Inhibition of tibialis anterior spinal reflex circuits using frequency-specific neuromuscular electrical stimulation.

BACKGROUND: Neuromuscular electrical stimulation (NMES) can generate muscle contractions and elicit excitability of neural circuits. However, the optimal stimulation frequency for effective neuromodulation remains unclear. METHODS: Eleven able-bodied individuals participated in our study to examine the effects of: (1) low-frequency NMES at 25 Hz, (2) high-frequency NMES at 100 Hz; and (3) mixed-frequency NMES at 25 and 100 Hz switched every second. NMES was delivered to the right tibialis anterior (TA) muscle for 1 min in each condition. The order of interventions was pseudorandomized between participants with a washout of at least 15 min between conditions. Spinal reflexes were elicited using single-pulse transcutaneous spinal cord stimulation applied over the lumbar enlargement to evoke responses in multiple lower-limb muscles bilaterally and maximum motor responses (Mmax) were elicited in the TA muscle by stimulating the common peroneal nerve to assess fatigue at the baseline and immediately, 5, 10, and 15 min after each intervention. RESULTS: Our results showed that spinal reflexes were significantly inhibited immediately after the mixed-frequency NMES, and for at least 15 min in follow-up. Low-frequency NMES inhibited spinal reflexes 5 min after the intervention, and also persisted for at least 10 min. These effects were present only in the stimulated TA muscle, while other contralateral and ipsilateral muscles were unaffected. Mmax responses were not affected by any intervention. CONCLUSIONS: Our results indicate that even a short-duration (1 min) NMES intervention using low- and mixed-frequency NMES could inhibit spinal reflex excitability of the TA muscle without inducing fatigue.

Soleus H-reflex amplitude modulation during walking remains physiological during transspinal stimulation in humans.

The soleus H-reflex modulation pattern was investigated during stepping following transspinal stimulation over the thoracolumbar region at 15, 30, and 50 Hz with 10 kHz carry-over frequency above and below the paresthesia threshold. The soleus H-reflex was elicited by posterior tibial nerve stimulation with a single 1 ms pulse at an intensity that the M-wave amplitudes ranged from 0 to 15% of the maximal M-wave evoked 80 ms after the test stimulus, and the soleus H-reflex was half the size of the maximal H-reflex evoked on the ascending portion of the recruitment curve. During treadmill walking, the soleus H-reflex was elicited every 2 or 3 steps, and stimuli were randomly dispersed across the step cycle which was divided in 16 equal bins. For each subject and condition, the soleus M-wave and H-reflex were normalized to the maximal M-wave. The soleus background electromyographic (EMG) activity was estimated as the linear envelope for 50 ms duration starting at 100 ms before posterior tibial nerve stimulation for each bin. The gain was determined as the slope of the relationship between the soleus H-reflex and the soleus background EMG activity. The soleus H-reflex phase-dependent amplitude modulation remained unaltered during transspinal stimulation, regardless frequency, or intensity. Similarly, the H-reflex slope and intercept remained the same for all transspinal stimulation conditions tested. Locomotor EMG activity was increased in knee extensor muscles during transspinal stimulation at 30 and 50 Hz throughout the step cycle while no effects were observed in flexor muscles. These findings suggest that transspinal stimulation above and below the paresthesia threshold at 15, 30, and 50 Hz does not block or impair spinal integration of proprioceptive inputs and increases activity of thigh muscles that affect both hip and knee joint movement. Transspinal stimulation may serve as a neurorecovery strategy to augment standing or walking ability in upper motoneuron lesions.

The association of total pulses with the efficacy of repetitive transcranial magnetic stimulation for treatment-resistant major depression: A dose-response meta-analysis.

