Transcranial magnetic stimulation over sensorimotor cortex disrupts anticipatory reflex gain modulation for skilled action

Abstract

Skilled interactions with new environments require flexible changes to the transformation from somatosensory signals to motor outputs. Transcortical reflex gains are known to be modulated according to task and environmental dynamics, but the mechanism of this modulation remains unclear. We examined reflex organization in the sensorimotor cortex. Subjects performed point-to-point arm movements into predictable force fields. When a small perturbation was applied just before the arm encountered the force field, reflex responses in the shoulder muscles changed according to the upcoming force field direction, indicating anticipatory reflex gain modulation. However, when a transcranial magnetic stimulation (TMS) was applied before the reflex response to such perturbations so that the silent period caused by TMS overlapped the reflex processing period, this modulation was abolished, while the reflex itself remained. Loss of reflex gain modulation could not be explained by reduced reflex amplitudes nor by peripheral effects of TMS on the muscles themselves. Instead, we suggest that TMS disrupted interneuronal networks in the sensorimotor cortex, which contribute to reflex gain modulation rather than reflex generation. We suggest that these networks normally provide the adaptability of rapid sensorimotor reflex responses by regulating reflex gains according to the current dynamical environment.

Figure 1.

Experimental setup. By using a PFM system, subjects performed point-to-point arm movements forward from the body. During the later part of movements, a leftward (L-FF) or rightward (R-FF) force field was applied in addition to null force (N-FF).

Figure 2.

Movement and EMG patterns with different force fields. A, Typical example of hand trajectories (left panel) and each hand curvature (right panel) in the right/left direction in the normal (N-FF, R-FF, and L-FF) and after-effect (aR-FF and aL-FF) trials with different force fields. The rectangular dashed area is force field location. The traces in the normal trials are the average of 12 trials. The traces in the after-effect trials are the average of 3 trials. In after-effect trials, either direction of force field was unexpectedly removed. Each bar in the right graph represents the mean and SE of hand curvature in the right/left direction for each condition. The asterisks express a significant difference between the normal and after-effect trials for each field (***p < 0.001). B, An example of the hand position profiles in the y-axis direction, the hand force profiles in the x-axis direction (upward is left direction), and the EMG waveforms in the shoulder flexor and extensor muscles during arm movements in the R-FF (black line) and L-FF (gray line) conditions. The data show results from a typical subject in baseline conditions with neither perturbation nor TMS. Each trace is the average of 12 trials. The rectangular dashed area denotes the force field period. Time 0 corresponds to a position trigger (0.03 m from the start position) shown in Figure 2A. The downward arrows in the bottom graph represent the time at which transcranial magnetic stimulation (dashed arrow) and perturbation (solid arrow) would be applied in other conditions as appropriate. Note that the muscle activity before the arm encountered the force fields was almost same between the R-FF and L-FF conditions.

Figure 3.

Differences in stretch reflex responses and hand reaction forces between the force fields. A, An example of the waveforms of hand position in the x-axis (right/left) direction, shoulder joint angular velocity in the flexion/extension direction, and EMG in the shoulder flexor and extensor muscles when a mechanical perturbation was applied (thick lines). The rightward (R-PTB; top panels) and leftward (L-PTB; bottom panels) perturbations applied at 50 ms indicated by the vertical dashed line induce reflex responses in the flexor and extensor muscles, respectively. The thin lines indicate the EMG waveforms in a control task in which the subject was instructed to make voluntary assistive reactions to perturbations. For example, the voluntary response to a leftward perturbation is used as a control for the reflex response to a rightward perturbation. Note the clear temporal separation between reflex and voluntary responses. B, Comparisons of reflex responses in the flexor and extensor muscles between the L-FF and R-FF conditions. Each bar represents the mean and SE for each muscle. The asterisks express a significant difference between the force fields (**p < 0.01). Note that the reflex amplitudes in the flexor and extensor muscles were larger in the R-FF and in the L-FF condition, respectively. C, Differences in the hand reaction force after reflex response between the force fields. The leftward and rightward reaction forces were calculated from the R-PTB and L-PTB trials, respectively. Other notations are the same as in B. Note that the leftward reaction force was larger in the R-FF condition, and, in contrast, the rightward force was larger in the L-FF condition (***p < 0.001).

Figure 4.

Effect of previous TMS on stretch reflex modulation. A, An example of the reflex responses in both muscles (thick lines) when TMS was applied 50 ms before the perturbation (vertical dashed line). The thin lines indicate the waveforms when only TMS was applied. B, Comparisons of reflex responses with TMS in both muscles between the force fields. Other notations are the same as in Figure 3B. C, Comparisons of the difference in reflex response between the fields (R-FF minus L-FF). The asterisks express a significant difference between the force fields (** p < 0.01). Note that the differences in reflex responses between the force fields were eliminated by applying previous TMS, whereas the reflex responses themselves were still clearly present.

Figure 5.

Effect of small perturbation on reflex modulation. The reflex responses in both muscles when normal PTB (20 N) with TMS (left panels) or small PTB (12.5 or 15 N; right panels) was applied. Each open and filled circle indicates the individual and mean values, respectively. Values are represented as percentages of the response induced by the PTB amplitudes used in the main experiment, in no-TMS conditions. The asterisks express a significant difference between the force fields (*p 0.05; **p < 0.01). Note that there were significant differences in reflex responses between the force fields even for the smaller reflexes after smaller perturbations, in contrast to the reflexes induced after TMS.

Figure 6.

Effect of previous peripheral nerve stimulation on reflex modulation. A, An example of the reflex responses (thick lines) in the flexor muscle when a PES at the right brachial plexus was applied (bottom panel) and was not (top panel). The thin lines demonstrate the waveforms without PTB. B, The reflex responses in both muscles in PES condition. Other notations are the same as in Figure 5. The asterisks express a significant difference between the force fields (**p < 0.01). Note that even when PES was applied, the modulation of reflex responses according to the cued force fields remained clear.