Low-frequency Stimulation Research Articles

Angiotensin 1-7 prevents the excessive force loss resulting from 14- and 28-day denervation in mouse EDL and soleus muscle.

Denervation leads to muscle atrophy, which is described as muscle mass and force loss, the latter exceeding expectation from mass loss. The objective of this study was to determine the efficiency of angiotensin (Ang) 1-7 at reducing muscle atrophy in mouse extensor digitorum longus (EDL) and soleus following 14- and 28-d denervation periods. Some denervated mice were treated with Ang 1-7 or diminazene aceturate (DIZE), an ACE2 activator, to increase Ang 1-7 levels. Ang 1-7/DIZE treatment had little effect on muscle mass loss and fiber cross-sectional area reduction. Ang 1-7 and DIZE fully prevented the loss of tetanic force normalized to cross-sectional area and accentuated the increase in twitch force in denervated muscle. However, they did not prevent the shift of the force-frequency relationship toward lower stimulation frequencies. The Ang 1-7/DIZE effects on twitch and tetanic force were completely blocked by A779, a MasR antagonist, and were not observed in MasR-/- muscles. Ang 1-7 reduced the extent of membrane depolarization, fully prevented the loss of membrane excitability, and maintained the action potential overshoot in denervated muscles. Ang 1-7 had no effect on the changes in α-actin, myosin, or MuRF-1, atrogin-1 protein content or the content of total or phosphorylated Akt, S6, and 4EPB. This is the first study that provides evidence that Ang 1-7 maintains normal muscle function in terms of maximum force and membrane excitability during 14- and 28-d periods after denervation.

Acute Brain Activation Patterns of High- Versus Low-Frequency Stimulation of the Anterior Nucleus of the Thalamus During Deep Brain Stimulation for Epilepsy.

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is an increasingly utilized treatment of drug-resistant epilepsy. To date, the effect of high-frequency stimulation (HFS) vs low-frequency stimulation (LFS) in ANT DBS is poorly understood. To assess differences in the acute effect of LFS vs HFS in ANT DBS utilizing blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI). In this prospective study of 5 patients with ANT DBS for epilepsy, BOLD activation and deactivation were modeled for 145-Hz and 30-Hz ANT stimulation using an fMRI block design. Data were analyzed with a general linear model and combined via 2-stage mixed-effects analysis. Z-score difference maps were nonparametrically thresholded using cluster threshold of z >3.1 and a (corrected) cluster significance threshold of P=.05. HFS produced significantly greater activation within multiple regions, in particular the limbic and default mode network (DMN). LFS produced minimal activation and failed to produce significant activation within these same networks. HFS produced widespread cortical and subcortical deactivation sparing most of the limbic and DMN regions. Meanwhile, LFS produced deactivation in most DMN and limbic structures. Our results show that HFS and LFS produce substantial variability in both local and downstream network effects. In particular, largely opposing effects were identified within the limbic network and DMN. These findings may serve as a mechanistic basis for understanding the potential of HFS vs LFS in various epilepsy syndromes.

Roles for α1-adrenoceptors during contractions by electrical field stimulation in mouse vas deferens.

We have investigated the relative roles of α1-adrenoceptors and purinoceptors in contractions to low and high frequency stimulation of the mouse vas deferens, in terms of the time course of responses. In separate experiments, isometric contractile responses were obtained to 10 pulses at 1 Hz and 40 pulses at 10 Hz. Responses to 1 Hz stimulation consisted of a series of discrete peaks. The α1A-adrenoceptor antagonist RS100329 (10–9M–10–7M) significantly reduced the response to the first pulse, the α1D-adrenoceptor antagonist BMY7378 (10–7M–10–6M) significantly reduced the response to the first two pulses, and the non-selective α1-adrenoceptor antagonist prazosin (10–8M) reduced the response to the first 4 pulses at 1 Hz. Responses to 10 Hz stimulation consisted of an early peak response and a maintained plateau response. RS100329 significantly reduced the peak response but did not significantly affect the plateau response. Prazosin, significantly reduced both the peak and plateau responses. The α1A-adrenoceptor antagonist RS17053 in high concentrations reduced mainly the plateau response leaving a clear early peak response. The plateau response of contraction was almost abolished by the purinoceptor antagonist suramin. These results suggest that there is a relatively minor early α1D-adrenoceptor and a larger early α1A-adrenoceptor component to stimulation-evoked contractions of mouse vas deferens, but the major α1-adrenoceptor component is revealed by prazosin to be α1B-adrenoceptor mediated. α1B-Adrenoceptor activation probably facilitates contractions mediated by other α1-adrenoceptors and by purinoceptors. These results suggest that combined non-selective α1-adrenoceptor blockade, particularly α1B-adrenoceptor blockade, in addition to P2X1-purinoceptor blockade is useful in reducing male fertility.