AIM: This study aimed to examine dose-effects of total pulses on improvement of depressive symptoms in patients with treatment-resistant depression (TRD) receiving repetitive transcranial magnetic stimulation (rTMS) over the left dorsal lateral prefrontal cortex (DLPFC). MATERIALS AND METHODS: The MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, PsycINFO, and ClinicalTrial.gov databases were systematically searched. We included randomized, double-blind, placebo-controlled trials (RCT) that used rTMS over left DLPFC in patients with TRD. Excluded studies were non-TRD, non-RCTs, or combined other brain stimulation interventions. The outcome of interest was the difference between rTMS arms and sham controls in improvement of depressive symptoms in a dose-response manner. A random-effects meta-analysis and dose-response meta-analysis(DRMA) was used to examine antidepressant efficacy of rTMS and association with total pulses. RESULTS: We found that rTMS over left DLPFC is superior to sham controls (reported as standardized mean difference[SMD] with 95% confidence interval: 0.77; 0.56-0.98). The best-fitting model of DRMA was bell-shaped (estimated using restricted cubic spline model; R2 =0.42), indicating that higher doses (>26,660 total pulses) were not associated with increased improvement of depressive symptoms. Stimulation frequency(R2 =0.53) and age(R2 =0.51) were significant moderators for the dose-response curve. Furthermore, 15-20 Hz rTMS was superior to 10 Hz rTMS (0.61, 0.15-1.10) when combining all doses. CONCLUSIONS: Our findings suggest higher doses(total pulses) of rTMS were not always associated with increased improvement of depressive symptoms in patients with TRD, and that the dose-response relationship was moderated by stimulation frequency and age. These associations emphasize the importance of determining dosing parameters to achieve maximum efficacy.

The Therapeutic Frequency Profile of Subthalamic Nucleus Deep Brain Stimulation in Rats Is Shaped by Antidromic Spike Failure.

The therapeutic mechanisms of subthalamic nucleus (STN) deep brain stimulation (DBS) may depend on antidromic activation of cortex via the hyperdirect pathway. However, hyperdirect pathway neurons cannot reliably follow high-stimulation frequencies, and the spike failure rate appears to correlate with symptom relief as a function of stimulation frequency. We hypothesized that antidromic spike failure contributes to the cortical desynchronization caused by DBS. We measured in vivo evoked cortical activity in female Sprague Dawley rats and developed a computational model of cortical activation from STN DBS. We modeled stochastic antidromic spike failure to determine how spike failure affected the desynchronization of pathophysiological oscillatory activity in cortex. We found that high-frequency STN DBS desynchronized pathologic oscillations via the masking of intrinsic spiking through a combination of spike collision, refractoriness, and synaptic depletion. Antidromic spike failure shaped the parabolic relationship between DBS frequency and cortical desynchronization, with maximum desynchronization at ∼130 Hz. These findings reveal that antidromic spike failure plays a critical role in mediating the dependency of symptom relief on stimulation frequency.SIGNIFICANCE STATEMENT Deep brain stimulation (DBS) is a highly effective neuromodulation therapy, yet it remains uncertain why conventionally used stimulation frequencies (e.g., ∼130 Hz) are optimal. In this study, we demonstrate a potential explanation for the stimulation frequency dependency of DBS through a combination of in vivo experimental measurements and computational modeling. We show that high-frequency stimulation can desynchronize pathologic firing patterns in populations of neurons by inducing an informational lesion. However, sporadic spike failure at these high frequencies limits the efficacy of the informational lesion, yielding a parabolic profile with optimal effects at ∼130 Hz. This work provides a potential explanation for the therapeutic mechanism of DBS, and highlights the importance of considering spike failure in mechanistic models of DBS.

Effect of 3D paradigm synchronous motion for SSVEP-based hybrid BCI-VR system.

A brain-computer interface (BCI) system and virtual reality (VR) are integrated as a more interactive hybrid system (BCI-VR) that allows the user to manipulate the car. A virtual scene in the VR system that is the same as the physical environment is built, and the object's movement can be observed in the VR scene. The four-class three-dimensional (3D) paradigm is designed and moves synchronously in virtual reality. The dynamic paradigm may affect their attention according to the experimenters' feedback. Fifteen subjects in our experiment steered the car according to a specified motion trajectory. According to our online experimental result, different motion trajectories of the paradigm have various effects on the system's performance, and training can mitigate this adverse effect. Moreover, the hybrid system using frequencies between 5 and 10 Hz indicates better performance than those using lower or higher stimulation frequencies. The experiment results show a maximum average accuracy of 0.956 and a maximum information transfer rate (ITR) of 41.033 bits/min. It suggests that a hybrid system provides a high-performance way of brain-computer interaction. This research could encourage more interesting applications involving BCI and VR technologies.

GDNet-EEG: An attention-aware deep neural network based on group depth-wise convolution for SSVEP stimulation frequency recognition.

