Hybrid brain-computer interface and functional electrical stimulation for sensorimotor training in participants with tetraplegia: a proof-of-concept study

Background and Purpose: Impaired hand function decreases quality of life in persons with tetraplegia. We tested functional electrical stimulation (FES) controlled by a hybrid brain-computer interface (BCI) for improving hand function in participants with tetraplegia. Methods: Two participants with subacute tetraplegia (participant 1: C5 Brown-Sequard syndrome, participant 2: complete C5 lesion) took part in this proof-of-concept study. The goal was to determine whether the BCI system could drive the FES device by accurately classifying participants' intent (open or close the hand). Participants 1 and 2 received 10 sessions and 4 sessions of BCI-FES, respectively. A novel time-switch BCI strategy based on motor imagery was used to activate the FES. In one session, we tested a hybrid BCI-FES based on 2 spontaneously generated brain rhythms: a sensory-motor rhythm during motor imagery to activate a stimulator and occipital alpha rhythms to deactivate the stimulator. Participants received BCI-FES therapy 2 to 3 times a week in addition to conventional therapy. Imagery ability and muscle strength were measured before and after treatment. Results: Visual feedback was associated with a 4-fold increase of brain response during motor imagery in both participants. For participant 1, classification accuracy (open/closed) for motor imagery-based BCI was 83.5% (left hand) and 83.8% (right hand); participant 2 had a classification accuracy of 83.8% for the right hand. Participant 1 had moderate improvement in muscle strength, while there was no change for participant 2. Discussion and Conclusion: We demonstrated feasibility of BCI-FES, using 2 naturally generated brain rhythms. Studies on a larger number of participants are needed to separate the effects of BCI training from effects of conventional therapy

A functional electrical stimulation system for human walking inspired by reflexive control principles

This study presents an innovative multichannel functional electrical stimulation gait-assist system which employs a well-established purely reflexive control algorithm, previously tested in a series of bipedal walking robots. In these robots, ground contact information was used to activate motors in the legs, generating a gait cycle similar to that of humans. Rather than developing a sophisticated closed-loop functional electrical stimulation control strategy for stepping, we have instead utilised our simple reflexive model where muscle activation is induced through transfer functions which translate sensory signals, predominantly ground contact information, into motor actions. The functionality of the functional electrical stimulation system was tested by analysis of the gait function of seven healthy volunteers during functional electrical stimulation–assisted treadmill walking compared to unassisted walking. The results demonstrated that the system was successful in synchronising muscle activation throughout the gait cycle and was able to promote functional hip and ankle movements. Overall, the study demonstrates the potential of human-inspired robotic systems in the design of assistive devices for bipedal walking

Enhancing Nervous System Recovery through Neurobiologics, Neural Interface Training, and Neurorehabilitation.

After an initial period of recovery, human neurological injury has long been thought to be static. In order to improve quality of life for those suffering from stroke, spinal cord injury, or traumatic brain injury, researchers have been working to restore the nervous system and reduce neurological deficits through a number of mechanisms. For example, neurobiologists have been identifying and manipulating components of the intra- and extracellular milieu to alter the regenerative potential of neurons, neuro-engineers have been producing brain-machine and neural interfaces that circumvent lesions to restore functionality, and neurorehabilitation experts have been developing new ways to revitalize the nervous system even in chronic disease. While each of these areas holds promise, their individual paths to clinical relevance remain difficult. Nonetheless, these methods are now able to synergistically enhance recovery of native motor function to levels which were previously believed to be impossible. Furthermore, such recovery can even persist after training, and for the first time there is evidence of functional axonal regrowth and rewiring in the central nervous system of animal models. To attain this type of regeneration, rehabilitation paradigms that pair cortically-based intent with activation of affected circuits and positive neurofeedback appear to be required-a phenomenon which raises new and far reaching questions about the underlying relationship between conscious action and neural repair. For this reason, we argue that multi-modal therapy will be necessary to facilitate a truly robust recovery, and that the success of investigational microscopic techniques may depend on their integration into macroscopic frameworks that include task-based neurorehabilitation. We further identify critical components of future neural repair strategies and explore the most updated knowledge, progress, and challenges in the fields of cellular neuronal repair, neural interfacing, and neurorehabilitation, all with the goal of better understanding neurological injury and how to improve recovery

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

Developing and Evaluating a Flexible Wireless Microcoil Array Based Integrated Interface for Epidural Cortical Stimulation.