Comparison of the subsequent LTP in hippocampal synapses primed by low frequency stimulations ranging from 0.5 to 5 Hz: An in vivo study

According to the Bienenstock,Cooper, andMunro’s (BCM) model, the level of afferent activity regulates the point of crossover from long-term depression (LTD) to long-term potentiation (LTP) of the active synapses. Although experimental results from the hippocampus and visual cortex have supported the BCM theory, it remains unclear whether previous activity of synapses regulates the output of neuron populations in vivo, as expected from the theory. In the present study, we studied the effects of priming stimulations at different frequencies (LFS, 0.5, 1, 2 and 5 Hz) on the magnitude of LTP at synaptic and somatic levels in the dentate gyrus of hippocampal formation. LTP in the dentate gyrus (DG) of LFS-primed or unprimed hippocampal formation was induced by delivering of tetanic stimulation to the perforant pathway (PP) in anesthetized rats. The field excitatory postsynaptic potential (fEPSP) slope and the population spike (PS) amplitude were evaluated to measure the magnitude of LTP. 1 Hz- and 5 Hz- (not 0.5 Hz and 2 Hz) stimulation of the PP led to an early LTD of fEPSP. The LTP of fEPSP was completely inhibited by previously delivering 0.5 Hz and 2 Hz LFS, but instead converted to LTD by 1 Hz LFS. However, none of the frequencies used was able to inhibit the LTP of PS. These results suggest that temporal dynamics which are critical to determine the direction of synaptic plasticity has no impact on the plasticity of neuronal output. We concluded that it is needed to explain why neuronal output does not behave within the framework of the BCM theory.

Electromagnetic Field Stimulation Attenuates Phasic Nociception after Complete Spinal Cord Injury in Rats.

Traumatic spinal cord injury (SCI) is one of the most incapacitating pathologies, leading to huge rehabilitation challenges besides a social-economic burden on SCI patients and their families. There is no complete curative treatment available so far. Non-invasive and patient-friendly use of extremely low-frequency electromagnetic field stimulation (EMF) has emerged as a therapeutic and rehabilitation option. In this study, we tested whole-body EMF stimulation on thoracic complete SCI-induced nociception including sensorimotor deficits in rats. The EMF application significantly attenuated hyperalgesia and allodynia to thermal, electrical, and chemical stimuli from 6 weeks onwards as well as restoration of spinal reflexes, viz., H-reflex and nociceptive flexion reflex at the study endpoint (week 8). Besides, massively increased glutamate at the SCI injury site was observed in SCI rats with no treatment, which was also attenuated significantly by EMF stimulation. Spinal cord histology of the injury area showed a decrease in lesion volume and glial population in the EMF-stimulated rats. These findings indicate the beneficial role of EMF stimulation after thoracic complete SCI in adult male rats and, thereby, a beneficial patient-friendly rehabilitation tool.

Effect of Low-Frequency Repetitive Transcranial Magnetic Stimulation on Executive Function and Its Neural Mechanism: An Event-Related Potential Study.

