Motor Evoked Potential Recruitment Curves Research Articles

Decoding firings of a large population of human motor units from high-density surface electromyogram in response to transcranial magnetic stimulation.

We describe a novel application of methodology for high-density surface electromyography (HDsEMG) decomposition to identify motor unit (MU) firings in response to transcranial magnetic stimulation (TMS). The method is based on the MU filter estimation from HDsEMG decomposition with convolution kernel compensation during voluntary isometric contractions and its application to contractions elicited by TMS. First, we simulated synthetic HDsEMG signals during voluntary contractions followed by simulated motor evoked potentials (MEPs) recruiting an increasing proportion of the motor pool. The estimation of MU filters from voluntary contractions and their application to elicited contractions resulted in high (>90%) precision and sensitivity of MU firings during MEPs. Subsequently, we conducted three experiments in humans. From HDsEMG recordings in first dorsal interosseous and tibialis anterior muscles, we demonstrated an increase in the number of identified MUs during MEPs evoked with increasing stimulation intensity, low variability in the MU firing latency and a proportion of MEP energy accounted for by decomposition similar to voluntary contractions. A negative relationship between the MU recruitment threshold and the number of identified MU firings was exhibited during the MEP recruitment curve, suggesting orderly MU recruitment. During isometric dorsiflexion we also showed a negative association between voluntary MU firing rate and the number of firings of the identified MUs during MEPs, suggesting a decrease in the probability of MU firing during MEPs with increased background MU firing rate. We demonstrate accurate identification of a large population of MU firings in a broad recruitment range in response to TMS via non-invasive HDsEMG recordings. KEY POINTS: Transcranial magnetic stimulation (TMS) of the scalp produces multiple descending volleys, exciting motor pools in a diffuse manner. The characteristics of a motor pool response to TMS have been previously investigated with intramuscular electromyography (EMG), but this is limited in its capacity to detect many motor units (MUs) that constitute a motor evoked potential (MEP) in response to TMS. By simulating synthetic signals with known MU firing patterns, and recording high-density EMG signals from two human muscles, we show the feasibility of identifying firings of many MUs that comprise a MEP. We demonstrate the identification of firings of a large population of MUs in the broad recruitment range, up to maximal MEP amplitude, with fewer required stimuli compared to intramuscular EMG recordings. The methodology demonstrates an emerging possibility to study responses to TMS on a level of individual MUs in a non-invasive manner.

Can tDCS affect acquisition of a simple motor skill in neurotypical adults?

Abstract Excitatory tDCS (positive current into the brain) enhances skill acquisition and task dependent adaptation (TDA). Little is known about tDCS impact on spinal cord. Spinal reflexes participate in movements, change through life, and can be modified by experience or injury (Ann Rev Neurosci 24: 807-843). People can change spinal reflex size through operant conditioning (J Neurosci 29: 5784-5792). Acquiring this simple motor skill (larger or smaller reflex size) requires supraspinal drive (J Neurophysiol 87: 645-652). This study asks if tDCS affects the magnitude or consistency of H-reflex conditioning. The MUSC IRB approved the study. Neurotypical participants receive Active (excitatory, 2mA, 0.06mA/cm2, 30m) or Sham tDCS over contralateral leg region of primary motor cortex during soleus H-reflex down-conditioning. Tibial nerve stimulation elicits H-reflexes. Participants stand comfortably and maintain soleus background activity in a defined range. In 4 Baseline (BL) sessions, H-reflexes are simply recorded (control trials, three 75-trial blocks). In 12 subsequent Conditioning sessions (CS), participants practice reducing the H-reflex (conditioning trials, 3 blocks of 75). Visual feedback about reflex size follows each conditioning trial. Every session collects H-reflex recruitment curves (RCs) and control reflexes. TMS MEP RCs are collected periodically. A 1-month follow-up examines retention. To date, 8 participants (4 women, 5 Active tDCS, Age 22-36) have completed the study. Final conditioned H-reflex sizes (mean of CSs 10-12 as % BL) were 58, 67, 90, 99, 215% for Active and 71,115,125% for Sham participants. MEPmax change was -0.66, -0.28, -0.07, +0.04, +0.30mv and +0.09, +0.11, +1.11mV, Active and Sham respectively. The study is ongoing. The full results may illuminate tDCS impact on skill acquisition and guide its therapeutic applications as a neuromodulator. Keywords: tDCS, Hoffman reflex, operant conditioning, motor learning

