Different contributions of primary motor cortex, reticular formation, and spinal cord to fractionated muscle activation

Abstract

Coordinated movement requires patterned activation of muscles. In this study, we examined differences in selective activation of primate upper limb muscles by cortical and subcortical regions. Five macaque monkeys were trained to perform a reach and grasp task, and electromyogram (EMG) was recorded from 10 to 24 muscles while weak single-pulse stimuli were delivered through microelectrodes inserted in the motor cortex (M1), reticular formation (RF), or cervical spinal cord (SC). Stimulus intensity was adjusted to a level just above threshold. Stimulus-evoked effects were assessed from averages of rectified EMG. M1, RF, and SC activated 1.5 ± 0.9, 1.9 ± 0.8, and 2.5 ± 1.6 muscles per site (means ± SD); only M1 and SC differed significantly. In between recording sessions, natural muscle activity in the home cage was recorded using a miniature data logger. A novel analysis assessed how well natural activity could be reconstructed by stimulus-evoked responses. This provided two measures: normalized vector length L, reflecting how closely aligned natural and stimulus-evoked activity were, and normalized residual R, measuring the fraction of natural activity not reachable using stimulus-evoked patterns. Average values for M1, RF, and SC were L = 119.1 ± 9.6, 105.9 ± 6.2, and 109.3 ± 8.4% and R = 50.3 ± 4.9, 56.4 ± 3.5, and 51.5 ± 4.8%, respectively. RF was significantly different from M1 and SC on both measurements. RF is thus able to generate an approximation to the motor output with less activation than required by M1 and SC, but M1 and SC are more precise in reaching the exact activation pattern required. Cortical, brainstem, and spinal centers likely play distinct roles, as they cooperate to generate voluntary movements. NEW & NOTEWORTHY Brainstem reticular formation, primary motor cortex, and cervical spinal cord intermediate zone can all activate primate upper limb muscles. However, brainstem output is more efficient but less precise in producing natural patterns of motor output than motor cortex or spinal cord. We suggest that gross muscle synergies from the reticular formation are sculpted and refined by motor cortex and spinal circuits to reach the finely fractionated output characteristic of dexterous primate upper limb movements.

Keywords: electromyogram; fractionation; motor cortex; reticular formation; spinal cord; synergy.

Fig. 1.

Illustration of methods. A–D: behavioral task. The monkey grasped (A) and pulled (B) a lever, which caused a clear plastic door to drop, revealing a food well. The monkey then reached into the well (C) and retrieved the food reward (“pick” event, detected by crossing an infrared beam; D). E: averaged rectified electromyogram (EMG) aligned to the “door drop” event of the task. Histogram at the top shows the distribution of the pick event relative to door drop. Vertical calibration bars to the right of each trace represent 50 µV. Monkey P, n = 81 trials. F: example responses to motor cortex (M1) stimulation (Stim) in monkey T. Each trace shows an average of rectified EMG from the muscle and stimulus indicated for n = 800 sweeps. Threshold intensity was determined as 20 µA for this site. G: photograph of data logger inside custom case and drawing illustrating how the data logger attached to the head implant on the monkey. H: example recording of natural activity from the data logger from monkey P. PD, posterior deltoid; AD, anterior deltoid; LD, latissimus dorsi; FDP, flexor digitorum profundus; FCR, flexor carpi radialis; FCU, flexor carpi ulnaris; FDS, flexor digitorum superficialis; PM, pectoralis major; AbPB, abductor pollicis brevis; 1DI, first dorsal interosseous; BR, brachioradialis; ECR, extensor carpi radialis; ECU, extensor carpi ulnaris; EDC, extensor digitorum communis; Tri, triceps; BicL, long head of biceps.

Fig. 2.

Reconstruction of stimulation sites. For M1, the calculated stereotaxic coordinates have been superimposed on tracings of cortical features based on MRI scans. For reticular formation (RF), the stereotaxic coordinates were rotated to the bicommissural (BC) plane and overlain on an atlas template with the representation of different reticular nuclei and landmarks. ac, Anterior commissure. The 3-dimensional plots show the penetrations sites in the T1-C3 segments of the spinal cord (SC). CS, central sulcus; Arc, arcuate sulcus; Rc, rostro-caudal; Ht, dorsoventral height.

Fig. 3.

Distribution of number of muscles activated per site, using a reduced set of 10 muscles for each area, and only sites activated at threshold intensity A: M1. B: RF. C: SC. D: same data as A–C, but replotted as a cumulative distribution to allow comparison of the different areas. Line colors correspond to the colors used in A–C. E: similar plot as D, but now using all muscles recorded in a given animal; abscissa is expressed as a percentage of the number of muscles available for analysis in each case. F–J: similar display as A–E, but now using all responses recorded, rather than just those at threshold.

Fig. 4.

Proportions of stimulated sites that activated different muscle groups. A–F: for responses at threshold. G–L: for all responses recorded. Muscle groups are specified at the top of each graph.

Fig. 5.

Proportions of sites that activated combinations of muscle groups singly or together. A: for sites stimulated at threshold. B: for all responses recorded. Pie charts show the results for M1, RF, and SC (rows) and different pairs of muscle groups (columns), as illustrated on the picture of an arm at the top.

Fig. 6.

Principal component analysis of stimulus-evoked and natural activity patterns. A–C: cumulative percentage of variance explained (CPVE) as a function of the number of principal components used to reduce the dimensionality of the data. ●, Results for stimulus-evoked activity; □, results for natural activity recorded with the data logger; ○, results for activity recorded in the laboratory during performance of the reach and grasp task. Each plot shows results from a different animal and area: M1 (A), RF (B), and SC (C). D: subspace similarity. For a given CPVE value (abscissa), the number of principal components required to represent at least that CPVE was determined for both stimulus-evoked and natural activity, and the subspace similarity (see methods) was calculated between these 2 vector spaces. Thin lines show results from individual animals and areas; thick lines show results averaged across the 2 animals available for each area. Red, M1; black, RF; blue, SC. Bars at the bottom indicate regions where pairs of similarity measures differ significantly (P < 0.05).

Fig. 7.

Reconstruction of natural activity from stimulus-evoked activity. A and B: schematic illustration of the analysis approach. Unit vectors representing stimulus-evoked activity (left panel, green, orange) are combined to reconstruct natural activity (middle panel, blue). The total length of the reconstruction as a percentage of the length of the natural activity provides the normalized length measure L. The size of the residual as a percentage of the length of the natural activity provides the normalized residual measure R. For display purposes, 2-dimensional vectors are shown; in reality, the vectors are in 10 dimensions, corresponding to the activity of 10 muscles. In A, a situation where natural activity cannot be reconstructed perfectly is shown, so a residual (error) term remains. In B, perfect reconstruction is possible. C: example reconstructions of short sections of natural EMG activity from M1 (monkey T), RF (monkey Sa), and SC (monkey P). Black traces show the recorded data; red traces show the reconstructions from stimulus-evoked vectors; 1 unit in the vertical calibration bar corresponds to the EMG 99th percentile. D: values of L calculated from this analysis using subsets of 30 stimulus-evoked responses. E: corresponding values of R. F: values of L calculated using subsets of 80 stimulus-evoked responses. G: corresponding values of R. □, Results from individual animals and areas; ●, average across 2 animals available for each area. Error bars indicate the standard deviation, computed with 50 different randomly drawn subsets of stimulus-evoked vectors. Brackets indicate significant pairwise differences between areas (P < 10⁻⁴; Monte Carlo test).