Comparison of operation of spinal locomotor networks activated by supraspinal commands and by epidural stimulation of the spinal cord in cats.

KEY POINTS: Epidural electrical stimulation (ES) of the spinal cord restores/improves locomotion in patients. ES-evoked locomotor movements differ to some extent from the normal ones. Operation of the locomotor network during ES is unknown. We compared the activity of individual spinal neurons during locomotion initiated by signals from the brainstem and by ES. We demonstrated that the spinal network generating locomotion under each of the two conditions is formed by the same neurons. A part of this network operates similarly under the two conditions, suggesting that it is essential for generation of locomotion under both conditions. Another part of this network operates differently under the two conditions, suggesting that it is responsible for differences in the movement kinematics observed under the two conditions. ABSTRACT: Locomotion is a vital motor function for both animals and humans. Epidural electrical stimulation (ES) of the spinal cord is used to restore/improve locomotor movements in patients. However, operation of locomotor networks during ES has never been studied. Here we compared the activity of individual spinal neurons recorded in decerebrate cats of either sex during locomotion initiated by supraspinal commands (caused by stimulation of the mesencephalic locomotor region, MLR) and by ES. We found that under both conditions, the same neurons had modulation of their activity related to the locomotor rhythm, suggesting that the network generating locomotion under the two conditions is formed by the same neurons. About 40% of these neurons had stable modulation (i.e. small dispersion of their activity phase in sequential cycles), as well as a similar phase and shape of activity burst in MLR- and ES-evoked locomotor cycles. We suggest that these neurons form a part of the locomotor network that operates similarly under the two conditions, and are critical for generation of locomotion. About 23% of the modulated neurons had stable modulation only during MLR-evoked locomotion. We suggest that these neurons are responsible for some differences in kinematics of MLR- and ES-evoked locomotor movements. Finally, 25% of the modulated neurons had unstable modulation during both MLR- and ES-evoked locomotion. One can assume that these neurons contribute to maintenance of the excitability level of locomotor networks necessary for generation of stepping, or belong to postural networks, activated simultaneously with locomotor networks by both MLR stimulation and ES.

Modulation of multisegmental monosynaptic responses in a variety of leg muscles during walking and running in humans.

Motor responses evoked by stimulating the spinal cord percutaneously between the T11 and T12 spinous processes were studied in eight human subjects during walking and running. Stimulation elicited responses bilaterally in the biceps femoris, vastus lateralis, rectus femoris, medial gastrocnemius, soleus, tibialis anterior, extensor digitorum brevis and flexor digitorum brevis. The evoked responses were consistent with activation of Ia afferent fibres through monosynaptic neural circuits since they were inhibited when a prior stimulus was given and during tendon vibration. Furthermore, the soleus motor responses were inhibited during the swing phase of walking as observed for the soleus H-reflex elicited by tibial nerve stimulation. Due to the anatomical site and the fibre composition of the peripheral nerves it is difficult to elicit H-reflex in leg muscles other than the soleus, especially during movement. In turn, the multisegmental monosynaptic responses (MMR) technique provides the opportunity to study modulation of monosynaptic reflexes for multiple muscles simultaneously. Phase-dependent modulation of the MMR amplitude throughout the duration of the gait cycle period was observed in all muscles studied. The MMR amplitude was large when the muscle was activated whereas it was generally reduced, or even suppressed, when the muscle was quiescent. However, during running, there was a systematic anticipatory increase in the amplitude of the MMR at the end of swing in all proximal and distal extensor muscles. The present findings therefore suggest that there is a general control scheme by which the transmission in the monosynaptic neural circuits is modulated in all leg muscles during stepping so as to meet the requirement of the motor task.

Rehabilitative therapies after spinal cord injury.

We review some basic and highly relevant concepts in the effort to develop improved rehabilitative interventions for subjects with spinal cord injury (SCI). Interventions that are likely to contribute to improved sensorimotor function include (1) practice of the specific motor task that needs to be improved; and (2) combining the training with one or more interventions--such as pharmacological modulation of the excitability of spinal neural networks, implantation of selected cell types such as olfactory ensheathing glia (OEG), and/or modulation of the excitability of the spinal cord via epidural stimulation. Upon improvement of the neural control of the musculature following SCI, it will always be prudent to maximize the torque output from these activation patterns by assuring that muscle mass is maintained. Therefore, it seems quite feasible that considerable improvement in locomotor performance can be achieved by improved coordination of motor pools, as well as effective recovery of muscle mass, which will assist in the potential generation of normal forces among agonistic and antagonistic muscle groups.