Transcutaneous Electrical Neuromodulation of the Cervical Spinal Cord Depends Both on the Stimulation Intensity and the Degree of Voluntary Activity for Training. A Pilot Study

Electrical enabling motor control (eEmc) through transcutaneous spinal cord stimulation offers promise in improving hand function. However, it is still unknown which stimulus intensity or which muscle force level could be better for this improvement. Nine healthy individuals received the following interventions: (i) eEmc intensities at 80%, 90% and 110% of abductor pollicis brevis motor threshold combined with hand training consisting in 100% handgrip strength; (ii) hand training consisting in 100% and 50% of maximal handgrip strength combined with 90% eEmc intensity. The evaluations included box and blocks test (BBT), maximal voluntary contraction (MVC), F wave persistency, F/M ratio, spinal and cortical motor evoked potentials (MEP), recruitment curves of spinal MEP and cortical MEP and short-interval intracortical inhibition. The results showed that: (i) 90% eEmc intensity increased BBT, MVC, F wave persistency, F/M ratio and cortical MEP recruitment curve; 110% eEmc intensity increased BBT, F wave persistency and cortical MEP and recruitment curve of cortical MEP; (ii) 100% handgrip strength training significantly modulated MVC, F wave persistency, F/M wave and cortical MEP recruitment curve in comparison to 50% handgrip strength. In conclusion, eEmc intensity and muscle strength during training both influence the results for neuromodulation at the cervical level.

Priming Effects of Water Immersion on Paired Associative Stimulation-Induced Neural Plasticity in the Primary Motor Cortex.

We aimed to verify whether indirect-wave (I-wave) recruitment and cortical inhibition can regulate or predict the plastic response to paired associative stimulation with an inter-stimulus interval of 25 ms (PAS25), and also whether water immersion (WI) can facilitate the subsequent PAS25-induced plasticity. To address the first question, we applied transcranial magnetic stimulation (TMS) to the M1 hand area, while alternating the direction of the induced current between posterior-to-anterior and anterior-to-posterior to activate two independent synaptic inputs to the corticospinal neurons. Moreover, we used a paired stimulation paradigm to evaluate the short-latency afferent inhibition (SAI) and short-interval intracortical inhibition (SICI). To address the second question, we examined the motor evoked potential (MEP) amplitudes before and after PAS25, with and without WI, and used the SAI, SICI, and MEP recruitment curves to determine the mechanism underlying priming by WI on PAS25. We demonstrated that SAI, with an inter-stimulus interval of 25 ms, might serve as a predictor of the response to PAS25, whereas I-wave recruitment evaluated by the MEP latency difference was not predictive of the PAS25 response, and found that 15 min WI prior to PAS25 facilitated long-term potentiation (LTP)-like plasticity due to a homeostatic increase in cholinergic activity.

The Effects of Biological Sex and Ovarian Hormones on Exercise-Induced Neuroplasticity

Acute aerobic exercise induces short-term neuroplasticity, although it remains unknown whether biological sex and ovarian hormones influence this response. The present study investigated the effects of biological sex and ovarian hormones on short-term neuroplasticity induced by acute aerobic exercise. Young active adults (n = 17 males and n = 17 females; 21 ± 2 years) participated in two sessions in which transcranial magnetic stimulation (TMS) measures were acquired immediately before and after a 20-min bout of moderate-intensity cycling at 65–70% of maximal heart rate. Females were tested in the follicular (~day 7) and luteal (~day 21) phases of the menstrual cycle. Males were tested on two sessions separated by ~14 days. Measures of motor-evoked potential (MEP) recruitment curves and short-interval intracortical inhibition (SICI) were obtained using TMS. Estradiol, progesterone, testosterone, brain-derived neurotrophic factor (BDNF), and insulin-like growth factor 1 (IGF-1) were measured in venous blood samples obtained prior to exercise. MEP recruitment curves increased and SICI decreased after exercise in both sexes, regardless of menstrual cycle phase. BDNF and IGF-1 were not different between sexes or across the menstrual cycle. Females had a greater estradiol to progesterone ratio (E:P) in the follicular phase compared to the luteal phase, while males had similar testosterone levels on both occasions. We conclude that biological sex and ovarian hormones do not impact short-term neuroplasticity induced by acute exercise. Significance StatementAcute exercise induces short-term changes indicative of neuroplasticity within the primary motor cortex and corticospinal pathway. This research reveals that increases in corticospinal excitability and decreases in intracortical inhibition occur similarly in males and females, and that female hormones do not influence these changes. These findings may be used to assist with developing exercise interventions aimed at promoting neuroplasticity in both sexes.

