Wakeful targeted memory reactivation during short rest periods modulates motor learning via the lateral orbitofrontal cortex network

Abstract This study investigated whether wakeful targeted memory reactivation (TMR) during short rest intervals improves motor learning. Participants were randomly assigned to the following four groups and performed a sequential key-press task under each condition: (1) TMR no group: no auditory stimuli, (2) TMR regular group: auditory cues played at the same speed as the previous task, (3) TMR fast group: auditory cues played 1.3 times faster, and (4) TMR random group: auditory cues randomized in pitch. The TMR regular group suppressed early learning gains compared with the TMR no and TMR fast groups. Electroencephalogram revealed reduced functional connectivity centered on the lateral orbitofrontal cortex (lOFC) in the TMR regular group. In contrast, the TMR fast group preserved early learning and exhibited improved lOFC-centered functional connectivity compared with the TMR regular group. Therefore, wakeful TMR might either hinder or support motor learning, depending on cue timing and structure, emphasizing the need to optimize sensory parameters for effective learning improvement.