Jul 2026· Research Square· 0 citations· 48 references
Medicine
TL;DR
This work demonstrates for the first time in humans that clinical-grade lumbosacral epidural paddle arrays capture sufficient fine-scale spatiotemporal structure to decode these overlapping inputs from highly overlapping, volume-conducted epidural fields.
Abstract
Restoration of dynamic motor function following neurological injury increasingly relies on adaptive neuroprostheses, which require real-time sensory feedback to continuously adjust to a user’s physical state. However, it remains unknown whether distinct afferent activity can even be decoded from highly overlapping, volume-conducted epidural fields. This challenge is particularly pronounced in the lumbosacral enlargement, where common fibular (CFN) and tibial nerve (TN) afferents converge extensively, producing highly similar cord dorsum potential (CDP) topographies. Here, we demonstrate for the first time in humans that clinical-grade lumbosacral epidural paddle arrays capture sufficient fine-scale spatiotemporal structure to decode these overlapping inputs. Using a 32-contact array and peripheral nerve stimulation, we constructed a 42-dimensional feature space capturing distributed amplitudes, field geometry, and waveform morphology. A support vector machine decoded four distinct afferent classes (left and right CFN and TN) with a median accuracy of 90.9% ± 0.3%. Shapley Additive Explanations revealed decoding was driven by contact-level voltage patterns and temporal waveform complexity, while the geometric features contributed minimally. These afferent-specific signatures persisted even at sub-motor threshold stimulation intensities. By utilizing standard clinical arrays, this approach provides a pathway toward rapid deployment of interpretable closed-loop neuromodulation, avoiding the surgical risks of penetrating or peripheral interfaces.
Spinal cord injury affects over 2.5 million people worldwide, yet current neuroprosthetic strategies remain fragmented, addressing motor, sensory, or autonomic function in isolation. Here we show that a single ultrathin circumferential electrode array, conforming to the spinal cord without penetrating neural tissue, can simultaneously decode motor intent, classify sensory inputs, and discriminate visceral sensory inputs. In freely moving rats during short-term implantation (up to three days), deep learning decoders achieved robust motor intent decoding (R² = 0.97) by exploiting low-frequency spinal oscillations aligned with central pattern generator rhythms. The same interface classified eight sensory modalities with 94.4% accuracy. In acutely anaesthetized pigs, cross-species validation confirmed translational scalability and reliably distinguished visceral sensory inputs. Uniquely, the two-row electrode configuration resolved directional propagation within spinal tracts while electrode-dense one-row devices enabled high-precision intraspinal source localization. By consolidating motor, sensory, and visceral afferent decoding within a single conformal interface, this approach positions the spinal cord as a target for multifunctional neuroprosthetic interfacing, offering a path toward integrated restoration of physiological function after neurological injury. Spinal cord injury disrupts motor, sensory, and autonomic functions. Here, the authors demonstrate that a single ultrathin circumferential intradural electrode array can decode motor intent, classify sensory inputs, and discriminate visceral afferent signals across rodent and porcine models.
S. El Hadwe, Rubén Ruiz-Mateos Serrano, George Psaltakis et al.· Nature Communications· 0 citations
OBJECTIVE
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established therapy for Parkinson's disease (PD), yet optimizing outcomes remains challenging due to the complexity of STN functional architecture and the subjectivity of intraoperative assessments. Furthermore, the encoding of fine versus gross movements across STN dorsoventral subregions remains poorly understood. This study aimed to characterize region- and movement-specific modulation of STN neuronal activity using synchronized electrophysiology and markerless motion tracking-derived kinematics.
APPROACH
We recorded intraoperative electrophysiological and videographic data from 11 subjects with PD (15 hemispheres) undergoing awake STN-DBS implantation surgery. Microelectrode recordings were synchronized with high-resolution kinematics during repeated trials of continuous upper-limb motor tasks involving both distal and proximal muscle groups. Instantaneous firing rate (IFR) and neuronal responsiveness metrics were quantified using a parameter-free Zenith of Event-based Time-locked Anomalies (ZETA) statistical framework and analyzed with linear mixed-effects models.