Background: Steady state visually evoked potentials (SSVEPs) based early glaucoma diagnosis requires effective data processing (e.g., deep learning) to provide accurate stimulation frequency recognition. Thus, we propose a group depth-wise convolutional neural network (GDNet-EEG), a novel electroencephalography (EEG)-oriented deep learning model tailored to learn regional characteristics and network characteristics of EEG-based brain activity to perform SSVEPs-based stimulation frequency recognition. Method: Group depth-wise convolution is proposed to extract temporal and spectral features from the EEG signal of each brain region and represent regional characteristics as diverse as possible. Furthermore, EEG attention consisting of EEG channel-wise attention and specialized network-wise attention is designed to identify essential brain regions and form significant feature maps as specialized brain functional networks. Two publicly SSVEPs datasets (large-scale benchmark and BETA dataset) and their combined dataset are utilized to validate the classification performance of our model. Results: Based on the input sample with a signal length of 1 s, the GDNet-EEG model achieves the average classification accuracies of 84.11, 85.93, and 93.35% on the benchmark, BETA, and combination datasets, respectively. Compared with the average classification accuracies achieved by comparison baselines, the average classification accuracies of the GDNet-EEG trained on a combination dataset increased from 1.96 to 18.2%. Conclusion: Our approach can be potentially suitable for providing accurate SSVEP stimulation frequency recognition and being used in early glaucoma diagnosis.

Optimization of signal-to-noise ratio in short-duration SEP recordings by variation of stimulation rate.

OBJECTIVE: The intraoperative averaging of the somatosensory evoked potential (SEP) requires reliable recordings within the shortest possible duration. We here systematically optimized the repetition rate of stimulus presentation. METHODS: We recorded medianus and tibial nerve SEP during 22 surgeries and varied the rate of stimulus presentation between 2.7 Hz and 28.7 Hz. We randomly sampled a number of sweeps corresponding to recording durations up to 20 s and calculated the signal-to-noise ratio (SNR). RESULTS: For the medianus nerve at 5 s recording duration, SEP stimulation rate at 12.7 Hz obtained the highest median SNR = 22.9 for the N20, which was higher than for rate 4.7 Hz (p = 1.5e-4). When increasing the stimulation rate, latency increased and amplitude decayed for cortical but not for peripheral recording sites. For the tibial nerve, the rate 4.7 Hz achieved the highest SNR for all durations. CONCLUSIONS: We determined the time-dependence of SNR for N20 and elucidated the underlying physiology. For short recordings, rapid reduction of noise through averaging at high stimulation rate outweighs the disadvantage of smaller amplitude. SIGNIFICANCE: For a short duration of medianus nerve SEP recording only, it may be advantageous to stimulate with a repetition rate of 12.7 Hz.

Does subthalamic nucleus deep brain stimulation affect the static balance at different frequencies? / ¿La estimulación cerebral profunda del núcleo subtalámico afecta el equilibrio estático en diferentes frecuencias?

Purpose To investigate the effects of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) with different stimulation frequencies on static balance. Materials and methods Twenty patients (15 males and 5 females), aged between 43 and 81 (mean: 60.05±7.4) years, who had been diagnosed with idiopathic Parkinson's disease (PD) and undergone STN-DBS surgery were included in the study. Static balance was assessed with TecnoBody Rehabilitation System at four different frequencies: 230, 130, 90 and 60Hz and off-stimulation. Static balance tests were ‘stabilometric test, stabilometric compared bipedal closed/opened eye, stabilometric compared mono pedal (right/left foot)’. These tests reported the centre of pressure data ‘ellipse area, perimeter, front/back and mediolateral standard deviations’. Results There were no statically differences between the static balance test results at any frequency (p>0.05), but results were found better at 90Hz. Stabilometric compared bipedal opened eye forward–backward standard deviation result was significant between off-stimulation and 130Hz (p=0.04). Different frequency stimulation affected the static balance categories percentage with no statistical significance between off-stimulation and others (all p>0.05). Conclusion This study showed that STN-DBS did not affect the static balance negatively. Low-frequency (LF) stimulation improved the static equilibrium. Posturography systems will give more precise and quantitative results in similar studies with wide frequency ranges (AU)

