Corticospinal Excitability Research Articles

Muscarinic acetylcholine activity modulates cortical silent period, but not motor evoked potentials, during muscle contractions

This study used transcranial magnetic stimulation (TMS) to determine if muscarinic receptor blockade affects muscle responses during voluntary contractions. Motor evoked potentials (MEPs) were recorded from biceps brachii in 10 subjects (age: 23 ± 2) during 10%, 25%, 50%, 75%, and 100% maximal voluntary contractions (MVCs). Each contraction intensity was examined under non-fatigued and fatigued conditions. All measurements were obtained post-ingestion of 25 mg promethazine or placebo. MEP area and the duration of the TMS-evoked silent period (SP) were calculated for all contractions. No drug-related differences were detected for MEP area during non-fatigued or fatigued contractions. A main effect of drug was detected for the SP (p = 0.019) where promethazine increased SP duration by an average of 0.023 pm 0.015 s. This drug effect was only identified for the unfatigued contractions and not following the sustained fatiguing contractions (p = 0.105). The cholinergic system does not influence corticospinal excitability during voluntary muscle contractions, but instead affects neural circuits associated with the TMS-evoked SP. Given the prevalence of cholinergic properties in prescription and over-the-counter medications, the current study enhances our understanding of mechanisms that may contribute to motor side-effects.

Enhanced skeletal muscle contractile function and corticospinal excitability precede strength and architectural adaptations during lower-limb resistance training

PurposeEvolving investigative techniques are providing greater understanding about the early neuromuscular responses to resistance training among novice exercisers. The aim of this study was to investigate the time-course of changes in muscle contractile mechanics, architecture, neuromuscular, and strength adaptation during the first 6-weeks of lower-limb resistance training.MethodsForty participants: 22 intervention (10 males/12 females; 173.48 ± 5.20 cm; 74.01 ± 13.13 kg) completed 6-week resistance training, and 18 control (10 males/8 females; 175.52 ± 7.64 cm; 70.92 ± 12.73 kg) performed no resistance training and maintained their habitual activity. Radial muscle displacement (Dm) assessed via tensiomyography, knee extension maximal voluntary contraction (MVC), voluntary activation (VA), corticospinal excitability and inhibition via transcranial magnetic stimulation, motor unit (MU) firing rate, and muscle thickness and pennation angle via ultrasonography were assessed before and after 2, 4, and 6-weeks of dynamic lower-limb resistance training or control.ResultsAfter 2-weeks training, Dm reduced by 19–25% in the intervention group; this was before any changes in neural or morphological measures. After 4-weeks training, MVC increased by 15% along with corticospinal excitability by 16%; however, there was no change in VA, corticospinal inhibition, or MU firing rate. After 6-weeks training there was further MVC increase by 6% along with muscle thickness by 13–16% and pennation angle by 13–14%.ConclusionEnhanced contractile properties and corticospinal excitability occurred before any muscle architecture, neural, and strength adaptation. Later increases in muscular strength can be accounted for by architectural adaptation.

Corticospinal excitability and reflex modulation in a contralateral non-stretched muscle following unilateral stretching.

Muscle stretching effect on the range of motion (ROM) and force deficit in non-stretched muscle, and the underlying mechanisms, is an ongoing issue. This study aimed to investigate crossover stretching effects and mechanisms on the plantar flexor muscles. Fourteen recreationally active females (n = 5) and males (n = 9) performed six sets of 45-s static stretching (SS) (15-s recovery) to the point of discomfort of the dominant leg (DL) plantar flexors or control (345-s rest). Participants were tested for a single 5-s pre- and post-test maximal voluntary isometric contraction (MVIC) with each plantar flexor muscle and were tested for DL and non-DL ROM. They were tested pre- and post-test (immediate, 10-s, 30-s) for the Hoffman (H)-reflex and motor-evoked potentials (MEP) from transcranial magnetic stimulation in the contralateral, non-stretched muscle. Both the DL and non-DL-MVIC force had large magnitude, significant (↓10.87%, p = 0.027, pƞ2 = 0.4) and non-significant (↓9.53%, p = 0.15, pƞ2 = 0.19) decreases respectively with SS. The SS also significantly improved the DL (6.5%, p < 0.001) and non-DL (5.35%, p = 0.002) ROM. The non-DL MEP/MMax and HMax/MMax ratio did not change significantly. Prolonged static stretching improved the stretched muscle's ROM. However, the stretched limb's force was negatively affected following the stretching protocol. The ROM improvement and large magnitude force impairment (statistically non-significant) were transferred to the contralateral muscles. The lack of significant changes in spinal and corticospinal excitability confirms that the afferent excitability of the spinal motoneurons and corticospinal excitability may not play a substantial role in non-local muscle's ROM or force output responses.

