Stimulation Amplitude Research Articles

Decoupling the effects of varying amplitude and frequency in the electrical stimulation of optic nerve fibers

Abstract Introduction. Computational models of optic nerve stimulation can allow to estimate the neural response of optic nerve fibers electrical stimulation and thus can be exploited to tune stimulation parameters to obtain a specific target perception. In principle, such tuning should be performed in an automatic way, so that the chosen stimulation parameters minimize some given cost function related to the quality of resulting the visual perception, but the use of such automatic methods is still under study and no satisfactory solution is available yet. In the absence of automatic methods, stimulation parameters are customarily set via manual tuning, which can be extremely time-consuming if performed in a non-principled way. Methods. We build biophysically-accurate hybrid models of monopolar and bipolar electrical stimulation of optic nerve fibers to study how the fibers firing rates depend upon the stimulation parameters. Results. In the case of monopolar sinusoidal stimulation of optic nerve fibers, we show that the amplitude of stimulation controls the size of the recruited cluster of fibers, and that the frequency controls their firing rate, independently. Instead, for bipolar stimulation, we show that when cross-talk is non negligible it is very difficult to obtain rules of thumb linking the firing rate of target fibers to stimulation parameters. Conclusion. We show that, if the stimulation amplitude is kept such that neighboring stimulating sites do not produce cross-talk, it is possible to reconstruct visual scenes “pixel-by-pixel” without needing any optimization process. If on the contrary current steering is required and cross-talk is non negligible, then it is very difficult to obtain rules of thumb and the development and use of automatic optimization techniques should be preferable.

Uncovering and leveraging the return of voluntary motor programs after paralysis using a bi-cortical neuroprosthesis.

Rehabilitative and neuroprosthetic approaches after spinal cord injury (SCI) aim to reestablish voluntary control of movement. Promoting recovery requires a mechanistic understanding of the return of volition over action, but the relationship between re-emerging cortical commands and the return of locomotion is not well established. We introduced a neuroprosthesis delivering targeted bi-cortical stimulation in a clinically relevant contusive SCI model. In healthy and SCI cats, we controlled hindlimb locomotor output by tuning stimulation timing, duration, amplitude, and site. In intact cats, we unveiled a large repertoire of motor programs. After SCI, the evoked hindlimb lifts were highly stereotyped, yet effective in modulating gait and alleviating bilateral foot drag. Results suggest that the neural substrate underpinning motor recovery had traded-off selectivity for efficacy. Longitudinal tests revealed that the return of locomotion after SCI was correlated with recovery of the descending drive, which advocates for rehabilitation interventions directed at the cortical target.

Student Competition (Technology Innovation) ID 1985239

Background Deep vein thrombosis (DVT) is a blood clot that forms in the deep veins and is the third most common cardiovascular disease today. One of the causes of DVT is venous stasis. Current methods of DVT prevention include anticoagulants and mechanical prophylaxis. Anticoagulant use is contraindicated in individuals with bleeding risks and mechanical interventions are often cumbersome and uncomfortable. Objective The overall goal of this project is to investigate a novel method for DVT prevention, termed intermittent electrical stimulation (IES). The current study investigated the effects of IES on healthy typical as well as post-stroke persons. Method Of the 32 participants, 22 were healthy subjects from Edmonton, and 10 were inpatient post-stroke subjects at the Glenrose Rehabilitation Hospital, Edmonton. A two-channel stimulator was used to administer IES through electrodes placed on the posterior and anterior sides of the leg and was applied in increasing stimulation amplitudes to the gastrocnemius muscle and the resulting plantar flexion force and changes in popliteal and femoral venous velocities were recorded for each stimulation respectively using B-mode ultrasound. Results IES-induced contractions produced significant increases in venous flow compared to baseline. Small contractions induced by comfortable levels of stimulation in typical and in post-stroke persons were sufficient to increase flow in the popliteal and femoral veins. Conclusion The results indicate that IES can sufficiently increase venous flow to prevent venous stasis and is comfortable for end users. Incorporation of IES into a clinical device could provide a feasible and effective alternative for DVT prophylaxis.