Propósito Investigar los efectos de la estimulación cerebral profunda del núcleo subtalámico bilateral (STN-DBS) con diferentes frecuencias de estimulación sobre el equilibrio estático. Materiales y métodos Se incluyó en el estudio a 20 pacientes (15 varones y 5 mujeres), con edades comprendidas entre 43 y 81 años (media: 60,05±7,4), que habían sido diagnosticados de enfermedad de Parkinson idiopática e intervenidos mediante cirugía STN-DBS. El equilibrio estático se evaluó con el sistema de rehabilitación TecnoBody en 4 frecuencias diferentes: 230, 130, 90 y 60Hz y sin estimulación. Las pruebas de equilibrio estático fueron: prueba estabilométrica, ojo cerrado/abierto bípedo comparado con estabilométrico, monopedal comparado con estabilométrico (pie derecho/izquierdo). Estas pruebas informaron el centro de datos de presión: área de elipse, perímetro, desviaciones estándar mediolateral y frontal/posterior. Resultados No hubo diferencias estadísticamente significativas entre los resultados de la prueba de equilibrio estático en cualquier frecuencia (p>0,05), pero los resultados fueron mejores con 90Hz. El resultado de la desviación estándar hacia adelante-atrás del ojo abierto bípedo comparado con el estabilométrico fue significativo entre la estimulación inactiva y 130Hz (p=0,04). La estimulación de diferente frecuencia afectó al porcentaje de categorías de equilibrio estático, sin significación estadística entre la estimulación inactiva y otras (todas p>0,05). Conclusión Este estudio mostró que STN-DBS no afectó negativamente al equilibrio estático. La estimulación de baja frecuencia mejoró el equilibrio estático. Los sistemas de posturografía darán resultados más precisos y cuantitativos en estudios similares con amplios rangos de frecuencia (AU)

Does subthalamic nucleus deep brain stimulation affect the static balance at different frequencies?

PURPOSE: To investigate the effects of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) with different stimulation frequencies on static balance. MATERIALS AND METHODS: Twenty patients (15 males and 5 females), aged between 43 and 81 (mean: 60.05±7.4) years, who had been diagnosed with idiopathic Parkinson's disease (PD) and undergone STN-DBS surgery were included in the study. Static balance was assessed with TecnoBody Rehabilitation System at four different frequencies: 230, 130, 90 and 60Hz and off-stimulation. Static balance tests were 'stabilometric test, stabilometric compared bipedal closed/opened eye, stabilometric compared mono pedal (right/left foot)'. These tests reported the centre of pressure data 'ellipse area, perimeter, front/back and mediolateral standard deviations'. RESULTS: There were no statically differences between the static balance test results at any frequency (p>0.05), but results were found better at 90Hz. Stabilometric compared bipedal opened eye forward-backward standard deviation result was significant between off-stimulation and 130Hz (p=0.04). Different frequency stimulation affected the static balance categories percentage with no statistical significance between off-stimulation and others (all p>0.05). CONCLUSION: This study showed that STN-DBS did not affect the static balance negatively. Low-frequency (LF) stimulation improved the static equilibrium. Posturography systems will give more precise and quantitative results in similar studies with wide frequency ranges.

Developmental characteristics of visual evoked potentials to different stimulation in normal children.

OBJECTIVE: To determine the developmental characteristics of flash visual evoked potentials (FVEP) and pattern-reversal visual evoked potentials (PVEP) of healthy children. METHODS: The data were collected with a Keypoint Workstation 9033A07; 168 children (2 months-13 years) were tested with FVEP and 101 (4-13 years) were tested with PVEP. RESULTS: A triphasic waveform with clear components (N2, P2, and N3) was recorded steadily after 1 year, with occurrence rates over 97% at all frequencies. FVEP latency significantly decreased with age. The amplitude difference of FVEP was greater for binocular than monocular fields. FVEP amplitude increased and amplitude differences decreased with stimulation frequency. The occurrence rate of PVEP was 100% after 4 years, and PVEP latency was significantly prolonged with age. N75 and P100 amplitudes and the N75-P100 amplitude difference increased with field of vision. CONCLUSION: FVEP can be evoked in normal children at less than 2 Hz. Stimulation frequency can be adjusted to improve early detection and verification of subclinical lesions. The PVEP waveform is simple and stable, and its results are easier to analyze and interpret than FVEP, but it is limited by visual acuity and fixation force, whereas FVEP is affected less by visual acuity. but it is necessary to establish normal reference values of each age in each laboratory because of complicated analysis. According to the specific situation of the patient (vision, fixation) and clinical demand, we need to choose the right stimulation.

