Stimulation Threshold Research Articles

Activation thresholds for electrical phrenic nerve stimulation at the neck: evaluation of stimulation pulse parameters in a simulation study

Abstract Objective. Phrenic nerve stimulation reduces ventilator-induced-diaphragmatic-dysfunction, which is a potential complication of mechanical ventilation. Electromagnetic simulations provide valuable information about the effects of the stimulation and are used to determine appropriate stimulation parameters and evaluate possible co-activation.
Approach. Using a multiscale approach, we built a novel detailed anatomical model of the neck and the phrenic nerve. The model consisted of a macroscale volume conduction model of the neck with 13 tissues, a mesoscale volume conduction model of the phrenic nerve with three tissues, and a microscale biophysiological model of axons with diameters ranging from 5 to 14 μm based on the McIntyre-Richardson-Grill-model for myelinated axons. This multiscale model was used to quantify activation thresholds of phrenic nerve fibers using different stimulation pulse parameters (pulse width, interphase delay, asymmetry of biphasic pulses, pulse polarity, and rise time) during non-invasive electrical stimulation. Electric field strength was used to evaluate co-activation of the other nerves in the neck.
Main results. For monophasic pulses with a pulse width of 150 μs, the activation threshold depended on the fiber diameter and ranged from 20 to 156 mA, with highest activation threshold for the smallest fiber diameter. The relationship was approximated using a power fit function x^−3. Biphasic (symmetric) pulses increased the activation threshold by 25 to 30 %. The use of asymmetric biphasic pulses or an interphase delay lowered the threshold close to the monophasic threshold. Possible co-activated nerves were the more superficial nerves and included the transverse cervical nerve, the supraclavicular nerve, the great auricular nerve, the cervical plexus, the brachial plexus, and the long thoracic nerve.
Significance. Our multiscale model and electromagnetic simulations provided insight into phrenic nerve activation and possible co-activation by non-invasive electrical stimulation and provided guidance on the use of stimulation pulse types with minimal activation threshold.

Molybdenum temporary epicardial pacing wires: function and biodegradation

Abstract Cardiac pacing with temporary epicardial pacing wires (TEPW) is used to treat rhythm disturbances after cardiac surgery. Wires typically begin to fail around postoperative day four and are extracted. Occasionally, TEPW cannot be mechanically removed, have to stay in the thorax and may rarely cause serious complications like migration and infection. We aim to develop novel, bioresorbable TEPW which will dissolve over time, even if postoperative removal is unsuccessful. We manufactured prototypical braided molybdenum (Mo) leads (16 Mo wires of 40 µM diameter each, length 18 cm for ex vivo, 7.5 cm for in vivo experiments) coated with the biodegradable polymers poly(lactide-co-glycolic acid) (PLGA, inner coating) and polycaprolactone (PCL, outer coating) for shaping and electrical insulation. Mo electrodes showed similar pacing and sensing properties to conventional steel electrodes (Osypka) in Langendorff-perfused rat hearts, even with somewhat lower stimulation thresholds. In artificial body fluid at 37°C, the polymer-coated Mo electrodes dissolved at a rate of 1.6 ± 0.3 µg/cm2·d (n = 5) compared to uncoated electrodes with 30.3 ± 0.8 µg/cm2·d (n = 4, p < 0.001). Assessing apoptosis and necrosis in human cardiomyocytes and cardiac fibroblasts, we detected no toxicity at Mo concentrations up to 0.52 mM. To test the in vivo properties of Mo TEPW, we sutured them epicardially onto the anterior wall of the heart of female Wistar rats, led them out of the thorax through an intercostal space and placed them in a subcutaneous pocket. We tested electrophysiological properties directly after implantation and after different time periods. Mo TEPW showed similar pacing and sensing properties directly upon implantation and after 2 weeks, with only impedance and slew rate of the sensed R-wave decreasing time-dependently. After one month, all but one pair of Mo electrodes were mechanically broken at their exit from the thorax, the site of assumedly highest mechanical stress. Progressive Mo degradation led to multiple fragmentation of the Mo TEPW after 6 months. The conventional steel TEPW we used as control had similar electrical properties directly after implantation, after 2 weeks and one month without signs of broken electrodes. After 6 months, all but one pair of steel electrodes were mechanically broken at their thorax exit site. Comparing urinary Mo concentration of Mo TEPW treated rats to controls, we saw similar values of 1.9 ± 1.9 µM (n = 6) vs. 0.6 ± 0.2 µM (n = 5, n.s.) after one week. In contrast, we saw a significant increase of 12.1 ± 9.7 µM (n = 5) vs. 1.0 ± 0.9 µM (n = 5, p < 0.001) after 6 months, reflecting the degradation progress. We demonstrate that Mo TEPW are a feasible option for epicardial pacing in vivo for up to 2 weeks and observed the progress of Mo degradation up to 6 months. These findings represent an important step in the development of bioresorbable TEPW as a novel and even safer approach to temporary epicardial pacing.Graphical AbstractIn Vivo Degradation Progress