Transcutaneous Auricular Vagus Nerve Stimulation Modulates Performance but Not Pupil Size During Nonnative Speech Category Learning.

Subthreshold transcutaneous auricular vagus nerve stimulation (taVNS) synchronized with behavioral training can selectively enhance nonnative speech category learning in adults. Prior work has demonstrated that behavioral performance increases when taVNS is paired with easier-to-learn Mandarin tone categories in native English listeners, relative to when taVNS is paired with harder-to-learn Mandarin tone categories or without taVNS. Mechanistically, this temporally precise plasticity has been attributed to noradrenergic modulation. However, prior work did not specifically utilize methodologies that indexed noradrenergic modulation and, therefore, was unable to explicitly test this hypothesis. Our goal for this study was to use pupillometry to gain mechanistic insights into taVNS behavioral effects. Thirty-eight participants learned to categorize Mandarin tones while pupillometry was recorded. In a double-blinded design, participants were divided into two taVNS groups that, as in the prior study, differed according to whether taVNS was paired with easier-to-learn tones or harder-to-learn tones. Learning performance and pupillary responses were measured using linear mixed-effects models. We found that taVNS did not have any tone-specific or group behavioral or pupillary effects. However, in an exploratory analysis, we observed that taVNS did lead to faster rates of learning on trials paired with stimulation, particularly for those who were stimulated at lower amplitudes. Our results suggest that pupillary responses may not be a reliable marker of locus coeruleus-norepinephrine system activity in humans. However, future research should systematically examine the effects of stimulation amplitude on both behavior and pupillary responses. https://doi.org/10.23641/asha.24036666.

Investigation of the intraoperative cortical responses to spinal motor mapping in a patient with chronic pain.

Intraoperative neurophysiological monitoring (IONM) in spinal cord stimulation (SCS) surgery for chronic pain is shown to provide effective guidance during device placement. Electromyography (EMG) is used to determine the laterality of the paddle. In some SCS cases, laterality cannot be obtained via EMG due to patient physiology. Electroencephalography (EEG) is already used in IONM to monitor cortical responses. Here, we show proof-of-concept of assessing the responses of epidurally evoked EMGs simultaneously with EEGs to determine laterality during IONM using a high-resolution (HR) SCS paddle. An 8-column HR-SCS paddle was acutely placed at T9-T10 interspace in patients with failed back surgery syndrome. EMG signals from 18 muscle groups were recorded simultaneously with 60-channel EEG signals at various stimulation amplitudes (0-10 mA). Particular attention was paid to regions associated with pain including the somatosensory cortex (S1), prefrontal cortex (PFC), and motor cortex (M1). When left and right lateral contacts were stimulated at low amplitudes (1-2 mA), significant changes were seen in θ, α, and β powers in the contralateral PFC but not in M1 or S1. There was a significant correlation between M1 and contralateral contacts in α power. At higher currents (7-8 mA), right-sided contacts resulted in α power change. We found significant differences in α, θ, and β powers in PFC for contralateral stimulation of the lateral SCS contacts at low amplitudes and in α power at higher amplitudes. The changes in PFC suggest the potential of EEG for understanding a cortical mechanism of action of SCS and provide insight into the pathophysiology of chronic pain.NEW & NOTEWORTHY Here, we present proof of concept of assessing the responses of epidurally evoked electromyography simultaneously with scalp electroencephalography to determine whether both laterality and insights into pain mechanisms can be elucidated. With stimulation, significant changes were seen in θ, α, and β band power in the contralateral prefrontal cortex and in α power in the motor cortex. We provide insight into the mechanism of action of SCS in preventing pain in this patient.

