Operant conditioning of the tibialis anterior motor evoked potential in people with and without chronic incomplete spinal cord injury

Abstract

The activity of corticospinal pathways is important in movement control, and its plasticity is essential for motor skill learning and re-learning after central nervous system (CNS) injuries. Therefore, enhancing the corticospinal function may improve motor function recovery after CNS injuries. Operant conditioning of stimulus-induced muscle responses (e.g., reflexes) is known to induce the targeted plasticity in a targeted pathway. Thus, an operant conditioning protocol to target the corticospinal pathways may be able to enhance the corticospinal function. To test this possibility, we investigated whether operant conditioning of the tibialis anterior (TA) motor evoked potential (MEP) to transcranial magnetic stimulation can enhance corticospinal excitability in people with and without chronic incomplete spinal cord injury (SCI). The protocol consisted of 6 baseline and 24 up-conditioning/control sessions over 10 wk. In all sessions, TA MEPs were elicited at 10% above active MEP threshold while the sitting participant provided a fixed preset level of TA background electromyographic activity. During baseline sessions, MEPs were simply measured. During conditioning trials of the conditioning sessions, the participant was encouraged to increase MEP and was given immediate feedback indicating whether MEP size was above a criterion. In 5/8 participants without SCI and 9/10 with SCI, over 24 up-conditioning sessions, MEP size increased significantly to ~150% of the baseline value, whereas the silent period (SP) duration decreased by ~20%. In a control group of participants without SCI, neither MEP nor SP changed. These results indicate that MEP up-conditioning can facilitate corticospinal excitation, which is essential for enhancing motor function recovery after SCI. NEW & NOTEWORTHY We investigated whether operant conditioning of the motor evoked potential (MEP) to transcranial magnetic stimulation can systematically increase corticospinal excitability for the ankle dorsiflexor tibialis anterior (TA) in people with and without chronic incomplete spinal cord injury. We found that up-conditioning can increase the TA MEP while reducing the accompanying silent period (SP) duration. These findings suggest that MEP up-conditioning produces the facilitation of corticospinal excitation as targeted, whereas it suppresses inhibitory mechanisms reflected in SP.

Keywords: corticospinal excitability; operant conditioning; plasticity; silent period; transcranial magnetic stimulation.

Fig. 1.

A: session schedule. Six baseline sessions were followed by 24 conditioning or control sessions that occurred at a rate of 3 sessions/wk. In the conditioning group participants (both those with and without spinal cord injury, SCI), 2 follow-up sessions occurred at 1 and 3 mo after the last conditioning session. Along with the session counts, the time elapsed since the beginning of motor evoked potential (MEP) conditioning (or control) is shown in weeks. B: setup view. MEPs were measured while the participant sat in a chair with ankle, knee, and hip angles fixed at approximately −10, 60, and 70° in a custom-made apparatus. C: composition of baseline, conditioning, and control sessions. Isometric maximum voluntary contraction (MVC) was measured as the tibialis anterior (TA) electromyography (EMG) amplitude. Common peroneal nerve (CPn) stimulation was used for the maximum M-wave and H-reflex measurements. D: visual feedback screens for control and conditioning trials. In all trials, the number of the current trial within its block is displayed at top right, and the background EMG panel shows the correct range (hatching) and the ongoing EMG activity (green vertical bar, updated every 200 ms). If TA EMG activity stays in the correct range for at least 2 s and at least 5.5 s has passed since the last trial, an MEP is elicited. In control trials (left), the MEP panel is not shown. In conditioning trials (right), hatching in the MEP panel indicates the rewarded MEP range for up-conditioning. The thick horizontal bar is the average MEP size of the baseline sessions, and the vertical bar is the MEP size [i.e., the average rectified EMG in the MEP interval (e.g., 35–50 ms after transcranial magnetic stimulation, TMS)] for the most recent trial (it appears 200 ms after TMS). If that MEP size reaches into the hatched area, the bar is green and the trial is a success. If it falls below the hatched area, the bar is red and the trial is a not a success. The running success rate for the current block is shown at bottom right.

Fig. 2.

Typical examples of tibialis anterior (TA) motor evoked potential (MEP) in a conditioning group participant (A and C) and a control group participant (B and D) without known neurological conditions. A: peristimulus raw electromyography (EMG) sweeps from the second 75-trial block of the 6th baseline session and the last (i.e., 24th) conditioning session. For each, 75 sweeps are superimposed. B: peristimulus raw EMG sweeps from the second 75-trial block of the 6th baseline session and the 24th control session. For each, 75 sweeps are superimposed. C: rectified EMG signals from the 6th baseline session (dashed) and the 24th conditioning session (solid). D: rectified EMG signals from the 6th baseline session (dashed) and the 24th control session (solid). For each sweep of C and D, 225 responses were averaged together. A shaded band indicates the time window for each participant’s MEP size calculation. The horizontal dashed line indicates the background EMG level. Arrows (B6 and C24) indicate the ends of silent period.

Fig. 3.

Time course of motor evoked potential (MEP) changes over the course of study in participants without known neurological conditions. A, C, and E: average (±SE) MEP values for baseline and conditioning sessions for conditioning participants in whom the MEP increased significantly (n = 5). B, D, and F: average (±SE) MEP values for control participants (n = 7). A and B: average conditioned MEP size. C and D: average control MEP size. E and F: average of conditioned MEP size minus control MEP size (i.e., task-dependent adaptation; for details see Thompson et al. 2009a).

Fig. 4.

Typical examples of tibialis anterior (TA) motor evoked potential (MEP) in a participant with chronic incomplete spinal cord injury. A: peristimulus raw electromyography (EMG) sweeps from the second 75-trial block of the 6th baseline session and the last (i.e., 24th) conditioning session. For each, 75 sweeps are superimposed. B: rectified EMG signals from the 6th baseline session (black) and the 24th conditioning session (red). For each sweep, 225 responses were averaged together. A shaded band indicates the time window for this participant’s MEP size calculation.

Fig. 5.

Motor evoked potential (MEP) changes over the course of study in participants with chronic incomplete spinal cord injury who were exposed to MEP up-conditioning. A–C: average (±SE) MEP values for baseline and conditioning sessions for participants in whom the MEP increased significantly (n = 9). A: average conditioned MEP size. B: average control MEP size. C: average of conditioned MEP size minus control MEP size. D: TA maximum voluntary contraction (MVC).

Fig. 6.

Time course of silent period (SP) changes over the course of study in neurologically normal participants and in participants with chronic incomplete spinal cord injury (SCI). Average (±SE) conditioned SP durations (A–C) and the SP-to-motor evoked potential (MEP) ratios (D–F) for baseline and conditioning sessions A and D are for conditioning participants without known neurological conditions in whom MEP size increased significantly (n = 5), B and E are for control participants without known neurological conditions (n = 7), and C and F are for conditioning participants with SCI in whom MEP size increased significantly and SP could be measured (C and F, n = 7).

Fig. 7.

Relationship of motor evoked potential (MEP) to silent period (SP) duration in conditioning groups of participants with spinal cord injury (SCI) and of participants without known neurological conditions. Final conditioned SP duration (i.e., average conditioned SP duration for conditioning sessions 22–24) is plotted against the final conditioned MEP size (i.e., average conditioned MEP size for conditioning sessions 22–24). Triangles indicate values for participants with SCI; circles indicate values for participants without known neurological conditions.