Tuning of motor outputs produced by spinal stimulation during voluntary control of torque directions in monkeys
- Neural Prosthetics Project, Tokyo Metropolitan Institute of Medical Science, Japan
- The Japan Society for the Promotion of Science, Japan
- Division of Neural Engineering, Graduate School of Medical and Dental Sciences, Niigata University, Japan
Figures
Figure 1
Experimental design.
(A) The platinum electrode array used for subdural spinal stimulation. (B) The platinum electrode array was slid into the subdural space from the caudal incision site at the C7 vertebra level and placed over the dorsal-lateral aspect of the C6–T2 spinal segments on right side. (C) Spinal stimulation applied during an isometric, eight-target wrist torque tracking task. (D) Raw traces of electromyograms (EMGs) and wrist torques during spinal stimulation. One pulse of a biphasic square-wave with a duration of 0.2 ms and an interval of 197 ms was applied at stimulus currents of 110 µA through a single electrode during the task. The yellow rectangles indicate duration and torque of targets. FCR, flexor carpi radialis; ECR, extensor carpi radialis; ECU, extensor carpi ulnaris; FCU, flexor carpi ulnaris; PL, palmaris longus. (E) Stimulus-triggered averages (StTAs) of rectified EMGs and torques during the hold period for a peripheral target at stimulus currents of 110 µA through electrode No. 2 (see A). Red and blue areas indicate post-stimulus facilitative (Facilitation) and suppressive (Suppression) effects evoked by spinal stimulation, respectively. Numbers give the magnitudes of post-stimulus effects (PStEs) for Facilitation or Suppression (μV·ms). The two gray lines in EMGs or torques represent ± 3 SDs or ± 10 SDs of StTAs calculated during the baseline period (30–10 ms preceding the stimulus trigger pulse), respectively. The data was obtained from monkey W.
Figure 2
Directional tuning of the stimulus-induced muscle responses during wrist torque tracking task.
(A–C) Muscle responses to spinal stimulation during the hold period for the eight-peripheral (peripheral panels) and the center targets (center of peripheral panels). Insets show the whole period of the task including hold and movement periods. The polar plots display magnitudes of Facilitation (red) and Suppression (blue) effects on post-stimulus effects (PStEs), as well as background electromyograms (EMGs) (green) for a 20 ms pre-stimulus window during the hold period for the eight-peripheral target locations, and the preferred directions (PDs) calculated by vector summation (bootstrap analysis, p<0.05). Typical examples of output type for (A) Facilitation (only Facilitation in all targets); (B) Suppression (only Suppression in all targets); (C) Facilitation+ and Suppression (stimulations induced both effects and larger magnitudes of Facilitation than Suppression). The green thick trace in each stimulus-triggered average (StTA) indicates background EMG activities composing its polar plots. Horizontal bars below the polar plots show the magnitudes of PStEs or background EMGs. ECU, extensor carpi ulnaris; FCU, flexor carpi ulnaris; FDP, flexor digitorum profundus. (D) Distributions of the Spinal, background EMG, and Normalized Spinal PDs. Spinal PD (top panels) and background EMG PD (middle panels) show the PDs calculated by the magnitudes of Facilitation or Suppression of PStEs and by the magnitudes of background EMG activity, respectively, during the hold period for the peripheral targets. Normalized Spinal PD (bottom panels) shows angles normalized by subtracting the background EMG PD from the Spinal PD. Red or blue thick lines indicate circular medians and significant nonuniform distributions (Rayleigh test, p<0.05) toward its direction (v-test; *, p<0.05; **, p<0.01; ***, p<0.001). Normalized Spinal PDs for Facilitation (bottom-left) and Suppression (bottom-right) show significant nonuniform distributions (Rayleigh test, p<0.05) around 0° (v-test; *, p<0.05; **, p<0.01; ***, p<0.001). Horizontal bars below the polar plots indicate the number of muscular conditions.