Correlation Between Abdominal Wall Stimulation and Spinal Cord Stimulator Tip Location: A Nonrandomized Clinical Trial

ObjectivesThis study aimed to investigate the correlation between the vertebral level of paddle placement and abdominal wall stimulation (AWS) after differential target multiplexed spinal cord stimulation (SCS) to improve the safety and effectiveness of SCS for patients with chronic pain, particularly those with low back pain (LBP). Materials and MethodsThe Correlation Between Abdominal Wall Stimulation and Spinal Cord Stimulator Tip Location study was a nonrandomized clinical trial that included 24 patients with SCS for persistent spinal pain syndrome (PSPS) type 2 (trial ID: NCT05565469). The intervention involved increasing stimulation amplitude to a maximum tolerable value and obtaining numerical rating scores for AWS. The primary outcome measure was the association between AWS, the neurostimulator tip, and conus medullaris location, whereas the secondary outcome was the pre-postinterventional difference in proportion of patients experiencing AWS. Patient demographics and postoperative imaging were assessed. Statistical analyses involved descriptive statistics, a descriptive logistic regression, and a McNemar test. ResultsThe results of the study showed that seven (29%) of the 24 patients experienced AWS either previously or during interventional stimulation. However, there was no significant correlation found between AWS and the location of the neurostimulator tip or conus medullaris, and there was no difference in the pre-postinterventional proportion of patients experiencing AWS. ConclusionsThe study concludes that a relatively high proportion of patients who received SCS for PSPS type 2 experienced or previously experienced AWS. There was no significant correlation found between the location of the neurostimulator tip and the occurrence of AWS. This suggests that AWS may not be solely dependent on the stimulation itself and emphasizes the need to consider other factors. Nonetheless, this study provides important insights into the occurrence of AWS in patients receiving SCS for PSPS type 2 and highlights the need for further research in this area. Clinical Trial RegistrationThe Clinicaltrials.gov registration number for the study is NCT05565469.

Less might be more: 1 mA but not 1.5 mA of tDCS improves tactile orientation discrimination

BackgroundTranscranial direct current stimulation (tDCS) is a frequently used brain stimulation method; however, studies on tactile perception using tDCS are inconsistent, which might be explained by the variations in endogenous and exogenous parameters that influence tDCS. ObjectivesWe aimed to investigate the effect of one of these endogenous parameters—the tDCS amplitude—on tactile perception. MethodsWe conducted this experiment on 28 undergraduates/graduates aged 18–36 years. In separate sessions, participants received 20 min of 1 mA or 1.5 mA current tDCS in a counterbalanced order. Half of the participants received anodal tDCS of the left SI coupled with cathodal tDCS of the right SI, and this montage was reversed for the other half. Pre- and post-tDCS tactile discrimination performance was assessed using the Grating Orientation Task (GOT). In this task, plastic domes with gratings of different widths cut into their surfaces are placed on the fingertip, and participants have to rate the orientation of the gratings. ResultsLinear modeling with amplitude, dome, and session as within factors and montage as between factors revealed the following: significant main effects of grating width, montage, and session and a marginally significant interaction effect of session and amplitude. Posthoc t-tests indicated that performance in GOT improved after 1 mA but not 1.5 mA tDCS independent of the montage pattern of the electrodes. ConclusionIncreasing the stimulation amplitude from 1 mA to 1.5 mA does not facilitate the tDCS effect on GOT performance. On the contrary, the effect seemed more robust for the lower-current amplitude.

