Repetitive Electrical Stimulation Research Articles

The impact of radiofrequency thermocoagulation on brain connectivity in drug-resistant epilepsy: Insights from stereo-electroencephalography and cortico-cortical evoked potentials.

To investigate whether local lesions created by stereo-electroencephalography (SEEG)-guided radiofrequency thermocoagulation (RFTC) affect distant brain connectivity and excitability in patients with focal, drug-resistant epilepsy (DRE). Ten patients with focal DRE underwent SEEG implantation and subsequently 1 Hz bipolar repetitive electrical stimulation (RES) for 30 s before and after RFTC. Root mean square (RMS) of cortico-cortical evoked potentials (CCEPs) was calculated for 15 ms to 300 ms post-stimulation with baseline correction. Contact pairs were categorized as both coagulated, hybrid, or both non-coagulated. The data were divided into nine categories based on the stimulating and recording contact pair combinations. RMS of CCEPs was compared before and after (<12 h) RFTC using a two-sample t test (Hochberg corrected, p < 0.05) for each patient. Boost score, indicating power increase during seizures before RFTC relative to baseline, was analyzed in 4 s windows with 1 s overlap during seizure duration. RFTC altered connectivity across all categories. Of interest, decreases and increases in RMS were observed in connections between non-coagulated contacts distant from coagulation site (range: 1.09-85 mm, median = 17.7 mm, interquartile range [IQR] 10.1-32.3). Contact pairs involved in significantly altered non-coagulated connections showed a higher boost score correlation in the theta, beta, and gamma bands, as well as a stronger maximum correlation with coagulated sites in the delta band than contacts for which connectivity did not change after RFTC. This study highlights how local lesions alter distant brain connectivity, providing insights for future research on epilepsy network changes and seizure outcomes following RFTC.

A Randomized Controlled Trial to Test the Effects of Repetitive Peripheral Magnetic Stimulation Versus Neuromuscular Electrical Stimulation in Patients with Spastic Hemiparesis After Stroke (REPMAST): Study Protocol.

Innovative therapies are needed to reduce disability, facilitate activities of daily living, and improve the quality of life in patients with stroke. Non-invasive methods of stimulating the peripheral and central nervous system are increasingly being used to enhance the effects of existing therapies in stroke rehabilitation. One potentially relevant method for achieving greater improvement is repetitive peripheral magnetic stimulation (rPMS). This randomized controlled trial (RCT), the Peripheral MAgnetic stimulation in patients with spastic hemiparesis after Stroke Trial (REPMAST), will investigate whether rPMS improves upper extremity function, spasticity, and activities of daily living in patients with stroke compared with neuromuscular stimulation (NMS). REPMAST is an interventional, randomized controlled single-blinded study. Patients with subacute stroke are randomized to receive rPMS or NMS five days a week for three weeks in addition to standard rehabilitation therapy. The primary outcome is the change in the Fugl-Meyer Assessment for Upper Extremity between the beginning and end of the stimulation sessions. Secondary outcomes include changes in the Katz Index of Independence in Activities of Daily Living, the Timed Up and Go Test, the Modified Ashworth Scale, and the Tardieu Scale. A total sample size of 138 patients (69 in each group) is required to investigate the superiority of rPMS compared with NMS. The aim of this RCT is to provide evidence for an effective peripheral stimulation treatment for stroke recovery.

A randomized study on the effect of a wearable device using 0.75 Hz transcranial electrical stimulation on sleep onset insomnia.