Effect of stimulation frequency on force, power and fatigue of isolated mouse extensor digitorum longus muscle.

This study examined the effect of stimulation frequency (140, 200, 230 and 260 Hz) on isometric force, work loop (WL) power and the fatigue resistance of extensor digitorum longus (EDL) muscle (n=32), isolated from 8- to 10-week-old CD-1 female mice. Stimulation frequency had significant effects on isometric properties of isolated mouse EDL, whereby increasing stimulation frequency evoked increased isometric force, quicker activation and prolonged relaxation (P<0.047) up to 230 Hz and above; thereafter, force and activation did not differ (P>0.137). Increasing stimulation frequency increased maximal WL power output (P<0.001; 140 Hz, 71.3±3.5; 200 Hz, 105.4±4.1; 230 Hz, 115.5±4.1; 260 Hz, 121.1±4.1 W kg-1), but resulted in significantly quicker rates of fatigue during consecutive WLs (P<0.004). WL shapes indicate impaired muscle relaxation at the end of shortening and subsequent increased negative work appeared to contribute to fatigue at 230 and 260 Hz, but not at lower stimulation frequencies. Cumulative work was unaffected by stimulation frequency, except at the start of the fatigue protocol, where 230 and 260 Hz produced more work than 140 Hz (P<0.039). We demonstrate that stimulation frequency affects force, power and fatigue, but these effects are not uniform between different assessments of contractile performance. Therefore, future work examining the contractile properties of isolated skeletal muscle should consider increasing the stimulation frequency beyond that needed for maximal force when examining maximal power but should utilise a sub-maximal stimulation frequency for fatigue assessments to avoid a high degree of negative work atypical of in vivo function.

Frequency-Specific Effects of Galvanic Vestibular Stimulation on Response-Time Performance in Parkinson's Disease.

Background: Galvanic vestibular stimulation (GVS) is being increasingly explored as a non-invasive brain stimulation technique to treat symptoms in Parkinson's disease (PD). To date, behavioral GVS effects in PD have been explored with only two stimulus types, direct current and random noise (RN). The interaction between GVS effects and anti-parkinsonian medication is unknown. In the present study, we designed multisine (ms) stimuli and investigated the effects of ms and RN GVS on motor response time. In comparison to the RN stimulus, the ms stimuli contained sinusoidal components only at a set of desired frequencies and the phases were optimized to improve participants' comfort. We hypothesized GVS motor effects were a function of stimulation frequency, and specifically, that band-limited ms-GVS would result in better motor performance than conventionally used broadband RN-GVS. Materials and Methods: Eighteen PD patients (PDMOFF/PDMON: off-/on-levodopa medication) and 20 healthy controls (HC) performed a simple reaction time task while receiving sub-threshold GVS. Each participant underwent nine stimulation conditions: off-stimulation, RN (4-200 Hz), ms-θ (4-8 Hz), ms-α (8-13 Hz), ms-ß (13-30 Hz), ms-γ (30-50 Hz), ms-h1 (50-100 Hz), ms-h2 (100-150 Hz), and ms-h3 (150-200 Hz). Results: The ms-γ resulted in shorter response time (RPT) in both PDMOFF and HC groups compared with the RN. In addition, the RPT of the PDMOFF group decreased during the ms-ß while the RPT of the HC group decreased during the ms-α, ms-h1, ms-h2, and ms-h3. There was considerable inter-subject variability in the optimum stimulus type, although the frequency range tended to fall within 8-100 Hz. Levodopa medication significantly reduced the baseline RPT of the PD patients. In contrast to the off-medication state, GVS did not significantly change RPT of the PD patients in the on-medication state. Conclusions: Using band-limited ms-GVS, we demonstrated that the GVS frequency for the best RPT varied considerably across participants and was >30 Hz for half of the PDMOFF patients. Moreover, dopaminergic medication was found to influence GVS effects in PD patients. Our results indicate the common "one-size-fits-all" RN approach is suboptimal for PD, and therefore personalized stimuli aiming to address this variability is warranted to improve GVS effects.

