Neuroccino 10th November 2025 - Mismatch in brain

Hippocampal mismatch signals are based on episodic memories and not schematic knowledge

Significance
Our brains use memories of the past to make sense of the present and predict the future. These memories might be of specific events or more general knowledge about the world. The hippocampus is widely implicated in signaling mismatches with memory-based predictions, but whether it uses specific episodic memories or generalized knowledge remains unclear. We show that the hippocampus selectively signals mismatches with episodic memories, while other brain networks respond to unexpected situations more broadly, regardless of memory type. These findings clarify the hippocampus’ role as a comparator, showing it is specialized for evaluating reality against episodic memories, and offer insight into how the brain uses past experiences to interpret the present and anticipate the future, shaping learning and memory.
Abstract
Prediction errors drive learning by signaling mismatches between expectations and reality, but the neural systems supporting these computations remain debated. The hippocampus is implicated in mismatch detection, yet it is not known whether it signals mismatches with episodic memories or generalized knowledge. Across three functional Magnetic Resonance Imaging (fMRI) experiments, we show that the hippocampus selectively responds to mismatches with episodic memories of specific events. In contrast, schematic mismatches engage Semantic Control and Multiple Demand Networks, as well as subcortical regions linked to prediction error signaling. Episodic mismatches also recruit the Default Mode Network. These findings challenge accounts that propose the hippocampus is a domain-general mismatch detector. Instead, the findings support a more specialized role for the hippocampus in learning that is underpinned by its well-established importance in processing episodic memories.

Paper link: https://www.pnas.org/doi/10.1073/pnas...