Biology subjects

Suminski, A.

Publications and source records attributed to Suminski, A..

4 recordsLinked to original sources

bioRxiv2026

Identification of low threshold off-target activation pathways during stimulation of carotid baroreceptor afferents in swine.

ObjectiveElectrical stimulation of the baroreceptors pathways at the carotid sinus bulb - known as baroreflex activation therapy (BAT) - is intended to change autonomic tone and ultimately reduce blood pressure and heart rate. BAT is pre-market approved by the United States Food and Drug Administration (FDA) for the treatment of heart failure and received an FDA humanitarian device exemption for drug resistant hypertension. However, responder rates are limited by side-effects including numbness in the head and neck, altered speech, respiratory constriction, dry cough, vomiting, and altered sensory and motor function of the tongue. We hypothesized that these side-effects are driven by activation of other nearby nerve fibers of similar or lower threshold than the carotid sinus nerve. In this study, we sought to identify the neural sources responsible for off-target muscle activation contributing to these side-effects. These sources would inform strategies mitigating off-target activation in BAT therapy. MethodsDomestic swine were used in this work as the diameter and thickness of the swine carotid artery are closer to human than those of canine models. A monopolar disk electrode mimicking the clinical CVRx(R) Neo electrode was surgically placed proximal to the carotid bifurcation with the position optimized for stimulation dose responsive changes in blood pressure. Evoked responses were recorded during dose response testing from multiple neck muscles, and the corresponding off-target nerve pathways were identified by sequential transection of nearby nerves. ResultsThe following activated off-target muscle groups and their corresponding nerve pathways were verified which included 1) the cricoarytenoid via recurrent laryngeal nerve, 2) cricothyroid via superior laryngeal nerve, 3) sternocleidomastoid via accessory nerve, and 4) the tongue via hypoglossal nerve. The constrictor muscle group was also activated through a more complex neural pathway. ConclusionWe identified multiple sources of therapy-limiting side-effects of BAT in the swine model. These results will help guide the design of improved stimulation electrodes, surgical placement, and parameter programming to reduce BAT-associated side-effects while increasing on-target activation in patients.

bioengineering↗

bioRxiv2025

Combined Central and Peripheral Nerve Stimulation Improves Functional Recovery of Mixed Peripheral Nerve Injury in a Rat Forelimb Model

IntroductionPeripheral nerve reinnervation following nerve injury is often a slow and incomplete process, resulting in significant morbidity and permanent loss of function of the injured extremity in many patients. Prior studies have shown the efficacy of electrical stimulation to synchronize the axonal regeneration of both motor and sensory neurons in peripheral nerve injury models. Moreover, separate investigations have also shown the use of cranial nerve stimulation, principally the vagus nerve, to improve functional outcomes. However, no study has investigated the synergistic effects of both intraoperative electrical stimulation and cranial nerve stimulation for functional improvement within a peripheral nerve injury model. This investigation quantifies the efficacy of combined intraoperative electrical stimulation and trigeminal nerve stimulation on motor and sensory functional recovery in a rat peripheral nerve injury model. MethodsTwelve adult male Lewis rats were trained in a reach and pull task for a food reward using their right forelimb with baseline force thresholds and percent success of the pull task recorded. Baseline sensory data was retrieved using an automated von Frey monofilament test. All rats underwent surgical transection and 2mm gap repair of their median and ulnar nerve of their right forelimb followed by 1 hour of intraoperative electrical stimulation. Trigeminal nerve stimulation throughout the rehabilitation period was completed via supraorbital nerve headcap electrodes. Motor and sensory data were compared to historic cohorts comprised of sham surgery (no nerve injury), brief intraoperative electrical stimulation, trigeminal nerve stimulation, and a sham peripheral and trigeminal nerve stimulation group. Polarization sensitive optical computed tomography (PS-OCT) was used to assess nerve regeneration in fixed tissue samples. ResultsThe combined cohort of rodents were able to recover to their pre-injury motor function by the third week of rehabilitation, faster than either of the singular electrical stimulation cohorts assessed previously. Moreover, functional sensory data of the combined stim cohort demonstrated no change when compared to their pre-injury baseline. ConclusionsPeripheral nerve electrical stimulation and trigeminal nerve stimulation are two separately acting mechanisms of therapy that employ electric waveforms to improve the functional recovery of injured peripheral nerves. The former acts within the periphery to synchronize axonal growth and regeneration of the injured neurons, while the latter acts centrally to augment neuroplasticity. When used simultaneously in a rodent peripheral nerve injury model, these modalities have shown to build upon each other to deliver a faster functional motor recovery, while sensory recovery outcomes remain to be demonstrated.

