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Objective.Minimally invasive neuromodulation therapies like the Injectrode, which is composed of a tightly wound polymer-coated Platinum/Iridium microcoil, offer a low-risk approach for administering electrical stimulation to the dorsal root ganglion (DRG). This flexible electrode is aimed to conform to the DRG. The stimulation occurs through a transcutaneous electrical stimulation (TES) patch, which subsequently transmits the stimulation to the Injectrode via a subcutaneous metal collector. However, it is important to note that the effectiveness of stimulation through TES relies on the specific geometrical configurations of the Injectrode-collector-patch system. Hence, there is a need to investigate which design parameters influence the activation of targeted neural structures.Approach.We employed a hybrid computational modeling approach to analyze the impact of Injectrode system design parameters on charge delivery and neural response to stimulation. We constructed multiple finite element method models of DRG stimulation, followed by the implementation of multi-compartment models of DRG neurons. By calculating potential distribution during monopolar stimulation, we simulated neural responses using various parameters based on prior acute experiments. Additionally, we developed a canonical monopolar stimulation and full-scale model of bipolar bilateral L5 DRG stimulation, allowing us to investigate how design parameters like Injectrode size and orientation influenced neural activation thresholds.Main results.Our findings were in accordance with acute experimental measurements and indicate that the minimally invasive Injectrode system predominantly engages large-diameter afferents (Aß-fibers). These activation thresholds were contingent upon the surface area of the Injectrode. As the charge density decreased due to increasing surface area, there was a corresponding expansion in the stimulation amplitude range before triggering any pain-related mechanoreceptor (Aδ-fibers) activity.Significance.The Injectrode demonstrates potential as a viable technology for minimally invasive stimulation of the DRG. Our findings indicate that utilizing a larger surface area Injectrode enhances the therapeutic margin, effectively distinguishing the desired Aßactivation from the undesired Aδ-fiber activation.
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Ganglios Espinales , Neuronas , Humanos , Ganglios Espinales/fisiología , Dolor , Estimulación Eléctrica , Simulación por ComputadorRESUMEN
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 multicompartment 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 multicompartment 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 Aδ 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 neuron's 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. Furthermore, 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.NEW & NOTEWORTHY We built a computational model of sensory neurons in the dorsal root ganglia to investigate factors that influence the extracellular waveforms recorded by microelectrodes. Our model demonstrates how the unique structure of these neurons can lead to diverse and often multiphasic waveform profiles depending on the location of the recording contact relative to microanatomical neural components. Our model also provides insight into the neurophysiological function of axon glomeruli that are often present in these neurons.
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Ganglios Espinales , Células Receptoras Sensoriales , Ganglios Espinales/fisiología , Microelectrodos , Potenciales de Acción/fisiología , Simulación por ComputadorRESUMEN
In this issue of Cell Reports Methods, Dedek et al. present RAMalgo-an AI-powered, automated platform for quantifying nociceptive behaviors in mice. With integrated video tracking and mechanical, thermal, and optogenetic stimulation, RAMalgo has the potential to increase standardization and throughput of pain behavior measurement in rodents.
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Dolor , Ratones , Animales , Dolor/diagnóstico , Dimensión del Dolor/métodosRESUMEN
Objective: Minimally invasive neuromodulation therapies like the Injectrode, which is composed of a tightly wound polymer-coated platinum/iridium microcoil, offer a low-risk approach for administering electrical stimulation to the dorsal root ganglion (DRG). This flexible electrode is aimed to conform to the DRG. The stimulation occurs through a transcutaneous electrical stimulation (TES) patch, which subsequently transmits the stimulation to the Injectrode via a subcutaneous metal collector. However, effectiveness of stimulation relies on the specific geometrical configurations of the Injectrode-collector-patch system. Hence, there is a need to investigate which design parameters influence the activation of targeted neural structures. Approach: We employed a hybrid computational modeling approach to analyze the impact of the Injectrode system design parameters on charge delivery and the neural response to stimulation. We constructed multiple finite element method models of DRG stimulation and multi-compartment models of DRG neurons. We simulated the neural responses using parameters based on prior acute preclinical experiments. Additionally, we developed multiple human-scale computational models of DRG stimulation to investigate how design parameters like Injectrode size and orientation influenced neural activation thresholds. Main results: Our findings were in accordance with acute experimental measurements and indicated that the Injectrode system predominantly engages large-diameter afferents (Aß-fibers). These activation thresholds were contingent upon the surface area of the Injectrode. As the charge density decreased due to increasing surface area, there was a corresponding expansion in the stimulation amplitude range before triggering any pain-related mechanoreceptor (Aδ-fibers) activity. Significance: The Injectrode demonstrates potential as a viable technology for minimally invasive stimulation of the DRG. Our findings indicate that utilizing a larger surface area Injectrode enhances the therapeutic margin, effectively distinguishing the desired Aß activation from the undesired Aδ-fiber activation.