Investigation of the input-output relationship of engineered neural networks using high-density microelectrode arrays

Bottom-up neuroscience utilizes small, engineered biological neural networks to study neuronal activity in systems of reduced complexity. We present a platform that establishes up to six independent networks formed by primary rat neurons on planar complementary metal–oxide–semiconductor (CMOS) microelectrode arrays (MEAs). We introduce an approach that allows repetitive stimulation and recording of network activity at any of the over 700 electrodes underlying a network. We demonstrate that the continuous application of a repetitive super-threshold stimulus yields a reproducible network answer within a 15 ms post-stimulus window. This response can be tracked with high spatiotemporal resolution across the whole extent of the network. Moreover, we show that the location of the stimulation plays a significant role in the networks' early response to the stimulus. By applying a stimulation pattern to all network-underlying electrodes in sequence, the sensitivity of the whole network to the stimulus can be visualized. We demonstrate that microchannels reduce the voltage stimulation threshold and induce the strongest network response. By varying the stimulation amplitude and frequency we reveal discrete network transition points. Finally, we introduce vector fields to follow stimulation-induced spike propagation pathways within the network. Overall we show that our defined neural networks on CMOS MEAs enable us to elicit highly reproducible activity patterns that can be precisely modulated by stimulation amplitude, stimulation frequency and the site of stimulation.

Obstructive sleep apnea improves with non-invasive hypoglossal nerve stimulation using temporal interference

BackgroundPeripheral nerve stimulation is used in both clinical and fundamental research for therapy and exploration. At present, non-invasive peripheral nerve stimulation still lacks the penetration depth to reach deep nerve targets and the stimulation focality to offer selectivity. It is therefore rarely employed as the primary selected nerve stimulation method. We have previously demonstrated that a new stimulation technique, temporal interference stimulation, can overcome depth and focality issues.MethodsHere, we implement a novel form of temporal interference, bilateral temporal interference stimulation, for bilateral hypoglossal nerve stimulation in rodents and humans. Pairs of electrodes are placed alongside both hypoglossal nerves to stimulate them synchronously and thus decrease the stimulation amplitude required to activate hypoglossal-nerve-controlled tongue movement.ResultsComparing bilateral temporal interference stimulation with unilateral temporal interference stimulation, we show that it can elicit the same behavioral and electrophysiological responses at a reduced stimulation amplitude. Traditional transcutaneous stimulation evokes no response with equivalent amplitudes of stimulation.ConclusionsDuring first-in-man studies, temporal interference stimulation was found to be well-tolerated, and to clinically reduce apnea-hypopnea events in a subgroup of female patients with obstructive sleep apnea. These results suggest a high clinical potential for the use of temporal interference in the treatment of obstructive sleep apnea and other diseases as a safe, effective, and patient-friendly approach. Trial registrationThe protocol was conducted with the agreement of the International Conference on Harmonisation Good Clinical Practice (ICH GCP), applicable United States Code of Federal Regulations (CFR) and followed the approved BRANY IRB File # 22-02-636-1279.

Encoding force modulation in two electrotactile feedback parameters strengthens sensory integration according to maximum likelihood estimation

Bidirectional human–machine interfaces involve commands from the central nervous system to an external device and feedback characterizing device state. Such feedback may be elicited by electrical stimulation of somatosensory nerves, where a task-relevant variable is encoded in stimulation amplitude or frequency. Recently, concurrent modulation in amplitude and frequency (multimodal encoding) was proposed. We hypothesized that feedback with multimodal encoding may effectively be processed by the central nervous system as two independent inputs encoded in amplitude and frequency, respectively, thereby increasing state estimate quality in accordance with maximum-likelihood estimation. Using an adaptation paradigm, we tested this hypothesis during a grasp force matching task where subjects received electrotactile feedback encoding instantaneous force in amplitude, frequency, or both, in addition to their natural force feedback. The results showed that adaptations in grasp force with multimodal encoding could be accurately predicted as the integration of three independent inputs according to maximum-likelihood estimation: amplitude modulated electrotactile feedback, frequency modulated electrotactile feedback, and natural force feedback (r2 = 0.73). These findings show that multimodal electrotactile feedback carries an intrinsic advantage for state estimation accuracy with respect to single-variable modulation and suggest that this scheme should be the preferred strategy for bidirectional human–machine interfaces with electrotactile feedback.

Acute pain drives different effects on local and global cortical excitability in motor and prefrontal areas: insights into interregional and interpersonal differences in pain processing.