MAIN RESULTS
STN single-unit activity (SUA) and multi-unit activity (MUA) features exhibited robust region- and movement-specific modulation. Firing rates for both SUA and MUA were significantly higher in the dorsal STN during active movements, particularly distal fine motor tasks, compared to ventral STN and baseline activity. ZETA-test analyses revealed significant movement-specific responsiveness across STN subregions, with more dextrous, distal movements eliciting stronger responses than more coordinated, proximal movements. Temporal dynamics of neuronal responsiveness also varied with STN depth and movement type, indicating hierarchical recruitment of STN subregions in the encoding of movement-specific temporal motifs.
SIGNIFICANCE
These findings demonstrate that STN motor representations are context-dependent, anatomically organized, and temporally distinct, reinforcing the STN's dynamic engagement during motor execution. By identifying objective electrophysiological features linked to movement context and STN region, this work provides a quantitative foundation for reducing reliance on subjective assessments to inform data-driven DBS targeting, programming, and closed-loop control strategies.
E. Radcliffe, Morgan K Hampton, H. Granberg et al.· Journal of Neural Engineerin...· 0 citations
Identifying objective translational biomarkers of spinal nociceptive processing is important to accelerate analgesic development. The primary negative component (N1) of spinal somatosensory evoked potentials (SEPs) has been proposed as such a biomarker. However, the cellular substrates of the N1 potential (evoked by innocuous electrical stimulation) and their relevance to nociceptive processing have not been directly demonstrated. Here, we employed a 64-channel multielectrode recording approach in the dorsal horn of anaesthetised Wistar rats to functionally characterise the neuronal populations activated during the generation of spinal SEPs and determine how their activity is modulated by tapentadol. Single units were classified based on their responses to mechanical stimulation of the hindpaw, and their electrically evoked responses to sciatic nerve stimulation. Of 59 well-isolated units, 47 (80%) were classified as wide dynamic range (WDR) neurons and 12 (20%) as low-threshold mechanoreceptive (LTMR) neurons, spatially distributed across spinal laminae III-V. Tapentadol (10 mg/kg, intraperitoneal (i.p)) selectively attenuated the mechanically- and electrically-evoked activity of WDR neurons without affecting LTMR responses. This WDR-inhibition was largely reversed by naloxone (0.25 mg/kg, i.p) but not by atipamezole (1 mg/kg, i.p), identifying a predominant opioid receptor-mediated mechanism of inhibition in the naïve state. The magnitude of WDR inhibition by tapentadol correlated with the degree of reduction of the N1 amplitude. These findings establish activity in WDR neurons as a core component of the N1 potential, supporting the use of spinal SEPs as a translational biomarker of analgesic target engagement within the dorsal horn. Summary Multielectrode recordings identify inhibition of WDR neurons as the mechanism by which tapentadol modulates spinal SEPs, supporting use as a biomarker of spinal nociceptive processing.
