Comparison of Transcallosal Inhibition Between Hemispheres and Its Relationship with Motor Behavior in Patients with Severe Upper Extremity Impairment After Subacute Stroke

ObjectiveTo compare corticospinal excitability and transcallosal inhibition between contralesional primary motor cortex (M1) and ipsilesional M1. We also investigated the correlation between transcallosal inhibition and upper extremity motor behavior.Materials and methods19 individuals with unilateral ischemic subacute stroke who had severe upper extremity impairment participated in this study. Corticospinal excitability was assessed by measuring the resting motor threshold, active motor threshold and motor evoked potential amplitude. Transcallosal inhibition was investigated by measuring the duration and depth of the ipsilateral silent period (ISP). The data from the two hemispheres were compared and the relationships of transcallosal inhibition with upper extremity motor impairment, grip strength and pinch strength were analyzed.ResultsResting motor threshold (p = 0.001) and active motor threshold (p = 0.001) were lower and motor evoked potential amplitude was higher (p = 0.001) in the contralesional M1 compared to the ipsilesional M1. However, there were no differences between the two M1s in ISP duration (p = 0.297) or ISP depth (p =0. 229). Transcallosal inhibition from the contralesional M1 was positively associated with motor impairment (ISP duration, p = 0.003; ISP depth, p = 0.017) and grip strength (ISP duration, p = 0.016; ISP depth, p = 0.045).ConclusionsSymmetric transcallosal inhibition between hemispheres and positive association of transcallosal inhibition from contralesional M1 with upper extremity motor behavior indicate that recruitment of contralesional M1 may be necessary for recovery in patients with severe upper extremity impairment after subacute ischemic stroke.     

Neurophysiology of motor skill learning in chronic stroke

ObjectiveMotor learning is relevant in chronic stroke for acquiring compensatory strategies to motor control deficits. However, the neurophysiological mechanisms underlying motor skill acquisition with the paretic upper limb have received little systematic investigation. The aim of this study was to assess the modulation of corticomotor excitability and intracortical inhibition within ipsilesional primary motor cortex (M1) during motor skill learning.MethodsTen people at the chronic stage after stroke and twelve healthy controls trained on a sequential visuomotor isometric wrist extension task. Skill was quantified before, immediately after, 24 hours and 7 days post-training. Transcranial magnetic stimulation was used to examine corticomotor excitability and short- and long-interval intracortical inhibition (SICI and LICI) pre- and post-training.ResultsThe patient group exhibited successful skill acquisition and retention, although absolute skill level was lower compared with controls. In contrast to controls, patients’ ipsilesional corticomotor excitability was not modulated during skill acquisition, which may be attributed to excessive ipsilesional LICI relative to controls. SICI decreased after training for both patient and control groups.ConclusionsOur findings indicate distinct inhibitory networks within M1 that may be relevant for motor learning after stroke.SignificanceThese findings have potential clinical relevance for neurorehabilitation adjuvants aimed at augmenting the recovery of motor function.     

Influence of post-stroke fatigue on reaction times and corticospinal excitability during movement preparation

ObjectivesReduced corticospinal excitability at rest is associated with post-stroke fatigue (PSF). However, it is not known if corticospinal excitability prior to a movement is also altered in fatigue which may then influence subsequent behaviour. We hypothesized that the levels of PSF can be explained by differences in modulation of corticospinal excitability during movement preparation.Methods73 stroke survivors performed an auditory reaction time task. Corticospinal excitability was measured using transcranial magnetic stimulation. Fatigue was quantified using the fatigue severity scale. The effect of time and fatigue on corticospinal excitability and reaction time was analysed using a mixed effects model.ResultsThose with greater levels of PSF showed reduced suppression of corticospinal excitability during movement preparation and increased facilitation immediately prior to movement onset (β = −0.0066, t = −2.22, p = 0.0263). Greater the fatigue, slower the reaction times the closer the stimulation time to movement onset (β = 0.0024, t = 2.47, p = 0.0159).ConclusionsLack of pre-movement modulation of corticospinal excitability in high fatigue may indicate poor sensory processing supporting the sensory attenuation model of fatigue.SignificanceWe take a systems-based approach and investigate the motor system and its role in pathological fatigue allowing us to move towards gaining a mechanistic understanding of chronic pathological fatigue.     

