Biology subjects

Lempka, S. F.

Publications and source records attributed to Lempka, S. F..

9 recordsLinked to original sources

bioRxiv2026

Parameter-Dependent Effects of Spinal Cord Stimulation on Neural Activation and Evoked Compound Action Potentials

ObjectiveSpinal evoked compound action potentials (ECAPs) provide a quantitative measure of the neural response during spinal cord stimulation (SCS) and can be leveraged in closed-loop applications to control dose in response to spinal cord movement. However, interpretation of ECAPs recorded in vivo is limited by susceptibility to noise, inter-subject variability, and other confounding factors. As SCS systems evolve and the clinical and research applications of ECAPs expand, it is critical to understand how physiological and technical factors influence ECAP generation and morphology. ApproachWe used a computational modeling framework to systematically investigate the influence of anatomical (e.g., dorsal cerebrospinal fluid (dCSF) thickness), stimulation (e.g., pulse width, waveform shape, stimulation configuration, stimulation frequency), and recording configurations on the neural responses and ECAPs generated during SCS. We employed a hybrid computational modeling approach, coupling finite element method models with multicompartment axon models to simulate neural responses to SCS. Using these models, we characterized the spatiotemporal dynamics of neural recruitment and the resulting ECAP waveforms. Main resultsNeural responses and model ECAPs were strongly influenced by factors, such as dCSF thickness, pulse width, and stimulation waveform shape. Stimulation parameters introduced trade-offs between axonal recruitment thresholds, neural activation selectivity, and ECAP timing and morphology. Notably, similar ECAP amplitudes could obscure differences in the underlying neural recruitment. Complex ECAP morphologies also emerged in response to distinct stimulation paradigms, reflecting changes in the spatiotemporal properties of axonal activation. Additionally, we demonstrate that the selection of recording electrodes can be optimized to enhance recorded ECAP amplitudes. SignificanceOur findings provide a theoretical framework to advance our mechanistic understanding of SCS-induced ECAPs and offer insights into optimization strategies to improve closed-loop SCS therapies.

bioengineering↗

bioRxiv2026

Functional Somatotopy of Lumbar Dorsal Rootlets and its Role in Selective Recruitment via Lateral Spinal Cord Stimulation

ObjectiveLateral spinal cord stimulation (LSCS) is a promising approach for restoring somatosensory feedback in lower-limb amputees, but its spatial selectivity remains limited. Percepts often spread to unintended regions of the residual limb, and reducing electrode contact size may not improve focality. This study investigated whether the anatomical organization of lumbar dorsal rootlets (DR) imposes fundamental constraints on LSCS selectivity. ApproachAcute neurophysiology experiments were performed in six adult cats. Both LSCS and individual DR stimulation were conducted in the same animals. For DR stimulation, bipolar hook electrodes were used to stimulate individual DR, while antidromic compound action potentials (CAPs) were recorded from femoral and sciatic nerve branches instrumented with nerve cuffs. For LSCS, custom 32-contact epidural paddle electrodes were placed over the lateral surface of the spinal cord at corresponding vertebral levels. Recruitment thresholds, dynamic ranges, and response patterns were analyzed across spinal levels, and DR recruitment patterns were directly compared to those evoked by LSCS within the same animals. Main resultsA clear rostrocaudal organization was observed across spinal levels during stimulation of individual DR, with femoral branches predominantly recruited at L4-L5 and sciatic branches at L6-L7. However, no somatotopic organization was found across DR within each spinal level; individual DR frequently co-activated multiple branches within the same group, and selective recruitment could only be maintained over a narrow dynamic range (median [~]10 {micro}A). LSCS exhibited even a narrower dynamic range ([~]5 {micro}A) but closely mirrored DR recruitment patterns, indicating that LSCS activates sensory afferents in a manner determined by the organizational structure of the DR. SignificanceThese findings demonstrate that the limited spatial selectivity of LSCS can largely be attributed to the coarse organization of DR within each root level rather than due to limitations of epidural electrode design. Moving electrodes intradurally or reducing contact size further is unlikely to substantially improve focality. Instead, improving paddle stability to ensure consistent placement over the appropriate spinal levels may be a more effective strategy for enhancing percept localization.

neuroscience↗

bioRxiv2026

Selectivity of Lateral Epidural Spinal Cord Stimulation with Varying Electrode Diameters and Stimulation Configurations

