Altered corticospinal function during movement preparation in humans with spinal cord injury

Abstract

Key points: In uninjured humans, transmission in the corticospinal pathway changes in a task-dependent manner during movement preparation. We investigated whether this ability is preserved in humans with incomplete chronic cervical spinal cord injury (SCI). Our results show that corticospinal excitability is altered in the preparatory phase of an upcoming movement when there is a need to suppress but not to execute rapid index finger voluntary contractions in individuals with SCI compared with controls. This is probably related to impaired transmission at a cortical and spinal level after SCI. Overall our findings indicate that deficits in corticospinal transmission in humans with chronic incomplete SCI are also present in the preparatory phase of upcoming movements.

Abstract: Corticospinal output is modulated in a task-dependent manner during the preparatory phase of upcoming movements in humans. Whether this ability is preserved after spinal cord injury (SCI) is unknown. In this study, we examined motor evoked potentials elicited by cortical (MEPs) and subcortical (CMEPs) stimulation of corticospinal axons and short-interval intracortical inhibition in the first dorsal interosseous muscle in the preparatory phase of a reaction time task where individuals with chronic incomplete cervical SCI and age-matched controls needed to suppress (NOGO) or initiate (GO) ballistic index finger isometric voluntary contractions. Reaction times were prolonged in SCI participants compared with control subjects and stimulation was provided ∼90 ms prior to movement onset in each group. During NOGO trials, both MEPs and CMEPs remained unchanged compared to baseline in SCI participants but were suppressed in control subjects. Notably, during GO trials, MEPs increased to a similar extent in both groups but CMEPs increased only in controls. The magnitude of short-interval intracortical inhibition increased in controls but not in SCI subjects during NOGO trials and decreased in both groups in GO trials. These novel observations reveal that humans with incomplete cervical SCI have an altered ability to modulate corticospinal excitability during movement preparation when there is a need to suppress but not to execute upcoming rapid finger movements, which is probably related to impaired transmission at a cortical and spinal level. Thus, deficits in corticospinal transmission after human SCI extend to the preparatory phase of upcoming movements.

Keywords: motor cortex; movement inhibition; movement preparation; spinal cord.

Figure 1. Schematic representation of the experimental setup during the GO/NOGO task

A fixation cross (white cross) appeared in the centre of the computer screen at the beginning of all trials, followed by an imperative visual signal instructing subjects to execute (GO = green square) or suppress (NOGO = red square) ballistic index finger abduction isometric voluntary contractions. Raw traces show the time at which motor evoked potentials (MEPs) and other physiological measurements were tested during GO (green), NOGO (red) and baseline (black) trials. Baseline MEPs were recorded ∼90 ms after the fixation cross and GO and NOGO MEPs were recorded ∼90 ms before the reaction time (RT) recorded during trials without stimulation.

Figure 2. Reaction times

A, traces showing rectified raw electromyographic activity in the first dorsal interosseous (FDI) muscle in a representative control and spinal cord injury (SCI) subject during GO trials without transcranial magnetic stimulation. Each waveform represents the average of 40 trials in a control (black traces) and an SCI (grey traces) participant. B and C, group data (Controls, n = 13; SCI, n = 18) showing reaction times in milliseconds (ms) during GO trials without TMS (B) and the time at which TMS was applied during GO trials with TMS (C) in both groups. Error bars indicate SEM. ^* P < 0.05.

Figure 3. Motor evoked potentials (MEPs)

A and B, raw traces of MEPs elicited by transcranial magnetic stimulation in the first dorsal interosseous (FDI) muscle in a representative control and spinal cord injury (SCI) subject during NOGO (A) and GO (B) trials. Each waveform represents the average of 20 MEPs at baseline and during GO (Control = black; SCI = grey) and NOGO (Control = black; SCI = grey) trials. Amplitude scales are different for the SCI and control representative participants to better show changes across task. C and D, group data (Controls, n = 13, black circles; SCI, n = 18, grey squares) show MEPs during NOGO (C) and GO (D). The horizontal dotted line shows the FDI MEP size at baseline. Data from individual subjects are shown in controls (open circles) and SCI subjects (open squares). Error bars indicate SEM. ^* P < 0.05, comparison between groups; ^¥ P < 0.05, comparison between baseline and GO or NOGO trials.

Figure 4. Short‐interval intracortical inhibition (SICI)

A and B, SICI tested in the FDI muscle during NOGO (A) and GO (B) trials. Each waveform represents the average of 20 rectified test (black) and conditioned (grey) MEPs. Arrows indicate the test and conditioned MEP. Amplitude scales are different for the SCI and control representative participants to better show changes across task. C and D, group data (Controls, n = 12, red circle NOGO and green circle GO; SCI, n = 12, pink square NOGO and light green square GO) show SICI during NOGO (C) and GO (D) trials. The horizontal dotted line shows SICI at baseline. Data from individual subjects are shown in controls (open red circles, NOGO; open green circles, GO) and SCI subjects (open pink squares, NOGO; open light green squares, GO). Error bars indicate SEM. ^* P < 0.05, comparison between groups; ^¥ P < 0.05, comparison between baseline and GO or NOGO trials.

Figure 5. Cervicomedullary MEPs (CMEPs)

A and B, CMEP elicited in FDI muscle by electrical stimulation at the cervicomedullary junction in a representative control and SCI subject during NOGO (A) and GO (B) trials. Each waveform represents the average of 10 rectified CMEPs at baseline (black), during NOGO (Control = red; SCI = light red), and GO (Control = green; SCI = light green) trials. Amplitude scales are different for the SCI and control representative participants to better show changes across task. C and D, group data (Controls, n = 7; SCI, n = 6) showing CMEPs expressed as % of M‐max in control (C) and SCI (D) participants during GO (Controls: green circle; SCI: light green square), NOGO (Controls: red circle, SCI: pink square) and baseline trials (Controls: black circle; SCI: black square). Data from individual subjects are shown in controls (circles) and SCI subjects (squares). Error bars indicate SEM. ^* P < 0.05, comparison between groups; ^¥ P < 0.05, comparison between baseline and GO or NOGO trials.