Stimulation Frequency Research Articles

Application of facial neuromuscular electrical stimulation (fNMES) in psychophysiological research: Practical recommendations based on a systematic review of the literature

Facial neuromuscular electrical stimulation (fNMES), which allows for the non-invasive and physiologically sound activation of facial muscles, has great potential for investigating fundamental questions in psychology and neuroscience, such as the role of proprioceptive facial feedback in emotion induction and emotion recognition, and may serve for clinical applications, such as alleviating symptoms of depression. However, despite illustrious origins in the 19th-century work of Duchenne de Boulogne, the practical application of fNMES remains largely unknown to today’s researchers in psychology. In addition, published studies vary dramatically in the stimulation parameters used, such as stimulation frequency, amplitude, duration, and electrode size, and in the way they reported them. Because fNMES parameters impact the comfort and safety of volunteers, as well as its physiological (and psychological) effects, it is of paramount importance to establish recommendations of good practice and to ensure studies can be better compared and integrated. Here, we provide an introduction to fNMES, systematically review the existing literature focusing on the stimulation parameters used, and offer recommendations on how to safely and reliably deliver fNMES and on how to report the fNMES parameters to allow better cross-study comparison. In addition, we provide a free webpage, to easily visualise fNMES parameters and verify their safety based on current density. As an example of a potential application, we focus on the use of fNMES for the investigation of the facial feedback hypothesis.

Temporal dynamics of normalization reweighting.

For decades, neural suppression in early visual cortex has been thought to be fixed. But recent work has challenged this assumption by showing that suppression can be reweighted based on recent history; when pairs of stimuli are repeatedly presented together, suppression between them strengthens. Here we investigate the temporal dynamics of this process using a steady-state visual evoked potential (SSVEP) paradigm that provides a time-resolved, direct index of suppression between pairs of stimuli flickering at different frequencies (5 and 7Hz). Our initial analysis of an existing electroencephalography (EEG) dataset (N = 100) indicated that suppression increases substantially during the first 2-5 seconds of stimulus presentation (with some variation across stimulation frequency). We then collected new EEG data (N = 100) replicating this finding for both monocular and dichoptic mask arrangements in a preregistered study designed to measure reweighting. A third experiment (N = 20) used source-localized magnetoencephalography and found that these effects are apparent in primary visual cortex (V1), consistent with results from neurophysiological work. Because long-standing theories propose inhibition/excitation differences in autism, we also compared reweighting between individuals with high versus low autistic traits, and with and without an autism diagnosis, across our three datasets (total N = 220). We find no compelling differences in reweighting that are associated with autism. Our results support the normalization reweighting model and indicate that for prolonged stimulation, increases in suppression occur on the order of 2-5 seconds after stimulus onset.

Desynchronization of neuronal firing in multiparameter ultrasound stimulation

Low-intensity transcranial ultrasound stimulation, a novel neuromodulation technique, that possesses the advantages of non-invasiveness, high penetration depth, and high spatial resolution, has achieved positive neuromodulation effects in animal studies. But the regulatory mechanism remains controversial. The intramembrane cavitation effect is considered one of the mechanisms for ultrasound neuromodulation. In this study, the modified equations of ultrasonic cavitation bubble dynamics were coupled with the dual-coupled neuron Hindmarsh-Rose model, small-world neural network model, and the Jansen-Rit neural mass model, which simulate simple coupled neurons, complex neuronal networks, and discharge signals in epileptic disorders respectively. The results demonstrated that ultrasound stimulation has an appreciable modulatory effect on neuronal firing desynchronization in Hindmarsh-Rose model and small-world neural network model. The desynchronization effect is related to the stimulation frequency and intensity. Furthermore, ultrasound stimulation has an inhibitory effect on epileptic seizures, and the effect is enhanced by increasing ultrasound frequency from 0.1–1.0 MHz. This is the first combination of ultrasonic intramembrane cavitation effect theory with neurons and neural network firing desynchronization, which can provide guidance of parametric and theories support for the studies of neurological diseases such as epilepsy and Parkinson’s disease.

Optimizing Noninvasive Vagus Nerve Stimulation for Systemic Lupus Erythematosus: Protocol for a Multicenter Randomized Controlled Trial.