Individualized beta-band oscillatory transcranial direct current stimulation over the primary motor cortex enhances corticomuscular coherence and corticospinal excitability in healthy individuals

BackgroundSimultaneously modulating individual neural oscillation and cortical excitability may be important for enhancing communication between the primary motor cortex and spinal motor neurons, which plays a key role in motor control. However, it is unknown whether individualized beta-band oscillatory transcranial direct current stimulation (otDCS) enhances corticospinal oscillation and excitability.ObjectiveThis study investigated the effects of individualized beta-band otDCS on corticomuscular coherence (CMC) and corticospinal excitability in healthy individuals.MethodsIn total, 29 healthy volunteers participated in separate experiments. They received the following stimuli for 10 min on different days: 1) 2-mA otDCS with individualized beta-band frequencies, 2) 2-mA transcranial alternating current stimulation (tACS) with individualized beta-band frequencies, and 3) 2-mA transcranial direct current stimulation (tDCS). The changes in CMC between the vertex and tibialis anterior (TA) muscle and TA muscle motor-evoked potentials (MEPs) were assessed before and after (immediately, 10 min, and 20 min after) stimulation on different days. Additionally, 20-Hz otDCS for 10 min was applied to investigate the effects of a fixed beta-band frequency on CMC.ResultsotDCS significantly increased CMC and MEPs immediately after stimulation, whereas tACS and tDCS had no effects. There was a significant negative correlation between normalized CMC changes in response to 20-Hz otDCS and the numerical difference between the 20-Hz and individualized CMC peak frequency before the stimulation.ConclusionsThese findings suggest that simultaneous modulation of neural oscillation and cortical excitability is critical for enhancing corticospinal communication. Individualized otDCS holds potential as a useful method in the field of neurorehabilitation.     

Myelin protein zero gene dose dependent axonal ion-channel dysfunction in a family with Charcot-Marie-Tooth disease

ObjectiveThe myelin impairment in demyelinating Charcot-Marie-Tooth (CMT) disease leads to various degrees of axonal degeneration, the ultimate cause of disability. We aimed to assess the pathophysiological changes in axonal function related to the neuropathy severity in hypo-/demyelinating CMT patients associated with myelin protein zero gene (MPZ) deficiency.MethodsWe investigated four family members (two parents and two sons) harboring a frameshift mutation (c.306delA, p.Asp104ThrfsTer14) in the MPZ gene, predicted to result in a nonfunctional P₀, by conventional conduction studies and multiple measures of motor axon excitability. In addition to the conventional excitability studies of the median nerve at the wrist, we tested the spinal accessory nerves. Control measures were obtained from 14 healthy volunteers.ResultsThe heterozygous parents (aged 56 and 63) had a mild CMT1B whereas their two homozygous sons (aged 31 and 39 years) had a severe Dejerine-Sottas disease phenotype. The spinal accessory nerve excitability could be measured in all patients. The sons showed reduced deviations during depolarizing threshold electrotonus and other depolarizing features which were not apparent in the accessory and median nerve studies of the parents. Mathematical modeling indicated impairment in voltage-gated sodium channels. This interpretation was supported by comparative modeling of excitability measurements in MPZ deficient mice.ConclusionOur data suggest that axonal depolarization in the context of abnormal voltage-gated sodium channels precedes axonal degeneration in severely hypo-/demyelinating CMT as previously reported in the mouse models.SignificanceMeasures of the accessory nerve excitability could provide pathophysiological markers of neurotoxicity in severe demyelinating neuropathies.     

Sarcolemmal depolarization in sporadic inclusion body myositis assessed with muscle velocity recovery cycles

ObjectiveTo study patients with sporadic inclusion body myositis (sIBM) with muscle velocity recovery cycles (MVRC) to assess muscle membrane excitability, pathophysiological mechanisms and potential biomarkers of this disorder.MethodsMVRC were recorded from 20 individuals with sIBM from tibialis anterior (TA) and rectus femoris (RF) muscles. Excitability parameters were compared with MVRC data obtained from 22 normal controls >50 years.ResultsMuscle relative refractory period was prolonged in both TA (6.4 ms vs 4.4 ms, P < 0.001) and RF (7.1 ms vs 3.9 ms, P < 0.001) of sIBM affected muscle when compared to controls. Early supernormality was reduced in both TA (3.6% vs 8.8% P = 0.001) and in RF (mean 5.4% vs 13% P < 0.001). Late supernormality was only decreased significantly in sIBM affected TA (1.8% vs 3.6% P = 0.001) but not in RF. No consistent correlations between MVRC parameters and clinical markers of sIBM disease severity were found.ConclusionThe resting sarcolemmal muscle membrane potential of sIBM muscle is depolarized relative to that of normal controls, which may be related to intramuscular amyloid deposition in sIBM.SignificanceSarcolemmal depolarization may play a role in muscle dysfunction and weakness observed in sIBM patients.     