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Figure 2—source data 1
Data used to generate polar plots and detailed statistics in Figure 2D.
- https://cdn.elifesciences.org/articles/78346/elife-78346-fig2-data1-v1.xlsx
Figure 3
Effect of current intensity on directional tuning of the stimulus-induced muscle responses.
(A and B) Polar plots of the post-stimulus effects (PStEs) for Facilitation, Suppression, and background electromyogram (EMG) at four different current intensities during the hold period for the eight peripheral targets. Vertical bars next to the polar plots show the magnitudes of PStEs or background EMGs. (A) Responses in the palmaris longus (PL) muscle at current intensities of 70 μA, 180 μA, 1000 μA, and 1700 μA through Elec. No. 3. (B) Responses in the flexor digitorum profundus (FDP) muscle by stimulation at current intensities of 70 μA, 200 μA, 1000 μA, and 1700 μA through Elec. No. 3. (C) Effect of current intensity on output type for PStEs. Facilitation, only Facilitation in all targets; Suppression, only Suppression in all targets; Facilitation+ and Suppression, stimulations induced both PStEs, and larger magnitudes of Facilitation than Suppression; Facilitation and Suppression+, stimulations induced both PStEs and larger magnitudes of Suppression than Facilitation; No response, no PStEs in all targets. (D) Mean values and SEs for the magnitudes of PStEs calculated in each current intensity. Statistics: one-way factorial ANOVA with Tukey-Kramer correction for post hoc multiple comparison (*, p<0.05; **, p<0.01; ***, p<0.001). (E and F) Population data of effect of current intensity on (E) Spinal PD and (F) Normalized Spinal PD. Red or blue thick lines indicate circular medians and significant nonuniform distributions (Rayleigh test, p<0.05) toward its direction (v-test; *, p<0.05; **, p<0.01; ***, p<0.001). Normalized Spinal PDs for Facilitation and Suppression evoked by lower (<1350 μA) intensity stimulation were significantly nonuniform (Rayleigh test, p<0.05) around 0° (v-test; *, p<0.05; **, p<0.01; ***, p<0.001), whereas Normalized Spinal PDs for Facilitation evoked by high intensity stimulation (≥1350 μA) was significantly nonuniform (Rayleigh test, p<0.05) around 180° (v-test; *, p<0.05; **, p<0.01; ***, p<0.001). Horizontal bars below each polar plot show the number of muscular conditions.
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Figure 3—source data 1
Data used to generate bar plots and detailed statistics in Figure 3D.
- https://cdn.elifesciences.org/articles/78346/elife-78346-fig3-data1-v1.xlsx
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Figure 3—source data 2
Data used to generate polar plots and detailed statistics in Figure 3E.
- https://cdn.elifesciences.org/articles/78346/elife-78346-fig3-data2-v1.xlsx
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Figure 3—source data 3
Data used to generate polar plots and detailed statistics in Figure 3F.
- https://cdn.elifesciences.org/articles/78346/elife-78346-fig3-data3-v1.xlsx
Figure 4 with 1 supplement
Effect of stimulus site on directional tuning of the stimulus-induced muscle responses.
