Biology subjects

Capogrosso, M.

Publications and source records attributed to Capogrosso, M..

11 recordsLinked to original sources

bioRxiv2026

Cervical spinal cord stimulation disrupts proprioception yet improves voluntary arm reaching

Whether proprioception is necessary for upper-limb motor control has been debated for decades. Classic studies in deafferented animals and humans suggested that proprioception may be dispensable for rapid, goal-directed movements. However, chronic sensory loss conflates the absence of proprioceptive input with years of compensatory adaptation. As a result, the field has lacked a strong causal test of proprioceptions contribution to motor control. Here, we leveraged a clinical trial of cervical spinal cord stimulation (SCS) in individuals with chronic post-stroke hemiparesis to study if electrical stimulation of sensory afferents causally perturbs proprioception and affects arm reaching. We found that turning SCS ON causally impaired proprioceptive perception and postural stabilization in response to force perturbations, and enhanced adaptation to visual errors during implicit learning. Yet visually and non-visually rapid, goal-directed reaching improved in smoothness, straightness and spatial accuracy. These findings provide strong causal evidence that proprioception is not required for rapid, goal-directed action, helping resolve a decades-long debate regarding its necessity for effective movement.

bioengineering↗

bioRxiv2025

SpIC3D imaging: Spinal In-situ Contrast 3D imaging

High-definition visualization techniques are critical for understanding the neuroanatomy of the spinal cord, an essential structure for sensorimotor and autonomic functions, in both healthy and pathological conditions. Magnetic resonance imaging (MRI) is a common method for visualizing neural structures in 3D. However, techniques for spinal cord MRI have historically achieved limited visualization of rootlets and nerves, especially at lower spinal levels, due to their highly complex and compact organization. Here we developed a spinal in-situ contrast 3D imaging (SpIC3D) method that allows visualization of spinal compartments in fixed animal and human specimens with ultra-high resolution at various spinal levels. Using SpIC3D, we achieved quantification of neuronal cell density in dorsal root ganglia, multi-segment identification of individual rootlets and roots, and volumetric reconstruction of multiple spinal structures for computational modeling. SpIC3D provides a basis for accelerated spinal pathology characterization and personalized spinal cord stimulation treatments.

neuroscience↗

bioRxiv2023

GABA Increases Sensory Transmission In Monkeys

Sensory input flow is central to voluntary movements. For almost a century, GABA was believed to modulate this flow by inhibiting sensory axons in the spinal cord to sculpt neural inputs into skilled motor output. Instead, here we show that GABA can also facilitate sensory transmission in monkeys and consequently increase spinal and cortical neural responses to sensory inputs challenging our understanding of generation and perception of movement.

neuroscience↗

bioRxiv2022

High-Frequency Stimulation Does Not Improve Comfort of Transcutaneous Spinal Cord Stimulation

Spinal cord neuromodulation has gained much attention for demonstrating improved motor recovery in people with spinal cord injury, motivating the development of clinically applicable technologies. Among them, transcutaneous spinal cord stimulation (tSCS) is attractive because of its non-invasive profile. Many tSCS studies employ a high-frequency (10 kHz) carrier, which has been reported to reduce stimulation discomfort. However, these claims have come under scrutiny in recent years. The purpose of this study was to determine whether high-frequency tSCS is more comfortable at therapeutic amplitudes, which evoke posterior root-muscle (PRM) reflexes. In 16 neurologically intact participants, tSCS was delivered using a 1-ms long monophasic pulse with and without a high-frequency carrier. Stimulation amplitude and pulse duration were varied and PRM reflexes were recorded from the soleus, gastrocnemius, and tibialis anterior muscles. Participants rated their discomfort during stimulation from 0-10 at PRM reflex threshold. At PRM reflex threshold, high-frequency stimulation (0.87 {+/-} 0.2) was equally comfortable as conventional stimulation (1.03 {+/-} 0.18) but required approximately double the charge to evoke the PRM reflex (conventional: 32.4 {+/-} 9.2 {micro}C; high-frequency: 62.5 {+/-} 11.1 {micro}C). Strength-duration curves for high-frequency stimulation had a rheobase that was 4.8X greater and a chronaxie that was 5.7X narrower than the conventional monophasic pulse, indicating that high-frequency stimulation was less efficient in recruiting neural activity in spinal roots. High-frequency tSCS is equally as comfortable as conventional stimulation at amplitudes required to stimulate spinal dorsal roots. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=178 SRC="FIGDIR/small/506783v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@f013f3org.highwire.dtl.DTLVardef@1aded5eorg.highwire.dtl.DTLVardef@1bad2e0org.highwire.dtl.DTLVardef@6aaf96_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2022