D-cycloserine normalizes long-term motor plasticity after transcranial magnetic intermittent theta-burst stimulation in major depressive disorder

ObjectivesMajor Depressive Disorder (MDD) is associated with glutamatergic alterations, including the N-methyl-D-aspartate receptor (NMDA-R). The NMDA-R plays an important role in synaptic plasticity, and individuals with MDD have been shown to have impairments in repetitive Transcranial Magnetic Stimulation (rTMS) motor plasticity. Here, we test whether D-cycloserine, a NMDA-R partial agonist, can rescue TMS motor plasticity in MDD.MethodsWe conducted randomized double-blind placebo-controlled crossover studies in healthy (n = 12) and MDD (n = 12) participants. We stimulated motor cortex using TMS intermittent theta burst stimulation (iTBS) with placebo or D-cycloserine (100 mg). Motor evoked potentials (MEPs) were sampled before and after iTBS. Stimulus response curves (SRC) were characterized at baseline, +90 minutes, and the following day.ResultsAcute iTBS MEP facilitation is reduced in MDD and is not rescued by D-cycloserine. After iTBS, SRCs shift to indicate sustained decrease in excitability in healthy participants, yet increased in excitability in MDD participants. D-cycloserine normalized SRC changes from baseline to the following day in MDD participants. In both healthy and MDD participants, D-cycloserine stabilized changes in SRC.ConclusionMDD is associated with alterations in motor plasticity that are rescued and stabilized by NMDA-R agonism.SignificanceAgonism of NMDA receptors rescues iTBS motor plasticity in MDD.     

Near-fiber electromyography

ObjectiveDescribe and evaluate the concepts of near fiber electromyography (NFEMG), the features used, including near fiber motor unit potential (NFMUP) duration and dispersion, which relate to motor unit distal axonal branch and muscle fiber conduction time dispersion, and NFMUP segment jitter, a new measure of the temporal variability of neuromuscular junction transmission (NMJ), and axonal branch and muscle fibre conduction for the near fibres (i.e. NF jitter), and the methods for obtaining their values.MethodsTrains of high-pass filtered motor unit potentials (MUPs) (i.e. NFMUP trains) were extracted from needle-detected EMG signals to assess changes in motor unit (MU) morphology and electrophysiology caused by neuromuscular disorders or ageing. Evaluations using simulated needle-detected EMG data were completed and example human data are presented.ResultsNFEMG feature values can be used to detect axonal sprouting, conduction slowing and NMJ transmission delay as well as changes in MU fiber diameter variability, and NF jitter. These changes can be detected prior to alterations of MU size or numbers.ConclusionsThe evaluations clearly demonstrate and the example data support that NFMUP duration and dispersion reflect MU distal axonal branching, conduction slowing and NMJ transmission delay and/or MU fiber diameter variability and that NFMUP jiggle and segment jitter reflect NF jitter.SignificanceNFEMG can detect early changes in MU morphology and/or electrophysiology and has the potential to augment clinical diagnosis and tracking of neuromuscular disorders.     

Age-related changes in late synaptic inputs to corticospinal neurons and their functional significance: A paired-pulse TMS study