(A) Locations of electrodes on the cervical cord. Yellow and green sites correspond with rostral (top rows) and caudal (bottom rows) electrodes on (B) and (C), respectively. (B and C) Polar plots of the muscle responses for Facilitation, Suppression, and background electromyogram (EMG) by stimulations from the rostral electrode and caudal electrode during the hold period for the eight peripheral targets. These muscle responses are obtained from the (B) biceps brachii (BB) muscle and (C) flexor digitorum profundus (FDP) muscle innervated by motoneurons located in the rostral and caudal cervical cord, respectively. Horizontal bars below the polar plots show the magnitudes of post-stimulus effects (PStEs) or background EMGs. (D) Effect of stimulations at rostral and caudal sites on PStE types in the rostrally and caudally innervated muscles. The color-coded representations are the same as in Figure 3C. (E and F) Mean values and SEs for the magnitudes of PStEs from rostral or caudal stimulus sites into (E) rostrally innervated muscles or (F) caudally innervated muscles (two-sided unpaired t-test; *, p<0.05; **, p<0.01; ***, p<0.001). (G and H) Distributions of the PDs for Facilitation and Suppression from (G) rostrally innervated muscles or (H) caudally innervated muscles by stimulation at rostral (top) or caudal (bottom) sites. The Normalized Spinal PDs for Facilitation and Suppression are significantly tuned (Rayleigh test, p<0.05) around 0° (v-test; *, p<0.05; **, p<0.01; ***, p<0.001), except for the cases of Facilitation in the rostrally innervated muscles through the stimulation at caudal sites (bottom-left panel of [G]). Red or blue thick lines indicate circular medians and significant nonuniform distributions (Rayleigh test, p<0.05) toward its direction (v-test; *, p<0.05; **, p<0.01; ***, p<0.001). Horizontal bars below each polar plot show the number of muscular conditions. Because higher currents of ≥1350 μA were administered using only caudal electrodes, the data obtained at high-intensity stimulation was excluded from the population analyses in Figure 4 to allow for fair comparison.
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Figure 4—source data 1
Data used to generate bar plots and detailed statistics in Figure 4E.
- https://cdn.elifesciences.org/articles/78346/elife-78346-fig4-data1-v1.xlsx
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Figure 4—source data 2
Data used to generate bar plots and detailed statistics in Figure 4F.
- https://cdn.elifesciences.org/articles/78346/elife-78346-fig4-data2-v1.xlsx
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Figure 4—source data 3
Data used to generate polar plots and detailed statistics in Figure 4G.
- https://cdn.elifesciences.org/articles/78346/elife-78346-fig4-data3-v1.xlsx
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Figure 4—source data 4
Data used to generate polar plots and detailed statistics in Figure 4H.
- https://cdn.elifesciences.org/articles/78346/elife-78346-fig4-data4-v1.xlsx
Figure 4—figure supplement 1
Definition of stimulus sites and muscles.
(A) Geomatical relationship between locations of the stimulus electrodes and motor nucleus. Definition of rostral or caudal stimulus site was determined based on evoked movement at each stimulus site under anesthesia (Table 1). Rostral elec.: The sites mainly induced proximal joint movements that were driven by the muscle innervated by the rostral motor nuclei of cervical enlargement. Caudal elec.: The sites mainly induced distal joint movements that were driven by the muscle innervated by the caudal motor nuclei of cervical enlargement. Gray scale bars indicate distributions of the motoneurons of the recorded muscles. (B) Skeletal positions of the recorded muscles.
Figure 5
Effect of background electromyogram (EMG) on the stimulus-induced muscle responses.
(A–C) Examples of background EMG-dependent modulations for the post-stimulus effects (PStEs). Representative examples of PStEs for (A) Facilitation only, (B) Suppression only, and (C) both Facilitation and Suppression (Faci/Supp). The leftmost insets show PStEs during the hold period for the center target. The rightmost panels for each muscular condition show two-sided Pearson’s correlation coefficients between the magnitudes of background EMGs and PStEs. Gray dots in right panels indicate the result during the hold period for the center target that were not included for the correlation analyses. (D) Population data of the correlation coefficients between the magnitudes of background EMGs and PStEs. Correlation coefficients are categorized by output type of PStEs altered depending on the magnitudes of background EMGs, which indicated only Facilitation (Facilitation, left), only Suppression (Suppression, center), and both the Facilitation and Suppression (Faci/Supp, right). There are strong positive correlations between the magnitudes of background EMGs and any type of PStEs (i.e. Facilitation, Suppression, and Faci/Supp). Hatched bars indicate the number of muscular conditions showing significant correlation between the magnitudes of PStEs and background EMGs (two-sided Pearson’s correlation test, p<0.05). Unhatched bars show the conditions with no statistical significance. The letter shown in each arrow identifies the muscular conditions in A, B, and C, respectively.