Stroke leads to serious long-term disability. Electrical epidural cortical stimulation has made significant improvements in stroke rehabilitation therapy. We developed a preliminary wireless implantable passive interface, which consists of a stimulating surface electrode, receiving coil, and single flexible passive demodulated circuit printed by flexible printed circuit (FPC) technique and output pulse voltage stimulus by inductively coupling an external circuit. The wireless implantable board was implanted in cats\u27 unilateral epidural space for electrical stimulation of the primary visual cortex (V1) while the evoked responses were recorded on the contralateral V1 using a needle electrode. The wireless implantable board output stable monophasic voltage stimuli. The amplitude of the monophasic voltage output could be adjusted by controlling the voltage of the transmitter circuit within a range of 5-20 V. In acute experiment, cortico-cortical evoked potential (CCEP) response was recorded on the contralateral V1. The amplitude of N2 in CCEP was modulated by adjusting the stimulation intensity of the wireless interface. These results demonstrated that a wireless interface based on a microcoil array can offer a valuable tool for researchers to explore electrical stimulation in research and the dura mater-electrode interface can effectively transmit electrical stimulation

Abdominal functional electrical stimulation to assist ventilator weaning in acute tetraplegia: a cohort study

Background Severe impairment of the major respiratory muscles resulting from tetraplegia reduces respiratory function, causing many people with tetraplegia to require mechanical ventilation during the acute stage of injury. Abdominal Functional Electrical Stimulation (AFES) can improve respiratory function in non-ventilated patients with sub-acute and chronic tetraplegia. The aim of this study was to investigate the clinical feasibility of using an AFES training program to improve respiratory function and assist ventilator weaning in acute tetraplegia.<p></p> Methods AFES was applied for between 20 and 40 minutes per day, five times per week on four alternate weeks, with 10 acute ventilator dependent tetraplegic participants. Each participant was matched retrospectively with a ventilator dependent tetraplegic control, based on injury level, age and sex. Tidal Volume (VT) and Vital Capacity (VC) were measured weekly, with weaning progress compared to the controls.<p></p> Results Compliance to training sessions was 96.7%. Stimulated VT was significantly greater than unstimulated VT. VT and VC increased throughout the study, with mean VC increasing significantly (VT: 6.2 mL/kg to 7.8 mL/kg VC: 12.6 mL/kg to 18.7 mL/kg). Intervention participants weaned from mechanical ventilation on average 11 (sd: ± 23) days faster than their matched controls.<p></p> Conclusion The results of this study indicate that AFES is a clinically feasible technique for acute ventilator dependent tetraplegic patients and that this intervention may improve respiratory function and enable faster weaning from mechanical ventilation.<p></p&gt

Functional electrical stimulation versus ankle foot orthoses for foot-drop: a meta-analysis of orthotic effects

Objective: To compare the effects on walking of Functional Electrical Stimulation (FES) and Ankle Foot Orthoses (AFO) for foot-drop of central neurological origin, assessed in terms of unassisted walking behaviours compared with assisted walking following a period of use (combined-orthotic effects). Data Sources: MEDLINE, AMED, CINAHL, Cochrane Central Register of Controlled Trials, Scopus, REHABDATA, PEDro, NIHR Centre for Reviews and Dissemination and clinicaltrials.gov. plus reference list, journal, author and citation searches. Study Selection: English language comparative Randomised Controlled Trials (RCTs). Data Synthesis: Seven RCTs were eligible for inclusion. Two of these reported different results from the same trial and another two reported results from different follow up periods so were combined; resulting in five synthesised trials with 815 stroke participants. Meta-analyses of data from the final assessment in each study and three overlapping time-points showed comparable improvements in walking speed over ten metres (p=0.04-0.95), functional exercise capacity (p=0.10-0.31), timed up-and-go (p=0.812 and p=0.539) and perceived mobility (p=0.80) for both interventions. Conclusion: Data suggest that, in contrast to assumptions that predict FES superiority, AFOs have equally positive combined-orthotic effects as FES on key walking measures for foot-drop caused by stroke. However, further long-term, high-quality RCTs are required. These should focus on measuring the mechanisms-of-action; whether there is translation of improvements in impairment to function, plus detailed reporting of the devices used across diagnoses. Only then can robust clinical recommendations be made

Evaluation of potassium channel blockers, 4-aminpyridine and 4-aminpyridine-3-methanol, in combination with electrical neuromodulation for functional upper limb recovery following incomplete cervical spinal cord injury

Cervical spinal cord injury (SCI) is a traumatic condition where individuals lose crucial motor and sensory functions in their hands and arms. These deficits can be caused by myelin damage, which exposes juxtaparanodal potassium channels leading to large potassium effluxes and ultimately, shortened and decreased conduction. However, potassium channel blockers such as 4-aminopyridine (4-AP) and the novel derivative, 4-aminopyridine-3-methanol (4-AP-3-MeOH) prevent potassium ion leakage and increase conduction to improve motor function. Currently, it is possible to regain voluntary motor control and strength in the forelimbs and hands by using complementary electrical stimulation, pharmacological agents and training to transform dormant spinal circuitry into active states. Here, we evaluated the extent to which potassium channel blockers, 4-AP and 4-AP-3-MeOH enable functional forelimb ability when used in combination with spinal stimulation and motor training after incomplete cervical SCI. 4-AP restored reaching and grasping function and muscle activation in rats after two weeks of treatment. 4-AP-3-MeOH, however, did not lead to improve motor functioning or muscle activation. Both drugs decreased muscle activation latency and allowed for earlier muscle activation. Our findings suggest 4-AP synergistically works with spinal stimulation and training to enable spared circuitry following SCI and can be used acutely to restore forelimb function