Enhanced corticospinal excitability in the tibialis anterior during static stretching of the soleus in young healthy individuals.

Corticospinal excitability is known to be affected by afferent inflow arising from the proprioceptors during active or passive muscle movements. Also during static stretching (SS) afferent activity is enhanced, but its effect on corticospinal excitability received limited attention and has only been investigated as a single average value spread over the entire stretching period. Using transcranial magnetic stimulation (TMS) the present study was conducted to explore the time course of corticospinal excitability during 30 seconds SS. Motor evoked potentials (MEPs) after TMS were recorded from soleus (SOL) and tibialis anterior (TA) muscles in 14 participants during: a passive dynamic ankle dorsiflexion (DF), at six different time points during maximal individual SS (3, 6, 9, 18, 21 and 25 seconds into stretching), during a passive dynamic ankle plantar flexion (PF) and following SS. To explore the time course of corticospinal excitability during the static lengthened phase of a muscle stretch, the stretching protocol was repeated several times so that it was possible to collect a sufficient number of stimulations at each specific time point into SS, as well as during DF and PF. During passive DF, MEPs amplitude was greater than baseline in both TA and SOL (p = .001 and p = .005 respectively). During SS, MEPs amplitude was greater than baseline in TA (p = .006), but not in SOL. No differences between the investigated time points were found and no trend was detected throughout the stretching time. No effect in either muscle was observed during passive PF and after SS. These results could suggest that an increased activity of secondary afferents from SOL muscle spindles exert a corticomotor facilitation on TA. The muscle-nonspecific response observed during passive DF could instead be attributed to an increased activation within the sensorimotor cortical areas as a result of the awareness of the foot passive displacements.

Aerobic exercise and action observation priming modulate functional connectivity.

Aerobic exercise and action observation are two clinic-ready modes of neural priming that have the potential to enhance subsequent motor learning. Prior work using transcranial magnetic stimulation to assess priming effects have shown changes in corticospinal excitability involving intra- and interhemispheric circuitry. The objective of this study was to determine outcomes exclusive to priming- how aerobic exercise and action observation priming influence functional connectivity within a sensorimotor neural network using electroencephalography. We hypothesized that both action observation and aerobic exercise priming would alter resting-state coherence measures between dominant primary motor cortex and motor-related areas in alpha (7-12 Hz) and beta (13-30 Hz) frequency bands with effects most apparent in the high beta (20-30 Hz) band. Nine unimpaired individuals (24.8 ± 3 years) completed a repeated-measures cross-over study where they received a single five-minute bout of action observation or moderate-intensity aerobic exercise priming in random order with a one-week washout period. Serial resting-state electroencephalography recordings acquired from 0 to 30 minutes following aerobic and action observation priming revealed increased alpha and beta coherence between leads overlying dominant primary motor cortex and supplementary motor area relative to pre- and immediate post-priming timepoints. Aerobic exercise priming also resulted in enhanced high beta coherence between leads overlying dominant primary motor and parietal cortices. These findings indicate that a brief bout of aerobic- or action observation-based priming modulates functional connectivity with effects most pronounced with aerobic priming. The gradual increases in coherence observed over a 10 to 30-minute post-priming window may guide the pairing of aerobic- or action observation-based priming with subsequent training to optimize learning-related outcomes.

