colleagues in their paper. “Although the hippocampus and medial prefrontal cortex (mPFC) are known to support such flexible planning, the neuronal mechanisms underlying their interaction remain unclear.”
Exploring how the brain supports flexible planning
To conduct their study, He, Wang and their colleagues recruited 28 patients with epilepsy who had electrodes implanted in their brain as part of their treatment. These participants were asked to complete two different tasks that required them to mentally combine familiar elements into new configurations.
The researchers subsequently analyzed brain activity recordings collected by the electrodes in the participants’ brains during the experiment. This allowed them to understand how brain activity changed while the participants were combining past knowledge to complete the task at hand.
“We recorded high-resolution intracranial electroencephalography simultaneously from the hippocampus and cortical regions of patients with epilepsy performing two LEGO-like inference tasks,” wrote He, Wang and their colleagues. “We replicated key neuroimaging findings and, crucially, reveal how mPFC representations are dynamically updated around hippocampal ripples to encode inferred solutions as compositional structures.”
The brain activity patterns observed by the researchers suggest that the hippocampus and mPFC closely coordinate to recombine familiar pieces of information into new mental structures. Short bursts of brain activity (i.e., ripples) in the hippocampus appear to help the brain to reorganize stored memories.
During these ripple events, the brain appears to rapidly replay sequences of information, reorganizing familiar building blocks into new combinations that are useful for solving the problem/task at hand. Concurrently, the mPFC appears to update its activity patterns to represent the newly identified solution to a problem.
“Hippocampal ripples shift mPFC representations toward the inferred relational configuration, facilitated by replay that reorganizes building blocks into candidate sequences,” wrote the authors. “Replay is strongest during ripple periods, closely coordinates with mPFC activity and is predictive of efficient inferential behavior. Together, hippocampal ripples and replay emerge as a key mechanism for dynamically updating cortical representations online to support planning and inference.”
Toward a better understanding of human flexible reasoning
This recent study offers new insight into how the human brain flexibly combines past knowledge to creatively tackle new tasks or problems. Further research could examine the neural mechanisms uncovered by the researchers more in-depth and shed more light on their contribution to decision-making.
In the future, this work could potentially help to better understand some neurological diseases and psychiatric disorders that are associated with difficulties with planning or reasoning. In addition, it could inspire the development of new artificial intelligence (AI) systems that emulate how the brain recombines previously acquired information.
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Publication details
Li He et al, Human hippocampal ripples coordinate planning sequences and compositional representations in neocortex, Nature Neuroscience (2026). DOI: 10.1038/s41593-026-02291-3
Journal information:
Nature Neuroscience
Key medical concepts
Clinical categories
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