Afferent Electrical Stimulation Research Articles

A case study to assess the effects of the Exo-pulse neuromodulation suit on pain, fatigue and sleep patterns of an individual diagnosed with CFS/ME

The Exopulse suit was initially an approach to reduce spasticity and improve motor function in individuals with lesions in the CNS. Anecdotal findings from Exopulse users suggest that it could benefit people with pain syndromes, fatigue, and disturbed sleeping patterns. The Exopulse neuromodulation suit was programmed to apply multi-site afferent electrical stimulation and subsequently worn for one hour daily for thirty days. The one-hour session was done at the same time every morning, 9 AM to 10 AM, while the patient was lying in bed. One-hour Exopulse treatments consistently led to improvements in activity and sleep patterns. Diary records indicate that results carried over into the following day, which may indicate a training effect. All baseline scores were improved in self-assessments and objective measurements. The patient's parents commented on the increased interaction with friends and family, the increased planning ahead, and decreased agitation. CFS/ME is a condition in which performance and alertness can change due to environmental and internal factors. The results of this single Case Study design need to be approached cautiously.

Evidence of two modes of spiking evoked in human firing motoneurones by Ia afferent electrical stimulation.

Neurone firing behaviour is a result of complex interaction between synaptic inputs and cellular intrinsic properties. Intriguing firing behaviour, delayed spiking, was shown in some neurones, in particular, in cat neocortical neurones and rat pyramidal hippocampal neurones. In contrast, the similar spiking mode was not reported for animal spinal motoneurones. In the present study, an attempt was made to look for possible evidence of delayed spiking in human motoneurones firing within the low-frequency, sub-primary range, characteristic for voluntary muscle contractions and postural tasks. Forty-seven firing motor units (MUs) were analyzed in ten experiments on three muscles (the flexor carpi ulnaris, the tibialis anterior, and the abductor pollicis brevis) in four healthy humans. Single MUs were activated by gentle voluntary muscle contractions. MU peri-stimulus time histograms, durations of inter-spike intervals, and motoneurone excitability changes within a target interspike interval were analyzed. It was found that during testing the firing motoneurone excitability by small, transient excitatory Ia afferent volley, depending firstly on volley timing within a target interspike interval and excitatory volley strength, the same motoneurone displayed either the direct short-latency response (the H-reflex) or the delayed response (with prolonged and variable latency). Thus, the findings, for the first time, provide evidence for a possibility of two modes of spiking in firing motoneurones. Methods of the estimation of delayed responses and their possible functional significance are discussed. It is emphasized that, for understanding of this issue, the integration of data from studies on experimental animals and humans is desirable.

The vagus nerve somatosensory evoked potential in the intact brain: state-of-evidence and some representative vignettes

Objective Scalp-recorded evoked potentials elicited by applying afferent electrical stimulation at the tragus region of the human external ear have shown inconsistent results. We aim to disentangle discrepant findings and interpretations, and put forward novel physiological explanations on the origin of the vagus nerve somatosensory evoked potentials (VSEP). Methods We systematically search and critically appraise in PubMed, Web of Science, and Scielo databases the scientific reports publishing VSEP findings elicited by afferent electrical stimulation at the tragus region from individuals without brain disorders. Eligible studies published from January 2000 to April 2020 were extracted. The following information was identified from each article: number of participants; age; gender; stimulating/recording and grounding electrodes as well as stimulus side, intensity, duration, frequency, and polarity. Information about physiological parameters and neurobiological variables was also extracted. Representative vignettes with novel scalp responses induced by stimulating the tragus were also included to add support to our conclusions. Results 140 healthy participants were identified from six selected reports. Mean age ranged from 24.3 to 61.5 years. Stimulating and recording aspects were miscellaneous among studies. Scalp responses marked as the VSEP were recorded in 76% of participants, and showed high variability, low validity and poor reproducibility. Age correlated with response latencies. There were not gender differences in scalp response parameters. Cardiovascular function was unaltered by tragus stimulation. Vignettes showed that the VSEP was scalp muscle responses. Conclusion VSEP did not fulfil evoked potential guidelines. VSEP corresponded to volume conduction propagating from muscles surrounding scalp recording sites.