Objective: Executive function refers to the conscious control of thinking and behavior in psychological process. Executive dysfunction widely exists in a variety of neuropsychiatric diseases, and is closely related to the decline of daily living ability and function. This study intends to explore the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) on executive function and its neural mechanism by using event-related potential (ERP), so as to provide basis for further study on the relationship between cerebral cortex and executive function.Methods: Task switching paradigm was used to study the cognitive flexibility in executive function. Thirty-one healthy subjects were randomly assigned to receive rTMS stimulations (1 Hz rTMS or sham rTMS) to the left dorsolateral prefrontal cortex (DLPFC) twice. The switching task and the electroencephalography EEG recordings were performed before (pre-rTMS/pre-sham rTMS) and immediately after the end of the rTMS application (post-rTMS/post-sham rTMS).Results: The analysis of RTs showed that the main effects of switching and time were statistically significant. Further analysis revealed that the RT of rTMS stimulation was longer than sham rTMS at post-stimulation. ERP analysis showed that there was a significant switching effect in frontal and central scalp location, and the P2 amplitude in switch trials was greater than that in non-switch trials. At post-stimulation, the N2 amplitude of rTMS is more negative than that of sham rTMS at non-switch trials, whereas no such difference was found at switch trials. The P3 amplitude and LPC amplitude are significantly reduced by rTMS at post-stimulation.Conclusion: Low-frequency rTMS of the left DLPFC can cause decline of cognitive flexibility in executive function, resulting in the change of N2 amplitude and the decrease of P3 and LPC components during task switching, which is of positive significance for the evaluation and treatment of executive function.

Voluntary Modulation of Evoked Responses Generated by Epidural and Transcutaneous Spinal Stimulation in Humans with Spinal Cord Injury.

Transcutaneous (TSS) and epidural spinal stimulation (ESS) are electrophysiological techniques that have been used to investigate the interactions between exogenous electrical stimuli and spinal sensorimotor networks that integrate descending motor signals with afferent inputs from the periphery during motor tasks such as standing and stepping. Recently, pilot-phase clinical trials using ESS and TSS have demonstrated restoration of motor functions that were previously lost due to spinal cord injury (SCI). However, the spinal network interactions that occur in response to TSS or ESS pulses with spared descending connections across the site of SCI have yet to be characterized. Therefore, we examined the effects of delivering TSS or ESS pulses to the lumbosacral spinal cord in nine individuals with chronic SCI. During low-frequency stimulation, participants were instructed to relax or attempt maximum voluntary contraction to perform full leg flexion while supine. We observed similar lower-extremity neuromusculature activation during TSS and ESS when performed in the same participants while instructed to relax. Interestingly, when participants were instructed to attempt lower-extremity muscle contractions, both TSS- and ESS-evoked motor responses were significantly inhibited across all muscles. Participants with clinically complete SCI tested with ESS and participants with clinically incomplete SCI tested with TSS demonstrated greater ability to modulate evoked responses than participants with motor complete SCI tested with TSS, although this was not statistically significant due to a low number of subjects in each subgroup. These results suggest that descending commands combined with spinal stimulation may increase activity of inhibitory interneuronal circuitry within spinal sensorimotor networks in individuals with SCI, which may be relevant in the context of regaining functional motor outcomes.

Transcranial magnetic stimulation modalities for psychiatric disorders: Publication trends from 1985 to 2019.

AimTranscranial magnetic stimulation (TMS) is a noninvasive brain stimulation technique that shows potential for treating psychiatric disorders. Although several studies have sought to investigate new TMS modalities for the treatment of various psychiatric disorders, no study has yet examined publication trends in research on TMS modalities for psychiatric disorders. This study investigated publication trends in TMS research for 13 psychiatric disorders, including addiction, dementia, major depressive disorder (MDD), and obsessive‐compulsive disorder (OCD), and schizophrenia, as well as 9 TMS modalities, including bilateral stimulation, deep TMS, high‐frequency stimulation, low‐frequency stimulation, and theta burst stimulation.MethodsArticles published in PubMed from 1985 to 2019 were searched to determine the number of published articles for each year in each category using the “Results by year” tool from the PubMed database.ResultsOver the past 30 years, an increasing number of articles were published regarding TMS research for the treatment of MDD, addiction, and dementia, which were among those most commonly investigated psychiatric disorders, whereas the number of articles addressing schizophrenia and OCD treated via TMS remained steady since 2015. Regarding TMS modalities, previous high‐frequency stimulation, low‐frequency stimulation, and bilateral stimulation were the most common topics, with research regarding deep TMS and theta burst stimulation having increased since 2000 and 2005, respectively.ConclusionTMS applications are rapidly developing and becoming increasingly ubiquitous in various psychiatric disorders. Determining publication trends in TMS research can be a useful method for monitoring TMS research interests and applications of new TMS modalities for psychiatric disorders.