Objective. Our prior studies have demonstrated that lateral spinal cord stimulation can evoke somatosensory percepts in the missing foot in individuals with a lower-limb amputation. However, subjects reported concurrent sensations in their residual limb. In this study, we evaluate the hypothesis that using high-density paddle electrodes with smaller contact sizes, and multipolar stimulation configurations could evoke more focal sensations in the foot over a wide range of stimulation amplitudes. Approach. We used a combination of electrophysiology and computational modelling methods to investigate the selective activation of distal nerve branches in response to lateral spinal cord stimulation in cats. In six acute feline experiments, we performed an L3-S1 laminectomy and placed custom 32-electrode paddles laterally over the dura of the spinal cord. We recorded antidromic action potentials in the distal branches of the sciatic and femoral nerve trunks in response to stimulation using three contact diameters (150, 500 and 1000 {micro}m) and two stimulation configurations - monopolar and bipolar stimulation. We replicated the neural recruitment patterns from those experiments in a computational model of the feline lumbar spinal cord. We then used the model to examine neural recruitment with 1.8 mm and 2.5 mm contacts, as well as a tripolar guarded-cathode configuration. Main results. In the electrophysiology experiments, the 500 {micro}m-diameter electrodes achieved the most selective nerve activation (68%) compared to 62% for both 150 and 1000 {micro}m-diameter electrodes. The minimum amplitudes for recruiting nerve branches (i.e., threshold) as well as the dynamic ranges were largely similar for the different contact diameters (median: 35 {micro}A) and stimulation configurations (30 {micro}A for bipolar stimulation; 35 {micro}A for monopolar stimulation). The computational model reproduced the finding that selectivity did not differ significantly among the three contact sizes tested in cat experiments, though it revealed that increasing contact diameter above 1000 {micro}m raised the minimum amplitude required for selective activation and reduced spinal root selectivity. Across both approaches, we consistently recruited large-diameter afferents that are critical for somatosensory applications of spinal cord stimulation. Significance. Our results indicate that, relative to clinical electrodes, reducing the contact diameter of stimulation electrodes can evoke focal sensations, but further reductions below 1000 {micro}m may fail to improve selectivity. This study highlights potential constraints with achieving focal selectivity that are not dependent on the design of the electrodes.

bioengineering↗

bioRxiv2024

Mechanisms for dysregulation of excitatory-inhibitory balance underlying allodynia in dorsal horn neural subcircuits

Chronic pain is a wide-spread condition that is debilitating and expensive to manage, costing the United States alone around $600 billion in 2010. In a common type of chronic pain called allodynia, non-painful stimuli produce painful responses with highly variable presentations across individuals. While the specific mechanisms remain unclear, allodynia is hypothesized to be caused by the dysregulation of excitatory-inhibitory (E-I) balance in pain-processing neural circuitry in the dorsal horn of the spinal cord. In this work, we analyze biophysically-motivated subcircuit structures that represent common motifs in neural circuits in layers I-II of the dorsal horn. These circuits are hypothesized to be part of the neural pathways that mediate two different types of allodynia: static and dynamic. We use neural firing rate models to describe the activity of populations of excitatory and inhibitory interneurons within each subcircuit. By accounting for experimentally-observed responses under healthy conditions, we specify model parameters defining populations of subcircuits that yield typical behavior under normal conditions. Then, we implement a sensitivity analysis approach to identify the mechanisms most likely to cause allodynia-producing dysregulation of the subcircuits E-I signaling. We find that disruption of E-I balance generally occurs either due to downregulation of inhibitory signaling so that excitatory neurons are "released" from inhibitory control, or due to upregulation of excitatory neuron responses so that excitatory neurons "escape" their inhibitory control. Which of these mechanisms is most likely to occur, the subcircuit components involved in the mechanism, and the proportion of subcircuits exhibiting the mechanism can vary depending on the subcircuit structure. These results suggest specific hypotheses about diverse mechanisms that may be most likely responsible for allodynia, thus offering predictions for the high interindividual variability observed in allodynia and identifying targets for further experimental studies on the underlying mechanisms of this chronic pain condition. Author summaryWhile chronic pain affects roughly 20% of the US adult population [1], symptoms and presentations of the condition are highly variable across individuals and its causes remain largely unknown. A prevailing hypothesis for the cause of a type of chronic pain called allodynia is that the balance between excitatory and inhibitory signaling pathways between neuron populations in the spinal cord dorsal horn may be disrupted. To help better understand neural mechanisms underlying allodynia, we analyze biologically-motivated mathematical models of subcircuits of neuron populations that are part of the pain processing signaling pathway in the dorsal horn of the spinal cord. We use a novel sensitivity analysis approach to identify mechanisms of subcircuit dysregulation that may contribute to two different types of allodynia. The model results identify specific subcircuit components that are most likely to contribute to each type of allodynia. These mechanisms suggest targets for further experimental study, as well as for pharmacological intervention for better pain treatments.

