Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

A Review of Different Stimulation Methods for Functional Reconstruction and Comparison of Respiratory Function after Cervical Spinal Cord Injury

A Review of Different Stimulation Methods for Functional Reconstruction and Comparison of... Hindawi Applied Bionics and Biomechanics Volume 2020, Article ID 8882430, 12 pages https://doi.org/10.1155/2020/8882430 Review Article A Review of Different Stimulation Methods for Functional Reconstruction and Comparison of Respiratory Function after Cervical Spinal Cord Injury 1 1 1 2 3 Jiaqi Chang, Dongkai Shen, Yixuan Wang, Na Wang , and Ya Liang School of Automation Science and Electrical Engineering, Beihang University, Beijing 100191, China Engineering Training Cent, Beihang University, Beijing 100191, China Nursing Department, Juancheng County People’s Hospital, Shandong 274600, China Correspondence should be addressed to Na Wang; lion_na987@buaa.edu.cn Received 8 May 2020; Revised 30 July 2020; Accepted 7 September 2020; Published 17 September 2020 Academic Editor: Jose Merodio Copyright © 2020 Jiaqi Chang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Spinal cord injury (SCI) is a common severe trauma in clinic, hundreds of thousands of people suffer from which every year in the world. In terms of injury location, cervical spinal cord injury (CSCI) has the greatest impact. After cervical spinal cord injury, the lack of innervated muscles is not enough to provide ventilation and other activities to complete the respiratory function. In addition to the decline of respiratory capacity, respiratory complications also have a serious impact on the life of patients. The most commonly used assisted breathing and cough equipment is the ventilator, but in recent years, the functional electrical stimulation method is being used gradually and widely. Methods. About hundred related academic papers are cited for data analysis. They all have the following characteristics: (1) basic conditions of patients were reported, (2) patients had received nerve or muscle stimulation and the basic parameters, and (3) the results were evaluated based on some indicators. Results. The papers mentioned above are classified as four kinds of stimulation methods: muscle electric/magnetic stimulation, spinal dural electric stimulation, intraspinal microstimulation, and infrared light stimulation. This paper describes the stimulation principle and application experiment. Finally, this paper will compare the indexes and effects of typical stimulation methods, as well as the two auxiliary methods: training and operation. Conclusions. Although there is limited evidence for the treatment of respiratory failure by nerve or muscle stimulation after cervical spinal cord injury, the two techniques seem to be safe and effective. At the same time, light stimulation is gradually applied to clinical medicine with its strong advantages and becomes the development trend of nerve stimulation in the future. 1. Introduction in respiratory function in more than 20 years [5]. The ability to breathe requires continuous movement of the skeletal Spinal cord injury is a common clinical severe trauma, which muscle [6]. The diaphragm, which is dominated by C3-C8, will disturb the communication between the brain and the is the main inspiratory muscle and the external intercostal muscles, which are dominated by T1-T11, produce about body, leading to the loss of control of other intact neuromus- cular system [1]. Around the world, according to the World 35-40% of a person’s vital capacity. For inspiratory and expi- Health Organization, between 250000 and 500000 people ratory steps [7], it is confirmed that inspiratory muscle suffer from spinal cord injury every year [2]. About 20% of strength has a more important effect on the respiration and spinal cord injuries occur between C1 and C4 levels. cough ability of SCI patients [8, 9]; also, positive muscle con- traction and the combination of abdominal wall is required After cervical spinal cord injury, the decline of pulmo- nary function is reflected in three areas: respiratory function, for expiratory performance and adequate ventilation to cough ability, and limitation of voice function [3], especially maintain a higher respiratory rate and volume [10]. After spi- in respiratory function [4], which has no significance worsen nal cord injury, the injury of neck and upper thoracic cord 2 Applied Bionics and Biomechanics The selected papers are divided into two categories: thera- destroyed the function of diaphragm, intercostal muscle, pararespiratory muscle, and abdominal muscle [11], which peutic reports and analytical reviews. means that the ventilation system cannot work in the best way, and muscle activity is often out of sync. 2.2. Data Extraction. In the systematic introduction part, In addition to the above three areas, patients with such stimulation method is used as a classification. In the compar- injuries have a high risk of respiratory complications [12]. ison part, we choose several representative articles with com- It is reported that nearly 84% of the patients with acute hos- plete data from each stimulation method, all of which are pitalized cervical spinal cord injury have respiratory compli- aiming at the reconstruction of respiratory function for com- cations, 20% receive tracheotomy and mechanical parison. The following data were extracted from the selected ventilation, and 4-5% need lifelong ventilation support [13]. therapeutic report: (1) participants’ condition, (2) treatment Spinal cord injury can lead to respiratory muscle injury, method, (3) stimulator and stimulation parameters, and (4) decreased vital capacity, ineffective cough, reduced lung and evaluation index. chest wall compliance, and excessive respiratory oxygen con- sumption due to distorted respiratory system [14]. As a 3. Results result, the ability of clearing respiratory secretions in patients with spinal cord injury is obviously impaired, which leads to 3.1. Muscles Stimulation. Functional electrical stimulation discomfort and inconvenience and develops into atelectasis (FES) is a kind of technology that uses a safe level current and recurrent respiratory infection [15, 16]. to activate the damaged or disabled neuromuscular system The most commonly used assisted breathing and cough for function reconstruction [18]. In a closed-loop system, equipment is the ventilator. The main work of ventilator- the parameters of electrical stimulation are constantly modi- dependent spinal cord injury patients is positive pressure fied by the computer through the feedback information of mechanical ventilation. In the early stage of mechanical ven- muscle strength and joint position, so as to stimulate differ- tilation, patients are passive breathing and provide tempo- ent muscle groups at the same time, which leads to the com- rary respiratory support. Due to the nature of these bination of muscle contraction required for complex and ventilator devices, patients cannot improve their respiratory complex functional activities (such as walking) [19]. The function, increase the risk of respiratory infection [13], and main problem related to the FES model is feedback control also accompany with bedsore and other problems. At the [18], which means more sensors are needed to measure mus- same time, getting rid of the ventilator requires medication cle strength, muscle fatigue, joint position, angular velocity, [17]. The idea of nerve stimulation to restore spinal cord and torso position, and all of them need microprocessor for function can be traced back to 1970s, but it has made remark- accurate analysis. As a response to all these sensory inputs, able progress in the 21st century [2]. FES system should be able to define stimulus parameters Although scholars have made positive results in the according to the feedback received, so as to provide more research of spinal nerve stimulation, there is no summary natural response and smoother transition. analysis of stimulation equipment and methods. The review The above theory has been confirmed by many scholars. can be used to collect the results of different studies, so as Lane induced the recovery of ipsilateral phrenic motoneu- to evaluate the therapeutic effect of various means. This rons and phrenic muscle activity under the condition of ter- review will introduce the current progress of function recon- minal neurophysiology and found a persistent spontaneous struction after spinal cord injury and make a key overview of recovery in this model [20]. Warren found that there was the reconstruction of respiratory function. At the same time, an endogenous plasticity mechanism after spinal cord injury this paper compares the stimulation parameters and effects of to promote respiration and help restore lung ventilation. several stimulation methods for respiratory function recon- These mechanisms include activation of alternative or poten- struction and discusses the influence of auxiliary means on tial pathways, endogenous germination or synaptic forma- the treatment effect. It will also introduce the hot issues in tion, and possible formation of new respiratory control this research field, so as to show that this field has a very high centers [21]. Horn pointed out that the autonomic nervous research prospect. system is an attractive target for medical treatment with elec- tronic devices due to its potential of selective control and few side effects. Courtine also summarized the progress of biolog- 2. Methods ical and engineering strategies in recent years to enhance 2.1. Literature Search and Selection. We searched the experi- neural plasticity and functional recovery in SCI animal mental articles of scholars who studied the functional recon- models. Many scholars apply these theories and related med- ical devices to clinical experiments [22]. struction of neural and muscle stimulation in Google academic. The key words used for searching are spinal cord Diaphragmatic pacing (DP) is a minimally invasive injury, nerve electrical stimulation, infrared light stimulation, method alternative to mechanical ventilation for the treat- respiratory function reconstruction, and cough function ment of cervical spinal cord palsy patients with high cervical reconstruction. References to identified articles were also spinal cord injury [23]. Sieg reviewed the application of phrenic nerve stimulator in spinal hypertension and central manually searched for articles that were not found in the ini- tial search. Some articles are excluded if they are non-English, ventricular fibrillation syndrome in 1980s [24]. DiMarco repetitive (or research participants are not independent of explored the feasibility of laparoscopic placement of intra- previous publications), meeting summaries, and editorials. muscular diaphragm electrodes for long-term ventilation Applied Bionics and Biomechanics 3 and release through electrical stimulation, and completed the support in patients with ventilator-dependent [25]. He also placed two diaphragm electrodes on each half diaphragm of assessment of grip strength [47]. Mangold stimulated exten- five subjects and compared the advantages of intramuscular sors and thumbs in all subjects to achieve lateral and palm grasping functions [48]. Popovic compared 21 patients with phrenic pacing and traditional phrenic nerve pacing [26]. Afterwards, he proposed several feasible DP systems, includ- C3-C7 new spinal cord injury and found that functional elec- ing the traditional DP system with electrodes directly placed trotherapy has potential therapeutic potential, which is an on the phrenic nerve via thoracotomy and the minimally effective method to restore the grasp function of patients with invasive DP system with electrodes placed in the phrenic quadriplegia [49]. Ragnarsson summed up the existing prob- lems and put forward the prospect that developing a fully nerve via laparoscopy [27]. Cosendai tested a RF powered pulse generator, a rechargeable battery-powered pulse gener- implantable, easy to manufacture, modular FES system, which ator, and the external pulse generator and determined that can be used for all purposes, such as upper and lower limbs, the implantable system can replace the external pulse gener- trunk, bladder, intestine, and diaphragm functions [50]. ator [28]. The safety and effectiveness of this technology has Compared with electrical stimulation, the research of magnetic stimulation is much less. Lin explored the role of also been concerned. Tedde explored the indications of inserting the DPS electrode under laparoscope and described functional magnetic stimulation in the conditioned reflex of the operation methods of five patients with quadriplegia [29]. the expiratory muscles of the patients with spinal cord injury Garara systematically reviewed the safety and efficacy of the [51]. Fawaz used a randomized controlled trial to compare intramuscular diaphragm stimulator in the treatment of the effects of two rehabilitation programs, one for FES and true magnetic stimulation, the other for FES and false mag- patients with traumatic high cervical trauma who depended on a ventilator for a long time, especially security due to the netic stimulation, on the hand function recovery of patients. insertion time of the stimulator [30]. Tarek reported that a The results showed that patients receiving magnetic stimula- 4-year-old child with spinal cord injury received diaphragm tion have recovered quickly [52]. pacing with low amplitude, changeable pulse width gradually 3.2. Epidural Electrical Stimulation. It is conformed that the got rid of ventilator [31]. Dean reviewed the safety and effec- tiveness of DP in pediatric, described the process of ventilator motor activity after spinal cord injury can be realized through disconnection and diaphragm regulation during inpatient the regulation of neural circuits by epidural stimulation [53]. rehabilitation, and pointed out that DP implantation is a safe According to Jackson [2], the idea of using electronic implants and effective treatment [32]. Franco Laghi increased the expi- to bypass damaged neural pathways can be traced back to the 1970s [54], but significant progress has been made in this field ratory flow of patients through the skin stimulation of abdominal muscles [33]. in the 21st century [55, 56]. It is not only verified in monkeys In addition to diaphragm, abdominal FES can also that the brain signal can control the stimulation of the cervical region at the top of the spinal cord to restore the movement of improve respiratory function. Based on previous experi- ments, McCaughey reviewed the evidence of improvement paralyzed arms and hands [57] but also the lumbar spinal cord stimulation has achieved good results in human experiments of respiratory function by abdominal FES after SCI. More- over, FES in abdomen can still significantly improve the peak to restore the leg to a certain degree of autonomous movement flow of cough. Electromyography is usually used to measure [58]. There is evidence that closed-loop stimulation can drive neural plasticity, which plays an important role in the rehabil- the recovery of cough function [34]. After abdominal FES training, there was also a significant increase in autonomic itation of partial spinal cord injury [59]. DiMarco produced an effective coughing mechanism by vital capacity, forced vital capacity, and maximum expiratory flow compared with baseline [35–43]. FES can also be used to stimulation of the spinal cord in the lower thoracic and upper reconstruct cough function. McBain stimulated abdominal lumbar segments. Three epidural electrodes were used in the spinal cord of T9, T11, and L1. The airway pressure was muscles with surface electric stimulation, placed electrodes 2 2 in the posterolateral position, and helped patients with 90 cm H O and 82 cm H O when stimulating T9 and L1 sep- high-level spinal cord injury clear airway secretions in com- arately, while the maximum expiratory velocity was 6.4 L/s bination with cough [44]. A Zupan et al. discussed the prob- and 5.0 L/s. When stimulation of T9 and L1 combined, air- lem of improving the cough efficiency of the abdominal wall way pressure and expiratory flow rate increased to 132 cm electrical stimulation through the experiment, so that the H O and 7.4 L/s, as shown in Figure 1 [60]. patients with high cervical spinal cord injury could get dia- DiMarco completed the experiment to measure the acti- phragm pacing in the treatment [45]. Cheng et al. verified vation ability of the lower thoracic spinal cord electrical stim- that the electric stimulation of thoracoabdominal muscles ulation on the expiratory muscles of the patients with can improve the cough ability and lung function of patients quadriplegia [15]. DiMarco then proposed that the peak air- with cervical spinal cord injury of quadriplegia [46]. flow and airway pressure generation with wire electrodes On the other hand, the restoration of hand grasping func- were the same as those with disk electrodes [61]. tion is also a research hotspot of muscle electrical stimulation. Minyaeva studied the dynamic changes of pulmonary Mulcahey studied the application and functional benefits of ventilation and gas exchange parameters when stimulating implanted functional electrical stimulation (FES) system in in T11-T12 in 10 young male subjects, as shown in patients with quadriplegia after spinal cord injury. He used five Figure 2, and concluded that step motion induced by percu- adolescents aged 16 to 18 with traumatic spinal cord injury as taneous spinal cord stimulation resulted in increased respira- samples to excite the key muscles of metacarpal, lateral grasp tory rate [62]. 