GABA-ergic tone hypothesis in hepatic encephalopathy – Revisited

ObjectiveThe GABA hypothesis of hepatic encephalopathy (HE) proposes an increased cerebral GABA-ergic tone in HE but has not been investigated in vivo in HE-patients yet. Cortical GABA-ergic and glutamatergic neurotransmission in HE-patients were evaluated using transcranial magnetic stimulation. MethodsTwenty-one patients with HE grade 1 and 2 and age matched controls participated in the study. GABA-ergic (short- and long-interval intracortical inhibition (SICI and LICI)) and glutamatergic (intracortical and short-interval intracortical facilitation (ICF and SICF)) excitability of the primary motor cortex (M1) and global corticospinal excitability (motor threshold, motor evoked potential recruitment curve (MEP-RC) were compared between the groups. SICI and ICF were correlated to the critical flicker frequency (CFF) as measure for disease severity. ResultsIn HE-patients, the slope of MEP-RC was significantly shallower compared to healthy controls. SICI was significantly reduced in patients with HE grade 2 compared to healthy controls. In HE-patients, SICI and ICF was significantly correlated to CFF. ConclusionAlthough global corticospinal excitability was reduced in HE-patients, GABA-ergic inhibition was reduced in M1 depending on HE severity. Moreover CFF related alteration of GABAergic and glutamatergic neurotransmission in patients with HE could support the notion of a severity dependent alteration of cortical excitability. SignificanceThe decrease of cortical GABA-ergic tone challenges the classical GABA hypothesis in HE.

Transcranial focused ultrasound neuromodulation of the human primary motor cortex

Transcranial focused ultrasound is an emerging form of non-invasive neuromodulation that uses acoustic energy to affect neuronal excitability. The effect of ultrasound on human motor cortical excitability and behavior is currently unknown. We apply ultrasound to the primary motor cortex in humans using a novel simultaneous transcranial ultrasound and magnetic stimulation paradigm that allows for concurrent and concentric ultrasound stimulation with transcranial magnetic stimulation (TMS). This allows for non-invasive inspection of the effect of ultrasound on motor neuronal excitability using the motor evoked potential (MEP). We test the effect of ultrasound on single pulse MEP recruitment curves and paired pulse protocols including short interval intracortical inhibition (SICI) and intracortical facilitation (ICF). In addition, we test the effect of ultrasound to motor cortex on a stimulus response reaction time task. Results show ultrasound inhibits the amplitude of single-pulse MEPs and attenuates intracortical facilitation but does not affect intracortical inhibition. Ultrasound also reduces reaction time on a simple stimulus response task. This is the first report of the effect of ultrasound on human motor cortical excitability and motor behavior and confirms previous results in the somatosensory cortex that ultrasound results in effective neuronal inhibition that confers a performance advantage.