BackgroundRecent work suggests that the function of intracortical interneurons activated by transcranial magnetic stimulation (TMS) is modified in older adults, with the circuits generating short-interval intracortical facilitation (SICF) at longer intervals appearing to be particularly affected.ObjectiveTo use SICF to quantify age-related changes in the excitability and recruitment of late synaptic inputs to corticospinal neurons, and investigate if changes within these circuits contribute to altered motor performance in older adults.MethodsSICF was recorded with 3 different conditioning intensities in 23 young (23.0 ± 4.2 years) and 21 older (67.1 ± 1.1 years) adults. These measures were performed with conventional (posterior-anterior, PA) and reverse (anterior-posterior, AP) current directions using interstimulus intervals targeting late synaptic inputs to corticospinal neurons (3.5–5.3 ms).ResultsPeak SICF recorded with a PA current (SICF_PA) was reduced in older adults (P < 0.0001), and occurred at a longer latency (P < 0.05). Furthermore, there was reduced recruitment of SICF_PA in older adults (P < 0.0001), but this did not interact with the age-related shift in SICF_PA (P = 0.2). In addition, reduced performance on the Purdue pegboard was predicted by increased SICF_PA (P < 0.04) occurring at longer latencies (P < 0.04) in old but not young adults. For SICF recorded with an AP current (SICF_AP), facilitation was again reduced at longer latencies in older adults (P < 0.0001), but recruitment was not different between groups (P = 0.7) and was unrelated to motor function.ConclusionThese results suggest that there are age-related changes in late synaptic inputs to corticospinal neurons and that these changes influence fine motor performance.     

Theta-burst versus 20 Hz repetitive transcranial magnetic stimulation in neuropathic pain: A head-to-head comparison

ObjectiveHigh-frequency repetitive transcranial magnetic stimulation (rTMS) has been shown to reduce neuropathic pain, but intermittent “theta-burst” stimulation (iTBS) could be a better alternative because of shorter duration and greater ability to induce cortical plasticity. Here we compared head-to-head the pain-relieving efficacy of the two modalities when applied daily for 5 days to patients with neuropathic pain.MethodsForty-six patients received 20 Hz-rTMS and/or iTBS protocols and 39 of them underwent the full two procedures in a random cross-over design. They rated pain intensity, sleep quality, fatigue and general health status daily during 5 consecutive weeks.ResultsPain relief during the month following stimulation was superior after 20 Hz-rTMS relative to iTBS (F(1,38) = 4.645; p = 0.037). Correlation between respective levels of maximal relief showed a significant deviation toward the 20 Hz-rTMS effect. A greater proportion of individuals responded to 20 Hz-rTMS (52% vs 32%, 95 %CI[0.095–3.27]; p = 0.06), and reports of fatigue significantly improved after 20 Hz-rTMS relative to iTBS (p = 0.01). General health and sleep quality scores did not differentiate both techniques.ConclusionsHigh-frequency rTMS appeared superior to iTBS for neuropathic pain relief.SignificanceAdequate matching between the oscillatory activity of motor cortex and that of rTMS may increase synaptic efficacy, thus enhancing functional connectivity of motor cortex with distant structures involved in pain regulation.     

Inter trial coherence of low-frequency oscillations in the course of stroke recovery

ObjectiveThe aim was to find a sensitive method to highlight the remodeling of the brain’s bioelectric activity in post-stroke repair.MethodsFifteen mild upper limb paretic stroke patients and age-matched healthy controls were included. Repeated trials of finger tapping around the 10th and 100th days after stroke onset were recorded with a 128-channel EEG. Power spectra and Inter Trial Coherence (ITC) calculations were synchronized to tappings. ITC was correlated with motor performance.ResultsITC, in low frequency bands, designates the motor related bioelectric activity in channel space in both healthy subjects and patients. Ten days after stroke onset, delta-theta ITC was severely reduced compared to baseline, while three months later ITC reorganized partially over the ipsilesional central-parietal areas reflecting the improvement of motor networks. Decreased ITC in the central-parietal area remained significant compared to controls. Delta band ITC over the dorsolateral-prefrontal cortex correlates with the performance on Nine Hole Peg Test. At post-recovery, non-paretic hand tappings show significantly decreased delta-theta ITC over the supplementary motor area, which reflects network remodeling.ConclusionsInter Trial Coherence is a useful measure of brain reorganization during stroke recovery.SignificanceDelta- theta ITC is a sensitive indicator of impaired motor execution.     

