筋収縮維持可能なmotor point追従刺激を用いた機能的電気刺激についての研究

　機能的電気刺激(以下FES)により連続的な筋収縮を行うと，FESによる筋収縮が弱化し運動誘発を起こしにくくなるという問題がある．これは臨床において，リハビリテーションを継続する時間やリハビリテーション中の安定的な運動補助に影響を与える可能性がある．　本研究は，FESによる筋収縮を持続的に誘発可能とすることを目的にしている．FESによる筋収縮の持続性向上のためNguyenらはSpatially distributed sequential stimulation (SDSS)を提案している． SDSSは下腿三頭筋において外側筋と内側筋とで刺激する筋肉を時間的に切り替える手法である．しかし，上腕二頭筋や上腕三頭筋，前脛骨筋といった筋肉は外側筋や内側筋が存在しないためSDSSを適用することはできず，SDSSは適用範囲に問題点かあると考えられる．　本研究は，FESによる筋収縮を持続的に誘発可能とするために多点表面電極を用いたMotor Pointの移動に応じた機能的電気刺激手法を提案する(以下Motor Point Tracking Stimulation: MPT)．Motor Pointとは一つの運動神経から複数の運等神経に分岐する分岐点で，Motor Pointの刺激によって筋収縮を生じやすくする位置のことである．Motor Pointに電気刺激することで筋収縮が小さいエネルギーで誘発できることが分かっている．その為Motor Pointの移動に依らずMotor Pointを刺激することで筋収縮を持続的に誘発できることが考えられる．　MPTの筋収縮の持続性を評価するためにMPTによる求心性収縮を継続した際の関節駆動域の時間変化について刺激位置を変化させない刺激及び異なった順序で刺激位置を変化させる刺激に対して比較した．結果としてMPTではほとんどの被験者において(5人7人中)比較対象と比べ関節駆動域の向上が確認できた．　これらの結果からMotor Pointに追従するように刺激位置を変化させることでFESによる筋収縮の持続性は改善することが確認できた．電気通信大学201

Evaluating Neuromuscular Function of the Biceps Brachii after Spinal Cord Injury: Assessment of Voluntary Activation and Motor Evoked Potential Input-Output Curves Using Transcranial Magnetic Stimulation

Activation of upper limb muscles is important for independent living after cervical spinal cord injury (SCI) that results in tetraplegia. An emerging, non-invasive approach to address post-SCI muscle weakness is modulation of the nervous system. A long-term goal is to develop neuromodulation techniques to reinnervate (i.e. resupply nerve to) muscle fiber and thereby increase muscle function in individuals with tetraplegia. Towards this goal, developing monitoring techniques to quantify neuromuscular function is needed to better direct neurorehabilitation. Assessment of voluntary activation (VA) is a promising approach because the location of the stimulus can be applied cortically using transcranial magnetic stimulation (TMS) or peripherally (VAPNS) to reveal what levels of the nervous system are disrupting the innervation of muscle fibers. Voluntary activation measured with TMS (VATMS) can indicate deficits in voluntary cortical drive to innervate muscle. However, measurement of VATMS is limited by technical challenges, including the difficulty in preferential stimulation of cortical neurons projecting to the target muscle and minimal stimulation of antagonists. Thus, the motor evoked potential (MEP) response to TMS in the target muscle compared to its antagonist (i.e. MEP ratio) may be an important parameter in the assessment of VATMS. Using current methodology, VATMS cannot be reliably assessed in patient populations including individuals with tetraplegia. The overall purpose of this work was to investigate novel TMS-based methods to evaluate neuromuscular function after spinal cord injury. First, we developed and evaluated new methodology to assess VATMS in individuals with tetraplegia. The objective of the first study was to optimize the biceps/triceps MEP ratio using modulation of isometric elbow flexion angle in nonimpaired participants and participants with tetraplegia following cervical SCI (C5-C6). We hypothesized that the more flexed elbow angle would increase the MEP ratio. The MEP ratio was only modulated in the nonimpaired group but not across the entire range of voluntary efforts used to estimate VATMS. However, we established that VATMS and VAPNS in individuals with tetraplegia were repeatable across days. In a second study, we aimed to optimize MEPs during the assessment of VATMS using paired pulse TMS to elicit intracortical facilitation and short-interval intracortical inhibition. We hypothesized that intracortical facilitation would lead to an increased MEP ratio compared to single pulse and that short-interval intracortical inhibition would lead to a lower MEP ratio. The MEP ratio was modulated in both groups but not across the entire range of voluntary efforts, and did not affect VATMS estimation compared to single pulse TMS. Paired pulse TMS outcomes revealed abnormal patterns of intracortical inhibition in individuals with tetraplegia. Further, VATMS was sensitive to the linearity of the voluntary moment and superimposed twitch relationship. Linearity was lower in SCI relative to nonimpaired participants. We discuss the limitations of VATMS in assessing neuromuscular impairments in tetraplegia. In a third study, we aimed to collect MEP input-output curves of the biceps in SCI and nonimpaired and evaluate curve-fitting methodology as well as their repeatability across sessions. We hypothesized that slopes would be greater in the SCI group compared to nonimpaired. Slopes obtained with linear regression were greater in tetraplegia compared to nonimpaired participants, suggesting compensatory reorganization of corticomotor pathways after SCI. Linear regression accurately represented the slope of the modeled data compared to sigmoidal function curve-fitting method. Slopes were also found to be repeatable across days in both groups. In a fourth study, we aimed to implement a low-cost navigated TMS system (\u3c $3000) that uses motion tracking, 3D printed parts and open-source software to monitor coil placement during stimulation. We hypothesized that using this system would improve coil position and orientation consistency and decrease MEP variability compared to the conventional method when targeting the biceps at rest and during voluntary contractions across two sessions in nonimpaired participants. Coil orientation error was reduced but the improvement did not translate to lower MEP variability. This low-cost approach is an alternative to expensive systems in tracking the motor hotspot between sessions and quantifying the error in coil placement when delivering TMS. Finally, we conclude and recommend future research directions to address the challenges that we identified during this work to improve our ability to monitor neuromuscular impairments and contribute to the development of more effective neurorehabilitation strategies

