Timing of Cortico-Muscle Transmission During Active Movement

Abstract

Numerous studies have reported large disparities between short cortico-muscle conduction latencies and long recorded delays between cortical firing and evoked muscle activity. Using methods such as spike- and stimulus-triggered averaging of electromyographic (EMG) activity, previous studies have shown that the time delay between corticomotoneuronal (CM) cell firing and onset of facilitation of forelimb muscle activity ranges from 6.7 to 9.8 ms, depending on the muscle group tested. In contrast, numerous studies have reported delays of 60-122 ms between cortical cell firing onset and either EMG or movement onset during motor tasks. To further investigate this disparity, we simulated rapid active movement by applying frequency-modulated stimulus trains to M1 cortical sites in a rhesus macaque performing a movement task. This yielded corresponding EMG modulations, the latency of which could be measured relative to the stimulus modulations. The overall mean delay from stimulus frequency modulation to EMG modulation was 11.5 ± 5.6 ms, matching closely the conduction time through the cortico-muscle pathway (12.6 ± 2.0 ms) derived from poststimulus facilitation peaks computed at the same sites. We conclude that, during active movement, the delay between modulated M1 cortical output and its impact on muscle activity approaches the physical cortico-muscle conduction time.

Keywords: EMG; cortico-muscle delay; forelimb; motor control; primary motor cortex.

Figure 1.

Unfolded map of the monkey's M1 forelimb representation in the left hemisphere with a view of the dorsal surface of the precentral gyrus and the rostral wall of the central sulcus. Anterior, posterior, medial, and lateral are indicated by the compass rose. Sites of frequency-modulated sinusoidal stimulation are indicated by the yellow dots, and are numbered in chronological order of stimulation. The color-coded muscle representation map was obtained from a previous StTA mapping study in this monkey (Griffin et al. 2014). Each hash mark represents a distance of 1 mm.

Figure 2.

Methodology for stimulation, recording, and cross-correlation. Stimulation was applied either on wrist flexion or extension, applying a combination of modulation frequency and carrier frequency. Stimulation at this modulated frequency was delivered to the stimulating electrode at a set stimulus intensity, and the output electromyography (EMG) activity was recorded. This stimulus-driven EMG activity was then rectified and smoothed using a 20-Hz Butterworth filter. This smoothed and rectified EMG was then cross-correlated with the signal used to drive frequency modulation to determine the overall phase shift offset between the modulated stimulus delivered to the cortex and the resulting modulated EMG activity. Only sections of data in which stimulation was delivered were used for analysis (dotted boxes). Data in this example used a modulation frequency of 4 Hz, a carrier frequency of 150 Hz, and stimulation intensity of 30 µA; EMG was recorded from extensor carpi radialis (ECR) and triggered on wrist extension.

Figure 3.

Baseline muscle activity and frequency-modulated activation of the same muscles. All records included in this figure were obtained from cortical site 5 (Fig. 1). (A and B) ED 4,5 and FDP EMG activity associated with wrist extension and flexion, respectively, in the absence of stimulation. (C) Stimulus-triggered averages for ED 4,5 and FDP acquired at 30 µA. The stimulus is shown as a light gray line superimposed on the EMG records. (D and E) Wrist extension and flexion, respectively, in response to frequency-modulated stimulation. The period of stimulation is represented by gray shading. (F) Frequency-modulated stimulation beginning midway through the dynamic phase of movement. (G) Response of ED4,5 during extension (i) and FDP during flexion (ii) in response to the first cycle of modulated stimulation (iii). Records are expansions of those in D, E, and F indicated by the corresponding colors. The number under each set of records is the number of events averaged. EMG activity has been uniformly scaled for each muscle. For muscle abbreviations, see Materials and Methods. Wrist position record (gray line) is superimposed on each EMG record, and ranges from 40° ± 10 in flexion to 30° ± 15 in extension. Upward deflection of the position record is flexion.

Figure 4.

(A) pE response. EMG activity increases in response to increasing stimulus frequency. (B) pI response. EMG activity decreases in response to increasing stimulus frequency. (C) tEI, or excitation transitioning to inhibition. EMG activity initially responds with an increase in activity in response to increasing stimulus frequency, but gradually transitions to inhibition as the stimulus train continues. Cross-correlations are included on the right for each example. Vertical scale bar is the magnitude of correlation. For muscle abbreviations, see Materials and Methods. Wrist position record (dashed line) is superimposed on each EMG record, and ranges from 40° ± 10 in flexion (upward deflection) to 30° ± 15 in extension (downward deflection). The 12-Hz signal used to modulate the stimulus train is superimposed on the EMG records (solid sinusoidal line).

Figure 5.

(A) Consistent modulation throughout stimulation. (B) Strong excitatory responses followed by almost complete loss of modulation after about 10 cycles. (C) Waxing and waning of EMG excitatory responses throughout the stimulus train. For muscle abbreviations, see Materials and Methods. Wrist position record (gray line) is superimposed on each EMG record, and ranges from 40° ± 10 in flexion to 30° ± 15 in extension. The stimulus modulation signal is shown as a sinusoidal line superimposed on the EMG records.