Systemic lupus erythematosus is a chronic, multisystem, inflammatory disease of autoimmune etiology occurring predominantly in women. A major hurdle to the diagnosis, treatment, and therapeutic advancement of this disease is its heterogeneous nature, which presents as a wide range of symptoms such as fatigue, fever, musculoskeletal involvement, neuropsychiatric disorders, and cardiovascular involvement with varying severity. The current therapeutic approach to this disease includes the administration of immunomodulatory drugs that may produce unfavorable secondary effects. This study explores the known relationship between the autonomic nervous system and inflammatory pathways to improve patient outcomes by treating autonomic nervous system dysregulation in patients via noninvasive vagus nerve stimulation. In this study, data including biomarkers, physiological signals, patient outcomes, and patient quality of life are being collected and analyzed. After completion of the clinical trial, a computer model will be developed to identify the biomarkers and physiological signals related to lupus activity in order to understand how they change with different noninvasive vagus nerve stimulation frequency parameters. Finally, we propose building a decision support system with integrated noninvasive wearable technologies for continuous cardiovascular and peripheral physiological sensing for adaptive, patient-specific optimization of the noninvasive vagus nerve stimulation frequency parameters in real time. The protocol was designed to evaluate the efficacy and safety of transauricular vagus nerve stimulation in patients with systemic lupus erythematosus. This multicenter, national, randomized, double-blind, parallel-group, placebo-controlled study will recruit a minimum of 18 patients diagnosed with this disease. Evaluation and treatment of patients will be conducted in an outpatient clinic and will include 12 visits. Visit 1 consists of a screening session. Subsequent visits up to visit 6 involve mixing treatment and evaluation sessions. Finally, the remaining visits correspond with early and late posttreatment follow-ups. On November 2022, data collection was initiated. Of the 10 participants scheduled for their initial appointment, 8 met the inclusion criteria, and 6 successfully completed the entire protocol. Patient enrollment and data collection are currently underway and are expected to be completed in December 2023. The results of this study will advance patient-tailored vagus nerve stimulation therapies, providing an adjunctive treatment solution for systemic lupus erythematosus that will foster adoption of technology and, thus, expand the population with systemic lupus erythematosus who can benefit from improved autonomic dysregulation, translating into reduced costs and better quality of life. ClinicalTrials.gov NCT05704153; https://clinicaltrials.gov/study/NCT05704153. DERR1-10.2196/48387.

Selective Activation of Subthalamic Nucleus Output Quantitatively Scales Movements.

The subthalamic nucleus (STN) is a common target for deep brain stimulation (DBS) treatments of Parkinsonian motor symptoms. According to the dominant model, the STN output can suppress movement by enhancing inhibitory basal ganglia (BG) output via the indirect pathway, and disrupting STN output using DBS can restore movement in Parkinson's patients. But the mechanisms underlying STN DBS remain poorly understood, as previous studies usually relied on electrical stimulation, which cannot selectively target STN output neurons. Here, we selectively stimulated STN projection neurons using optogenetics and quantified behavior in male and female mice using 3D motion capture. STN stimulation resulted in movements with short latencies (10-15 ms). A single pulse of light was sufficient to generate movement, and there was a highly linear relationship between stimulation frequency and kinematic measures. Unilateral stimulation caused movement in the ipsiversive direction (toward the side of stimulation) and quantitatively determined head yaw and head roll, while stimulation of either STN raises the head (pitch). Bilateral stimulation does not cause turning but raised the head twice as high as unilateral stimulation of either STN. Optogenetic stimulation increased the firing rate of STN neurons in a frequency-dependent manner, and the increased firing is responsible for stimulation-induced movements. Finally, stimulation of the STN's projection to the brainstem mesencephalic locomotor region was sufficient to reproduce the behavioral effects of STN stimulation. These results question the common assumption that the STN suppresses movement, and instead suggest that STN output can precisely specify action parameters via direct projections to the brainstem.SIGNIFICANCE STATEMENT Our results question the common assumption that the subthalamic nucleus (STN) suppresses movement, and instead suggest that STN output can precisely specify action parameters via direct projections to the brainstem.