Deep Brain Stimulation Can Differentiate Subregions of the Human Subthalamic Nucleus Area by EEG Biomarkers.

Introduction: Precise lead localization is crucial for an optimal clinical outcome of subthalamic nucleus (STN) deep brain stimulation (DBS) treatment in patients with Parkinson's disease (PD). Currently, anatomical measures, as well as invasive intraoperative electrophysiological recordings, are used to locate DBS electrodes. The objective of this study was to find an alternative electrophysiology tool for STN DBS lead localization.Methods: Sixty-one postoperative electrophysiology recording sessions were obtained from 17 DBS-treated patients with PD. An intraoperative physiological method automatically detected STN borders and subregions. Postoperative EEG cortical activity was measured, while STN low frequency stimulation (LFS) was applied to different areas inside and outside the STN. Machine learning models were used to differentiate stimulation locations, based on EEG analysis of engineered features.Results: A machine learning algorithm identified the top 25 evoked response potentials (ERPs), engineered features that can differentiate inside and outside STN stimulation locations as well as within STN stimulation locations. Evoked responses in the medial and ipsilateral fronto-central areas were found to be most significant for predicting the location of STN stimulation. Two-class linear support vector machine (SVM) predicted the inside (dorso-lateral region, DLR, and ventro-medial region, VMR) vs. outside [zona incerta, ZI, STN stimulation classification with an accuracy of 0.98 and 0.82 for ZI vs. VMR and ZI vs. DLR, respectively, and an accuracy of 0.77 for the within STN (DLR vs. VMR)]. Multiclass linear SVM predicted all areas with an accuracy of 0.82 for the outside and within STN stimulation locations (ZI vs. DLR vs. VMR).Conclusions: Electroencephalogram biomarkers can use low-frequency STN stimulation to localize STN DBS electrodes to ZI, DLR, and VMR STN subregions. These models can be used for both intraoperative electrode localization and postoperative stimulation programming sessions, and have a potential to improve STN DBS clinical outcomes.

Contribution of Postjunctional M2 Muscarinic Receptors to Cholinergic Nerve-Mediated Contractions of Murine Airway Smooth Muscle.

Postjunctional M2Rs on airway smooth muscle (ASM) outnumber M3Rs by a ratio of 4:1 in most species, however, it is the M3Rs that are thought to mediate the bronchoconstrictor effects of acetylcholine. In this study, we describe a novel and profound M2R-mediated hypersensitization of M3R-dependent contractions of ASM at low stimulus frequencies.. Contractions induced by 2Hz EFS were augmented by > 2.5-fold when the stimulus interval was reduced from 100 to 10 s. This effect was reversed by the M2R antagonists, methoctramine, and AFDX116, and was absent in M2R null mice. The M3R antagonist 4-DAMP abolished the entire response in both WT and M2R KO mice. The M2R-mediated potentiation of EFS-induced contractions was not observed when the stimulus frequency was increased to 20 Hz. A subthreshold concentration of carbachol enhanced the amplitude of EFS-evoked contractions in WT, but not M2R null mice. These data highlight a significant M2R-mediated potentiation of M3R-dependent contractions of ASM at low frequency stimulation that could be relevant in diseases such as asthma and COPD.

Model-based optogenetic stimulation to regulate beta oscillations in Parkinsonian neural networks.