Modulating motor resonance with paired associativestimulation: Neurophysiological and behavioral outcomes

In the human brain, paired associative stimulation (PAS), a non-invasive brain stimulation technique based on Hebbian learning principles, can be used to model motor resonance, the inner activation of an observer's motor system by action observation. Indeed, the newly developed mirror PAS (m-PAS) protocol, through the repeatedly pairing of transcranial magnetic stimulation (TMS) pulses over the primary motor cortex (M1) and visual stimuli depicting index–finger movements, allows the emergence of a new, atypical pattern of cortico-spinal excitability. In the present study, we performed two experiments to explore (a) the debated hemispheric lateralization of the action-observation network and (b) the behavioral after-effects of m-PAS, particularly concerning a core function of the MNS: automatic imitation.In Experiment 1, healthy participants underwent two sessions of m-PAS, delivered over the right and left M1. Before and after each m-PAS session, motor resonance was assessed by recording motor-evoked potentials induced by single-pulse TMS applied to the right M1 while observing contralateral (left) and ipsilateral (right) index–finger movements or static hands. In Experiment 2, participants performed an imitative compatibility task before and after the m-PAS targeting the right M1. Results showed that only m-PAS targeting the right hemisphere, non-dominant in right-handed people, induced the emergence of motor resonance for the conditioned movement, absent before the stimulation. This effect is not present when m-PAS target the M1 of the left hemisphere. Importantly, the protocol also affects behavior, modulating automatic imitation in a strictly somatotopic fashion (i.e., influencing the imitation of the conditioned finger movement).Overall, this evidence shows that the m-PAS can be used to drive new associations between the perception of actions and their corresponding motor programs, measurable both at a neurophysiological and behavioral level. At least for simple, not goal-directed, movements, the induction of motor resonance and automatic imitation effects are governed by mototopic and somatotopic rules.

Motor corticospinal excitability abnormalities differ between distinct chronic low back pain syndromes

ObjectivesIt is not known whether cortical plastic changes reported in low-back pain (LBP) are present in all etiologies of LBP. Here we report on the assessment of patients with three LBP conditions: non-specific-LBP (ns-LBP), failed back surgery syndrome (FBSS), and sciatica (Sc). MethodsPatients underwent a standardized assessment of clinical pain, conditioned pain modulation (CPM), and measures of motor evoked potential (MEPs)-based motor corticospinal excitability (CE) by transcranial magnetic stimulation, including short interval intracortical inhibition (SICI), and intracortical facilitation (ICF). Comparisons were also made with normative data from sex- and age-matched healthy volunteers. Results60 patients (42 women, 55.1±9.1 years old) with LBP were included (20 in each group). Pain intensity was higher in patients with neuropathic pain [FBSS (6.8±1.3), and Sc (6.4±1.4)] than in those with ns-LBP (4.7±1.0, P<0.001). The same was shown for pain interference (5.9±2.0, 5.9±1.8, 3.2±1.9, P<0.001), disability (16.4±3.3, 16.3±4.3, 10.4±4.3, P<0.001), and catastrophism (31.1±12.3, 33.0±10.4, 17.4±10.7, P<0.001) scores for FBSS, Sc, and ns-LBP groups, respectively. Patients with neuropathic pain (FBSS, Sc) had lower CPM (-14.8±1.9, -14.1±16.7, respectively) compared to ns-LBP (-25.4±16.6; P<0.02). 80.0% of the FBSS group had defective ICF compared to the other two groups (52.5% for ns-LBP, P=0.025 and 52.5% for Sc, P=0.046). MEPs (140%-rest motor threshold) were low in 50.0% of patients in the FBSS group compared to 20.0% of ns-LBP (P=0.018) and 15.0% of Sc (P=0.001) groups. Higher MEPs were correlated with mood scores (r=0.489), and with lower neuropathic pain symptom scores(r=-0.415) in FBSS. ConclusionsDifferent types of LBP were associated with different clinical, CPM and CE profiles, which were not uniquely related to the presence of neuropathic pain. These results highlight the need to further characterize patients with LBP in psychophysics and cortical neurophysiology studies.

Effectiveness of Repetitive Transcranial Magnetic Stimulation Combined with Visual Feedback Training in Improving Neuroplasticity and Lower Limb Function after Chronic Stroke: A Pilot Study.

After a stroke, sustained gait impairment can restrict participation in the activities listed in the International Classification of Functioning, Disability, and Health model and cause poor quality of life. The present study investigated the effectiveness of repetitive transcranial magnetic stimulation (rTMS) and visual feedback training (VF) training in improving lower limb motor performance, gait, and corticospinal excitability in patients with chronic stroke. Thirty patients were randomized into three groups that received either rTMS or sham stimulation over the contralesional leg region accompanied by VF training groups in addition to the conventional rehabilitation group. All participants underwent intervention sessions three times per week for four weeks. Outcome measures included the motor-evoked potential (MEP) of the anterior tibialis muscle, Berg Balance Scale (BBS) scores, Timed Up and Go (TUG) test scores, and Fugl-Meyer Assessment of Lower Extremity scores. After the intervention, the rTMS and VF group had significantly improved in MEP latency (p = 0.011), TUG scores (p = 0.008), and BBS scores (p = 0.011). The sham rTMS and VF group had improved MEP latency (p = 0.027). The rTMS and VF training may enhance the cortical excitability and walking ability of individuals with chronic stroke. The potential benefits encourage a larger trial to determine the efficacy in stroke patients.

