A Computational Model of the Interaction Between Residual Cortico-Spinal Inputs and Spinal Cord Stimulation After Paralysis

Balaguer, Josep-Maria; Capogrosso, Marco

doi:10.1109/ner49283.2021.9441219

Cited by 5 publications

(12 citation statements)

References 16 publications

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“…2a , top and middle panels). In our model, the slow calcium dynamics of spinal motoneurons expectedly limited their firing rate to 40 Hz 27 ( Fig. 2a , bottom panel).…”

Section: Resultsmentioning

confidence: 93%

“…Second, electrical stimulation causes simultaneous depolarization in all recruited afferents, thereby producing non-natural volleys of action potentials. Third, in contrast to this non-natural input, supraspinal drive can be modeled as a stochastic process of non-synchronized axon firing 26,27 . Fourth, a lesion reduces the number of available excitatory supraspinal fibers, thus impacting the ability of the cortex to produce action potentials in spinal motoneurons.…”

Section: Resultsmentioning

confidence: 99%

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Supraspinal control of motoneurons after paralysis enabled by spinal cord stimulation

Balaguer,

Prat-Ortega,

Verma

et al. 2023

Preprint

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Spinal cord stimulation (SCS) restores motor control after spinal cord injury (SCI) and stroke. This evidence led to the hypothesis that SCS facilitates residual supraspinal inputs to spinal motoneurons. Instead, here we show that SCS does not facilitate residual supraspinal inputs but directly triggers motoneurons action potentials. However, supraspinal inputs can shape SCS-mediated activity, mimicking volitional control of motoneuron firing. Specifically, by combining simulations, intraspinal electrophysiology in monkeys and single motor unit recordings in humans with motor paralysis, we found that residual supraspinal inputs transform subthreshold SCS-induced excitatory postsynaptic potentials into suprathreshold events. We then demonstrated that only a restricted set of stimulation parameters enables volitional control of motoneuron firing and that lesion severity further restricts the set of effective parameters. Our results explain the facilitation of voluntary motor control during SCS while predicting the limitations of this neurotechnology in cases of severe loss of supraspinal axons.

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“…2a , top and middle panels). In our model, the slow calcium dynamics of spinal motoneurons expectedly limited their firing rate to 40 Hz 27 ( Fig. 2a , bottom panel).…”

Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Supraspinal control of motoneurons after paralysis enabled by spinal cord stimulation

Balaguer,

Prat-Ortega,

Verma

et al. 2023

Preprint

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“…We first aimed at assessing the theoretical validity of our hypothesis using computer simulations 31,34,35 . Specifically, we adapted a Hodgkin-Huxley model of spinal motoneurons' membrane potential [36][37][38] with data from mice with SMA to reproduce the biophysical signatures of motoneuron dysfunction in SMA: hyperexcitability, low firing rates and decreased synaptic inputs from Ia-afferents 5,6 . For this, we first adjusted the motoneuron model ion conductances to mimic the hyperexcitability of SMA-affected motoneurons characterized by a high input resistance (Methods, Fig.…”

Section: Predicted Effects Of Scs In a Model Of Sma-affected Spinal M...mentioning

confidence: 99%

“…We then used the model to check if SCS could yield beneficial motor assistance in SMA (hypothesis 1). For this, we modeled the effects of SCS on the network as a synchronous recruitment of Ia-afferents at the stimulation frequency as we demonstrated in the past 31,[37][38][39] (Fig. 1f).…”

Section: Predicted Effects Of Scs In a Model Of Sma-affected Spinal M...mentioning

confidence: 99%

Targeted Stimulation of the Sensory Afferents Improves Motoneuron Function in Humans With a Degenerative Motoneuron Disease

Prat-Ortega,

Ensel,

Donadio

et al. 2024

Preprint

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Spinal Muscular Atrophy (SMA) is an inherited neurodegenerative disease causing motoneuron dysfunction, muscle weakness and early mortality. Three therapies can slow disease progression enabling people to survive albeit with lingering motoneuron dysfunction and severe motor impairments. Here we introduce a neurotechnological approach that improved spinal motoneuron function, muscle strength and walking in three adults with SMA. Starting from preclinical evidence showing that motoneuron dysfunction in SMA originates from the loss of excitatory inputs from primary afferents we hypothesized that augmentation of sensory neural activity with targeted electrical stimulation could compensate for this loss thereby improving motoneuron function. To test this hypothesis we implanted three adults with SMA with epidural electrodes over the lumbosacral spinal cord to stimulate the sensory axons of the legs. We stimulated participants for 4 weeks 2 hours per day while they executed tested walking and strength tasks. Remarkably, our neurostimulation regime led to robust improvements in strength, walking and fatigue paralleled by reduced neuronal hyperexcitability, increased sensory inputs and higher motoneuron firing rates. Our data indicate that targeted neurostimulation can reverse degenerative processes of circuit dysfunction thus promoting disease modifying effects in a human neurodegenerative disease.

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“…In the spinal manifold, firing rates projected robust and closed trajectories in response to proprioceptive stimuli. Obviously, the robustness of our trajectories across animals stems from the fact that we produced artificial proprioceptive stimuli using electrical stimulation of the peripheral nerves, which produces strong synchronized volleys of activity rather than asynchronous burst of inputs 45,46 . Nevertheless, their reproducibility allowed us to appreciate quantitative changes in shape and features occurring at various conditions, i.e., reduced proprioceptive input or concurrent stimulation of cutaneous afferents.…”

Section: Analysis Of Neural Manifolds Reveals Disruption Of Intra-spinal Processing Of Proprioceptive Informationmentioning

confidence: 99%

Neural population dynamics reveals disruption of spinal sensorimotor computations during electrical stimulation of sensory afferents

Katic

Balaguer

Gorskii

et al. 2021

Preprint

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Restoration of proprioception with neurotechnology is critical to improve effectiveness of robotic neuro-prostheses. Unfortunately, after initial enthusiasm clinical results showed that unlike touch, proprioception could not be reliably induced. Here we show that concurrent activation of multiple sensory modalities may trigger unwanted sensory regulation mechanisms that disrupt proprioception. We recorded intra-spinal neural activity induced by stimulation of proprioceptive afferents from the radial nerve in three monkeys. Then, we superimposed stimulation of the radial nerve cutaneous branch and quantified its impact on spinal neural activity via population analysis. Proprioceptive pulses produced robust neural trajectories in the neural manifold that were disrupted by concurrent stimulation of cutaneous afferents. This disruption correlated with a reduction of afferent volleys and multi-unit activity both in the spinal cord and somatosensory cortex. Our results suggest that limited specificity not only impacts localization of artificial percepts, but also their nature to an extent that was never considered.

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A Computational Model of the Interaction Between Residual Cortico-Spinal Inputs and Spinal Cord Stimulation After Paralysis

Cited by 5 publications

References 16 publications

Supraspinal control of motoneurons after paralysis enabled by spinal cord stimulation

Supraspinal control of motoneurons after paralysis enabled by spinal cord stimulation

Targeted Stimulation of the Sensory Afferents Improves Motoneuron Function in Humans With a Degenerative Motoneuron Disease

Neural population dynamics reveals disruption of spinal sensorimotor computations during electrical stimulation of sensory afferents

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