Mirror Symmetric Bimanual Movement Priming Can Increase Corticomotor Excitability and Enhance Motor Learning

Repetitive mirror symmetric bilateral upper limb may be a suitable priming technique for upper limb rehabilitation after stroke. Here we demonstrate neurophysiological and behavioural after-effects in healthy participants after priming with 20 minutes of repetitive active-passive bimanual wrist flexion and extension in a mirror symmetric pattern with respect to the body midline (MIR) compared to an control priming condition with alternating flexion-extension (ALT). Transcranial magnetic stimulation (TMS) indicated that corticomotor excitability (CME) of the passive hemisphere remained elevated compared to baseline for at least 30 minutes after MIR but not ALT, evidenced by an increase in the size of motor evoked potentials in ECR and FCR. Short and long-latency intracortical inhibition (SICI, LICI), short afferent inhibition (SAI) and interhemispheric inhibition (IHI) were also examined using pairs of stimuli. LICI differed between patterns, with less LICI after MIR compared with ALT, and an effect of pattern on IHI, with reduced IHI in passive FCR 15 minutes after MIR compared with ALT and baseline. There was no effect of pattern on SAI or FCR H-reflex. Similarly, SICI remained unchanged after 20 minutes of MIR. We then had participants complete a timed manual dexterity motor learning task with the passive hand during, immediately after, and 24 hours after MIR or control priming. The rate of task completion was faster with MIR priming compared to control conditions. Finally, ECR and FCR MEPs were examined within a pre-movement facilitation paradigm of wrist extension before and after MIR. ECR, but not FCR, MEPs were consistently facilitated before and after MIR, demonstrating no degradation of selective muscle activation. In summary, mirror symmetric active-passive bimanual movement increases CME and can enhance motor learning without degradation of muscle selectivity. These findings rationalise the use of mirror symmetric bimanual movement as a priming modality in post-stroke upper limb rehabilitation

MEPs and H-reflexes (A–C) were obtained from passive FCR at baseline and 0, 15 and 30 minutes after 20 minutes of active-passive movement made in either a mirror symmetric or alternating pattern.

<p>The only difference between sessions was the phase relation of the active hand with respect to the passive hand. <b>A.</b> Intracortical Inhibition Protocols (Top to Bottom): Single-pulse TMS of left M1 elicits a non-conditioned MEP. The test stimulus intensity is set to produce an MEP roughly half of the maximum amplitude obtainable in that muscle. Long interval intracortical inhibition (LICI, Exp 1) was examined with two supra-threshold stimuli applied 100 ms apart. Short interval afferent inhibition (SAI, Exp 1) was examined by applying cutaneous stimulation through ring electrode on the right index finger 40 ms prior to TMS at the test intensity. Short interval intracortical inhibition (SICI, Exp 5) was examined by applying a subthreshold stimulus 2 ms before the test stimulus. Suppression of the test MEP is evident during LICI, SAI and SICI protocols. Each trace is the average of twenty sweeps. <b>B.</b> Interhemispheric Inhibition. Top: Single-pulse TMS of left M1 elicits a test MEP in pre-activated right FCR. Bottom: To examine interhemispheric inhibition (IHI, Exp 2), TMS of right M1 is applied 10 ms before TMS of left M1. Suppression of the test MEP is evident. Each trace is the average of twenty sweeps. <b>C.</b> H-Reflex. H-reflexes were obtained in the resting right FCR (Exp 3). The stimulus artefact is followed closely by an M-wave that is approximately 10% of the maximum M-wave amplitude (not shown), followed by the H-wave. The trace is an average of thirty sweeps.</p

Neurophysiological and functional effects of MIR on corticomotor excitability (CME) and selective facilitation of ECR MEPs during the reaction time (RT) period preceding voluntary wrist extension (Exp 5).

