Changes In Amplitude Of Motor Evoked Potentials Research Articles

Transspinal direct current stimulation with an intensity of 2.5 mA does not affect the corticospinal system excitability and motor skills

BACKGROUND: Noninvasive brain stimulation effectively affects movements, including the spinal cord level. Stimulation effects are very sensitive to montage and protocols of applied stimulation because they can involve different neuronal mechanisms. AIM: This study aimed to estimate the effect of anodal transspinal direct current stimulation (tsDCS) with an intensity of 2.5 mA applied at the spinal cord level (C7–Th1 segments) with cervical enlargement on the corticospinal system excitability and motor skills. METHODS: The study involved 54 healthy adults aged 21.19±3.20 years. The effect of tsDCS was assessed using motorevoked potentials from the first dorsal interosseous (FDI) muscle by transcranial magnetic stimulation in the primary motor cortex before stimulation, immediately after stimulation, and after 15 min. RESULTS: The application of an 11-min anodal tsDCS with a current value of 2.5 mA at the C7–Th1 level did not affect the motorevoked potentials of FDI. Statistically, changes in motorevoked potentials amplitudes did not differ between groups receiving anodal tsDCS and sham stimulation. In addition, anodal tsDCS did not affect motor skills. An individual’s ability to coordinate fingers and manipulate objects effectively (a measure of dexterity) in the nine-hole peg test and pressing a key in response to a visual stimulus in the serial reaction time task did not differ from that with sham stimulation. CONCLUSION: 2.5 mA anodal tsDCS on cervical enlargement does not affect the corticospinal system excitability or change motor skills associated with precise hand movements.

Comparison of Motor Evoked Potentials Neuromonitoring Following Pre- and Postoperative Transcranial Magnetic Stimulation and Intraoperative Electrical Stimulation in Patients Undergoing Surgical Correction of Idiopathic Scoliosis.

The relationships between the results of pre- and intraoperative motor evoked potential recordings during neuromonitoring and whether idiopathic scoliosis (IS) surgical correction improves the spinal efferent transmission have not been specified in detail. This study aims to compare the results of surface-recorded electromyography (EMG), electroneurography (ENG, M, and F-waves), and especially motor evoked potential (MEP) recordings from tibialis anterior muscle (TA) bilaterally in 353 girls with right idiopathic scoliosis (types 1-3 according to Lenke classification). It has not yet been documented whether the results of MEP recordings induced by transcranial single magnetic stimulus (TMS, pre- and postoperatively) and trains of electrical stimuli (TES; intraoperatively in T0-before surgery, T1-after pedicle screws implantation, and T2-after scoliosis curvature distraction and derotation following two-rod implantation) can be compared for diagnostic verification of the improvement of spinal cord neural transmission. We attempted to determine whether the constant level of optimal anesthesia during certain surgical steps of scoliosis treatment affects the parameters of MEPs recorded during neuromonitoring procedures. No neurological deficits have been observed postoperatively. The values of amplitudes but not latencies in MEP recordings evoked with TMS in IS patients compared before and after surgery indicated a slight improvement in efferent neural transmission. The results of all neurophysiological studies in IS patients were significantly asymmetrical and recorded worse on the concave side, suggesting greater neurological motor deficits at p = 0.04. The surgeries brought significant improvement (p = 0.04) in the parameters of amplitudes of sEMG recordings; however, the consequences of abnormalities in the activity of TA motor units were still reflected. ENG study results showed the symptoms of the axonal-type injury in peroneal motor fibers improving only on the concave side at p = 0.04, in parallel with F-wave parameters, which suggests that derotation and distraction might result in restoring the proper relations of the lumbar ventral roots in the spinal central canal, resembling their decompression. There were no significant differences detected in the amplitudes or latencies of MEPs induced with TMS or TES when comparing the parameters recorded preoperatively and intraoperatively in T0. The amplitudes of TES-evoked MEPs increased gradually at p = 0.04 in the subsequent periods (T1 and T2) of observation. A reduction in MEP latency at p = 0.05 was observed only at the end of the IS surgery. Studies on the possible connections between the level of anesthesia fluctuations and the required TMS stimulus strength, as well as the MEP amplitude changes measured in T0-T2, revealed a lack of relationships. These might not be the factors influencing the efferent transmission in spinal pathways beside the surgical procedures. Pre- (TMS-evoked) and intraoperative (TES-evoked) recordings are reliable for evaluating the patient's neurological status before and during surgical scoliosis correction procedures. An increase in MEP amplitude parameters recorded on both sides after scoliosis surgery proves the immediate improvement of the total efferent spinal cord transmission. Considering comparative pre- and postoperative sEMG and ENG recordings, it can be concluded that surgeries might directly result in additional lumbar ventral root decompression. We can conclude that MEP parameter changes are determined by the surgery procedures during neuromonitoring, not the anesthesia conditions if they are kept stable, which influences a decrease in the number of false-positive neuromonitoring warnings.

