Vibration decreases the responsiveness of Ia afferents and spinal motoneurons in humans

Vibration decreased the responsiveness of Ia afferents from the muscle exposed to vibration, and the duration of depressive effect was modulated by the duration and frequency of the vibration: a longer duration and a higher frequency of vibration led to a longer recovery time of the depression. In addition to this presynaptic effect, it also depressed the responsiveness of spinal motoneurons, indicating postsynaptic inhibition through specific circuits triggered by Ia impulses.

Mechanisms modulating spinal excitability after nerve stimulation inducing extra torque

The study included 3 experiments aiming to examine the mechanisms responsible for spinal excitability modulation, as assessed by the H-reflex, following stimulation trains delivered at two different frequencies (20 and 100Hz) inducing extra torque (ET). A first experiment (n=15) was conducted to evaluate changes in presynaptic inhibition acting on Ia afferents induced by these electrical stimulation trains, assessed by conditioning the soleus H-reflex (tibial nerve stimulation) with stimulation of the common peroneal nerve (D1 inhibition) and of the femoral nerve (heteronymous Ia facilitation, HF). A second experiment (n=12) permitted to investigate homosynaptic post-activation depression (HPAD) changes after the stimulation trains. A third experiment (n=14) analysed changes in motoneuron intrinsic properties after the stimulation trains, by electrically stimulating the descending corticospinal tract at the thoracic level, evoking thoracic motor evoked potentials (TMEP). Main results showed that in all experiments spinal excitability decreased after the 20-Hz train (P<0.05), while this parameter significantly increased after the 100-Hz stimulation (P<0.05). D1 and HF were not significantly modified after either stimulation. HPAD was significantly decreased only after the 20-Hz train, while TMEP was significantly increased only after the 100-Hz train (P<0.05). It is concluded that the decreased spinal excitability observed after the 20-Hz train cannot be attributed to D1 presynaptic inhibition but rather to increased HPAD of the Ia afferents terminals, while the increase of this parameter obtained after the 100-Hz train can be assigned to changes in intrinsic motoneuron properties allowing to maintain Ia - alpha motoneurons transmission efficacy.

Selectivity and excitability of upper-limb muscle activation during cervical transcutaneous spinal cord stimulation in humans

Cervical transcutaneous spinal cord stimulation (tSCS) efficacy for rehabilitation of upper-limb motor function was suggested to depend on recruitment of Ia afferents. However, selectivity and excitability of motor activation with different electrode configurations remains unclear. In this study, activation of upper-limb motor pools was examined with different cathode and anode configurations during cervical tSCS in 10 able-bodied individuals. Muscle responses were measured from six upper-limb muscles simultaneously. First, post-activation depression was confirmed with tSCS paired pulses (50 ms interval) for each cathode configuration (C6, C7, and T1 vertebral levels), with anode on the anterior neck. Selectivity and excitability of activation of the upper-limb motor pools were examined by comparing the recruitment curves (10-100 mA) of first evoked responses across muscles and cathode configurations. Our results showed that hand muscles were preferentially activated when the cathode was placed over T1 compared to the other vertebral levels, while there was no selectivity for proximal arm muscles. Furthermore, higher stimulation intensities were required to activate distal hand muscles than proximal arm muscles, suggesting different excitability thresholds between muscles. In a separate protocol, responses were compared between anode configurations (anterior neck, shoulders, iliac crests, and back), with one selected cathode configuration. The level of discomfort was also assessed. Largest muscle responses were elicited with the anode configuration over the anterior neck, while there were no differences in the discomfort. Our results therefore inform methodological considerations for electrode configuration to help optimize recruitment of Ia afferents during cervical tSCS.

Facilitation of sensory axon conduction to motoneurons during cortical or sensory evoked primary afferent depolarization (PAD) in humans

Sensory and cortical pathways activate GABAergic interneurons with axo-axonic connections onto proprioceptive (Ia) afferents that depolarize these afferents (termed primary afferent depolarization, PAD). In rodents sensory-evoked PAD is produced by GABAA receptors at nodes of Ranvier in Ia-afferents, rather than at presynaptic terminals, and facilitates action potential propagation to motoneurons by preventing branch point failures, rather than causing presynaptic inhibition. Here we examined if PAD likewise facilitates the Ia-afferent mediated H-reflex in humans by evoking PAD with both sensory and corticospinal tract (CST) stimulation. H-reflexes in several lower limb muscles were facilitated by prior conditioning from low-threshold proprioceptive, cutaneous or CST pathways, with a similar time course (~200 ms) to the PAD measured in rodent Ia-afferents. Long trains of repeated cutaneous or proprioceptive afferent stimulation produced long-lasting facilitation of the H-reflex for up to 2 minutes, consistent with the tonic depolarization of rodent Ia-afferents mediated by nodal α5-GABAA receptors for similar stimulation trains. Facilitation of the conditioned H-reflexes was not mediated by direct facilitation of the motoneurons because isolated stimulation of sensory or CST pathways did not modulate the firing rate of tonically activated motor units in tested muscles. Furthermore, cutaneous conditioning increased the firing probability of a single motor unit during the H-reflex without increasing its firing rate at this time, indicating that the underlying excitatory postsynaptic potential (EPSP) was more probable, but not larger. These results are consistent with sensory and CST pathways activating nodal GABAA receptors that reduce intermittent failure of action potentials propagating into Ia-afferent branches.