Intensity and Dose of Neuromuscular Electrical Stimulation Influence Sensorimotor Cortical Excitability

Neuromuscular electrical stimulation (NMES) of the nervous system has been extensively used in neurorehabilitation due to its capacity to engage the muscle fibers, improving muscle tone, and the neural pathways, sending afferent volleys toward the brain. Although different neuroimaging tools suggested the capability of NMES to regulate the excitability of sensorimotor cortex and corticospinal circuits, how the intensity and dose of NMES can neuromodulate the brain oscillatory activity measured with electroencephalography (EEG) is still unknown to date. We quantified the effect of NMES parameters on brain oscillatory activity of 12 healthy participants who underwent stimulation of wrist extensors during rest. Three different NMES intensities were included, two below and one above the individual motor threshold, fixing the stimulation frequency to 35 Hz and the pulse width to 300 μs. Firstly, we efficiently removed stimulation artifacts from the EEG recordings. Secondly, we analyzed the effect of amplitude and dose on the sensorimotor oscillatory activity. On the one hand, we observed a significant NMES intensity-dependent modulation of brain activity, demonstrating the direct effect of afferent receptor recruitment. On the other hand, we described a significant NMES intensity-dependent dose-effect on sensorimotor activity modulation over time, with below-motor-threshold intensities causing cortical inhibition and above-motor-threshold intensities causing cortical facilitation. Our results highlight the relevance of intensity and dose of NMES, and show that these parameters can influence the recruitment of the sensorimotor pathways from the muscle to the brain, which should be carefully considered for the design of novel neuromodulation interventions based on NMES.This study was funded by the Bundesministerium für Bildung und Forschung BMBF MOTORBIC (FKZ 13GW0053), AMORSA (FKZ 16SV7754), and the Fortüne-Program of the University of Tübingen (2422-0-1 and 2556-0-

Event-related desynchronization during movement attempt and execution in severely paralyzed stroke patients: An artifact removal relevance analysis

The electroencephalogram (EEG) constitutes a relevant tool to study neural dynamics and to develop brain-machine interfaces (BMI) for rehabilitation of patients with paralysis due to stroke. However, the EEG is easily contaminated by artifacts of physiological origin, which can pollute the measured cortical activity and bias the interpretations of such data. This is especially relevant when recording EEG of stroke patients while they try to move their paretic limbs, since they generate more artifacts due to compensatory activity. In this paper, we study how physiological artifacts (i.e., eye movements, motion artifacts, muscle artifacts and compensatory movements with the other limb) can affect EEG activity of stroke patients. Data from 31 severely paralyzed stroke patients performing/attempting grasping movements with their healthy/paralyzed hand were analyzed offline. We estimated the cortical activation as the event-related desynchronization (ERD) of sensorimotor rhythms and used it to detect the movements with a pseudo-online simulated BMI. Automated state-of-the-art methods (linear regression to remove ocular contaminations and statistical thresholding to reject the other types of artifacts) were used to minimize the influence of artifacts. The effect of artifact reduction was quantified in terms of ERD and BMI performance. The results reveal a significant contamination affecting the EEG, being involuntary muscle activity the main source of artifacts. Artifact reduction helped extracting the oscillatory signatures of motor tasks, isolating relevant information from noise and revealing a more prominent ERD activity. Lower BMI performances were obtained when artifacts were eliminated from the training datasets. This suggests that artifacts produce an optimistic bias that improves theoretical accuracy but may result in a poor link between task-related oscillatory activity and BMI peripheral feedback. With a clinically relevant dataset of stroke patients, we evidence the need of appropriate methodologies to remove artifacts from EEG datasets to obtain accurate estimations of the motor brain activity.This study was funded by the fortüne-Program of the University of Tübingen (2422-0-1 and 2452-0-0), the Bundesministerium für Bildung und Forschung BMBF MOTORBIC (FKZ 13GW0053) and AMORSA (FKZ 16SV7754), the Deutsche Forschungsgemeinschaft (DFG), the Basque Government Science Program (EXOTEK: KK 2016/00083). The work of A. Insausti-Delgado was supported by the Basque Government's scholarship for predoctoral students

Challenges of neural interfaces for stroke motor rehabilitation

More than 85% of stroke survivors suffer from different degrees of disability for the rest of their lives. They will require support that can vary from occasional to full time assistance. These conditions are also associated to an enormous economic impact for their families and health care systems. Current rehabilitation treatments have limited efficacy and their long-term effect is controversial. Here we review different challenges related to the design and development of neural interfaces for rehabilitative purposes. We analyze current bibliographic evidence of the effect of neuro-feedback in functional motor rehabilitation of stroke patients. We highlight the potential of these systems to reconnect brain and muscles. We also describe all aspects that should be taken into account to restore motor control. Our aim with this work is to help researchers designing interfaces that demonstrate and validate neuromodulation strategies to enforce a contingent and functional neural linkage between the central and the peripheral nervous system. We thus give clues to design systems that can improve or/and re-activate neuroplastic mechanisms and open a new recovery window for stroke patients

Brain-spine interface for the volitional control of trans-spinal magnetic stimulation to rehabilitate movement in paralyzed patients