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Dorsal root ganglion stimulation (DRGS) is a neurostimulation therapy used to manage chronic pain that does not respond to conventional therapies. Unfortunately, not all patients receive sufficient pain relief from DRGS, leaving them with few other treatment options. Presently, our understanding of the mechanisms of action of DRGS is incomplete, preventing us from determining why some patients do not receive analgesia from the therapy. One hypothesis suggests that DRGS augments the filtering of action potentials (APs) at the T-junction of nociceptive C-neurons. To test this hypothesis, we utilized a computational modeling approach in which we developed a population of one thousand biophysically distinct C-neuron models which each produced electrophysiological characteristics (e.g., AP height, AP duration) reported in previous experimental studies. We used this population of model C-neurons to study how morphological and electrophysiological characteristics affected the propagation of APs through the T-junction. We found that trains of APs can propagate through the T-junction in the orthodromic direction at a higher frequency than in the antidromic direction due to the decrease in axonal diameter from the peripheral to spinal axon. Including slow outward conductances in the axonal compartments near the T-junction reduced following frequencies to ranges measured experimentally. We next used the population of C-neuron models to investigate how DRGS affected the orthodromic propagation of APs through the T-junction. Our data suggest that suprathreshold DRGS augmented the filtering of APs at the T-junction of some model C-neurons while increasing the activity of other model C-neurons. However, the stimulus pulse amplitudes required to induce activity in C-neurons (i.e., several mA) fell outside the range of stimulation pulse amplitudes used clinically (i.e., typically ≤1â mA). Furthermore, our data suggest that somatic GABA currents activated directly or indirectly by the DRGS pulse may produce diverse effects on orthodromic AP propagation in C-neurons. These data suggest DRGS may produce differential effects across a population of C-neurons and indicate that understanding how inherent biological variability affects a neuron's response to therapeutic electrical stimulation may be helpful in understanding its mechanisms of action.
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Chronic itch is associated with sensitization of the somatosensory nervous system. Recent studies have identified the neural circuits transmitting acute itch; however, the mechanisms by which itch transforms into a pathological state remain largely unknown. We have previously shown that Aß low-threshold mechanoreceptors, together with spinal urocortin 3-positive (Ucn3+) excitatory interneurons and neuropeptide Y-positive (NPY+) inhibitory interneurons, form a microcircuit that transmits and gates acute mechanical itch. Here, using whole-cell patch-clamp recordings, we observed increased excitability in spinal Ucn3+ neurons under chronic itch conditions. In contrast to Ucn3+ neurons, the excitability of spinal NPY+ neurons was largely reduced under chronic itch conditions. To explore the molecular mechanisms underlying sensitization of this microcircuit, we examined the mRNA expression levels of voltage-gated ion channels in recorded spinal Ucn3+ and NPY+ neurons by single-cell quantitative real-time PCR (qRT-PCR). We found that the expression levels of Nav1.6 and Cav2.3 channels were increased in spinal Ucn3+ neurons in chronic itch mice, while the expression level of SK3 channels was decreased. By contrast, the expression levels of Nav1.6 and BK channels were decreased in spinal NPY+ neurons in chronic itch mice. To determine the contribution of different ion channels in chronic itch sensitization, we then used a Markov Chain Monte Carlo method to parameterize a large number of biophysically distinct multicompartment models of Ucn3+ and NPY+ neurons. These models included explicit representations of the ion channels that we found to be up- or down-regulated under chronic itch conditions. Our models demonstrated that changes in Nav1.6 conductance are predominantly responsible for the changes in excitability of both Ucn3+ and NPY+ neurons during chronic itch pathogenesis. Furthermore, when simulating microcircuits of our Ucn3+ and NPY+ models, we found that reduced Nav1.6 conductance in NPY+ models played a major role in opening the itch gate under chronic itch conditions. However, changing SK, BK, or R-type calcium channel conductance had negligible effects on the sensitization of this circuit. Therefore, our results suggest that Nav1.6 channels may play an essential role in mechanical itch sensitization. The findings presented here may open a new avenue for developing pharmaceutical strategies to treat chronic itch.