Preferential activation of proprioceptive and cutaneous sensory fibers compared to motor fibers during cervical transcutaneous spinal cord stimulation: A computational study

ObjectiveCervical transcutaneous spinal cord stimulation (tSCS) is a promising technology that can support motor function recovery of upper-limbs after spinal cord injury. Its efficacy may depend on the ability to recruit sensory afferents and convey excitatory inputs onto motoneurons. Therefore, understanding its physiological mechanisms is critical to accelerate its development towards clinical applications. In this study, we used an anatomically realistic computational model of the cervical spine to compare -motor, A-sensory, and A{beta}-sensory fiber activation thresholds and activation sites. ApproachWe developed a tridimensional geometry of the cervical body and tSCS electrodes with a cathode centred at the C7 spinous process and an anode placed over the anterior neck. The geometrical model was used to estimate the electric potential distributions along motor and sensory fiber trajectories at the C7 spinal level using a finite element method. We implemented dedicated motor and sensory fiber models to simulate the -motor and A-sensory fibers using 12, 16, and 20 m diameter fibers, and A{beta}-sensory fibers using 6, 9, and 12 m diameter fibers. We estimated nerve fiber activation thresholds and sites for a 2 ms monophasic stimulating pulse and compared them across the fiber groups. Main resultsOur results showed lower activation thresholds of A- and A{beta}-sensory fibers compared with -motor fibers, suggesting preferential sensory fiber activation. We also found no differences between activation thresholds of A-sensory and large A{beta}-sensory fibers, implying they were co-activated. The activation sites were located at the dorsal and ventral root levels. SignificanceUsing a realistic computational model, we demonstrated preferential activation of dorsal root A- and A{beta}-sensory fibers compared with ventral root -motor fibers during cervical tSCS. These findings suggest high proprioceptive and cutaneous contributions to neural activations during cervical tSCS, which inform the underlying mechanisms of upper-limb functional motor recovery.

neuroscience↗

bioRxiv2021

Disruption Of Proprioceptive Information During Electrical Stimulation Of The Cutaneous Afferents

While neurostimulation technologies are rapidly approaching clinical applications for sensorimotor disorders, the impact of electrical stimulation on network dynamics is still unknown. Given the high degree of shared processing in neural structures, it is critical to understand if neurostimulation affects functions that are related to, but not targeted by the intervention. Here we approached this question by studying the effects of electrical stimulation of cutaneous afferents on unrelated processing of proprioceptive inputs. We recorded intra-spinal neural activity in four monkeys while generating proprioceptive inputs from the radial nerve. We then applied continuous stimulation to the radial nerve cutaneous branch and quantified the impact of the stimulation on spinal processing of proprioceptive inputs via neural population dynamics. Proprioceptive pulses consistently produced neural trajectories that were disrupted by concurrent cutaneous stimulation. This disruption propagated to the somatosensory cortex, suggesting that electrical stimulation can perturb natural information processing across the neural axis.

neuroscience↗

bioRxiv2020

Electrical Stimulation Of The Cervical Dorsal Roots Enables Functional Arm And Hand Movements In Monkeys With Cervical Spinal Cord Injury

Recovering arm control is a top priority for people with paralysis. Unfortunately, the complexity of the neural mechanisms underlying arm control practically limited the effectiveness of neurotechnology approaches. Here, we exploited the neural function of surviving spinal circuits to restore voluntary arm and hand control in three monkeys with spinal cord injury using spinal cord stimulation. Our neural interface leverages the functional organization of the dorsal roots to convey artificial excitation via electrical stimulation to relevant spinal segments at appropriate movement phases. Stimulation bursts targeting specific spinal segments produced sustained arm movements enabling monkeys with arm paralysis to perform an unconstrained reach-and-grasp task. Stimulation specifically improved strength, task performances and movement quality. Electrophysiology suggested that residual descending inputs were necessary to produce coordinated movements. The efficacy and reliability of our approach hold realistic promises of clinical translation.

bioengineering↗

bioRxiv2020

Motor cortical dynamics are shaped by multiple distinct subspaces during naturalistic behavior