Kenneth A J Steel, Tony Blockeel, E. Ajay et al.· bioRxiv· 0 citations
The spinal cord serves as a crucial relay for motor commands, yet the role of its local circuitry in sensorimotor integration remains poorly understood. Most non-invasive cortical stimulation studies, rely on electrophysiological readouts or inferred spinal function from corticospinal anatomy, leaving the downstream impact of cortical stimulation on spinal circuitry largely uncharted in vivo. Advances in spinal cord functional MRI (SC-fMRI) now enable spatially resolved imaging of segmental gray and white matter and their interactions with descending cortical inputs. Here, we introduce a multimodal framework that combines single-pulse transcranial magnetic stimulation (TMS) of the primary motor cortex with SC-fMRI to probe TMS-evoked spinal activity in humans. Using graded TMS intensities, we examined blood oxygenation level-dependent (BOLD) responses in the cervical spinal cord and asked how spinal activation depends on effective engagement of the descending motor system. Our findings reveal robust, intensity-dependent spinal BOLD responses aligned with descending pathways, with activation concentrated in expected territories such as the lateral corticospinal tract and ventral horn at segments innervating the stimulated hand muscle. By linking peripheral output to segment- and pathway-resolved spinal signals, these results demonstrate that concurrent TMS–SCfMRI can capture, in vivo, how cortical drive is expressed within human spinal circuitry and provide a new framework to measure spinal contributions to sensorimotor control with spatial specificity beyond traditional peripheral readouts. Graphical Abstract
E. Sareen, Rebecca Jones, E. Raffin et al.· bioRxiv· 0 citations
Humans perform a variety of complex hand movements to manipulate objects, requiring precise control of changing forces. Understanding the role of sensorimotor cortex and the cortical dynamics underlying these actions is crucial for developing interventions that restore dexterous hand function after injury or disease. In this study, two male individuals with tetraplegia resulting from cervical spinal cord injury attempted a series of isometric grasps. Neural activity was recorded from the motor and somatosensory cortices using intracortical microelectrode arrays while participants attempted to exert a static or ramping force up and down. Despite their inability to execute movement and limited afferent input, the spiking activity in motor and somatosensory cortex was modulated with the task. Within the neural response we identified independent neural modes - distinct patterns of population-level neural activity that were informative about both the timing and magnitude of the attempted force. Moreover, distinct neural modes were observed during static and dynamic grasping conditions, suggesting independent control schemes for maintaining and changing forces. These modes were related to phases of the task, including the onset, offset, holding periods, as well as increasing and decreasing attempted forces. These results will inform the design of intracortical brain-computer interface (iBCI) systems that can leverage the patterns of grasp and force control evident in sensorimotor cortex during attempted movement to restore dexterous hand function.Significance Statement Restoring dexterous hand function after injury remains a major challenge, partly due to an incomplete understanding of the cortical dynamics underlying grasping and force control. In this study, we investigated neural activity within the motor and somatosensory cortices of individuals with tetraplegia attempting to perform grasps to different target forces with varying temporal profiles. We identified distinct neural modes modulated during specific phases of grasp that encode attempted force information throughout the task. These findings suggest that brain-computer interfaces could leverage these neural modes to restore grasping and force modulation.
G. Blumenthal, B. Dekleva, C. Gontier et al.· Journal of Neuroscience· 0 citations
Upper limb prostheses fail to deliver complete tactile sensation, so most users depend on visual guidance and excessively adjust their grasping movements. The core research focus has shifted from integrating sensory feedback to selecting optimal stimulation strategies for generating tactile perception that is functional, anatomically consistent and neurophysiologically natural. This paper presents a PRISMA-informed scoping review of recent tactile feedback published from January 1, 2020, to May 31, 2026, then integrates classic anatomy and neuroprosthetic papers to build a compact evaluation framework. The initial search retrieved 136 records from PubMed. After removing 4 duplicate entries, 132 unique articles were screened by title and abstract. A total of 20 full-text articles were evaluated, among which 16 studies were finally included. Another eight landmark studies were manually retrieved from Google Scholar, Web of Science and IEEE Xplore to supplement the analysis of cortical mapping, mechanoreceptors, proprioception, motor unit recruitment and interface evolution. The synthesis shows that the strongest studies do not optimize stimulus intensity alone. They align stimulation site, encoding rule, and evaluation metrics with the upper limb afferent route from cutaneous receptors to somatotopic hand area (S1) and with the motor route that stabilizes grasp through corticospinal drive and residual muscle recruitment. On the basis of the synthesis, this work proposes a neuroanatomical mechanism diagram and a three-part evaluation criterion covering perceptual realism, functional utility, and neural congruence. The proposed framework provides a practical evaluation scaffold for selecting tactile feedback strategies in future bionic limb studies.
Xinbi Luo· Theoretical and Natural Scie...· 0 citations