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Due to the prevalence of chronic pain worldwide, there is an urgent need to improve pain management strategies. While opioid drugs have long been used to treat chronic pain, their use is severely limited by adverse effects and abuse liability. Neurostimulation techniques have emerged as a promising option for chronic pain that is refractory to other treatments. While different neurostimulation strategies have been applied to many neural structures implicated in pain processing, there is variability in efficacy between patients, underscoring the need to optimize neurostimulation techniques for use in pain management. This optimization requires a deeper understanding of the mechanisms underlying neurostimulation-induced pain relief. Here, we discuss the most commonly used neurostimulation techniques for treating chronic pain. We present evidence that neurostimulation-induced analgesia is in part driven by the release of endogenous opioids and that this endogenous opioid release is a common endpoint between different methods of neurostimulation. Finally, we introduce technological and clinical innovations that are being explored to optimize neurostimulation techniques for the treatment of pain, including multidisciplinary efforts between neuroscience research and clinical treatment that may refine the efficacy of neurostimulation based on its underlying mechanisms.
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Dorsal root ganglion stimulation (DRGS) is a neuromodulation therapy for chronic pain that is refractory to conventional medical management. Currently, the mechanisms of action of DRGS-induced pain relief are unknown, precluding both our understanding of why DRGS fails to provide pain relief to some patients and the design of neurostimulation technologies that directly target these mechanisms to maximize pain relief in all patients. Due to the heterogeneity of sensory neurons in the dorsal root ganglion (DRG), the analgesic mechanisms could be attributed to the modulation of one or many cell types within the DRG and the numerous brain regions that process sensory information. Here, we summarize the leading hypotheses of the mechanisms of DRGS-induced analgesia, and propose areas of future study that will be vital to improving the clinical implementation of DRGS. PERSPECTIVE: This article synthesizes the evidence supporting the current hypotheses of the mechanisms of action of DRGS for chronic pain and suggests avenues for future interdisciplinary research which will be critical to fully elucidate the analgesic mechanisms of the therapy.
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Dolor Crónico/terapia , Terapia por Estimulación Eléctrica , Ganglios Espinales , Neuroestimuladores Implantables , Neuralgia/terapia , Evaluación de Resultado en la Atención de Salud , HumanosRESUMEN
For epiretinal prostheses, disc electrodes stimulate retinal ganglion cells (RGCs) with electric current to create visual percepts. Prior studies have determined that the sodium channel band (SOCB), located on the RGC axon (30-50 µm from the soma) is the most sensitive site to extracellular stimulation because of its high sodium channel density. Biophysical cable models used to study RGC activation in silico often rely on simplified axon trajectories, disregarding the non-uniform paths that axons follow to the optic disc. However, since axonal activation is a critical mechanism in epiretinal stimulation, it is important to investigate variable RGC axon trajectories. In this study, we use a computational model to perform a sensitivity analysis examining how the morphology of an RGC axon affects predictions of retinal activation. We determine that RGC cable models are sensitive to changes in the ascending axon trajectory between the soma and nerve fiber layer. On the other hand, RGC cable models are relatively robust to trajectory deviations in the plane parallel to the disc electrode's surface. Overall, our results suggest that incorporating natural variations of soma depth and nerve fiber layer entry angle could result in a more realistic model of the retina's response to epiretinal stimulation and a better understanding of elicited visual percepts.
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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® 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.
