The aim of the present study was to examine the time course of corticospinal excitability during SS of the plantar flexors as well as to monitor potential variation during dynamic DF and PF. For both SOL and TA, the amplitude of the MEPs evoked during DF was significantly higher compared to baseline. Throughout the entire 30 sec SS the corticomotor excitability was significantly increased for TA and did not show a time-dependent trend.
Response modulation during SS
During the 30 seconds SS, MEPs were collected at six time points: 3, 6, 9, 18, 21 and 25 seconds into stretching. Since we observed a clear facilitation during the DF movement required to bring the foot to maximal individual static DF position, we could have expected to capture a long-lasting effect within the first measurement at 3 seconds. Looking at Figure 2 this seems to be confirmed in most of the subjects, and from the group average it is immediately visible a pattern consisting in a sharp facilitation at 3 seconds into stretching, a reduction of this from 3 to 6 seconds, followed by a more or less linear increase. Both muscles showed the same behaviour, although no differences between time points into stretching were observed. Interestingly, such behaviour appears specular to the H-reflex inhibition we previously observed 18. Figure 5 was constructed with the data of H-reflexes in a previous experiment 18. The group average 96% increase in MEPs size at 3 seconds is matched by a 59% decrease in H-reflex, from 3 to 6 seconds MEPs size decreased whilst H-reflex increased.
This symmetry, that ends from 6 seconds on, seems again to support the hypothesis of a relationship between variation in peripheral afferent input and corticospinal excitability and specifically suggests that increased Ia afferents from SOL muscle spindles, are responsible for facilitation on corticospinal excitability of its antagonist TA. This crossed agonist/antagonist effect has already been shown by Bertolasi and colleagues 35 who demonstrated an effect of forearm flexor muscle afferents on excitability of corticospinal projections to antagonist muscles. Although the authors reported an inhibitory action to the antagonist, it has to be considered the relevance of the adopted conditioning-test intervals 27: in Bertolasi et al. 35 it was circa 20 ms whilst a minimum 500 ms elapsed from the beginning of the stretch to the TMS stimulation in our study. Moreover, the stimulus was not a short electrical input, but a prolonged passive displacement. Thus, we can hypothesise that afferent projections from one muscle have a crossed effect on the cortical excitability of its agonist, but whether this has an inhibitory or facilitatory effect is in relation to several factors including stimulus duration/modality, conditioning-test interval and muscles tested.
From 3 seconds into stretching, the Ia activity can be expected to be markedly reduced, whilst firing frequency of muscle spindle secondary afferents (group II) increases. Afferents from SOL secondary endings seem to affect TA corticospinal excitability in a similar, although weaker, way (Figure 4B). Increased activity from secondary muscle spindle afferents can depress Renshaw cells recurrent inhibition, as demonstrated both on decerebrated cats 36 and through computer modelling 37, resulting therefore in the observed facilitation.
Response modulation during dynamic DF
The observed corticomotor facilitation during DF was registered for both the elongated (SOL) and the shortened (TA) muscles. While the increased corticomotor excitability of TA during DF is in line with studies showing increased MEP during passive muscle shortening 12,13,16,17,21,25, the simultaneously recorded facilitation in the elongated muscle SOL is not supported by previous findings, which commonly report reduced MEP amplitude during lengthening of the wrist and elbow flexors and extensors 12,13,16,17,21,38. However, differently to the upper limb, responses in the lower limb are sometimes contradictory being susceptible to more variables 22–26. For example Škarabot and colleagues reported a facilitation in the shortened TA in young 25 but not in old participants 26 and no effect on the lengthened SOL 25,26, whilst Hultborn and colleagues 20 did not report any facilitation in neither TA nor SOL, and in the present study we witnessed a facilitation in both TA and SOL.
On the origin of the facilitation we observed, potential sites of modulation of the MEP in response to TMS include intrinsic cortical inputs to the pyramidal tract neurons in M1, the activity of the α-motoneurons and interneuron network at spinal level and the afferent signals arising from activated sensory receptors. Considering that TMS activates predominantly monosynaptic pathways to the α-motoneurons and these connections are not exposed to presynaptic inhibition 13, it seems that the observed excitability alterations during DF can be attributed either to cortical inputs to the corticospinal pathways or to postsynaptic inputs directly modulating the α-motoneurons. However, a recent study showed that during passive ankle movements, the excitability at the lumbar spinal segmental level was not modulated in neither TA nor SOL 25, suggesting supraspinal rather than postsynaptic contributions to the observed MEP facilitation.