P067 Stage dependent alteration of cortical excitability in patients with hepatic encephalopathy

Altered cortical excitability is supposed to play a relevant role in the pathophysiology of hepatic encephalopathy (HE). However, most data is based on animal studies and only limited data of patients with HE is available. We therefore investigated cortical excitability in HE-patients at different disease stages using transcranial magnetic stimulation. In eleven patients with HE stage 1, ten patients with HE stage 2 and ten age matched healthy control subjects several measures for cortical excitability of the primary motor cortex, i. e. motor threshold, motor evoked potential recruitment curve (MEP-RC), short interval intracortical inhibition (SICI), long interval intracortical inhibition, intracortical facilitation and short interval intracortical facilitation were compared. The critical flicker frequency (CFF) was also measured as one marker of disease severity. In HE-patients the slope of the MEP-RC was shallower compared to healthy controls. Moreover SICI was significantly reduced in HE stage 2 patients compared to healthy controls and a relevant correlation between SICI and CFF was found. No differences were found in the other measures. Our results suggest a disease stage dependent alteration of motor cortical and corticospinal excitability in patients with HE.

Recent History of Effector Use Modulates Practice-Dependent Changes in Corticospinal Excitability but Not Motor Learning.

The theory of homeostatic metaplasticity has significant implications for human motor cortical plasticity and motor learning. Previous work has shown that the extent of recent effector use before exogenously-induced plasticity can affect the direction, magnitude and variability of aftereffects. However, the impact of recent effector use on motor learning and practice-dependent plasticity is not known. We hypothesized that reducing effector use for 8 hours via hand/wrist immobilization would facilitate practice-dependent changes in corticospinal excitability and TMS-evoked thumb movement kinematics, while also promoting 24-hour retention of a ballistic motor skill. Subjects participated in a crossover study involving two conditions. During the immobilization condition, subjects wore a splint that restricted motion of the left hand and thumb for 8 hours. While wearing the splint, subjects were instructed to avoid using their left hand as much as possible. During the control condition, subjects did not wear a splint at any time nor were they instructed to avoid hand use. After either an 8 hour period of immobilization or normal hand use, we collected MEP and TMS-evoked thumb movement recruitment curves, and subjects practiced a ballistic motor skill involving rapid thumb extension. After motor practice, MEP and TMS-evoked thumb movement recruitment curves were re-tested. Retention of the motor skill was tested 30 minutes and 24 hours after motor practice. Reduced effector use did not impact pre-practice corticospinal excitability but did facilitate practice-dependent changes in corticospinal excitability, and this enhancement was specific to the trained muscle. In contrast, reducing effector use did not affect practice-dependent changes in TMS-evoked thumb movements nor did it promote acquisition or retention of the skill. Finally, we detected some associations between pre-practice excitability levels, plasticity effects and learning effects, but these did not reach our adjusted criterion for significance. Experimentally enhancing practice-dependent changes in corticospinal excitability is not sufficient to promote learning or memory of a ballistic motor skill.

Stage dependent alteration of cortical excitability in patients with hepatic encephalopathy

Question Altered cortical excitability is supposed to play a relevant role in the pathophysiology of hepatic encephalopathy (HE). However, most data is based on animal studies and only limited data of patients with HE is available. We therefore investigated cortical excitability in HE-patients at different disease stages using transcranial magnetic stimulation. Methods In eleven patients with HE stage 1, ten patients with HE stage 2 and ten age matched healthy control subjects several measures for cortical excitability of the primary motor cortex, i. e. motor threshold, motor evoked potential recruitment curve (MEP-RC), short interval intracortical inhibition (SICI), long interval intracortical inhibition, intracortical facilitation and short interval intracortical facilitation were compared. The critical flicker frequency (CFF) was also measured as one marker of disease severity. Results In HE-patients the slope of the MEP-RC was shallower compared to healthy controls. Moreover SICI was significantly reduced in HE stage 2 patients compared to healthy controls and a relevant correlation between SICI and CFF was found. No differences were found in the other measures. Conclusion Our results suggest a disease stage dependent alteration of motor cortical and corticospinal excitability in patients with HE.

