The Role Of Dorsolateral Prefrontal Cortex During Motor Sequence Learning

Objective: Neuroimaging studies have implicated the dorsolateral prefrontal cortex(DLPFC)in working memory(WM)during motor sequence learning,in terms of selection,integration and organization of the temporarily stored perceptual,centralsymbolic and motor representations for the forthcoming sequence movements.However,direct evidence linking activation of the DLPFC and the functional connectivity between DLPFC and contralateral primary motor cortex(M1)to motor sequence learning in real-time is rare.Repetitive transcranial magnetic stimulation(r TMS)produces long-term potentiation-like effects or long-term depression-like effects depending on the stimulation frequency.Continuous theta burst stimulation(c TBS)is a novel paradigm of r TMS that produces long-term depression-like effects by mimicking theta-gamma coupling.The causal relationship between DLPFC and motor sequence learning could be revealed by comparing the performance of motor sequence learning before and after c TBS over DLPFC.The dual-site transcranial magnetic stimulation(ds TMS)paradigm can be used to reveal the inhibitory or facilitatory effects that a neural system exerts over another and establish the causal nature of the association between brain regions.The study combined sequential fingertapping task with c TBS and ds TMS paradigm and aimed to investigate the role of DLPFC and the functional connectivity between DLPFC and contralateral M1 in motor sequence learning.Methods: The first study introduced c TBS to decrease cortical excitability of left and right DLPFC.Forty-eight participants were randomly assigned to two groups,which received c TBS and sham stimulation over left or right DLPFC.Before and after stimulation,participants performed a sequential finger-tapping task containing repeated sequence and non-repeated sequence trials.The number of correct sequences(No CS)and reproduction error rate were analyzed.The second study introduced ds TMS paradigm to probe the functional connectivity between left DLPFC and contralateral M1.Twenty-four participants were randomly assigned to two groups,which required to complete the repeated motor sequence learning task or non-repeated motor sequence learning task.Before and after the task,participants received ds TMS over left DLPFC and contralateral M1.The motor evoked potentials and the No CS were analyzed.Results:(1)The first study found that learning gains improved significantly with the practice for both sequence types in the presence of either stimulation type.Compared to sham stimulation,c TBS over the left DLPFC resulted in a significantly reduced learning gains for non-repeated sequences.(2)The second study found that the MEP ratio after learning was significantly higher than the MEP ratio before learning at the interstimulus intervals of 50 ms.Conclusion:(1)These results suggest that the left DLPFC contributes to motor sequence learning of non-repeated sequence.(2)The left DLPFC-right M1 interhemispheric inhibition was released after motor sequence learning of non-repeated sequence,indicating the functional connectivity between left DLPFC and contralateral M1 contributes to motor sequence learning for non-repeated sequence.The present study provides further evidences for the role of the left DLPFC in motor sequence learning.