Intersession reliability of quadriceps corticospinal excitability: A functional transcranial magnetic stimulation study

Recording transcranial magnetic stimulation-derived measures during a closed kinetic chain task can serve as a functional technique to assess corticomotor function, which may have implications for activities of daily living or lower extremity injury in physically active individuals. Given the novelty of TMS use in this way, our purpose was to first determine the intersession reliability of quadriceps corticospinal excitability during a single-leg squat. We used a descriptive laboratory study to assess 20 physically active females (22.1 ± 2.5 years, 1.7 ± 0.7 m, 66.3 ± 13.6 kg, Tegner Activity Scale: 5.90 ± 1.12) over a 14-day period. Two-way mixed effects Intraclass Correlation Coefficients (3,1) (ICC) for absolute agreement were used to assess intersession reliability. The active motor threshold (AMT) and normalized motor evoked potential (MEP) amplitudes were assessed in the vastus medialis of each limb. The dominant limb AMTs demonstrated moderate-to-good reliability (ICC = 0.771, 95% CI = 0.51–0.90; p < 0.001). The non-dominant limb AMTs (ICC = 0.364, 95% CI = 0.00–0.68, p = 0.047), dominant limb MEPs (ICC = 0.192, 95% CI = 0.00–0.71; p = 0.340), and non-dominant limb MEPs (ICC = 0.272, 95% CI = 0.00–0.71; p = 0.235) demonstrated poor-to-moderate reliability. These findings may provide insight into corticomotor function during activities requiring weight-bearing, single-leg movement. However, variability in agreement suggests further work is warranted to improve the standardization of this technique prior to incorporating in clinical outcomes research.

Reduced connectivity of primary auditory and motor cortices during exposure to auditory white noise

Auditory white noise (WN) is widely used in daily life for inducing sleep, and in neuroscience to mask unwanted environmental noise and cues. However, WN was recently reported to influence corticospinal excitability and behavioral performance. Here, we expand previous preliminary findings on the influence of WN exposure on cortical functioning, and we hypothesize that it may modulate cortical connectivity.We tested our hypothesis by performing magnetoencephalography in 20 healthy subjects.WN reduces cortical connectivity of the primary auditory and motor regions with very distant cortical areas, showing a right lateralized connectivity reduction for primary motor cortex.The present results, together with previous finding concerning WN impact on corticospinal excitability and behavioral performance, further support the role of WN as a modulator of cortical function. This suggest avoiding its unrestricted use as a masking tool, while purposely designed and controlled WN application could be exploited to harness brain function and to treat neuropsychiatric conditions.

Cortical oscillations and interareal synchronization as a preparatory activity for postural response.

Neural mechanisms of human standing are expected to be elucidated for preventing fallings. Postural response evoked by sudden external perturbation originates from various areas in the central nervous system. Recent studies have revealed that the corticospinal pathway is one of key nodes for an appropriate postural response. The corticospinal pathway that mediates the early part of electromyographic response is modulated with prediction before a perturbation occurs. Temporal prediction explicitly exhibiting an onset timing contributes to enhancing corticospinal excitability. However, how the cortical activities in the sensorimotor area with temporal prediction are processed before the corticospinal pathway enhancement remains unclear. In this study, using electroencephalography, we investigated how temporal prediction affects both neural oscillations and synchronization between sensorimotor and distal areas. Our results revealed that desynchronization of cortical oscillation at α- and β-bands was observed in the sensorimotor and parietooccipital areas (Cz, CPz, Pz, and POz), and those are nested in the phase at θ-band frequency. Furthermore, a reduction in the interareal phase synchrony in the α-band was induced after the timing cue for the perturbation onset. The phase synchrony at the low-frequency can relay the temporal prediction among the distant areas and initiate the modulation of the local cortical activities. Such modulations contribute to the preparation for sensory processing and motor execution that are necessary for optimal responses.