Temporary Occlusion of Common Carotid Arteries Does Not Evoke Total Inhibition in the Activity of Corticospinal Tract Neurons in Experimental Conditions.

Temporary occlusion of the common cervical artery is the reason for ischemic stroke in 25% of patients. Little data is provided on its effects, especially regarding neurophysiological studies verifying the neural efferent transmission within fibers of the corticospinal tract in experimental conditions. Studies were performed on 42 male Wistar rats. In 10 rats, ischemic stroke was evoked by permanent occlusion of the right carotid artery (group A); in 11 rats, by its permanent bilateral occlusion (B); in 10 rats, by unilateral occlusion and releasing after 5 min (C); and in 11 rats, by bilateral occlusion and releasing after 5 min (D). Efferent transmission of the corticospinal tract was verified by motor evoked potential (MEP) recordings from the sciatic nerve after transcranial magnetic stimulation. MEPs amplitude and latency parameters, oral measurements of temperature, and verification of ischemic effects in brain slides stained with hematoxylin and eosin staining (H + E) were analyzed. In all groups of animals, the results showed that five minutes of uni- or bilateral occlusion of the common carotid artery led to alterations in brain blood circulation and evoked changes in MEP amplitude (by 23.2% on average) and latency parameters (by 0.7 ms on average), reflecting the partial inability of tract fibers to transmit neural impulses. These abnormalities were associated with a significant drop in the body temperature by 1.5 °C on average. Ten minutes occlusion in animals from groups A and B resulted in an MEP amplitude decrease by 41.6%, latency increase by 0.9 ms, and temperature decrease by 2.9 °C of the initial value. In animals from groups C and D, five minutes of recovery of arterial blood flow evoked stabilization of the MEP amplitude by 23.4%, latency by 0.5 ms, and temperature by 0.8 °C of the initial value. In histological studies, the results showed that ischemia was most prominent bilaterally in sensory and motor areas, mainly for the forelimb, rather than the hindlimb, innervation of the cortex, putamen and caudate nuclei, globulus pallidus, and areas adjacent to the fornix of the third ventricle. We found that the MEP amplitude parameter is more sensitive than the latency and temperature variability in monitoring the ischemia effects course following common carotid artery infarction, although all parameters are correlated with each other. Temporary five-minute lasting occlusion of common carotid arteries does not evoke total and permanent inhibition in the activity of corticospinal tract neurons in experimental conditions. The symptoms of rat brain infarction are much more optimistic than those described in patients after stroke, and require further comparison with the clinical observations.

Changes in Corticospinal Excitability and Motor Control During Cerebellar Transcranial Direct Current Stimulation in Healthy Individuals.

