Functional Role Of Dorsolateral Prefrontal-m1 Connectivity During Procedural Motor Learning

OBJECTIVE: As a major functional area of the frontal cortex,the dorsolateral prefrontal cortex(DLPFC),particularly BA 46,plays an important role in decision making,cognitive control,and linking cognition to action.Its cortico-cortical connections reach the primary motor cortex(M1)and transfer crucial information for the execution of motor output.Clinical and neuroimaging studies assessing the relationship between the prefrontal and primary cortices have shown that the DLPFC is involved in inhibitory stimulus control,and pointed to the existence of anatomical and functional connectivity between these cortices.However,the physiological functions of pathways from the DLPFC to M1 remain elusive,and there is no causal evidence for the role of DLPFC in different motor learning tasks and its connection with M1.In this study,series response time task(SRTT)and neuroelectrophysiology were used to explore whether the connectivity between left DLPFC and M1 played different roles in two different kinds of procedural motor learning in random and sequence order.METHODS: In the first study,subjects were intervened by intermittent and continuous theta burst stimulation(iTBS/cTBS)of DLPFC to observe the changes in excitability and inhibitory of M1.Also,there was a control experiment with sham-TBS applied to DLPFC to confirm the results of the main experiment.In the second study,participants first received dual-site paired-pulse transcranial magnetic stimulation(TMS)at baseline to detect the DLPFC-M1 connectivity and obtain the best projection time point;in the second step,subjects were divided into sequence learning group and random learning group to participate the SRTT,and according to the best projection point obtained from the first experiment,using single-pulse TMS and paired-pulse TMS to test the input-output curve of DLPFC-M1 before and after learning respectively.RESULTS:(1)In study 1,we assessed the effect of rTMS on the DPLFC.We found that iTBS600 to the DLPFC decreased the MEP amplitude in M1 at T0.Conversely,cTBS600 to the DLPFC increased the MEP amplitude in M1 at T15.Both after-effects of TBS intervention disappeared at T60.The amplitude after iTBS600 at T0 was significantly correlated with the peak increase in MEP amplitude after cTBS600 at T15.(2)In study 2,we found that the excitability of DLPFC-M1 projection was significantly inhibited at 10 ms interval and significantly enhanced at 25 ms interval;(3)The learning effect of sequential learning group was better,and response time decreased significantly with the progress of learning.The MEP generated by single-pulse TMS did not change under both sequence and random learning conditions,while the paired-pulse MEP showed that the DLPFC-M1 connectivity changed under sequence condition and did not change under random condition at the 110%RMT input intensity.CONCLUSIONS:(1)There are homeostatic inhibitory and facilitatory plasticity mechanisms between the DLPFC and M1.This could help us better understand the allocation of the cognitive resources to achieve optimal motion output.(2)Under a more precise time projection process,there are two significant inhibition or facilitation pathways when the projection time intervals are 10 ms and 25 ms,respectively.(3)Sequence learning produces better plasticity changes,and the change of DLPFC-M1 connectivity starts with sequence learning group rather than random sequence learning group.It shows that DLPFC is better involved in sequence learning leads to better behavior improvement.