Reassessment of Non-Monosynaptic Excitation from the Motor Cortex to Motoneurons in Single Motor Units of the Human Biceps Brachii

Abstract

Corticospinal excitation is mediated by polysynaptic pathways in several vertebrates, including dexterous monkeys. However, indirect non-monosynaptic excitation has not been clearly observed following transcranial electrical stimulation (TES) or cervicomedullary stimulation (CMS) in humans. The present study evaluated indirect motor pathways in normal human subjects by recording the activities of single motor units (MUs) in the biceps brachii (BB) muscle. The pyramidal tract was stimulated with weak TES, CMS, and transcranial magnetic stimulation (TMS) contralateral to the recording side. During tasks involving weak co-contraction of the BB and hand muscles, all stimulation methods activated MUs with short latencies. Peristimulus time histograms (PSTHs) showed that responses with similar durations were induced by TES (1.9 ± 1.4 ms) and CMS (2.0 ± 1.4 ms), and these responses often showed multiple peaks with the PSTH peak having a long duration (65.3% and 44.9%, respectively). Such long-duration excitatory responses with multiple peaks were rarely observed in the finger muscles following TES or in the BB following stimulation of the Ia fibers. The responses obtained with TES were compared in the same 14 BB MUs during the co-contraction and isolated BB contraction tasks. Eleven and three units, respectively, exhibited activation with multiple peaks during the two tasks. In order to determine the dispersion effects on the axon conduction velocities (CVs) and synaptic noise, a simulation study that was comparable to the TES experiments was performed with a biologically plausible neuromuscular model. When the model included the monosynaptic-pyramidal tract, multiple peaks were obtained in about 34.5% of the motoneurons (MNs). The experimental and simulation results indicated the existence of task-dependent disparate inputs from the pyramidal tract to the MNs of the upper limb. These results suggested that intercalated interneurons are present in the spinal cord and that these interneurons might be equivalent to those identified in animal experiments.

Keywords: humans; motor unit; primary motor cortex (M1); pyramidal tract; transcranial electrical stimulation (TES); transcranial magnetic stimulation (TMS).

Figure 1

(A) Experimental set up and (B) schematic diagram of the different simulation scenarios. The Monosynaptic-Ia (Msyn-Ia) model involved activation of a monosynaptic reflex pathway by Ia afferents from muscle spindles (blue arrow and dark gray square). The descending monosynaptic pathway is indicated by the Monosynaptic-Pyramidal tract (Msyn-Py) model (green arrow and light gray square). Irrespective of the model (Msyn-Ia or Msyn-Py), 145 stimuli were delivered to a given pathway every 200 ms (stimulus rate, 5 Hz). The values (m) on the right (from bottom to top) indicate the distances between the muscle and the stimulus point (subclavicular fossa; d1), stimulus point and motoneuron (MN) pool (d2), and MN pool and scalp (d3), respectively. The range of the conduction velocities (CVs) for the descending axons (CV_DA), motor axons (CV_MA) and Ia afferents (CV_Ia) are listed near the arrows. The box diagrams at the bottom represent the workflow for the simulation protocols. The workflow of the simulation is illustrated at the bottom.

Figure 2

Recordings from one representative motor unit (MU) following transcranial electrical stimulation (TES) and transcranial magnetic stimulation (TMS) during the co-contraction task. (A) Superimposed recordings of the activity of a single MU after TES. The upward arrow indicates 17 ms after TES. (B) Peristimulus time histograms (PSTHs) that were created from the recordings shown in (A). The identities of the spike activities were confirmed offline with a spike template-matching algorithm. The upward arrows along the abscissa indicate the onset and offset of the evoked activities. The gray line plots the moving average of the PSTH, together with the fitted curve (black line). The downward arrows indicate the peaks for which the latencies were measured. (C) The PSTH that was created with the recordings after TMS of the same MU as shown in (A,B). The timing of some peaks is indicated by vertical broken lines.

Figure 3

(A) Cumulative histograms for the duration of the excitations observed following cervicomedullary stimulation (CMS; gray line), TES (black line) and Ia stimulation (gray dashed line) in the biceps brachii (BB) muscle. The corresponding histograms for the flexor digitorum superficialis (FDS; gray dash-dot line) and first dorsal interosseous (FDI; black dashed line) after TES are also shown. (B) Scatter plots of the duration after TES against motor-evoked potential (MEP) size in simultaneously recorded surface electromyography (i.e., stimulus strength). The filled symbols represent responses with multiple peaks. (C–E) PSTHs obtained from MUs of the FDS (C) and FDI (D) after TES and BB after Ia afferent fiber stimulation (E). The upward arrows indicate the onset or offset of the evoked activities, and the downward arrows indicate the measured peaks.

Figure 4

PSTHs from five MUs. The results obtained with TES are shown in (A1,B,D), while those obtained with CMS are shown in (A2,C,E). (A1,A2) are from the same MU. The upward arrows indicate the onset or offset of the evoked activities, and the downward arrows indicate the measured peaks.

Figure 5

PSTHs (A,B) and compound MEPs (C) obtained from a single MU and surface electromyography that was generated by the same TES, respectively. The PSTHs that were obtained during the co-contraction task are presented in (A), and those obtained during the isolated contraction task are presented in (B). The timing of some peaks is indicated by vertical broken lines. The downward arrows indicate the measured peaks in the smoothed PSTH. The MEPs in the co-contraction (black line) and isolated (gray line) tasks exhibited simila sizes and shapes (C).

Figure 6

PSTHs that were obtained with the monosynaptic pyramidal tract model and three different MUs (A–C). The insets (A–C) show the moving average of the PSTH (gray curve) and the fitted curve (black curve), with their respective r² values.