Modulation of corticospinal excitability related to the forearm muscle during robot-assisted stepping in humans

In recent years, the neural control mechanisms of the arms and legs during human bipedal walking have been clarified. Rhythmic leg stepping leads to suppression of monosynaptic reflex excitability in forearm muscles. However, it is unknown whether and how corticospinal excitability of the forearm muscle is modulated during leg stepping. The purpose of the present study was to investigate the excitability of the corticospinal tract in the forearm muscle during passive and voluntary stepping. To compare the neural effects on corticospinal excitability to those on monosynaptic reflex excitability, the present study also assessed the excitability of the H-reflex in the forearm muscle during both types of stepping. A robotic gait orthosis was used to produce leg stepping movements similar to those of normal walking. Motor evoked potentials (MEPs) and H-reflexes were evoked in the flexor carpi radialis (FCR) muscle during passive and voluntary stepping. The results showed that FCR MEP amplitudes were significantly enhanced during the mid-stance and terminal-swing phases of voluntary stepping, while there was no significant difference between the phases during passive stepping. Conversely, the FCR H-reflex was suppressed during both voluntary and passive stepping, compared to the standing condition. The present results demonstrated that voluntary commands to leg muscles, combined with somatosensory inputs, may facilitate corticospinal excitability in the forearm muscle, and that somatosensory inputs during walking play a major role in monosynaptic reflex suppression in forearm muscle.

Cortico-cortical paired associative stimulation (ccPAS) over premotor-motor areas affects local circuitries in the human motor cortex via Hebbian plasticity

Transcranial magnetic stimulation (TMS) studies have shown that cortico-cortical paired associative stimulation (ccPAS) can strengthen connectivity between the ventral premotor cortex (PMv) and the primary motor cortex (M1) by modulating convergent input over M1 via Hebbian spike-timing-dependent plasticity (STDP). However, whether ccPAS locally affects M1 activity remains unclear. We tested 60 right-handed young healthy humans in two studies, using a combination of dual coil TMS and ccPAS over the left PMv and M1 to probe and manipulate PMv-to-M1 connectivity, and single- and paired-pulse TMS to assess neural activity within M1. We provide convergent evidence that ccPAS, relying on repeated activations of excitatory PMv-to-M1 connections, acts locally over M1. During ccPAS, motor-evoked potentials (MEPs) induced by paired PMv-M1 stimulation gradually increased. Following ccPAS, the threshold for inducing MEPs of different amplitudes decreased, and the input-output curve (IO) slope increased, highlighting increased M1 corticospinal excitability. Moreover, ccPAS reduced the magnitude of short-interval intracortical inhibition (SICI), reflecting suppression of GABA-ergic interneuronal mechanisms within M1, without affecting intracortical facilitation (ICF). These changes were specific to ccPAS Hebbian strengthening of PMv-to-M1 connectivity, as no modulations were observed when reversing the order of the PMv-M1 stimulation during a control ccPAS protocol. These findings expand prior ccPAS research that focused on the malleability of cortico-cortical connectivity at the network-level, and highlight local changes in the area of convergent activation (i.e., M1) during plasticity induction. These findings provide new mechanistic insights into the physiological basis of ccPAS that are relevant for protocol optimization.

Effects of trunk neuromuscular electrical stimulation on the motor circuits of able-bodied individuals

Upper- and lower-limb neuromuscular electrical stimulation (NMES) is known to modulate the excitability of the neural motor circuits. However, it remains unclear whether short-duration trunk muscle NMES could achieve similar neuromodulation effects. We assessed motor evoked potentials (MEPs) elicited through transcranial magnetic stimulation of the primary motor cortex representation of the trunk extensor muscles to evaluate corticospinal excitability. Moreover, cervicomedullary motor evoked potentials (CMEPs) were assessed through cervicomedullary junction magnetic stimulation to evaluate subcortical excitability. Twelve able-bodied individuals participated in the MEP study, and another twelve in the CMEP study. During the interventions, NMES was applied bilaterally to activate the erector spinae muscle and produce intermittent contractions (20 s ON/20 s OFF) for a total of 20 min while participants remained seated. Assessments were performed: (i) before; (ii) during (in brief periods when NMES was OFF); and (iii) immediately after the interventions to compare MEP or CMEP excitability. Our results showed that MEP responses were not affected by trunk NMES, while CMEP responses were facilitated for approximately 8 min during the intervention, and returned to baseline before the end of the 20 min stimulating period. Our findings therefore suggest that short-duration NMES of the trunk extensor muscles likely does not affect the corticospinal excitability, but it has a potential to facilitate subcortical neural circuits immediately after starting the intervention. These findings indicate that short-duration application of NEMS may be helpful in rehabilitation to enhance neuromodulation of the trunk subcortical neural motor circuits.

