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Calvert, J. S.

Publications and source records attributed to Calvert, J. S..

4 recordsLinked to original sources

A modular, high-bandwidth, bidirectional implantable device for neural interrogation

Modern neuroelectronic interfaces have shown great potential to diagnose conditions, address neurological dysfunction, and advance neuroscientific knowledge. However, neural interface systems today require tethered connections that restrict mobility, prevent testing across ecological contexts, and inhibit clinical translation to at-home use. Fully implantable commercial systems have previously been developed, but exhibit significant constraints, including a bulky design, limited modularity, low bandwidth, or unidirectional communication (e.g. deep brain stimulation systems, DBS; spinal cord stimulation systems, SCS). Here, we have developed the Modular Bionic Interface (MBI), a system composed of a fully implantable device and a worn unit for high-bandwidth, bidirectional interfacing with the nervous system. The MBI can record high fidelity electrophysiological signals and deliver spatiotemporally modulated electrical stimulation for clinical and research purposes through flexible interaction with third party implantable devices. We performed benchtop evaluation to validate the recording and stimulation capabilities of the MBI across a diverse range of inputs and outputs. We then evaluated the MBI system in vivo through chronic implantation within a sheep, where results were stable for the length of evaluation, over three months. While connected to an actively powered, third-party high-resolution spinal cord stimulation electrode array, the MBI system was able to deliver stimulation to evoke lower extremity motor responses and record spinal compound action potentials evoked by peripheral nerve and spinal stimulation. Through rigorous evaluation, we demonstrate a fully implantable system with a small footprint capable of high-resolution, bi-directional communication with the nervous system via modular connections to third-party devices. We expect that modular devices will further our ability to treat complex neurological disease and injury.

neuroscience↗

An active electronic bidirectional interface for high resolution interrogation of the spinal cord

ObjectiveEpidural electrical stimulation (EES) has shown promise as both a clinical therapy and research tool for studying nervous system function. However, available clinical EES paddles are limited to using a small number of contacts due to the burden of wires necessary to connect each contact to the therapeutic delivery device, limiting the treatment area or density of epidural electrode arrays. We aimed to eliminate this burden using advanced on-paddle electronics. ApproachWe developed a smart EES paddle with a 60-electrode programmable array, addressable using an active electronic multiplexer embedded within the electrode paddle body. The electronics are sealed in novel, ultra-low profile hermetic packaging. We conducted extensive reliability testing on the novel array, including a battery of ISO 10993-1 biocompatibility tests and determination of the hermetic package leak rate. We then evaluated the EES device in vivo, placed on the epidural surface of the ovine lumbosacral spinal cord for 15 months. Main resultsThe active paddle array performed nominally when implanted in sheep for over 15 months and no device-related malfunctions were observed. The onboard multiplexer enabled bespoke electrode arrangements across, and within, experimental sessions. We identified stereotyped responses to stimulation in lower extremity musculature, and examined local field potential responses to EES using high-density recording bipoles. Finally, spatial electrode encoding enabled machine learning models to accurately perform EES parameter inference for unseen stimulation electrodes, reducing the need for extensive training data in future deep models. SignificanceWe report the development and chronic large animal in vivo evaluation of a high-density EES paddle array containing active electronics. Our results provide a foundation for more advanced computation and processing to be integrated directly into devices implanted at the neural interface, opening new avenues for the study of nervous system function and new therapies to treat neural injury and dysfunction.

bioengineering↗

Uncovering biomarkers during therapeutic neuromodulation with PARRM: Period-based Artifact Reconstruction and Removal Method

Advances in device development have enabled concurrent stimulation and recording at adjacent locations in the central nervous system. However, stimulation artifacts obscure the sensed underlying neural activity. Here, we developed a novel method, termed Period-based Artifact Reconstruction and Removal Method (PARRM), to remove stimulation artifacts from neural recordings by leveraging the exact period of stimulation to construct and subtract a high-fidelity template of the artifact. Benchtop saline experiments, computational simulations, five unique in vivo paradigms across animal and human studies, and an obscured movement biomarker were used for validation. Performance was found to exceed that of state-of-the-art filters in recovering complex signals without introducing contamination. PARRM has several advantages: it is 1) superior in signal recovery; 2) easily adaptable to several neurostimulation paradigms; and 3) low-complexity for future on-device implementation. Real-time artifact removal via PARRM will enable unbiased exploration and detection of neural biomarkers to enhance efficacy of closed-loop therapies. SummaryOnline, real-time artifact removal via PARRM will enable unbiased exploration of neural biomarkers previously obscured by stimulation artifact.

neuroscience↗

Large propulsion demands increase locomotor learning at the expense of step length asymmetry

There is a clinical interest in increasing the extent of locomotor learning induced by split-belt treadmills that move each leg at different speeds. However, factors facilitating locomotor learning are poorly understood. We hypothesized that augmenting the braking forces, rather than propulsion forces, experienced at the feet would increase locomotor adaptation and learning. To test this, forces were modulated during split-belt walking with distinct slopes: inclined (larger propulsion than braking), declined (larger braking than propulsion), and flat (similar propulsion and braking). These groups were compared using step length asymmetry, which is a clinically relevant measure robustly adapted on split-belt treadmills. Unexpectedly, the group with larger propulsion demands (i.e., the incline group) adapted faster and more, and had larger after-effects when the split-belt perturbation was removed. We also found that subjects who propelled more during baseline and experienced larger disruptions of propulsion forces in early adaptation exhibited greater after-effects, which further highlights the catalytic role of propulsion on locomotor learning. The relevance of mechanical demands on shaping our movements was also indicated by the steady state split-belt behavior, during which each group recovered their baseline leg orientation to meet leg-specific force demands at the expense of step length symmetry. Notably, the flat group was nearly symmetric, whereas the incline and decline group overshot and undershot symmetry, respectively. Taken together, our results indicate that forces propelling the body facilitate gait adaptation during split-belt walking. Therefore, interventions that increase propulsion demands may be a viable strategy for augmenting locomotor learning in individuals with hemiparesis.\n\nKey Points SummaryO_LISplit-belt walking (i.e., legs moving at different speeds) can induce locomotor learning and even improve hemiparetic gait, but little is known about how to facilitate this process.\nC_LIO_LIWe investigated the effect of braking and propulsion forces on locomotor learning by testing young unimpaired subjects on the split-belt condition at different slopes (i.e., flat, decline, and incline), which distinctively modified these forces.\nC_LIO_LIPropulsion forces facilitated locomotor learning indicated by 1) greater adaptation and after-effects following split-belt walking of the inclined group, which experienced larger propulsion demands and 2) a positive correlation between individual after-effects and subject-specific propulsion during regular walking and initial steps in the split condition.\nC_LIO_LIInterestingly, incline and decline groups self-selected asymmetric step lengths at steady state in the split condition, challenging the prominent view that step length asymmetry is a biomarker for inefficient gait.\nC_LIO_LIOur results suggest that interventions augmenting propulsion demands could correct hemiparetic gait more effectively.\nC_LI

neuroscience↗