Distributed and gradual microstructure changes are associated with the emergence of behavioural benefit from memory reactivation.

Memory reactivation during sleep is known to have an impact upon the gradual consolidation of memory traces, but the nature of plastic changes induced by such reactivation remains unclear. Here, we use diffusion-weighted imaging to track the location and timescale of microstructural changes associated with behavioural effects of Targeted Memory Reactivation (TMR) 20 days post-manipulation, when the behavioural effect first became significant. Because we used a serial reaction time task that is known to draw on the sensorimotor system as well as both medial temporal and striatal memory systems, we included all these areas as regions of interest. We also included precuneus, a structure known for plasticity relating to the neural engram. Our analysis was based on correlations between behavioural benefit of TMR and microstructural plasticity over early (first 24 h) and late (24 h to 10 days) consolidation periods. This showed significant TMR-related microstructural plasticity in the striatum over the early period. Over the late period, we observed TMR-related microstructural changes in both sensorimotor cortex and precuneus. Taken together, these findings demonstrate that TMR-related microstructural changes correlate with subsequent memory benefits across multiple brain regions.