Biology subjects

Bonizzato, M.

Publications and source records attributed to Bonizzato, M..

5 recordsLinked to original sources

bioRxiv2025

Combining cortical and spinal stimulation maximizes improvement of gait after spinal cord injury

Most spinal cord injuries (SCI) spare descending motor pathways and sublesional networks, which can be activated through motor cortex and spinal cord stimulation to mitigate locomotor deficits. However, the potential synergy between cortical and spinal stimulation as a neuroprosthetic intervention remains unknown. Here, we first investigated phase-locked electrical stimulation of the motor cortex and lumbar spinal cord at 40 Hz in a rat model of unilateral SCI. Combining cortical and lumbar stimulation around the anticipated lift synergistically enhanced leg movements. When integrated into rehabilitation training, cortical stimulation proved essential for recovery of skilled locomotion. As a further refinement, we next investigated the effects of high-frequency (330 Hz) lumbar and sacral stimulation combined with cortical stimulation. Timely integration during the swing phase showed that cortical and rostral lumbar stimulations enhance the initial and mid-swing phases, while sacral stimulation improves extension velocity in the late swing. These findings indicate that supraspinal and sublesional neuromodulation offer complementary neuroprosthetic effects in targeted SCI gait rehabilitation. HighlightsO_LICortical and spinal stimulations summate motor outputs via distinct pathways. C_LIO_LIEach improves gait post-SCI, but combined stimulation maximizes gait improvement. C_LIO_LIIntegrating cortico-spinal stimulation into rehabilitation promotes lasting recovery. C_LIO_LIEES capabilities extended using high-frequency lumbosacral protocols. C_LI

neuroscience↗

bioRxiv2024

Modulation of leg trajectory by transcranial magnetic stimulation during walking

The primary motor cortex is involved in initiation and adaptive control of locomotion. However, the role of the motor cortex in controlling gait trajectories remains unclear. In animals, cortical neuromodulation allows for precise control of step height. We hypothesized that a similar control framework applies to humans, whereby cortical stimulation would primarily increase foot elevation. Transcranial magnetic stimulation (TMS) was applied over the motor cortex to assess the involvement of the corticospinal tract over the limb trajectory during human walking. Eight healthy adults (aged 20-32 years) participated in treadmill walking at 1.5 km/h. TMS was applied over the left motor cortex at an intensity of 120% of the threshold to elicit a dorsiflexion of the right ankle during the swing phase of gait. Electromyographic (EMG) measurements and three-dimensional (3D) lower limb kinematics were collected. When delivered during the early swing phase, TMS led to a significant increase in the maximum height of the right toe by a mean of 40.7% {+/-} 14.9% (25.6mm {+/-} 9.4 mm, p = 0.0352) and knee height by 57.8%{+/-} 16.8%; (32mm {+/-} 9.3 mm; p = 0.008) across participants. These findings indicate that TMS can influence limb trajectory during walking, highlighting its potential as a tool for studying cortical control of locomotion.

neuroscience↗

bioRxiv2023

Uncovering and exploiting the return of voluntary motor programs after paralysis using a bi-cortical neuroprosthesis

Rehabilitative and neuroprosthetic approaches after spinal cord injury (SCI) aim to reestablish voluntary control of movement. Promoting recovery requires a mechanistic understanding of the return of volition over action, but the relationship between re-emerging cortical commands and the return of locomotion is not well established. We introduced a neuroprosthesis delivering targeted bi-cortical stimulation in a clinically relevant contusive SCI model. In healthy and SCI cats, we controlled hindlimb locomotor output by tuning stimulation timing, duration, amplitude, and site. In intact cats, we unveiled a large repertoire of motor programs. After SCI, the evoked hindlimb lifts were highly stereotyped, yet effective in modulating gait and alleviating bilateral foot drag. Results suggest that the neural substrate underpinning motor recovery had traded-off selectivity for efficacy. Longitudinal tests revealed that the return of locomotion after SCI was time-locked with recovery of the descending drive, which advocates for rehabilitation interventions directed at the cortical target. HighlightsO_LIA bilateral cortical implant allowed for the delivery of alternate bilateral stimulation coherently with locomotion, which modulated gait trajectories. C_LIO_LIWe analyzed the effects of stimulation parameters - timing, duration, amplitude, and site of stimulation - to maximize the improvement of locomotor output after paralysis. C_LIO_LIA varied repertoire of motor programs evoked in intact cats was reduced to one stereotyped response after spinal cord injury (SCI) consisting in flexion modulation that efficiently alleviated hindlimb dragging. C_LIO_LIAfter SCI, the return of cortical gait control emerged in synchrony with locomotor recovery. C_LI

neuroscience↗

bioRxiv2021

Cortical neuroprosthesis-mediated functional ipsilateral control of locomotion in rats with incomplete spinal cord injury

Control of voluntary limb movement is predominantly attributed to the contralateral motor cortex. However, increasing evidence suggests the involvement of ipsilateral cortical networks in this process, especially in motor tasks requiring bilateral coordination, such as locomotion. In this study, we combined a unilateral thoracic spinal cord injury (SCI) with a cortical neuroprosthetic approach to investigate the functional role of the ipsilateral motor cortex in rat movement through spared contralesional pathways. Our findings reveal that in all SCI rats, stimulation of the ipsilesional motor cortex promoted a bilateral synergy. This synergy involved the elevation of the contralateral foot along with ipsilateral hindlimb extension. Additionally, in two out of seven animals, stimulation of a sub-region of the hindlimb motor cortex modulated ipsilateral hindlimb flexion. Importantly, ipsilateral cortical stimulation delivered after SCI immediately alleviated multiple locomotor and postural deficits, and this effect persisted after ablation of the homologous motor cortex. These results provide strong evidence of a causal link between cortical activation and precise ipsilateral control of hindlimb movement. This study has significant implications for the development of future neuroprosthetic technology and our understanding of motor control in the context of spinal cord injury.

neuroscience↗

bioRxiv2019

Learning to evoke complex motor outputs with spatiotemporal neurostimulation using a hierarchical and adaptive optimization algorithm.

The development of neurostimulation techniques to evoke motor patterns is an active area of research. It serves as a crucial experimental tool to probe computation in neural circuits, and it has applications in neuroprostheses used to aid recovery of function after stroke or injury. There are two important challenges when designing algorithms to unveil and control neurostimulation-to-motor mappings, thereby linking spatiotemporal patterns of neural stimulation to muscle activation: (1) the exploration of motor maps needs to be fast and efficient (exhaustive search is to be avoided for clinical and experimental reasons) (2) online learning needs to be flexible enough to track ongoing changes in these maps. We propose a stimulation search algorithm to address these issues, and demonstrate its efficacy with experiments in non-human primate models. Our solution is a novel iterative process using Bayesian Optimization via Gaussian Processes on increasingly complex signal spaces. We show that our algorithm can successfully and rapidly learn mappings between complex stimulation patterns and evoked muscle activation patterns, where standard approaches fail. Importantly, we uncover nonlinear circuit-level computations in M1 that would not have been possible to identify using conventional mapping techniques.

neuroscience↗