Intensity-Dependent Effects of Low-Frequency Subthreshold rTMS on Primary Motor Cortex Excitability and Interhemispheric Inhibition in Elderly Participants: A Randomized Trial.

Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) protocols targeting primary motor cortex (M1) are used in rehabilitation of neurological diseases for their therapeutic potential, safety, and tolerability. Although lower intensity LF-rTMS can modulate M1 neurophysiology, results are variable, and a systematic assessment of its dose effect is lacking. To determine the dose-response of LF-rTMS on stimulated and non-stimulated M1. In a sham-controlled randomized double-blind crossover study the effect of LF-TMS protocols were determined in 20 right-handed older healthy participants. In 3 sessions, 1 Hz rTMS at 80% (rTMS80), 90% (rTMS90) of motor threshold or sham stimulation were applied to left upper extremity M1. Outcome measures were curve parameters of the stimulus-response curve (maximum motor evoked potential [MEPMAX], slope and the intensity to evoke 50% MEPMAX), short-interval intracortical inhibition (SICI), and interhemispheric inhibition (IHI). Within LF-rTMS sessions, rTMS90, increased MEPMAX in the stimulated M1. Furthermore, rTMS90, increased the slope in the non-stimulated M1. LF-rTMS effects on SICI were dependent on the participants' baseline SICI, hemisphere, and intensity of conditioning pulse. Finally, rTMS90 increased whereas rTMS80 decreased IHI, for both IHI directions. These changes were dependent on baseline IHI and hemisphere and were no longer significant when baseline IHI was accounted for. Intensity of subthreshold LF-rTMS has differential effects on excitation and inhibition of stimulated and non-stimulated M1. The effects were small and were only demonstrated within the LF-rTMS sessions but were not different when compared to sham. rTMS related changes in SICI and IHI were dependent on baseline level. NCT02544503, NCT01726218.

Industry-Scalable Reusable Textile Electrodes for Neurostimulation Applications.

Neurostimulation delivers electrical pulses to modulate neuromuscular activity. Commonly used in medical interventions from pain relief to rehabilitation, neurostimulation typically uses manually placed hydrogel electrodes over the treated region. However, this method limits interventions requiring frequent, long-term daily use. To address this, novel fully textile electrodes are developed using industrial programmable knitting machines. These electrodes are designed to be washable, reusable, flexible, and breathable, with embedded interconnects. Textile electrodes are made of yarns with stainless steel and PEDOT-coated stainless steel conductive components. The electrodes' performance are compared with gel electrodes, characterizing impedance, sensorimotor stimulation thresholds, recruitment of induced movements, sensation levels, and perceived sensations. The effects of residential wash cycles and continuous use duration are also investigated. The proposed electrodes are found to perform similarly to hydrogel electrodes in all characterized metrics. No degradation in electrode performance is found after at least 30 wash cycles. Electrodes remained functionally intact after 1000 cycles of stretch loading at 50% of break strain. The textile electrodes consistently induced comfortable sensorimotor responses for at least six hours after donning. The proposed textile electrodes offer a novel and effective solution for neurostimulation interventions, paving the way for integration into smart garments and long-term wearable health technologies.

A Method for Electrical Stimulus Artifact Removal Exploiting Neural Refractoriness: Validation by Contrasting Cathodic and Anodic Stimulation.