6. The Fampridine Upper Limb Study: Baseline clinical and electrophysiological data

Aim To describe initial clinical and electrophysiological results from the Fampridine Upper Limb Study, conducted in patients with Multiple Sclerosis (MS) and upper limb impairment. Methods This randomised, double-blinded placebo controlled trial of modified-release fampridine comprises three groups: patients on drug, patients on placebo and healthy controls. Baseline assessments conducted prior to initiation of drug (fampridine-MR 10 mg bd) or placebo included the following clinical tests: 9-hole peg test, manual grip strength, sensory discrimination capacity, visual acuity & contrast sensitivity, Fatigue Impact Scale score. Baseline electrophysiological tests included the following: visual evoked potential latency and amplitude, somatosensory evoked potential, median motor and sensory nerve conduction studies & F-waves, resting motor threshold, MEP latency, paired-pulse transcranial magnetic stimulation, MEP recruitment curves. Comparisons were made at baseline between MS patients and controls, and between patients with different MS subtypes (RRMS, PPMS, SPMS). Correlations were made between clinical and electrophysiological measures at baseline. Results 40 patients (60% female, median age 52 years) with MS and upper limb impairment and 20 healthy controls (60% female, median age 53 years) were studied. Of the patients, 9 had RRMS, 18 had SPMS and 13 had PPMS. The results of clinical measures of hand function (9-hole peg test, manual grip strength) and electrophysiological tests of nervous system function (VEP latency & amplitude, SSEP latency, MEP latency, resting motor threshold, MEP recruitment and PPTMS) are reported and compared between patients and controls and between patients with different subtypes of MS disease course. Conclusion Evoked potentials and TMS measures differ between MS patients and healthy controls, with observable differences between patients with different subtypes of MS. Such electrophysiological markers may represent useful surrogate markers in clinical trials of symptomatic and disease-modifying therapies for MS.

Distinct interneuronal networks influence excitability of the surround during movement initiation.

Surround inhibition (SI) is a feature of motor control in which activation of task-related muscles is associated with inhibition of neighboring, nonprotagonist muscles, allowing selective motor control. The physiological basis for SI still remains unknown. In all previous studies, SI in the motor system was measured during movement initiation by using transcranial magnetic stimulation (TMS) to deliver a posteroanterior current at a single suprathreshold intensity. To expand our understanding of SI, we explored this phenomenon at a wide range of intensities and by stimulating motor cortex with currents along anteroposterior and lateromedial directions. Fifteen healthy volunteers performed a brief isometric index finger flexion on hearing a tone. Electromyography was recorded from the synergist and surround finger muscles. Single-pulse TMS was applied to stimulate the surround muscle at different intensities at rest or movement initiation. The motor evoked potential (MEP) amplitudes were then plotted against stimulation intensities to obtain the MEP recruitment curves for the rest and movement initiation conditions and for the three current directions for every subject. From the recruitment curves, we found that surround inhibition could be elicited only by the posteroanterior current. Hence, we postulate that surround inhibition is mediated by intracortical circuits in the motor cortex. Also, for the first time, we observed surround facilitation when the motor cortex was stimulated with anteroposterior current. Further studies are needed to investigate the mechanisms underlying both these phenomena individually in healthy subjects and patients with dystonia and other movement disorders.

Assessment of corticospinal excitability after traumatic spinal cord injury using MEP recruitment curves: a preliminary TMS study.

Transcranial magnetic stimulation study. To further investigate the corticospinal excitability changes after spinal cord injury (SCI), as assessed by means of transcranial magnetic stimulation (TMS). Merano (Italy) and Salzburg (Austria). We studied resting motor threshold (RMT), motor evoked potential (MEP) amplitude and recruitment curve in five subjects with good recovery after traumatic incomplete cervical SCI. RMT did not differ significantly between patients and controls, whereas the slope of MEP recruitment curve was significantly increased in the patients. This abnormal finding may represent an adaptive response after SCI. The impaired ability of the motor cortex to generate proper voluntary movement may be compensated by increasing spinal excitability. The easily performed measurement of MEP recruitment curve may provide a useful additional tool to improve the assessment and monitoring of motor cortical function in subjects with SCI. Increasing our knowledge of the corticospinal excitability changes in the functional recovery after SCI may also support the development of effective therapeutic strategies.

Short-latency afferent inhibition in chronic spinal cord injury.