Potassium-induced potentiation of subtetanic force in rat skeletal muscles: influences of ß2-activation, lactic acid, and temperature.

Moderate elevations of extracellular K+ concentration ([K+]o) occur during exercise and have been shown to potentiate force during contractions elicited with subtetanic frequencies. Here, we investigated whether lactic acid (reduced chloride conductance), ß2-adrenoceptor activation, and increased temperature would influence the potentiating effect of potassium in slow- and fast-twitch muscles. Isometric contractions were elicited by electrical stimulation at various frequencies in isolated rat soleus and extensor digitorum longus (EDL) muscles incubated at normal (4 mM) or elevated K+, in combination with salbutamol (5 µM), lactic acid (18.1 mM), 9-anthracene-carboxylic acid (9-AC; 25 µM), or increased temperature (30-35°C). Elevating [K+]o from 4 mM to 7 mM (soleus) and 10 mM (EDL) potentiated isometric twitch and subtetanic force while slightly reducing tetanic force. In EDL, salbutamol further augmented twitch force (+27 ± 3%, P < 0.001) and subtetanic force (+22 ± 4%, P < 0.001). In contrast, salbutamol reduced subtetanic force (-28 ± 6%, P < 0.001) in soleus muscles. Lactic acid and 9-AC had no significant effects on isometric force of muscles already exposed to moderate elevations of [K+]o. The potentiating effect of elevated [K+]o was still well maintained at 35°C. Addition of salbutamol exerts a further force-potentiating effect in fast-twitch but not in slow-twitch muscles already potentiated by moderately elevated [K+]o, whereas lactic acid, 9-AC, or increased temperature does not exert any further augmentation. However, the potentiating effect of elevated [K+]o was still maintained in the presence of these, thus emphasizing the positive influence of moderately elevated [K+]o for contractile performance during exercise.

The Effect of Spinal Cord Stimulation Frequency on the Neural Response and Perceived Sensation in Patients With Chronic Pain.

BACKGROUND: The effect of spinal cord stimulation (SCS) amplitude on the activation of dorsal column fibres has been widely studied through the recording of Evoked Compound Action Potentials (ECAPs), the sum of all action potentials elicited by an electrical stimulus applied to the fibres. ECAP amplitude grows linearly with stimulus current after a threshold, and a larger ECAP results in a stronger stimulus sensation for patients. This study investigates the effect of stimulus frequency on both the ECAP amplitude as well as the perceived stimulus sensation in patients undergoing SCS therapy for chronic back and/or leg pain. METHODS: Patients suffering with chronic neuropathic lower-back and/or lower-limb pain undergoing an epidural SCS trial were recruited. Patients were implanted according to standard practice, having two 8-contact leads (8 mm inter-electrode spacing) which overlapped 2-4 contacts around the T9/T10 interspace. Both lead together thus spanning about three vertebral levels. Neurophysiological recordings were taken during the patient's trial phase at two routine follow-ups using a custom external stimulator capable of recording ECAPs in real-time from all non-stimulating contacts. Stimulation was performed at various vertebral levels, varying the frequency (ranging from 2 to 455 Hz) while all other stimulating variables were kept constant. During the experiments subjects were asked to rate the stimulation-induced sensation (paraesthesia) on a scale from 0 to 10. RESULTS: Frequency response curves showed an inverse relationship between stimulation sensation strength and ECAP amplitude, with higher frequencies generating smaller ECAPs but stronger stimulation-induced paraesthesia (at constant stimulation amplitude). Both relationships followed logarithmic trends against stimulus frequency meaning that the effects on ECAP amplitude and sensation are larger for smaller frequencies. CONCLUSION: This work supports the hypothesis that SCS-induced paraesthesia is conveyed through both frequency coding and population coding, fitting known psychophysics of tactile sensory information processing. The inverse relationship between ECAP amplitude and sensation for increasing frequencies at fixed stimulus amplitude questions common assumptions of monotonic relationships between ECAP amplitude and sensation strength.

Biomechanical conditioning of the motor unit transitory force decrease following a reduction in stimulation rate.