Cortical mechanisms underlying variability in intermittent theta-burst stimulation-induced plasticity: A TMS-EEG study

ObjectiveTo test the hypothesis that intermittent theta burst stimulation (iTBS) variability depends on the ability to engage specific neurons in the primary motor cortex (M1).MethodsIn a sham-controlled interventional study on 31 healthy volunteers, we used concomitant transcranial magnetic stimulation (TMS) and electroencephalography (EEG). We compared baseline motor evoked potentials (MEPs), M1 iTBS-evoked EEG oscillations, and resting-state EEG (rsEEG) between subjects who did and did not show MEP facilitation following iTBS. We also investigated whether baseline MEP and iTBS-evoked EEG oscillations could explain inter and intraindividual variability in iTBS aftereffects.ResultsThe facilitation group had smaller baseline MEPs than the no-facilitation group and showed more iTBS-evoked EEG oscillation synchronization in the alpha and beta frequency bands. Resting-state EEG power was similar between groups and iTBS had a similar non-significant effect on rsEEG in both groups. Baseline MEP amplitude and beta iTBS-evoked EEG oscillation power explained both inter and intraindividual variability in MEP modulation following iTBS.ConclusionsThe results show that variability in iTBS-associated plasticity depends on baseline corticospinal excitability and on the ability of iTBS to engage M1 beta oscillations.SignificanceThese observations can be used to optimize iTBS investigational and therapeutic applications.     

Practice-dependent motor cortex plasticity is reduced in non-disabled multiple sclerosis patients

ObjectivesSkill acquisition after motor training involves synaptic long-term potentiation (LTP) in primary motor cortex (M1). In multiple sclerosis (MS), LTP failure ensuing from neuroinflammation could contribute to worsen clinical recovery. We therefore addressed whether practice-dependent plasticity is altered in MS.MethodsEighteen relapsing-remitting (RR)-MS patients and eighteen healthy controls performed 600 fast abductions of index finger in 30 blocks of 20 movements. Before and after practice, transcranial magnetic stimulation (TMS) was delivered over the hot spot of the trained first dorsal interosseous muscle. Movements kinematics, measures of cortical excitability, and the input/output curves of motor evoked potentials (MEPs) were assessed.ResultsKinematic variables of movement improved with practice in patients and controls to a similar extent, although patients showed lower MEPs amplitude increase after practice. Practice did not change the difference in resting motor threshold values observed between patients and controls, nor did modulate short-interval intracortical inhibition. Clinical/radiological characteristics were not associated to practice-dependent effects.ConclusionsPractice-induced reorganization of M1 is altered in non-disabled RR-MS patients, as shown by impaired MEPs modulation after motor learning.SignificanceThese findings suggest that in RR-MS physiological mechanisms of practice-dependent plasticity are altered.     

Semi-quantitative electromyography as a predictor of nerve transfer outcome

ObjectivesEvaluate correlation between donor nerve semi-quantitative electromyography (sqEMG) and strength outcome in nerve transfer surgery.MethodsRetrospective review of pre-operative donor nerve semi-quantitative neurophysiology and post-operative recipient muscle force after at least one-year follow-up. The semi-quantitative technique is the average motor unit number estimate associated with needle recorded interference patterns in the donor muscle (IP-AMUNE), which was correlated with hand-held manometry, standardized as a percent of the contralateral arm, using multivariable linear regression with backward selection.ResultsTwenty-eight nerve transfer cases were included. The correlation between the donor nerve IP-AMUNE and the recipient muscle strength was moderate to strong and highly significant (r = 0.67, p < 0.001). Medical Research Council (MRC) grading did not predict strength (p > 0.54).ConclusionsIP-AMUNE is a good predictor of strength after nerve transfer surgery and should be considered in the evaluation and planning of patients undergoing nerve transfer to aid in donor nerve selection.SignificanceIP-AMUNE may significantly benefit those undergoing nerve transfer surgery for the restoration of movement.     

Excitability of motor and sensory axons in multifocal motor neuropathy

ObjectiveTo assess excitability differences between motor and sensory axons of affected nerves in patients with multifocal motor neuropathy (MMN).MethodsWe performed motor and sensory excitability tests in affected median nerves of 20 MMN patients and in 20 age-matched normal subjects. CMAPs were recorded from the thenar and SNAPs from the 3rd digit. Clinical tests included assessment of muscle strength, two-point discrimination and joint position.ResultsAll MMN patients had weakness of the thenar muscle and normal sensory tests. Motor excitability testing in MMN showed an increased threshold for a 50% CMAP, increased rheobase, decreased stimulus-response slope, fanning-out of threshold electrotonus, decreased resting I/V slope, shortened refractory period, and more pronounced superexcitability. Sensory excitability testing in MMN revealed decreased accommodation half-time and S2-accommodation and less pronounced subexcitability. Mathematical modeling indicated increased Barrett-Barrett conductance for motor fibers and increase in internodal fast potassium conductance for sensory fibers.ConclusionsExcitability findings in MMN suggest myelin sheath or paranodal seal involvement in motor fibers and, possibly, paranodal detachment in sensory fibers.SignificanceExcitability properties of affected nerves in MMN differ between motor and sensory nerve fibers.     