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OBJECTIVE: Dorsal root ganglion stimulation (DRGS) is an effective therapy for chronic pain, though its mechanisms of action are unknown. Currently, we do not understand how clinically controllable parameters (e.g., electrode position, stimulus pulse width) affect the direct neural response to DRGS. Therefore, the goal of this study was to utilize a computational modeling approach to characterize how varying clinically controllable parameters changed neural activation profiles during DRGS. MATERIALS AND METHODS: We coupled a finite element model of a human L5 DRG to multicompartment models of primary sensory neurons (i.e., Aα-, Aß-, Aδ-, and C-neurons). We calculated the stimulation amplitudes necessary to elicit one or more action potentials in each neuron, and examined how neural activation profiles were affected by varying clinically controllable parameters. RESULTS: In general, DRGS predominantly activated large myelinated Aα- and Aß-neurons. Shifting the electrode more than 2 mm away from the ganglion abolished most DRGS-induced neural activation. Increasing the stimulus pulse width to 500 µs or greater increased the number of activated Aδ-neurons, while shorter pulse widths typically only activated Aα- and Aß-neurons. Placing a cathode near a nerve root, or an anode near the ganglion body, maximized Aß-mechanoreceptor activation. Guarded active contact configurations did not activate more Aß-mechanoreceptors than conventional bipolar configurations. CONCLUSIONS: Our results suggest that DRGS applied with stimulation parameters within typical clinical ranges predominantly activates Aß-mechanoreceptors. In general, varying clinically controllable parameters affects the number of Aß-mechanoreceptors activated, although longer pulse widths can increase Aδ-neuron activation. Our data support several Neuromodulation Appropriateness Consensus Committee guidelines on the clinical implementation of DRGS.
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Dolor Crónico , Ganglios Espinales , Potenciales de Acción , Humanos , NeuronasRESUMEN
OBJECTIVE: Spinal cord stimulation (SCS) is a common neurostimulation therapy to treat chronic pain. Computational models represent a valuable tool to study the potential mechanisms of action of SCS and to optimize the design and implementation of SCS technologies. However, it is imperative that these computational models include the appropriate level of detail to accurately predict the neural response to SCS and to correlate model predictions with clinical outcomes. Therefore, the goal of this study was to investigate several anatomic and technical factors that may affect model-based predictions of neural activation during thoracic SCS. APPROACH: We developed computational models that consisted of detailed finite element models of the lower thoracic spinal cord, surrounding tissues, and implanted SCS electrode arrays. We positioned multicompartment models of sensory axons within the spinal cord to calculate the activation threshold for each sensory axon. We then investigated how activation thresholds changed as a function of several anatomical variables (e.g. spine geometry, dorsal rootlet anatomy), stimulation type (i.e. voltage-controlled vs. current-controlled), electrode impedance, lead position, lead type, and electrical properties of surrounding tissues (e.g. dura conductivity, frequency-dependent conductivity). MAIN RESULTS: Several anatomic and modeling factors produced significant percent differences or errors in activation thresholds. Rostrocaudal positioning of the cathode with respect to the vertebrae had a large effect (up to 32%) on activation thresholds. Variability in electrode impedance produced significant changes in activation thresholds for voltage-controlled stimulation (38% to 51%), but had little effect on activation thresholds for current-controlled stimulation (less than 13%). Changing the dura conductivity also produced significant differences in activation thresholds. SIGNIFICANCE: This study demonstrates several anatomic and technical factors that can affect the neural response to SCS. These factors should be considered in clinical implementation and in future computational modeling studies of thoracic SCS.
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Estimulación de la Médula Espinal , Axones , Electrodos Implantados , Espacio Epidural , Médula EspinalRESUMEN
GOAL: Retinal prosthesis performance is limited by the variability of elicited phosphenes. The stimulating electrode's position with respect to retinal ganglion cells (RGCs) affects both perceptual threshold and phosphene shape. We created a modeling framework incorporating patient-specific anatomy and electrode location to investigate RGC activation and predict inter-electrode differences for one Argus II user. METHODS: We used ocular imaging to build a three-dimensional finite element model characterizing retinal morphology and implant placement. To predict the neural response to stimulation, we coupled electric fields with multi-compartment cable models of RGCs. We evaluated our model predictions by comparing them to patient-reported perceptual threshold measurements. RESULTS: Our model was validated by the ability to replicate clinical impedance and threshold values, along with known neurophysiological trends. Inter-electrode threshold differences in silico correlated with in vivo results. CONCLUSIONS: We developed a patient-specific retinal stimulation framework to quantitatively predict RGC activation and better explain phosphene variations.