Effect of afferent electrical stimulation with mirror therapy on motor function, balance, and gait in chronic stroke survivors: a randomized controlled trial.

When solely mirror therapy is applied for a long period of time, spatial perception and attention to the damaged side may decrease, and the effect of mirror therapy may be limited. To overcome this limitation, it has recently been suggested that the combination of mirror therapy with mirror treatment is effective. The aim of this study was to investigate the effects of afferent electrical stimulation with mirror therapy on motor function, balance, and gait in chronic stroke survivors. A randomized controlled trial. Rehabilitation center. Thirty stroke survivors were randomly assigned to two groups: the experimental group (N.=15) and the control group (N.=15). Participants of the experimental group received afferent electrical stimulation with mirror therapy, and participants of the control group received sham afferent electrical stimulation with sham mirror therapy for 60 minutes per day, 5 days per week, for 4 weeks. Motor function was measured using a handheld dynamometer and the Modified Ashworth Scale, balance was measured using the Berg Balance Scale, and gait was assessed using the GAITRite® (GAITRite, CIR System Inc., Franklin, NJ, USA) pressure-sensitive walkway at baseline and after 4 weeks. The experimental group showed significant differences in muscle strength, Modified Ashworth Scale, and Berg Balance Scale results, and velocity, cadence, step length, stride length, and double support time of their gait (P<0.05) in the pre-post intervention comparison. Significant differences between the two groups in muscle strength, Berg Balance Scale, gait velocity, step length, and stride length (P<0.05) were found. Mirror therapy with afferent electrical stimulation may effectively improve muscle strength and gait and balance abilities in hemiplegic stroke survivors. Afferent electrical stimulation combined with mirror therapy can be used as an effective intervention to improve lower limb motor function, balance, and gait in chronic stroke survivors in clinical settings.

Lipopolysaccharide-induced inflammation does not alter muscle spindle afferent mechanosensation or sensory integration in the spinal cord of adult mice.

Inflammation is known to alter nervous system function, but its effect on muscle spindle afferent mechanosensation and sensory integration in the spinal cord has not been well studied. We tested the hypothesis that systemic inflammation induced by an intraperitoneal injection of the endotoxin lipopolysaccharide (LPS; 7.5 × 105 endotoxin units/kg 18 h before experiment) would alter muscle spindle afferent mechanosensation and spinal cord excitability to Group Ia input in male and female adult C57Bl/6 mice. LPS injection caused a systemic immune response, evidenced by decreased white blood cell, monocyte, and lymphocyte concentrations in the blood, increased blood granulocyte concentration, and body weight loss. The immune response in both sexes was qualitatively similar. We used an in vitro muscle‐nerve preparation to assay muscle spindle afferent response to stretch and vibration. LPS injection did not significantly change the response to stretch or vibration, with the exception of small decreases in the ability to entrain to high‐frequency vibration in male mice. Similarly, LPS injection did not alter spinal cord excitability to Group Ia muscle spindle afferent input as measured by the Hoffman's reflex test in anesthetized mice (100 mg/kg ketamine, 10 mg/kg xylazine). Specifically, there were no changes in M or H wave latencies nor in the percentage of motor neurons excited by electrical afferent stimulation (Hmax/Mmax). Overall, we found no major alterations in muscle proprioceptor function or sensory integration following exposure to LPS at a dose and time course that causes changes in nociceptor function and central processing.

Afferent electrical stimulation during cycling improves spinal processing of sensorimotor function after incomplete spinal cord injury.

Appropriate afferent feedback delivery during the execution of motor tasks is important for rehabilitation after incomplete spinal cord injury (iSCI). However, during leg-cycling therapy, the plantar afferent feedback is minimal. We hypothesize that the augmentation of sensory input by combining cycling with a locomotor-like stimulation of plantar cutaneous innervations (ES-cycling), might help to restore proper spinal processing of sensorimotor function. Thirteen non-injured subjects and 10 subjects with iSCI performed 10 minutes of cycling and, on another session, of ES-cycling. To assess spinal processing of sensorimotor function, soleus H-reflex response was tested following a conditioning plantar electrical stimulation applied at 25-100 ms inter-stimulus intervals (ISI's), measured before and after the execution of the tasks. Before tasks execution, the conditioned H-reflex response was modulated in non-injured subjects, and absent in subjects with iSCI; after cycling, modulation profiles were unchanged. However, after ES-cycling a significant increase in H-reflex excitability was observed in the non-injured group at 100 ms ISI (p < 0.05), and in the iSCI group between 50-75 ms ISI (p < 0.001). The loss of reflex modulation in subjects with iSCI suggests reduced spinal processing of sensorimotor function. Reflex modulation recovery after ES-cycling may indicate the partial reactivation of these mechanisms.