The normal transition to sleep is characterized by a reduction in higher frequency activity and an increase in lower frequency activity in frontal brain regions. In sleep onset insomnia these changes in activity are weaker and may prolong the transition to sleep. Using a wearable device, we compared 30min of short duration repetitive transcranial electric stimulation (SDR-tES) at 0.75Hz, prior to going to bed, with an active control at 25Hz in the same individuals. Treatment with 0.75Hz significantly reduced sleep onset latency (SOL) by 53% when compared with pre-treatment baselines and was also significantly more effective than stimulation with 25Hz which reduced SOL by 30%. Reductions in SOL with 25Hz stimulation displayed order effects suggesting the possibility of placebo. No order effects were observed with 0.75Hz stimulation. The decrease in SOL with 0.75Hz treatment was proportional to an individual's baseline wherein those suffering from the longest pre-treated SOLs realized the greatest benefits. Changes in SOL were correlated with left/right frontal EEG signal coherence around the stimulation frequency, providing a possible mechanism and target for more focused treatment. Stimulation at both frequencies also decreased perceptions of insomnia symptoms measured with the Insomnia Severity Index, and comorbid anxiety measured with the State Trait Anxiety Index. Our study identifies a new potential treatment for sleep onset insomnia that is comparably effective to current state-of-practice options including pharmacotherapy and cognitive behavioral therapy and is safe, effective, and can be delivered in the home.

Effects of Non-Invasive Brain Stimulation for Degenerative Cerebellar Ataxia: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aimed to assess the effectiveness of non-invasive brain stimulation (NIBS), including repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (tES), as a neurological intervention for degenerative cerebellar ataxia (DCA) based on preregistration (PROSPERO: CRD42023379192). We aimed to explore clinical outcomes and examine the parameters associated with NIBS efficacy in DCA patients. The PubMed, Cochrane Library, CHINAL, and PEDro databases were searched for relevant randomized controlled trials (RCTs). Data extraction, quality assessment, and heterogeneity analyses were conducted; the Grading, Recommendations, Assessment, Development, and Evaluation was used to assess the quality of evidence and a meta-analysis was performed. Seventeen RCTs that included 661 patients on the scale for assessment and rating of ataxia (SARA) and 606 patients on the International Cooperative Ataxia Rating Scale (ICARS) were included. These RCTs showed a serious risk of bias (RoB) and low certainty of evidence for both outcomes. NIBS significantly reduced SARA (MD = -2.49, [95% confidence interval: -3.34, -1.64]) and ICARS (-5.27 [-7.06, -3.47]); the subgroup analysis showed significant effects: rTMS and tES reduced both outcomes. However, there were no significant differences in the effects of rTMS and tES. Additional subgroup analysis indicated the impact of rTMS frequency and the total number of tES sessions on ataxia. Non-invasive brain stimulation may reduce ataxia in DCA patients, but the estimated effect size may change in future studies because the RoB was serious and the certainty of evidence was low, and the heterogeneity was high. To establish evidence for selecting NIBS methods and parameters, continued high-quality RCTs are required.

Locomotion Control of Cyborg Insects by Charge-Balanced Biphasic Electrical Stimulation.

The integration of electronic stimulation devices with insects in the context of cyborg insect systems has great application potential, particularly in the fields of environmental monitoring, urban surveillance, and rescue missions. Despite considerable advantages compared to the current robot technology, including flexibility, durability, and low energy consumption, this integration faces certain challenges related to the potential risk of charge accumulation caused by prolonged and repetitive electrical stimulations. To address these challenges, this study proposes a universal system for remote signal output control using infrared signals. The proposed system integrates high-precision digital-to-analog converters capable of generating customized waveform electrical stimulation signals within defined ranges. This enhances the accuracy of locomotion control in cyborg insects while maintaining real-time control and dynamic parameter adjustment. The proposed system is verified by experiments. The experimental results show that the signals generated by the proposed system have a success rate of over 76.25% in controlling the turning locomotion of cyborg insects, which is higher than previously reported results. In addition, the charge-balanced characteristics of these signals can minimize muscle tissue damage, thus substantially enhancing control repeatability. This study provides a comprehensive solution for the remote control and monitoring of cyborg insects, whose flexibility and adaptability can meet various application and experimental requirements. The results presented in this study lay a robust foundation for further advancement of various technologies, particularly those related to cyborg insect locomotion control systems and wireless control mechanisms for cyborg insects.

Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies.