Optogenetic stimulation, an effective stimulation technique, is applied to the treatment of Parkinson's disease (PD) to compete with the current neuromodulation technology that focuses on the electrical stimulation. Using the cortical-thalamic-basal ganglia model, we systematically study the effect of optogenetic stimulation on pathological parkinsonian rhythmic neural activity. Based on the experimental studies, four types of neurons are selected as stimulation targets. Our results indicate that both the optogenetic excitatory stimulation of D1 medium spiny neurons and inhibitory stimulation of globus pallidus internal (GPi) can directly suppress the abnormal discharge of GPi neurons. The former stimulation pattern drives the model to health state with smaller stimulation parameters, suggesting that inhibiting the GPi abnormal discharge through synaptic action seems to be more effective. Compared with electrical stimulation, it is found that 120Hz optogenetic excitatory stimulation does not accurately activate the action potential of subthalamic nucleus (STN). In contrast, only optogenetic excitatory stimulation of globus pallidus externa (GPe) can reduce the firing rate of STN and GPi simultaneously. Finally, we study the difference between the effects of high-frequency low pulse width stimulation and low-frequency high pulse width stimulation while maintaining the same pulse duty cycle. For GPe, different stimulation patterns play a positive role as long as the stimulation frequency is not in the beta-band. Although the feasibility of optogenetic stimulation remains to be clinically explored, the results obtained help us understand the pathophysiology of PD.

Kinetics of muscular function and architecture changes during of chronic low-frequency electrical stimulation

Kinetics of muscular function and architecture changes during of chronic low-frequency electrical stimulation

Effects of low-frequency repetitive transcranial magnetic stimulation combined with cerebellar continuous theta burst stimulation on spasticity and limb dyskinesia in patients with stroke

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has been reported to treat muscle spasticity in post-stroke patients. The purpose of this study was to explore whether combined low-frequency rTMS (LF-rTMS) and cerebellar continuous theta burst stimulation (cTBS) could provide better relief than different modalities alone for muscle spasticity and limb dyskinesia in stroke patients.MethodsThis study recruited ninety stroke patients with hemiplegia, who were divided into LF-rTMS+cTBS group (n=30), LF-rTMS group (n=30) and cTBS group (three pulse bursts at 50 Hz, n=30). The LF-rTMS group received 1 Hz rTMS stimulation of the motor cortical (M1) region on the unaffected side of the brain, the cTBS group received cTBS stimulation to the cerebellar region, and the LF-rTMS+cTBS group received 2 stimuli as described above. Each group received 4 weeks of stimulation followed by rehabilitation. Muscle spasticity, motor function of limb and activity of daily living (ADL) were evaluated by modified Ashworth Scale (MAS), Fugl-Meyer Assessment (FMA) and Modified Barthel Index (MBI) scores, respectively.ResultsThe MAS score was markedly decreased, FMA and MBI scores were markedly increased in the three groups after therapy than before therapy. In addition, after therapy, LF-rTMS+cTBS group showed lower MAS score, higher FMA and MBI scores than the LF-rTMS group and cTBS group.ConclusionMuscle spasticity and limb dyskinesia of the three groups are all significantly improved after therapy. Combined LF-rTMS and cTBS treatment is more effective in improving muscle spasticity and limb dyskinesia of patients after stroke than LF-rTMS and cTBS treatment alone.

Structural connectivity changes in the motor execution network after stroke rehabilitation.

Background:Although quite a very few studies have tested structural connectivity changes following an intervention, it reflects only selected key brain regions in the motor network. Thus, the understanding of structural connectivity changes related to the motor recovery process remains unclear.Objective:This study investigated structural connectivity changes of the motor execution network following a combined intervention of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) and intensive occupational therapy (OT) after a stroke using graph theory approach.Methods:Fifty-six stroke patients underwent Fugl-Meyer Assessment (FMA), Wolf Motor Function Test-Functional Ability Scale (WMFT-FAS), diffusion tensor imaging (DTI), and T1 weighted imaging before and after the intervention. We examined graph theory measures related to twenty brain regions using structural connectomes.Results:The ipsilesional and contralesional hemisphere showed structural connectivity changes post-intervention after stroke. We found significantly increased regional centralities and nodal efficiency within the frontal pole and decreased degree centrality and nodal efficiency in the ipsilesional thalamus. Correlations were found between network measures and clinical assessments in the cuneus, postcentral gyrus, precentral gyrus, and putamen of the ipsilesional hemisphere. The contralesional areas such as the caudate, cerebellum, and frontal pole also showed significant correlations.Conclusions:This study was helpful to expand the understanding of structural connectivity changes in both hemispheric networks during the motor recovery process following LF-rTMS and intensive OT after stroke.