An upper limb Functional Electrical Stimulation controller based on Reinforcement Learning: A feasibility case study.

Controllers for Functional Electrical Stimulation (FES) are still not able to restore natural movements in the paretic arm. In this work, Reinforcement Learning (RL) is used for the first time to control a hybrid upper limb robotic system for stroke rehabilitation in a real environment. The feasibility of the FES controller is tested on one healthy subject during elbow flex-extension in the horizontal plane. Results showed an absolute position error <1.2° for a maximum range of motion of 50°

Transcutaneous Nerve Bundle Stimulation for Dexterous Hand Grasp Patterns: Development and Exploration of an Alternative Stimulation Method

Impairment of the hand following a neurological injury such as stroke is a major contributing factor to the loss of independence and self-sufficiency. Neuromuscular Electrical Stimulation (NMES) is a widely utilized technique to help alleviate lost muscle strength by electrically eliciting muscle contractions. However, conventional NMES applied directly over the muscle belly often faces various limitations, which prevent long-term use and efficacy. Traditional NMES techniques induce rapid muscle fatigue due to non-physiological activation of fibers resulting in a decline of muscle force. For the hand, stimulation at the skin surface typically only activates the superficial extrinsic hand muscles, leading to limited multi-joint control. To overcome these limitations, we sought to develop an alternative stimulation technique that used a high-density surface electrode array to directly target major nerve bundles at a location more proximal to the muscles. First, we designed an automated stimulation paradigm to characterize the different patterns of finger flexion elicitable via the nerve stimulation method. Randomized pairs in the electrode array were used to search for the best stimulation locations. We demonstrated that the nerve stimulation can generate a variety of single and multi-finger flexion patterns, with selective sets of nerve fiber activation and high activation redundancy. Secondly, we compared the force sustainability of the proximal nerve stimulation with conventional muscle belly stimulation. We found that, with prolonged force-matched stimulations, the proximal nerve stimulation technique can significantly delay the decline of force production over time, which allowed us to elicit sustained muscle force output. Lastly, we investigated the ability of the proximal nerve stimulation to activate both the superficial and deep extrinsic finger flexors. We obtained ultrasound images of the cross section of the flexor muscles in the forearm, and image deformation was used as a surrogate measure of muscle contraction. We found that superficial and deep muscles could be separately or concurrently activated. Overall, this work demonstrated the appealing features of our nerve stimulation method in selectively recruiting different finger flexor muscles with sustained activation. The outcomes also lay the theoretical foundation for further development of proximal nerve stimulation as an alternative approach for effective hand rehabilitation.Doctor of Philosoph