Supraspinal structures can indeed be affected by proprioceptive afferents. During passive lengthening movements, Ia fibres from muscle spindles respond to changes in muscle length by increasing their firing rate 39,40. The respective inflows projecting primarily to the area 3a in the primary somatosensory cortex (S1) 41, can activate indirectly the cortical inputs to the pyramidal tract neurons in M1. Such co-activation within the S1 area and the motor areas (M1 and SMA) in response to passive proprioceptive stimulation (passive fingers’ flexion and extension) was demonstrated in a fMRI study 42. It is known that the finely scaled topographic maps of S1 and M1 enable both areas to have highly specialized responses to changes in the periphery 43,44. As shown in a sensorimotor slice 45, the anatomical and functional sensorimotor connections are reciprocal and their localization in cortical layers V and VI allow descending outputs also to the spinal cord 46. In our study we can expect that the increase in Ia afferents activity from SOL during DF reached the somatosensory area (3a), which transmits these inputs further to the M1 output neurons, increasing the excitability of the descending corticomotor pathway.
Such increased excitability originating from the cortex with related facilitation on the descending drive, could be a compensation mechanism for the spinal inhibition (typically observed as decrease in H-reflex during lengthening movements for review see 10), as shown in a study with active muscle lengthening 21. However, if an increased Ia activity provoked an increase in corticospinal excitability or reduced cerebello-cortical inhibition on projections on the homonymous muscle, we should have observed not only greater MEPs in the SOL during DF, but also in the TA during PF movement. Alternatively, in case of projections on the antagonist muscles, we should have observed greater MEPs in the TA during DF together with greater MEPs in the SOL during PF movement, but neither of these two scenarios was the case (Figure 4).
A possible explanation of this not muscle-specific response could be attributed to the awareness of the subjects of the foot passive displacements, that, for methodological requirements, was repeated 60 times. Indeed, in healthy individuals, passive movements are shown to activate not only the primary somatosensory cortex but also the primary motor cortex, supplementary motor area, and posterior parietal cortex as well as the secondary somatosensory cortex (S2) (for review see 47). Moreover, passive movements can selectively increase the cortical excitability dependent on the duration and velocity of movements, the presence of rest, but also on whether attention was directed to the movement. Attention to the stimulated side during an intervention (peripheral afferent stimulation, passive movements) decreases the activity of the inhibitory cortical circuits, and thus increases corticospinal excitability. In our study the subjects were instructed to avoid observing the stretching extremity. Nevertheless, the effect of attention to the movement throughout the experimental procedure cannot be completely excluded. In addition, passive movements repeated with the same amplitude and velocity for a certain time might be able to induce attempted movement, thereby activating neurons in M1 48 and resulting in increased MEPs during DF for both TA and SOL muscles.
Despite the precise mechanisms responsible for the increased excitability cannot be clarified with this study, the findings may have clinical potential in neurorehabilitation, where passive movements are commonly applied in physiotherapy. For example in patients with paresis of the lower extremity passive dorsi- and plantar flexions can be repeatedly performed using robotic devices. It is expected that the augmented proprioceptive input facilitating motor cortical excitability, may promote motor activation and thus can improve motor recovery.
In the present study M-max were only recorded from the SOL. Therefore MEP/M-max normalisation would be only possible for this muscle. However, M-max is known not to be affected during and after stretching, therefore we could normalise our data by expressing them as a percentage of variation from baseline values.
Since the stretching protocol and respectively the stimulations at specific time points into and after the stretch had to be repeated several times, the TMS hot spot was located for stimulating the SOL, and we did not perform separate stimulations targeting specifically the TA. Nevertheless, we could observe differential MEP changes also in TA.
Finally, the inevitable methodological requirement of repeating the stretching procedure several times, could have influeced muscle stiffness with related consequences for muscle afferent feedback and proprioception.
In conclusion, it was shown that passive dynamic dorsiflexion of the plantar flexors and their static stretching facilitated the MEP after TMS recorded from both, the stretched and the shortened muscles.
This faciliation did not show a time-dependent trend or a tendency to recover during the stretching period.