To present a novel method for removing stimulus transient that exploits the absolute refractory period of electrically excitable neural tissues. Electrical stimulation often generates significant signal artifacts that can obscure important physiological signals. Removal of the artifact and understanding latent information from these signals could provide objective measures of circuit engagement, potentially driving advancements in neuromodulation research and therapies. We conducted intracranial physiology studies on five consecutive patients with Parkinson's disease who underwent deep brain stimulation (DBS) surgery as part of their routine care. Monopolar stimuli (either cathodic or anodic) were delivered in pairs through the DBS electrode across a range of inter-stimulus intervals. Recordings from adjacent unused electrode contacts used broadband sampling and precise synchronization to generate a robust template for the stimulus transient during the absolute refractory period. These templates of stimulus transient were then subtracted from recordings at different intervals to extract and analyze the residual neural potentials. After artifact removal, the residual signals exhibited absolute and relative refractory periods with timing indicative of neural activity. Cathodic and anodic DBS pulses generated distinct patterns of local tissue activation, showing phase independence from the prior stimulus. The earliest detectable neural responses occurred at short peak latencies (ranging from 0.19 to 0.38 ms post-stimulus) and were completely or partially obscured by the stimulus artifact prior to removal. Cathodic stimuli produced stronger local tissue responses than anodic stimuli, aligning with clinical observations of lower activation thresholds for cathodic stimulation. However, cathodic and anodic pulses induced artifact patterns that were equivalent but opposite. The proposed artifact removal technique enhances prior approaches by allowing direct measurement of local tissue responses without requirements for stimulus polarity reversal, template scaling, or specialized filters. This approach could be integrated into future neuromodulation systems to visualize stimulus-evoked neural potentials that would otherwise be obscured by stimulus artifacts.

Magnetoelectrics for Implantable Bioelectronics: Progress to Date.

ConspectusThe coupling of magnetic and electric properties manifested in magnetoelectric (ME) materials has unlocked numerous possibilities for advancing technologies like energy harvesting, memory devices, and medical technologies. Due to this unique coupling, the magnetic properties of these materials can be tuned by an electric field; conversely, their electric polarization can be manipulated through a magnetic field.Over the past seven years, our lab work has focused on leveraging these materials to engineer implantable bioelectronics for various neuromodulation applications. One of the main challenges for bioelectronics is to design miniaturized solutions that can be delivered with minimally invasive procedures and yet can receive sufficient power to directly stimulate tissue or power electronics to perform functions like communication and sensing.Magnetoelectric coupling in ME materials is strongest when the driving field matches a mechanical resonant mode. However, miniaturized ME transducers typically have resonance frequencies >100 kHz, which is too high for direct neuromodulation as neurons only respond to low frequencies (typically <1 kHz). We discuss two approaches that have been proposed to overcome this frequency mismatch: operating off-resonance and rectification. The off-resonance approach is most common for magnetoelectric nanoparticles (MENPs) that typically have resonance frequencies in the gigahertz range. In vivo experiments on rat models have shown that MENPs could induce changes in neural activity upon excitation with <200 Hz magnetic fields. However, the neural response has latencies of several seconds due to the weak coupling in the off-resonance regime.To stimulate neural responses with millisecond precision, we developed methods to rectify the ME response so that we could drive the materials at their resonant frequency but still produce the slowly varying voltages needed for direct neural stimulation. The first version of the stimulator combined a ME transducer and analog electronics for rectification. To create even smaller solutions, we introduced the first magnetoelectric metamaterial (MNM) that exhibits self-rectification. Both designs have effectively induced neural modulation in rat models with less than 5 ms latency.Based on our experience with in vivo testing of the rectified ME stimulators, we found it challenging to deliver the precisely controlled therapy required for clinical applications, given the ME transducer's sensitivity to the external transmitter alignment. To overcome this challenge, we developed the ME-BIT (MagnetoElectric BioImplanT), a digitally programmable stimulator that receives wireless power and data through the ME link.We further expanded the utility of this technology to neuromodulation applications that require high stimulation thresholds by introducing the DOT (Digitally programmable Overbrain Therapeutic). The DOT has voltage compliance up to 14.5 V. We have demonstrated the efficacy of these designs through various in vivo studies for applications like peripheral nerve stimulation and epidural cortical stimulation.To further improve these systems to be adaptive and enable a network of coordinated devices, we developed a bidirectional communication system to transmit data to and from the implant. To enable even greater miniaturization, we developed a way to use the same ME transducer for wireless power and data communication by developing the first ME backscatter communication protocol.

The Difference between Traditional Magnetic Stimulation and Microcoil Stimulation: Threshold and the Electric Field Gradient

This paper considers the threshold value of the activating function needed for stimulation in traditional magnetic stimulation and microcoil stimulation. Two analyses of excitation have been studied: spatial frequency analysis and active membrane analysis using the Hodgkin−Huxley model. The activating function depends on the spatial distribution of the electric field gradient in the active membrane analysis and the spatial frequency in the spatial frequency analysis. Both analyses show that a microcoil (tens of microns in size) has a higher threshold than a traditional coil (tens of millimeters in size) when the spatial frequency is large or the spatial extent of the activating function is small. Consequently, the stimulation threshold for a microcoil is much higher than that for a conventional coil.

