And yet it moves: Recovery of volitional control after spinal cord injury

Abstract

Preclinical and clinical neurophysiological and neurorehabilitation research has generated rather surprising levels of recovery of volitional sensory-motor function in persons with chronic motor paralysis following a spinal cord injury. The key factor in this recovery is largely activity-dependent plasticity of spinal and supraspinal networks. This key factor can be triggered by neuromodulation of these networks with electrical and pharmacological interventions. This review addresses some of the systems-level physiological mechanisms that might explain the effects of electrical modulation and how repetitive training facilitates the recovery of volitional motor control. In particular, we substantiate the hypotheses that: (1) in the majority of spinal lesions, a critical number and type of neurons in the region of the injury survive, but cannot conduct action potentials, and thus are electrically non-responsive; (2) these neuronal networks within the lesioned area can be neuromodulated to a transformed state of electrical competency; (3) these two factors enable the potential for extensive activity-dependent reorganization of neuronal networks in the spinal cord and brain, and (4) propriospinal networks play a critical role in driving this activity-dependent reorganization after injury. Real-time proprioceptive input to spinal networks provides the template for reorganization of spinal networks that play a leading role in the level of coordination of motor pools required to perform a given functional task. Repetitive exposure of multi-segmental sensory-motor networks to the dynamics of task-specific sensory input as occurs with repetitive training can functionally reshape spinal and supraspinal connectivity thus re-enabling one to perform complex motor tasks, even years post injury.

Keywords: Electrical stimulation; Motor training; Neuromodulation; Spinal networks.

Graphical abstract

Fig. 1

Wiring diagram suggesting the role of propriospinal and reticulospinal systems in initiation of stepping. Spinal cord includes the dorsal and ventral parts of the lateral funiculus (DLF and VLF) and gray matter (GM). The spinal neurons that send their axons to DLF are termed D neurons, while V neurons send their axons to VLF. MLR, mesencephalic “locomotor region”; HB, hindbrain; thoracic (Th) and lumbar (L) segments of the spinal cord.; IS, interneurons assembling stepping; M, motoneurons; RS, reticulospinal neurons; St, stepping strip (modified fromShik, Motor Control, 1997).

Fig. 2

Facilitation of stepping-like volitional oscillations using non-invasive transcutaneous electrical spinal cord stimulation in SCI subject. (A) Position of the participant in the gravity-neutral apparatus. (B) Biphasic electrical stimulation was delivered using unique waveforms consisting of 0.3–1.0 ms bursts filled by 10 kHz frequency that were administered at 5–40 Hz. (C) EMG activity of right soleus (RSol), right tibialis anterior (RTA), right medial gastrocnemius (RMG), right hamstrings (RHam), right vastus lateralis (RVL), right rectus femoris (RRF) and angular displacement in the knee and hip joints of both legs during leg oscillations with a voluntary effort alone (Vol), stimulation at T11 (Stim), and Vol + Stim are shown. (D) Schematics demonstrating the approximate location of transcutaneous electrodes above the lumbosacral enlargement, in relation to the location of the motor pools based on Kendall et al. (1993) and Sharrard (1964).

Fig. 3

Neuromodulatory mechanisms for the recovery of volitional control after SCI (simplified depiction). This cartoon illustrates some of the proposed targets and mechanisms of neuromodulation of the spinal cord, as discussed in the body of the present review. Physiologically (A), a plethora of propriospinal neurons (red dots) establishes a diffused dynamic network of synaptic contacts along the grey matter of the entire thoracolumbar spinal cord. CPGs responsible for the genesis and the control of different motor tasks are represented by circumscribed areas of the networks as functional subgroups of interneurons that project in a continuously changing pattern toward different combinations of motor pools. Fibers descending from supraspinal centers (top black lines) reach the propriospinal network and eventually the spinal motoneurons (purple). Descending volitional command is represented by a single depolarizing input that reaches the motor threshold for network activation (yellow box with black line). Afferent input from the periphery alone (green line) can reach the motor pools via the interneuronal network systems noted above, which is capable of conveying subthreshold and suprathreshold phasic output (yellow box with green line). For example, during locomotion asynchronous discharges of subthreshold and suprathreshold input (yellow box with red lines) converges (white arrows) onto interneuronal networks with CPG qualities (highly ordered activation of networks that process proprioceptive input in real time) with sufficient precision to control movements as complex as locomotion (locoCPG; pale yellow circle). The locomotor CPG uses the subthreshold background noise from the propriospinal network and the subthreshold phasic rhythm from afferents to organize rhythmic and alternated patterns (locomotor pattern). The locomotor pattern passes the threshold in order to sequentially activate motoneuronal pools (purple lines) and thus muscles in a highly time-dependent actition pattern of muscles (not shown). For the sake of simplicity, we only represented the motor pools on one side, but the output from the interneuronal networks having CPG qualities is however to be considered bilateral. Following a spinal lesion (B), the descending pathway directed to motor neurons is interrupted, while the propriospinal network below lesion mostly appears to be functionally silent and afferent input reduced because of damage and paralysis. Thus, the locomotor CPG does not receive an adequate amount of subthreshold input, hence the inability to voluntarily evoke motor patterns. An innovative treatment (C), which pairs an appropriate subthreshold multi-site electrical stimulation of the thoracolumbar spinal cord with a specific motor training, can reactivate part of the sublesional elements of the propriospinal network, thus restoring the subthreshold background activity that, although reduced in frequency due to the more exiguous network extension, can still reach the CPG (yellow box with red lines). Although the direct descending fibers remain interrupted, descending input can now reach motoneurons through the polysynaptic pattern of propriospinal connections now transformed from electrically non-responsive to responsive. The descending volitional command, although with reduced amplitude and increased latency, can be processed by the spinal networks so that well-coordinated patterns of muscular activation can be generated.