4 Applied Bionics and Biomechanics 200 3.3. Intraspinal Microstimulation. In addition to dural stimu- lation, due to electrical stimulation of motor cortex that can affect the conduction of central motor tract [66], some scholars have also carried out ISMS researches. The first is 50 the research of ISMS on muscle response, and the second is the reconstruction function of ISMS. As an interdisciplinary subject, some scholars focus on the development of ISMS equipment and the control algorithm. Moritz recorded the forelimb responses induced by cervi- cal spinal cord stimulation that were applied in C6 to T1 sites Spinal cord segment in primates. Of the 745 stimulated areas, finger (76% of the FRC effective area), wrist (15%), elbow (26%), and shoulder TLC (17%) induced movement. Therefore, the stimulation usually activating multiple muscles together [67]. Mushahwar used Figure 1: Airway pressure of different plans to activate cough. five adult cats that fully spinal at the T12 to record the right hindlimb movements produced by muscle (n =4), extra- % neural membrane (n =2), and spinal cord (n =3) stimula- tion. For muscle and epineurial stimulation, bipolar monophasic pulse sequences (300 microseconds, 50 pulses/- second) with duration of 0.7-0.8 s were delivered through implanted electrodes at the amplitude of 0.18-4.00 mA and 16-510 μA. They then concluded that motoneuron pools –2 from in the intermediate and ventral regions can be activated –4 by spinal cord stimulation [68]. Holinski has developed a –6 –8 feedback-driven isms system, which proved that ISMS can VE VT RF Ti Te VO RQ PetO PetCO SpO –10 2 2 2 2 enhance the stepping function by reducing muscle fatigue and activating the spinal cord neural network to generate Figure 2: Changes of lung ventilation and gas exchange parameters cooperative movement [69]. Bamford also completed an during the increase of autonomic movement (gray strip) and ISMS task. They activated the skeletal muscle to restore mus- stimulation (white strip). cle activity in rats by electrically stimulating the gray matter of abdominal wall. Compared with the peripheral FES method, ISMS is easy to achieve the stable contraction level In addition to breathing, more focus has been placed on of less than 50% of the maximum spontaneous activation [70], as shown in Figure 4. the reconstruction of walking function. Formento explored the reasons for the differences in the effects of spinal epidural In terms of reconstruction function of ISMS, Mercier explored the ISMS in C4 spinal cord segment of adult rats electrical stimulation in animal models of spinal cord injury and in humans. They concluded that the interspecificdiffer- after C2 hemisection in the background of respiratory move- ence was due to the interference between EES and human ment. The stimulation mode was 250 ms (100 Hz, 100-200a) each time. The experiment was carried out successfully and ontological sensory information. Therefore, the inspiration of this study for the recovery of walking function is that sud- induced the short-term enhancement of spontaneous inspi- den stimulation and spatiotemporal stimulation can reduce ratory activity of 70% of the subjects, which provided the the elimination of proprioceptive information, so as to basis for the closed-loop ISMS method to maintain ventila- achieve robust control of motor neuron activity. Figure 3 tion after severe spinal cord injury [71]. In addition, Bamford focused on the application of ISMS in the recovery of bladder shows the comparison of the probability of reverse collision between human and mouse [63]. function after spinal cord injury [72]. Harkema also pointed out that epidural spinal stimula- Shahboost combined the integrated circuit technology tion can regulate the spinal cord circuit to a physiological for the interface of corticospinal cord with the embedded sig- state and make the sensory input of standing and stepping nal processing technology based on FPGA to prove that the ISMS controlled in real time by the spike wave in the corti- motion the source of neural control. They placed a 16 electrodes array on the dura mater (L1-S1 spinal cord cospinal cord can activate certain muscles of experimental segment) surgically on a 23-year-old male with C7-T1 rats [73] and then reported a closed-loop control method subluxated paraplegia and successfully reactivate the previ- for the ISMS [74]. Troyk reported a wireless stimulator ously silent standby neural circuit after severe paralysis device for animal experiments. They used ISMS to activate the residual motor control neural network in the ventral horn [64]. Wagner provided a series of spatial selective stimulation of the spinal cord below the injury level after spinal cord to the lumbosacral spinal cord by using the implanted pulse injury and induced bilateral walking mode of the lower limbs. generator. After a few months, participants resumed volun- Combined with the advanced feedback algorithm, the walk- tary control of previously paralyzed muscles without stimula- ing distance recovered by ISMS exceeds that generated by other types of functional electrical stimulation. As shown in tion [65]. Airway pressure (cmH O) T9 T1 L1 T9+L1 T9+T11 T11+L1 T9+T11+L1 Applied Bionics and Biomechanics 5 Rats ESS-induced antidromic activity (20-100 lmp/s) Spinal cord Antidromic collision Muscle spindles activity (0-200 lmp/s) Peripheral nerves 10 200 Natural aer ff ent firing rate (lmp/s) Humans Spinal cord Electrical stimulation induced antidromic activity (0-60 lmp/s) Proximal nerves Antidromic 0 collision Muscle spindles Distal activity (0-50 lmp/s) nerves 10 200 Natural aer ff ent firing Commonly used EES frequency rate (lmp/s) Physiological firing rates Figure 3: Probability of retrograde AP in sensory afferent fibers under EES. NCS ISMS 1.00 1.00 0.75 0.75 0.50 0.50 0.25 0.25 0.00 0.00 0 100 200 300 400 0 100 200 300 400 Amplitude (𝜇A) Amplitude (𝜇A) Figure 4: Muscle force changes after ISMS and NCS. Figure 5, after implantation of ISMS microfilaments, the cat a fuzzy logic control and used multi electrodes to study the was placed in a safety belt and suspended on a treadmill. A closed-loop control of ankle motion. In order to compensate microaccelerometer was placed on the legs of the cat to pro- the effect of time delay, the future value of expected response vide a simulated sensory feedback signal. The spinal cord of was taken as the input and error signal of FLC. The results of animal experiments show that the proposed control frame- the cat was stimulated to produce a gait like pattern [75]. Because the neuromusculoskeletal system has obvious work can provide good tracking performance [77]. nonlinear, time-varying, large latency, and time constant as well as muscle fatigue, it is a very difficult task to control 3.4. Infrared Light Stimulation. Near-infrared light directly limbs accurately and stably by using ISMS. Many scholars irradiates the nerve tissue with infrared light, which causes put forward different ISMS control methods. Asadi proposed the instantaneous energy accumulation in the tissue, the tem- a robust control method to determine the stimulation mode, perature gradient established by which can generate light and and enables the controller to compensate for the dynamic heat in the tissue, thus inducing the nerve activity [78]. Com- interaction between the pool of motor neurons and the elec- pared with traditional electrical stimulation, INS uses fiber- trode positions. The control method is based on the combi- optic coupling laser to stimulate nerve tissue, which solves nation of sliding mode control, fuzzy logic, and neural the problem of mechanical damage caused by contact elec- control. A large number of experiments have been carried trodes in electrical stimulation; meanwhile, laser stimulation out on 6 rats, and the robustness, stability, and tracking accu- has good spatial accuracy, which can stimulate a single neu- racy of this method have been proved [76]. Roshani proposed ron without range effect; in addition, the stimulus signal does Normalized TWitch force Propagation time: 10 ms Propagation time: 20 ms Propagation time: 2 ms EES frequency (Hz) EES frequency (Hz) Normalized TWitch force EES frequency (Hz) Antidronic collision Antidronic collision probability probability Antidronic collision probability 6 Applied Bionics and Biomechanics showed under the radiation of 0.53-1.23 J/cm , 63% of the Interface for nerves appeared activation of human dorsal root, and ther- ISMS implant Reflective joint ISMS mal damage was found at 1.09 J/cm ; meanwhile, the safety markers implant ratio of 2 : 1 was determined. These findings proved the suc- Reconstructed cess of INS as a new way to activate human nerves in vivo and stick figures provided necessary safety data, which provided necessary Accelerometers impetus for the clinical application and diagnosis. The equipment used in the experiment is the high-power high-frequency clinical system light box [83]. The high- energy laser from the optical fiber adjusted its output fre- quency and situation by the pulse generator and sterilized handheld bracket. Stationary platform Force plates Now, it has been confirmed in many ins researches that for forelimbs in order to reduce the change of spot size, a fixed-point light Figure 5: Bilateral walking experiment of activation by ISMS. source or a collimated beam is usually used. Fried et al. also proved that compared with the standard Gaussian beam, not affect the detected response signal because of the differ- the collimated beam reduces the stimulation threshold and ence between the nature of stimulation (light signal) and improves the reliability of the system. The advantages of response (electrical signal). It is also examined that infrared the device also include that the setting of the main switch radiation increases the frequency of spontaneous synaptic and the pulse generator increases the safety and controllabil- events and the response size is proportional to the output ity, and the external micromanipulator and the handheld of the excitation light [79]. bracket make it flexibly used in different positions. However, Many scholars have done extensive research on the prin- the device also has shortcomings. The handheld probe used ciple of light stimulation. Generally speaking, the interaction in this study was determined as a limitation, because it is dif- of light and biology includes light pressure effect, photo- ficult to keep the distance between the probe and the tissue at chemistry effect, photomechanical effect, and photomagnetic 1.5 mm, which may lead to uncontrollable changes in radia- effect. Richter’s and Lenarz’s experiments exclude the photo- tion exposure. It should be more effective if a device that chemical effect, because the laser used is a low-energy infra- can accurately stabilize the probe distance was added. red laser [80], and the infrared photon energy is too low As is shown in Figure 6, Wolf provided a position- (<0.1 eV), and there is not enough energy to produce photo- sensitive NIR reflex measurement device and method for chemical reaction directly. Wells et al. of Vanderbilt Univer- automatic regulation of spinal cord stimulation. The system sity exclude photomagnetic effect by using a 750 nm laser to consists of an electrode assembly and an integrated optical stimulate peripheral nerves in mice. They found that the laser fiber sensor for sensing spinal cord position. The integrated triggered nerve impulses may be related to the light absorp- optical fiber sensor includes a set of optical elements for emit- tion of tissues, but not to the electric field effect [80]. Then, ting light from a set of infrared transmitters and collecting Vanderbilt University researchers propose that photome- the reflected light into a set of infrared photodetectors to chanical effect cannot trigger nerve impulse by observing determine a set of measured light intensity. With the change whether the duration of the laser pulse has an impact on of spinal cord position, the incident angle of light from infra- the stimulation threshold [81]. Wells’ team used a noncon- red transmitter and the measured light intensity also change. tact infrared thermometer to measure the surface tempera- Then, the device adjusts the pulse characteristics of the elec- ture of peripheral nerve tissue under the action of laser and trode in real time [84]. found that it could cause nerve excitation when the tempera- In addition to the experiments in human body, some ture increased to 6-10 C. By analyzing the distribution of light stimulation devices are also used in animals such as rats. Entwisle et al. have detected the membrane and synaptic laser energy in nerve tissue, it can be concluded that about 64% of light energy is concentrated in axon, causing the tem- responses of solitary tract neurons recorded in acute sections of rats. They used a 1890 nm compact waveguide laser to perature to rise about 3.8-6.4 C. The temperature gradient can activate the cell transmembrane ion channel and trigger stimulate neurons and send light through a single-mode fiber neural action potential [82]. to a small target the size of a single cell and found that the response was proportional to the laser output [79]. A Therefore, based on the photothermal effect, some light stimulation devices have been developed and used in prelim- thulium-doped glass waveguide laser is used in the experi- inary experiments. In the infrared stimulation of human spi- ment. The laser is customized by internal facilities. The out- nal nerve root completed by Cayce and Wells of Vanderbilt put light of 1.89 μm is coupled to the single-mode fiber University, a high-power and high-frequency clinical system with 14 μm mode field diameter, and the nominal power out- put of 7.8 mw is measured at the fiber end. The fiber was light box was used to verify the safety and effectiveness of INS in human body. In 7 subjects, INS was used to stimulate two placed in the micromanipulator 45 meters away from the and three parts of each nerve, and electromyogram records water plane and placed about 100 μm away from the target were obtained during the whole stimulation process. At the cell. The external digital trigger was used to control the power same time, histological examination was carried out to deter- output and pulse length of the laser. In a complete one- second pulse, the pulse energy calculated on the cell surface mine the thermal damage threshold of INS. The result Applied Bionics and Biomechanics 7 exhaled from the lungs as hard and fast as possible when measured from the total vital capacity, while flow of peak 0° cough (CPF) is the maximum rate of air exhaled from the lungs when coughing. The maximum expiratory pressure 90° (MEP) refers to the maximum pressure generated in the mouth to resist the blocked airway when exhaling from the total lung capacity. Pressure of gastric (PGA) and pressure of esophageal (PES) can be used to measure the pressure of pleura when expiratory muscles contract. These indexes can PD PD indicate the strength of expiratory muscles.VC, FVC, and 180° FEV1 can be used to evaluate