A - 88 Parkinson's Disease and Deep Brain Stimulation (DBS) Device Settings: Effects of Amplitude, Pulse Width, and Frequency on Cognitive Performance.

Frontal systems decline after DBS for Parkinson's disease has been consistently reported, with high frequency settings (>130Hz) correlating with decreased executive functioning and verbal fluency. The present study replicates and expands upon these findings. Six DBS recipients underwent standardized pre/post-surgical neuropsychological testing. Two-tailed T-tests assessed changes in cognitive scores. Correlational analyses explored relationships between cognitive scores and UPDRS, H&Y, and stimulator settings (amplitude, pulse width, and frequency). All participants underwent bilateral STN stimulation. Pre/post averages were: UPDRS (43.0 and 26.2) and H&Y (2.7 and 2.3) with average stimulator settings of amplitude (2.7V), pulse width (60.8μs), and frequency (151.7Hz). Pre/post neuropsychological testing revealed significant decline on the Behavioral Dyscontrol Scale (p = <0.01) with an average raw score decline of 3.17 points. All other cognitive scores showed non-significant improvement (p-value range = 0.22-0.89). H&Y change significantly correlated with semantic fluency (r = 0.96). UPDRS change significantly correlated with motoric processing speed (r = 0.91), semantic fluency (r = -0.93), and confrontation naming (r = -0.86). Stimulator amplitude significantly correlated with auditory attention (r = 0.82); simple planning (r = 0.96); and verbal memory (r = -0.86). Stimulator frequency significantly correlated with auditory attention (r = 0.87), simple planning (r = 0.97), and verbal memory (r = -0.96). Simulator pulse width was not significant. The study examines effects of bilateral STN stimulation on cognitive outcomes in patients with PD. A significant improvement in motor function was accompanied by a significant decline in performance on upper motor bilateral dexterity and inhibition. Correlation analysis shows the relationship between changes in cognition and motor function, as well as the correlation between stimulator settings and specific cognitive functions.

Amplitude- and frequency-dependent activation of layer II/III neurons by intracortical microstimulation

Intracortical microstimulation (ICMS) has been used for the development of brain machine interfaces. However, further understanding about the spatiotemporal responses of neurons to different electrical stimulation parameters is necessary to inform the design of optimal therapies. In this study, we employed invivo electrophysiological recording, two-photon calcium imaging, and electric field simulation to evaluate the acute effect of ICMS on layer II/III neurons. Our results show that stimulation frequency non-linearlymodulates neuronal responses, whereas the magnitude of responses is linearly correlated to the electric field strength and stimulation amplitude before reaching a steady state. Temporal dynamics of neurons' responses depends more on stimulation frequency and their distance to the stimulation electrode. In addition, amplitude-dependent post-stimulation suppression was observed within ∼500μm of the stimulation electrode, as evidenced by both calcium imaging and local field potentials. These findings provide insights for selecting stimulation parameters to achieve desirable spatiotemporal specificity of ICMS.

Optogenetic activation of visual thalamus generates artificial visual percepts.

The lateral geniculate nucleus (LGN), a retinotopic relay center where visual inputs from the retina are processed and relayed to the visual cortex, has been proposed as a potential target for artificial vision. At present, it is unknown whether optogenetic LGN stimulation is sufficient to elicit behaviorally relevant percepts, and the properties of LGN neural responses relevant for artificial vision have not been thoroughly characterized. Here, we demonstrate that tree shrews pretrained on a visual detection task can detect optogenetic LGN activation using an AAV2-CamKIIα-ChR2 construct and readily generalize from visual to optogenetic detection. Simultaneous recordings of LGN spiking activity and primary visual cortex (V1) local field potentials (LFP) during optogenetic LGN stimulation show that LGN neurons reliably follow optogenetic stimulation at frequencies up to 60 Hz, and uncovered a striking phase locking between the V1 local field potential (LFP) and the evoked spiking activity in LGN. These phase relationships were maintained over a broad range of LGN stimulation frequencies, up to 80 Hz, with spike field coherence values favoring higher frequencies, indicating the ability to relay temporally precise information to V1 using light activation of the LGN. Finally, V1 LFP responses showed sensitivity values to LGN optogenetic activation that were similar to the animal's behavioral performance. Taken together, our findings confirm the LGN as a potential target for visual prosthetics in a highly visual mammal closely related to primates.