BackgroundShort-latency afferent inhibition (SAI) results when somatosensory afferent input inhibits the corticospinal output from primary motor cortex (M1). The present study examined SAI in the flexor carpi radialis (FCR) muscle in individuals with spinal cord injury (SCI) and uninjured controls.MethodsShort-latency afferent inhibition (SAI) was evoked by stimulating the median nerve at the elbow at intervals of 15, 20 and 25 ms in advance of a transcranial magnetic stimulation (TMS) pulse over M1. SAI was tested with the FCR at rest and also during ~20% of maximum voluntary contraction. Corticospinal output was assessed through measuring both motor thresholds and motor evoked potential (MEP) recruitment curves. The afferent volley was assessed via the N20–P25 amplitude of the somatosensory evoked potential (SEP) and the amplitude of sensory nerve action potentials (SNAP) recorded over the median nerve at the elbow.ResultsSAI is reduced in SCI in both the contracted and non-contracted FCR muscle. MEP recruitment curves and thresholds were decreased in SCI only in the active state and not the resting state. N20–P25 amplitude was similar between groups in both the resting and active states although SNAP was significantly reduced in SCI at rest.ConclusionsWe conclude that reduced SAI in SCI is likely attributed to neuroplasticity altering the intrinsic M1 circuitry mediating SAI and/or reduced afferent input traversing a direct thalamocortical route to M1. These data provide a new avenue of research aimed at identifying therapeutic approaches to alter SAI to improve upper limb function in individuals with SCI.

Enhanced motor cortex excitability after spinal cord injury.

Enhanced motor cortex excitability after spinal cord injury.

119. Cortical excitability in patients affected by brain tumors

In this study we investigated cortical excitability, inhibitory and excitatory intracortical circuitries, by using transcranial magnetic stimulation, in both hemispheres of patients affected by brain tumors. Cortical excitability was probed with transcranial magnetic stimulation in 10 right-handed patients (3 women), aged 49–70 years (mean age: 54.8 years) and 10 age-matched healthy controls. We tested motor thresholds (MT), motor evoked potential (MEP) recruitment curve, cortical silent period (CSP), short and long intracortical inhibition (SICI and LICI), intracortical facilitation (ICF), short and long afferent inhibition (SAI and LAI) and inter-hemispheric inhibition (IHI). RMT and AMT were higher in both hemispheres of patients with brain tumors than healthy controls. The slope of MEP recruitment curve was deeper in both hemispheres of patients with brain tumors. SICI, LICI, SAI and LAI are reduced in patients with brain tumors compared with aged matched healthy controls. Cortical excitability, specially inhibitory intracortical circuitries, are impaired in both hemispheres of patients affected by brain tumors.

P 14. A detailed evaluation of surround inhibition in human motor cortex using transcranial magnetic stimulation

Surround inhibition (SI) is a feature of motor control for which the physiology is still unknown (Beck and Hallett, 2011) . This phenomenon is impaired in patients with focal hand dystonia Sohn and Hallett, 2004 , Beck et al., 2008 and hence it becomes relevant to study it more in detail. Several studies have demonstrated SI in the human motor system using transcranial magnetic stimulation (TMS) Beck et al., 2008 , Sohn and Hallett, 2004 , Kassavetis et al., 2012 . In all these studies SI was measured by applying a single suprathreshold TMS pulse during the movement initiation phase. The figure of eight coil was positioned such that it induced current along the postero-anterior direction in the brain. We were interested to study SI not just at a single intensity, but at intensities ranging from sub-threshold to supra-threshold levels. Also, we wanted to explore if SI could be elicited when the motor cortex was stimulated along other directions (antero-posterior, latero-medial). 10 healthy volunteers participated in the study. Their task was to perform a brief isometric index finger flexion on hearing a tone. EMG was recorded from the first dorsal interosseous (active muscle) and the abductor pollicis brevis (surround muscle). Single pulse TMS was applied at intensities ranging from 20% to 100% of maximum stimulator output at 5% intervals either before the tone (rest) or after the tone ∼75 ms before expected onset of muscle activity (SI). The MEP amplitudes were then plotted against stimulation intensities to obtain the MEP recruitment curves for the rest and SI conditions separately. The recruitment curves were plotted with the coil held in three directions (P-A, A-P, L-M) for every subject. We found that SI can be elicited when the coil was positioned in the P-A direction and only within a certain range of supra-threshold intensities. Maximum SI was seen around 150%MT. Stimulating the motor cortex along the A-P direction did not elicit SI, rather showed facilitation that peaked at around 120%MT. We can therefore conclude that SI can be elicited in those neuronal groups that can be stimulated best along the PA direction.