Physiological, Anatomical and Metabolic Correlates of Aerobic Fitness in Human Primary Motor Cortex: A Multimodal Study

Physical activity (PA) has been shown to benefit various cognitive functions and promote neuroplasticity. Whereas the effects of PA on brain anatomy and function have been well documented in older individuals, data are scarce in young adults. Whether high levels of cardiorespiratory fitness (CRF) achieved through regular PA are associated with significant structural and functional changes in this age group remains largely unknown. In the present study, twenty young adults that engaged in at least 8 hours per week of aerobic exercise during the last 5 years were compared to twenty sedentary controls on measures of cortical excitability, white matter microstructure, cortical thickness and metabolite concentration. All measures were taken in the left primary motor cortex and CRF was assessed with VO2max. Transcranial magnetic stimulation (TMS) revealed higher corticospinal excitability in high- compared to low-fit individuals reflected by greater input/output curve amplitude and slope. No group differences were found for other TMS (short-interval intracortical inhibition and intracortical facilitation), diffusion MRI (fractional anisotropy and apparent fiber density), structural MRI (cortical thickness) and magnetic resonance spectroscopy (NAA, GABA, Glx) measures. Taken together, the present data suggest that brain changes associated with increased CRF are relatively limited, at least in primary motor cortex, in contrast to what has been observed in older adults.

Relationship between Corticospinal Excitability While Gazing at the Mirror and Motor Imagery Ability

Mirror therapy (MT) helps stroke survivors recover motor function. Previous studies have reported that an individual's motor imagery ability is related to the areas of brain activity during motor imagery and the effectiveness of motor imagery training. However, the relationship between MT and motor imagery ability and between corticospinal tract excitability during mirror gazing, an important component of MT, and motor imagery ability is unclear. This study determined whether the motor-evoked potential (MEP) amplitude while gazing at the mirror relates to participants' motor imagery abilities. Twenty-four healthy right-handed adults (seven males) were recruited. Transcranial magnetic stimulation was performed while gazing at the mirror, and MEP of the first dorsal interosseous muscle of the right hand were measured. Motor imagery ability was measured using the Kinesthetic and Visual Imagery Questionnaire (KVIQ), which assesses the vividness of motor imagery ability. Additionally, a mental chronometry (MC) task was used to assess time aspects. The results showed a significant moderate correlation between changes in MEP amplitude values while gazing at the mirror, as compared with resting conditions, and assessment scores of KVIQ. This study shows that corticospinal excitability because of mirror gazing may be related to the vividness of motor imagery ability.

Neural bases of motor fatigue in multiple sclerosis: A multimodal approach using neuromuscular assessment and TMS-EEG

Motor fatigue is one of the most common symptoms in multiple sclerosis (MS) patients. Previous studies suggested that increased motor fatigue in MS may arise at the central nervous system level. However, the mechanisms underlying central motor fatigue in MS are still unclear.This paper investigated whether central motor fatigue in MS reflects impaired corticospinal transmission or suboptimal primary motor cortex (M1) output (supraspinal fatigue). Furthermore, we sought to identify whether central motor fatigue is associated with abnormal M1 excitability and connectivity within the sensorimotor network.Twenty-two patients affected by relapsing-remitting MS and 15 healthy controls (HCs) performed repeated blocks of contraction at different percentages of maximal voluntary contraction with the right first dorsal interosseus muscle until exhaustion. Peripheral, central, and supraspinal components of motor fatigue were quantified by a neuromuscular assessment based on the superimposed twitch evoked by peripheral nerve and transcranial magnetic stimulation (TMS). Corticospinal transmission, excitability and inhibition during the task were tested by measurement of motor evoked potential (MEP) latency, amplitude, and cortical silent period (CSP). M1 excitability and connectivity was measured by TMS-evoked electroencephalography (EEG) potentials (TEPs) elicited by M1 stimulation before and after the task.Patients completed fewer blocks of contraction and showed higher values of central and supraspinal fatigue than HCs. We found no MEP or CSP differences between MS patients and HCs. Patients showed a post-fatigue increase in TEPs propagation from M1 to the rest of the cortex and in source-reconstructed activity within the sensorimotor network, in contrast to the reduction observed in HCs. Post-fatigue increase in source-reconstructed TEPs correlated with supraspinal fatigue values.To conclude, MS-related motor fatigue is caused by central mechanisms related explicitly to suboptimal M1 output rather than impaired corticospinal transmission. Furthermore, by adopting a TMS-EEG approach, we proved that suboptimal M1 output in MS patients is associated with abnormal task-related modulation of M1 connectivity within the sensorimotor network. Our findings shed new light on the central mechanisms of motor fatigue in MS by highlighting a possible role of abnormal sensorimotor network dynamics. These novel results may point to new therapeutical targets for fatigue in MS.