Repetitive transcranial magnetic stimulation in central post-stroke pain: current status and future perspective.

Central post-stroke pain (CPSP) is an incapacitating disorder that impacts a substantial proportion of stroke survivors and can diminish their quality of life. Conventional therapies for CPSP, including tricyclic antidepressants, anticonvulsants, and opioids, are frequently ineffective, necessitating the investigation of alternative therapeutic strategies. Repetitive transcranial magnetic stimulation (rTMS) is now recognized as a promising noninvasive pain management method for CPSP. rTMS modulates neural activity through the administration of magnetic pulses to specific cortical regions. Trials analyzing the effects of rTMS on CPSP have generated various outcomes, but the evidence suggests possible analgesic benefits. In CPSP and other neuropathic pain conditions, high-frequency rTMS targeting the primary motor cortex (M1) with figure-eight coils has demonstrated significant pain alleviation. Due to its associaton with analgesic benefits, M1 is the most frequently targeted area. The duration and frequency of rTMS sessions, as well as the stimulation intensity, have been studied in an effort to optimize treatment outcomes. The short-term pain relief effects of rTMS have been observed, but the long-term effects (> 3 months) require further investigation. Aspects such as stimulation frequency, location, and treatment period can influence the efficacy of rTMS and ought to be considered while planning the procedure. Standardized guidelines for using rTMS in CPSP would optimize therapy protocols and improve patient outcomes. This review article provides an up-to-date overview of the incidence, clinical characteristics, outcome of rTMS in CPSP patients, and future perspective in the field.

Measurement of distortion-product otoacoustic emissions at low frequency and effect of contralateral acoustic stimulation on its level

Measurement of distortion-product otoacoustic emissions (DPOAEs) is one of the functional tests for the outer hear cells in the cochlea. Since the sound levels of the DPOAEs are quite low, it is easy to be buried in noise especially in the low frequency range, and frequency analysis and time averaging are required to detect them. In this study, focusing on the frequency stability of two stimulus sounds and a most prominent DPOAE-component, we tried to reduce noise floor and shorten the measurement time by choosing an adequate time window length for averaging the sound pressure waveform in the ear canal and the number of the averaging. As a result, it has become possible to measure DPOAEs at the low frequencies around 300 Hz in a relatively short time. Using this method, the changes in the DPOAE level induced by contralateral acoustic stimulation, which are caused by medial olivocochlear reflex, were measured. Although some exceptions were observed, the DPOAE was suppressed with increasing the sound pressure of the contralateral stimulus, and the degree of suppression was greater for the lower-frequency DPOAEs.

Multivariable closed-loop control of deep brain stimulation for Parkinson’s disease

Objective. Closed-loop deep brain stimulation (DBS) methods for Parkinson’s disease (PD) to-date modulate either stimulation amplitude or frequency to control a single biomarker. While good performance has been demonstrated for symptoms that are correlated with the chosen biomarker, suboptimal regulation can occur for uncorrelated symptoms or when the relationship between biomarker and symptom varies. Control of stimulation-induced side-effects is typically not considered. Approach. A multivariable control architecture is presented to selectively target suppression of either tremor or subthalamic nucleus beta band oscillations. DBS pulse amplitude and duration are modulated to maintain amplitude below a threshold and avoid stimulation of distal large diameter axons associated with stimulation-induced side effects. A supervisor selects between a bank of controllers which modulate DBS pulse amplitude to control rest tremor or beta activity depending on the level of muscle electromyographic (EMG) activity detected. A secondary controller limits pulse amplitude and modulates pulse duration to target smaller diameter axons lying close to the electrode. The control architecture was investigated in a computational model of the PD motor network which simulated the cortico-basal ganglia network, motoneuron pool, EMG and muscle force signals. Main results. Good control of both rest tremor and beta activity was observed with reduced power delivered when compared with conventional open loop stimulation, The supervisor avoided over- or under-stimulation which occurred when using a single controller tuned to one biomarker. When DBS amplitude was constrained, the secondary controller maintained the efficacy of stimulation by increasing pulse duration to compensate for reduced amplitude. Dual parameter control delivered effective control of the target biomarkers, with additional savings in the power delivered. Significance. Non-linear multivariable control can enable targeted suppression of motor symptoms for PD patients. Moreover, dual parameter control facilitates automatic regulation of the stimulation therapeutic dosage to prevent overstimulation, whilst providing additional power savings.