Long-term plasticity in identified hippocampal GABAergic interneurons in the CA1 area in vivo

Long-term plasticity is well documented in synapses between glutamatergic principal cells in the cortex both in vitro and in vivo. Long-term potentiation (LTP) and -depression (LTD) have also been reported in glutamatergic connections to hippocampal GABAergic interneurons expressing parvalbumin (PV+) or nitric oxide synthase (NOS+) in brain slices, but plasticity in these cells has not been tested in vivo. We investigated synaptically-evoked suprathreshold excitation of identified hippocampal neurons in the CA1 area of urethane-anaesthetized rats. Neurons were recorded extracellularly with glass microelectrodes, and labelled with neurobiotin for anatomical analyses. Single-shock electrical stimulation of afferents from the contralateral CA1 elicited postsynaptic action potentials with monosynaptic features showing short delay (9.95 ± 0.41 ms) and small jitter in 13 neurons through the commissural pathway. Theta-burst stimulation (TBS) generated LTP of the synaptically-evoked spike probability in pyramidal cells, and in a bistratified cell and two unidentified fast-spiking interneurons. On the contrary, PV+ basket cells and NOS+ ivy cells exhibited either LTD or LTP. An identified axo-axonic cell failed to show long-term change in its response to stimulation. Discharge of the cells did not explain whether LTP or LTD was generated. For the fast-spiking interneurons, as a group, no correlation was found between plasticity and local field potential oscillations (1–3 or 3–6 Hz components) recorded immediately prior to TBS. The results demonstrate activity-induced long-term plasticity in synaptic excitation of hippocampal PV+ and NOS+ interneurons in vivo. Physiological and pathological activity patterns in vivo may generate similar plasticity in these interneurons.

Closed-loop afferent electrical stimulation for recovery of hand function in individuals with motor incomplete spinal injury: early clinical results.

Afferent electrical stimulation is known to augment the effect of rehabilitative therapy through use-dependent cortical plasticity. Experiments pairing transcranial magnetic stimulation (TMS) with peripheral nerve stimulation (PNS) have shown a timing-dependent effect on motor evoked potential (MEP) amplitude suggesting that PNS applied in closed-loop (CL) mode could augment this effect through positive reinforcement. We present early results from a clinical trial in which an EEG brain-machine interface (BMI) was used to apply PNS to two subjects in response to motor intent detected from sensorimotor cortex in a cue-driven hand grip task. Both subjects had stable incomplete cervical spinal cord injury (SCI) with impaired upper limb function commensurate with the injury level. Twelve sessions of CL-PNS applied over a 4-6 week period yielded results suggesting improved hand grip strength and increased task-related modulation of the EEG in one hand of both subjects, and increased TMS-measured motor map area in one. These observations suggest that rehabilitation using such interactive therapies could benefit affected individuals.

A novel single compartment in vitro model for electrophysiological research using the perfluorocarbon FC-770.

Electrophysiological studies of whole organ systems in vitro often require measurement of nerve activity and/or stimulation of the organ via the associated nerves. Currently two-compartment setups are used for such studies. These setups are complicated and require two fluids in two separate compartments and stretching the nerve across one chamber to the other, which may damage the nerves. We aimed at developing a simple single compartment setup by testing the electrophysiological properties of FC-770 (a perfluorocarbon) for in vitro recording of bladder afferent nerve activity and electrical stimulation of the bladder. Perflurocarbons are especially suitable for such a setup because of their high oxygen carrying capacity and insulating properties. In male Wistar rats, afferent nerve activity was recorded from postganglionic branches of the pelvic nerve in vitro, in situ and in vivo. The bladder was stimulated electrically via the efferent nerves. Organ viability was monitored by recording spontaneous contractions of the bladder. Additionally, histological examinations were done to test the effect of FC-770 on the bladder tissue. Afferent nerve activity was successfully recorded in a total of 11 rats. The bladders were stimulated electrically and high amplitude contractions were evoked. Histological examinations and monitoring of spontaneous contractions showed that FC-770 maintained organ viability and did not cause damage to the tissue. We have shown that FC-770 enables a simple, one compartment in vitro alternative for the generally used two compartment setups for whole organ electrophysiological studies.