the strength of vital capacity. These evaluation indexes are characterized by the need for active control of breathing, as well as subjects’ prediction Figure 6: Construction and reflex measurement of spinal cord stimulation device. and motivation, noninvasive. Spirometry has been used in all five studies. (2) Plethysmography: parameters mentioned are respiratory rate (F), tidal volume (VT), and minute ven- is 261 J/cm , and the spot size calculated after the light diver- gence is 42:8 μm×26:7 μm, which shows that the device with tilation volume (VE). Only the fourth study clearly indicated this structure can be used for a specific single cell. This device that tidal volume testing was carried out. (3) Electromyogra- phy: electromyography reflects muscle activity, which is can be improved and applied in clinic. characterized by the fact that long-term electrode placement can be used for repeated measurement. Electrodes are often 4. Discussion placed on the skin surface, which reduces the accuracy of 4.1. Experimental Comparison of Different Stimulation recording. EMG electrodes were applied to the left lateral oblique muscle in the fourth study. (4) Diaphragm com- Methods. I selected 5 cases about the recovery of diaphragm function by stimulation, involving 66 people in total, most pound motor action potential (CMAP): the electrode is placed on the skin, and the nerve function is indirectly mea- of them were in C4-C6 spinal cord segment, and a few of them had T4-T6 injury. The age of these patients ranged sured by evaluating the nerve integrity. None of the five stud- from 16 to 67, most of them were men, and some of them ies used this evaluation method. By comparing the five experiments, it can be found that had smoking history. The causes include gunshot wounds, car accidents, and falls. The participants are shown in the PEF-TLC of the first group is 5.8-8.8 L/s, while the mag- Table 1. netic stimulation is only 4.3 L/s. When referring to MEP- The first, third, fourth, and fifth experiments were electric TLC, the first group is 120-150 cm H O, while the average stimulation; the second was magnetic stimulation; the first of the second group is 55.3 cm H O. When referring to and second were spinal nerve stimulation; the third, fourth, PEF-FRC and MEP-FRC, it can also be seen that although and fifth were muscle stimulation. Different stimulation the magnetic stimulation treatment has made progress com- methods and locations will result in different stimulation pared with nonstimulation, it is far less than that of electric parameters and results. The duration of stimulation in spinal stimulation. Direct stimulation of spinal cord was better than nerve electrical stimulation is only 5-10 minutes, while the muscle stimulation. The PEF-TLC of the first study (single rest is no less than 20 minutes. The stimulator of spinal nerve stimulus point: 5.8-8.6 L/s; double stimulation points: 7.8- is placed between T9 and L1, while others are placed in mus- 8.8 L/s) was greater than that of the fourth study (increased cle. The maximum stimulation frequency of these experi- from 5:1±0:6 L/s to 6:1±0:5 L/s) and the fifth study ments is no more than 50 Hz. The pulse width of spinal (4.24 L/s), which were muscle stimulation studies. The results cord stimulation experiment is lower than that of muscle of the last study and the second study were similar in FVC stimulation. Authors in the first study use voltage to measure (2:5± 0:1 L in the second study and 2.51 L in the fifth study), the stimulus intensity, while the fifth study used the current. FEV1 (2:0±0:1 L in the second study and 2.3 L/s in the fifth In the selection of stimulator, electrodes were used in spinal study), and PEF-TLC (4:3±0:5 L/s in the second study and cord electrical stimulation, while circular magnetic coil 4.24 L/s in the fifth study), which indicated that the effect of (outer diameter 20 cm) was used in spinal cord magnetic magnetic stimulation of spinal cord was less than that of elec- stimulation. Two pairs of surface electrodes were selected trical stimulation of spinal cord, but similar to that of electri- for muscle electrical stimulation. In the fourth study, the cal stimulation of muscle. In addition, in terms of anterior electrode was placed in the rectus abdominis muscle complications, 5 subjects in the first study had mild edema under costal margin and above pubic symphysis, and the in the test site, while in the fifth study, one case (7.7%) in ventrolateral electrode was at the intersection of the inferior the treatment group had pulmonary complication. It is diffi- margin of costal margin and axillary midline, above the ante- cult to see the effect of different stimulation situations on rior superior iliac spine. complications. Generally speaking, there are many indexes to evaluate respiratory and cough function. The indexes used in the five 4.2. Auxiliary Treatments of Functional Reconstruction. cited experiments can be classified as follows. (1) Spirometry: Many scholars added training as auxiliary treatment in the peak expiratory flow (PEF) is the maximum rate of air experiment of functional reconstruction of spinal cord 8 Applied Bionics and Biomechanics Table 1: Characteristics of participants of included studies. Aetiology(SCI Num Author Country or region Number of participants Mean of age Male (%) Injury time level) 1 Anthony F. DiMarco [15] USA SCI(C3-C6) 9 41 89 13.11 years 2 Vernon W. Lin [51] USA C4-C7 T5 8 51.25 100 17.75 years 3 A Zupan [45], Slovenia C4-C7 13 26.9 84.62 7 months 4 Franco Laghi [33] USA C5-C7 T4-T6 10 47.3 Unknown 10.66 years 5 Pao-Tsai Cheng [46] Taiwan C4-C7 26 34.7 84.62 In 3 months injury. Boswell explored the feasibility of respiratory muscle 5. Conclusion training (RMT) as an improvement of lung function in According to the results of our study, we may conclude that, patients with cervical spinal cord injury [85]. Tamplin although the evidence is presently limited, spinal nerve stim- explored the effect of RMT on pulmonary function in ulation and muscle stimulation are very effective in the recov- patients with quadriplegia [86]. Paleville combined 80 exer- ery of respiratory function impairment caused by cervical cises with electrical stimulation of L1-S1 spinal cord. It is spinal cord injury. Both magnetic stimulation and electrical concluded that the combination of task-specific training stimulation can improve the airflow rate and airway pressure and epidural stimulation may improve the vascular fitness trend to a normal state, but the effect of magnetic stimulation and body composition of patients with cervical or upper tho- is not as good as electrical stimulation, while the effect of racic spinal cord injury [87]. Field evaluated the effects of muscle stimulation is not as good as spinal nerve stimulation. body weight support (BWS), FES, and treadmill training on In addition, the treatment device has its own characteristics ground walking speed, treadmill walking speed, and distance, according to its components and function content. and concluded that in the training process, all indexes were At the same time, the research means and research tools significantly improved [88]. Gee proved the effect of RMT of functional light stimulation are also used for reference. on strengthening respiratory muscle strength, reducing exer- Light stimulation is gradually applied to clinical medicine cise lung capacity, and increasing exercise ability through with its strong advantages. In the experiment of functional training disabled athletes with cervical spinal cord injury reconstruction of spinal cord injury, training and improved [89]. By analyzing the vital capacity of patients with SCI, Tif- surgical methods can be used as adjuvant treatment. It can tik compared the effect of combination of exercise training be predicted that in the future, the research on spinal cord and simple rehabilitation only program on the lung function electrical stimulation and nerve light stimulation after cervi- of SCI patients and emphasized the importance of exercise cal spinal cord injury is promising and has a positive effect on training [90]. Stenson evaluated the effect of expiratory mus- the treatment of respiratory injury caused by cervical spinal cle training on pulmonary function in patients with spinal cord injury. cord injury and got the conclusion that resistance training group has a good pulmonary function effect [91]. Liaw did Conflicts of Interest similar experiments and obtained that RMT can improve respiratory function, respiratory resistance, and dyspnea of The authors declare that they have no conflicts of interest. patients with cervical spinal cord injury [92]. Roy pointed out that the plasticity of repetitive training can expand the Acknowledgments rehabilitation methods [93]. In addition to the auxiliary effect of training, the The research is funded by the China Postdoctoral Science improvement of surgical methods can also greatly improve Foundation (2019M660392). the cure rate. Nandra extended phrenic pacing treatment to paraplegia patients with high cervical spinal cord injury References between C3 and C5. Four patients with high cervical spinal cord injury were selected as the study object. Each patient [1] C. H. Ho, R. J. Triolo, A. L. Elias et al., “Functional Electrical had phrenic nerve deficiency and received intercostal phrenic Stimulation and Spinal Cord Injury,” Physical Medicine and nerve transplantation and phrenic nerve pacemaker implan- Rehabilitation Clinics of North America, vol. 25, no. 3, tation. Then, it is found that patient can breathe well with pp. 631–654, 2014. diaphragm [94]. Yang suspended the posterior rib on the [2] A. Jackson, “Spinal-cord injury: neural interfaces take another lower angle of the scapula with titanium cable and suspended step forward,” Nature, vol. 539, no. 7628, pp. 177-178, 2016. the muscle and myofascial tissue in the area under the scap- [3] M. Nygren-Bonnier, L.-L. Normi, B. Klefbeck, and G. Biguet, ula. This method partially restored thoracic respiration in “Experiences of decreased lung function in people with cervi- patients with high CSCI, thus improving respiratory, cough, cal spinal cord injury,” Disability and Rehabilitation, vol. 33, and expectoration functions [13]. Tedde implanted laparo- no. 6, pp. 530–536, 2010. scopic diaphragm pacemaker in 5 cases of high cervical trau- [4] D. G. L. Terson de Paleville, W. B. McKay, R. J. Folz, and A. V. matic spinal cord injury [95]. Ovechkin, “Respiratory Motor Control Disrupted by Spinal Applied Bionics and Biomechanics 9 and the European Section of the Cervical Spine Research Soci- Cord Injury: Mechanisms, Evaluation, and Restoration,” Translational Stroke Research, vol. 2, no. 4, pp. 463–473, 2011. ety, vol. 17, no. 9, pp. 1256–1269, 2008. [5] L. van Silfhout, A. E. J. Peters, D. J. Berlowitz, R. Schembri, [19] P. H. Gorman, “An update on functional electrical stimulation D. Thijssen, and M. Graco, “Long-term change in respiratory after spinal cord Injury,” Neurorehabilitation and Neural function following spinal cord injury,” Spinal Cord, vol. 54, Repair, vol. 14, no. 4, pp. 251–263, 2000. no. 9, pp. 714–719, 2016. [20] M. A. Lane, K. Z. Lee, D. D. Fuller, and P. J. Reier, “Spinal cir- [6] P. M. Warren, B. I. Awad, and W. J. Alilain, “Drawing breath cuitry and respiratory recovery following spinal cord injury,” without the command of effectors: the control of respiration Respiratory Physiology & Neurobiology, vol. 169, no. 2, following spinal cord injury,” Respiratory Physiology & Neuro- pp. 123–132, 2009. biology, vol. 203, pp. 98–108, 2014. [21] C. C. Horn, J. L. Ardell, and L. E. Fisher, “Electroceutical tar- [7] J. T. Hachmann, J. S. Calvert, P. J. Grahn, D. I. Drubach, K. H. geting of the autonomic nervous System,” Physiology, vol. 34, no. 2, pp. 150–162, 2019. Lee, and I. A. Lavrov, “Review of epidural spinal cord stimula- tion for augmenting cough after spinal cord injury,” Frontiers [22] G. Courtine and M. V. Sofroniew, “Spinal cord repair: in Human Neuroscience, vol. 11, 2017. advances in biology and technology,” Nature Medicine, [8] J. H. Park, S.-W. Kang, S. C. Lee, W. A. Choi, and D. H. Kim, vol. 25, no. 6, pp. 898–908, 2019. “How Respiratory Muscle Strength Correlates with Cough [23] A. Alshekhlee, R. P. Onders, T. U. Syed, M. Elmo, and Capacity in Patients with Respiratory Muscle Weakness,” Yon- B. Katirji, “Phrenic nerve conduction studies in spinal cord sei Medical Journal, vol. 51, no. 3, pp. 392–397, 2010. injury: applications for diaphragmatic pacing,” Muscle & Nerve, vol. 38, no. 6, pp. 1546–1552, 2008. [9] S. W. Kang, J. C. Shin, C. I. Park, J. H. Moon, D. W. Rha, and D.-h. Cho, “Relationship between inspiratory muscle strength [24] E. P. Sieg, R. A. Payne, S. Hazard, and E. Rizk, “Evaluating the and cough capacity in cervical spinal cord injured patients,” evidence: is phrenic nerve stimulation a safe and effective tool Spinal Cord, vol. 44, no. 4, pp. 242–248, 2006. for decreasing ventilator dependence in patients with high cer- vical spinal cord injuries and central hypoventilation?,” Childs [10] C. R. West, I. G. Campbell, R. E. Shave, and L. M. Romer, Nervous System, vol. 32, no. 6, pp. 1033–1038, 2016. “Effects of abdominal binding on cardiorespiratory function in cervical spinal cord injury,” Respiratory Physiology & Neu- [25] A. F. DiMarco, R. P. Onders, A. Ignagni, K. E. Kowalski, and robiology, vol. 180, no. 2-3, pp. 275–282, 2012. J. T. Mortimer, “Phrenic nerve pacing via intramuscular dia- phragm electrodes in tetraplegic subjects,” Chest, vol. 127, [11] G. J. Schilero, A. M. Spungen, W. A. Bauman, M. Radulovic, no. 2, pp. 671–678, 2005. and M. Lesser, “Pulmonary function and spinal cord injury,” Respiratory Physiology & Neurobiology, vol. 166, no. 3, [26] A. F. Dimarco, “Restoration of respiratory muscle function fol- pp. 129–141, 2009. lowing spinal cord injury: review of electrical and magnetic stimulation techniques,” Respiratory Physiology and Neurobi- [12] F. Urdaneta, A. J. Layon, B. Guiot, E. Mendel, and R. R. Kirby, ology, vol. 147, no. 2-3, pp. 273–287, 2005. “Respiratory complications in patients with traumatic cervical spine injuries: case report and review of the literature,” Journal [27] A. F. DiMarco, R. P. Onders, A. Ignagni, and K. E. Kowalski, of Clinical Anesthesia, vol. 15, no. 5, pp. 398–405, 2003. “Inspiratory muscle pacing in spinal cord injury: case report and clinical commentary,” The Journal of Spinal Cord Medi- [13] M. L. Yang, J. J. Li, F. Gao et al., “A preliminary evaluation of cine, vol. 29, no. 2, pp. 95–108, 2016. the surgery to reconstruct thoracic breathing in patients with high cervical spinal cord injury,” Spinal Cord, vol. 52, no. 7, [28] G. Cosendai, C. de Balthasar, A. R. Ignagni et al., “A prelimi- pp. 564–569, 2014. nary feasibility study of different implantable pulse generators technologies for diaphragm pacing system,” Neuromodulation, [14] R. Brown, A. F. DiMarco, J. D. Hoit, and E. Garshick, “Respi- vol. 8, no. 3, pp. 203–211, 2005. ratory dysfunction and management in spinal cord injury,” Respiratory Care, vol. 51, pp. 853–868, 2006. [29] M. L. Tedde, R. P. Onders, M. J. Teixeira et al., “Electric venti- lation: indications for and technical aspects of diaphragm pac- [15] A. F. DiMarco, K. E. Kowalski, R. T. Geertman, and D. R. Hro- ing stimulation surgical implantation[J],” Jornal brasileiro de myak, “Lower thoracic spinal cord stimulation to restore pneumologia: publicacao oficial da Sociedade Brasileira de cough in patients with spinal cord injury: results of a National Pneumologia e Tisilogia, vol. 38, no. 5, pp. 566–572, 2012. Institutes of Health–sponsored clinical trial. Part I: methodol- ogy and effectiveness of expiratory muscle activation,” [30] B. Garara, A. Wood, H. J. Marcus, K. Tsang, M. H. Wilson, and Archives of Physical Medicine & Rehabilitation, vol. 90, no. 5, M. Khan, “Intramuscular diaphragmatic stimulation for pp. 717–725, 2009. patients with traumatic high cervical injuries and ventilator dependent respiratory failure: a systematic review of safety [16] T. Liebscher, A. Niedeggen, B. Estel, and R. O. Seidl, “Airway and effectiveness,” Injury, vol. 47, no. 3, pp. 539–544, 2016. complications in traumatic lower cervical spinal cord injury: a retrospective study,” The Journal of Spinal Cord Medicine, [31] T. R. Hazwani, B. Alotaibi, W. Alqahtani, A. Awadalla, and vol. 38, no. 5, pp. 607–614, 2015. A. Al Shehri, “Pediatric diaphragmatic pacing,” Pediatric reports, vol. 11, no. 1, 2019. [17] E. C. Zakrasek, J. L. Nielson, J. J. Kosarchuk, J. D. Crew, A. R. Ferguson, and S. L. McKenna, “Pulmonary outcomes follow- [32] J. M. Dean, R. P. Onders, and M. J. Elmo, “Diaphragm pacers in ing specialized respiratory management for acute cervical spi- pediatric patients with cervical spinal cord injury: a review and nal cord injury: a retrospective analysis,” Spinal Cord, vol. 55, implications for inpatient rehabilitation,” Current Physical Med- no. 6, pp. 559–565, 2017. icine and Rehabilitation Reports, vol. 6, no. 4, pp. 257–263, 2018. [18] S. Hamid and R. Hayek, “Role of electrical stimulation for [33] F. Laghi, V. Maddipati, T. Schnell, W. E. Langbein, and M. J. rehabilitation and regeneration after spinal cord injury: an Tobin, “Determinants of cough effectiveness in patients with overview,” European spine journal : official publication of the respiratory muscle weakness,” Respiratory Physiology & Neu- European Spine Society, the European Spinal Deformity Society, robiology, vol. 240, pp. 17–25, 2017. 