Spectrum of PAH gene mutations and genotype-phenotype correlation in patients with phenylalanine hydroxylase deficiency from Shanxi province

BackgroundPhenylalanine hydroxylase deficiency (PAHD) is an autosomal recessive inborn error that affects phenylalanine (Phe) metabolism. It has a complex phenotype with many variants and genotypes among different populations. Shanxi province is a high-prevalence area of PAHD in China.MethodsIn this study, eighty-nine PAHD patients were subjected to genetic testing using Sanger sequencing, followed by multiplex ligation-dependent probe amplification analysis (MLPA). Allelic and genotypic phenotype values (APV and GPV, respectively) were used for genotype-based phenotypic prediction.ResultsFifty-one types of variants, including three novel forms, were identified. The predominant variant was p.R243Q (22.09%), followed by p.R53H (10.47%), p.EX6-96A > G (9.30%), p.V399V (5.23%) and p.R413P (3.49%). Notably, mild hyperphenylalaninemia (MHP) has a high prevalence in this region (up to 45.76%), and the variant p.R53H was solely observed in patients of MHP. According to the genotype–phenotype prediction, the APV/GPV system was well correlated with the metabolic phenotype of most PAHD patients.ConclusionWe have systematically constructed the mutational and phenotypic spectrum of PAH in Shanxi province. Hence, this study will help to further understand the genotype-phenotype associations in PAHD patients, and it may offer more reliable genetic counseling and management.     

Muscle responses to radicular stimulation during lumbo-sacral dorsal rhizotomy for spastic diplegia: Insights to myotome innervation

ObjectiveMost of knowledge on muscle radicular innervation was from explorations in root/spinal cord pathologies. Direct and individual access to each of the lumbar-sacral -ventral and dorsal- nerve roots during dorsal rhizotomy for spastic diplegia allows precise study of the corresponding muscle innervation. Authors report the lumbo-sacral segmental myotomal organization obtained from recordings of muscle responses to root stimulation in a 20-children prospective series.MethodsSeven key-muscles in each lower limb and anal sphincter were Electromyography (EMG)-recorded and clinically observed by physiotherapist during L2-to-S2 dorsal rhizotomy. Ventral roots (VR), for topographical mapping, and dorsal roots (DR), for segmental excitability testing, were stimulated, just above threshold for eliciting muscular response.ResultsIn 70% of the muscles studied, VR innervation was pluri-radicular, from 2-to-4 roots, with 1 or 2 roots being dominant at each level. Overlapping was important. Muscle responses to DR stimulation were 1.75 times more extended compared to VR stimulation. Inter-individual variability was important.ConclusionsAccuracy of root identification and stimulation with the used method brings some more precise information to radicular functional anatomy.SignificanceThose neurophysiological findings plead for performing Intra-Operative Neuromonitoring when dealing with surgery in the lumbar-sacral roots.     

