Targeted neurotechnology restores walking in humans with spinal cord injury

Wagner, Fabien; Mignardot, Jean‐Baptiste; Goff-Mignardot, Camille G. Le; Demesmaeker, Robin; Komi, Salif; Capogrosso, Marco; Rowald, Andreas; Seáñez, Ismael; Caban, Miroslav; Pirondini, Elvira; Vat, Molywan; McCracken, Laura; Heimgartner, Roman; Fodor, Isabelle; Watrin, Anne; Séguin, P.; Paoles, Edoardo; Keybus, Katrien Van Den; Eberle, Grégoire; Schurch, Brigitte; Pralong, Étienne; Becce, Fabio; Prior, John O.; Buse, Nicholas; Buschman, Rik; Neufeld, Esra; Kuster, Niels; Carda, Stefano; Zitzewitz, Joachim von; Delattre, Vincent; Denison, Timothy; Lambert, Hendrik; Minassian, Karen; Bloch, Jocelyne; Courtine, Grégoire

doi:10.1038/s41586-018-0649-2

Cited by 733 publications

(652 citation statements)

References 44 publications

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“…Indeed, recent evidence suggests that increased physical activity after SCI may promote remyelination. Currently there is much excitement in the SCI field over the remarkable results being obtained with activity‐based training and epidural stimulation in SCI individuals (Capogrosso et al, ; Formento et al, ; Gill et al, ; Moraud et al, ; Wagner et al, ; Wenger et al, ). The most common form of activity‐based therapy is body weight supported treadmill training in which SCI subjects are placed in a harness and trainers move their limbs to provide sufficient input to the neuromuscular system (Dobkin et al, ).…”

Section: Additional Factors To Consider In Opc Responses and Myelinatmentioning

confidence: 99%

Myelin status and oligodendrocyte lineage cells over time after spinal cord injury: What do we know and what still needs to be unwrapped?

Pukos

Goodus

Sahinkaya

et al. 2019

Glia

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Spinal cord injury (SCI) affects over 17,000 individuals in the United States per year, resulting in sudden motor, sensory and autonomic impairments below the level of injury. These deficits may be due at least in part to the loss of oligodendrocytes and demyelination of spared axons as it leads to slowed or blocked conduction through the lesion site. It has long been accepted that progenitor cells form new oligodendrocytes after SCI, resulting in the acute formation of new myelin on demyelinated axons. However, the chronicity of demyelination and the functional significance of remyelination remain contentious. Here we review work examining demyelination and remyelination after SCI as well as the current understanding of oligodendrocyte lineage cell responses to spinal trauma, including the surprisingly long‐lasting response of NG2+ oligodendrocyte progenitor cells (OPCs) to proliferate and differentiate into new myelinating oligodendrocytes for months after SCI. OPCs are highly sensitive to microenvironmental changes, and therefore respond to the ever‐changing post‐SCI milieu, including influx of blood, monocytes and neutrophils; activation of microglia and macrophages; changes in cytokines, chemokines and growth factors such as ciliary neurotrophic factor and fibroblast growth factor‐2; glutamate excitotoxicity; and axon degeneration and sprouting. We discuss how these changes relate to spontaneous oligodendrogenesis and remyelination, the evidence for and against demyelination being an important clinical problem and if remyelination contributes to motor recovery.

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Section: Additional Factors To Consider In Opc Responses and Myelinatmentioning

confidence: 99%

Myelin status and oligodendrocyte lineage cells over time after spinal cord injury: What do we know and what still needs to be unwrapped?

Pukos

Goodus

Sahinkaya

et al. 2019

Glia

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“…An emerging new avenue of brain stimulation strongly relies on a close link between the stimulation effects and pathophysiology and follows the rationale of replacing pathophysiologically missing signals via on‐demand electric stimulation, thereby normalizing neural coding in downstream brain regions . The therapeutic potential of targeted neuromodulatory stimulation for restoration of human motor control was recently evidenced by 3 breakthrough studies in the treatment of paralysis after spinal cord injury . For stroke, an on‐demand neurostimulation was recently shown to improve skillful reaching and grasping after stroke in rodents .…”

mentioning

confidence: 99%

“…9,11,12 The therapeutic potential of targeted neuromodulatory stimulation for restoration of human motor control was recently evidenced by 3 breakthrough studies in the treatment of paralysis after spinal cord injury. [13][14][15] For stroke, an ondemand neurostimulation was recently shown to improve skillful reaching and grasping after stroke in rodents. 16 Movement-related low-frequency oscillations (LFOs) in the motor cortex served as the stimulation target.…”