10 Applied Bionics and Biomechanics [48] S. Mangold, T. Keller, A. Curt, and V. Dietz, “Transcutaneous [34] F. S. Macedo, A. F. Rocha, C. J. Miosso, and S. R. M. Mateus, “Use of electromyographic signals for characterization of vol- functional electrical stimulation for grasping in subjects with untary coughing in humans with and without spinal cord cervical spinal cord injury,” Spinal Cord, vol. 43, no. 1, pp. 1– injury-A systematic review,” Physiotherapy Research Interna- 13, 2005. tional, vol. 24, no. 2, p. e1761, 2019. [49] M. R. Popovic, T. A. Thrasher, M. E. Adams, V. Takes, [35] E. J. McCaughey, R. J. Borotkanics, H. Gollee, R. J. Folz, and V. Zivanovic, and M. I. Tonack, “Functional electrical therapy: A. J. McLachlan, “Abdominal functional electrical stimulation retraining grasping in spinal cord injury,” Spinal Cord, vol. 44, to improve respiratory function after spinal cord injury: a sys- no. 3, pp. 143–151, 2006. tematic review and meta-analysis,” Spinal Cord, vol. 54, no. 9, [50] K. T. Ragnarsson, “Functional electrical stimulation after spi- pp. 628–639, 2016. nal cord injury: current use, therapeutic effects and future [36] J. E. Butler, J. Lim, R. B. Gorman et al., “Posterolateral surface directions,” Spinal Cord, vol. 46, no. 4, pp. 255–274, 2008. electrical stimulation of abdominal expiratory muscles to [51] V. W. Lin, I. N. Hsiao, E. Zhu, and I. Perkash, “Functional enhance cough in spinal cord injury,” Neurorehabilitation magnetic stimulation for conditioning of expiratory muscles and Neural Repair, vol. 25, no. 2, pp. 158–167, 2011. in patients with spinal cord injury,” Archives of Physical Med- [37] H. Gollee, K. J. Hunt, D. B. Allan, M. H. Fraser, and A. N. icine & Rehabilitation, vol. 82, no. 2, pp. 162–166, 2001. McLean, “A control system for automatic electrical stimula- [52] S. Fawaz, F. Kamel, A. El Yasaky et al., “The therapeutic appli- tion of abdominal muscles to assist respiratory function in tet- cation of functional electrical stimulation and transcranial raplegia,” Medical Engineering & Physics, vol. 29, no. 7, magnetic stimulation in rehabilitation of the hand function pp. 799–807, 2007. in incomplete cervical spinal cord injury,” Egyptian Rheuma- [38] R. J. Jaeger, R. M. Turba, G. M. Yarkony, and E. J. Roth, tology and Rehabilitation, vol. 46, no. 1, p. 21, 2019. “Cough in spinal cord injured patients: comparison of three [53] J. S. Calvert, P. J. Grahn, K. D. Zhao, and K. H. Lee, “Emer- methods to produce cough,” Archives of Physical Medicine gence of epidural electrical stimulation to facilitate sensorimo- and Rehabilitation, vol. 74, no. 12, pp. 1358–1361, 1993. tor network functionality after spinal cord injury,” [39] W. E. Langbein, C. Maloney, F. Kandare, U. Stanic, Neuromodulation: Technology at the Neural Interface, vol. 22, B. Nemchausky, and R. J. Jaeger, “Pulmonary function testing no. 3, pp. 244–252, 2019. in spinal cord injury: effects of abdominal muscle stimulation,” [54] M. D. Craggs, “Cortical control of motor prostheses: using the The Journal of Rehabilitation Research and Development, cord-transected baboon as the primate model for human para- vol. 38, no. 5, pp. 591–597, 2001. plegia,” Advances in Neurology, vol. 10, no. 10, pp. 91–101, [40] S. H. Linder, “Functional electrical stimulation to enhance cough in quadriplegia,” Chest, vol. 103, no. 1, pp. 166–169, [55] L. R. Hochberg, M. D. Serruya, G. M. Friehs et al., “Neuronal ensemble control of prosthetic devices by a human with tetra- [41] J. Sorli, F. Kandare, R. J. Jaeger, and U. Stanic, “Ventilatory plegia,” Nature, vol. 442, no. 7099, pp. 164–171, 2006. assistance using electrical stimulation of abdominal muscles,” [56] L. R. Hochberg, D. Bacher, B. Jarosiewicz et al., “Reach and IEEE Transactions on Rehabilitation Engineering, vol. 4, grasp by people with tetraplegia using a neurally controlled no. 1, pp. 1–6, 1996. robotic arm,” Nature, vol. 485, no. 7398, pp. 372–375, 2012. [42] U. Stanic, F. Kandare, R. Jaeger, and J. Sorli, “Functional elec- [57] J. B. Zimmermann and A. Jackson, “Closed-loop control of trical stimulation of abdominal muscles to augment tidal vol- spinal cord stimulation to restore hand function after paraly- ume in spinal cord injury,” IEEE Transactions on sis,” Frontiers in Neuroscience, vol. 8, 2014. Rehabilitation Engineering, vol. 8, no. 1, pp. 30–34, 2000. [58] C. A. Angeli, V. R. Edgerton, Y. P. Gerasimenko, and S. J. Har- [43] A. J. McLachlan, A. N. McLean, D. B. Allan, and H. Gollee, kema, “Altering spinal cord excitability enables voluntary “Changes in pulmonary function measures following a passive movements after chronic complete paralysis in humans,” abdominal functional electrical stimulation training program,” Brain, vol. 137, no. 5, pp. 1394–1409, 2014. The Journal of Spinal Cord Medicine, vol. 36, no. 2, pp. 97–103, [59] M. Capogrosso, T. Milekovic, D. Borton et al., “A brain–spine interface alleviating gait deficits after spinal cord injury in pri- [44] R. A. McBain, C. L. Boswell-Ruys, B. B. Lee, S. C. Gandevia, mates,” Nature, vol. 539, no. 7628, pp. 284–288, 2016. and J. E. Butler, “Electrical Stimulation of Abdominal Muscles [60] A. F. DiMarco, K. E. Kowalski, R. T. Geertman, and D. R. Hro- to Produce Cough in Spinal Cord Injury,” Neurorehabilitation myak, “Spinal cord stimulation: a new method to produce an and Neural Repair, vol. 29, no. 4, pp. 362–369, 2014. effective cough in patients with spinal cord injury,” American [45] A. Zupan, R. Šavrin, T. Erjavec et al., “Effects of respiratory Journal of Respiratory and Critical Care Medicine, vol. 173, muscle training and electrical stimulation of abdominal mus- no. 12, pp. 1386–1389, 2006. cles on respiratory capabilities in tetraplegic patients,” Spinal [61] A. F. DiMarco, R. T. Geertman, K. Tabbaa, R. R. Polito, and Cord, vol. 35, no. 8, pp. 540–545, 1997. K. E. Kowalski, “Case report: Minimally invasive method to [46] P. T. Cheng, C. L. Chen, C. M. Wang, and C. Y. Chung, “Effect activate the expiratory muscles to restore cough,” The journal of neuromuscular electrical stimulation on cough capacity and of spinal cord medicine, vol. 41, no. 5, pp. 562–566, 2018. pulmonary function in patients with acute cervical cord injury,” Journal of Rehabilitation Medicine, vol. 38, no. 1, [62] A. V. Minyaeva, S. A. Moiseev, A. M. Pukhov, A. A. Savokhin, Y. P. Gerasimenko, and T. R. Moshonkina, “Response of exter- pp. 32–36, 2006. nal inspiration to the movements induced by transcutaneous [47] M. J. Mulcahey, R. R. Betz, B. T. Smith, A. A. Weiss, and S. E. spinal cord stimulation,” Human Physiology, vol. 43, no. 5, Davis, “Implanted functional electrical stimulation hand sys- pp. 524–531, 2017. tem in adolescents with spinal injuries: an evaluation,” Archives of Physical Medicine and Rehabilitation, vol. 78, [63] E. Formento, K. Minassian, F. Wagner et al., “Electrical spinal no. 6, pp. 597–607, 1997. cord stimulation must preserve proprioception to enable Applied Bionics and Biomechanics 11 [77] A. Roshani and A. Erfanian, “Fuzzy logic control of ankle locomotion in humans with spinal cord injury,” Nature Neuro- science, vol. 21, no. 12, pp. 1728–1741, 2018. movement using multi-electrode intraspinal microstimula- tion,” in 2013 35th Annual International Conference of the [64] S. Harkema, Y. Gerasimenko, J. Hodes et al., “Effect of epidural IEEE Engineering in Medicine and Biology Society (EMBC), stimulation of the lumbosacral spinal cord on voluntary move- Osaka, Japan, 2013. ment, standing, and assisted stepping after motor complete paraplegia: a case study,” Lancet, vol. 377, no. 9781, [78] J. Wells, C. Kao, K. Mariappan et al., “Optical stimulation of pp. 1938–1947, 2011. neural tissue in vivo,” Optics Letters, vol. 30, no. 5, pp. 504– 506, 2005. [65] F. B. Wagner, J.-B. Mignardot, C. G. Le Goff-Mignardot et al., “Targeted neurotechnology restores walking in humans with [79] B. Entwisle, S. McMullan, P. Bokiniec, S. Gross, R. Chung, and spinal cord injury,” Nature, vol. 563, no. 7729, pp. 65–71, 2018. M. Withford, “In vitro neuronal depolarization and increased [66] P. D. Thompson, J. P. R. Dick, P. Asselman et al., “Examina- synaptic activity induced by infrared neural stimulation,” Bio- medical Optics Express, vol. 7, no. 9, pp. 3211–3219, 2016. tion of motor function in lesions of the spinal cord by stimula- tion of the motor cortex,” Annals of neurology, vol. 21, no. 4, [80] J. Wells, C. Kao, P. Konrad, A. Mahadevan-Jansen, and E. D. pp. 389–396, 1987. Jansen, “Biophysical mechanisms responsible for pulsed low- [67] C. T. Moritz, T. H. Lucas, S. I. Perlmutter, and E. E. Fetz, level laser excitation of neural tissue,” in Optical Interactions “Forelimb movements and muscle responses evoked by micro- with Tissue and Cells XVII, vol. 6084, pp. 227–233, 2006. stimulation of cervical spinal cord in sedated monkeys,” Jour- [81] A. Fishman, P. Winkler, J. Mierzwinski et al., “Stimulation of nal of Neurophysiology, vol. 97, no. 1, pp. 110–120, 2007. the human auditory nerve with optical radiation,” in Photons [68] V. K. Mushahwar, Y. Aoyagi, R. B. Stein, and A. Prochazka, and Neurons, vol. 7180no. 2, pp. 149–160, 2009. “Movements generated by intraspinal microstimulation in [82] S. M. Rajguru, A. I. Matic, A. M. Robinson et al., “Optical the intermediate gray matter of the anesthetized, decerebrate, cochlear implants: evaluation of surgical approach and laser and spinal cat,” Canadian Journal of Physiology and Pharma- parameters in cats,” Hearing Research, vol. 269, no. 1-2, cology, vol. 82, no. 8-9, pp. 702–714, 2004. pp. 102–111, 2010. [69] B. J. Holinski, K. A. Mazurek, D. G. Everaert, R. B. Stein, and [83] S. Tozburun, G. A. Lagoda, A. L. Burnett, and N. M. Fried, V. K. Mushahwar, “Restoring Stepping After Spinal Cord “Infrared laser nerve stimulation as a potential diagnostic Injury Using Intraspinal Microstimulation and Novel Control method for intra-operative identification and preservation of Strategies,” in 2011 Annual International Conference of the the prostate cavernous nerves,” IEEE Journal of Selected Topics IEEE Engineering in Medicine and Biology Society, Boston, in Quantum Electronics, vol. 20, no. 2, pp. 299–306, 2014. MA, USA, 2011. [84] E. W. Wolf, Apparatus and Method Using near Infrared Reflec- [70] J. A. Bamford, C. T. Putman, and V. K. Mushahwar, “Muscle tometry to Reduce the Effect of Positional Changes during Spi- plasticity in rat following spinal transection and chronic nal Cord Stimulation, Patent and Trademark Office, Intraspinal microstimulation,” IEEE transactions on neural Washington, DC, 2014. systems and rehabilitation engineering: a publication of the [85] C. L. Boswell-Ruys, C. R. H. Lewis, S. C. Gandevia, and J. E. IEEE Engineering in Medicine and Biology Society, vol. 19, Butler, “Respiratory muscle training may improve respiratory no. 1, pp. 79–83, 2011. function and obstructive sleep apnoea in people with cervical [71] L. M. Mercier, E. J. Gonzalez-Rothi, K. A. Streeter et al., spinal cord injury,” Spinal Cord Series And Cases, vol. 1, “Intraspinal microstimulation and diaphragm activation after no. 1, 2015. cervical spinal cord injury,” Journal of Neurophysiology, [86] J. Tamplin and D. J. Berlowitz, “A systematic review and meta- vol. 117, no. 2, pp. 767–776, 2017. analysis of the effects of respiratory muscle training on pulmo- [72] J. A. Bamford and V. K. Mushahwar, “Intraspinal microstimu- nary function in tetraplegia,” Spinal Cord, vol. 52, no. 3, lation for the recovery of function following spinal cord pp. 175–180, 2014. injury,” Progress in Brain Research, vol. 194, no. 1, pp. 227– [87] D. G. L. Terson de Paleville, S. J. Harkema, and C. A. Angeli, 239, 2011. “Epidural stimulation with locomotor training improves body [73] S. Shahdoost, S. Frost, C. Dunham et al., “Cortical control of composition in individuals with cervical or upper thoracic motor intraspinal microstimulation: toward a new approach for res- complete spinal cord injury: A series of case studies,” The Journal toration of function after spinal cord injury,” in 2015 37th of Spinal Cord Medicine,vol.42, no.1,pp.32–38, 2019. Annual International Conference of the IEEE Engineering in [88] E. C. Field-Fote, “Combined use of body weight support, func- Medicine and Biology Society (EMBC), Milan, Italy, 2015. tional electric stimulation, and treadmill training to improve [74] S. Shahdoost, S. Frost, D. Guggenmos et al., “A Miniaturized walking ability in individuals with chronic incomplete spinal Brain-Machine-Spinal Cord Interface (BMSI) for Closed- cord injury,” Archives of Physical Medicine and Rehabilitation, Loop Intraspinal Microstimulation,” in 2016 IEEE Biomedical vol. 82, no. 6, pp. 818–824, 2001. Circuits and Systems Conference (BioCAS), Shanghai, China, [89] C. M. Gee, A. M. Williams, A. W. Sheel, N. D. Eves, and C. R. West, “Respiratory muscle training in athletes with cervical [75] P. R. Troyk, V. K. Mushahwar, R. B. Stein et al., “An implant- spinal cord injury: effects on cardiopulmonary function and able neural stimulator for intraspinal microstimulation,” in exercise capacity,” The Journal of Physiology., vol. 597, 2012 Annual International Conference of the IEEE Engineering no. 14, pp. 3673–3685, 2019. in Medicine and Biology Society, pp. 900–903, San Diego, CA, [90] T. Tiftik, N. K. O. Gökkaya, F. Ü. Malas et al., “Does locomotor USA, 2012. training improve pulmonary function in patients with spinal [76] A. Asadi and A. Erfanian, “Adaptive neuro-fuzzy sliding mode cord injury?,” Spinal Cord, vol. 53, no. 6, pp. 467–470, 2015. control of multi-joint movement using intraspinal microsti- mulation,” IEEE Transactions on Neural Systems and Rehabil- [91] E. J. Roth, K. W. Stenson, S. Powley et al., “Expiratory Muscle itation Engineering, vol. 20, no. 4, pp. 499–509, 2012. Training in Spinal Cord Injury: A Randomized Controlled 12 Applied Bionics and Biomechanics Trial,” Archives of Physical Medicine & Rehabilitation, vol. 91, no. 6, pp. 857–861, 2010. [92] M. Y. Liaw, M. C. Lin, P. T. Cheng, M. K. A. Wong, and F. T. Tang, “Resistive inspiratory muscle training: its effectiveness in patients with acute complete cervical cord injury,” Archives of Physical Medicine and Rehabilitation, vol. 81, no. 6, pp. 752– 756, 2000. [93] R. R. Roy, S. J. Harkema, and V. R. Edgerton, “Basic concepts of activity-based interventions for improved recovery of motor function after spinal cord injury,” Archives of Physical Medi- cine and Rehabilitation, vol. 93, no. 9, pp. 1487–1497, 2012. [94] K. S. Nandra, M. Harari, T. P. Price, P. J. Greaney, and M. S. Weinstein, “Successful reinnervation of the diaphragm after intercostal to phrenic nerve neurotization in patients with high spinal cord injury,” Annals of Plastic Surgery, vol. 79, no. 2, pp. 180–182, 2017. [95] M. L. Tedde, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Heart Institute (InCor), Tho- racic Surgery Department, São Paulo/SP, Brazil, P. V. Filho et al., “Diaphragmatic pacing stimulation in spinal cord injury: Anesthetic and perioperative management,” Clinics, vol. 67, no. 11, pp. 1265–1269, 2012. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Applied Bionics and Biomechanics Hindawi Publishing Corporation

A Review of Different Stimulation Methods for Functional Reconstruction and Comparison of Respiratory Function after Cervical Spinal Cord Injury

Loading next page...