Epilepsy is a severe, relapsing, and multifactorial neurological disorder. Studies regarding the accurate diagnosis, prognosis, and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy. The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression, protein expression, ion channel activity, energy metabolites, and gut microbiota composition. Satisfactory results are lacking for conventional treatments for epilepsy. Surgical resection of lesions, drug therapy, and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy. Non-pharmacological treatments, such as a ketogenic diet, gene therapy for nerve regeneration, and neural regulation, are currently areas of research focus. This review provides a comprehensive overview of the pathogenesis, diagnostic methods, and treatments of epilepsy. It also elaborates on the theoretical basis, treatment modes, and effects of invasive nerve stimulation in neurotherapy, including percutaneous vagus nerve stimulation, deep brain electrical stimulation, repetitive nerve electrical stimulation, in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation. Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures. Additionally, many new technologies for the diagnosis and treatment of epilepsy are being explored. However, current research is mainly focused on analyzing patients' clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level, which has led to a lack of consensus regarding the mechanisms related to the disease.

Relationship between Volitional and Non-Volitional Quadriceps Muscle Endurance in Patients with Chronic Obstructive Pulmonary Disease.

Volitional assessment of quadriceps muscle endurance is clinically relevant in patients with chronic obstructive pulmonary disease (COPD). However, studies that determine the construct validity of volitional tests by comparing them to non-volitional measures are lacking. Therefore, the aim of the current study is to evaluate the correlation between volitional and non-volitional quadriceps muscle endurance in patients with COPD. Quadriceps muscle endurance was evaluated in twenty-six patients with COPD. A volitional isometric and a volitional isokinetic protocol were performed on a computerised dynamometer to determine the isometric time and isokinetic work fatigue index, respectively. Non-volitional assessment of quadriceps muscle endurance was evaluated using repetitive electrical stimulations to establish the isometric muscle force decline. Sixteen patients (61 ± 8 years, 63% male, FEV1 47 (32-53)%) performed all three quadriceps endurance tests conforming to pre-defined test criteria. Both volitional isometric time and isokinetic work fatigue index did not significantly correlate with non-volitional muscle force decline (both p > 0.05). There was a strong correlation between volitional isometric time and isokinetic work fatigue index (rho = -0.716, p = 0.002). To conclude, this study suggests that volitional measures evaluate partly different aspects of quadriceps muscle endurance compared to non-volitional measures. Accordingly, these outcome measures cannot be used interchangeably.

Alteration in Resting-State Brain Activity in Stroke Survivors After Repetitive Finger Stimulation.

This quasi-experimental study examined the effect of repetitive finger stimulation on brain activation in eight stroke and seven control subjects, measured by quantitative electroencephalogram. We applied 5 mins of 2-Hz repetitive bilateral index finger transcutaneous electrical nerve stimulation and compared differences pre- and post-transcutaneous electrical nerve stimulation using quantitative electroencephalogram metrics delta/alpha ratio and delta-theta/alpha-beta ratio. Between-group differences before and after stimulation were significantly different in the delta/alpha ratio ( z = -2.88, P = 0.0040) and the delta-theta/alpha-beta ratio variables ( z = -3.90 with P < 0.0001). Significant decrease in the delta/alpha ratio and delta-theta/alpha-beta ratio variables after the transcutaneous electrical nerve stimulation was detected only in the stroke group (delta/alpha ratio diff = 3.87, P = 0.0211) (delta-theta/alpha-beta ratio diff = 1.19, P = 0.0074). The decrease in quantitative electroencephalogram metrics in the stroke group may indicate improved brain activity after transcutaneous electrical nerve stimulation. This finding may pave the way for a future novel therapy based on transcutaneous electrical nerve stimulation and quantitative electroencephalogram measures to improve brain recovery after stroke.

Blast Overpressures as a Military and Occupational Health Concern.