A denoising algorithm for surface EMG decomposition

The goal of the present thesis was to investigate a novel motor unit potential train (MUPT) editing routine, based on decreasing the variability in shape (variance ratio, VR) of the MUP ensemble. Decomposed sEMG data from 20 participants at 60% MVC of wrist flexion was used. There were two levels of denoising (relaxed and strict) criteria for removing discharge times associated with waveforms that did not decrease the VR and increase its signal-to-noise ratio (SNR) of the MUP ensemble. The peak-to-peak amplitude and the duration between the positive and negative peaks for the MUP template were dependent on the level of denoising (p’s 0.05). The same was true between denoising criteria (p>0.05). Editing the MUPT based on MUP shape resulted in significant differences in measures extracted from the MUP template, with trivial difference between the standard error of estimate for mean IDIs between the complete and denoised MUPTs

Muscle fatigue and other factors influencing forearm muscle activity

The wrist extensor muscles of the forearm exhibit relatively greater muscle activity than the wrist flexors during most hand/wrist tasks. Since the extensors operate at a greater percentage of maximum to balance wrist joint moments, this could contribute to their higher incidence of overuse injury. However, current knowledge of forearm muscle function comes primarily from isometric research or from studies examining isolated motor tasks. Conclusions derived from this work may not translate to tasks of daily living, which are typically dynamic and performed by multiple muscle actions simultaneously. Additionally, while fatigue develops more rapidly in the extensors than the flexors, the consequences of fatigue between these two muscle groups are presently unclear. The objectives of this thesis were broken into two parts. Part 1: Quantify forearm muscle recruitment during the simultaneous execution of various handgrip and wrist forces (Chapter 3) and during dynamic wrist exertions (Chapter 4). Part 2: Characterize the effects of sustained isometric wrist flexion and wrist extension contractions on hand-tracking accuracy (Chapter 5) and investigate the underlying central mechanisms that may contribute to accuracy impairments (Chapter 6). In Part 1, we identified that the muscle activity of the wrist flexors was highly sensitive to changes in dual-task parameters (grip and wrist exertions), while the activity of the extensors was consistently greater than the flexors during both dual-task and dynamic contractions. In some conditions, the wrist extensors exceeded flexor activity even during pure wrist flexion contractions. In Part 2, it was found that inducing fatigue separately through sustained wrist extension and wrist flexion contractions significantly impaired hand-tracking accuracy. However, there were no differences in hand-tracking accuracy between the two methods of inducing fatigue. This was surprising, given that follow-up work demonstrated both muscle activity and corticospinal differences between the muscle groups following sustained contractions. This thesis provides a robust examination of the factors that can influence forearm muscle recruitment. It is also the first work to document the consequences of fatigue in opposing muscle groups of the forearm. The conclusions drawn from this research are essential in furthering our understanding of overuse injury development in the distal upper-limb

Intermittent Theta Burst Stimulation: Application to Spinal Cord Injury Rehabilitation and Computational Modeling