Commentary: GABA Depolarizes Immature Neurons and Inhibits Network Activity in the Neonatal Neocortex In vivo.

Commentary: GABA Depolarizes Immature Neurons and Inhibits Network Activity in the Neonatal Neocortex In vivo.

Adenosine A1 Receptor Suppresses Tonic GABAA Receptor Currents in Hippocampal Pyramidal Cells and in a Defined Subpopulation of Interneurons.

Adenosine is an endogenous neuromodulator that decreases excitability of hippocampal circuits activating membrane-bound metabotropic A1 receptor (A1R). The presynaptic inhibitory action of adenosine A1R in glutamatergic synapses is well documented, but its influence on inhibitory GABAergic transmission is poorly known. We report that GABAA receptor (GABAAR)-mediated tonic, but not phasic, transmission is suppressed by A1R in hippocampal neurons. Adenosine A1R activation strongly inhibits GABAAR agonist (muscimol)-evoked currents in Cornu Ammonis 1 (CA1) pyramidal neurons and in a specific subpopulation of interneurons expressing axonal cannabinoid receptor type 1. In addition, A1R suppresses tonic GABAAR currents measured in the presence of elevated ambient GABA as well as in naïve slices. The inhibition of GABAergic currents involves both protein kinase A (PKA) and protein kinase C (PKC) signaling pathways and decreases GABAAR δ-subunit expression. On the contrary, no A1R-mediated modulation was detected in phasic inhibitory postsynaptic currents evoked either by afferent electrical stimulation or by spontaneous quantal release. The results show that A1R modulates extrasynaptic rather than synaptic GABAAR-mediated signaling, and that this modulation selectively occurs in hippocampal pyramidal neurons and in a specific subpopulation of inhibitory interneurons. We conclude that modulation of tonic GABAAR signaling by adenosine A1R in specific neuron types may regulate neuronal gain and excitability in the hippocampus.

Innervation of enteric mast cells by primary spinal afferents in guinea pig and human small intestine.

Mast cells express the substance P (SP) neurokinin 1 receptor and the calcitonin gene-related peptide (CGRP) receptor in guinea pig and human small intestine. Enzyme-linked immunoassay showed that activation of intramural afferents by antidromic electrical stimulation or by capsaicin released SP and CGRP from human and guinea pig intestinal segments. Electrical stimulation of the afferents evoked slow excitatory postsynaptic potentials (EPSPs) in the enteric nervous system. The slow EPSPs were mediated by tachykinin neurokinin 1 and CGRP receptors. Capsaicin evoked slow EPSP-like responses that were suppressed by antagonists for protease-activated receptor 2. Afferent stimulation evoked slow EPSP-like excitation that was suppressed by mast cell-stabilizing drugs. Histamine and mast cell protease II were released by 1) exposure to SP or CGRP, 2) capsaicin, 3) compound 48/80, 4) elevation of mast cell Ca²⁺ by ionophore A23187, and 5) antidromic electrical stimulation of afferents. The mast cell stabilizers cromolyn and doxantrazole suppressed release of protease II and histamine when evoked by SP, CGRP, capsaicin, A23187, electrical stimulation of afferents, or compound 48/80. Neural blockade by tetrodotoxin prevented mast cell protease II release in response to antidromic electrical stimulation of mesenteric afferents. The results support a hypothesis that afferent innervation of enteric mast cells releases histamine and mast cell protease II, both of which are known to act in a diffuse paracrine manner to influence the behavior of enteric nervous system neurons and to elevate the sensitivity of spinal afferent terminals.