Cholinergic Deep Brain Stimulation for Memory and Cognitive Disorders.

Memory and cognitive impairment as sequelae of neurodegeneration in Alzheimer’s disease and age-related dementia are major health issues with increasing social and economic burden. Deep brain stimulation (DBS) has emerged as a potential treatment to slow or halt progression of the disease state. The selection of stimulation target is critical, and structures that have been targeted for memory and cognitive enhancement include the Papez circuit, structures projecting to the frontal lobe such as the ventral internal capsule, and the cholinergic forebrain. Recent human clinical and animal model results imply that DBS of the nucleus basalis of Meynert can induce a therapeutic modulation of neuronal activity. Benefits include enhanced activity across the cortical mantle, and potential for amelioration of neuropathological mechanisms associated with Alzheimer’s disease. The choice of stimulation parameters is also critical. High-frequency, continuous stimulation is used for movement disorders as a way of inhibiting their output; however, no overexcitation has been hypothesized in Alzheimer’s disease and lower stimulation frequency or intermittent patterns of stimulation (periods of stimulation interleaved with periods of no stimulation) are likely to be more effective for stimulation of the cholinergic forebrain. Efficacy and long-term tolerance in human patients remain open questions, though the cumulative experience gained by DBS for movement disorders provides assurance for the safety of the procedure.

Differential Influence of the Dorsal Premotor and Primary Somatosensory Cortex on Corticospinal Excitability during Kinesthetic and Visual Motor Imagery: A Low-Frequency Repetitive Transcranial Magnetic Stimulation Study.

Consistent evidence suggests that motor imagery involves the activation of several sensorimotor areas also involved during action execution, including the dorsal premotor cortex (dPMC) and the primary somatosensory cortex (S1). However, it is still unclear whether their involvement is specific for either kinesthetic or visual imagery or whether they contribute to motor activation for both modalities. Although sensorial experience during motor imagery is often multimodal, identifying the modality exerting greater facilitation of the motor system may allow optimizing the functional outcomes of rehabilitation interventions. In a sample of healthy adults, we combined 1 Hz repetitive transcranial magnetic stimulation (rTMS) to suppress neural activity of the dPMC, S1, and primary motor cortex (M1) with single-pulse TMS over M1 for measuring cortico-spinal excitability (CSE) during kinesthetic and visual motor imagery of finger movements as compared to static imagery conditions. We found that rTMS over both dPMC and S1, but not over M1, modulates the muscle-specific facilitation of CSE during kinesthetic but not during visual motor imagery. Furthermore, dPMC rTMS suppressed the facilitation of CSE, whereas S1 rTMS boosted it. The results highlight the differential pattern of cortico-cortical connectivity within the sensorimotor system during the mental simulation of the kinesthetic and visual consequences of actions.

Calcium-Permeable AMPA Receptors Mediate Timing-Dependent LTP Elicited by Low Repeat Coincident Pre- and Postsynaptic Activity at Schaffer Collateral-CA1 Synapses.

