Biology subjects

Pirondini, E.

Publications and source records attributed to Pirondini, E..

8 recordsLinked to original sources

bioRxiv2026

Noninvasive Focal Gene Delivery of Functional Neural Actuators to the Primate Spinal Cord using Focused Ultrasound

Pathologies of the spinal cord -- from degenerative diseases to chronic pain -- represent a substantial global health burden. Although surgical and pharmacological treatments for spinal cord pathologies have advanced considerably, therapies capable of addressing the cellular mechanisms underlying these conditions remain limited. Viral gene therapies present a compelling alternative, allowing for delivery of therapeutic genes that directly target the pathological processes in specific cell-types. Effective viral delivery to the spinal cord, however, remains constrained by a fundamental tradeoff between procedural invasiveness and spatial precision. As such, there remains a need for clinically tractable methods -- that are both noninvasive and focal -- to deliver gene therapeutics across the restrictive vascular boundaries of the blood-spinal cord barrier (BSCB). Here, we demonstrate noninvasive, focal disruption of the BSCB and delivery of systemically administered chemogenetic gene payloads to the cervical and thoracic spinal cord in marmoset nonhuman primates (Callithrix jacchus) using focused ultrasound (FUS). Through systematic testing of ultrasonic pressures and central frequencies, we establish a FUS parameter set optimized for robust, spatially constrained molecular delivery across the marmoset BSCB. Using these optimized parameters, we show that FUS BSCB disruption permitted focal penetrance of systemically administered viral vectors for transduction of both fluorescent transgenes and excitatory chemogenetics within targeted spinal segments. Positron emission tomography (PET) imaging following chemogenetic actuation revealed significantly increased metabolic demand within the targeted region of the spinal cord, demonstrating in vivo evidence of functional transgene expression. Behavioral and histopathological assessments demonstrated preserved neurological function and tissue integrity, supporting the safety of FUS BSCB disruption and viral delivery in nonhuman primates. To facilitate broad application of this platform for noninvasive delivery of receptor-based gene therapeutics in marmosets, we generated an ultra-high-resolution (74 m) multimodal MRI/CT spinal cord template for precise targeting and anatomical localization. We also provide open-access engineering drawings and CAD files for our M-FRAME system (Marmoset Fixation and Reorientation Apparatus for Multimodal Experiments), enabling precise and repeatable spinal targeting without surgical fixation. Together, these results establish FUS-mediated BSCB disruption as a safe and effective approach for noninvasive, focal gene delivery to the primate spinal cord.

neuroscience↗

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↗

bioRxiv2024

An open-source MRI compatible frame for multimodal presurgical mapping in macaque and capuchin monkeys

HighlightsO_LIWe present a compact MRI-compatible stereotaxic frame for large nonhuman primates. C_LIO_LIThe design is 3D printable, inexpensive, and matches size of an adult human head. C_LIO_LIEnabled real-time, accurate, MRI-guided deep-brain viral vector injection. C_LIO_LIFacilitated multimodal alignment for deep-brain electrophysiology planning. C_LIO_LIAll computer-aided-design files are modularized and publicly available and editable. C_LI BackgroundHigh-precision neurosurgical targeting in nonhuman primates (NHPs) often requires presurgical anatomy mapping with noninvasive neuroimaging techniques (MRI, CT, PET), allowing for translation of individual anatomical coordinates to surgical stereotaxic apparatus. Given the varied tissue contrasts that these imaging techniques produce, precise alignment of imaging-based coordinates to surgical apparatus can be cumbersome. MRI-compatible stereotaxis with radiopaque fiducial markers offer a straight-forward and reliable solution, but existing commercial options do not fit in conformal head coils that maximize imaging quality. New methodWe developed a compact MRI-compatible stereotaxis suitable for a variety of NHP species (Macaca mulatta, Macaca fascicularis, and Cebus apella) that allows multimodal alignment through technique-specific fiducial markers. Comparison with existing methodsWith the express purpose of compatibility with clinically available MRI, CT, and PET systems, the frame is no larger than a human head, while allowing for imaging NHPs in the supinated position. This design requires no marker implantation, special software, or additional knowledge other than the operation of a common large animal stereotaxis. ResultsWe demonstrated the applicability of this 3D-printable apparatus across a diverse set of experiments requiring presurgical planning: 1) We demonstrate the accuracy of the fiducial system through a within-MRI cannula insertion and subcortical injection of viral vectors. 2) We also demonstrated accuracy of multimodal (MRI and CT) alignment and coordinate transfer to guide a surgical robot electrode implantation for deep-brain electrophysiology. ConclusionsThe computer-aided design files and engineering drawings are publicly available, with the modular design allowing for low cost and manageable manufacturing.