 
/lp/hindawi-publishing-corporation/a-review-of-different-stimulation-methods-for-functional-GD81GupXRi
Publisher
Hindawi Publishing Corporation
Copyright
Copyright © 2020 Jiaqi Chang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ISSN
1176-2322
eISSN
1754-2103
DOI
10.1155/2020/8882430
Publisher site
See Article on Publisher Site

Abstract

Hindawi Applied Bionics and Biomechanics Volume 2020, Article ID 8882430, 12 pages https://doi.org/10.1155/2020/8882430 Review Article A Review of Different Stimulation Methods for Functional Reconstruction and Comparison of Respiratory Function after Cervical Spinal Cord Injury 1 1 1 2 3 Jiaqi Chang, Dongkai Shen, Yixuan Wang, Na Wang , and Ya Liang School of Automation Science and Electrical Engineering, Beihang University, Beijing 100191, China Engineering Training Cent, Beihang University, Beijing 100191, China Nursing Department, Juancheng County People’s Hospital, Shandong 274600, China Correspondence should be addressed to Na Wang; lion_na987@buaa.edu.cn Received 8 May 2020; Revised 30 July 2020; Accepted 7 September 2020; Published 17 September 2020 Academic Editor: Jose Merodio Copyright © 2020 Jiaqi Chang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Spinal cord injury (SCI) is a common severe trauma in clinic, hundreds of thousands of people suffer from which every year in the world. In terms of injury location, cervical spinal cord injury (CSCI) has the greatest impact. After cervical spinal cord injury, the lack of innervated muscles is not enough to provide ventilation and other activities to complete the respiratory function. In addition to the decline of respiratory capacity, respiratory complications also have a serious impact on the life of patients. The most commonly used assisted breathing and cough equipment is the ventilator, but in recent years, the functional electrical stimulation method is being used gradually and widely. Methods. About hundred related academic papers are cited for data analysis. They all have the following characteristics: (1) basic conditions of patients were reported, (2) patients had received nerve or muscle stimulation and the basic parameters, and (3) the results were evaluated based on some indicators. Results. The papers mentioned above are classified as four kinds of stimulation methods: muscle electric/magnetic stimulation, spinal dural electric stimulation, intraspinal microstimulation, and infrared light stimulation. This paper describes the stimulation principle and application experiment. Finally, this paper will compare the indexes and effects of typical stimulation methods, as well as the two auxiliary methods: training and operation. Conclusions. Although there is limited evidence for the treatment of respiratory failure by nerve or muscle stimulation after cervical spinal cord injury, the two techniques seem to be safe and effective. At the same time, light stimulation is gradually applied to clinical medicine with its strong advantages and becomes the development trend of nerve stimulation in the future. 1. Introduction in respiratory function in more than 20 years [5]. The ability to breathe requires continuous movement of the skeletal Spinal cord injury is a common clinical severe trauma, which muscle [6]. The diaphragm, which is dominated by C3-C8, will disturb the communication between the brain and the is the main inspiratory muscle and the external intercostal muscles, which are dominated by T1-T11, produce about body, leading to the loss of control of other intact neuromus- cular system [1]. Around the world, according to the World 35-40% of a person’s vital capacity. For inspiratory and expi- Health Organization, between 250000 and 500000 people ratory steps [7], it is confirmed that inspiratory muscle suffer from spinal cord injury every year [2]. About 20% of strength has a more important effect on the respiration and spinal cord injuries occur between C1 and C4 levels. cough ability of SCI patients [8, 9]; also, positive muscle con- traction and the combination of abdominal wall is required After cervical spinal cord injury, the decline of pulmo- nary function is reflected in three areas: respiratory function, for expiratory performance and adequate ventilation to cough ability, and limitation of voice function [3], especially maintain a higher respiratory rate and volume [10]. After spi- in respiratory function [4], which has no significance worsen nal cord injury, the injury of neck and upper thoracic cord 2 Applied Bionics and Biomechanics The selected papers are divided into two categories: thera- destroyed the function of diaphragm, intercostal muscle, pararespiratory muscle, and abdominal muscle [11], which peutic reports and analytical reviews. means that the ventilation system cannot work in the best way, and muscle activity is often out of sync. 2.2. Data Extraction. In the systematic introduction part, In addition to the above three areas, patients with such stimulation method is used as a classification. In the compar- injuries have a high risk of respiratory complications [12]. ison part, we choose several representative articles with com- It is reported that nearly 84% of the patients with acute hos- plete data from each stimulation method, all of which are pitalized cervical spinal cord injury have respiratory compli- aiming at the reconstruction of respiratory function for com- cations, 20% receive tracheotomy and mechanical parison. The following data were extracted from the selected ventilation, and 4-5% need lifelong ventilation support [13]. therapeutic report: (1) participants’ condition, (2) treatment Spinal cord injury can lead to respiratory muscle injury, method, (3) stimulator and stimulation parameters, and (4) decreased vital capacity, ineffective cough, reduced lung and evaluation index. chest wall compliance, and excessive respiratory oxygen con- sumption due to distorted respiratory system [14]. As a 3. Results result, the ability of clearing respiratory secretions in patients with spinal cord injury is obviously impaired, which leads to 3.1. Muscles Stimulation. Functional electrical stimulation discomfort and inconvenience and develops into atelectasis (FES) is a kind of technology that uses a safe level current and recurrent respiratory infection [15, 16]. to activate the damaged or disabled neuromuscular system The most commonly used assisted breathing and cough for function reconstruction [18]. In a closed-loop system, equipment is the ventilator. The main work of ventilator- the parameters of electrical stimulation are constantly modi- dependent spinal cord injury patients is positive pressure fied by the computer through the feedback information of mechanical ventilation. In the early stage of mechanical ven- muscle strength and joint position, so as to stimulate differ- tilation, patients are passive breathing and provide tempo- ent muscle groups at the same time, which leads to the com- rary respiratory support. Due to the nature of these bination of muscle contraction required for complex and ventilator devices, patients cannot improve their respiratory complex functional activities (such as walking) [19]. The function, increase the risk of respiratory infection [13], and main problem related to the FES model is feedback control also accompany with bedsore and other problems. At the [18], which means more sensors are needed to measure mus- same time, getting rid of the ventilator requires medication cle strength, muscle fatigue, joint position, angular velocity, [17]. The idea of nerve stimulation to restore spinal cord and torso position, and all of them need microprocessor for function can be traced back to 1970s, but it has made remark- accurate analysis. As a response to all these sensory inputs, able progress in the 21st century [2]. FES system should be able to define stimulus parameters Although scholars have made positive results in the according to the feedback received, so as to provide more research of spinal nerve stimulation, there is no summary natural response and smoother transition. analysis of stimulation equipment and methods. The review The above theory has been confirmed by many scholars. can be used to collect the results of different studies, so as Lane induced the recovery of ipsilateral phrenic motoneu- to evaluate the therapeutic effect of various means. This rons and phrenic muscle activity under the condition of ter- review will introduce the current progress of function recon- minal neurophysiology and found a persistent spontaneous struction after spinal cord injury and make a key overview of recovery in this model [20]. Warren found that there was the reconstruction of respiratory function. At the same time, an endogenous plasticity mechanism after spinal cord injury this paper compares the stimulation parameters and effects of to promote respiration and help restore lung ventilation. several stimulation methods for respiratory function recon- These mechanisms include activation of alternative or poten- struction and discusses the influence of auxiliary means on tial pathways, endogenous germination or synaptic forma- the treatment effect. It will also introduce the hot issues in tion, and possible formation of new respiratory control this research field, so as to show that this field has a very high centers [21]. Horn pointed out that the autonomic nervous research prospect. system is an attractive target for medical treatment with elec- tronic devices due to its potential of selective control and few side effects. Courtine also summarized the progress of biolog- 2. Methods ical and engineering strategies in recent years to enhance 2.1. Literature Search and Selection. We searched the experi- neural plasticity and functional recovery in SCI animal mental articles of scholars who studied the functional recon- models. Many scholars apply these theories and related med- ical devices to clinical experiments [22]. struction of neural and muscle stimulation in Google academic. The key words used for searching are spinal cord Diaphragmatic pacing (DP) is a minimally invasive injury, nerve electrical stimulation, infrared light stimulation, method alternative to mechanical ventilation for the treat- respiratory function reconstruction, and cough function ment of cervical spinal cord palsy patients with high cervical reconstruction. References to identified articles were also spinal cord injury [23]. Sieg reviewed the application of phrenic nerve stimulator in spinal hypertension and central manually searched for articles that were not found in the ini- tial search. Some articles are excluded if they are non-English, ventricular fibrillation syndrome in 1980s [24]. DiMarco repetitive (or research participants are not independent of explored the feasibility of laparoscopic placement of intra- previous publications), meeting summaries, and editorials. muscular diaphragm electrodes for long-term ventilation Applied Bionics and Biomechanics 3 and release through electrical stimulation, and completed the support in patients with ventilator-dependent [25]. He also placed two diaphragm electrodes on each half diaphragm of assessment of grip strength [47]. Mangold stimulated exten- five subjects and compared the advantages of intramuscular sors and thumbs in all subjects to achieve lateral and palm grasping functions [48]. Popovic compared 21 patients with phrenic pacing and traditional phrenic nerve pacing [26]. Afterwards, he proposed several feasible DP systems, includ- C3-C7 new spinal cord injury and found that functional elec- ing the traditional DP system with electrodes directly placed trotherapy has potential therapeutic potential, which is an on the phrenic nerve via thoracotomy and the minimally effective method to restore the grasp function of patients with invasive DP system with electrodes placed in the phrenic quadriplegia [49]. Ragnarsson summed up the existing prob- lems and put forward the prospect that developing a fully nerve via laparoscopy [27]. Cosendai tested a RF powered pulse generator, a rechargeable battery-powered pulse gener- implantable, easy to manufacture, modular FES system, which ator, and the external pulse generator and determined that can be used for all purposes, such as upper and lower limbs, the implantable system can replace the external pulse gener- trunk, bladder, intestine, and diaphragm functions [50]. ator [28]. The safety and effectiveness of this technology has Compared with electrical stimulation, the research of magnetic stimulation is much less. Lin explored the role of also been concerned. Tedde explored the indications of inserting the DPS electrode under laparoscope and described functional magnetic stimulation in the conditioned reflex of the operation methods of five patients with quadriplegia [29]. the expiratory muscles of the patients with spinal cord injury Garara systematically reviewed the safety and efficacy of the [51]. Fawaz used a randomized controlled trial to compare intramuscular diaphragm stimulator in the treatment of the effects of two rehabilitation programs, one for FES and true magnetic stimulation, the other for FES and false mag- patients with traumatic high cervical trauma who depended on a ventilator for a long time, especially security due to the netic stimulation, on the hand function recovery of patients. insertion time of the stimulator [30]. Tarek reported that a The results showed that patients receiving magnetic stimula- 4-year-old child with spinal cord injury received diaphragm tion have recovered quickly [52]. pacing with low amplitude, changeable pulse width gradually 3.2. Epidural Electrical Stimulation. It is conformed that the got rid of ventilator [31]. Dean reviewed the safety and effec- tiveness of DP in pediatric, described the process of ventilator motor activity after spinal cord injury can be realized through disconnection and diaphragm regulation during inpatient the regulation of neural circuits by epidural stimulation [53]. rehabilitation, and pointed out that DP implantation is a safe According to Jackson [2], the idea of using electronic implants and effective treatment [32]. Franco Laghi increased the expi- to bypass damaged neural pathways can be traced back to the 1970s [54], but significant progress has been made in this field ratory flow of patients through the skin stimulation of abdominal muscles [33]. in the 21st century [55, 56]. It is not only verified in monkeys In addition to diaphragm, abdominal FES can also that the brain signal can control the stimulation of the cervical region at the top of the spinal cord to restore the movement of improve respiratory function. Based on previous experi- ments, McCaughey reviewed the evidence of improvement paralyzed arms and hands [57] but also the lumbar spinal cord stimulation has achieved good results in human experiments of respiratory function by abdominal FES after SCI. More- over, FES in abdomen can still significantly improve the peak to restore the leg to a certain degree of autonomous movement flow of cough. Electromyography is usually used to measure [58]. There is evidence that closed-loop stimulation can drive neural plasticity, which plays an important role in the rehabil- the recovery of cough function [34]. After abdominal FES training, there was also a significant increase in autonomic itation of partial spinal cord injury [59]. DiMarco produced an effective coughing mechanism by vital capacity, forced vital capacity, and maximum expiratory flow compared with baseline [35–43]. FES can also be used to stimulation of the spinal cord in the lower thoracic and upper reconstruct cough function. McBain stimulated abdominal lumbar segments. Three epidural electrodes were used in the spinal cord of T9, T11, and L1. The airway pressure was muscles with surface electric stimulation, placed electrodes 2 2 in the posterolateral position, and helped patients with 90 cm H O and 82 cm H O when stimulating T9 and L1 sep- high-level spinal cord injury clear airway secretions in com- arately, while the maximum expiratory velocity was 6.4 L/s bination with cough [44]. A Zupan et al. discussed the prob- and 5.0 L/s. When stimulation of T9 and L1 combined, air- lem of improving the cough efficiency of the abdominal wall way pressure and expiratory flow rate increased to 132 cm electrical stimulation through the experiment, so that the H O and 7.4 L/s, as shown in Figure 1 [60]. patients with high cervical spinal cord injury could get dia- DiMarco completed the experiment to measure the acti- phragm pacing in the treatment [45]. Cheng et al. verified vation ability of the lower thoracic spinal cord electrical stim- that the electric stimulation of thoracoabdominal muscles ulation on the expiratory muscles of the patients with can improve the cough ability and lung function of patients quadriplegia [15]. DiMarco then proposed that the peak air- with cervical spinal cord injury of quadriplegia [46]. flow and airway pressure generation with wire electrodes On the other hand, the restoration of hand grasping func- were the same as those with disk electrodes [61]. tion is also a research hotspot of muscle electrical stimulation. Minyaeva studied the dynamic changes of pulmonary Mulcahey studied the application and functional benefits of ventilation and gas exchange parameters when stimulating implanted functional electrical stimulation (FES) system in in T11-T12 in 10 young male subjects, as shown in patients with quadriplegia after spinal cord injury. He used five Figure 2, and concluded that step motion induced by percu- adolescents aged 16 to 18 with traumatic spinal cord injury as taneous spinal cord stimulation resulted in increased respira- samples to excite the key muscles of metacarpal, lateral grasp tory rate [62]. 