Loss of motor function from spinal cord injuries (SCI) results in loss of independence. Rehabilitation efforts are targeted to enhance the ability to perform activities of daily living (ADLs), but outcomes from physical therapy alone are often insufficient. Neuromodulation techniques that induce neuroplasticity may push the limits on recovery. Neuromodulation by intermittent theta burst transcranial magnetic stimulation (iTBS) induces neuroplasticity by increasing corticomotor excitability, though this has most frequently been studied with motor targets and on individuals not in need of rehabilitation. Increased corticomotor excitability is associated with motor learning. The response to iTBS, however, is highly variable and unpredictable, while the mechanisms are not well understood. Studies have proposed brain anatomy and individual subject differences as a source of variability but have not quantified the effects. Existing models have not incorporated known neurotransmitter changes at the synaptic level to pair mechanisms to cell output in a neural circuit. To use iTBS in practical rehabilitative efforts, the technique must either be consistent, have a predictable responsiveness, or present with enough mechanistic understanding to improve its efficacy. To that effect, this study has two primary objectives for the improvement of rehabilitation techniques. The first is to establish how iTBS affects both a motor target and population that typically undergoes physical rehabilitation often with unsatisfactory outcomes, in this case the biceps brachii in individuals with SCI and relate the empirical effects of iTBS to individual anatomy. This will establish the consistency of the technique and predictability of its effects, relevant to rehabilitative efforts. The secondary objective is to create the foundation of a model that exhibits circuit organization, which would start the development of a motor neuroplasticity functional unit with simulation of the synaptic long-term potentiation (LTP) like effects of iTBS. Summary of Methods: iTBS was performed targeting the biceps, on multiple cohorts, with changes in motor evoked potential amplitude (MEP) tracked after sham and active intervention. This was compared between nonimpaired individuals and those with SCI. Furthermore, iTBS of both biceps and first dorsal interosseus (FDI) was compared to simulation of TMS on MRI derived head models to establish the impact of individualized neuroanatomy. Finally, a motor canonical neural circuit was programmed to display fundamental physiological spiking behavior of membrane potentials. Summary of Results: iTBS did facilitate corticomotor excitability in the biceps of nonimpaired individuals and in those with SCI. iTBS had no group-wide effect on the FDI, highlighting the variability in response to the protocol. TMS response (motor thresholds) and iTBS response (change in MEPs) both were related to parameters extracted from MRI-derived head models representing variations in individual neuroanatomy. The neural circuit model represents a canonical networked unit. In the future, this can be further tuned to exhibit biological variability and generate population-based values being run in parallel, while matching the understood mechanisms of neuroplasticity: disinhibition and LTP. Conclusion: These studies provide missing information of iTBS responsivity by (1) determining group-wide responsiveness in a clinically relevant target; (2) establishing individual level influences that affect responsivity which can be measured prior to iTBS; and (3) beginning design of a tool to test a single neural circuit and its mechanistic responses

A single session of submaximal grip strength training with or without high-definition anodal-TDCS produces no cross-education of maximal force

BACKGROUND: Previous studies suggest that cross-education of strength may be modulated by increased corticospinal excitability of the ipsilateral primary motor cortex (M1) due to cross-activation. However, no study has examined the influence of bilateral TDCS of both M1 and how it affects corticospinal excitability, cross-activation and cross-education of muscle strength.METHOD: Twelve participants underwent three conditions in a randomized crossover design: (1) submaximal grip training and single-site unilateral-high definition-TDCS (2) submaximal grip training and bilateral anodal-high definition-TDCS, and (3) submaximal grip training and sham-high definition-TDCS. Submaximal gripping task involved a single-session of unilateral training which was squeezing the transducer at 70% of maximum voluntary isometric contraction (MVIC) grip force and performing four sets of 10 isometric contractions. Anodal-high definition-TDCS was applied for 15 min at 1.5 mA over right M1 or left and right M1s, and in a sham condition. Participants were pseudorandomized to receive either single-site or bilateral M1 stimulation with each session separated by one-week. Before and after each session, MVIC force of ipsilateral and contralateral gripping, ipsilateral stimulus-response curve, short-interval intracortical inhibition, cortical silent period, intracortical facilitation, long-interval intracortical inhibition, and cross-activation were measured.RESULTS: MVIC of the trained arm decreased by 43% (P=0.04) after training. We observed no changes in MVIC of the untrained hand and in any of the TMS measures (all P&gt;0.05).CONCLUSION: A single session of submaximal grip training with or without anodal-high definition-TDCS produces no cross-education of maximal grip force nor does it affect the excitability of the ipsilateral M1

Effects of local muscle temperature manipulations on neuromuscular function

Human muscle can operate through a wide range of temperature; however optimal function may occur throughout a much narrower range. Muscle cooling results in an impairment in muscle contractile properties and maximal force, whereas heating the muscle fosters faster and more powerful contractions. However, what neural compensatory mechanisms exist such that the muscle can still function adequately throughout a wide range of temperatures are unknown and forms the purpose of this dissertation. To this end, muscle contractile and motor unit properties of the flexor carpi radialis were examined during three separate projects involving forearm temperature manipulations. Chapter 4 investigates the effects of local forearm cooling on motor unit properties during an isometric wrist flexion contraction to 50% of baseline maximal force. Chapter 5 builds upon Chapter 4 to include local heating and contraction intensities above and below the motor unit recruitment range of the flexor carpi radialis. Finally, Chapter 6 investigates how different muscle temperatures affect manual performance – assessed through a staircase isometric force tracking task. Local cooling did not affect the ability to perform voluntary contractions to 50% of baseline force, but motor control was achieved through changes in the relationship between motor unit firing rate and recruitment threshold, indicating either faster motor unit firing rates and/or earlier motor unit recruitment to accomplish a task at the same absolute force (Chapter 4). However, these differences were not present when force requirements were made relative to muscle capacity of the respective temperature conditions. We found that motor units were recruited earlier in the cold when contraction intensity was above the motor unit recruitment range (Chapter 5). The altered relationship between motor unit firing rate and recruitment threshold observed in Chapter 4 with muscle cooling at an absolute force level did not affect isometric force tracking ability (Chapter 6). Collectively, this thesis found that the motor unit recruitment threshold may be depressed in the cold due to cutaneous stimulation, and that manual function during an isometric force tracking task involving relatively light loads is not impaired with muscle temperature changes

