There are several challenges and considerations that need to be addressed when testing the feasibility of BCI-FES systems to restore functional movements of body and face in locked-in individuals for the purpose of communication.
Clinical considerations about LIS
The first challenge relates to the variability of conditions that can potentially lead to LIS. LIS can be caused by various conditions, such as brainstem stroke, trauma, or a progressive neurodegenerative disease (e.g., ALS), and each of them likely differently affects the neuromuscular integrity of limbs and face and therefore the potential success of complementing a communication BCI with FES.
In a situation where paralysis is caused by a disruption of the neural connections between the upper neural pathways and the peripheral and cranial nerves, as is typically the case in brainstem stroke or trauma, it may be feasible to use FES successfully. Notably, individuals with LIS caused by brainstem lesion usually preserve spontaneous involuntary facial expressions while being unable to produce voluntary facial expressions [
125,
287]. This dissociation of reflexive and voluntary control may indicate that the facial muscles and peripheral nerves can in principle be excited to produce target expressions, but the upper neural pathways involved in voluntary facial movements are impaired. Thus, a BCI-FES combination may help bypass the impaired pathways and restore voluntary facial expressions and potentially other movements that could serve communication in locked-in individuals with a brainstem stroke.
Another important consideration in paralysis that needs to be taken into account is the degree of muscle denervation. Muscle denervation refers to the reduction of nerve inputs into the muscle that causes a decrease in neural input necessary for muscle activation and promotes muscle atrophy. Previous work, however, has shown that transcutaneous FES can be used to induce movement of denervated muscles even several years after the onset of paralysis [
15,
141,
156]. Activation of denervated muscles with FES may be possible partly due to the process called reinnervation, in which intact neural pathways take over the damaged nerves in controlling muscle activation.
In a neurodegenerative disease, such as ALS, however, the ongoing reinnervation may not be sufficient to preserve functional motor units and as the disease progresses, it will not help compensate for the continually increasing amount of muscle denervation [
110]. Over time, this will inevitably lead to muscle thinning, muscle atrophy, muscle infiltration with fatty tissue and nerve atrophy [
22,
204]. Limited earlier work has demonstrated successful muscle excitation with electrical stimulation in individuals with ALS [
6,
109]. It has been speculated that FES-based therapy could conceivably attenuate or even delay the disease progression by decreasing muscle tightness and increasing muscle strength [
109]. However, other work called into question the feasibility and benefits of electrical stimulation in ALS, especially in the context of muscle denervation at later stages of the disease [
12,
120]. Therefore, the stage and progression of the disease may be the determining factor of success in applying FES to restore muscle movement in individuals with ALS. More research on muscle denervation in ALS and FES application in denervated muscles is, however, needed to make more specific prognosis about potential outcomes of FES application in LIS caused by a neurodegenerative disease.
The timing of introducing FES and BCI assistive technology to individuals with LIS may also affect how successful its use will be. Previous work shows that introducing BCI to people in total LIS may produce unreliable BCI control. It appears that the longer the person stays in the total LIS state, the harder it may become for them to elicit goal-directed behavior. A hypothesis called “extinction of goal-directed thinking” [
33,
150] suggests that loss of motor control can be associated with cessation of voluntary cognitive activity. In addition to this, prolonged total LIS may lead to alterations in consciousness and arousal [
313]. Under the “extinction of goal-directed thinking” hypothesis, it seems reasonable to assume that the loss of cognitive activity occurs gradually due to the progressive lack of sensorimotor feedback. In that regard, it may be worthwhile to investigate whether FES-based assistive technology offered to people at earlier stages of ALS could stimulate active motor control, thereby potentially leading to more reliable performance of BCI-based communication at later stages of the disease.
Finally, a combination of motor and cognitive decline in LIS may pose an additional challenge for the choice of strategy for the BCI-FES control. LIS caused by lesion or disease can lead to structural changes in target cortical circuits of face and hand leading to functional deterioration of the corresponding motor networks [
295]. One could consider addressing this challenge by remapping of triggers to outputs, and, for example, using various mental strategies to spell or control a computer cursor. However, it may be questionable how intuitive and user-friendly a non-motor based mental strategy would be for FES control. Overall, severe cognitive, motor and structural impairments in LIS pose a fundamental problem for long-term use and use in total LIS for any assistive technology for communication, and it needs to be studied systematically, not only in the context of FES.
In the case where FES cannot successfully induce movements for communication, such as likely during the late stages of ALS, alternative techniques combined with BCI may still apply and benefit from the knowledge gained with existing successful FES applications. Understanding the neural musculature of body and face, the mapping between cortical neural signals and muscle movements and factors determining successful muscle activation with stimulation could inform novel assistive technology. Such technology could be based on virtual reality, including facial avatars and digital twin development, robotics, orthotics, bionic facial masks, and gloves to provide alternative means of communication and interaction with the world for the locked-in individuals.