A comparative study of simulated electric fields of transcranial magnetic stimulation targeting different cortical motor regions.

This computational simulation study investigates the strength of transcranial magnetic stimulation (TMS)-induced electric fields (EF) in primary motor cortex (M1) and secondary motor areas. Our results reveal high interindividual variability in the strength of TMS-induced EF responses in secondary motor areas, relative to the stimulation threshold in M1. Notably, the activation of the supplementary motor area requires high-intensity stimulation, which could be attributed to the greater scalp-to-cortex distance observed over this area. These findings emphasize the importance of individualized planning using computational simulation for optimizing neuromodulation strategies targeting the cortical motor system.

Multimodal and Repeated Localization of Primary Hand Motor Function to the Lateral Postcentral Gyrus in a Case of Frontal Motor Area Brain Metastasis

BACKGROUND AND IMPORTANCE: The human motor homunculus is a well-known topographical map of the functional-anatomical relationships of the precentral gyrus. Within this homunculus, the primary hand motor area is considered one of the least plastic functional-anatomical relationships. Only a few cases in the literature describe relocation of functional hand representation away from the classical anatomical location. These cases have been reported in the context of children, primary gliomas, or arteriovenous malformations. CLINICAL PRESENTATION: Here, we describe a unique case where the area of lowest hand motor stimulation threshold (ie, hand motor representation) was found in the postcentral gyrus in an older adult with a metastasis in the premotor area of the brain. This localization was based on intraoperative cortical stimulation–evoked motor potentials and confirmed with electrophysiological phase reversal and MRI-based neuronavigation. This mapping was repeated and consistent 2 months later during a reoperation for recurrence. In addition, the remapped anatomical location was found in an area that was active during finger tapping on preoperative functional MRI. CONCLUSION: These findings suggest that neuroplastic remapping of hand motor cortex to the postcentral gyrus can occur in brain metastases even in adults. This has implications for planning tumor resections and interventional neurorehabilitation strategies, and it suggests that the motor homunculus may have more plastic potential in adulthood than previously recognized.

Predictors of pharyngeal electrical stimulation treatment success in tracheotomised stroke patients with dysphagia: Secondary analysis from PHADER cohort study

Pharyngeal electrical stimulation (PES) has emerged as a promising intervention for neurogenic dysphagia, with potential benefits in reducing dysphagia severity in stroke patients. PES may facilitate decannulation in tracheotomised stroke patients with dysphagia, yet the predictive factors for treatment success have not been investigated in detail. This study used data from the PHAryngeal electrical stimulation for treatment of neurogenic Dysphagia European Registry (PHADER) study to identify predictive factors for PES treatment success among patients with post stroke dysphagia who required mechanical ventilation and tracheotomy. Multiple linear regression was performed to predict treatment success, as measured in improvement in dysphagia severity rating scale (DSRS), accounting for age, sex, stroke type, lesion location, baseline National Institutes of Health Stroke Scale (NIHSS) score, feeding status, time from stroke onset to PES, PES perceptual threshold and PES stimulation intensity at the first session. Cox regression was conducted to identify the predictors for decannulation for all participants. Ninety-eight participants (mean [SD] age ​= ​66.6 [13.0]; male 73.5%) were included in the analyses. Regression analyses showed that early intervention (p ​= ​0.004) and younger age (p ​= ​0.049) were significant predictors for treatment success. For participants who received PES during tracheotomy (n ​= ​60; mean [SD] age ​= ​66.6 [11.2]; male 73.3%), supratentorial stroke (p ​= ​0.033) and feeding status at baseline (p ​= ​0.025) were predictors of treatment success. Among all participants, early intervention was associated with higher likelihood of decannulation (p ​= ​0.026). These results highlight the importance of timely intervention, age and stroke location in PES treatment success for stroke patients with mechanical ventilation and tracheotomy.