neuroscience↗

bioRxiv2024

High-frequency amplitude-modulated sinusoidal stimulation induces desynchronized yet controllable neural firing

Regaining sensory feedback is critical for people living with limb amputation. Electrical stimulation of sensory fibers in peripheral nerves has been shown to restore focal percepts in the missing limb. However, conventional rectangular current pulses induce sensations often described as unnatural, likely due to the synchronous and periodic nature of activity they evoke. Here we introduce a fast-oscillating amplitude-modulated sinusoidal (FAMS) stimulation waveform that desynchronizes neural activity. Using computational modeling, we show that sinusoidal waveforms evoke asynchronous and irregular firing patterns, with frequency-dependent effects. Leveraging both low- and high-frequency mechanisms, FAMS exploits membrane nonlinearities to enhance neuron-specific differences. In a feline model of peripheral nerve stimulation, FAMS evoked activity that was more asynchronous than conventional rectangular pulses, while remaining easily controllable with simple stimulation parameters. Importantly, in human experiments using noninvasive stimulation of the median nerve, participants reported that FAMS evoked more natural sensations compared to rectangular biphasic pulses in a two-alternative forced-choice task. The preference for FAMS increased at higher intensities above sensory threshold, despite intensity-matched stimulation across waveform types. These findings provide evidence that reduced synchrony in afferent recruitment translates into more naturalistic and comfortable sensory percepts. Together, our results establish FAMS as a promising biomimetic stimulation strategy with potential for clinical applications in sensory feedback restoration. One Sentence SummaryA new electrical stimulation waveform allows for evoking and controlling more naturalistic neural activity than can be achieved with traditional stimulation waveforms.

bioengineering↗

bioRxiv2023

Multiformity of extracellular microelectrode recordings from Aδ neurons in the dorsal root ganglia: A computational modeling study

Microelectrodes serve as a fundamental tool in electrophysiology research throughout the nervous system, providing a means of exploring neural function with a high resolution of neural firing information. We constructed a hybrid computational model using the finite element method and multi-compartment cable models to explore factors that contribute to extracellular voltage waveforms that are produced by sensory pseudounipolar neurons -- specifically, smaller A-type neurons -- and that are recorded by microelectrodes in dorsal root ganglia. The finite element method model included a dorsal root ganglion, surrounding tissues, and a planar microelectrode array. We built a multi-compartment neuron model with multiple trajectories of the glomerular initial segment found in many A-type sensory neurons. Our model replicated both the somatic intracellular voltage profile of A{delta} low-threshold mechanoreceptor neurons and the unique extracellular voltage waveform shapes that are observed in experimental settings. Results from this model indicated that tortuous glomerular initial segment geometries can introduce distinct multiphasic properties into a neurons recorded waveform. Our model also demonstrated how recording location relative to specific microanatomical components of these neurons, and recording distance from these components, can contribute to additional changes in the multiphasic characteristics and peak-to-peak voltage amplitude of the waveform. This knowledge may provide context for research employing microelectrode recordings of pseudounipolar neurons in sensory ganglia, including functional mapping and closed-loop neuromodulation. Further, our simulations gave insight into the neurophysiology of pseudounipolar neurons by demonstrating how the glomerular initial segment aids in increasing the resistance of the stem axon and mitigating rebounding somatic action potentials.