Technical considerations of FES
In the case of translating existing BCI-FES setups to restore motor functioning of upper and lower limb, there may be a number of technical challenges. Optimal choice of stimulation parameters especially in transcutaneous FES needs particular care. Research shows that, in general, paralyzed limbs and face require higher stimulation amplitudes [
182,
245,
297], which may lead to adverse effects of stimulation. Some studies show that increasing another parameter—pulse duration, may lead to muscle contraction at lower amplitudes [
156] and thereby decrease user pain and discomfort [
96,
297]. At the same time, the use of larger pulse durations results in lowered frequency of stimulation. The latter, however, is recommended to be set at 20–40 Hz for inducing smooth continuous movements [
78,
222]. Further systematic investigation of optimal parameter configurations may be crucial for acceptability of FES and BCI-FES technologies as a therapeutic tool.
Another challenge in the case of FES applied to facial muscles is the precise electrode placement given the overlapping nature and very small size of facial muscles. Some effort has started on developing recommendations and protocols regarding electrode size and fixation for application of transcutaneous FES to facial muscles [
247]. Regarding electrode type and placement, transcutaneous facial FES research has relied on existing electromyography guidelines [
92]. Many studies, however, note the lack of an electromyography site “atlas” available for the facial musculature, and that relevant data is only available for three facial muscles: cheek (zygomaticus major), eyebrow (corrugator supercilia), and forehead (lateral frontalis) muscles. Some researchers are developing facial mapping techniques to identify the facial sites that induces the strongest contraction of the relevant facial muscle [
96], but this practice is not yet widely used in the field.
Another potential challenge is the FES-induced muscle fatigue due to the fact the FES currents may activate muscles in a way and order that are different from naturally induced movements. Specifically, during natural voluntary movement, activation of small fatigue-resistant fibers happens first and then propagates to larger more fatigable muscles, whereas FES may activate larger muscles first or activate muscles non-selectively compromising the natural order of muscle contractions [
88,
104,
290]. Animal studies show that stimulation with implanted electrodes may be able to manipulate muscle recruitment order and tackle fatigue [
84,
85]. With transcutaneous FES, it has been shown that manipulating stimulation parameters can have an effect on fatigue with larger pulse frequencies increasing it [
102,
105] and longer pulse durations potentially decreasing it [
131]. Several studies underline the importance of muscle conditioning and training in reducing fatigue [
107]. Despite these efforts, a lot remains unknown about the mechanisms of muscle fatigue and its prevention, and in many cases individual differences between participants continue to determine FES results.
Finally, it is worth considering that using percutaneous and implantable FES electrodes may hold additional benefits for targeted activation of face and body muscles compared to transcutaneous FES. Implantable FES systems may not only be more practical for long-term use, but they may also offer better positioning of the electrodes, do not suffer from issues with electrode–skin impedance on the skin and bypass skin pain receptors. Given that current percutaneous and implantable FES research, especially with facial muscles, shows promising results but remains limited, this could be a potentially noteworthy direction for explorative research on its own and in combination with BCI.
Potential of combined BCI-FES communication systems for long-term use
Several studies have demonstrated successful long-term use of individual FES and BCI systems [
4,
68,
107,
108,
193]. They show promising results regarding performance and user satisfaction and should be used as guidance in development of combined BCI-FES setups. One important aspect this work can explore is long-term effects of using an assistive technology. In the BCI field, this work focuses on long-term stability of recorded neural control signal and aims to incorporate adaptive data processing methods [
68,
250,
264]. Both BCI and FES research indicate the importance and challenges associated with training, motivation, and practical implementation of the system [
107,
147,
196,
207]. Work with FES highlights its potential in some cases to counteract muscle denervation and promote muscle growth [
140,
275]. Studying long-term use of combined BCI-FES technology is necessary to further understand the long-term effects of this technology on the users.
For long-term use, fully-implantable systems may be preferred. This is more practical and esthetically pleasing, which decreases the burden on the user, family, and caregivers. Fully-implantable systems, however, are associated with increased risks of infection, and in the case of a fully-implantable BCI-FES, a potentially large number of components may need to be implanted, leading to an extensive invasive surgery on user’s body and head. Importantly, one of the biggest concerns about the use of implantable FES systems today is increased risk of infection [
144]. Overall, various factors need to be carefully considered in designing long-term BCI-FES systems in order to minimize risks yet maximize benefits for the users.