<p><b>A.</b> Each bar represents the average of 12 participants. At rest, CME was increased after MIR as indicated by a Time main effect and facilitation of MEP relative to baseline. <b>B.</b> Example EMG traces from a typical participant showing MEPs in ECR and FCR during the reaction time (RT) period of the pre-movement facilitation paradigm. Thick traces are ECR. TMS was applied early (top) or late (bottom) in the RT interval. Pre-movement facilitation is evident in ECR but not FCR, as increase in MEP size from early to late. <b>C.</b> Each bar represents the average of 12 participants. ECR and FCR MEP area during RT interval preceding wrist extension. ECR MEP area increased from early to late in the RT interval whereas FCR MEP area did not. There was no effect of Time or any interaction. * <i>P</i>&lt;0.05, ANOVA; ** <i>P</i>&lt;0.01, corrected one sample t-test. Error bars = 1 SE.</p

Neurophysiological effects after active-passive movement priming.

<p>Black bars are group averages from the mirror symmetric (MIR) session; white bars are group averages from the alternating (ALT) session. <b>A.</b> Corticomotor excitability increased after MIR but not ALT. There was a main effect of Pattern for non-conditioned ECR and FCR MEP area (Exp 1). Bars represent average ECR and FCR MEP area from 13 participants collapsed across all three post time points expressed as a percentage of baseline (100%). One-sample t-tests indicated significant MEP facilitation in both muscles after mirror symmetric but not parallel movement. <b>B.</b> Long interval intracortical inhibition (LICI) was modulated by Pattern (Exp 1). There was a main effect of Pattern for ΔLICI. Bars represent average change in LICI from ECR and FCR MEPs of 8 participants at each Post time point relative to baseline (0%). Relative to baseline, there was a non-significant trend for reduced LICI after the mirror session (<i>P</i>&lt;0.1) and a trend for increased LICI in the alternating session (<i>P</i>&lt;0.06). <b>C.</b> Interhemispheric inhibition (IHI) was modulated by Pattern and Time reduced after the MIR, but not PAR, session (Exp 2) indicated by a Pattern×Time interaction for ΔIHI. Bars represent average change in IHI from FCR MEPs of 13 participants at each Post time point relative to baseline (0%). At Post₁₅, ΔIHI was less in the MIR session compared to the ALT session, but did not differ at other time points. One-sample t-tests indicated a significant reduction of IHI at Post₁₅ relative to baseline after MIR only.</p

Participant details, design, and summary of main results for each experiment.

<p>Exp = Experiment; N = number of participants; EH = Edinburgh Handedness (−100 = left-handed; +100 = right-handed) MIR = mirror-symmetric; ALT = alternating; CME = corticomotor excitability of the passive M1; SAI = short afferent inhibition; LICI = long interval intracortical inhibition; IHI = Interhemispheric inhibition; SICI = short interval intracortical inhibition; H amp = H-reflex amplitude; PMF = pre-movement facilitation; ↑ Increase; ↓ Decrease; ←→ No change. All MIR effects are relative to baseline, except * = relative to ALT.</p

The active-passive movement protocol.

<p>Average left (active) and right (passive) FCR EMG traces from a single participant (1 s of data, average of 60 traces). For clarity EMG is shown from a mirror symmetric condition only. The marked difference in EMG activity can be seen between the active FCR (grey trace) and passive FCR (black trace) during the movement. A schematic of passive (black trace) and active wrist angle from mirror symmetric and alternating session of Exp 1 is shown.</p

Functional effects of active-passive movement priming on motor learning (Exp 4).

<p><b>A.</b> Normalized times taken to complete Grooved Pegboard test for MIR, ALT and NONE conditions. Each point represents the average of 11 participants. <b>B.</b> Rate of learning was quantified as the slope of normalized times obtained within each Block. ALT and NONE did not differ and were combined into a single control group (CON, N = 22). A Mixed ANOVA indicated a main effect of Block and a Group×Block interaction. Slopes were steeper in Block 1 than Block 2 and 3, which did not differ. MIR slope was steeper than CON for During Block only. * <i>P</i>&lt;0.05; ** <i>P</i>&lt;0.005.</p