Transcutaneous Electrical Stimulation of the Abdomen, Ear, and Tibial Nerve Modulates Bladder Contraction in a Rat Detrusor Overactivity Model: A Pilot Study.

The global prevalence of overactive bladder (OAB) is estimated at 11.8%. Despite existing treatment options such as sacral neuromodulation, a substantial number of patients remain untreated. One potential alternative is noninvasive transcutaneous electrical stimulation. This form of stimulation does not necessitate the implantation of an electrode, thereby eliminating the need for highly skilled surgeons, expensive implantable devices, or regular hospital visits. We hypothesized that alternative neural pathways can impact bladder contraction. In this pilot study, we conducted transcutaneous electrical stimulation of the abdominal wall (T6-L1), the ear (vagus nerve), and the ankle (tibial nerve) of 3 anesthetized female Sprague-Dawley rats. Stimulation was administered within a range of 20 Hz to 20 kHz, and its impact on intravesical pressure was measured. We focused on 3 primary outcomes related to intravesical pressure: (1) the pressure change from the onset of a contraction to its peak, (2) the average duration of contraction, and (3) the number of contractions within a specified timeframe. These measurements were taken while the bladder was filled with either saline or acetic acid (serving as a model for OAB). Transcutaneous stimulation of the abdominal wall, ear, and ankle at a frequency of 20 Hz decreased the number of bladder contractions during infusion with acetic acid. As revealed by a comparison of various stimulation frequencies of the tibial nerve during bladder infusion with acetic acid, the duration of contraction was significantly shorter during stimulation at 1 kHz and 3 kHz relative to stimulation at 20 Hz (P = 0.025 and P = 0.044, respectively). The application of transcutaneous electrical stimulation to the abdominal wall, ear, and tibial nerve could provide less invasive and more cost-effective treatment options for OAB relative to percutaneous tibial nerve stimulation and sacral neuromodulation. A follow-up study involving a larger sample size is recommended.

Optimal parameters for rapid (invisible) frequency tagging using MEG

Frequency tagging has been demonstrated to be a useful tool for identifying representational-specific neuronal activity in the auditory and visual domains. However, the slow flicker (<30 Hz) applied in conventional frequency tagging studies is highly visible and might entrain endogenous neuronal oscillations. Hence, stimulation at faster frequencies that is much less visible and does not interfere with endogenous brain oscillatory activity is a promising new tool. In this study, we set out to examine the optimal stimulation parameters of rapid frequency tagging (RFT/RIFT) with magnetoencephalography (MEG) by quantifying the effects of stimulation frequency, size and position of the flickering patch. Rapid frequency tagging using flickers above 50 Hz results in almost invisible stimulation which does not interfere with slower endogenous oscillations; however, the signal is weaker as compared to tagging at slower frequencies so certainty over the optimal parameters of stimulation delivery are crucial. The here presented results examining the frequency range between 60 Hz and 96 Hz suggest that RFT induces brain responses with decreasing strength up to about 84 Hz. In addition, even at the smallest flicker patch (2°) focally presented RFT induces a significant and measurable oscillatory brain signal (steady state visual evoked potential/field, SSVEP/F) at the stimulation frequency (66 Hz); however, the elicited response increases with patch size. While focal RFT presentation elicits the strongest response, off-centre presentations do generally mainly elicit a measureable response if presented below the horizontal midline. Importantly, the results also revealed considerable individual differences in the neuronal responses to RFT stimulation. Finally, we discuss the comparison of oscillatory measures (coherence and power) and sensor types (planar gradiometers and magnetometers) in order to achieve optimal outcomes. Based on our extensive findings we set forward concrete recommendations for using rapid frequency tagging in human cognitive neuroscience investigations.