The role of substance P in acupuncture signal transduction and effects

BackgroundAcupuncture has been used to treat a wide variety of diseases, disorders, and conditions for more than 2500 years. While the anatomical structures of acupuncture points (or acupoints) are largely unknown, our previous studies have suggested that many acupoints can be identified as cutaneous neurogenic inflammatory spots (neurogenic spots or Neuro-Sps), arising from the release of neuropeptides from activated small diameter sensory afferents at topographically distinct body surfaces due to the convergence of visceral and somatic afferents. In turn, the neuropeptides released during neurogenic inflammation may play important roles in the effects of acupuncture as well as the formation of active acupoints. Thus, the present study has focused on the role of substance P (SP) in acupuncture signal transduction and effects.MethodsNeuro-Sps were detected by using in vivo fluorescence imaging after intravenous injection of Evans blue dye (EBD) and compared with traditional acupoints. Stimulatory effects of the Neuro-Sps were examined in a rat model of immobilization-induced hypertension (IMH). The roles of increased SP in Neuro-Sps were also investigated by using immunohistochemistry, in vivo single-fiber peripheral nerve recordings, and in vivo midbrain extracellular recordings.ResultsNeurogenic inflammation quickly appeared at acupoints on the wrist and was fully developed within 15 min in IMH model. The Neuro-Sps showed an increased release of SP from afferent nerve terminals. Mechanical stimulation of these Neuro-Sps increased cell excitability in the midbrain (rostral ventrolateral medulla) and alleviated the development of hypertension, which was blocked by the local injection of the SP receptor antagonist CP-99994 into Neuro-Sps prior to acupuncture and mimicked by the local injection of capsaicin. Single fiber recordings of peripheral nerves showed that increased SP into the Neuro-Sps elevated the sensitivity of A- and C-fibers in response to acupuncture stimulation. In addition, the discharge rates of spinal wide dynamic response (WDR) neurons significantly increased following SP or acupuncture treatment in Neuro-Sps in normal rats, but decreased following the injection of CP-99994 into Neuro-Sps in IMH rats.ConclusionsOur findings suggest that SP released during neurogenic inflammation enhances the responses of sensory afferents to the needling of acupoints and triggers acupuncture signaling to generate acupuncture effects.     

Corticospinal excitability enhancement with simultaneous transcranial near-infrared stimulation and anodal direct current stimulation of motor cortex

ObjectivesNon-invasive brain stimulation (NIBS) is beneficial to many neurological and psychiatric disorders by modulating neuroplasticity and cortical excitability. However, recent studies evidence that single type of NIBS such as transcranial direct current stimulation (tDCS) does not have meaningful clinical therapeutic responses due to their small effect size. Transcranial near-infrared stimulation (tNIRS) is a novel form of NIBS. Both tNIRS and tDCS implement its therapeutic effects by modulating cortical excitability but with different mechanisms. We hypothesized that simultaneous tNIRS and tDCS is superior to single stimulation, leading to a greater cortical excitability.MethodsSixteen healthy subjects participated in a double-blind, sham-controlled, cross-over designed study. Motor evoked potentials (MEPs) were used to measure motor cortex excitability. The changes of MEP were calculated and compared in the sham condition, tDCS stimulation condition, tNIRS condition and the simultaneous tNIRS and anodal tDCS condition.ResultstDCS alone and tNIRS alone both elicited higher MEP after stimulation, while the MEP amplitude in the simultaneous tNIRS and tDCS condition was significantly higher than either tNIRS alone or tDCS alone. The enhancement lasted up to at least 30 minutes after stimulation, indicating simultaneous 820 nm tNIRS with 2 mA anodal tDCS have a synergistic effect on cortical plasticity.ConclusionsSimultaneous application of tNIRS with tDCS produces a stronger cortical excitability effect.SignificanceThe simultaneous tNIRS and tDCS is a promising technology with exciting potential as a means of treatment, neuro-enhancement, or neuro-protection.     

Improved object recognition memory using post-encoding repetitive transcranial magnetic stimulation

BackgroundBrain stimulation is known to affect canonical pathways and proteins involved in memory. However, there are conflicting results on the ability of brain stimulation to improve to memory, which may be due to variations in timing of stimulation.HypothesisWe hypothesized that repetitive transcranial magnetic stimulation (rTMS) given following a learning task and within the time period before retrieval could help improve memory.MethodsWe implanted male B6129SF2/J mice (n = 32) with a cranial attachment to secure the rTMS coil so that the mice could be given consistent stimulation to the frontal area whilst freely moving. Mice then underwent the object recognition test sampling phase and given treatment +3, +24, +48 h following the test. Treatment consisted of 10 min 10 Hz rTMS stimulation (TMS, n = 10), sham treatment (SHAM, n = 11) or a control group which did not do the behavior test or receive rTMS (CONTROL n = 11). At +72 h mice were tested for their exploration of the novel vs familiar object.ResultsAt 72-h's, only the mice which received rTMS had greater exploration of the novel object than the familiar object. We further show that promoting synaptic GluR2 and maintaining synaptic connections in the perirhinal cortex and hippocampal CA1 are important for this effect. In addition, we found evidence that these changes were linked to CAMKII and CREB pathways in hippocampal neurons.ConclusionBy linking the known biological effects of rTMS to memory pathways we provide evidence that rTMS is effective in improving memory when given during the consolidation and maintenance phases.