Figure 6
Effect of current intensity on the relationship between the stimulus-induced muscle responses and background electromyograms (EMGs).
(A–D) Examples of stimulus-intensity-dependent modulation of post-stimulus effects (PStEs) on background EMGs. Stimulus-triggered averages (StTAs) by stimulation at stimulus intensities of (A) 70 μA, (B) 150 μA, (C) 1000 μA, and (D) 1700 μA were obtained from the flexor carpi radialis (FCR) muscle through Elec. No. 3 of monkey W. The leftmost insets show PStEs during hold period for the center target intended to relax the wrist. The rightmost panels indicate two-sided Pearson’s correlation coefficients between the magnitudes of background EMGs and PStEs. Gray dots in right panels indicate the result during hold period for the center target that were not included for the correlation analyses. (E) The distributions of two-sided Pearson’s correlation coefficients between the magnitudes of background EMGs and PStEs at stimulus intensities of <150 μA, 150–750 μA, 750–1350 μA, and ≥1350 μA. Correlation coefficient for each muscular condition was categorized as ‘Facilitation only’ (Facilitation, left panels), ‘Suppression only’ (Suppression, center panels), and ‘Facilitation and Suppression’ (Faci/Supp, right panels) according to the output type of PStEs. The magnitudes of PStEs at lower current stimulation show positive correlation with those of background EMGs, whereas the magnitudes of PStEs at higher current stimulation exhibit negative correlation with those of background EMGs. Hatched and unhatched bars indicate the number of muscular conditions as in Figure 5D. The letter shown in each arrow indicates the muscular conditions in A, B, C, and D, respectively.
Figure 7 with 1 supplement
Directional tuning of the stimulus-induced wrist torque.
(A) The structure of B–D. The center panel shows evoked torque trajectory about wrist joint (top) and evoked electromyogram (EMG) (bottom) during the hold period for the center target. Inner- (gray circles) and outer-peripheral panels (black circles) indicate evoked torque trajectory and evoked EMG on the eight-peripheral targets, respectively. (B–D) Stimulus-triggered averages (StTAs) of rectified EMGs (outer peripheral panels and center-bottom panel) and StTAs of wrist torque trajectories (inner peripheral panels and center-top panel). The length of arrows and the direction of arrowhead in inner peripheral panels express the magnitudes and directions of statistically significant evoked torques (Evoked Torque), respectively (see ‘Materials and methods’). The absence of an arrow for the radial-flexion location of (C) indicates no statistically significant Evoked Torque. Color-coded numbers near each arrow indicate the direction of Evoked Torque. Normalized Torque (insets of B-D) was exhibited by subtracting the direction of voluntary torque productions from the direction of Evoked Torque for the eight-peripheral targets. Vertical bars of polar plots (insets of B-D) display the magnitudes of Normalized Torque. Typical examples of Evoked Torque type. (B) Convergence, stimulation at 110 µA induced torque toward the center in the eight-peripheral targets. (C) Divergence, stimulation at 300 µA induced outward torque in the eight-peripheral targets. (D) Ulnar-flexion direction, stimulation at 1700 µA induced torque toward the ulnar-flexion direction in the eight-peripheral targets. (E) Mean values and SEs for the magnitudes of Evoked Torque for the eight-peripheral targets calculated in each current intensity. Statistics: one-way ANOVA with Tukey-Kramer correction for post hoc multiple comparison (*, p<0.05; **, p<0.01; ***, p<0.001). (F) Distributions for the directions of the Evoked Torque (left panels) and the Normalized Torque (right panels) for the eight-peripheral targets. Pink lines indicate circular medians and significant nonuniform distributions (Rayleigh test, p<0.05) toward its direction (v-test; *, p<0.05; **, p<0.01; ***, p<0.001). The Normalized Torque at <150 μA and 150–1350 μA significantly tuned (Rayleigh test, p<0.05) around 0 and 180° (v-test; *, p<0.05; **, p<0.01; ***, p<0.001), respectively. Vertical bars below the polar plots indicate the number of muscular conditions.