Low-level voluntary input enhances corticospinal excitability during ankle dorsiflexion neuromuscular electrical stimulation in healthy young adults.

Previous evidence indicated that interventions with combined neuromuscular electrical stimulation (NMES) and voluntary muscle contractions could have superior effects on corticospinal excitability when the produced total force is larger than each single intervention. However, it is unclear whether the superior effects exist when the produced force is matched between the interventions. Ten able-bodied individuals performed three intervention sessions on separate days: (i) NMES-tibialis anterior (TA) stimulation; (ii) NMES+VOL-TA stimulation combined with voluntary ankle dorsiflexion; (iii) VOL-voluntary ankle dorsiflexion. Each intervention was exerted at the same total output of 20% of maximal force and applied intermittently (5 s ON / 19 s OFF) for 16 min. Motor evoked potentials (MEP) of the right TA and soleus muscles and maximum motor response (Mmax) of the common peroneal nerve were assessed: before, during, and for 30 min after each intervention. Additionally, the ankle dorsiflexion force-matching task was evaluated before and after each intervention. Consequently, the TA MEP/Mmax during NMES+VOL and VOL sessions were significantly facilitated immediately after the interventions started until the interventions were over. Compared to NMES, larger facilitation was observed during NMES+VOL and VOL sessions, but no difference was found between them. Motor control was not affected by any interventions. Although superior combined effects were not shown compared to voluntary contractions alone, low-level voluntary contractions combined with NMES resulted in facilitated corticospinal excitability compared to NMES alone. This suggests that the voluntary drive could improve the effects of NMES even during low-level contractions, even if motor control is not affected.

Femoral cortical excitability differs between people with knee osteoarthritis and healthy controls: a pilot study

BACKGROUND: Knee osteoarthritis (OA) is associated with changes in corticospinal and intracortical excitability which may be due to persistent pain. OBJECTIVE: To investigate the cortical excitability profile of the femoral quadriceps in people with knee OA and healthy volunteers. METHODS: Cortical excitability was assessed using transcranial magnetic stimulation (TMS) in 7 participants with knee OA and 6 age- and sex-matched healthy volunteers. The motor evoked potential (MEP), cortical silent period (CSP), short intracortical inhibition (SICI) and intracortical facilitation (ICF) of the rectus femoris (RF), vastus medialis (VM) and vastus lateralis (VL) were measured using standard single pulse and paired-pulse TMS techniques. Data analysis was performed using Mann-Whitney test considering alpha &lt;0.05. RESULTS: Participants with knee OA demonstrated reduced MEP amplitude in the RF and VM muscles and augmented MEP amplitude in the VL muscle. SICI was reduced only in the RF and ICF was reduced in the VM and VL. CSP was reduced in all muscles. CONCLUSION: People with knee OA exhibit altered corticospinal and intracortical excitability profile in specific portions of the quadriceps muscle. This suggests a possible adaptive strategy to maintain quadriceps motor activity.

P-132 Bidirectional changes in corticospinal excitability following quadri-pulse theta burst stimulation with individually (I-wave) adapted and fixed interstimulus intervals – Preliminary results

P-132 Bidirectional changes in corticospinal excitability following quadri-pulse theta burst stimulation with individually (I-wave) adapted and fixed interstimulus intervals – Preliminary results