Cerebellar transcranial direct current stimulation (ctDCS) modulates the primary motor cortex (M1) via cerebellar brain inhibition (CBI), which affects motor control in humans. However, the effects of ctDCS on motor control are inconsistent because of an incomplete understanding of the real-time changes in the M1 excitability that occur during ctDCS, which determines motor output under regulation by the cerebellum. This study investigated changes in corticospinal excitability and motor control during ctDCS in healthy individuals. In total, 37 healthy individuals participated in three separate experiments. ctDCS (2mA) was applied to the cerebellar hemisphere during the rest condition or a pinch force-tracking task. Motor-evoked potential (MEP) amplitude and the F-wave were assessed before, during, and after ctDCS, and pinch force control was assessed before and during ctDCS. The MEP amplitudes were significantly decreased during anodal ctDCS from 13min after the onset of stimulation, whereas the F-wave was not changed. No significant changes in MEP amplitudes were observed during cathodal and sham ctDCS conditions. The MEP amplitudes were decreased during anodal ctDCS when combined with the pinch force-tracking task, and pinch force control was impaired during anodal ctDCS relative to sham ctDCS. The MEP amplitudes were not significantly changed before and after all ctDCS conditions. Motor cortical excitability was suppressed during anodal ctDCS, and motor control was unskilled during anodal ctDCS when combined with a motor task in healthy individuals. Our findings provided a basic understanding of the clinical application of ctDCS to neurorehabilitation.

Neurophysiological assessment of juvenile parkinsonism due to primary monoamine neurotransmitter disorders

No studies have investigated voluntary movement abnormalities and their neurophysiological correlates in patients with parkinsonism due to inherited primary monoamine neurotransmitter (NT) disorders. Nine NT disorders patients and 16 healthy controls (HCs) were enrolled. Objective measurements of repetitive finger tapping were obtained using a motion analysis system. Primary motor cortex (M1) excitability was assessed by recording the input/output (I/O) curve of motor-evoked potentials (MEP) and using a conditioning test paradigm for short-interval intracortical inhibition (SICI) assessment. M1 plasticity-like mechanisms were indexed according to MEPs amplitude changes after the paired associative stimulation protocol. Patient values were considered abnormal if they were greater or lower than two standard deviations from the average HCs value. Patients with aromatic amino acid decarboxylase, tyrosine hydroxylase, and 6-pyruvoyl-tetrahydropterin synthase defects showed markedly reduced velocity (5/5 patients), reduced movement amplitude, and irregular rhythm (4/5 patients). Conversely, only 1 out of 3 patients with autosomal-dominant GTPCH deficiency showed abnormal movement parameters. Interestingly, none of the patients had a progressive reduction in movement amplitude or velocity during the tapping sequence (no sequence effect). Reduced SICI was the most prominent neurophysiological abnormality in patients (5/9 patients). Finally, the I/O curve slope correlated with movement velocity and rhythm in patients. We provided an objective assessment of finger tapping abnormalities in monoamine NT disorders. We also demonstrated M1 excitability changes possibly related to alterations in motor execution. Our results may contribute to a better understanding of the pathophysiology of juvenile parkinsonism due to dopamine deficiency.

Association Between Responsiveness to Transcranial Magnetic Stimulation and Interhemispheric Functional Connectivity of Sensorimotor Cortex in Older Adults.

Introduction: Repetitive transcranial magnetic stimulation (rTMS) is a promising therapeutic technique, and is believed to accomplish its effect by influencing the stimulated and remotely connected areas. However, responsiveness to rTMS shows high interindividual variability, and this intersubject variability is particularly high in older adults. It remains unclear whether baseline resting-state functional connectivity (rsFC) contributes to this variability in older adults. The aims of this study are to (1) examine rTMS effects over the primary motor cortex (M1) in older adults, and (2) identify baseline network properties that may contribute to the interindividual variability. Methods: We tested response to intermittent theta burst stimulation (iTBS), an effective rTMS protocol, over M1 by using both electromyography and resting-state functional magnetic resonance imaging in older adults. Outcome measures included motor-evoked potential (MEP) elicited by single-pulse transcranial magnetic stimulation and rsFC before and after an iTBS session. Results: iTBS significantly increased MEP amplitudes and rsFC between the stimulation site, sensorimotor cortex, and supplementary motor area (SMA) in older adults. iTBS-induced changes in MEP amplitude were positively correlated with increases in interhemispheric rsFC after iTBS. Furthermore, older adults with lower baseline interhemispheric rsFC between sensorimotor cortex and SMA exhibited stronger MEP response after iTBS. Discussion: Findings of the study suggest that different levels of interhemispheric communication during resting state might contribute to the response heterogeneity to iTBS in older adults. Interhemispheric rsFC may have great potential serving as a useful marker for predicting iTBS responsiveness in older adults. ClinicalTrials.gov ID: 1707654427 Impact statement Factors contributing to interindividual variability of the responsive to repetitive transcranial magnetic stimulation (rTMS) in older adults remain poorly understood. In this study, we examined the effects of rTMS over the primary motor cortex in older adults, and found that response to rTMS is associated with prestimulation interhemispheric connectivity in the sensorimotor and premotor areas. Findings of the study have great potential to be translated into a connectivity-based strategy for identification of responders for rTMS in older adults.