Pain-related depression of corticomotor excitability has been explored using transcranial magnetic stimulation-elicited motor-evoked potentials. Transcranial magnetic stimulation-electroencephalography now enables non-motor area cortical excitability assessments, offering novel insights into cortical excitability changes during pain states. Here, pain-related cortical excitability changes were explored in the dorsolateral prefrontal cortex and primary motor cortex (M1). Cortical excitability was recorded in 24 healthy participants before (Baseline), during painful heat (Acute Pain), and non-noxious warm (Warm) stimulation at the right forearm in a randomized sequence, followed by a pain-free stimulation measurement. Local cortical excitability was assessed as the peak-to-peak amplitude of early transcranial magnetic stimulation evoked potential, whereas global-mean field power measured the global excitability. Relative to the Baseline, Acute Pain decreased the peak-to-peak amplitude in M1 and dorsolateral prefrontal cortex compared with Warm (both P < 0.05). A reduced global-mean field power was only found in M1 during Acute Pain compared with Warm (P = 0.003). Participants with the largest reduction in local cortical excitability under Acute Pain showed a negative correlation between dorsolateral prefrontal cortex and M1 local cortical excitability (P = 0.006). Acute experimental pain drove differential pain-related effects on local and global cortical excitability changes in motor and non-motor areas at a group level while also revealing different interindividual patterns of cortical excitability changes, which can be explored when designing personalized treatment plans.

Bringing the Clinic Home: An At-Home Multi-Modal Data Collection Ecosystem to Support Adaptive Deep Brain Stimulation.

Adaptive deep brain stimulation (aDBS) shows promise for improving treatment for neurological disorders such as Parkinson's disease (PD). aDBS uses symptom-related biomarkers to adjust stimulation parameters in real-time to target symptoms more precisely. To enable these dynamic adjustments, parameters for an aDBS algorithm must be determined for each individual patient. This requires time-consuming manual tuning by clinical researchers, making it difficult to find an optimal configuration for a single patient or to scale to many patients. Furthermore, the long-term effectiveness of aDBS algorithms configured in-clinic while the patient is at home remains an open question. To implement this therapy at large scale, a methodology to automatically configure aDBS algorithm parameters while remotely monitoring therapy outcomes is needed. In this paper, we share a design for an at-home data collection platform to help the field address both issues. The platform is composed of an integrated hardware and software ecosystem that is open-source and allows for at-home collection of neural, inertial, and multi-camera video data. To ensure privacy for patient-identifiable data, the platform encrypts and transfers data through a virtual private network. The methods include time-aligning data streams and extracting pose estimates from video recordings. To demonstrate the use of this system, we deployed this platform to the home of an individual with PD and collected data during self-guided clinical tasks and periods of free behavior over the course of 1.5 years. Data were recorded at sub-therapeutic, therapeutic, and supra-therapeutic stimulation amplitudes to evaluate motor symptom severity under different therapeutic conditions. These time-aligned data show the platform is capable of synchronized at-home multi-modal data collection for therapeutic evaluation. This system architecture may be used to support automated aDBS research, to collect new datasets and to study the long-term effects of DBS therapy outside the clinic for those suffering from neurological disorders.

Design and Evaluation of a Multisensory Concert for Cochlear Implant Users

This article describes the design, implementation, and evaluation of vibrotactile concert furniture, aiming to improve the live music experience of people with hearing loss using hearing technology such as cochlear implants (CI). The system was the result of a series of participatory design sessions involving CI users with different hearing assistive setups (bi-implant, bimodal, and monoimplant), and it was evaluated in a concert scenario (drums, bass, and female vocals) at the Royal Danish Academy of Music. The project aimed to improve the music appreciation for CI users by providing a multisensory concert designed with CI challenges in mind, but not excluding normal-hearing individuals or individuals with other forms of hearing aids from participating in the event. The evaluation was based on (video-recorded) observations and postexperience semistructured interviews; the data were analyzed using event analysis and meaning condensation. The results indicate that tactile augmentation provides a pleasant experience for CI users. However, concertgoers with residual hearing reported being overwhelmed if the tactile stimulation amplitude exceeds a certain threshold. Furthermore, devices that highlight instrument segregation are preferred over ones that present a tactile mixdown of multiple auditory streams.