4 Applied Bionics and Biomechanics 200 3.3. Intraspinal Microstimulation. In addition to dural stimu- lation, due to electrical stimulation of motor cortex that can affect the conduction of central motor tract [66], some scholars have also carried out ISMS researches. The first is 50 the research of ISMS on muscle response, and the second is the reconstruction function of ISMS. As an interdisciplinary subject, some scholars focus on the development of ISMS equipment and the control algorithm. Moritz recorded the forelimb responses induced by cervi- cal spinal cord stimulation that were applied in C6 to T1 sites Spinal cord segment in primates. Of the 745 stimulated areas, finger (76% of the FRC effective area), wrist (15%), elbow (26%), and shoulder TLC (17%) induced movement. Therefore, the stimulation usually activating multiple muscles together [67]. Mushahwar used Figure 1: Airway pressure of different plans to activate cough. five adult cats that fully spinal at the T12 to record the right hindlimb movements produced by muscle (n =4), extra- % neural membrane (n =2), and spinal cord (n =3) stimula- tion. For muscle and epineurial stimulation, bipolar monophasic pulse sequences (300 microseconds, 50 pulses/- second) with duration of 0.7-0.8 s were delivered through implanted electrodes at the amplitude of 0.18-4.00 mA and 16-510 μA. They then concluded that motoneuron pools –2 from in the intermediate and ventral regions can be activated –4 by spinal cord stimulation [68]. Holinski has developed a –6 –8 feedback-driven isms system, which proved that ISMS can VE VT RF Ti Te VO RQ PetO PetCO SpO –10 2 2 2 2 enhance the stepping function by reducing muscle fatigue and activating the spinal cord neural network to generate Figure 2: Changes of lung ventilation and gas exchange parameters cooperative movement [69]. Bamford also completed an during the increase of autonomic movement (gray strip) and ISMS task. They activated the skeletal muscle to restore mus- stimulation (white strip). cle activity in rats by electrically stimulating the gray matter of abdominal wall. Compared with the peripheral FES method, ISMS is easy to achieve the stable contraction level In addition to breathing, more focus has been placed on of less than 50% of the maximum spontaneous activation [70], as shown in Figure 4. the reconstruction of walking function. Formento explored the reasons for the differences in the effects of spinal epidural In terms of reconstruction function of ISMS, Mercier explored the ISMS in C4 spinal cord segment of adult rats electrical stimulation in animal models of spinal cord injury and in humans. They concluded that the interspecificdiffer- after C2 hemisection in the background of respiratory move- ence was due to the interference between EES and human ment. The stimulation mode was 250 ms (100 Hz, 100-200a) each time. The experiment was carried out successfully and ontological sensory information. Therefore, the inspiration of this study for the recovery of walking function is that sud- induced the short-term enhancement of spontaneous inspi- den stimulation and spatiotemporal stimulation can reduce ratory activity of 70% of the subjects, which provided the the elimination of proprioceptive information, so as to basis for the closed-loop ISMS method to maintain ventila- achieve robust control of motor neuron activity. Figure 3 tion after severe spinal cord injury [71]. In addition, Bamford focused on the application of ISMS in the recovery of bladder shows the comparison of the probability of reverse collision between human and mouse [63]. function after spinal cord injury [72]. Harkema also pointed out that epidural spinal stimula- Shahboost combined the integrated circuit technology tion can regulate the spinal cord circuit to a physiological for the interface of corticospinal cord with the embedded sig- state and make the sensory input of standing and stepping nal processing technology based on FPGA to prove that the ISMS controlled in real time by the spike wave in the corti- motion the source of neural control. They placed a 16 electrodes array on the dura mater (L1-S1 spinal cord cospinal cord can activate certain muscles of experimental segment) surgically on a 23-year-old male with C7-T1 rats [73] and then reported a closed-loop control method subluxated paraplegia and successfully reactivate the previ- for the ISMS [74]. Troyk reported a wireless stimulator ously silent standby neural circuit after severe paralysis device for animal experiments. They used ISMS to activate the residual motor control neural network in the ventral horn [64]. Wagner provided a series of spatial selective stimulation of the spinal cord below the injury level after spinal cord to the lumbosacral spinal cord by using the implanted pulse injury and induced bilateral walking mode of the lower limbs. generator. After a few months, participants resumed volun- Combined with the advanced feedback algorithm, the walk- tary control of previously paralyzed muscles without stimula- ing distance recovered by ISMS exceeds that generated by other types of functional electrical stimulation. As shown in tion [65]. Airway pressure (cmH O) T9 T1 L1 T9+L1 T9+T11 T11+L1 T9+T11+L1 Applied Bionics and Biomechanics 5 Rats ESS-induced antidromic activity (20-100 lmp/s) Spinal cord Antidromic collision Muscle spindles activity (0-200 lmp/s) Peripheral nerves 10 200 Natural aer ff ent firing rate (lmp/s) Humans Spinal cord Electrical stimulation induced antidromic activity (0-60 lmp/s) Proximal nerves Antidromic 0 collision Muscle spindles Distal activity (0-50 lmp/s) nerves 10 200 Natural aer ff ent firing Commonly used EES frequency rate (lmp/s) Physiological firing rates Figure 3: Probability of retrograde AP in sensory afferent fibers under EES. NCS ISMS 1.00 1.00 0.75 0.75 0.50 0.50 0.25 0.25 0.00 0.00 0 100 200 300 400 0 100 200 300 400 Amplitude (𝜇A) Amplitude (𝜇A) Figure 4: Muscle force changes after ISMS and NCS. Figure 5, after implantation of ISMS microfilaments, the cat a fuzzy logic control and used multi electrodes to study the was placed in a safety belt and suspended on a treadmill. A closed-loop control of ankle motion. In order to compensate microaccelerometer was placed on the legs of the cat to pro- the effect of time delay, the future value of expected response vide a simulated sensory feedback signal. The spinal cord of was taken as the input and error signal of FLC. The results of animal experiments show that the proposed control frame- the cat was stimulated to produce a gait like pattern [75]. Because the neuromusculoskeletal system has obvious work can provide good tracking performance [77]. nonlinear, time-varying, large latency, and time constant as well as muscle fatigue, it is a very difficult task to control 3.4. Infrared Light Stimulation. Near-infrared light directly limbs accurately and stably by using ISMS. Many scholars irradiates the nerve tissue with infrared light, which causes put forward different ISMS control methods. Asadi proposed the instantaneous energy accumulation in the tissue, the tem- a robust control method to determine the stimulation mode, perature gradient established by which can generate light and and enables the controller to compensate for the dynamic heat in the tissue, thus inducing the nerve activity [78]. Com- interaction between the pool of motor neurons and the elec- pared with traditional electrical stimulation, INS uses fiber- trode positions. The control method is based on the combi- optic coupling laser to stimulate nerve tissue, which solves nation of sliding mode control, fuzzy logic, and neural the problem of mechanical damage caused by contact elec- control. A large number of experiments have been carried trodes in electrical stimulation; meanwhile, laser stimulation out on 6 rats, and the robustness, stability, and tracking accu- has good spatial accuracy, which can stimulate a single neu- racy of this method have been proved [76]. Roshani proposed ron without range effect; in addition, the stimulus signal does Normalized TWitch force Propagation time: 10 ms Propagation time: 20 ms Propagation time: 2 ms EES frequency (Hz) EES frequency (Hz) Normalized TWitch force EES frequency (Hz) Antidronic collision Antidronic collision probability probability Antidronic collision probability 6 Applied Bionics and Biomechanics showed under the radiation of 0.53-1.23 J/cm , 63% of the Interface for nerves appeared activation of human dorsal root, and ther- ISMS implant Reflective joint ISMS mal damage was found at 1.09 J/cm ; meanwhile, the safety markers implant ratio of 2 : 1 was determined. These findings proved the suc- Reconstructed cess of INS as a new way to activate human nerves in vivo and stick figures provided necessary safety data, which provided necessary Accelerometers impetus for the clinical application and diagnosis. The equipment used in the experiment is the high-power high-frequency clinical system light box [83]. The high- energy laser from the optical fiber adjusted its output fre- quency and situation by the pulse generator and sterilized handheld bracket. Stationary platform Force plates Now, it has been confirmed in many ins researches that for forelimbs in order to reduce the change of spot size, a fixed-point light Figure 5: Bilateral walking experiment of activation by ISMS. source or a collimated beam is usually used. Fried et al. also proved that compared with the standard Gaussian beam, not affect the detected response signal because of the differ- the collimated beam reduces the stimulation threshold and ence between the nature of stimulation (light signal) and improves the reliability of the system. The advantages of response (electrical signal). It is also examined that infrared the device also include that the setting of the main switch radiation increases the frequency of spontaneous synaptic and the pulse generator increases the safety and controllabil- events and the response size is proportional to the output ity, and the external micromanipulator and the handheld of the excitation light [79]. bracket make it flexibly used in different positions. However, Many scholars have done extensive research on the prin- the device also has shortcomings. The handheld probe used ciple of light stimulation. Generally speaking, the interaction in this study was determined as a limitation, because it is dif- of light and biology includes light pressure effect, photo- ficult to keep the distance between the probe and the tissue at chemistry effect, photomechanical effect, and photomagnetic 1.5 mm, which may lead to uncontrollable changes in radia- effect. Richter’s and Lenarz’s experiments exclude the photo- tion exposure. It should be more effective if a device that chemical effect, because the laser used is a low-energy infra- can accurately stabilize the probe distance was added. red laser [80], and the infrared photon energy is too low As is shown in Figure 6, Wolf provided a position- (<0.1 eV), and there is not enough energy to produce photo- sensitive NIR reflex measurement device and method for chemical reaction directly. Wells et al. of Vanderbilt Univer- automatic regulation of spinal cord stimulation. The system sity exclude photomagnetic effect by using a 750 nm laser to consists of an electrode assembly and an integrated optical stimulate peripheral nerves in mice. They found that the laser fiber sensor for sensing spinal cord position. The integrated triggered nerve impulses may be related to the light absorp- optical fiber sensor includes a set of optical elements for emit- tion of tissues, but not to the electric field effect [80]. Then, ting light from a set of infrared transmitters and collecting Vanderbilt University researchers propose that photome- the reflected light into a set of infrared photodetectors to chanical effect cannot trigger nerve impulse by observing determine a set of measured light intensity. With the change whether the duration of the laser pulse has an impact on of spinal cord position, the incident angle of light from infra- the stimulation threshold [81]. Wells’ team used a noncon- red transmitter and the measured light intensity also change. tact infrared thermometer to measure the surface tempera- Then, the device adjusts the pulse characteristics of the elec- ture of peripheral nerve tissue under the action of laser and trode in real time [84]. found that it could cause nerve excitation when the tempera- In addition to the experiments in human body, some ture increased to 6-10 C. By analyzing the distribution of light stimulation devices are also used in animals such as rats. Entwisle et al. have detected the membrane and synaptic laser energy in nerve tissue, it can be concluded that about 64% of light energy is concentrated in axon, causing the tem- responses of solitary tract neurons recorded in acute sections of rats. They used a 1890 nm compact waveguide laser to perature to rise about 3.8-6.4 C. The temperature gradient can activate the cell transmembrane ion channel and trigger stimulate neurons and send light through a single-mode fiber neural action potential [82]. to a small target the size of a single cell and found that the response was proportional to the laser output [79]. A Therefore, based on the photothermal effect, some light stimulation devices have been developed and used in prelim- thulium-doped glass waveguide laser is used in the experi- inary experiments. In the infrared stimulation of human spi- ment. The laser is customized by internal facilities. The out- nal nerve root completed by Cayce and Wells of Vanderbilt put light of 1.89 μm is coupled to the single-mode fiber University, a high-power and high-frequency clinical system with 14 μm mode field diameter, and the nominal power out- put of 7.8 mw is measured at the fiber end. The fiber was light box was used to verify the safety and effectiveness of INS in human body. In 7 subjects, INS was used to stimulate two placed in the micromanipulator 45 meters away from the and three parts of each nerve, and electromyogram records water plane and placed about 100 μm away from the target were obtained during the whole stimulation process. At the cell. The external digital trigger was used to control the power same time, histological examination was carried out to deter- output and pulse length of the laser. In a complete one- second pulse, the pulse energy calculated on the cell surface mine the thermal damage threshold of INS. The result Applied Bionics and Biomechanics 7 exhaled from the lungs as hard and fast as possible when measured from the total vital capacity, while flow of peak 0° cough (CPF) is the maximum rate of air exhaled from the lungs when coughing. The maximum expiratory pressure 90° (MEP) refers to the maximum pressure generated in the mouth to resist the blocked airway when exhaling from the total lung capacity. Pressure of gastric (PGA) and pressure of esophageal (PES) can be used to measure the pressure of pleura when expiratory muscles contract. These