Neural basis for hand muscle synergies in the primate spinal cord

Abstract

Grasping is a highly complex movement that requires the coordination of multiple hand joints and muscles. Muscle synergies have been proposed to be the functional building blocks that coordinate such complex motor behaviors, but little is known about how they are implemented in the central nervous system. Here we demonstrate that premotor interneurons (PreM-INs) in the primate cervical spinal cord underlie the spatiotemporal patterns of hand muscle synergies during a voluntary grasping task. Using spike-triggered averaging of hand muscle activity, we found that the muscle fields of PreM-INs were not uniformly distributed across hand muscles but rather distributed as clusters corresponding to muscle synergies. Moreover, although individual PreM-INs have divergent activation patterns, the population activity of PreM-INs reflects the temporal activation of muscle synergies. These findings demonstrate that spinal PreM-INs underlie the muscle coordination required for voluntary hand movements in primates. Given the evolution of neural control of primate hand functions, we suggest that spinal premotor circuits provide the fundamental coordination of multiple joints and muscles upon which more fractionated control is achieved by superimposed, phylogenetically newer, pathways.

Keywords: motor control; muscle synergies; nonhuman primate; precision grip; spinal interneurons.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.

Spatial and temporal similarity between PreM-IN output effects and muscle synergies. (A) Spike-triggered averages of rectified EMGs triggered on spikes of an excitatory PreM-IN (24,337 spikes). Gray rectangles indicate the test windows for the postspike effects (3 to 15 ms after the spike). Asterisks indicate significant postspike facilitation (P < 0.05). (B) Similarity of spatial outputs between the PreM-IN (shown in A) and muscle synergies (Syn1 to 3). The amplitude of postspike facilitation was quantified as a mean percentage increase (black bars) and compared with muscle synergy weights. The similarity was quantified as the cosine of the angle between the two vectors in the muscle dimension. Error bars indicate SEMs. (C) Similarity of temporal activities between the PreM-IN (shown in A) and muscle synergies. The profile was aligned to grip onset and averaged across trials (133 trials). (C, Top to Bottom) Grip force, PreM-IN activity, and synergy activities (Syn1 to 3). The similarity was quantified in the same way as in B but in the time dimension. AbDM, abductor digiti minimi; AbPB, abductor pollicis brevis; ADP, adductor pollicis; ECU, extensor carpi ulnaris; ED23, extensor digitorum-2,3; EDC, extensor digitorum communis; FCR, flexor carpi radialis; FCU, flexor carpi ulnaris; FDI, first dorsal interosseous; FDPr and FDPu, radial and ulnar parts of the flexor digitorum profundus; FDS, flexor digitorum superficialis. au, arbitrary unit; sps, spikes per second.

Fig. S1.

Experimental procedures. (A) Recording setup. We recorded spinal neuron activity as well as muscle activity of hand and arm muscles while the monkey was performing a precision grip task. (B) Spinal recording sites in each monkey. Dots indicate the locations where we recorded the spinal neurons. Letters on the left indicate the number of spinal segments, and those on the right indicate the number of vertebrae. Dorsal views are shown. (C) Example recordings of neural and muscle activity during two successive trials. (C, Top to Bottom) PreM-IN activity, muscle activity (n = 12), and grip force. (D) Example of spike-triggered averaging. Rectified EMG (FDS muscle) was aligned to the spikes of a single spinal neuron (shown in C) and averaged (2,242 spikes). Significant postspike effects are detected by comparing with baseline (Materials and Methods). Scale bar, 10% increase from the baseline amplitude. (E) Schematic illustration of the PreM-IN output. Postspike effects reflect the synaptic connections of the PreM-IN (IN) to the target motoneurons (MN).

Fig. S2.

Selection of the number of muscle synergies. (A) Variance accounted for (R2) as a function of the number of extracted synergies (R2 curve) for week 1 EMG data of monkeys E (Left) and A (Right). The R2 curve was obtained by the fourfold cross-validation of the original EMG data (filled circles). To evaluate the chance level of the R2 curve, we repeated the same procedure for the shuffled EMGs (open circles). Error bars indicate SDs. (B) Increment of the R2 curves (∆R2) for each monkey. The number of muscle synergies (vertical dotted line) was defined by a saturation point, where the ∆R2 of the original data (filled bars) became significantly smaller than the ∆R2 of the shuffled data (open bars). *P < 0.05, t test. Error bars indicate SDs.

Fig. S3.

Muscle synergies during a precision grip task. (A) Muscle activities were reconstructed by a weighted sum of muscle synergy activities. Week 1 data for monkey E. The activities were aligned to grip onset and averaged across trials. (B) Muscle activity in the same session. Solid lines indicate the original EMG profile, and shaded areas indicate the reconstruction by muscle synergies (Syn1 to 3). (C and D) Same format as A and B but of data from week 1 for monkey A. Scale bars, 2 normalized units. (E) Similarity of weights of muscle synergies (Syn1 to 3) between monkeys E (vertical axis) and A (horizontal axis). Color indicates the similarity between each pair of muscle synergies, which was quantified using the cosines of the angles between the muscle synergy vectors. Asterisks denote that the similarity exceeded the chance level obtained by shuffling (P < 0.05).

Fig. S4.