This tutorial reviews effects of environmental stressors like blast overpressures and other well-known acoustic contaminants (continuous, intermittent, and impulsive noise) on hearing, tinnitus, vestibular, and balance-related functions. Based on the overall outcome of these effects, detailed consideration is given to the health and well-being of individuals. Because hearing loss and tinnitus are consequential in affecting quality of life, novel neuromodulation paradigms are reviewed for their positive abatement and treatment-related effects. Examples of clinical data, research strategies, and methodological approaches focus on repetitive transcranial magnetic stimulation (rTMS) and electrical stimulation of the vagus nerve paired with tones (VNSt) for their unique contributions to this area. Acoustic toxicants transmitted through the atmosphere are noteworthy for their propensity to induce hearing loss and tinnitus. Mounting evidence also indicates that high-level rapid onset changes in atmospheric sound pressure can significantly impact vestibular and balance function. Indeed, the risk of falling secondary to loss of, or damage to, sensory receptor cells in otolith organs (utricle and saccule) is a primary reason for this concern. As part of the complexities involved in VNSt treatment strategies, vocal dysfunction may also manifest. In addition, evaluation of temporospatial gait parameters is worthy of consideration based on their ability to detect and monitor incipient neurological disease, cognitive decline, and mortality. Highlighting these respective areas underscores the need to enhance information exchange among scientists, clinicians, and caregivers on the benefits and complications of these outcomes.

Electroconvulsive therapy-induced volumetric brain changes converge on a common causal circuit in depression

Neurostimulation is a mainstream treatment option for major depression. Neuromodulation techniques apply repetitive magnetic or electrical stimulation to some neural target but significantly differ in their invasiveness, spatial selectivity, mechanism of action, and efficacy. Despite these differences, recent analyses of transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS)-treated individuals converged on a common neural network that might have a causal role in treatment response. We set out to investigate if the neuronal underpinnings of electroconvulsive therapy (ECT) are similarly associated with this causal depression network (CDN). Our aim here is to provide a comprehensive analysis in three cohorts of patients segregated by electrode placement (N = 246 with right unilateral, 79 with bitemporal, and 61 with mixed) who underwent ECT. We conducted a data-driven, unsupervised multivariate neuroimaging analysis Principal Component Analysis (PCA) of the cortical and subcortical volume changes and electric field (EF) distribution to explore changes within the CDN associated with antidepressant outcomes. Despite the different treatment modalities (ECT vs TMS and DBS) and methodological approaches (structural vs functional networks), we found a highly similar pattern of change within the CDN in the three cohorts of patients (spatial similarity across 85 regions: r = 0.65, 0.58, 0.40, df = 83). Most importantly, the expression of this pattern correlated with clinical outcomes (t = −2.35, p = 0.019). This evidence further supports that treatment interventions converge on a CDN in depression. Optimizing modulation of this network could serve to improve the outcome of neurostimulation in depression.

Modulation of the swallowing reflex by stimulation of the gigantocellular reticular nucleus in the rat

ObjectivesThe gigantocellular reticular nucleus (Gi) projects to the nuclues of the solitary tract nucleus (NTS) and the lateral reticular formation (LRF) above the nucleus ambiguus. The swallowing central pattern generator comprises the NTS and the LRF. The present study examined whether stimulation of the Gi affects the swallowing reflex. MethodsExperiments were performed on urethane-anesthetized rats. The swallowing reflex was evoked by repetitive electrical stimulation of the superior laryngeal nerve and responses were recorded from the mylohyoid muscle on an electromyogram. The Gi was stimulated electrically. In addition, glutamate was injected into the Gi. The Friedman's test, followed by the Wilcoxon signed-rank test with Bonferroni correction, were used to assess the effects of electrical stimulation of the Gi. The Wilcoxon signed-rank test was used to assess the effects of glutamate injection into the Gi. Differences were considered significant at the P < 0.05 level. ResultsThe number of swallows was significantly increased or decreased by electrical stimulation of the Gi or after injection of glutamate into the Gi. In both electrical stimulation of the Gi and injection of glutamate into the Gi, the onset latency of the first swallow was prolonged when the number of swallows was decreased but showed no change when the number of swallows was increased. ConclusionsThe present results suggest that the Gi is involved in the control of swallowing.