Network Model of Nociceptive Processing in the Superficial Spinal Dorsal Horn Reveals Mechanisms of Hyperalgesia, Allodynia, and Spinal Cord Stimulation.

The spinal dorsal horn (DH) processes sensory information and plays a key role in transmitting nociception to supraspinal centers. Loss of DH inhibition during neuropathic pain unmasks a pathway from non-nociceptive Aβ-afferent inputs to superficial dorsal horn (SDH) nociceptive-specific (NS) projection neurons, and this change may contribute to hyperalgesia and allodynia. We developed and validated a computational model of SDH neuronal circuitry that linked non-nociceptive Aβ-afferent inputs in lamina II/III to a NS projection neuron in lamina I via a network of excitatory interneurons. The excitatory pathway and the NS projection neuron were in turn gated by inhibitory interneurons with connections based on prior patch clamp recordings. Changing synaptic weights in the computational model to replicate neuropathic pain states unmasked a low-threshold excitatory pathway to NS neurons similar to experimental recordings. Spinal cord stimulation (SCS) is an effective therapy for neuropathic pain, and accumulating experimental evidence indicates that NS neurons in the SDH also respond to SCS. Accounting for these responses may inform therapeutic improvements, and we quantified responses to SCS in the SDH network model and examined the role of different modes of inhibitory control in modulating NS neuron responses to SCS. We combined the SDH network model with a previously published model of the deep dorsal horn (DDH) and identified optimal stimulation frequencies across different neuropathic pain conditions. Finally, we found that SCS-generated inhibition did not completely suppress model NS activity during simulated pinch inputs, providing an explanation of why SCS does not eliminate acute pain.

Disease severity, arrhythmogenesis, and fibrosis are related to longer action potentials in tetralogy of Fallot.

Arrhythmias may originate from surgically unaffected right ventricular (RV) regions in patients with tetralogy of Fallot (TOF). We aimed to investigate action potential (AP) remodelling and arrhythmia susceptibility in RV myocardium of patientswith repaired and with unrepaired TOF, identify possible correlations with clinical phenotype and myocardial fibrosis, and compare findings with data from patients with atrial septal defect (ASD), a less severe congenital heart disease. Intracellular AP were recorded ex vivo in RV outflow tract samples from 22 TOF and three ASD patients. Arrhythmias were provoked by superfusion with solutions containing reduced potassium and barium chloride, or isoprenaline. Myocardial fibrosis was quantified histologically and associations between clinical phenotype, AP shape, tissue arrhythmia propensity, and fibrosis were examined. Electrophysiological abnormalities (arrhythmias, AP duration [APD] alternans, impaired APD shortening at increased stimulation frequencies) were generally present in TOF tissue, even from infants, but rare or absent in ASD samples. More severely diseased and acyanotic patients, pronounced tissue susceptibility to arrhythmogenesis, and greater fibrosis extent were associated with longer APD. In contrast, APD was shorter in tissue from patients with pre-operative cyanosis. Increased fibrosis and repaired-TOF status were linked to tissue arrhythmia inducibility. Functional and structural tissue remodelling may explain arrhythmic activity in TOF patients, even at a very young age. Surprisingly, clinical acyanosis appears to be associated with more severe arrhythmogenic remodelling. Further research into the clinical drivers of structural and electrical myocardial alterations, and the relation between them, is needed to identify predictive factors for patients at risk.

Multifrequency Analysis of Masseter Vestibular Evoked Myogenic Potentials in Young Adults.

The purpose of this study was to explore the dynamics of multifrequency tone bursts on the masseter vestibular evoked myogenic potential (mVEMP) parameters. Furthermore, it sought to determine the optimal frequency tuning of mVEMP responses. Twenty young adults with normal hearing sensitivity participated in the study. Bilateral tone burst evoked mVEMPs were obtained using the zygomatic montage at 250-, 500-, 750-, 1000-, 1500-, and 2000-Hz stimulation frequencies. Self-monitoring biofeedback was given during the procedure to confirm the tension of the masseter muscle between 49.9 and 150.6 rms. Furthermore, the electromyography (EMG) scaling was done to avoid any muscle-related irregularities. Tone burst evoked mVEMPs were found to be 100% present at the stimulation frequencies of 250, 500, 750, and 1000 Hz. There were no ear and gender effects seen for any of the frequencies. Significant shortening of the P1 and N1 latencies with increasing stimulation frequencies was observed. The peak-to-peak amplitude was the highest at 500 Hz and lowest at 2000 Hz tone bursts under both EMG scaled and unscaled conditions. The present revealed higher response rates and larger amplitudes study of mVEMP at lower frequencies, and, therefore, the frequency tuning was seen for the stimulation frequency at 500 Hz.