indexes can PD PD indicate the strength of expiratory muscles.VC, FVC, and 180° FEV1 can be used to evaluate the strength of vital capacity. These evaluation indexes are characterized by the need for active control of breathing, as well as subjects’ prediction Figure 6: Construction and reflex measurement of spinal cord stimulation device. and motivation, noninvasive. Spirometry has been used in all five studies. (2) Plethysmography: parameters mentioned are respiratory rate (F), tidal volume (VT), and minute ven- is 261 J/cm , and the spot size calculated after the light diver- gence is 42:8 μm×26:7 μm, which shows that the device with tilation volume (VE). Only the fourth study clearly indicated this structure can be used for a specific single cell. This device that tidal volume testing was carried out. (3) Electromyogra- phy: electromyography reflects muscle activity, which is can be improved and applied in clinic. characterized by the fact that long-term electrode placement can be used for repeated measurement. Electrodes are often 4. Discussion placed on the skin surface, which reduces the accuracy of 4.1. Experimental Comparison of Different Stimulation recording. EMG electrodes were applied to the left lateral oblique muscle in the fourth study. (4) Diaphragm com- Methods. I selected 5 cases about the recovery of diaphragm function by stimulation, involving 66 people in total, most pound motor action potential (CMAP): the electrode is placed on the skin, and the nerve function is indirectly mea- of them were in C4-C6 spinal cord segment, and a few of them had T4-T6 injury. The age of these patients ranged sured by evaluating the nerve integrity. None of the five stud- from 16 to 67, most of them were men, and some of them ies used this evaluation method. By comparing the five experiments, it can be found that had smoking history. The causes include gunshot wounds, car accidents, and falls. The participants are shown in the PEF-TLC of the first group is 5.8-8.8 L/s, while the mag- Table 1. netic stimulation is only 4.3 L/s. When referring to MEP- The first, third, fourth, and fifth experiments were electric TLC, the first group is 120-150 cm H O, while the average stimulation; the second was magnetic stimulation; the first of the second group is 55.3 cm H O. When referring to and second were spinal nerve stimulation; the third, fourth, PEF-FRC and MEP-FRC, it can also be seen that although and fifth were muscle stimulation. Different stimulation the magnetic stimulation treatment has made progress com- methods and locations will result in different stimulation pared with nonstimulation, it is far less than that of electric parameters and results. The duration of stimulation in spinal stimulation. Direct stimulation of spinal cord was better than nerve electrical stimulation is only 5-10 minutes, while the muscle stimulation. The PEF-TLC of the first study (single rest is no less than 20 minutes. The stimulator of spinal nerve stimulus point: 5.8-8.6 L/s; double stimulation points: 7.8- is placed between T9 and L1, while others are placed in mus- 8.8 L/s) was greater than that of the fourth study (increased cle. The maximum stimulation frequency of these experi- from 5:1±0:6 L/s to 6:1±0:5 L/s) and the fifth study ments is no more than 50 Hz. The pulse width of spinal (4.24 L/s), which were muscle stimulation studies. The results cord stimulation experiment is lower than that of muscle of the last study and the second study were similar in FVC stimulation. Authors in the first study use voltage to measure (2:5± 0:1 L in the second study and 2.51 L in the fifth study), the stimulus intensity, while the fifth study used the current. FEV1 (2:0±0:1 L in the second study and 2.3 L/s in the fifth In the selection of stimulator, electrodes were used in spinal study), and PEF-TLC (4:3±0:5 L/s in the second study and cord electrical stimulation, while circular magnetic coil 4.24 L/s in the fifth study), which indicated that the effect of (outer diameter 20 cm) was used in spinal cord magnetic magnetic stimulation of spinal cord was less than that of elec- stimulation. Two pairs of surface electrodes were selected trical stimulation of spinal cord, but similar to that of electri- for muscle electrical stimulation. In the fourth study, the cal stimulation of muscle. In addition, in terms of anterior electrode was placed in the rectus abdominis muscle complications, 5 subjects in the first study had mild edema under costal margin and above pubic symphysis, and the in the test site, while in the fifth study, one case (7.7%) in ventrolateral electrode was at the intersection of the inferior the treatment group had pulmonary complication. It is diffi- margin of costal margin and axillary midline, above the ante- cult to see the effect of different stimulation situations on rior superior iliac spine. complications. Generally speaking, there are many indexes to evaluate respiratory and cough function. The indexes used in the five 4.2. Auxiliary Treatments of Functional Reconstruction. cited experiments can be classified as follows. (1) Spirometry: Many scholars added training as auxiliary treatment in the peak expiratory flow (PEF) is the maximum rate of air experiment of functional reconstruction of spinal cord 8 Applied Bionics and Biomechanics Table 1: Characteristics of participants of included studies. Aetiology(SCI Num Author Country or region Number of participants Mean of age Male (%) Injury time level) 1 Anthony F. DiMarco [15] USA SCI(C3-C6) 9 41 89 13.11 years 2 Vernon W. Lin [51] USA C4-C7 T5 8 51.25 100 17.75 years 3 A Zupan [45], Slovenia C4-C7 13 26.9 84.62 7 months 4 Franco Laghi [33] USA C5-C7 T4-T6 10 47.3 Unknown 10.66 years 5 Pao-Tsai Cheng [46] Taiwan C4-C7 26 34.7 84.62 In 3 months injury. Boswell explored the feasibility of respiratory muscle 5. Conclusion training (RMT) as an improvement of lung function in According to the results of our study, we may conclude that, patients with cervical spinal cord injury [85]. Tamplin although the evidence is presently limited, spinal nerve stim- explored the effect of RMT on pulmonary function in ulation and muscle stimulation are very effective in the recov- patients with quadriplegia [86]. Paleville combined 80 exer- ery of respiratory function impairment caused by cervical cises with electrical stimulation of L1-S1 spinal cord. It is spinal cord injury. Both magnetic stimulation and electrical concluded that the combination of task-specific training stimulation can improve the airflow rate and airway pressure and epidural stimulation may improve the vascular fitness trend to a normal state, but the effect of magnetic stimulation and body composition of patients with cervical or upper tho- is not as good as electrical stimulation, while the effect of racic spinal cord injury [87]. Field evaluated the effects of muscle stimulation is not as good as spinal nerve stimulation. body weight support (BWS), FES, and treadmill training on In addition, the treatment device has its own characteristics ground walking speed, treadmill walking speed, and distance, according to its components and function content. and concluded that in the training process, all indexes were At the same time, the research means and research tools significantly improved [88]. Gee proved the effect of RMT of functional light stimulation are also used for reference. on strengthening respiratory muscle strength, reducing exer- Light stimulation is gradually applied to clinical medicine cise lung capacity, and increasing exercise ability through with its strong advantages. In the experiment of functional training disabled athletes with cervical spinal cord injury reconstruction of spinal cord injury, training and improved [89]. By analyzing the vital capacity of patients with SCI, Tif- surgical methods can be used as adjuvant treatment. It can tik compared the effect of combination of exercise training be predicted that in the future, the research on spinal cord and simple rehabilitation only program on the lung function electrical stimulation and nerve light stimulation after cervi- of SCI patients and emphasized the importance of exercise cal spinal cord injury is promising and has a positive effect on training [90]. Stenson evaluated the effect of expiratory mus- the treatment of respiratory injury caused by cervical spinal cle training on pulmonary function in patients with spinal cord injury. cord injury and got the conclusion that resistance training group has a good pulmonary function effect [91]. Liaw did Conflicts of Interest similar experiments and obtained that RMT can improve respiratory function, respiratory resistance, and dyspnea of The authors declare that they have no conflicts of interest. patients with cervical spinal cord injury [92]. Roy pointed out that the plasticity of repetitive training can expand the Acknowledgments rehabilitation methods [93]. In addition to the auxiliary effect of training, the The research is funded by the China Postdoctoral Science improvement of surgical methods can also greatly improve Foundation (2019M660392). the cure rate. Nandra extended phrenic pacing treatment to paraplegia patients with high cervical spinal cord injury References between C3 and C5. Four patients with high cervical spinal cord injury were selected as the study object. Each patient [1] C. H. Ho, R. J. Triolo, A. L. Elias et al., “Functional Electrical had phrenic nerve deficiency and received intercostal phrenic Stimulation and Spinal Cord Injury,” Physical Medicine and nerve transplantation and phrenic nerve pacemaker implan- Rehabilitation Clinics of North America, vol. 25, no. 3, tation. Then, it is found that patient can breathe well with pp. 631–654, 2014. diaphragm [94]. Yang suspended the posterior rib on the [2] A. Jackson, “Spinal-cord injury: neural interfaces take another lower angle of the scapula with titanium cable and suspended step forward,” Nature, vol. 539, no. 7628, pp. 177-178, 2016. the muscle and myofascial tissue in the area under the scap- [3] M. Nygren-Bonnier, L.-L. Normi, B. Klefbeck, and G. Biguet, ula. This method partially restored thoracic respiration in “Experiences of decreased lung function in people with cervi- patients with high CSCI, thus improving respiratory, cough, cal spinal cord injury,” Disability and Rehabilitation, vol. 33, and expectoration functions [13]. Tedde implanted laparo- no. 6, pp. 530–536, 2010. scopic diaphragm pacemaker in 5 cases of high cervical trau- [4] D. G. L. Terson de Paleville, W. B. McKay, R. J. Folz, and A. V. matic spinal cord injury [95]. Ovechkin, “Respiratory Motor Control Disrupted by Spinal Applied Bionics and Biomechanics 9 and the European Section of the Cervical Spine Research Soci- Cord Injury: Mechanisms, Evaluation, and Restoration,” Translational Stroke Research, vol. 2, no. 4, pp. 463–473, 2011. ety, vol. 17, no. 9, pp. 1256–1269, 2008. [5] L. van Silfhout, A. E. J. Peters, D. J. Berlowitz, R. Schembri, [19] P. H. Gorman, “An update on functional electrical stimulation D. Thijssen, and M. Graco, “Long-term change in respiratory after spinal cord Injury,” Neurorehabilitation and Neural function following spinal cord injury,” Spinal Cord, vol. 54, Repair, vol. 14, no. 4, pp. 251–263, 2000. no. 9, pp. 714–719, 2016. [20] M. A. Lane, K. Z. Lee, D. D. Fuller, and P. J. Reier, “Spinal cir- [6] P. M. Warren, B. I. Awad, and W. J. Alilain, “Drawing breath cuitry and respiratory recovery following spinal cord injury,” without the command of effectors: the control of respiration Respiratory Physiology & Neurobiology, vol. 169, no. 2, following spinal cord injury,” Respiratory Physiology & Neuro- pp. 123–132, 2009. biology, vol. 203, pp. 98–108, 2014. [21] C. C. Horn, J. L. Ardell, and L. E. Fisher, “Electroceutical tar- [7] J. T. Hachmann, J. S. Calvert, P. J. Grahn, D. I. Drubach, K. H. geting of the autonomic nervous System,” Physiology, vol. 34, no. 2, pp. 150–162, 2019. Lee, and I. A. Lavrov, “Review of epidural spinal cord stimula- tion for augmenting cough after spinal cord injury,” Frontiers [22] G. Courtine and M. V. Sofroniew, “Spinal cord repair: in Human Neuroscience, vol. 11, 2017. advances in biology and technology,” Nature Medicine, [8] J. H. Park, S.-W. Kang, S. C. Lee, W. A. Choi, and D. H. Kim, vol. 25, no. 6, pp. 898–908, 2019. “How Respiratory Muscle Strength Correlates with Cough [23] A. Alshekhlee, R. P. Onders, T. U. Syed, M. Elmo, and Capacity in Patients with Respiratory Muscle Weakness,” Yon- B. Katirji, “Phrenic nerve conduction studies in spinal cord sei Medical Journal, vol. 51, no. 3, pp. 392–397, 2010. injury: applications for diaphragmatic pacing,” Muscle & Nerve, vol. 38, no. 6, pp. 1546–1552, 2008. [9] S. W. Kang, J. C. Shin, C. I. Park, J. H. Moon, D. W. Rha, and D.-h. Cho, “Relationship between inspiratory muscle strength [24] E. P. Sieg, R. A. Payne, S. Hazard, and E. Rizk, “Evaluating the and cough capacity in cervical spinal cord injured patients,” evidence: is phrenic nerve stimulation a safe and effective tool Spinal Cord, vol. 44, no. 4, pp. 242–248, 2006. for decreasing ventilator dependence in patients with high cer- vical spinal cord injuries and central hypoventilation?,” Childs [10] C. R. West, I. G. Campbell, R. E. Shave, and L. M. Romer, Nervous System, vol. 32, no. 6, pp. 1033–1038, 2016. “Effects of abdominal binding on cardiorespiratory function in cervical spinal cord injury,” Respiratory Physiology & Neu- [25] A. F. DiMarco, R. P. Onders, A. Ignagni, K. E. Kowalski, and robiology, vol. 180, no. 2-3, pp. 275–282, 2012. J. T. Mortimer, “Phrenic nerve pacing via intramuscular dia- phragm electrodes in tetraplegic subjects,” Chest, vol. 127, [11] G. J. Schilero, A. M. Spungen, W. A. Bauman, M. Radulovic, no. 2, pp. 671–678, 2005. and M. Lesser, “Pulmonary function and spinal cord injury,” Respiratory Physiology & Neurobiology, vol. 166, no. 3, [26] A. F. Dimarco, “Restoration of respiratory muscle function fol- pp. 129–141, 2009. lowing spinal cord injury: review of electrical and magnetic stimulation techniques,” Respiratory Physiology and Neurobi- [12] F. Urdaneta, A. J. Layon, B. Guiot, E. Mendel, and R. R. Kirby, ology, vol. 147, no. 2-3, pp. 273–287, 2005. “Respiratory complications in patients with traumatic cervical spine injuries: case report and review of the literature,” Journal [27] A. F. DiMarco, R. P. Onders, A. Ignagni, and K. E. Kowalski, of Clinical Anesthesia, vol. 15, no. 5, pp. 398–405, 2003. “Inspiratory muscle pacing in spinal cord injury: case report and clinical commentary,” The Journal of Spinal Cord Medi- [13] M. L. Yang, J. J. Li, F. Gao et al., “A preliminary evaluation of cine, vol. 29, no. 2, pp. 95–108, 2016. the surgery to reconstruct thoracic breathing in patients with high cervical spinal cord injury,” Spinal Cord, vol. 52, no. 7, [28] G. Cosendai, C. de Balthasar, A. R. Ignagni et al., “A prelimi- pp. 564–569, 2014. nary feasibility study of different implantable pulse generators technologies for diaphragm pacing system,” Neuromodulation, [14] R. Brown, A. F. DiMarco, J. D. Hoit, and E. Garshick, “Respi- vol. 8, no. 3, pp. 203–211, 2005. ratory dysfunction and management in spinal cord injury,” Respiratory Care, vol. 51, pp. 853–868, 2006. [29] M. L. Tedde, R. P. Onders, M. J. Teixeira et al., “Electric venti- lation: indications for and technical aspects of diaphragm pac- [15] A. F. DiMarco, K. E. Kowalski, R. T. Geertman, and D. R. Hro- ing stimulation surgical implantation[J],” Jornal brasileiro de myak, “Lower thoracic spinal cord stimulation to restore pneumologia: publicacao oficial da Sociedade Brasileira de cough in patients with spinal cord injury: results of a National Pneumologia e Tisilogia, vol. 38, no. 5, pp. 566–572, 2012. Institutes of Health–sponsored clinical trial. Part I: methodol- ogy and effectiveness of expiratory muscle activation,” [30] B. Garara, A. Wood, H. J. Marcus, K. Tsang, M. H. Wilson, and Archives of Physical Medicine & Rehabilitation, vol. 90, no. 5, M. Khan, “Intramuscular diaphragmatic stimulation for pp. 717–725, 2009. patients with traumatic high cervical injuries and ventilator dependent respiratory failure: a systematic review of safety [16] T. Liebscher, A. Niedeggen, B. Estel, and R. O. Seidl, “Airway and effectiveness,” Injury, vol. 47, no. 3, pp. 539–544, 2016. complications in traumatic lower cervical spinal cord injury: a retrospective study,” The Journal of Spinal Cord Medicine, [31] T. R. Hazwani, B. Alotaibi, W. Alqahtani, A. Awadalla, and vol. 38, no. 5, pp. 607–614, 2015. A. Al Shehri, “Pediatric diaphragmatic pacing,” Pediatric reports, vol. 11, no. 1, 2019. [17] E. C. Zakrasek, J. L. Nielson, J. J. Kosarchuk, J. D. Crew, A. R. Ferguson, and S. L. McKenna, “Pulmonary outcomes follow- [32] J. M. Dean, R. P. Onders, and M. J. Elmo, “Diaphragm pacers in ing specialized respiratory management for acute cervical spi- pediatric patients with cervical spinal cord injury: a review and nal cord injury: a retrospective analysis,” Spinal Cord, vol. 55, implications for inpatient rehabilitation,” Current Physical Med- no. 6, pp. 559–565, 2017. icine and Rehabilitation Reports, vol. 6, no. 4, pp. 257–263, 2018. [18] S. Hamid and R. Hayek, “Role of electrical stimulation for [33] F. Laghi, V. Maddipati, T. Schnell, W. E. Langbein, and M. J. rehabilitation and regeneration after spinal cord injury: an Tobin, “Determinants of cough effectiveness in patients with overview,” European spine journal : official publication of the respiratory muscle weakness,” Respiratory Physiology & Neu- European Spine Society, the European Spinal Deformity Society, robiology, vol. 240, pp. 17–25, 2017. 