Effects of non-invasive brain stimulation for degenerative cerebellar ataxia: a protocol for a systematic review and meta-analysis

IntroductionTo date, the medical and rehabilitation needs of people with degenerative cerebellar ataxia (DCA) are not fully met because no curative treatment has yet been established. Movement disorders such as...

The effect of the subthreshold oscillation induced by the neurons' resonance upon the electrical stimulation-dependent instability.

Repetitive electrical nerve stimulation can induce a long-lasting perturbation of the axon's membrane potential, resulting in unstable stimulus-response relationships. Despite being observed in electrophysiology, the precise mechanism underlying electrical stimulation-dependent (ES-dependent) instability is still an open question. This study proposes a model to reveal a facet of this problem: how threshold fluctuation affects electrical nerve stimulations. This study proposes a new method based on a Circuit-Probability theory (C-P theory) to reveal the interlinkages between the subthreshold oscillation induced by neurons' resonance and ES-dependent instability of neural response. Supported by in-vivo studies, this new model predicts several key characteristics of ES-dependent instability and proposes a stimulation method to minimize the instability. This model provides a powerful tool to improve our understanding of the interaction between the external electric field and the complexity of the biophysical characteristics of axons.

Identification of patients with chronic migraine by using sensory-evoked oscillations from the electroencephalogram classifier

To examine whether the modulating evoked cortical oscillations could be brain signatures among patients with chronic migraine, we investigated cortical modulation using an electroencephalogram with machine learning techniques. We directly record evoked electroencephalogram activity during nonpainful, painful, and repetitive painful electrical stimulation tasks. Cortical modulation for experimental pain and habituation processing was analyzed and used to differentiate patients with chronic migraine from healthy controls using a validated machine-learning model. This study included 80 participants: 40 healthy controls and 40 patients with chronic migraine. Evoked somatosensory oscillations were dominant in the alpha band. Longer latency (nonpainful and repetitive painful) and augmented power (nonpainful and repetitive painful) were present among patients with chronic migraine. However, for painful tasks, alpha increases were observed among healthy controls. The oscillatory activity ratios between repetitive painful and painful tasks represented the frequency modulation and power habituation among healthy controls, respectively, but not among patients with chronic migraine. The classification models with oscillatory features exhibited high performance in differentiating patients with chronic migraine from healthy controls. Altered oscillatory characteristics of sensory processing and cortical modulation reflected the neuropathology of patients with chronic migraine. These characteristics can be reliably used to identify patients with chronic migraine using a machine-learning approach.

The Role of Transcranial Magnetic Stimulation, Peripheral Electrotherapy, and Neurophysiology Tests for Managing Incomplete Spinal Cord Injury

Efforts to find therapeutic methods that support spinal cord functional regeneration continue to be desirable. Natural recovery is limited, so high hopes are being placed on neuromodulation methods which promote neuroplasticity, such as repetitive transcranial magnetic stimulation (rTMS) and electrical stimulation used as treatment options for managing incomplete spinal cord injury (iSCI) apart from kinesiotherapy. However, there is still no agreement on the methodology and algorithms for treatment with these methods. The search for effective therapy is also hampered by the use of different, often subjective in nature, evaluation methods and difficulties in assessing the actual results of the therapy versus the phenomenon of spontaneous spinal cord regeneration. In this study, an analysis was performed on the database of five trials, and the cumulative data are presented. Participants (iSCI patients) were divided into five groups on the basis of the treatment they had received: rTMS and kinesiotherapy (N = 36), peripheral electrotherapy and kinesiotherapy (N = 65), kinesiotherapy alone (N = 55), rTMS only (N = 34), and peripheral electrotherapy mainly (N = 53). We present changes in amplitudes and frequencies of the motor units' action potentials recorded by surface electromyography (sEMG) from the tibialis anterior-the index muscle for the lower extremity and the percentage of improvement in sEMG results before and after the applied therapies. The increase in values in sEMG parameters represents the better ability of motor units to recruit and, thus, improvement of neural efferent transmission. Our results indicate that peripheral electrotherapy provides a higher percentage of neurophysiological improvement than rTMS; however, the use of any of these additional stimulation methods (rTMS or peripheral electrotherapy) provided better results than the use of kinesiotherapy alone. The best improvement of tibialis anterior motor units' activity in iSCI patients provided the application of electrotherapy conjoined with kinesiotherapy and rTMS conjoined with kinesiotherapy. We also undertook a review of the current literature to identify and summarise available works which address the use of rTMS or peripheral electrotherapy as neuromodulation treatment options in patients after iSCI. Our goal is to encourage other clinicians to implement both types of stimulation into the neurorehabilitation program for subjects after iSCI and evaluate their effectiveness with neurophysiological tests such as sEMG so further results and algorithms can be compared across studies. Facilitating the motor rehabilitation process by combining two rehabilitation procedures together was confirmed.