BACKGROUND: The biomechanical background of the transitory force decrease following a sudden reduction in the stimulation frequency under selected experimental conditions was studied on fast resistant motor units (MUs) of rat medial gastrocnemius in order to better understand the mechanisms of changes in force transmission. METHODS: Firstly, MUs were stimulated with three-phase trains of stimuli (low-high-low frequency pattern) to identify patterns when the strongest force decrease (3-36.5%) following the middle high frequency stimulation was observed. Then, in the second part of experiments, the MUs which presented the largest force decrease in the last low-frequency phase were alternatively tested under one of five conditions to analyse the influence of biomechanical factors of the force decrease: (1) determine the influence of muscle stretch on amplitude of the force decrease, (2) determine the numbers of interpulse intervals necessary to evoke the studied phenomenon, (3) study the influence of coactivation of other MUs on the studied force decrease, (4) test the presence of the transitory force decrease at progressive changes in stimulation frequency, (5) and perform mathematical analysis of changes in twitch-shape responses to individual stimuli within a tetanus phase with the studied force decrease. RESULTS: Results indicated that (1) the force decrease was highest when the muscle passive stretch was optimal for the MU twitch (100 mN); (2) the middle high-frequency burst of stimuli composed of at least several pulses was able to evoke the force decrease; (3) the force decrease was eliminated by a coactivation of 10% or more MUs in the examined muscle; (4) the transitory force decrease occured also at the progressive decrease in stimulation frequency; and (5) a mathematical decomposition of contractions with the transitory force decrease into twitch-shape responses to individual stimuli revealed that the force decrease in question results from the decrease of twitch forces and a shortening in contraction time whereas further force restitution is related to the prolongation of relaxation. CONCLUSIONS: High sensitivity to biomechanical conditioning indicates that the transitory force decrease is dependent on disturbances in the force transmission predominantly by collagen surrounding active muscle fibres.

Initial force production before sag is enhanced by prior contraction followed by a 3-minute rest period in fast motor units of the rat medial gastrocnemius.

Unfused tetanic contractions evoked in fast motor units exhibit extra-efficient force production at the onset of contraction, an effect called "boost". Boost is diminished in subsequent contractions if there is a short rest period between contractions, but can be re-established with a longer period of rest. We tested the hypothesis that contractile activity and rest could enhance boost-related metrics. Two sets of 3 unfused tetani were evoked 3 min apart in fast fatigable (FF) and fast fatigue-resistant (FR) motor units of the rat medial gastrocnemius. The greatest changes occurred in the first unfused tetanic contractions. Relative to the first contraction in the first set, the first contraction in the second set exhibited higher peak force during boost in a subset of motor units (76% of FF and 48% of FR). Enhanced force during boost was influenced by interaction of slowing of twitch contraction time (up to 20% and 25%, for FF and FR motor units, respectively), half-relaxation time (up to 37% and 49% for FF and FR motor units, respectively), and potentiation of the first twitch (up to 13% and 5% for FF and FR motor units, respectively). Examination of twitches evoked between sets suggested opportunity for greater enhancement of boost with shorter intervening rest periods. The phenomenon of enhanced boost following motor unit activity may interest sports scientists.

The effects of direct brain stimulation in humans depend on frequency, amplitude, and white-matter proximity.

BACKGROUND: Researchers have used direct electrical brain stimulation to treat a range of neurological and psychiatric disorders. However, for brain stimulation to be maximally effective, clinicians and researchers should optimize stimulation parameters according to desired outcomes. OBJECTIVE: The goal of our large-scale study was to comprehensively evaluate the effects of stimulation at different parameters and locations on neuronal activity across the human brain. METHODS: To examine how different kinds of stimulation affect human brain activity, we compared the changes in neuronal activity that resulted from stimulation at a range of frequencies, amplitudes, and locations with direct human brain recordings. We recorded human brain activity directly with electrodes that were implanted in widespread regions across 106 neurosurgical epilepsy patients while systematically stimulating across a range of parameters and locations. RESULTS: Overall, stimulation most often had an inhibitory effect on neuronal activity, consistent with earlier work. When stimulation excited neuronal activity, it most often occurred from high-frequency stimulation. These effects were modulated by the location of the stimulating electrode, with stimulation sites near white matter more likely to cause excitation and sites near gray matter more likely to inhibit neuronal activity. CONCLUSION: By characterizing how different stimulation parameters produced specific neuronal activity patterns on a large scale, our results provide an electrophysiological framework that clinicians and researchers may consider when designing stimulation protocols to cause precisely targeted changes in human brain activity.