THE USE OF NERVE MONITORIZATION IN PAROTID, SUBMANDIBULAR GLAND AND FACIAL SURGERY AND ITS EFFECT ON PROGNOSIS

Objective: The facial nerve and its branches are at risk during facial surgery. The surgery with the highest risk is parotid and submandibular gland surgery. An attempt was made to determine threshold values in terms of paralysis in nerve monitoring parameters. These determined values could not be used to predict facial nerve function after surgery. The aim of this study is to investigate the relationship between the parameters detected by nerve stimulation during surgery and postoperative facial nerve dysfunction in patients who underwent parotid and submandibular gland surgery. Material and Methods: A total of 29 facial nerve branches of 13 patients who underwent superficial parotidectomy or submandibular gland resection were examined. Patients were examined in two groups: those who did not develop paralysis after surgery and those who developed paralysis or sequelae. The relationship between the patient's pre- and postoperative House-Brackmann staging and potential changes detected during surgery was investigated. Results: Paralysis was detected in 8 of 29 nerves that were stimulated, and the affected branches were the cervicofacial branch and the marginal mandibular branch. No difference was observed in the mean threshold stimulation values and responses determined before, during and at the end of dissection between patients who developed paralysis and those who did not. Conclusion: Unlike the literature, it is determined that no electrophysiological measurement result can predict the postoperative phase as a result of ROC-curve analysis and logistic regression analysis. It is thought that these results are caused by the fact that the developing paralysis is at low stages and heal within one month.

Recordings of Superior Laryngeal Nerve Sensory Nerve Action Potentials in a Rat Model.

Superior laryngeal nerve (SLN) function is critical to laryngeal sensation. Sensory dysfunction in the larynx, mediated through the internal branch of the superior laryngeal nerve (iSLN), is thought to occur with aging and neurodegenerative disease. However, objective analysis of iSLN neurophysiology is difficult due to its anatomic location and small diameter. This study measures sensory nerve action potentials (SNAP) from the iSLN in a rat model. SNAP data were obtained from two adult rat strains (Sprague-Dawley, SD and Fischer 344 × Brown Norway F1 Hybrid rats, FBN). Evoked responses were obtained by stimulating the main trunk of the SLN and recording the response using a 160-μm cuff electrode placed around the iSLN. SNAP were averaged from 10 stimulations. Laryngeal adductor reflex (LAR) threshold measurements were obtained with stimulation of the iSLN and direct laryngoscopy. The sections of the iSLN were obtained for histologic analysis. SLN-evoked responses were successfully obtained in 18 hemi-laryngeal preparations (SD n = 13 and FBN n = 5) with corresponding LAR threshold measurements. Mean(±SD) SNAP latency, total duration, amplitude, negative durations, and intensity were 2.28 ms (±0.56), 2.13 ms (±0.70), 879 μV (±535), and 0.69 mA (±0.25), respectively. SLN stimulation threshold to elicit an LAR was of 0.84 mA (±0.31). It is feasible to record evoked SLN responses in two adult rat strains. This work may lead to a tractable animal model for objective measurements of SLN neurophysiology with various disease states. N/A Laryngoscope, 2024.

Cell‐Anchored Lead‐Free Piezoelectric KNN NPs Resisting Washout for Low‐Intensity Ultrasound Driven Neuromodulation

AbstractPiezoelectric nanomaterials for wireless neuromodulation is a promising alternative to traditional electrical stimulation. However, the low‐avidity between piezoelectric nanomaterials and cellular membranes leads to low efficiency of electrical signal transmission, which requires high‐intensity thresholds of ultrasound stimulation (US). Here, lead‐free piezoelectric (K,Na)NbO3 (KNN) nanoparticles (NPs) with cholesterol coating (KNNC) are presented, in which Cholesterol can be accommodated in the membrane and make them append on the plasma membrane. Compared to non‐modified nanoparticles, cell‐anchored KNNC NPs highly resist convective washout owing to high affinity of cholesterol to biological membranes, which enables highly efficient wireless electrical stimulation to activate cell impulses under low‐intensity ultrasound. Meanwhile, after perfusion washing, the KNNC NPs distributed around the cells are washed away, while part of KNNC NPs remain on the surface of cell membrane still can induce significant Ca2+ influx under US, similar to the group without washing, indicating the KNNC NPs appended on the cell play a major role in wireless electrical stimulation. Furthermore, the highly efficient electrical transmission of KNNC enables neural differentiation of stem cells in regulating synaptic plasticity by modulating Ca2+ influx, demonstrating that KNNC NPs offer a perspective toward minimally invasive wireless neuromodulation therapies for neurological diseases.