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Dorsal root ganglia (DRG), which contain the somata of primary sensory neurons, have increasingly been considered as novel targets for clinical neural interfaces, both for neuroprosthetic and pain applications. Effective use of either neural recording or stimulation technologies requires an appropriate spatial position relative to the target neural element, whether axon or cell body. However, the internal three-dimensional spatial organization of human DRG neural fibers and somata has not been quantitatively described. In this study, we analyzed 202 cross-sectional images across the length of 31 human L4 and L5 DRG from 10 donors. We used a custom semi-automated graphical user interface to identify the locations of neural elements in the images and normalize the output to a consistent spatial reference for direct comparison by spinal level. By applying a recursive partitioning algorithm, we found that the highest density of cell bodies at both spinal levels could be found in the inner 85% of DRG length, the outer-most 25-30% radially, and the dorsal-most 69-76%. While axonal density was fairly homogeneous across the DRG length, there was a distinct low density region in the outer 7-11% radially. These findings are consistent with previous qualitative reports of neural distribution in DRG. The quantitative measurements we provide will enable improved targeting of future neural interface technologies and DRG-focused pharmaceutical therapies, and provide a rigorous anatomical description of the bridge between the central and peripheral nervous systems.
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Ganglios Espinales/citología , Neuronas/citología , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagenología Tridimensional/métodos , Vértebras LumbaresRESUMEN
OBJECTIVES: Spinal cord stimulation (SCS) for pain is typically implemented in an open-loop manner using parameters that remain largely unchanged. To improve the overall efficacy and consistency of SCS, one closed-loop approach proposes to use evoked compound action potentials (ECAPs) recorded from the SCS lead(s) as a feedback control signal to guide parameter selection. The goal of this study was to use a computational modeling approach to investigate the source of these ECAP recordings and technical and physiological factors that affect their composition. METHODS: We developed a computational model that coupled a finite element model of lower thoracic SCS with multicompartment models of sensory axons within the spinal cord. We used a reciprocity-based approach to calculate SCS-induced ECAPs recorded from the SCS lead. RESULTS: Our model ECAPs contained a triphasic, P1, N1, P2 morphology. The model P2-N1 amplitudes and conduction velocities agreed with previous experimental data from human subjects. Model results suggested that the ECAPs are dominated by the activation of axons with diameters 8.7-10.0 µm located in the dorsal aspect of the spinal cord. We also observed changes in the ECAP amplitude and shape due to the electrode location relative to the vertebrae and spinal cord. CONCLUSION: Our modeling results suggest that clinically effective SCS relies on the activation of numerous axons within a narrow fiber diameter range and that several factors affect the composition of the ECAP recordings. These results can improve how we interpret and implement these recordings in a potential closed-loop approach to SCS.
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Simulación por Computador , Potenciales Evocados/fisiología , Modelos Anatómicos , Manejo del Dolor/métodos , Estimulación de la Médula Espinal/métodos , Médula Espinal/fisiología , HumanosRESUMEN
OBJECTIVE: The goal of this project was to use computational models to investigate which types of primary sensory neurons are modulated by dorsal root ganglion stimulation (DRGS) to provide pain relief. METHODS: We modeled DRGS by coupling an anatomical finite element model of a human L5 dorsal root ganglion to biophysical models of primary sensory neurons. We calculated the stimulation amplitude needed to elicit an action potential in each neuron, and examined how DRGS affected sensory neuron activity. RESULTS: We showed that within clinical ranges of stimulation parameters, DRGS drives the activity of large myelinated Aß-fibers but does not directly activate small nonmyelinated C-fibers. We also showed that the position of the active and return electrodes and the polarity of the stimulus pulse influence neural activation. CONCLUSIONS: Our results indicate that DRGS may provide pain relief by activating pain-gating mechanisms in the dorsal horn via repeated activation of large myelinated afferents. SIGNIFICANCE: Understanding the mechanisms of action of DRGS-induced pain relief may lead to innovations in stimulation technologies that improve patient outcomes.
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Dolor Crónico/terapia , Ganglios Espinales/fisiología , Modelos Biológicos , Fibras Nerviosas Mielínicas/fisiología , Fibras Nerviosas Amielínicas/fisiología , Estimulación de la Médula Espinal/métodos , Dolor Crónico/fisiopatología , HumanosRESUMEN
Non-arthroplasty treatment options for pseudoparalysis of the shoulder are preferable in the younger patient population. Although there are differing philosophies among shoulder surgeons, many prefer to avoid reversed total shoulder arthroplasty for patients under age 60 years. Arthroscopically assisted latissimus dorsi transfer may be a good alternative for these patients, but how the results compare with arthroscopic superior capsular reconstruction is the question.