P 79. Effects of brain derived neurotrophic factor polymorphism on cortical excitability measured by transcranial magnetic stimulation

Variation in the brain derived neurotrophic factor (BDNF) gene affects neural plasticity. With the commonly studied single nucleotide polymorphism (SNP) BDNF Val66Met, the Met allele is associated with reduced plasticity. However, little is known about the baseline excitability measures of rarer form Met/Met compared to other forms and the response to plasticity and metaplasticity protocols using transcranial magnetic stimulation (TMS). To investigate the effects of the BDNF Val66Met SNP on motor cortex excitability, inhibition, facilitation, plasticity and metaplasticity. From 177 healthy volunteers we selected 7 subjects with the rare (around 5–10% of population) Met/Met genotype and compared them to 9 age-and gender-matched Val allele carriers on various excitability measures using TMS. Motor threshold, recruitment curves, short and long interval intracortical inhibition (SICI and LICI), short interval intracortical facilitation (SICF) and time courses of these circuits were studied. Potentiation [high frequency rTMS and paired associative stimulation at 25 ms latency (PAS25)] and depression (low frequency rTMS and PAS10) protocols as well as interactions of these plasticity protocols (metaplasticity) were studied with sessions separated at least by a week (6 sessions in total). Met/Met subjects showed higher motor threshold (61.7 ± 8.6% stimulator output compared to 48.7 ± 9.5; p = 0.01), and less steep recruitment curves (significant main effects and interaction for BDNF genotype and TMS intensity). There was no significant difference between the groups in terms of intracortical inhibitory circuits, the time course and recruitment curves for SICI/LICI. There was a trend for reduced facilitation at the peaks (1.5, 3 and 4 ms) for SICF in Met/Met compared to non-Met/Met subjects. For plasticity protocols, there was significantly higher potentiation of MEP amplitude with high frequency rTMS (main effects of BDNF genotype) and a trend of greater MEP depression with PAS10 in non-Met/Met subjects. No difference was noted in the other plasticity and metaplasticity protocols. Met/Met subjects had higher motor threshold, less steep MEP recruitment curves and reduced peaks of SICF, implying lower cortical excitability compared to non-Met/Met genotypes. This decreased excitability in Met/Met subjects is associated with less potentiation induced by high frequency rTMS. Our study is ongoing and more subjects are being recruited to compare the three BDNF genotypes (Met/Met, Val/Met and Val/Val genotypes) of subjects. Support by Canadian Institutes of Health Research.

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.

Increased motor cortical excitability after whole-hand electrical stimulation: A TMS study

To examine the neuromodulatory effect of whole-hand mesh-glove (MG) stimulation on motor cortical pathways, we explored motor cortical excitability before and after suprathreshold whole-hand MG stimulation using transcranial magnetic stimulation (TMS). Twenty-eight healthy volunteers (14 controls) were studied at baseline, immediately post and 1h post-MG stimulation for 30 min. Motor thresholds (MTs), motor evoked potentials (MEPs) recruitment curve, short intracortical inhibition (SICI) and intracortical facilitation (ICF) after paired magnetic stimuli were evaluated. After MG stimulation the MTs were significantly reduced and slope of MEP recruitment curve significantly increased; furthermore, the stimulation led to a sustained decrease of SICI and increase of ICF in the contralateral motor cortex. These effects lasted for at least 60 min and were stronger 1h post-stimulation compared with testing immediately after stimulation. A sham group did not show any differences before and after MG stimulation. We provide a first demonstration that MG whole-hand stimulation induces increases in motor cortical excitability lasting at least 1h. Both the strength of the corticospinal projections and the inhibitory and facilitatory intracortical mechanisms are involved. Synaptic modifications such as long-term potentiation mechanisms may underlie this stimulation-induced cortical plasticity changes. Present results prove the MG stimulation to be a promising tool in neurorehabilitation.