Altered motor cortical plasticity in patients with hepatic encephalopathy: A paired associative stimulation study

ObjectiveHepatic encephalopathy (HE) is a potentially reversible brain dysfunction caused by liver failure. Altered synaptic plasticity is supposed to play a major role in the pathophysiology of HE. Here, we used paired associative stimulation with an inter-stimulus interval of 25 ms (PAS25), a transcranial magnetic stimulation (TMS) protocol, to test synaptic plasticity of the motor cortex in patients with manifest HE. Methods23 HE-patients and 23 healthy controls were enrolled in the study. Motor evoked potential (MEP) amplitudes were assessed as measure for cortical excitability. Time courses of MEP amplitude changes after the PAS25 intervention were compared between both groups. ResultsMEP-amplitudes increased after PAS25 in the control group, indicating PAS25-induced synaptic plasticity in healthy controls, as expected. In contrast, MEP-amplitudes within the HE group did not change and were lower than in the control group, indicating no induction of plasticity. ConclusionsOur study revealed reduced synaptic plasticity of the primary motor cortex in HE. SignificanceReduced synaptic plasticity in HE provides a link between pathological changes on the molecular level and early clinical symptoms of the disease. This decrease may be caused by disturbances in the glutamatergic neurotransmission due to the known hyperammonemia in HE patients.

CO 2 Effects on Intermittent Hypoxia‐Induced Respiratory Motor Plasticity in Humans: In Progress Study

Intermittent hypoxia (IH) elicits respiratory motor plasticity (known as ventilatory long-term facilitation [LTF]) in humans and other mammals. However, awake humans exhibit ventilatory LTF only when CO2 levels are raised slightly above eupneic levels in a sustained or intermittent fashion during the IH protocol. In this ongoing study, we seek to determine the effect of CO2 on IH-induced respiratory motor plasticity by examining multiple, distinct mechanisms contributing to the ventilatory response during and following acute intermittent hypercapnic hypoxia (IHH). We hypothesized that IHH elicits a prolonged increase in cortico-diaphragmatic conduction, resting neural drive to breathe, and respiratory motor output versus poikilocapnic IH and a normoxic, normocapnic control (CTRL). Five healthy young adults (age = 32 ± 5 years; 3 female) completed four study visits. Day 1 consisted of general subject characterization. On Days 2, 3 and 4 (separated by ≥72 h), subjects were randomly assigned to receive either: IHH (PETO2 = 55 ± 4 Torr, PETCO2 = 44 ± 3 Torr), IH (PETO2 = 55 ± 3 Torr, PETCO2 = 37 ± 2 Torr), or CTRL (PETO2 = 107 ± 3 Torr, PETCO2 = 36 ± 2 Torr). Protocols consisted of 15 episodes of 60 s exposure with 90 s breathing ambient room air. Cardiovascular responses (heart rate, blood pressure and oxygen saturation) were monitored throughout. Cortico-diaphragmatic conduction was quantified by recording motor evoked potentials (MEPs) using transcranial magnetic stimulation and surface EMG electrodes. Resting neural drive to breathe was assessed using the mouth occlusion pressure technique (i.e. P0.1). Respiratory motor output was measured as minute ventilation () during resting isocapnic conditions (PETCO2 maintained within 1 mmHg of baseline) and adjusted based on the rate of metabolic CO2 production (/). Dependent variables were assessed at baseline, and 30-60 min post. Following IHH, IH and CTRL, the mean change in MEP amplitude was +34 ± 48%, +9 ± 21%, and +2 ± 22%; the mean change in P0.1 was +26 ± 17%, +15 ± 16%, and +7 ± 16%; and the mean change in was +0.3 ± 1.0 L·min-1, +0.3 ± 1.1 L·min-1, and +0.3 ± 0.8 L·min-1. When adjusted for , the mean change in / was -0.5 ± 1.0, +0.4 ± 1.8, and -0.2 ± 1.1. Based on these preliminary data in 5 subjects, we suggest that IHH elicits greater increases in cortico-diaphragmatic conduction and resting neural drive to breathe vs. poikilocapnic IH and CTRL. Conversely, our IHH protocol does not elicit ventilatory LTF. We reason that measures such as MEP amplitude and P0.1 are less sensitive to behavioral influences vs. , and may provide unique insights into mechanisms of IH-induced respiratory motor plasticity in awake healthy humans.

