Hammerstein modeling of the relation between epimysial electromyography signals (obtained from the undersurface of the whisker pad musculature) to evoked whisk movement demonstrated excellent predictive capacity (Fig. 8), with the model accounting for more than 96 percent of the variance in whisker displacements.
A 30-kHz sine wave with a peak-to-peak amplitude of 5 V was found to be optimal for inducing blockade of evoked and spontaneous whisking activity in the rat using the customized nerve cuff electrode. In anesthetized animals, this achieved an approximately 90 percent reduction in evoked whisking amplitude, without restriction of distal neuromuscular excitability (Fig. 9, left and center). In awake animals, a similar reduction in behavioral whisking power was observed between blocked and normal sides with high-frequency alternating current application (Fig. 9, right). (See Video, Supplemental Digital Content 3, which demonstrates neural blockade of physiologic whisking activity in the live awake rat, with concurrent electrical stimulation to evoke blink and whisk by means of implanted nerve cuff electrodes. Nerve cuff electrodes were positioned around intact zygomatic and buccal branches of the facial nerve, as demonstrated in Fig. 6, left. Neural blockade was achieved by delivery of high-frequency alternating current, as demonstrated in Fig. 9, center, available in the “Related Videos” section of the full-text article on PRSJournal.com or, for Ovid users, available at http://links.lww.com/PRS/D169.) No differences were observed in whisking amplitudes between sides with prolonged unilateral daily delivery of high-frequency alternating current (Fig. 10). Full results of this series of experiments will be reported in more detail in subsequent publications.
Although the basic concept of using signals from the contralateral face to drive functional electrical stimulation of paralyzed facial muscles has been demonstrated,53–63 prior work has not addressed critical issues relevant to the long-term implementation of this approach. Optimal functional electrical stimulation of dysfunctional muscle requires three conditions: muscle must be neurotized, capable of being stimulated in purposeful and timely fashion, and devoid of undesirable activity. Neurotization of muscle prevents denervation atrophy and permits functional electrical stimulation through neural stimulation without the need for direct muscle stimulation. Although direct muscle stimulation of denervated muscle may prevent atrophy, it requires delivery of high and potentially injurious stimulus amplitudes to evoke contractions.64–66 Such an approach is not feasible in the setting of facial palsy because of excessive power demands on an implanted neuroprosthetic device, coupled with regional nociceptive fiber activation that would result from the delivery of high stimulus amplitudes. In the setting of facial palsy, neurotization of facial muscles may occur spontaneously following neural insult, through interposition graft repair or through nerve transfer. In cases of longstanding or congenital facial palsy, dynamic facial reanimation may be achieved by functional muscle transfer. Here, we propose that muscle contraction be evoked through stimulation of distal native facial nerve branches (or transferred nerves) using electrically shielded nerve cuff electrodes. Such distal facial nerve branches to individual paired muscles or functional muscle groups of the face are straightforward to access surgically. Likewise, in cases where nerve or muscle transfers are required for dynamic reanimation, nerve branches to the target muscle are readily accessible for cuff implantation at the time of reanimation surgery or during future reexploration.
Dynamic reanimation of muscle requires an adequate control signal to effect desired movements at appropriate times. Use of myoelectric activity to reliably drive neuroprostheses has already been demonstrated.67 , 68 In this article, we have demonstrated that electromyography signals from contralateral, healthy facial muscles may be used as control signals to drive functional electrical stimulation of the paretic hemiface. In this study, electromyographic activity was captured through the use of implanted epimysial electrode arrays, obviating the need for external sensors, and a clear mathematical relationship capable of predicting facial displacements from electromyographic inputs was demonstrated. Use of the contralateral healthy hemiface for dynamic reanimation of unilateral facial paralysis is a natural choice, as the majority of—especially positive expressions—are symmetric.69 The neuroprosthetic device proposed in this study could evoke paired-muscle contraction without a conspicuous phase delay in movement onset between sides. Modern implantable application-specific integrated circuits achieve delays of 5 msec or better on signal receiving and stimulus transmitting arms, with submillisecond processing times for most functional electrical stimulation applications. When coupled with typical delays on the order of 10 msec for physiologic transduction of the neural stimulus to effect myocyte depolarization, the maximum expected delay between healthy-side detected electromyographic activity (and subsequent muscular contraction) and paretic-side neural stimulation is on the order of 20 msec, below the approximately 33-msec threshold above which humans are able to detect asymmetric movement.70 , 71
Although stimulation of desirable muscle activity is necessary for functional reanimation, concurrent inhibition of undesirable neural activity is often just as important. No prior work has addressed the vexing issue of how to prevent undesirable muscle activation from aberrantly regenerated axons (i.e., in the case of aberrantly regenerated native facial nerve) or from the normal functioning of transferred cranial nerves (e.g., prandial activation of muscle innervated by transfer of the masseteric branch of the trigeminal nerve). In this article, we describe for the first time the use of concurrent proximal application of high-frequency alternating current over prolonged periods to prevent such undesired facial contractions. Delivery of high-frequency alternating current to peripheral nerve trunks results in reversible induction of localized blockade of propagating action potentials, without impeding distal neuromuscular excitability72–83; proximal application of high-frequency alternating current to a motor nerve squelches physiologic activity and maintains the capacity for distal functional electrical stimulation. Although there exists brief tetanic onset and offset responses with high-frequency alternating current application,72 , 75 , 84 such repeated responses would be avoided through continual proximal delivery of high-frequency alternating current during waking hours concurrent with distal functional electrical stimulation to drive expression. The device could also be implemented in “functional electrical stimulation–only” mode to allow physiologic action potentials to pass concurrent with evoked potentials, or “neural blockade–only” mode to induce targeted flaccidity.
This work has demonstrated the feasibility of using epimysial electromyography signals from healthy-side facial musculature captured using biocompatible and fully implantable miniature electrodes as a means for control of a functional electrical stimulation paradigm to drive reanimation of symmetric expression in hemifacial palsy. The capacity to effect independent facial movements of varied duration and amplitudes by means of functional electrical stimulation of distal facial nerve branches was established. Importantly, the efficacy and safety of proximal neural blockade by means of continuous high-frequency alternating current delivery as a means of extinguishing undesirable facial muscle activity arising from the intrinsic activity of damaged or transferred nerves have been proposed and demonstrated.
The combination of proximal high-frequency alternating current with distal functional electrical stimulation to achieve total extrinsic control over a motor nerve has clinical implications elsewhere where undesirable activity of a peripheral nerve resulting from disease, injury, or nerve transfer exists. Future work will seek to study this paradigm over the long term using a fully implantable, miniaturized, application-specific integrated circuit currently under development. Beyond functional electrical stimulation applications, application of high-frequency alternating current to peripheral nerves might ultimately prove efficacious for management of spastic disorders and painful neuropathies, as focal blockade of action potential propagation occurs for efferent and afferent pathways.85
This study was supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke (5R01NS071067-07).
Patients provided written consent for the use of patients’ images.
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