Contextual interference enhances motor learning through increased resting brain connectivity during memory consolidation.

Increasing contextual interference (CI) during practice benefits learning, making it a desirable difficulty. For example, interleaved practice (IP) of motor sequences is generally more difficult than repetitive practice (RP) during practice but leads to better learning. Here we investigated whether CI in practice modulated resting-state functional connectivity during consolidation. 26 healthy adults (11 men/15 women, age = 23.3 ± 1.3 years) practiced two sets of three sequences in an IP or RP condition over 2 days, followed by a retention test on Day 5 to evaluate learning. On each practice day, functional magnetic resonance imaging (fMRI) data were acquired during practice and also in a resting state immediately after practice. The resting-state fMRI data were processed using independent component analysis (ICA) followed by functional connectivity analysis, showing that IP on Day 1 led to greater resting connectivity than RP between the left premotor cortex and left dorsolateral prefrontal cortex (DLPFC), bilateral posterior cingulate cortices, and bilateral inferior parietal lobules. Moreover, greater resting connectivity after IP than RP on Day 1, between the left premotor cortex and the hippocampus, amygdala, putamen, and thalamus on the right, and the cerebellum, was associated with better learning following IP. Mediation analysis further showed that the association between enhanced resting premotor-hippocampal connectivity on Day 1 and better retention performance following IP was mediated by greater task-related functional activation during IP on Day 2. Our findings suggest that the benefit of CI to motor learning is likely through enhanced resting premotor connectivity during the early phase of consolidation.