mentioning

confidence: 99%

Low‐Frequency Brain Oscillations Track Motor Recovery in Human Stroke

Bönstrup

Krawinkel

Schulz

et al. 2019

Annals of Neurology

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Objective The majority of patients with stroke survive the acute episode and live with enduring disability. Effective therapies to support recovery of motor function after stroke are yet to be developed. Key to this development is the identification of neurophysiologic signals that mark recovery and are suitable and susceptible to interventional therapies. Movement preparatory low‐frequency oscillations (LFOs) play a key role in cortical control of movement. Recent animal data point to a mechanistic role of motor cortical LFOs in stroke motor deficits and demonstrate neuromodulation intervention with therapeutic benefit. Their relevance in human stroke pathophysiology is unknown. Methods We studied the relationship between movement‐preparatory LFOs during the performance of a visuomotor grip task and motor function in a longitudinal (<5 days, 1 and 3 months) cohort study of 33 patients with motor stroke and in 19 healthy volunteers. Results Acute stroke–lesioned brains fail to generate the LFO signal. Whereas in healthy humans, a transient occurrence of LFOs preceded movement onset at predominantly contralateral frontoparietal motor regions, recordings in patients revealed that movement‐preparatory LFOs were substantially diminished to a level of 38% after acute stroke. LFOs progressively increased at 1 and 3 months. This re‐emergence closely tracked the recovery of motor function across several movement qualities including grip strength, fine motor skills, and synergies and was frequency band specific. Interpretation Our results provide the first human evidence for a link between movement‐preparatory LFOs and functional recovery after stroke, promoting their relevance for movement control. These results suggest that it may be interesting to explore targeted, LFOs‐restorative brain stimulation therapy in human stroke patients. ANN NEUROL 2019;86:853–865

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“…Electrical stimulation has been widely applied to treat neurological disorders and to recover lost functions caused by nerve injuries, such as deep brain stimulation to relieve Parkinson's disease, [21,22] cochlear nerve stimulation to restore acoustic hearing, [23] spinal cord stimulation to augment recovery and restore limb functions, [24][25][26] and peripheral nerve stimulation to assist bladder functions. Electrical stimulation has been widely applied to treat neurological disorders and to recover lost functions caused by nerve injuries, such as deep brain stimulation to relieve Parkinson's disease, [21,22] cochlear nerve stimulation to restore acoustic hearing, [23] spinal cord stimulation to augment recovery and restore limb functions, [24][25][26] and peripheral nerve stimulation to assist bladder functions.…”

Section: Introductionmentioning

confidence: 99%

Investigation of Low‐Current Direct Stimulation for Rehabilitation Treatment Related to Muscle Function Loss Using Self‐Powered TENG System

Wang

et al. 2019

Advanced Science

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Muscle function loss is characterized as abnormal or completely lost muscle capabilities, and it can result from neurological disorders or nerve injuries. The currently available clinical treatment is to electrically stimulate the diseased muscles. Here, a self‐powered system of a stacked‐layer triboelectric nanogenerator (TENG) and a multiple‐channel epimysial electrode to directly stimulate muscles is demonstrated. Then, the two challenges regarding direct TENG muscle stimulation are further investigated. For the first challenge of improving low‐current TENG stimulation efficiency, it is found that the optimum stimulation efficiency can be achieved by conducting a systematic mapping with a multiple‐channel epimysial electrode. The second challenge is TENG stimulation stability. It is found that the force output generated by TENGs is more stable than using the conventional square wave stimulation and enveloped high frequency stimulation. With modelling and in vivo measurements, it is confirmed that the two factors that account for the stable stimulation using TENGs are the long pulse duration and low current amplitude. The current waveform of TENGs can effectively avoid synchronous motoneuron recruitment at the two stimulation electrodes to reduce force fluctuation. Here, after investigating these two challenges, it is believed that TENG direct muscle stimulation could be used for rehabilitative and therapeutic purpose of muscle function loss treatment.

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Targeted neurotechnology restores walking in humans with spinal cord injury

Cited by 733 publications

References 44 publications

Myelin status and oligodendrocyte lineage cells over time after spinal cord injury: What do we know and what still needs to be unwrapped?

Myelin status and oligodendrocyte lineage cells over time after spinal cord injury: What do we know and what still needs to be unwrapped?

Low‐Frequency Brain Oscillations Track Motor Recovery in Human Stroke

Investigation of Low‐Current Direct Stimulation for Rehabilitation Treatment Related to Muscle Function Loss Using Self‐Powered TENG System

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