Neuromodulación en aneyaculación. Reporte de caso revisión de la literatura

Introduction and objectivesSacral root neuromodulation (SRN) is a procedure used to treat urinary function, as well as bowel and sexual disorders. In sexual disorders, there is some data suggesting benefits in erectile dysfunction, with very little evidence on ejaculation disorders. The objective of this report is to review the theory of SRN operation and its indications in order to propose a hypothesis on the mechanism and why our patient improved his ejaculation disorder after the SRN procedure. We suggest the SRN as an alternative treatment in the management of refractory anejaculation. Methods and materialsReview of patient's medical chart. A literature search was performed using MEDLINE and OVID. The search was limited to papers published in the last 10 years. MESH terms used were “sacral plexus”, “sacral region”, “ejaculation”, “neurobiology”, “spinal cord stimulation”, “transcutaneous electric nerve stimulation”, and also a non-MESH term “neuromodulation”. ResultsWe present the first report of anejaculation, secondary to pelvic surgical dissection in a young patient with a previously normal sexual life. Ejaculation improved significantly after the SRN procedure. The mechanism of action of SRN is not entirely known. It is possible that afferent electrical stimulation allows the modulation of spinal reflexes by restoring the balance between inhibition and activation at a central level. It has been used in the management of urinary, bowel, sexual, and nervous disorders. Based on this positive response, our hypothesis is that the surgical procedure altered the transmission of efferent signals of the pelvic nerves. The SRN procedure could improve the regulation of spinal reflexes and transmission of ejaculatory signals mediated by serotonin and noradrenaline transported by pelvic and pudenda nerves. ConclusionsThe SRN is presented as an alternative in the management of anejaculation despite the lack of evidence to support the standardization of the procedure.© 2012 Sociedad Colombiana de Urología. Published by Elsevier España, S.L. All rights reserved.

Nanomolar Oxytocin Synergizes with Weak Electrical Afferent Stimulation to Activate the Locomotor CPG of the Rat Spinal Cord In Vitro

Synergizing the effect of afferent fibre stimulation with pharmacological interventions is a desirable goal to trigger spinal locomotor activity, especially after injury. Thus, to better understand the mechanisms to optimize this process, we studied the role of the neuropeptide oxytocin (previously shown to stimulate locomotor networks) on network and motoneuron properties using the isolated neonatal rat spinal cord. On motoneurons oxytocin (1 nM–1 μM) generated sporadic bursts with superimposed firing and dose-dependent depolarization. No desensitization was observed despite repeated applications. Tetrodotoxin completely blocked the effects of oxytocin, demonstrating the network origin of the responses. Recording motoneuron pool activity from lumbar ventral roots showed oxytocin mediated depolarization with synchronous bursts, and depression of reflex responses in a stimulus and peptide-concentration dependent fashion. Disinhibited bursting caused by strychnine and bicuculline was accelerated by oxytocin whose action was blocked by the oxytocin antagonist atosiban. Fictive locomotion appeared when subthreshold concentrations of NMDA plus 5HT were coapplied with oxytocin, an effect prevented after 24 h incubation with the inhibitor of 5HT synthesis, PCPA. When fictive locomotion was fully manifested, oxytocin did not change periodicity, although cycle amplitude became smaller. A novel protocol of electrical stimulation based on noisy waveforms and applied to one dorsal root evoked stereotypic fictive locomotion. Whenever the stimulus intensity was subthreshold, low doses of oxytocin triggered fictive locomotion although oxytocin per se did not affect primary afferent depolarization evoked by dorsal root pulses. Among the several functional targets for the action of oxytocin at lumbar spinal cord level, the present results highlight how small concentrations of this peptide could bring spinal networks to threshold for fictive locomotion in combination with other protocols, and delineate the use of oxytocin to strengthen the efficiency of electrical stimulation to activate locomotor circuits.

GABAA receptors in the nucleus raphe magnus modulate firing of neurons in the trigeminocervical complex

Methods We used a model of trigeminovascular nociception in Sprague Dawley rats that measures transmission of craniovascular nociception in the trigeminocervical complex (TCC) by the firing of TCC neurons evoked in response to electrical stimulation of afferents from the middle meningeal artery, its branches, and periarterial meninges (MMA). To determine whether GABA receptors in the NRM modulate this nociceptive transmission, and to characterize the modulation, we microinjected GABA, and GABAAand GABAB-receptor agonists and antagonists into the NRM.