Tunnel silicon nitride manipulated reconfigurable bi-mode nociceptor analog

Neuromorphic applications have shown great promise not only for efficient parallel computing mode to hold certain computational tasks, such as perception and recognition, but also as key biomimetic elements for the intelligent sensory system of next-generation robotics. However, achieving such a biomimetic nociceptor that can adaptively switch operation mode with a stimulation threshold remains a challenge. Through rational design of material properties and device structures, we realized an easily-fabricated, low-energy, and reconfigurable nociceptor. It is capable of threshold-triggered adaptive bi-mode jump that resembles the biological alarm system. With a tunnel silicon nitride (Si3N4) we mimicked the intensity- and rehearsal-triggered jump by means of the tunneling mode transition of Si3N4 dielectric. Under threshold signals the device can also express some common synaptic functions with an extremely low energy density of 33.5 fJ/μm2. In addition, through the modulation of Si3N4 thickness it is relatively easy to fabricate the device with differing pain degree. Our nociceptor analog based on a tunneling layer provides an opportunity for the analog pain alarm system and opens up a new path toward threshold-related novel applications.

The role of spinal cord neuroanatomy in the variances of epidural spinal recordings

BackgroundSpinal cord stimulation (SCS) has demonstrated multiple benefits in treating chronic pain and other clinical disorders related to sensorimotor dysfunctions. However, the underlying mechanisms are still not fully understood, including how electrode placement in relation to the spinal cord neuroanatomy influences epidural spinal recordings (ESRs). To characterize this relationship, this study utilized stimulation applied at various anatomical sections of the spinal column, including at levels of the intervertebral disc and regions correlating to the dorsal root entry zone.MethodTwo electrode arrays were surgically implanted into the dorsal epidural space of the swine. The stimulation leads were positioned such that the caudal-most electrode contact was at the level of a thoracic intervertebral segment. Intraoperative cone beam computed tomography (CBCT) images were utilized to precisely determine the location of the epidural leads relative to the spinal column. High-resolution microCT imaging and 3D-model reconstructions of the explanted spinal cord illustrated precise positioning and dimensions of the epidural leads in relation to the surrounding neuroanatomy, including the spinal rootlets of the dorsal and ventral columns of the spinal cord. In a separate swine cohort, implanted epidural leads were used for SCS and recording evoked ESRs.ResultsReconstructed 3D-models of the swine spinal cord with epidural lead implants demonstrated considerable distinctions in the dimensions of a single electrode contact on a standard industry epidural stimulation lead compared to dorsal rootlets at the dorsal root entry zone (DREZ). At the intervertebral segment, it was observed that a single electrode contact may cover 20-25% of the DREZ if positioned laterally. Electrode contacts were estimated to be ~0.75 mm from the margins of the DREZ when placed at the midline. Furthermore, ventral rootlets were observed to travel in proximity and parallel to dorsal rootlets at this level prior to separation into their respective sides of the spinal cord. Cathodic stimulation at the level of the intervertebral disc, compared to an ‘off-disc’ stimulation (7 mm rostral), demonstrated considerable variations in the features of recorded ESRs, such as amplitude and shape, and evoked unintended motor activation at lower stimulation thresholds. This substantial change may be due to the influence of nearby ventral roots. To further illustrate the influence of rootlet activation vs. dorsal column activation, the stimulation lead was displaced laterally at ~2.88 mm from the midline, resulting in variances in both evoked compound action potential (ECAP) components and electromyography (EMG) components in ESRs at lower stimulation thresholds.ConclusionThe results of this study suggest that the ECAP and EMG components of recorded ESRs can vary depending on small differences in the location of the stimulating electrodes within the spinal anatomy, such as at the level of the intervertebral segment. Furthermore, the effects of sub-centimeter lateral displacement of the stimulation lead from the midline, leading to significant changes in electrophysiological metrics. The results of this pilot study reveal the importance of the small displacement of the electrodes that can cause significant changes to evoked responses SCS. These results may provide further valuable insights into the underlying mechanisms and assist in optimizing future SCS-related applications.