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Figure 7—source data 1
Data used to generate bar plots and detailed statistics in Figure 7E.
- https://cdn.elifesciences.org/articles/78346/elife-78346-fig7-data1-v1.xlsx
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Figure 7—source data 2
Data used to generate polar plots and detailed statistics in Figure 7F.
- https://cdn.elifesciences.org/articles/78346/elife-78346-fig7-data2-v1.xlsx
Figure 7—figure supplement 1
Subdural spinal stimulation simultaneously evoked facilitative and suppressive effects in multiple muscles and activated synergistic muscle groups.
(A–C) Stimulus-triggered averages (StTAs) of rectified electromyograms (EMGs) in five wrist muscles during the hold period for the center and the four peripheral targets. Each polar plot was normalized by the maximum value of each muscle. Each example in (A–C) corresponds to the cases of Figure 7B–D, respectively. At low and medium currents of stimulations, large magnitudes of post-stimulus effects (PStEs) were observed in the muscles with high background EMG. For instance, stimulation given at the flexion directed target in (B) strongly facilitated wrist flexor muscles (e.g. flexor carpi radialis [FCR], palmaris longus [PL], and flexor carpi ulnaris [FCU]), while stimuli at the extension directed target strongly facilitated wrist extensor muscles (e.g. extensor carpi radialis [ECR] and extensor carpi ulnaris [ECU]). On the other hand, at high current of stimulation, the magnitudes of PStEs hardly changed regardless of the magnitudes of background EMGs and the directions of voluntary torque.
Figure 8
Latency of stimulus-induced muscle responses.
(A and B) Post-stimulus effects (PStEs) and their onset latencies at four different current intensities during the whole period of the task. Dashed lines indicate the onset of responses. Red and blue lines indicate Facilitation effects and Suppression effects, respectively. N is the number of stimuli for averaged evoked muscle responses. (A) Examples of PStE changing from Facilitation to Suppression. (B) Examples of PStE for Facilitation. (C) Directional tuning of PStEs and their onset latencies in the palmaris longus (PL) muscle at four different current intensities through Elec. No. 3 during the hold period for each target. Red and blue lines show Facilitation and Suppression effects, respectively. N is the number of stimuli for averaged evoked muscle responses. (D) Distributions of onset latencies for Facilitation and Suppression effects at four different current intensities during the hold period for the eight peripheral targets. Gray vertical lines indicate the medians of onset latencies for Facilitation and Suppression effects.
Tables
Table 1
Evoked movements at movement threshold.
| Elec. No. | Monkey H | Monkey W | ||||
|---|---|---|---|---|---|---|
| Threshold | Evoked movements | Category of stimulation site | Threshold | Evoked movements | Category of stimulation site | |
| 1 | 150 μA | Elbow | Rostral | 120 μA | Elbow | Rostral |
| 2 | 90 μA | Elbow | Rostral | 70 μA | Finger | Caudal |
| 3 | 50 μA | Elbow | Rostral | 40 μA | Thumb | Caudal |
| 4 | 40 μA | Elbow | Rostral | 50 μA | Thumb | Caudal |
| 5 | 30 μA | Thumb | Caudal | 90 μA | Thumb | Caudal |
| 6 | 40 μA | Thumb | Caudal | 80 μA | Wrist | Caudal |
| 7 | 50 μA | Thumb | Caudal | |||
Additional files
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Transparent reporting form
- https://cdn.elifesciences.org/articles/78346/elife-78346-transrepform1-v1.docx
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Supplementary file 1
Summary of collected data.
- https://cdn.elifesciences.org/articles/78346/elife-78346-supp1-v1.docx
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Tuning of motor outputs produced by spinal stimulation during voluntary control of torque directions in monkeys
eLife 11:e78346.
https://doi.org/10.7554/eLife.78346