Light or Deep Pressure: Medical Staff Members Differ Extensively in Their Tactile Stimulation During Preterm Apnea.

Background: Even though tactile stimulation is common practice to terminate preterm apnea, the style and intensity of these interventions is not specified during theoretical or practical training and has never been clinically evaluated. Objective: The present study was designed to analyze the various modes of tactile stimulation used to terminate preterm apnea and measure the pressure intensity and frequency of these stimulations. Methods: A model with the size and weight of an actual preterm infant was equipped with sensor technology to measure stimulation pressure and frequency of tactile stimulation. Additionally a camera system was used to record hand positions and stimulation modes. Seventy medical staff members took part in the experiment. Results: We found extreme between subjects differences in stimulation pressure that could not be explained by professional experience but, to a degree, depended on apnea intensity. Pressures ranged from 11.11 to 226.87 mbar during low intensity apnea and from 9.89 to 428.15 mbar during high intensity apnea. The majority of participants used rhythmic stimulation movements with a mean frequency of ~1 Hz. Different modes (rubbing, squeezing, tickling, and tapping) and finger positions were used. Conclusion: Medical staff members intuitively adjust their tactile stimulation pressure depending on the premature infants' apnea intensity. However, mean pressure values varied greatly between subjects, with similar pressure ranges for low and high intensity apnea. The question remains which pressure intensities are necessary or sufficient for the task. It is reasonable to assume that some stimulation types may be more effective in rapidly terminating an apneic event.

Optimal Stimulation Protocol in a Bistable Synaptic Consolidation Model.

Synaptic changes induced by neural activity need to be consolidated to maintain memory over a timescale of hours. In experiments, synaptic consolidation can be induced by repeating a stimulation protocol several times and the effectiveness of consolidation depends crucially on the repetition frequency of the stimulations. We address the question: is there an understandable reason why induction protocols with repetitions at some frequency work better than sustained protocols-even though the accumulated stimulation strength might be exactly the same in both cases? In real synapses, plasticity occurs on multiple time scales from seconds (induction), to several minutes (early phase of long-term potentiation) to hours and days (late phase of synaptic consolidation). We use a simplified mathematical model of just two times scales to elucidate the above question in a purified setting. Our mathematical results show that, even in such a simple model, the repetition frequency of stimulation plays an important role for the successful induction, and stabilization, of potentiation.

Moderately elevated extracellular [K+] potentiates submaximal force and power in skeletal muscle via increased [Ca2+]i during contractions.

The extracellular K+ concentration ([K+]o) increases during physical exercise. We here studied whether moderately elevated [K+]o may increase force and power output during contractions at in vivo-like subtetanic frequencies and whether such potentiation was associated with increased cytosolic free Ca2+ concentration ([Ca2+]i) during contractions. Isolated whole soleus and extensor digitorum longus (EDL) rat muscles were incubated at different levels of [K+]o, and isometric and dynamic contractility were tested at various stimulation frequencies. Furthermore, [Ca2+]i at rest and during contraction was measured along with isometric force in single mouse flexor digitorum brevis (FDB) fibers exposed to elevated [K+]o. Elevating [K+]o from 4 mM up to 8 mM (soleus) and 11 mM (EDL) increased isometric force at subtetanic frequencies, 2-15 Hz in soleus and up to 50 Hz in EDL, while inhibition was seen at tetanic frequency in both muscle types. Elevating [K+]o also increased peak power of dynamic subtetanic contractions, with potentiation being more pronounced in EDL than in soleus muscles. The force-potentiating effect of elevated [K+]o was transient in FDB single fibers, reaching peak after ~4 and 2.5 min in 9 and 11 mM [K+]o, respectively. At the time of peak potentiation, force and [Ca2+]i during 15-Hz contractions were significantly increased, whereas force was slightly decreased and [Ca2+]i unchanged during 50-Hz contractions. Moderate elevation of [K+]o can transiently potentiate force and power during contractions at subtetanic frequencies, which can be explained by a higher [Ca2+]i during contractions.