# Biologically-constrained spiking neural network for neuromodulation in locomotor recovery after spinal cord injury

## TL;DR

A computer model of spinal circuits shows how therapies like spinal stimulation and drugs can reduce excessive inhibition and improve walking after spinal cord injury.

## Contribution

A biologically constrained spiking neural network model to study neuromodulation effects on locomotor recovery after SCI.

## Key findings

- Reducing GABAergic inhibition on flexor motoneurons facilitates more physiological flexor activation during locomotion.
- Neuromodulatory therapy with body-weight support modulates synaptic excitation and inhibition in ankle flexor motoneurons.
- Excessive inhibition in ankle flexor circuits can be mitigated through combined therapies.

## Abstract

Presynaptic inhibition after spinal cord injury (SCI) has been hypothesised to disproportionately affect flexion reflex loops in locomotor spinal circuitry. Reducing gamma-aminobutyric acid (GABA) inhibitory activity increases the excitation of flexion circuits, restoring muscle activation and stepping ability. Conversely, nociceptive sensitisation and muscular spasticity can emerge from insufficient GABAergic inhibition. To investigate the effects of neuromodulation and proprioceptive sensory afferents in the spinal cord, a biologically constrained spiking neural network (SNN) was developed. The network describes the ankle flexor motoneuron (MN) reflex loop with inputs from ipsilateral Ia- and II-fibres and tonically firing interneurons. The model was tuned to a Baseline level of locomotive activity before simulating an inhibitory-dominant and body-weight supported (BWS) SCI state. Electrical stimulation (ES) and serotonergic agonists were simulated by the excitation of dorsal fibres and reduced conductance in excitatory neurons. ES was applied across all afferent fibres without phase- or muscle-specific protocols. The present computational findings suggest that reducing stance-phase GABAergic inhibition on flexor motoneurons could facilitate more physiological flexor activation during locomotion. The model further predicts that neuromodulatory therapy, together with body-weight support, modulates the balance of synaptic excitation and inhibition in ankle flexor motoneurons to mitigate excessive inhibitory drive in the ankle flexor circuitry.

SCI is a life-altering condition that often leaves young adults paralysed and reliant on others for support. Restoring the ability to walk is a critical goal to help improve independence and quality of life for people living with SCI. Promising new treatments, such as spinal cord stimulation and drug therapies, aim to reawaken the neurons that control walking. However, scientists still do not entirely understand how these treatments work. In this study, we developed a detailed computer model of the neural circuits involved in walking to test how therapies such as serotonin-boosting drugs, ES, and BWS training might help. Our findings suggest that these treatments can work together to reduce excessive inhibition that blocks ankle movement, leading to smoother and more coordinated steps. This research helps uncover how these therapies work and provides insights to develop better rehabilitation strategies for improving walking after SCI.