Neurological pathologies damaging communication between central nervous system (CNS) and peripheral nervous system (PNS), such as stroke, can result in permanent motor impairment. Around 20% of stroke patients making a partial recovery remain with foot drop, which is expressed as weakness of ankle joint and abnormal muscle activations and movement coordination during locomotion. For these patients, the accident has an enormous impact in their life quality, social integration and economic situation. Currently, there is no effective treatment for this pathology and, given the rising worldwide prevalence of stroke during the upcoming years, there is a great need of improving existing rehabilitative interventions. In this line, much research has focused on developing technology to improve rehabilitation and motor restoration of paralyzed patients. Advances in technology have considerably contributed to the capacity of acquiring, decoding and manipulating neural activity, and has been applied in clinical environments demonstrating its rehabilitative efficacy. Spinal cord stimulation (SCS) has emerged as a powerful tool for manipulation the spinal circuitry to generate walking-like patterns and to regain partial motor control of paralyzed limbs. Comparing to passive SCS, using brain activity to activate the stimulation is a more natural approach and allows volitional control of it. Brain-spine interfaces (BSI) have appeared as a technology to acquire, process and transform neural signals into commands to control SCS. BSIs enable associative connection between brain neural activity encoding motor intentions and activation of spinal pools and muscles, which may trigger Hebbian mechanisms that favor neuroplasticity boosting rehabilitative effects. To date, only implantable BSIs have been devised and tested in animals. Developing non-invasive BSIs would broaden the field of applicability of this rehabilitative technology on patients with motor disorders. This thesis works on the development of a non-invasive BSI, based on continuous control of trans-spinal magnetic stimulation (ts-MS) using electroencephalographic activity (EEG), for motor rehabilitation of patients with lower limb paralysis. To this end, a set of 6 studies is presented, addressing the challenges and questions from three lines of work: (1) relevance of artifact removal methods, (2) neuromodulation by electromagnetic stimulation, and (3) conception of a brain-spine interface for motor rehabilitation. Firstly, towards integrating neurostimulators in closed-loop systems, we characterize how artifacts of electromagnetic and neurophysiological origin interfere with electrophysiological recordings reflecting active participation of the patient and simulate their impact in closed-loop control. Contamination of electrophysiological recordings hampers the estimation of neural activity of interest and directly affects the performance of rehabilitative systems. Particularly for brain-controlled neural interfaces, we propose a median filter to minimize stimulation artifacts and statistical thresholding to eliminate neurophysiological artifacts. We demonstrate the need of adequate artifact removal methods that avoid bias in the quantification of task-related motor activity allowing contingent peripheral feedback. Secondly, we investigate the modulatory effects of electromagnetic stimulators on the nervous system at different levels and discuss its implications in neurorehabilitation. Two studies are proposed: one evaluates the influence of neuromuscular electrical stimulation (NMES) on sensorimotor excitability, and one investigates the influence of ts-MS on cortico-spino-muscular excitability. We evidence that intensity and dose of NMES can produce immediate and cumulative effects on sensorimotor excitability measured with EEG. Our exploratory study shows that lumbar ts-MS strengthens the corticomuscular efficacy. Understanding how passive stimulation interacts with the nervous system could help us to improve interventions based on closed-loop stimulation. The third line of work composing this thesis focuses on the development and validation of a BSI for lower-limb motor rehabilitation. Given the knowledge acquired from the other two lines of work, we aim at engineering the first non-invasive BSI that integrates ts-MS controlled by EEG activity. We prove the effectiveness and robustness of the system to work in real-time eliminating stimulation artifacts and engaging motor and sensory nervous system. We test and validate the BSI system in healthy participants and stroke patients and measure the neurophysiological, clinical and behavioral changes induced by an intervention based on our system. Our results show that the BSI increases the excitability of corticomuscular pathways, improves sensorimotor function, enhances balance and walking speed, and decreases spasticity. In summary, this thesis proposes a novel non-invasive BSI that enables contingent connection between CNS and PNS, and evaluates its feasibility for rehabilitation of patients with motor paralysis. The here presented system provide relevant insights towards designing and developing of this innovative technology and may set the basis for future new investigations.Dissertation ist gesperrt bis 03.12.2023 !

Non-invasive brain-spine interface: Continuous control of trans-spinal magnetic stimulation using EEG

Brain-controlled neuromodulation has emerged as a promising tool to promote functional recovery in patients with motor disorders. Brain-machine interfaces exploit this neuromodulatory strategy and could be used for restoring voluntary control of lower limbs. In this work, we propose a non-invasive brain-spine interface (BSI) that processes electroencephalographic (EEG) activity to volitionally control trans-spinal magnetic stimulation (ts-MS), as an approach for lower-limb neurorehabilitation. This novel platform allows to contingently connect motor cortical activation during leg motor imagery with the activation of leg muscles via ts-MS. We tested this closed-loop system in 10 healthy participants using different stimulation conditions. This BSI efficiently removed stimulation artifacts from EEG regardless of ts-MS intensity used, allowing continuous monitoring of cortical activity and real-time closed-loop control of ts-MS. Our BSI induced afferent and efferent evoked responses, being this activation ts-MS intensity-dependent. We demonstrated the feasibility, safety and usability of this non-invasive BSI. The presented system represents a novel non-invasive means of brain-controlled neuromodulation and opens the door towards its integration as a therapeutic tool for lower-limb rehabilitation