Development of a hybrid robotic system based on an adaptive and associative assistance for rehabilitation of reaching movement after stroke

Stroke causes irreversible neurological damage. Depending on the location and the size of this brain injury, different body functions could result affected. One of the most common consequences is motor impairments. The level of motor impairment affectation varies between post-stroke subjects, but often, it hampers the execution of most activities of daily living. Consequently, the quality of life of the stroke population is severely decreased. The rehabilitation of the upper-limb motor functions has gained special attention in the scientific community due the poor reported prognosis of post-stroke patients for recovering normal upper-extremity function after standard rehabilitation therapy. Driven by the advance of technology and the design of new rehabilitation methods, the use of robot devices, functional electrical stimulation and brain-computer interfaces as a neuromodulation system is proposed as a novel and promising rehabilitation tools. Although the uses of these technologies present potential benefits with respect to standard rehabilitation methods, there still are some milestones to be addressed for the consolidation of these methods and techniques in clinical settings. Mentioned evidences reflect the motivation for this dissertation. This thesis presents the development and validation of a hybrid robotic system based on an adaptive and associative assistance for rehabilitation of reaching movements in post-stroke subjects. The hybrid concept refers the combined use of robotic devices with functional electrical stimulation. Adaptive feature states a tailored assistance according to the users’ motor residual capabilities, while the associative term denotes a precise pairing between the users’ motor intent and the peripheral hybrid assistance. The development of the hybrid platform comprised the following tasks: 1. The identification of the current challenges for hybrid robotic system, considering twofold perspectives: technological and clinical. The hybrid systems submitted in literature were critically reviewed for such purpose. These identified features will lead the subsequent development and method framed in this work. 2. The development and validation of a hybrid robotic system, combining a mechanical exoskeleton with functional electrical stimulation to assist the execution of functional reaching movements. Several subsystems are integrated within the hybrid platform, which interact each other to cooperatively complement the rehabilitation task. Complementary, the implementation of a controller based on functional electrical stimulation to dynamically adjust the level of assistance is addressed. The controller is conceived to tackle one of the main limitations when using electrical stimulation, i.e. the highly nonlinear and time-varying muscle response. An experimental procedure was conducted with healthy and post-stroke patients to corroborate the technical feasibility and the usability evaluation of the system. 3. The implementation of an associative strategy within the hybrid platform. Three different strategies based on electroencephalography and electromyography signals were analytically compared. The main idea is to provide a precise temporal association between the hybrid assistance delivered at the periphery (arm muscles) and the users’ own intention to move and to configure a feasible clinical setup to be use in real rehabilitation scenarios. 4. Carry out a comprehensive pilot clinical intervention considering a small cohort of patient with post-stroke patients to evaluate the different proposed concepts and assess the feasibility of using the hybrid system in rehabilitation settings. In summary, the works here presented prove the feasibility of using the hybrid robotic system as a rehabilitative tool with post-stroke subjects. Moreover, it is demonstrated the adaptive controller is able to adjust the level of assistance to achieve successful tracking movement with the affected arm. Remarkably, the accurate association in time between motor cortex activation, represented through the motor-related cortical potential measured with electroencephalography, and the supplied hybrid assistance during the execution of functional (multidegree of freedom) reaching movement facilitate distributed cortical plasticity. These results encourage the validation of the overall hybrid concept in a large clinical trial including an increased number of patients with a control group, in order to achieve more robust clinical results and confirm the presented herein.Programa Oficial de Doctorado en Ingeniería Eléctrica, Electrónica y AutomáticaPresidente: Ramón Ceres Ruiz.- Secretario: Luis Enrique Moreno Lorente.- Vocal: Antonio Olivier