Synaptic depression in the CA1 region of freely behaving mice is highly dependent on afferent stimulation parameters

Persistent synaptic plasticity has been subjected to intense study in the decades since it was first described. Occurring in the form of long-term potentiation (LTP) and long-term depression (LTD), it shares many cellular and molecular properties with hippocampus-dependent forms of persistent memory. Recent reports of both LTP and LTD occurring endogenously under specific learning conditions provide further support that these forms of synaptic plasticity may comprise the cellular correlates of memory. Most studies of synaptic plasticity are performed using in vitro or in vivo preparations where patterned electrical stimulation of afferent fibers is implemented to induce changes in synaptic strength. This strategy has proven very effective in inducing LTP, even under in vivo conditions. LTD in vivo has proven more elusive: although LTD occurs endogenously under specific learning conditions in both rats and mice, its induction has not been successfully demonstrated with afferent electrical stimulation alone. In this study we screened a large spectrum of protocols that are known to induce LTD either in hippocampal slices or in the intact rat hippocampus, to clarify if LTD can be induced by sole afferent stimulation in the mouse CA1 region in vivo. Low frequency stimulation at 1, 2, 3, 5, 7, or 10 Hz given in the range of 100 through 1800 pulses produced, at best, short-term depression (STD) that lasted for up to 60 min. Varying the administration pattern of the stimuli (e.g., 900 pulses given twice at 5 min intervals), or changing the stimulation intensity did not improve the persistency of synaptic depression. LTD that lasts for at least 24 h occurs under learning conditions in mice. We conclude that a coincidence of factors, such as afferent activity together with neuromodulatory inputs, play a decisive role in the enablement of LTD under more naturalistic (e.g., learning) conditions.

Effect of repetitive afferent electrical stimulation of the lower limb on corticomotor excitability and implications for rehabilitation

Despite the extensive work published on the effects of electrical stimulation on corticomotor excitability, very few studies have focused on lower limb muscles. The aim of the present study was to determine the effect of high-frequency afferent electrical stimulation of the anterior thigh area on the corticomotor excitability of lower limb muscles. Twenty-two healthy subjects (mean age 23±7years) participated in the study. Electrical stimulation was applied for 60minutes on the anterior thigh area (frequency 100Hz, pulse duration 60μs, intensity below motor threshold). Motor-evoked potentials (MEP) of the rectus femoris (RF) and biceps femoris (BF) muscles were recorded before, and after, the electrical stimulation paradigm with a Magstim 200 stimulator. Analyses revealed a significant modulation in MEP amplitude for the RF but not for the BF muscle. Specifically, there was a significant reduction in MEP amplitude for the RF muscle immediately, 15minutes and 30minutes after the end of electrical stimulation when compared with baseline. Our results indicate that a 60-minute high-frequency electrical stimulation protocol applied on the anterior thigh area decreases the corticomotor excitability of the RF muscle. Although the exact duration remains unknown, the pattern of modulation observed indicates that the inhibitory effect lasts for more than 30minutes after the end of stimulation, giving enough time for clinicians to work on the desired motor task during rehabilitation.

Endogenous hippocampal LTD that is enabled by spatial object recognition requires activation of NMDA receptors and the metabotropic glutamate receptor, mGlu5

Learning-facilitated synaptic plasticity describes the ability of hippocampal synapses to respond with persistent plasticity to afferent stimulation when coupled with a spatial learning event, whereby the afferent stimulation normally produces short-term plasticity or no change in synaptic strength if given in the absence of novel learning. Recently, it was reported that in the mouse hippocampus intrinsic long-term depression (LTD > 24 h) occurs when test-pulse afferent stimulation is coupled with a novel spatial learning. It is not known to what extent this phenomenon shares molecular properties with synaptic plasticity that is typically induced by means of patterned electrical afferent stimulation. In previous work, we showed that a novel spatial object recognition task facilitates LTD at the Schaffer collateral-CA1 synapse of freely behaving adult mice, whereas reexposure to the familiar spatial configuration ∼24 h later elicited no such facilitation. Here we report that treatment with the NMDA receptor antagonist, (±)-3-(2-Carboxypiperazin-4-yl)-propanephosphonic acid (CPP), or antagonism of metabotropic glutamate (mGlu) receptor, mGlu5, using 2-methyl-6-(phenylethynyl) pyridine (MPEP), completely prevented LTD under the novel learning conditions. Behavioral assessment during re-exposure after application of the antagonists revealed that the animals did not remember the object during novel exposure and treated them as if they were novel. Under these circumstances, where the acquisition of novel spatial information was involved, LTD was facilitated. Our data support that the endogenous LTD that is enabled through novel spatial learning in adult mice is critically dependent on the activation of both the NMDA receptors and mGlu5.