neuroscience↗

bioRxiv2021

Augmented Transcutaneous Stimulation Using an Injectable Electrode

Minimally invasive neuromodulation technologies seek to marry the neural selectivity of implantable devices with the low-cost and non-invasive nature of transcutaneous electrical stimulation (TES). The Injectrode(R) is a needle-delivered electrode that is injected onto neural structures under image guidance. Power is then transcutaneously delivered to the Injectrode using surface electrodes. The Injectrode serves as a low-impedance conduit to guide current to the deep on-target nerve, reducing activation thresholds by an order of magnitude compared to using only surface stimulation electrodes. To minimize off-target recruitment of cutaneous fibers, the energy transfer efficiency from the surface electrodes to the Injectrode must be optimized. TES energy is transferred to the Injectrode through both capacitive and resistive mechanisms. Electrostatic finite element models generally used in TES research consider only the resistive means of energy transfer by defining tissue conductivities. Here, we present an electroquasistatic model, taking into consideration both the conductivity and permittivity of tissue, to understand transcutaneous power delivery to the Injectrode. The model was validated with measurements taken from (n=4) swine cadavers. We used the validated model to investigate system and anatomic parameters that influence the coupling efficiency of the Injectrode energy delivery system. Our work suggests the relevance of electroquasistatic models to account for capacitive charge transfer mechanisms when studying TES, particularly when high-frequency voltage components are present, such as those used for voltage-controlled pulses and sinusoidal nerve blocks.

bioengineering↗

bioRxiv2021

Stimulation of the Dorsal Root Ganglion using an Injectrode

ObjectiveThe goal of this work was to compare afferent fiber recruitment by dorsal root ganglion (DRG) stimulation using an injectable polymer electrode (Injectrode(R)) and a more traditional cylindrical metal electrode. ApproachWe exposed the L6 and L7 DRG in four cats via a partial laminectomy or burr hole. We stimulated the DRG using an Injectrode or a stainless steel electrode using biphasic pulses at three different pulse widths (80, 150, 300 s) and pulse amplitudes spanning the range used for clinical DRG stimulation. We recorded antidromic evoked compound action potentials (ECAPs) in the sciatic, tibial, and common peroneal nerves using nerve cuffs. We calculated the conduction velocity of the ECAPs and determined the charge-thresholds and recruitment rates for ECAPs from A, A{beta}, and A{delta} fibers. We also performed electrochemical impedance spectroscopy measurements for both electrode types. Main ResultsThe ECAP thresholds for the Injectrode did not differ from the stainless steel electrode across all primary afferents (A, A{beta}, A{delta}) and pulse widths; charge-thresholds increased with wider pulse widths. Thresholds for generating ECAPs from A{beta} fibers were 100.0 {+/-} 32.3 nC using the stainless steel electrode, and 90.9 {+/-} 42.9 nC using the Injectrode. The ECAP thresholds from the Injectrode were consistent over several hours of stimulation. The rate of recruitment was similar between the Injectrodes and stainless steel electrode and decreased with wider pulse widths. SignificanceThe Injectrode can effectively excite primary afferents when used for DRG stimulation within the range of parameters used for clinical DRG stimulation. The Injectrode can be implanted through minimally invasive techniques while achieving similar neural activation to conventional electrodes, making it an excellent candidate for future DRG stimulation and neuroprosthetic applications.

bioengineering↗

bioRxiv2019

Realistic Anatomically Detailed Open-Source Spinal Cord Stimulation (RADO-SCS) Model

ObjectiveComputational current flow models of spinal cord stimulation (SCS) are widely used in device development, clinical trial design, and patient programming. Proprietary models of varied sophistication have been developed. An open-source model with state-of-the-art precision would serve as a standard for SCS simulation. ApproachWe developed a sophisticated SCS modeling platform, named Realistic Anatomically Detailed Open-Source Spinal Cord Stimulation (RADO-SCS) model. This platform consists of realistic and detailed spinal cord and ancillary tissues anatomy derived based on prior imaging and cadaveric studies. Represented tissues within the T9-T11 spine levels include vertebrae, intravertebral discs, epidural space, dura, CSF, white-matter, gray-matter, dorsal and ventral roots and rootlets, dorsal root ganglion, sympathetic chain, thoracic aorta, epidural space vasculature, white-matter vasculature, and thorax. As an exemplary, a bipolar SCS montage was simulated to illustrate the model workflow from the electric field calculated from a finite element model (FEM) to activation thresholds predicted for individual axons populating the spinal cord. Main ResultsCompared to prior models, RADO-SCS meets or exceeds detail for every tissue compartment. The resulting electric fields in white and gray-matter, and axon model activation thresholds are broadly consistent with prior stimulations. SignificanceThe RADO-SCS can be used to simulate any SCS approach with both unprecedented resolution (precision) and transparency (reproducibility). Freely available online, the RADO-SCS will be updated continuously with version control.

neuroscience↗