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Artroscopía/métodos , Lesiones del Manguito de los Rotadores/cirugía , Articulación del Hombro/cirugía , Músculos Superficiales de la Espalda/cirugía , Transferencia Tendinosa/métodos , Fenómenos Biomecánicos , Humanos , Rango del Movimiento ArticularRESUMEN
Hydrocephalus, where cerebrospinal fluid (CSF) production rate is greater than reabsorption rate, leads to impaired neurological function if left untreated. Ventriculoperitoneal shunts (VPS) are implanted in the brain ventricles to route CSF. VPS systems have a high failure rate, and failure symptoms resemble symptoms of common maladies. The current gold standard for shunt diagnosis, surgical intervention, poses high risk and requires an expensive procedure for patients. Current non-invasive methods lack proper insight to assist physicians. We propose a noninvasive method of characterizing the oscillation of the shunt's pressure-relief valve to assist physicians in shunt diagnosis. Brightness-mode and motion-mode ultrasound images can be used to determine fluid flow. Blockage in the system could be detected by observing the phase change of the ultrasound signal in different flow cases with or without perturbation. Future testing and implementation can allow for the use of this method in localizing and identifying the modality of failure.
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Ultrasonografía , Derivación Ventriculoperitoneal , Líquido Cefalorraquídeo/metabolismo , Femenino , Humanos , Hidrocefalia/fisiopatología , Procesamiento de Imagen Asistido por Computador , Masculino , ReologíaRESUMEN
In vitro neuronal networks cultured on microelectrode arrays enable the study of network electrophysiology on a fundamental level. Neuronal response to electrical stimulation is an area of interest at the laboratory bench and in the clinic, given its wide application for remedying neurological disorders. Here we investigated the change in cortical network response over time to varied amounts of charge used for stimulation, which may lead to a phenomenon known as selective adaptation. There is a charge threshold that invokes a reverberating network response; when stimulating at 900 mV, five stimulation electrodes were required to elicit a response across the entire network. Stimulating with more charge leads to greater synaptic depression over time when constant periodic stimulation is applied. Stimulating with 5 electrodes led to a decrease in network response to stimulation, whereas stimulating with 12 electrodes led to an extinction of network response. The previously hypothesized selective adaptation mechanism was not observed, implying that our random cortical assemblies have homogeneous excitatory and inhibitory subnetworks.
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Depresión Sináptica a Largo Plazo/fisiología , Neuronas/fisiología , Estimulación Eléctrica , Humanos , Microelectrodos , Red Nerviosa/fisiologíaRESUMEN
PURPOSE: The superior-medial (SM) shoulder arthroscopic portal (Neviaser portal) is the portal anatomically closest to the suprascapular nerve, and any potential benefits of this portal would be mitigated if risk of suprascapular nerve injury were significant. The purpose of this study is to determine the safety of the SM arthroscopic shoulder portal. We hypothesize that the SM shoulder arthroscopic portal is safe. METHODS: Twelve fresh cadaveric shoulders were securely positioned to simulate shoulder arthroscopy in the beach-chair position with the arm at the patient's side in neutral rotation. An SM portal was established 1 cm medial to the acromion and 1 cm posterior to the clavicle, and a 5.5-mm burr sheath was oriented toward the acromioclavicular joint. The skin and trapezius were resected, the supraspinatus was retracted, and the suprascapular nerve was identified. The distance between the sheath and the nerve was measured by 2 independent observers with calipers. A safe distance was defined as 10 mm. RESULTS: The measured distances between the nerve and burr ranged from 18.5 to 35.7 mm, with a mean of 24.2 +/- 5 mm. The distance is significantly greater than the safe distance of 10 mm (P < .0001). CONCLUSIONS: This study shows that the SM portal is safe. The distance between an instrument oriented toward the acromioclavicular joint via the SM portal and the suprascapular nerve was 18.5 mm or greater in all specimens. CLINICAL RELEVANCE: Our study has clinical relevance because the SM portal is useful for arthroscopic rotator cuff repair, arthroscopic superior labrum repair, and arthroscopic distal clavicle excision.