High-frequency stimulation induced long-term potentiation (LTP) and low-frequency stimulation induced LTD are considered as cellular models of memory formation. Interestingly, spike timing-dependent plasticity (STDP) can induce equally robust timing-dependent LTP (t-LTP) and t-LTD in response to low frequency repeats of coincident action potential (AP) firing in presynaptic and postsynaptic cells. Commonly, STDP paradigms relying on 25-100 repeats of coincident AP firing are used to elicit t-LTP or t-LTD, but the minimum number of repeats required for successful STDP is barely explored. However, systematic investigation of physiologically relevant low repeat STDP paradigms is of utmost importance to explain learning mechanisms in vivo. Here, we examined low repeat STDP at Schaffer collateral-CA1 synapses by pairing one presynaptic AP with either one postsynaptic AP (1:1t-LTP), or a burst of 4 APs (1:4t-LTP) and found 3-6 repeats to be sufficient to elicit t-LTP. 6× 1:1t-LTP required postsynaptic Ca2+ influx via NMDARs and L-type VGCCs and was mediated by increased presynaptic glutamate release. In contrast, 1:4t-LTP depended on postsynaptic metabotropic GluRs and ryanodine receptor signaling and was mediated by postsynaptic insertion of AMPA receptors. Unexpectedly, both 6× t-LTP variants were strictly dependent on activation of postsynaptic Ca2+-permeable AMPARs but were differentially regulated by dopamine receptor signaling. Our data show that synaptic changes induced by only 3-6 repeats of mild STDP stimulation occurring in ≤10s can take place on time scales observed also during single trial learning.

Regulating random mechanical motion using the principle of auto-winding mechanical watch for driving TENG with constant AC output – An approach for efficient usage of high entropy energy

The world is fulfilled with low-quality, irregular, and widely distributed energy, but highly efficient harvesting of such high-entropy energy is hardly possible due to the limitation of currently existing technologies. Recently, triboelectric nanogenerators (TENGs) were invented to harvest random and ambient mechanical energy, and have shown wide applications because of their high efficiency and low-cost. However, the output of the TENG is dictated by the irregularity of the input mechanical agitation. This paper reports a mechanical regulator using the principle of auto-winding mechanical watch for driving the triboelectric nanogenerator with constant AC output (Constant Output TENG, CO-TENG). The device which comprised energy harvest and storage module, energy controllable release module, and energy conversion module can achieve energy harvesting-storage-release not only steadily but also continually under even low-frequency (0.5 Hz) and random working stimulation. The CO-TENG has been successfully applied to harvest the energy of random waves, wind, and water flows, through the adjustment of the input gear train and energy collection parts, such as water turbine, wind scoop, and oscillating buoy. The CO-TENG can steadily and continually produce an open-circuit voltage of 550 V, a short-circuit current of 6 μA, and transferred charges of 190 nC under low-frequency and random mechanical stimulation. With the rectifier filter, a commercial thermometer and 450 LEDs in serial connection were separately powered by the CO-TENG. It demonstrates that the CO-TENG is a potential solution for effective usage of high entropy energy that has a random amplitude and irregular low-frequency. The paper reports a mechanical regulator using the principle of auto-winding mechanical watch for driving the triboelectric nanogenerator, which can steadily and continually release electric energy without manual intervention under random and low-frequency conditions, such as random waves, wind, and water flows. • A mechanical regulator is proposed which is using the principle of auto-winding mechanical watch for driving the TENG. • The device can steadily and continually produce AC output under random and low-frequency excitation. • An escapement was designed to control release of energy, with reference to the working principle of mechanical watches.

The Clinical Efficacy and Possible Mechanism of Combination Treatment of Cerebral Ischemic Stroke with Ginkgo Biloba Extract and Low-Frequency Repetitive Transcranial Magnetic Stimulation