Children and adolescents with primary headaches exhibit altered sensory profiles – a multi-modal investigation

BackgroundPediatric headache is an increasing medical problem that has adverse effects on children’s quality of life, academic performance, and social functioning. Children with primary headaches exhibit enhanced sensory sensitivity compared to their healthy peers. However, comprehensive investigations including multimodal sensory sensitivity assessment are lacking. This study aimed to compare sensory sensitivity of children with primary headaches with their healthy peers across multiple sensory domains.MethodsThe study included 172 participants aged 6 to 17 years (M = 13.09, SD = 3.02 years; 120 girls). Of these 80 participants were patients with migraine, 23 were patients with tension-type headache, and 69 were healthy controls. The following sensory measures were obtained: Mechanical Detection Threshold (MDT), Mechanical Pain Threshold (MPT), Mechanical Pain Sensitivity (MPS), detection and pain threshold for Transcutaneous Electrical Nerve Stimulation (TENS), olfactory and intranasal trigeminal detection threshold, and odor identification ability. Sensory sensitivity was compared between groups with a series of Kruskal-Wallis tests. Binomial regression models were used to compare the relative utility of sensory sensitivity measures in classifying participants into patients and healthy controls, as well as into patients with migraine and tension-type headache.ResultsPatients with migraine had lower MPT measured at the forearm than patients with tension-type headaches and healthy controls. MPS was higher in patients with migraine than in healthy controls. All patients with headaches had lower detection threshold of TENS and higher olfactory sensitivity. Healthy controls showed increased intranasal trigeminal sensitivity. Scores in MPS, TENS, and olfactory and trigeminal thresholds were significantly predicting presence of primary headaches. Additionally, scores in MPT, olfactory and trigeminal threshold were positive predictors of type of headache.ConclusionsChildren with primary headaches exhibit different sensory profiles than healthy controls. The obtained results suggest presence of increased overall, multimodal sensitivity in children with primary headaches, what may negatively impact daily functioning and contribute to further pain chronification.Trial registrationThe study was registered in the German Registry of Clinical Trials (DRKS) DRKS00021062.

New pacing strategies for heart failure

In patients with areduced left ventricular (LV) systolic function (ejection fraction < 35%) and aleft bundle branch block with a QRS duration > 130 ms, cardiac resynchronization therapy (CRT) can contribute to an improvement in the quality of life and areduction in mortality. The resynchronization is mostly achieved by pacing via an epicardial LV lead in the coronary sinus; however, this approach is often limited by the patient's venous anatomy and an increase in the stimulation threshold over time. In addition, up to 30% of patients do not respond to the intervention. New treatment approaches involve direct stimulation of the conduction system by pacing of the bundle of His or left bundle branch. This enables a more physiological propagation of the stimulus. Pacing of the left bundle branch is achieved by advancing the lead into the right ventricle and screwing it deep into the interventricular septum. Due to the relatively large target area of the left bundle branch the success rate is very high (currently > 90%). Observational studies have shown agreater reduction in the QRS duration, amore pronounced improvement in systolic function and alower hospitalization rate for heart failure associated with conduction system pacing compared to CRT using acoronary sinus lead. These findings have been confirmed in small randomized trials. Therefore, the use of left bundle branch pacing should be considered not only as abail out in the case of failed resynchronization using coronary sinus lead placement but increasingly also as an initial pacing strategy. The results of the first large randomized trials are expected to be released in late 2024.

Harvesting, Embedding, and Culturing Dorsal Root Ganglia in Multi-compartment Devices to Study Peripheral Neuronal Features.

The most common peripheral neuronal feature of pain is a lowered stimulation threshold or hypersensitivity of terminal nerves from the dorsal root ganglia (DRG). One proposed cause of this hypersensitivity is associated with the interaction between immune cells in the peripheral tissue and neurons. In vitro models have provided foundational knowledge in understanding how these mechanisms result in nociceptor hypersensitivity. However, in vitro models face the challenge of translating efficacy to humans. To address this challenge, a physiologically and anatomically relevant in vitro model has been developed for the culture of intact dorsal root ganglia (DRGs) in three isolated compartments in a 48-well plate. Primary DRGs are harvested from adult Sprague Dawley rats after humane euthanasia. Excess nerve roots are trimmed, and the DRG is cut into appropriate sizes for culture. DRGs are then grown in natural hydrogels, enabling robust growth in all compartments. This multi-compartment system offers anatomically relevant isolation of the DRG cell bodies from neurites, physiologically relevant cell types, and mechanical properties to study the interactions between neural and immune cells. Thus, this culture platform provides a valuable tool for investigating treatment isolation strategies, ultimately leading to an improved screening approach for predicting pain.