Real World Clinical Utility of Neurophysiological Measurement Utilizing Closed-Loop Spinal Cord Stimulation in a Chronic Pain Population: The ECAP Study Protocol.

Spinal cord stimulation (SCS) is an established chronic pain treatment, but the effectiveness of traditional, open-loop paradigms has been plagued by variable sustainability in a real-world setting. A new approach, utilizing evoked compound action potential (ECAP) controlled closed-loop (CL) SCS, continuously monitors spinal cord activation and automatically adjusts the stimulation amplitude of every pulse, maintaining stimulation at the prescribed ECAP level through this continual feedback mechanism. Recent studies demonstrated the long-term safety and efficacy of ECAP-controlled CL-SCS. Here, we report the design of a prospective, multicenter, single-arm feasibility study to characterize clinical outcomes in a real-world chronic pain population utilizing ECAP-controlled CL-SCS. Objective neurophysiological measurements such as device performance and patient therapy compliance, will be analyzed against baseline biopsychosocial assessments, to explore the clinical utility of these objective physiologic biomarkers in patient phenotyping. This study will enroll up to 300 subjects with chronic, intractable trunk and/or limb pain in up to 25 United States investigation sites. Subjects meeting eligibility criteria will undergo a trial procedure and a permanent implant following a successful trial. Neurophysiological measurements (measured in-clinic and continuously during home use) and clinical outcomes including pain, quality-of-life, psychological, emotional, and functional assessments will be collected at baseline, trial end, and up to 24-months post-implantation. Associations between objective neurophysiological data, clinical evaluation and patient-reported outcomes may have important clinical and scientific implications. They may provide novel insights about the chronic pain pathophysiology, its modulation during CL-SCS, and identification of pain phenotypes and/or mechanisms associated with treatment response during SCS trials and long-term therapy. Data from the ECAP study could lead to improvements in diagnosis, assessment, patient identification and management of chronic pain. It could also provide the foundation for development of a new SCS treatment approach customized by the patient's pain phenotype, unique neurophysiology, and disease severity.

Alteration of Excitation/Inhibition Imbalance in the Hippocampus and Amygdala of Drug-Resistant Epilepsy Patients Treated with Acute Vagus Nerve Stimulation.

An imbalance between excitation (E) and inhibition (I) in the brain has been identified as a key pathophysiology of epilepsy over the years. The hippocampus and amygdala in the limbic system play a crucial role in the initiation and conduction of epileptic seizures and are often referred to as the transfer station and amplifier of seizure activities. Existing animal and imaging studies reveal that the hippocampus and amygdala, which are significant parts of the vagal afferent network, can be modulated in order to generate an antiepileptic effect. Using stereo-electroencephalography (SEEG) data, we examined the E/I imbalance in the hippocampus and amygdala of ten drug-resistant epilepsy children treated with acute vagus nerve stimulation (VNS) by estimating the 1/f power slope of hippocampal and amygdala signals in the range of 1-80 Hz. While the change in the 1/f power slope from VNS-BASE varied between different stimulation amplitudes and brain regions, it was more prominent in the hippocampal region. In the hippocampal region, we found a flatter 1/f power slope during VNS-ON in patients with good responsiveness to VNS under the optimal stimulation amplitude, indicating that the E/I imbalance in the region was improved. There was no obvious change in 1/f power slope for VNS poor responders. For VNS non-responders, the 1/f power slope slightly increased when the stimulation was applied. Overall, this study implies that the regulation of E/I imbalance in the epileptic brain, especially in the hippocampal region, may be an acute intracranial effect of VNS.