To study the effect of the combination treatment of ginkgo biloba extract and low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) on the oxidative stress and brain neurotransmitters of patients who had cerebral ischemic stroke (CIS). A retrospective analysis was conducted, and 93 CIS patients admitted to the Sichuan Academy of Medical Sciences/Sichuan Provincial People's Hospital from January 2018 to January 2020 were included in the study. They were divided into three groups, the regular treatment group (31 cases), the LF-rTMS group (31 cases), and the combination treatment group (31 cases). Patients in the regular treatment group were given the conventional drug therapy and exercise regimen. The LF-rTMS group received LF-rTMS therapy (for 20-30 min each time, 1 time/d and 5 times/week) in addition to the treatment given to the regular treatment group. The combination treatment group was given ginkgo biloba extract (intravenous drips, once per day) in addition to the treatment given to the LF-rTMS group. The treatment was given continuously for 4 weeks and comparison was made at the end of the 4-week treatment regarding the clinical efficacy, oxidative stress response, cerebral oxygen metabolism, and brain neurotransmitter as shown by the three groups. The treatment efficacy in the combination treatment group (96.77%) was higher than those of the LF-rTMS group (80.65%) and the regular treatment group (54.84%). The LF-rTMS group showed higher treatment efficacy than that of the regular group. The serum superoxide dismutase (SOD) of the combination treatment group was higher than that of the LF-rTMS group and that of the routine group, while the malondialdehyde (MDA) and endothelin-1 (ET-1) of the combination treatment group were lower than those of the LF-rTMS group and the regular treatment group ( P<0.05). The serum SOD of the LF-rTMS group was higher than that of the regular treatment group, while the MDA and ET-1 of the group was lower than those of the regular treatment group ( P<0.05). The arterial oxygen content (CaO 2), arterio-venous oxygen content difference (Ca-vO 2) and cerebral extraction rate of oxygen (CERO 2) in the combination treatment group were lower than those of the LF-rTMS group and the regular treatment group ( P<0.05). The levels of these three indicators of the LF-rTMS group were lower than those of the regular treatment group ( P<0.05). EEG frequencies of gamma-aminobutyric acid (GABA), 5-hydroxytryptamine (5-HT) and dopamine (DA) of the combination treatment group were higher than those of the LF-rTMS group and the regular treatment group, while the acetylcholine (Ach) EEG frequency of the combination treatment group was lower than that of the LF-rTMS group and regular treatment group ( P<0.05). The LF-rTMS group showed higher GABA, 5-HT and DA EEG frequencies than those of the regular treatment group, while the Ach EEG frequency of the group was lower than that of the regular treatment group ( P<0.05). All the patients were followed up for 6 months, and recurrence rate was lower in the combination treatment group (3.23%) than that of the LF-rTMS group (19.35%) and the regular treatment group (25.81%) ( P<0.05). The combination treatment of ginkgo biloba extract and LF-rTMS helped to improve the clinical outcome of CIS patients, which may be related to the inhibition of oxidative stress, improvement in cerebral oxygen metabolism, and regulation of brain neurotransmitter.

Changes in brain morphometry after motor rehabilitation in chronic stroke

Purpose Recent studies have revealed structural changes after motor rehabilitation, but its morphological changes related to upper limb motor behaviours have not been studied exhaustively. Therefore, we aimed to map the grey matter (GM) changes associated with motor rehabilitation after stroke using voxel-based morphometry (VBM), deformation-based morphometry (DBM), and surface-based morphometry (SBM). Methods Forty-one patients with chronic stroke received twelve sessions of low-frequency repetitive transcranial magnetic stimulation plus intensive occupational therapy. MRI data were obtained before and after the intervention. Fugl-Meyer Assessment and Wolf Motor Function Test-Functional Ability Scale were assessed at the two-time points. We performed VBM, DBM, and SBM analyses using T1-weighted images. A correlation analysis was performed between cortical thickness in motor areas and clinical outcomes. Results Clinical outcomes significantly improved after the intervention. VBM showed significant GM volume changes in ipsilesional and contralesional primary motor regions. DBM results demonstrated GM changes contralesionally and ipsilesionally after the intervention. SBM results showed significant cortical thickness changes in posterior visuomotor coordination, precentral, postcentral gyri of the ipsilesional hemisphere and contralesional visuomotor area after the intervention. A combination of threshold p < .05, False Discovery Rate and p < .001 (uncorrected) were considered significant. In addition, cortical thickness changes of the ipsilesional motor areas were significantly correlated with the clinical outcome changes. Conclusions We found GM structural changes in areas involved in motor, visuomotor and somatosensory functions after the intervention. Furthermore, our findings suggest that structural plasticity changes in chronic stroke could occur in the ipsilesional and contralesional hemispheres after motor rehabilitation.