Consistency of muscle synergies across different sessions. (A) R2 curves for EMG data of weeks 1, 2, 3, and 4 from monkeys E (Top) and A (Bottom). The muscle synergy number of 3 was consistently selected in both monkeys and all different sessions (vertical dashed lines). Error bars indicate SDs. (B) Comparison of weights of muscle synergies across different experimental days (weeks 1 to 4). The numbers below indicate the similarity (the cosine of the angle) of synergy weights compared with week 1.

Fig. S5.

Number of muscle synergies selected using different algorithms. This plot compares how many muscle synergies were selected using different algorithms proposed by previous studies and the present study. Each algorithm was applied to eight different datasets (4 wk of two monkeys), and each horizontal bar indicates the probability of a given number of muscle synergies being selected by each algorithm. The algorithms are classified into two groups (groups 1 and 2). Group 1 uses the R2 value [the threshold method (, , , –43)] and group 2 uses the difference between R2 values [the ΔR2, original ΔR2 < shuffle ΔR2 (0.75) (40), three-point curvature (18), linear regression (44), original ΔR2 < shuffle ΔR2 (t test), and original ΔR2 > shuffle ΔR2 methods].

Fig. 2.

Spatial and temporal similarity between excitatory PreM-INs and muscle synergies. (A) Spatial similarity of excitatory PreM-INs with muscle synergies (Syn1 to 3) in monkey E (Top; n = 14) and monkey A (Bottom; n = 4). Colors indicate the result of the unsupervised clustering of spatial similarity (k-means clustering; silhouette value 0.79, P = 0.021 and silhouette value 0.87, P = 0.138 for monkeys E and A, respectively). (B) Comparison of spatial similarity between the preferred and nonpreferred synergies. The preferred synergy was defined as the closest axis to each cluster in A, and the two nonpreferred synergies were defined as the other axes. Connected circles indicate the spatial similarities of the individual PreM-IN with the preferred or nonpreferred synergy. Each PreM-IN yields two pairs of preferred and nonpreferred synergies, and are counted individually. Data from both monkeys were pooled (n = 36). Boxplots indicate the median and interquartile range. Whiskers and notches indicate the max–min values, except outliers, and the 95% confidence intervals of the medians. (C) Temporal similarity of the same PreM-INs with muscle synergies (Syn1 to 3) in each monkey. The colors indicate the clusters obtained in A. (D) Comparison of temporal similarity between the preferred and nonpreferred synergies. Same format as B. **P < 0.01, *P < 0.05, Wilcoxon signed-rank test.

Fig. S6.

Muscle fields of each PreM-IN and their preferred muscle synergy. The muscle fields of all PreM-INs (n = 23) are displayed with their preferred muscle synergy (Syn1, Syn2, and Syn3). (A) Excitatory PreM-INs of monkey E, (B) excitatory PreM-INs of monkey A, and (C) inhibitory PreM-INs of all monkeys. The figure format is the same as in Fig. 1B, and muscle synergies are color-coded as in Fig. S3. The PreM-INs are grouped according to the results of clustering (clusters 1 to 3 for monkey E, and clusters 1 and 2 for monkey A; Fig. 2A) and displayed according to the spatial similarity to the preferred synergy (numbers in parentheses). Note that for the inhibitory PreM-INs (C), the preferred synergy and similarity to it are not shown because the clustering was not significant for this population. In addition, the horizontal axis is inverted to display their negative MPI values for the inhibitory PreM-INs (C). The spatial similarity of all PreM-IN and muscle synergy pairs is summarized in Table S1. N/A, data not available.

Fig. S7.

Spatial (A) and temporal (B) similarities between inhibitory PreM-INs and muscle synergies. Same format as in Fig. 2 A and C but for the inhibitory PreM-INs (n = 5). Note that the clustering failed for the inhibitory PreM-INs and therefore the plots are not grouped.

Fig. S8.

Temporal profiles for each PreM-IN and their preferred muscle synergies. The temporal activity of all PreM-INs (n = 23) is displayed with the temporal activity of their preferred synergy (Top; Syn1 to 3) using the same format as in Fig. 1C. (A) Excitatory PreM-INs of monkey E, (B) excitatory PreM-INs of monkey A, and (C) inhibitory PreM-INs for all monkeys. The muscle synergies are color-coded as in Fig. S3. The PreM-INs are grouped according to the result of clustering (Clus1 to 3) and displayed according to the spatial similarity (not temporal similarity) with the preferred synergy as in Fig. S6. Numbers in parentheses indicate temporal similarity with their preferred synergy. Note that for the inhibitory PreM-INs (C), the preferred synergy and similarity to it are not shown, as the clustering was not significant. The temporal similarity of all PreM-IN and muscle synergy pairs is summarized in Table S1. Scale bars, 1 normalized unit for muscle synergies and 10 spikes per s for PreM-INs.

Fig. 3.

Similarity between muscle synergy activity and PreM-IN population activity. (A) Synergy trajectory during a mean grip movement by monkey E. Axes indicate the activity of muscle synergy (Syn1 to 3). Colors indicate the time course of the grip: 0, grip onset; 1, release onset. (A, Right) The activity of each muscle synergy (Syn1 to 3). (B) Neural trajectory during the same movement of the same monkey. Axes indicate the population activity of the PreM-IN cluster (Clus1 to 3) as defined in Fig. 2A. (B, Right) The activity of each cluster (Clus1 to 3). Same format as A. *P < 0.01, permutation test.