Challenges and opportunities in restoring function after paralysis

Abstract

Neurotechnology has made major advances in development of interfaces to the nervous system that restore function in paralytic disorders. These advances enable both restoration of voluntary function and activation of paralyzed muscles to reanimate movement. The technologies used in each case are different, with external surface stimulation or percutaneous stimulation generally used for restoration of voluntary function, and implanted stimulators generally used for neuroprosthetic restoration. The opportunity to restore function through neuroplasticity has demonstrated significant advances in cases where there are retained neural circuits after the injury, such as spinal cord injury and stroke. In cases where there is a complete loss of voluntary neural control, neural prostheses have demonstrated the capacity to restore movement, control of the bladder and bowel, and respiration and cough. The focus of most clinical studies has been primarily toward activation of paralyzed nerves, but advances in inhibition of neural activity provide additional means of addressing the paralytic complications of pain and spasticity, and these techniques are now reaching the clinic. Future clinical advances necessitate having a better understanding of the underlying mechanisms, and having more precise neural interfaces that will ultimately allow individual nerve fibers or groups of nerve fibers to be controlled with specificity and reliability. While electrical currents have been the primary means of interfacing to the nervous system to date, optical and magnetic techniques under development are beginning to reach the clinic, and provide great opportunity. Ultimately, techniques that combine approaches are likely to be the most effective means for restoring function, for example combining regeneration and neural plasticity to maximize voluntary activity, combined with neural prostheses to augment the voluntary activity to functional levels of performance. It is a substantial challenge to bring any of these techniques through clinical trials, but as each of the individual techniques is sufficiently developed to reach the clinic, these present great opportunities for enabling patients with paralytic disorders to achieve substantial independence and restore their quality of life.

Figures

Fig. 1

Various implanted electrodes used with neuroprostheses. These electrodes all stimulate nerve fibers and cause activation or inactivation of the nerve, depending upon the stimulus waveform that is used. Electrodes can also be used for recording of signals from nerve or muscle.

Fig. 2

An advanced neuroprosthesis consisting of distributed modules. Left: This networked neuroprosthesis has modules for power, stimulus delivery and for recording physiological or physical activity, network cabling and electrodes. This system is fully implanted, and can be externally programmed and/or controlled in real time. Right: Networked neuroprosthesis as configured for an upper extremity system for spinal cord injury. Each module can be placed close to the site of stimulation or recording.

Fig. 3

Mirroring system for stroke survivors. The subject wears a sensor glove on the unaffected limb, and surface electrodes on the affected limb. Intention on the unaffected limb generates stimulation to the affected limb, allowing tasks to be performed. This relatively simple concept has demonstrated one manifestation of using neural plasticity for recovery of function. Work of Knutson and Chae [10].

Fig. 4

Intraspinal microstimulation (ISMS) delivered after spinal cord contusion demonstrates improved reaching capabilities in rats. Transfer of this technique to humans is a considerable way off, but demonstrates another opportunity for altering neural circuitry after spinal cord injury. Work of Kasten, Sunshine, and Moritz [11].

Fig. 5

High frequency currents may be used to block neural activity. Applications include blocking painful sensations and spasticity, or undesired muscle contraction, in disorders that are wide ranging and include stroke, amputation, spinal cord injury, cerebral palsy, and multiple sclerosis. With the application of current in this animal model, neural firing is suppressed for the duration of the stimulus block and reversed quickly upon cessation of the blocking current. Work of Bhadra and Kilgore [20].

Fig. 6

Walking system with an implanted neuroprosthesis. Stimulation and coordination of multiple muscles together is provided by the neuroprosthesis. Individual muscle actions are stimulated by implanted intramuscular or nerve cuff electrodes, and coordination of the actions are programmed into the external controller. Communication between the controller and implanted stimulators is via radio frequency signals. Control is provided by an external switch. Work of Triolo, Anderson, and Hoyen [14].

Fig. 7

Implanted neuroprosthesis for the upper extremity in spinal cord injured patients. A similar technological implementation as the lower extremity, but control is more intimate and is provided by myoelectric signals from muscles that retain voluntary control. Bilateral systems have been developed. Work of Kilgore, Keith, Hoyen, and Peckham [15].

Fig. 8

Restoring sensation has been a significant unmet challenge in the case of paralysis and limb loss. Newer technology that provides selective stimulation of individual fascicles of nerves may be a means of generating percepts distributed to areas of the lost limb. Areas of sensory perception in the hand from nerve electrodes are shown in one amputee subject. Work of Tyler, Schieffer, Tan, Keith and Anderson [19].