3D electronic implants in subretinal space: Long-term follow-up in rodents

Clinical results with photovoltaic subretinal prosthesis (PRIMA) demonstrated restoration of sight via electrical stimulation of the interneurons in degenerated retina, with resolution matching the 100 μm pixel size. Since scaling the pixels below 75 μm in the current bipolar planar geometry will significantly limit the penetration depth of the electric field and increase stimulation threshold, we explore the possibility of using smaller pixels based on a novel 3-dimensional honeycomb-shaped design. We assessed the long-term biocompatibility and stability of these arrays in rats by investigating the anatomical integration of the retina with flat and 3D implants and response to electrical stimulation over lifetime – up to 32–36 weeks post-implantation in aged rats. With both flat and 3D implants, signals elicited in the visual cortex decreased after the day of implantation by more than 3-fold, and gradually recovered over the next 12–16 weeks. With 25 μm high honeycomb walls, the majority of bipolar cells migrate into the wells, while amacrine and ganglion cells remain above the cavities, which is essential for selective network-mediated stimulation of the retina. Retinal thickness and full-field stimulation threshold with 40 μm-wide honeycomb pixels were comparable to those with planar devices – 0.05 mW/mm2 with 10 ms pulses. However, fewer cells from the inner nuclear layer migrated into the 20 μm-wide wells, and stimulation threshold increased over 12–16 weeks, before stabilizing at about 0.08 mW/mm2. Such threshold is still significantly lower than 1.8 mW/mm2 with a previous design of flat bipolar pixels, confirming the promise of the 3D honeycomb-based approach to high resolution subretinal prosthesis.

(135) DYSORGASMIA IN A FEMALE PATIENT FOLLOWING TRAM RECONSTRUCTIVE SURGERY

Abstract Introduction Many women struggle with sexual dysfunction, either in desire, arousal, orgasm, and/or pain. Despite the incidence of dysorgasmia in the general population, there is a paucity of literature focusing on its causes and treatment, especially when attributed to medical conditions and surgery. Objective This case report describes an unusual presentation of post-orgasmic pain following breast reconstruction surgery using abdominal tissue. Methods A 73-year old woman presented with chronic orgasmic pain in the deep pelvic area following transverse rectus abdominal muscle (TRAM) flap reconstruction for a mastectomy in the setting of breast cancer treatment. The patient was diagnosed with ductal carcinoma breast cancer in 2011, where she received a lumpectomy with radiation. After 2 years, in 2013, she was diagnosed with a recurrence of breast cancer. She underwent a mastectomy with no complications, with a transverse rectus abdominal muscle flap reconstruction surgery conducted five days later. Following the TRAM reconstruction, the patient consistently began to observe pain with orgasm. Results Prior to this surgery, the patient had experienced normal sexual intercourse and orgasm throughout her life. The patient describes pain with orgasm associated with self-stimulation, manual stimulation, oral stimulation, and vaginal penetration. The patient describes the pain associated with orgasm as a “deep, dull pain” causing nausea and is often associated with abdominal spasms. The pain lasts 2-3 minutes following orgasm and is rated as a 5-6/10 on the pain scale. The pain is not associated with urinary incontinence, urinary fullness, or bowel dysfunction. Physical exam revealed a tense abdominal wall consistent with TRAM reconstruction, well healed incisions, a normal clitoris in terms of appearance and sensation and normal pelvic floor muscles. Conclusions An orgasm is a complex process which involves interplays between the clitoris, the glans pubis, and the sympathetic activation system. A four-phase model for orgasm has been explored, which separates the orgasm response into: desire (the urge to participate in sexual activities), arousal (increased genital blood flow and clitorial erection), orgasm (after the threshold for stimulation has been reached), and resolution. Dysorgasmia can be multifactorial, and while still unclear, etiologies include pelvic floor dysfunction and/or spasm. While the pathophysiology of how the pelvic floor is connected to orgasm is not exactly understood, it is theorized to be due to dysregulated coordination of pelvic floor muscles. A transverse rectus abdominis muscle (TRAM) flap is a common breast reconstructive procedure following mastectomy. The most common complications of a TRAM flap surgery are hernias/abdominal bulges, fat necrosis, and loco-regional occurance. Interestingly, TRAM surgeries have previously been associated with pelvic floor dysfunction in women due to an increase in abdominal pressure. Since the pelvic floor is tightly connected to the mechanism of an orgasm, it is possible that disruptions to the pelvic floor may lead to painful spasms during orgasms. This is also consistent with the patient’s sensation of abdominal “spasms” during/after orgasm. While not all TRAM surgeries cause dysorgasmia, this patient’s dysorgasmia may be postulated to be secondary to pelvic floor dysfunction. Disclosure No.