Brief Submotor-Threshold Electrical Stimulation Applied Synchronously Over Wrist Flexor and Extensor Muscles does Not Suppress Essential Tremor, Independent of Stimulation Frequency.

Electrical stimulation of muscles below motoneuron threshold has shown potential as a low-cost and minimally invasive treatment for Essential Tremor (ET). Prior studies have stimulated wrist flexor and extensor muscles synchronously with diverging results, calling for further investigation. Also, prior studies have only used a narrow range of stimulation parameters, so stimulation parameters have not been optimized. Our purpose was to further investigate synchronous submotor stimulation and identify the effect of stimulation frequency on tremor suppression. We quantified the effect of brief, synchronous stimulation at 15 different frequencies from 10-150 Hz applied over wrist flexors and extensors on both tremor power and frequency in 20 ET patients. We compared tremor power and frequency from hand acceleration and sEMG between pre-, per-, and post-stimulation phases. Our stimulation paradigm did not result in significant tremor suppression or tremor frequency changes at any tested stimulation frequency, showing no significant interaction between phase and stimulation frequency for tremor power measured by either hand acceleration (p = 0.69) or sEMG (p = 0.07). Additionally, the effect of phase interacting with stimulation frequency on tremor frequency was statistically insignificant for acceleration (p = 0.64) and sEMG (p = 0.37). We conclude that brief synchronous submotor-threshold stimulation does not reduce tremor in ET patients, independent of stimulation frequency (from 10 to 150 Hz). Our results are consistent with the hypothesis that brief submotor-threshold stimulation suppresses tremor via reciprocal inhibition, which requires asynchronous stimulation. In contrast, it is hypothesized that synchronous stimulation might require longer stimulation durations to affect supraspinal tremor networks. We studied the effects of synchronous submotor electrical stimulation over wrist flexor and extensor muscles on Essential Tremor. Our results indicate that suppressing tremor with brief synchronous stimulation is ineffective. Based on recently hypothesized mechanisms of peripheral tremor suppression, we hypothesize that asynchronous stimulation or long-duration synchronous stimulation are more effective approaches to peripheral tremor suppression.

Abstract P382: Long-term Consequences Of Early Childhood Obesity In The Endothelial And Erectile Function Of Male Rats

The consequences of obesity to endothelial and erectile dysfunction are well documented, however, the consequences of obesity in early childhood in later years are unknown. We hypothesize that early childhood obesity induced by postnatal overfeeding impairs aortic reactivity, erectile function, and blood pressure in prepubertal and adult male rats. At postnatal day (PND) 1, Wistar rats were divided into a normal litter (NL, dams were kept with 5 female and 5 male pups) or small litter (SL, dams were kept with 2 male and 1 female pup). The rats were evaluated at two time points prepubertal (PND 40), and in adulthood (PND 120). Body weight (g) and retroperitoneal adipose tissue (fat pad weight/100g of the body n=9-13) were evaluated. The mean blood pressure (MBP, mmHg n=6-7) was measured in conscious rats by indirect tail-cuff method. Aorta and corpus cavernosum were removed. Vascular function was performed via pin myograph and erectile function via strip myograph. Concentration-response curves to phenylephrine (PE) or acetylcholine (ACh) were performed. Prepubertal SL rats had higher body weight (NL 148±2 vs. SL 185±4, g, p&lt;0.05), and adipose tissue deposition (NL 0.17±0.09 vs. SL 0.32±0.03, p&lt;0.05). SL at PND 120 had higher body weight (NL 419±9 vs SL 462±5, g, p&lt;0.05) and retroperitoneal adipose tissue (NL 1.2±0.9 vs SL 1.6±0.1, p&lt;0.05]), and SL rats presented increased MBP (NL 114.9±0.58 vs SL 120.5±1.20). No changes in endothelium-dependent relaxation were observed in the aorta at PND 40 or 120. However, there was an increase in vascular contractility in SL group at PND 40 (Emax: NL 1.17±0.40 vs SL 1.47±0.06, g, p&lt;0.05). In the corpus cavernosum, the relaxation induced by electrical field stimulation was significantly decreased for all frequencies of stimulation in SL rats at PD120 compared to NL rats (1 Hz: NL 0.77 ± 0.18% vs SL 0.27 ± 0.09%; 4 Hz: NL 2.48 ± 0.26% vs SL 1.36 ± 0.41%; 16 Hz: NL 3.06 ± 0.28% vs SL 2.39 ± 0.53%). Our data suggest that obesity in early childhood can cause long-lasting vascular damage to males that can be associated with erectile dysfunction in adulthood.