Modulation of corticomuscular coherence by peripheral stimuli

The purpose of this study was to investigate the effects of peripheral afferent stimuli on the synchrony between brain and muscle activity as estimated by corticomuscular coherence (CMC). Electroencephalogram (EEG) from sensorimotor cortex and electromyogram (EMG) from two intrinsic hand muscles were recorded during a key grip motor task, and the modulation of CMC caused by afferent electrical and mechanical stimulation was measured. The particular stimuli used were graded single-pulse electrical stimuli, above threshold for perception and activating cutaneous afferents, applied to the dominant or non-dominant index finger, and a pulsed mechanical displacement of the gripped object causing the subject to feel as if the object may be dropped. Following electrical stimulation of the dominant index finger, the level of β-range (14-36 Hz) CMC was reduced in a stimulus intensity-dependent fashion for up to 400 ms post-stimulus, then returned with greater magnitude before falling to baseline levels over 2.5 s, outlasting the reflex and evoked changes in EMG and EEG. Subjects showing no baseline β-range CMC nevertheless showed post-stimulus increases in β-range CMC with the same time course as those with baseline β-range CMC. The mechanical stimuli produced similar modulation of β-range CMC. Electrical stimuli to the non-dominant index finger produced no significant increase in β-range CMC. The results suggest that both cutaneous and proprioceptive afferents have access to circuits generating CMC, but that only a functionally relevant stimulus produces significant modulation of the background β-range CMC, providing further evidence that β-range CMC has an important role in sensorimotor integration.

Modulation of motor cortex excitability by different levels of whole-hand afferent electrical stimulation

Objective In a previous transcranial magnetic stimulation (TMS) study we demonstrated that suprathreshold mesh-glove (MG) whole-hand stimulation elicits lasting changes in motor cortical excitability. Currently, there is no consensus with regard to the optimal parameters for the induction of sensorimotor cortical plasticity using peripheral electrical stimulation. Thus, in the present study we explore the modulatory effects of MG stimulation at different stimulus intensities and different frequencies in order to identify an optimal stimulation protocol. Methods MG stimulation was performed on 12 healthy subjects in separate sessions at different stimulation levels: sub-sensory at 50 Hz, sensory at 50 Hz and motor at 2 Hz. To verify if stimulation at lower frequencies is less effective, an additional experiment at sensory level with 2 Hz was performed. TMS was used to assess motor threshold (MT), motor evoked potentials (MEPs) recruitment curve (RC), short latency intracortical inhibition (SICI) and intracortical facilitation (ICF) to paired-pulse TMS at baseline ( T0), immediately after ( T1) and 1 h ( T2) after 30 min of MG stimulation. F-wave studies were performed to assess spinal motoneuron excitability. Results MG stimulation at sub-sensory/50 Hz and sensory/2 Hz level determines no significant cortical excitability changes; at sensory/50 Hz level and at motor/2 Hz level we found decreased MT, increased MEP RC as well as reduced SICI and increased ICF at T1 and T2. Conclusions MG stimulation at sensory/50 Hz and motor/2 Hz level induces similar long-lasting modulatory effects on motor cortical excitability. Both the strength of the corticospinal projections and the intracortical networks are influenced to the same extend. Significance The study provides further evidence that stimulation intensity and frequency can independently modulate motor cortical plasticity. The selection of optimal stimulation parameters has potentially important implications for the neurorehabilitation of patients after brain damage (e.g. stroke, traumatic brain injury) with hand motor deficits.