Repetitive transcranial magnetic stimulation use in neuropathic pain with comorbid depression: a review of efficient treatment protocols’ parameters

Neuropathic pain affects 7 % of the general population worldwide, it is often resistant to analgesic treatments and is complicated with depressive states in 57–65 % of this patients’ cohort. Ongoing research of current therapeutic approaches, including repetitive transcranial magnetic stimulation (rTMS) use in neuropathic pain and depression, grants new data about the details of treatment protocols’ designs. The aim of our literature review was to evaluate those parameters of the treatment protocols which proved significant efficacy in the management of the neuropathic pain with comorbid depression.Focusing on the Scopus, Elsevier and PubMed databases search, we have found 639 peer‑review articles. 23 studies have been included into the data analysis, whereas others were excluded based on their heterogeneous study design. Across the data analysis we evaluated such rTMS parameters as the type of a coil, type of stimulation area, locus of gained evoked motor potential, amplitude of stimulation, duration of session, frequency/number of sessions per day/month, tie duration between sessions, number and frequency of trains, amount and frequency of pulses containing and efficacy of treatment. Those studies that performed repetitive transcranial magnetic stimulation using the figure‑of‑8 coil over the M1 brain area, for 10 or more daily sessions with duration from 7 up to 40 minutes, of 10–20 Hz frequency, intensity 80–90 % of resting motor threshold and total pulses number over 1500 per session demonstrated the greater efficacy in pain level decrease and depression scores reduction among neuropathic pain patients with comorbid depression. Conducting an additional maintenance phase of treatment prolonged the therapeutic effect of the course.Based on the data review, the parameters of the most efficient rTMS protocols’ designs in management of patients with neuropathic pain and comorbid depression have been revealed. Further research requires investigation of other promising indicators of rTMS efficacy use in neuropathic pain with comorbid depression, such as stimulation over multiple brain areas, the duration/timing of additional maintenance phase of treatment, and the figure‑of‑8 coil orientation options.

Closed-loop parameter optimization for patient-specific phrenic nerve stimulation.

Ventilator-induced diaphragm dysfunction occurs rapidly following the onset of mechanical ventilation and has significant clinical consequences. Phrenic nerve stimulation has shown promise in maintaining diaphragm function by inducing diaphragm contractions. Non-invasive stimulation is an attractive option as it minimizes the procedural risks associated with invasive approaches. However, this method is limited by sensitivity to electrode position and inter-individual variability in stimulation thresholds. This makes clinical application challenging due to potentially time-consuming calibration processes to achieve reliable stimulation. We applied non-invasive electrical stimulation to the phrenic nerve in the neck in healthy volunteers. A closed-loop system recorded the respiratory flow produced by stimulation and automatically adjusted the electrode position and stimulation amplitude based on the respiratory response. By iterating over electrodes, the optimal electrode was selected. A binary search method over stimulation amplitudes was then employed to determine an individualized stimulation threshold. Pulse trains above this threshold were delivered to produce diaphragm contraction. Nine healthy volunteers were recruited. Mean threshold stimulation amplitude was 36.17 ± 14.34 mA (range 19.38-59.06 mA). The threshold amplitude for reliable nerve capture was moderately correlated with BMI (Pearson's r = 0.66, p = 0.049). Repeating threshold measurements within subjects demonstrated low intra-subject variability of 2.15 ± 1.61 mA between maximum and minimum thresholds on repeated trials. Bilateral stimulation with individually optimized parameters generated reliable diaphragm contraction, resulting in significant inhaled volumes following stimulation. We demonstrate the feasibility of a system for automatic optimization of electrode position and stimulation parameters using a closed-loop system. This opens the possibility of easily deployable individualized stimulation in the intensive care setting to reduce ventilator-induced diaphragm dysfunction.