Optical imaging of neurons related to fictive swallowing using GCaMP6f in an arterially perfused rat preparation

ObjectiveIt is difficult to comprehensively study the activity patterns and distribution of neurons in the brainstem that control the act of swallowing, as they are located deep in the brain. In this study, we aimed to evaluate the usefulness of calcium imaging using GCaMP6f in arterially perfused preparations to study the activity of swallowing-related neurons in the brainstem. MethodsArterially perfused rat preparations were prepared 3–4 weeks after the injection of a neuron-specific virus expressing GCaMP6f. Fictive swallowing was induced by repetitive electrical stimulation of the superior laryngeal nerve (SLN). Simultaneously, the activity of GCaMP6f-expressing neurons in the dorsal brainstem, between 0.1 and 4.8 mm rostral to the obex, was assessed by changes in the intracellular calcium concentration using confocal laser microscopy. ResultsNeurons responding to stimulation of the SLN included swallowing-related neurons (48%), which showed an increase in fluorescence intensity at the time of swallowing bursts in the cervical vagus nerve, and stimulation-related neurons (52%), which showed an increase in fluorescence intensity through stimulation, regardless of the swallowing bursts. Despite a broad search area, swallowing-related neurons were localized exclusively in and around the solitary nucleus. In contrast, most stimulation-related neurons were located in the brainstem reticular formation, which is more rostral than the solitary nucleus. ConclusionsCalcium imaging using GCaMP in arterially perfused rat preparations is useful for an efficient search of the activity pattern and distribution of neurons located in a wide area of the brainstem.

Stimulation of the center of the lateral reticular nucleus suppresses the swallowing reflex in rats

Morphological studies have demonstrated that the lateral reticular nucleus (LRt) receives fibers projected from sites that are related to control of the swallowing reflex. Although the LRt may therefore be related to control of the swallowing reflex, the functional role of the LRt in the swallowing reflex remains unknown. The present study examined whether the swallowing reflex is modulated by stimulation of the LRt. These experiments were performed on rats anesthetized by urethane. The swallowing reflex was evoked by repetitive electrical stimulation of the superior laryngeal nerve (SLN) and was identified by electromyographic activities from the mylohyoid muscle. Electrical stimulation was applied to the LRt or glutamate was injected into the LRt. The number of swallows was reduced, and the latency of the onset of the first swallow was increased during electrical stimulation near the middle of the rostrocaudal direction of the LRt. The number of swallows was reduced, and the latency of onset of the first swallow increased after microinjection of glutamate near the rostrocaudal center of the LRt. The present study suggests that the LRt is involved in control of the swallowing reflex.