Effects of eccentric contraction on force enhancement in rat fast-twitch muscle.

The aim of this study was to elucidate the effects of eccentric contraction (ECC) on force enhancement in rat fast-twitch skeletal muscle. Gastrocnemius (GAS) muscles were subjected to 200 ECCs in situ by electrical stimulation. Immediately before and after the stimulation, isometric torque produced by ankle flexion was measured at an ankle angle of 90°. After the second torque measurement, the superficial regions of the muscles were dissected and subjected to biochemical and skinned fiber analysis. ECC did not induce changes in the amount of degraded titin. After ECC, isometric torques in the GAS muscles were markedly reduced, especially at low stimulation frequency. ECC increased passive torque in whole muscle and passive force in skinned fibers. Passive force enhancement and the ratio of passive force to the maximal Ca2+ -activated force, but not residual force enhancement, were augmented in the skinned fibers subjected to ECC. An ECC-induced increase in titin-based stiffness may contribute to the increased PFE. These results suggest that skeletal muscle is endowed with a force potentiation system that can attenuate ECC-induced force reductions.

Post-activation depression of the Hoffman reflex is not altered by galvanic vestibular stimulation in healthy subjects.

The comprehension of the neural elements interacting in the spinal cord affected by vestibular input will contribute to the understanding of movement execution in normal and pathological conditions. In this context, Hoffman's reflex (H-reflex) has been used to evaluate transient excitability changes on the spinal cord descending pathways. The post-activation depression (P-AD) of the H-reflex consists of evoking consecutive responses (>1 Hz) provoking an amplitude depression, which has been shown to diminish in pathological conditions (i.e., spasticity, diabetic neuropathy). Galvanic Vestibular Stimulation (GVS) is a non-invasive method that activates the vestibular afferents and has been used to study the excitability of the H-reflex applied as a conditioning pulse. To our knowledge, there are no reports evaluating the P-AD during and after GVS. Our primary aim was to determine if GVS alters the P-AD evoked by stimulating the tibial nerve at 0.1, 1, 5, and 10 Hz, recording in the gastrocnemius and soleus muscles. Direct current stimulation of 2.0 ± 0.6 mA with the cathode ipsilateral (Ipsi) or contralateral (Contra) to the H-reflex electrode montage was applied bilaterally over the mastoid process in 19 healthy subjects. The P-AD's immediate post-GVS response (P Ipsi, P Contra) was also analyzed. Secondarily, we analyzed the excitability of the H-reflex during GVS. Responses evoked at 0.1 Hz with GVS, post-GVS, and a Control (no GVS) condition were used for comparisons. Our results show that P-AD persisted in all subjects despite increased excitability induced by GVS: statistical significance was found when comparing P-AD at 1, 5, and 10 Hz with the corresponding condition (Control, Ipsi, P Ipsi, Contra, P Contra) at 0.1 Hz (p < 0.001). Additionally, the increase in excitability produced by GVS was quantified for the first H-reflex of each P-AD stimulation frequency. The percentage change for all GVS conditions surpassed the Control by at least 20%, being statistically significant for Contra compared to Control (p < 0.01). In summary, although GVS increases the excitability of the vestibulospinal pathway at a premotor level, the neural inhibitory mechanism present in P-AD remains unaltered in healthy subjects.