10 Applied Bionics and Biomechanics [48] S. Mangold, T. Keller, A. Curt, and V. Dietz, “Transcutaneous [34] F. S. Macedo, A. F. Rocha, C. J. Miosso, and S. R. M. Mateus, “Use of electromyographic signals for characterization of vol- functional electrical stimulation for grasping in subjects with untary coughing in humans with and without spinal cord cervical spinal cord injury,” Spinal Cord, vol. 43, no. 1, pp. 1– injury-A systematic review,” Physiotherapy Research Interna- 13, 2005. tional, vol. 24, no. 2, p. e1761, 2019. [49] M. R. Popovic, T. A. Thrasher, M. E. Adams, V. Takes, [35] E. J. McCaughey, R. J. Borotkanics, H. Gollee, R. J. Folz, and V. Zivanovic, and M. I. Tonack, “Functional electrical therapy: A. J. McLachlan, “Abdominal functional electrical stimulation retraining grasping in spinal cord injury,” Spinal Cord, vol. 44, to improve respiratory function after spinal cord injury: a sys- no. 3, pp. 143–151, 2006. tematic review and meta-analysis,” Spinal Cord, vol. 54, no. 9, [50] K. T. Ragnarsson, “Functional electrical stimulation after spi- pp. 628–639, 2016. nal cord injury: current use, therapeutic effects and future [36] J. E. Butler, J. Lim, R. B. Gorman et al., “Posterolateral surface directions,” Spinal Cord, vol. 46, no. 4, pp. 255–274, 2008. electrical stimulation of abdominal expiratory muscles to [51] V. W. Lin, I. N. Hsiao, E. Zhu, and I. Perkash, “Functional enhance cough in spinal cord injury,” Neurorehabilitation magnetic stimulation for conditioning of expiratory muscles and Neural Repair, vol. 25, no. 2, pp. 158–167, 2011. in patients with spinal cord injury,” Archives of Physical Med- [37] H. Gollee, K. J. Hunt, D. B. Allan, M. H. Fraser, and A. N. icine & Rehabilitation, vol. 82, no. 2, pp. 162–166, 2001. McLean, “A control system for automatic electrical stimula- [52] S. Fawaz, F. Kamel, A. El Yasaky et al., “The therapeutic appli- tion of abdominal muscles to assist respiratory function in tet- cation of functional electrical stimulation and transcranial raplegia,” Medical Engineering & Physics, vol. 29, no. 7, magnetic stimulation in rehabilitation of the hand function pp. 799–807, 2007. in incomplete cervical spinal cord injury,” Egyptian Rheuma- [38] R. J. Jaeger, R. M. Turba, G. M. Yarkony, and E. J. Roth, tology and Rehabilitation, vol. 46, no. 1, p. 21, 2019. “Cough in spinal cord injured patients: comparison of three [53] J. S. Calvert, P. J. Grahn, K. D. Zhao, and K. H. Lee, “Emer- methods to produce cough,” Archives of Physical Medicine gence of epidural electrical stimulation to facilitate sensorimo- and Rehabilitation, vol. 74, no. 12, pp. 1358–1361, 1993. tor network functionality after spinal cord injury,” [39] W. E. Langbein, C. Maloney, F. Kandare, U. Stanic, Neuromodulation: Technology at the Neural Interface, vol. 22, B. Nemchausky, and R. J. Jaeger, “Pulmonary function testing no. 3, pp. 244–252, 2019. in spinal cord injury: effects of abdominal muscle stimulation,” [54] M. D. Craggs, “Cortical control of motor prostheses: using the The Journal of Rehabilitation Research and Development, cord-transected baboon as the primate model for human para- vol. 38, no. 5, pp. 591–597, 2001. plegia,” Advances in Neurology, vol. 10, no. 10, pp. 91–101, [40] S. H. Linder, “Functional electrical stimulation to enhance cough in quadriplegia,” Chest, vol. 103, no. 1, pp. 166–169, [55] L. R. Hochberg, M. D. Serruya, G. M. Friehs et al., “Neuronal ensemble control of prosthetic devices by a human with tetra- [41] J. Sorli, F. Kandare, R. J. Jaeger, and U. Stanic, “Ventilatory plegia,” Nature, vol. 442, no. 7099, pp. 164–171, 2006. assistance using electrical stimulation of abdominal muscles,” [56] L. R. Hochberg, D. Bacher, B. Jarosiewicz et al., “Reach and IEEE Transactions on Rehabilitation Engineering, vol. 4, grasp by people with tetraplegia using a neurally controlled no. 1, pp. 1–6, 1996. robotic arm,” Nature, vol. 485, no. 7398, pp. 372–375, 2012. [42] U. Stanic, F. Kandare, R. Jaeger, and J. Sorli, “Functional elec- [57] J. B. Zimmermann and A. Jackson, “Closed-loop control of trical stimulation of abdominal muscles to augment tidal vol- spinal cord stimulation to restore hand function after paraly- ume in spinal cord injury,” IEEE Transactions on sis,” Frontiers in Neuroscience, vol. 8, 2014. Rehabilitation Engineering, vol. 8, no. 1, pp. 30–34, 2000. [58] C. A. Angeli, V. R. Edgerton, Y. P. Gerasimenko, and S. J. Har- [43] A. J. McLachlan, A. N. McLean, D. B. Allan, and H. Gollee, kema, “Altering spinal cord excitability enables voluntary “Changes in pulmonary function measures following a passive movements after chronic complete paralysis in humans,” abdominal functional electrical stimulation training program,” Brain, vol. 137, no. 5, pp. 1394–1409, 2014. The Journal of Spinal Cord Medicine, vol. 36, no. 2, pp. 97–103, [59] M. Capogrosso, T. Milekovic, D. Borton et al., “A brain–spine interface alleviating gait deficits after spinal cord injury in pri- [44] R. A. McBain, C. L. Boswell-Ruys, B. B. Lee, S. C. Gandevia, mates,” Nature, vol. 539, no. 7628, pp. 284–288, 2016. and J. E. Butler, “Electrical Stimulation of Abdominal Muscles [60] A. F. DiMarco, K. E. Kowalski, R. T. Geertman, and D. R. Hro- to Produce Cough in Spinal Cord Injury,” Neurorehabilitation myak, “Spinal cord stimulation: a new method to produce an and Neural Repair, vol. 29, no. 4, pp. 362–369, 2014. effective cough in patients with spinal cord injury,” American [45] A. Zupan, R. Šavrin, T. Erjavec et al., “Effects of respiratory Journal of Respiratory and Critical Care Medicine, vol. 173, muscle training and electrical stimulation of abdominal mus- no. 12, pp. 1386–1389, 2006. cles on respiratory capabilities in tetraplegic patients,” Spinal [61] A. F. DiMarco, R. T. Geertman, K. Tabbaa, R. R. Polito, and Cord, vol. 35, no. 8, pp. 540–545, 1997. K. E. Kowalski, “Case report: Minimally invasive method to [46] P. T. Cheng, C. L. Chen, C. M. Wang, and C. Y. Chung, “Effect activate the expiratory muscles to restore cough,” The journal of neuromuscular electrical stimulation on cough capacity and of spinal cord medicine, vol. 41, no. 5, pp. 562–566, 2018. pulmonary function in patients with acute cervical cord injury,” Journal of Rehabilitation Medicine, vol. 38, no. 1, [62] A. V. Minyaeva, S. A. Moiseev, A. M. Pukhov, A. A. Savokhin, Y. P. Gerasimenko, and T. R. Moshonkina, “Response of exter- pp. 32–36, 2006. nal inspiration to the movements induced by transcutaneous [47] M. J. Mulcahey, R. R. Betz, B. T. Smith, A. A. Weiss, and S. E. spinal cord stimulation,” Human Physiology, vol. 43, no. 5, Davis, “Implanted functional electrical stimulation hand sys- pp. 524–531, 2017. tem in adolescents with spinal injuries: an evaluation,” Archives of Physical Medicine and Rehabilitation, vol. 78, [63] E. Formento, K. Minassian, F. Wagner et al., “Electrical spinal no. 6, pp. 597–607, 1997. cord stimulation must preserve proprioception to enable Applied Bionics and Biomechanics 11 [77] A. Roshani and A. Erfanian, “Fuzzy logic control of ankle locomotion in humans with spinal cord injury,” Nature Neuro- science, vol. 21, no. 12, pp. 1728–1741, 2018. movement using multi-electrode intraspinal microstimula- tion,” in 2013 35th Annual International Conference of the [64] S. Harkema, Y. Gerasimenko, J. Hodes et al., “Effect of epidural IEEE Engineering in Medicine and Biology Society (EMBC), stimulation of the lumbosacral spinal cord on voluntary move- Osaka, Japan, 2013. ment, standing, and assisted stepping after motor complete paraplegia: a case study,” Lancet, vol. 377, no. 9781, [78] J. Wells, C. Kao, K. Mariappan et al., “Optical stimulation of pp. 1938–1947, 2011. neural tissue in vivo,” Optics Letters, vol. 30, no. 5, pp. 504– 506, 2005. [65] F. B. Wagner, J.-B. Mignardot, C. G. Le Goff-Mignardot et al., “Targeted neurotechnology restores walking in humans with [79] B. Entwisle, S. McMullan, P. Bokiniec, S. Gross, R. Chung, and spinal cord injury,” Nature, vol. 563, no. 7729, pp. 65–71, 2018. M. Withford, “In vitro neuronal depolarization and increased [66] P. D. Thompson, J. P. R. Dick, P. Asselman et al., “Examina- synaptic activity induced by infrared neural stimulation,” Bio- medical Optics Express, vol. 7, no. 9, pp. 3211–3219, 2016. tion of motor function in lesions of the spinal cord by stimula- tion of the motor cortex,” Annals of neurology, vol. 21, no. 4, [80] J. Wells, C. Kao, P. Konrad, A. Mahadevan-Jansen, and E. D. pp. 389–396, 1987. Jansen, “Biophysical mechanisms responsible for pulsed low- [67] C. T. Moritz, T. H. Lucas, S. I. Perlmutter, and E. E. Fetz, level laser excitation of neural tissue,” in Optical Interactions “Forelimb movements and muscle responses evoked by micro- with Tissue and Cells XVII, vol. 6084, pp. 227–233, 2006. stimulation of cervical spinal cord in sedated monkeys,” Jour- [81] A. Fishman, P. Winkler, J. Mierzwinski et al., “Stimulation of nal of Neurophysiology, vol. 97, no. 1, pp. 110–120, 2007. the human auditory nerve with optical radiation,” in Photons [68] V. K. Mushahwar, Y. Aoyagi, R. B. Stein, and A. Prochazka, and Neurons, vol. 7180no. 2, pp. 149–160, 2009. “Movements generated by intraspinal microstimulation in [82] S. M. Rajguru, A. I. Matic, A. M. Robinson et al., “Optical the intermediate gray matter of the anesthetized, decerebrate, cochlear implants: evaluation of surgical approach and laser and spinal cat,” Canadian Journal of Physiology and Pharma- parameters in cats,” Hearing Research, vol. 269, no. 1-2, cology, vol. 82, no. 8-9, pp. 702–714, 2004. pp. 102–111, 2010. [69] B. J. Holinski, K. A. Mazurek, D. G. Everaert, R. B. Stein, and [83] S. Tozburun, G. A. Lagoda, A. L. Burnett, and N. M. Fried, V. K. Mushahwar, “Restoring Stepping After Spinal Cord “Infrared laser nerve stimulation as a potential diagnostic Injury Using Intraspinal Microstimulation and Novel Control method for intra-operative identification and preservation of Strategies,” in 2011 Annual International Conference of the the prostate cavernous nerves,” IEEE Journal of Selected Topics IEEE Engineering in Medicine and Biology Society, Boston, in Quantum Electronics, vol. 20, no. 2, pp. 299–306, 2014. MA, USA, 2011. [84] E. W. Wolf, Apparatus and Method Using near Infrared Reflec- [70] J. A. Bamford, C. T. Putman, and V. K. Mushahwar, “Muscle tometry to Reduce the Effect of Positional Changes during Spi- plasticity in rat following spinal transection and chronic nal Cord Stimulation, Patent and Trademark Office, Intraspinal microstimulation,” IEEE transactions on neural Washington, DC, 2014. systems and rehabilitation engineering: a publication of the [85] C. L. Boswell-Ruys, C. R. H. Lewis, S. C. Gandevia, and J. E. IEEE Engineering in Medicine and Biology Society, vol. 19, Butler, “Respiratory muscle training may improve respiratory no. 1, pp. 79–83, 2011. function and obstructive sleep apnoea in people with cervical [71] L. M. Mercier, E. J. Gonzalez-Rothi, K. A. Streeter et al., spinal cord injury,” Spinal Cord Series And Cases, vol. 1, “Intraspinal microstimulation and diaphragm activation after no. 1, 2015. cervical spinal cord injury,” Journal of Neurophysiology, [86] J. Tamplin and D. J. Berlowitz, “A systematic review and meta- vol. 117, no. 2, pp. 767–776, 2017. analysis of the effects of respiratory muscle training on pulmo- [72] J. A. Bamford and V. K. Mushahwar, “Intraspinal microstimu- nary function in tetraplegia,” Spinal Cord, vol. 52, no. 3, lation for the recovery of function following spinal cord pp. 175–180, 2014. injury,” Progress in Brain Research, vol. 194, no. 1, pp. 227– [87] D. G. L. Terson de Paleville, S. J. Harkema, and C. A. Angeli, 239, 2011. “Epidural stimulation with locomotor training improves body [73] S. Shahdoost, S. Frost, C. Dunham et al., “Cortical control of composition in individuals with cervical or upper thoracic motor intraspinal microstimulation: toward a new approach for res- complete spinal cord injury: A series of case studies,” The Journal toration of function after spinal cord injury,” in 2015 37th of Spinal Cord Medicine,vol.42, no.1,pp.32–38, 2019. Annual International Conference of the IEEE Engineering in [88] E. C. Field-Fote, “Combined use of body weight support, func- Medicine and Biology Society (EMBC), Milan, Italy, 2015. tional electric stimulation, and treadmill training to improve [74] S. Shahdoost, S. Frost, D. Guggenmos et al., “A Miniaturized walking ability in individuals with chronic incomplete spinal Brain-Machine-Spinal Cord Interface (BMSI) for Closed- cord injury,” Archives of Physical Medicine and Rehabilitation, Loop Intraspinal Microstimulation,” in 2016 IEEE Biomedical vol. 82, no. 6, pp. 818–824, 2001. Circuits and Systems Conference (BioCAS), Shanghai, China, [89] C. M. Gee, A. M. Williams, A. W. Sheel, N. D. Eves, and C. R. West, “Respiratory muscle training in athletes with cervical [75] P. R. Troyk, V. K. Mushahwar, R. B. Stein et al., “An implant- spinal cord injury: effects on cardiopulmonary function and able neural stimulator for intraspinal microstimulation,” in exercise capacity,” The Journal of Physiology., vol. 597, 2012 Annual International Conference of the IEEE Engineering no. 14, pp. 3673–3685, 2019. in Medicine and Biology Society, pp. 900–903, San Diego, CA, [90] T. Tiftik, N. K. O. Gökkaya, F. Ü. Malas et al., “Does locomotor USA, 2012. training improve pulmonary function in patients with spinal [76] A. Asadi and A. Erfanian, “Adaptive neuro-fuzzy sliding mode cord injury?,” Spinal Cord, vol. 53, no. 6, pp. 467–470, 2015. control of multi-joint movement using intraspinal microsti- mulation,” IEEE Transactions on Neural Systems and Rehabil- [91] E. J. Roth, K. W. Stenson, S. Powley et al., “Expiratory Muscle itation Engineering, vol. 20, no. 4, pp. 499–509, 2012. Training in Spinal Cord Injury: A Randomized Controlled 12 Applied Bionics and Biomechanics Trial,” Archives of Physical Medicine & Rehabilitation, vol. 91, no. 6, pp. 857–861, 2010. [92] M. Y. Liaw, M. C. Lin, P. T. Cheng, M. K. A. Wong, and F. T. Tang, “Resistive inspiratory muscle training: its effectiveness in patients with acute complete cervical cord injury,” Archives of Physical Medicine and Rehabilitation, vol. 81, no. 6, pp. 752– 756, 2000. [93] R. R. Roy, S. J. Harkema, and V. R. Edgerton, “Basic concepts of activity-based interventions for improved recovery of motor function after spinal cord injury,” Archives of Physical Medi- cine and Rehabilitation, vol. 93, no. 9, pp. 1487–1497, 2012. [94] K. S. Nandra, M. Harari, T. P. Price, P. J. Greaney, and M. S. Weinstein, “Successful reinnervation of the diaphragm after intercostal to phrenic nerve neurotization in patients with high spinal cord injury,” Annals of Plastic Surgery, vol. 79, no. 2, pp. 180–182, 2017. [95] M. L. Tedde, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Heart Institute (InCor), Tho- racic Surgery Department, São Paulo/SP, Brazil, P. V. Filho et al., “Diaphragmatic pacing stimulation in spinal cord injury: Anesthetic and perioperative management,” Clinics, vol. 67, no. 11, pp. 1265–1269, 2012.

Journal

Applied Bionics and BiomechanicsHindawi Publishing Corporation

Published: Sep 17, 2020

References