Trans-Sclera Electrical Stimulation Improves Retinal Function in a Mouse Model of Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is a photoreceptor-degenerating disease with no effective treatment. Trans-corneal electrical stimulation has neuroprotective effects in degenerating retinas, but repeated applications cause corneal injury. To avoid the risk of corneal damage, here we tested whether repetitive trans-sclera electrical stimulation (TsES) protects degenerating retinas in rd10 mice, a model of RP. At postnatal day 20 (P20), the right eyes of rd10 mice were exposed to 30 min of TsES daily or every other day till P25, at the amplitude of 50 or 100 μA, with zero current as the sham. Immunostaining, multi-electrode-array (MEA) recording, and a black-and-white transition box were applied to examine the morphological and functional changes of the treated retina. Functionally, TsES modified the retinal light responses. It also reduced the high spontaneous firing of retinal ganglion cells. TsES at 100 μA but not 50 μA increased the light sensitivities of ganglion cells as well as their signal-to-noise ratios. TsES at 100 μA increased the survival of photoreceptors without improving the visual behavior of rd10 mice. Our data suggest that repetitive TsES improves the retinal function of rd10 mice at the early degenerating stage, therefore, it might be an effective long-term strategy to delay retinal degeneration in RP patients.

Activity-dependent decline and recovery of synaptic transmission in central parts of surviving primary afferents after their peripheral cut in crayfish.

Axons deprived of their nucleus degenerate within a few days in mammals but survive for several months in crustaceans. However, it is not known whether central synapses from sensory axons may preserve their molecular machinery in the absence of spiking activity. To assess this, we used peripheral axotomy, which removes their nuclei combined with electrophysiology techniques and electron microscopy imaging. We report the following. (1) Electron microscopy analysis confirms previous observations that glial cell nuclei present in the sensory nerve proliferate and migrate to axon tubes, where they form close contacts with surviving axons. (2) After peripheral axotomy performed in vivo on the coxo-basipodite chordotonal organ (CBCO), the sensory nerve does not convey any sensory message, but antidromic volleys are observed. (3) Central synaptic transmission from the CBCO to motoneurons (MNs) progressively declines over 200 days (90% of monosynaptic excitatory transmission is lost after 3 weeks, whereas 60% of disynaptic inhibitory transmission persists up to 6 months). After 200 days, no transmission is observed. (4) However, this total loss is apparent only because repetitive electrical stimulation of the sensory nerve in vitro progressively restores first inhibitory post-synaptic potentials and then excitatory post-synaptic potentials. (5) The loss of synaptic transmission can be prevented by in vivo chronic sensory nerve stimulation. (6) Using simulations based on the geometric arrangements of synapses of the monosynaptic excitatory transmission and disynaptic inhibitory pathways, we show that antidromic activity in the CBCO nerve could play a role in the maintenance of synaptic function of inhibitory pathways to MNs, but not monosynaptic excitatory transmission to MNs. Our study confirms the deep changes in glial nuclei observed in axons deprived of their nucleus. We further show that the machinery for spike conduction and synaptic release persists for several months, even if there is no longer any activity. Indeed, we were able to restore, with electrical activity, spike conduction and synaptic function after long silent periods (>6 months).

Effectiveness of Repetitive Facilitative Exercise Combined with Electrical Stimulation Therapy to Improve Very Severe Paretic Upper Limbs in with Stroke Patients: A Randomized Controlled Trial

Background The difference in the effects of combined therapy with repetitive facilitative exercise (RFE) and neuromuscular electrical stimulation (NMES) on stroke upper limb paralysis was only reported by a pilot study; it has not been investigated in many patients. Objective We investigated the effect of combined therapy with RFE and NMES on stroke patients with severe upper paresis. Methods This study included 99 of the very severe paresis stroke patients with scores of zero or 1a in the Finger-Function test of the Stroke Impairment Assessment Set (SIAS). We randomly divided the patients into four groups, namely, NMES, RFE, RFE under NMES, and conventional training (CT) groups. A total of 20 min of group-specific training in addition to 40 min of conventional exercise per day, seven times a week for 4 weeks after admission, was performed. The upper extremity items of the Fugl-Meyer Assessment (FMA) were evaluated before and after the training period. Results The total score gains of the FMA, FMA wrist item, and FMA finger item were significantly larger in the RFE under NMES group than those in the CT group (p < 0.05). Conclusion The combination of voluntary movement and electrical stimulation may promote the activation of paralyzed muscles and improve distal function for very severe paralyzed upper limbs.