Neurostimulation und Schlaf bei Epilepsie – Englische Version

Abstract Background Chronic sleep disturbance may affect seizure frequency and efficacy of treatment in epilepsy patients. Vagus nerve stimulation (VNS) and deep brain stimulation (DBS) can both induce sleep disturbance as a side effect. Aim The goal of this review is to provide information and clinical advice about potential interactions between DBS at the anterior nucleus of the thalamus (ANT) and sleep as well as between VNS and sleep. Materials and methods We provide an up-to-date overview of the currently available literature, giving insights for diagnostics and therapy based on clinical studies, and experience in two epilepsy centers with longitudinal cohorts of patients under chronic neurostimulation. Results In patients with chronic ANT-DBS and VNS, stimulation-correlated, probably dose-dependent sleep disturbances have been reported in several studies. The reason for this is assumed to be an accidental co-stimulation of the ascending reticular arousal system in the case of DBS, and an indirect effect via induction of sleep-related breathing disorders in the case of VNS. Furthermore, VNS might also influence sleep through modulation of noradrenergic and dopaminergic, arousal-inducing systems in the pons and midbrain. Reduction of stimulation amplitudes, changes in stimulation parameters, and localization of the active stimulation zone are discussed as treatment strategies in DBS. In the case of VNS-induced sleep disturbance, a nocturnal reduction of stimulation (bilevel therapy) can be offered. Conclusion As data are currently still sparse, it seems important to optimize treatment regimens for VNS and DBS in order not to antagonize their potential anticonvulsant effects by inducing sleep fragmentation.

ID: 203988 Spinal ECAP Thresholds Relative to Evoked Muscle Activation in Rats With Clinically Translatable Paradigms

Rats are commonly used as a translational model of pain and spinal cord stimulation (SCS), with stimulation amplitudes often programmed relative to visual motor threshold (vMT). Recent work1 explored both vMTs and spinal evoked compound action potentials (ECAPs)—a sensed measured of neural activation—in rats using SCS with a 2 Hz rate and a 20 μs pulse width (PW). However, this rate and PW are slower and narrower, respectively, than those typically used clinically. In this study2, we used clinically relevant SCS traditional parameters to characterize the relationship between ECAP thresholds (ECAPTs) and evoked muscle activity as measured both by evoked compound muscle action potential thresholds (ECMAPTs) and vMTs.

Sacral Neuromodulation for Fecal Incontinence and Constipation: Evidence, Programming and Long-term Management

Over the last two decades, sacral neuromodulation (SNM) has established its role in the treatment of functional pelvic organ-/pelvic floor disorders. Even though the mode of action is not fully understood, SNM has become the preferred surgical treatment of fecal incontinence. A literature search was carried out on programming sacral neuromodulation and long-term outcomes in treating fecal incontinence and constipation.Sacral neuromodulation was found to be successful in the long term. Over the years, the spectrum of indications has expanded, and now includes patients presenting with anal sphincter lesions. The use of SNM for low anterior resection syndrome (LARS) is currently under clinical investigation. Findings of SNM for constipation are less convincing. In several randomised crossover studies, no success was demonstrated, even though it is possible that subgroups may benefit from the treatment. Currently the application cannot be recommended in general.The pulse generator programming sets the electrode configuration, amplitude, pulse frequency and pulse width. Usually pulse frequency and pulse width follow a default setting (14Hz, 210s), while electrode configuration and stimulation amplitude are adjusted individually to the patient need and perception of stimulation.Despite low infection rates and few electrode-/pulse generator dysfunctions, up to 65% of patients require surgical reintervention during long term follow-up - in 50% of cases because of battery depletion, which is an expected event. At least one reprogramming is necessary in about 75% of the patients during the course of the treatment, mostly because of changes in effectiveness, but rarely because of pain. Regular follow-up visits appear to be advisable. Sacral neuromodulation can be considered to be a safe and effective long-term therapy of fecal incontinence. To optimise the therapeutic effect, a structured follow-up regime is advisable.