bioengineering↗

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↗

bioRxiv2023

Understanding Age-Related Changes in Proprioception through Active and Passive Tasks

Voluntary control of motor actions requires precise regulation of proprioceptive and somatosensory functions. While aging has demonstrated to decline sensory processing functions, the effect of age on proprioception remains less clear. Indeed, previous studies contradict on whether passive proprioception (i.e., during externally driven movements) is affected over age. Moreover, no studies explored age-related modifications in active proprioception (i.e., during voluntary movements). Understanding these changes is critical to identify and prevent possible causes of reduced movement performances and mobility, in particular in age-related neurological conditions such as stroke or Parkinson disease. Here, we first refined a robotic protocol to assess upper-limb active proprioception and demonstrated the robustness and reliability of outcome measures over sessions. We then compared performances between young and elderly subjects during active and passive proprioceptive tasks. We found that while the two populations of subjects performed similarly in passive proprioception, elderly subjects acuity declined during active proprioception. Importantly, we confirmed that the decline could not be explained by impairments in voluntary motor control. Our data and robotic protocols further elucidate the debate over proprioception in elderly subjects and provide evidence that robust proprioceptive assessments should be an essential measurement in clinical settings. New & NoteworthyUpper limb position sense has been previously evaluated using passive matching protocols with the contralateral arm. These studies have found contradicting results regarding a possible decline in passive proprioception over age. Here we replicated this passive protocol and compared it to its active counterpart. Our results suggest that aging has an effect only in the active condition, leading to the hypothesis of a potential role of the cortico-spinal and cerebellar pathways in proprioception decline.

bioengineering↗

bioRxiv2023

Transient brain activity dynamics discriminate levels of consciousness during anesthesia

The awake mammalian brain is functionally organized in terms of large-scale distributed networks that are constantly interacting. Loss of consciousness might disrupt this temporal organization leaving patients unresponsive. We hypothesized that characterizing brain activity in terms of transient events may provide a signature of consciousness. For this, we analyzed temporal dynamics of spatiotemporally overlapping functional networks obtained from fMRI transient activity across different states of consciousness. We first show a striking homology in spatial organization of networks between monkeys and humans, indicating cross-species similarities in resting- state fMRI structure. We then tracked how network organization shifts under different anesthesia conditions in macaque monkeys. While the spatial aspect of the networks was preserved, their temporal dynamics were highly affected by anesthesia. Networks expressed for longer durations and co-activated in an anesthetic-specific configuration. Additionally, hierarchical brain organization was disrupted with a consciousness-level- signature role of the default mode network. In conclusion, network temporal dynamics is a reliable and robust cortical signature of consciousness, paving the way to its clinical translation.

neuroscience↗

bioRxiv2019

Motor improvement estimation and task adaptation for personalized robot-aided therapy: a feasibility study

BackgroundIn the past years, robotic systems have become increasingly popular in both upper and lower limb rehabilitation. Nevertheless, clinical studies have so far not been able to confirm superior efficacy of robotic therapy over conventional methods. The personalization of robot-aided therapy according to the patients individual motor deficits has been suggested as a pivotal step to improve the clinical outcome of such approaches.\n\nMethodsHere, we present a model-based approach to personalize robot-aided rehabilitation therapy within training sessions. The proposed method combines the information from different motor performance measures recorded from the robot to continuously estimate patients motor improvement for a series of point-to-point reaching movements in different directions and comprises a personalization routine to automatically adapt the rehabilitation training. We engineered our approach using an upper limb exoskeleton and tested it with seventeen healthy subjects, who underwent a motor-adaptation paradigm, and two subacute stroke patients, exhibiting different degrees of motor impairment, who participated in a pilot test.\n\nResultsThe experiments illustrated the models capability to differentiate distinct motor improvement progressions among subjects and subtasks. The model suggested personalized training schedules based on motor improvement estimations for each movement in different directions. Patients motor performances were retained when training movements were reintroduced at a later stage.\n\nConclusionsOur results demonstrated the feasibility of the proposed model-based approach for the personalization of robot-aided rehabilitation therapy. The pilot test with two subacute stroke patients further supported our approach, while providing auspicious results for the applicability in clinical settings.\n\nTrial registrationThis study is registered in ClinicalTrials.gov (NCT02770300, registered 30 March 2016, https://clinicaltrials.gov/ct2/show/NCT02770300).

bioengineering↗