TRAINING SESSION INTERVALS SHAPE FUNCTIONAL CONNECTIVITY IN SPATIAL LEARNING: A BRAIN-WIDE ANALYSIS

Gosetti di Sturmeck, T.; Bergamo, S.; Mastrorilli, V.; Patrizi, A.; Nuzzi, D.; Pezzulo, G.; Del Ferraro, G.; Rinaldi, A.; Mele, A.

doi:10.64898/2026.02.12.705541

bioRxiv · 10.64898/2026.02.12.705541

TRAINING SESSION INTERVALS SHAPE FUNCTIONAL CONNECTIVITY IN SPATIAL LEARNING: A BRAIN-WIDE ANALYSIS

Gosetti di Sturmeck, T.·Bergamo, S.·Mastrorilli, V.·Patrizi, A.·Nuzzi, D.·Pezzulo, G.·Del Ferraro, G.·Rinaldi, A.·Mele, A.

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Abstract

A substantial body of research indicates that spaced training, characterized by longer inter-trial intervals between training epochs, consistently outperforms massed training in promoting durable memory. To investigate the neural mechanisms underlying this difference, we quantified c-Fos expression across 126 brain regions and mapped network activity following both spatial and cue-based learning under massed and spaced training protocols. While both training regimens (spaced and massed) and memory types (spatial and cue-based) produced small-world networks with similar overall topology, they differed in the functional organization of specific circuits. Massed spatial training preferentially activated hippocampal-thalamic and claustrum-basal ganglia-thalamic pathways. In contrast, spaced spatial training promoted stronger cortico-thalamic interactions and enhanced communication between the hippocampus and basal ganglia, indicating a shift toward a more integrated, cortically mediated network. These findings suggest that temporal spacing of training reorganizes memory-related brain networks, enhancing cortical-thalamic dynamics to support more efficient spatial memory. Finally, spaced networks were more sensitive to targeted disruptions of key connector hubs--identified through betweenness centrality analysis--than massed networks, pointing to a potential systems-level trade-off.

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Gosetti di Sturmeck, T., Bergamo, S., Mastrorilli, V., Patrizi, A., Nuzzi, D., Pezzulo, G., Del Ferraro, G., Rinaldi, A., Mele, A.. 2026-02-13. TRAINING SESSION INTERVALS SHAPE FUNCTIONAL CONNECTIVITY IN SPATIAL LEARNING: A BRAIN-WIDE ANALYSIS. https://doi.org/10.64898/2026.02.12.705541

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