Physiological Markers of Motor Inhibition during Human Behavior

Abstract

Transcranial magnetic stimulation (TMS) studies in humans have shown that many behaviors engage processes that suppress excitability within the corticospinal tract. Inhibition of the motor output pathway has been extensively studied in the context of action stopping, where a planned movement needs to be abruptly aborted. Recent TMS work has also revealed markers of motor inhibition during the preparation of movement. Here, we review the evidence for motor inhibition during action stopping and action preparation, focusing on studies that have used TMS to monitor changes in the excitability of the corticospinal pathway. We discuss how these physiological results have motivated theoretical models of how the brain selects actions, regulates movement initiation and execution, and switches from one state to another.

Keywords: action selection; corticospinal excitability; inhibitory control; reactive and proactive inhibition; transcranial magnetic stimulation.

Figure 1. Transcranial magnetic stimulation (TMS) as a probe of corticospinal excitability

A. The TMS coil is placed over primary motor cortex (M1) at the “hotspot” (depicted in yellow), the position at which the largest motor-evoked potentials (MEPs) can be recorded in the EMG signal from a targeted muscle. B. TMS over M1 activates corticospinal (CS) neurons directly or indirectly via the stimulation of intracortical circuits that project to CS neurons. Transcortical inputs from premotor, prefrontal and parietal cortices, as well as axons of subcortical cells projecting onto M1 are also activated by TMS over M1. Depending on the position and intensity of stimulation, a series of descending volleys (D- wave and I-wave) are transmitted from M1 to the motorneurons in the spinal cord. These signals are further influenced by inputs at the spinal level before they jointly give rise to an MEP in the targeted, contralateral muscle (first dorsal interosseus [FDI] in the present example). C. The MEP is a bi-phasic response recorded from a targeted muscle via electrodes placed on the surface of the skin. It has a latency of approximately 18 ms after the TMS pulse when elicited in hand muscles. While the latency is relatively invariant, the peak-to-peak amplitude fluctuates, reflecting the sum of cortical, subcortical, and spinal contributions to the descending signals to the muscle.

Figure 2. Study of motor inhibition during action stopping

The standard stop task (upper panel) often requires subjects to choose between left (L) and right (R) finger responses (L index finger trial in this example) occasionally interrupted by a stop signal (~33% of trials). The time between the go signal and the stop signal, or stop signal delay (SSD), is adjusted so that participants succeed in stopping on a targeted proportion of trials (usually 50%). When transcranial magnetic stimulation (TMS) is applied after the stop signal (A), motor evoked potentials (MEPs; expressed as a percentage of baseline) elicited in selected (L index), non-selected (R index) and irrelevant (L pinky or leg) muscles are globally suppressed reflecting widespread reactive inhibition. In selective tasks (lower panel), subjects make bimanual movements (e.g. with index fingers); a cue is presented at the beginning of each trial, indicating the hand that may have to be stopped if a stop signal occurs (L index strop trial in this example). In this task, MEPs measured after the stop signal (C) are suppressed in only the agonist muscle that was cued for stopping, reflecting selective reactive inhibition. When TMS is applied before the stop signal in this type of selective stop task (B), MEPs are also only suppressed in the muscle that may have to be stopped, indicating selective proactive inhibition in anticipation of the stop signal.

Figure 3. Study of motor inhibition during action preparation

Reaction time (RT) tasks (upper panel) often require subjects to perform left (L) or right (R) finger responses in a simple or choice setting (L index finger trial in a choice RT task in this example). When transcranial magnetic stimulation (TMS) is applied immediately after the go signal (A), motor evoked potentials (MEPs; expressed as a percentage of baseline) elicited in selected (L index), non-selected (R index) and irrelevant finger (L pinky) muscles are globally suppressed reflecting widespread inhibition during the EARLY stage of the pre-movement period. Close to movement onset (LATE, B), the amplitude of MEPs is increased when the finger muscle is the agonist for the selected response and is attenuated if the muscle is not selected or irrelevant. Dashed grey bars are used to represent hypothetical leg MEPs (not investigated to date) based on evidence in instructed-delay RT tasks. In these delay tasks, a cued response is prepared but withheld until the go signal. When TMS is applied at the end of the delay period (LATE, D), MEPs are suppressed regardless of whether the finger muscle is selected, non-selected or task-irrelevant, indicating broad preparatory inhibition, although inhibition does not seem to extend to leg muscle representations. Notably, inhibition is often stronger for selected than non-selected muscles, suggesting some additional focal inhibition targeted at agonist muscles. MEP suppression is not observed when TMS is applied a long time before the go signal, close to the preparatory cue (EARLY, C).

Figure 4. Models of preparatory inhibition

Illustration of the inhibition for competition resolution hypothesis (left column), the dual-process model (middle column) and the spotlight model (right column) in the context of a task in which a cue indicates if the forthcoming response will require a left (L) or right (R) index finger movement (L index finger trial in the current example). Dark and light blue circles are used to illustrate the neural representation of the L and R index fingers, respectively, in the motor cortex (upper panel) and in the spinal cord (middle panel). Dark and light grey circles are used to display irrelevant leg and pinky muscle representations, respectively. The circle size reflects the activation level of the motor representation. Inhibitory influences are displayed as red arrows. The lower panel shows the amplitude of motor-evoked potentials (MEPs) elicited in the L and R index muscles, as well as in irrelevant pinky and leg muscles. Based on the competition resolution idea, activation of the selected (L index) effector produces a selective suppression of the non-selected finger (R index). In the dual-process model, a second source of inhibition is directed at the selected effector, probably at the spinal level, resulting in suppressed MEPs in the selected effector despite increasing activation of its cortical representation. Finally, in the spotlight model, the inhibitory influences are centered on the selected effector, with inhibition extending to adjacent effectors (e.g. L pinky) and, to a lower degree, to homologous representations in the contralateral hemisphere, perhaps through transcallosal connections. The colored arrows point to the feet and hand muscles from which the corresponding MEPs are recorded. For illustration purposes, the spotlight is shown influencing cortical excitability, although this type of inhibition may occur elsewhere. Neither model predicts inhibition of leg muscles, reflecting the idea that the scope of preparatory inhibition may be more narrow during action preparation than action stopping. CS = corticospinal.