Changes in Intracortical Inhibitory Processes Are Associated With the Development of Implicit Learning of a Motor Task

Objective: We aim to show that the development of implicit knowledge of a motor task is associated with decrease in intracortical GABA-related inhibition (ICI) in the trained muscles (accompanying increasing MEP amplitudes) and increase in ICI in non-trained neighboring muscles and that, after the knowledge becomes explicit, ICI modifications become less prominent. It would be useful to know the role of ICI during learning. As some interventions or drugs are known to modify GABA activity, this study may even provide a rationale for using these interventions and drugs to enhance plastic changes in patients with impaired motor learning capabilities. Several studies have shown that learning a motor task with one hand can be transferred to the contralateral hand (37, 43, 45, 46, 47). Studies have demonstrated that learning a finger sequence task (Serial Reaction Time test, SRTT) with the dominant-hand (trained) can be transferred to the contralateral hand (un-trained) (43,49,50). In this additional experiment we propose to investigate the effect of disrupting M1 (by using 1 Hz TMS, inhibitory effect) on motor learning in the trained hand (dominant) and in the un-trained hand (non-dominant). Evidence has shown that there is transcallosal connections between M1 of both hemispheres (40). Since M1 is active during implicit learning (41, 42) we expect 1 Hz TMS stimulation (inhibitory effect) over M1 will deteriorate implicit learning in the trained hand (dominant) as well as in the un-trained hand (non-dominant). This will be evaluated by assessing their effect on reaction times and accuracy of motor performance in both hands. Study Population: 72 healthy volunteers, aged 18-40 will participate in the study. Subjects will be randomly assigned to either the test session or the control session. Design: Subjects will complete a unique session. They will perform a serial-reaction-time task. The subjects will be instructed to push a button on a 4-button pad in response to a visual GO signal (which can appear at 4 different positions) using the appropriate digit and the appropriate button. There will be 9 blocks of 120 trials each. In the test group, in blocks 1, 4 and 7 the Go signal appears in a random order; in blocks 2-3, 5-6 and 8-9 the same 12-trial sequence is repeated 10 times. In the control group Go signals will appear in a random order in all blocks. Subjects won't be informed about the sequence but will be asked to notify anything they noticed about the task. If they do notice and report about a sequence they will be considered as having explicit knowledge. Between each block subjects will receive transcranial magnetic stimulations to assess ICI. ICI will be assessed on subjects at rest. Outcome Measures: Behavioral effect of the motor training will be assessed by measuring the mean reaction times (RT) for digits II and V and the percentage of correct responses for each block. Implicit learning will be assessed by the difference in RTs between block 3 and 4 and between block 6 and 7. Time at which explicit learning occurs will be assessed by verbal report and the degree of explicit learning by the number of correct items when repeating the sequence. Implicit learning will be assessed in the trained hand (dominant) (see above) and in the un-trained hand. The un-trained hand will be tested by asking subjects to repeat two random blocks (familiarization) and two sequence blocks. One of these sequence blocks is a repetition of the same sequence that they learned with the dominant hand. The other sequence block is a new sequence containing the same number of characters as the previous sequence. Implicit learning on the un-trained hand will be assessed by the difference in RTs, between random block and the sequence block. In addition, implicit learning on the un-trained hand will be evaluated by testing the difference between the two sequence blocks repeated by the un-trained hand. The time at which explicit learning occurs will be assessed by verbal report and the degree of explicit learning by the number of correct items when repeating the sequence. Intracortical inhibitory processes will be assessed by measuring the amount of ICI in trained muscles (first dorsal interosseus: FDI and adductor digit minimi: ADM) and a non-trained muscle (opponens pollicis brevis: OPB).