neuroscience↗

bioRxiv2024

Epidural Spinal Cord Recordings (ESRs): Sources of Artifact in Stimulation Evoked Compound Action Potentials

IntroductionEvoked compound action potentials (ECAPs) measured using epidural spinal recordings (ESRs) during epidural spinal cord stimulation (SCS) can help elucidate fundamental mechanisms for the treatment of pain, as well as inform closed-loop control of SCS. Previous studies have used ECAPs to characterize the neural response to various neuromodulation therapies and have demonstrated that ECAPs are highly prone to multiple sources of artifact, including post-stimulus pulse capacitive artifact, electromyography (EMG) bleed-through, and motion artifact resulting from disturbance of the electrode/tissue interface during normal behavior. However, a thorough characterization has yet to be performed for how these sources of artifact may contaminate recordings within the temporal window commonly used to determine activation of A-beta fibers in a large animal model. MethodsWe characterized the sources of artifacts that can contaminate the recording of ECAPs in an epidural SCS swine model using the Abbott Octrode lead. Muscle paralytics were administered to block muscle activation preventing EMG from contaminating the recorded ECAPs. Concurrent EMG recordings of the longissimus, a long muscle of the back, were used to confirm a 2-4 millisecond (ms) latency source of EMG bleed-through that frequently contaminated the A-beta temporal window. Additionally, we obtained recordings approximately 5-10 minutes post-mortem after clear evoked A-beta and associated EMG responses ceased to characterize the representation of stimulation artifact across the array. ResultsSpinal ECAP recordings can be contaminated by capacitive artifact, short latency EMG from nearby long muscles of the back, and motion artifact from multiple sources. In many cases, the capacitive artifact can appear nearly identical in duration and waveshape to evoked A-beta responses. These sources of EMG can have phase shifts across the electrode array, very similar to the phase shift anticipated by propagation of an evoked A-beta fiber response across the array. This short latency EMG is often evident at currents similar to those needed to activate A-beta fibers associated with the treatment of pain. Changes in cerebrospinal fluid between the cord and dura, and motion induced during breathing created a cyclic oscillation in all evoked components of the recorded ECAP signal. ConclusionCareful controls must be implemented to accurately separate neural signal from the sources of artifact in spinal cord ECAPs. To address this, we suggest experimental procedures and associated reporting requirements necessary to disambiguate the underlying neural response from these confounds. These data are important to better understand the conceptual framework for recorded ESRs, with components such as ECAPs, EMG responses and artifacts, and have important implications for closed-loop control algorithms to account for transient motion such as postural changes and cough.

neuroscience↗

bioRxiv2019

Graded recruitment of pupil-linked neuromodulation by parametric stimulation of the vagus nerve

AO_SCPLOWBSTRACTC_SCPLOWVagus nerve stimulation (VNS) is thought to affect neural activity by recruiting brain-wide release of neuromodulators. VNS is used in treatment-resistant epilepsy, and is increasingly being explored for other disorders, such as depression, and as a cognitive enhancer. However, the promise of VNS is only partially fulfilled due to a lack of mechanistic understanding of the transfer function between stimulation parameters and neuromodulatory response, together with a lack of biosensors for assaying stimulation efficacy in real time. We here develop an approach to VNS in head-fixed mice on a treadmill and show that pupil dilation is a reliable and convenient biosensor for VNS-evoked cortical neuromodulation. In an optimal zone of stimulation parameters, current leakage and off-target effects are minimized and the extent of pupil dilation tracks VNS-evoked basal-forebrain cholinergic axon activity in neocortex. Thus, pupil dilation is a sensitive readout of the moment-by-moment, titratable effects of VNS on brain state.

neuroscience↗