Behavior relies on continuous influx of sensory information about the body. In primates, motor cortex must integrate somatic feedback to accurately reach and manipulate objects. Yet, prior work demonstrates that motor cortex is well-described with deterministic, rather than input-driven, dynamics. Deterministic dynamics facilitate robust movement generation, but flexible motor output requires rapid responses to unexpected inputs. Here, we resolved this paradox by simultaneously recording neural population activity in motor and somatosensory cortex from four monkeys performing a naturalistic object interaction behavior resulting in occasional errors. Motor cortex was strikingly input-driven surrounding behavioral error correction. Intriguingly, input-driven dynamics were isolated to a subspace of the population activity that putatively captured somatosensory feedback. Using electrical stimulation of ascending somatosensory tracts, we causally verified that this feedback subspace captured peripheral inputs to cortex. Our results demonstrate that cortical activity is compartmentalized within distinct subspaces, enabling flexible integration of salient inputs for robust behavior.

neuroscience↗

bioRxiv2020

RECRUITMENT OF UPPER-LIMB MOTONEURONS WITH EPIDURAL ELECTRICAL STIMULATION OF THE PRIMATE CERVICAL SPINAL CORD

Epidural electrical stimulation (EES) of lumbosacral sensorimotor circuits improves leg motor control in animals and humans with spinal cord injury (SCI). Upper-limb motor control involves similar circuits, located in the cervical spinal cord, suggesting that EES could also improve arm and hand movements after quadriplegia. However, the ability of cervical EES to selectively modulate specific upper-limb motor nuclei remains unclear. Here, we combined a realistic computational model of EES of the cervical spinal cord with experiments in macaque monkeys to explore the mechanisms of this modulation and characterize the recruitment selectivity of cervical stimulation interfaces. Our results indicate that interfaces with lateral electrodes can target individual posterior roots and achieve selective modulation of arm motoneurons via the direct recruitment of pre-synaptic pathways. Intraoperative recordings suggested similar properties in humans. These results provide a framework for the design of neuro-technologies to improve arm and hand control in humans with quadriplegia.

bioengineering↗

bioRxiv2019

Spatiotemporal Maps of Proprioceptive Inputs to the Cervical Spinal Cord During Three-Dimensional Reaching and Grasping

Proprioceptive feedback is a critical component of voluntary movement planning and execution. Neuroprosthetic technologies aiming at restoring movement must interact with it to restore accurate motor control. Optimization and design of such technologies depends on the availability of quantitative insights into the neural dynamics of proprioceptive afferents during functional movements. However, recording proprioceptive neural activity during unconstrained movements in clinically relevant animal models presents formidable challenges. In this work, we developed a computational framework to estimate the spatiotemporal patterns of proprioceptive inputs to the cervical spinal cord during three-dimensional arm movements in monkeys. We extended a biomechanical model of the monkey arm with ex-vivo measurements, and combined it with models of mammalian group-Ia, Ib and II afferent fibers. We then used experimental recordings of arm kinematics and muscle activity of two monkeys performing a reaching and grasping task to estimate muscle stretches and forces with computational biomechanics. Finally, we projected the simulated proprioceptive firing rates onto the cervical spinal roots, thus obtaining spatiotemporal maps of spinal proprioceptive inputs during voluntary movements. Estimated maps show complex and markedly distinct patterns of neural activity for each of the fiber populations spanning the spinal cord rostro-caudally. Our results indicate that reproducing the proprioceptive information flow to the cervical spinal cord requires complex spatio-temporal modulation of each spinal root. Our model can support the design of neuroprosthetic technologies as well as in-silico investigations of the primate sensorimotor system.

bioengineering↗

bioRxiv2019

A VERSATILE ROBOTIC PLATFORM FOR THE DESIGN OF NATURAL, THREE-DIMENSIONAL REACHING AND GRASPING TASKS IN MONKEYS

Translational studies on motor control and neurological disorders require detailed monitoring of sensorimotor components of natural limb movements in relevant animal models. However, available experimental tools do not provide a sufficiently rich repertoire of behavioral signals. Here, we developed a robotic platform that enables the monitoring of kinematics, interaction forces, and neurophysiological signals during user-definable upper limb tasks for monkeys. We configured the platform to position instrumented objects in a three-dimensional workspace and provide an interactive dynamic force-field. We show the relevance of our platform for fundamental and translational studies with three example applications. First, we study the kinematics of natural grasp in response to variable interaction forces. We then show simultaneous and independent encoding of kinematic and forces in single unit intra-cortical recordings from sensorimotor cortical areas. Lastly, we demonstrate the relevance of our platform to develop clinically relevant brain computer interfaces in a kinematically unconstrained motor task

neuroscience↗