Multimodal Assessment of Precentral Anodal TDCS: Individual Rise in Supplementary Motor Activity Scales With Increase in Corticospinal Excitability.

BackgroundTranscranial direct current stimulation (TDCS) targeting the primary motor hand area (M1-HAND) may induce lasting shifts in corticospinal excitability, but after-effects show substantial inter-individual variability. Functional magnetic resonance imaging (fMRI) can probe after-effects of TDCS on regional neural activity on a whole-brain level.ObjectiveUsing a double-blinded cross-over design, we investigated whether the individual change in corticospinal excitability after TDCS of M1-HAND is associated with changes in task-related regional activity in cortical motor areas.MethodsSeventeen healthy volunteers (10 women) received 20 min of real (0.75 mA) or sham TDCS on separate days in randomized order. Real and sham TDCS used the classic bipolar set-up with the anode placed over right M1-HAND. Before and after each TDCS session, we recorded motor evoked potentials (MEP) from the relaxed left first dorsal interosseus muscle after single-pulse transcranial magnetic stimulation(TMS) of left M1-HAND and performed whole-brain fMRI at 3 Tesla while participants completed a visuomotor tracking task with their left hand. We also assessed the difference in MEP latency when applying anterior-posterior and latero-medial TMS pulses to the precentral hand knob (AP-LM MEP latency).ResultsReal TDCS had no consistent aftereffects on mean MEP amplitude, task-related activity or motor performance. Individual changes in MEP amplitude, measured directly after real TDCS showed a positive linear relationship with individual changes in task-related activity in the supplementary motor area and AP-LM MEP latency.ConclusionFunctional aftereffects of classical bipolar anodal TDCS of M1-HAND on the motor system vary substantially across individuals. Physiological features upstream from the primary motor cortex may determine how anodal TDCS changes corticospinal excitability.

Modulation of Motor Cortex Plasticity by Repetitive Paired-Pulse TMS at Late I-Wave Intervals Is Influenced by Intracortical Excitability.

The late indirect (I)-waves recruited by transcranial magnetic stimulation (TMS) over primary motor cortex (M1) can be modulated using I-wave periodicity repetitive TMS (iTMS). The purpose of this study was to determine if the response to iTMS is influenced by different interstimulus intervals (ISIs) targeting late I-waves, and whether these responses were associated with individual variations in intracortical excitability. Seventeen young (27.2 ± 6.4 years, 12 females) healthy adults received iTMS at late I-wave intervals (4.0, 4.5, and 5.0 ms) in three separate sessions. Changes due to each intervention were examined with motor evoked potential (MEP) amplitudes and short-interval intracortical facilitation (SICF) using both posterior-anterior (PA) and anterior-posterior (AP) TMS current directions. Changes in MEP amplitude and SICF were influenced by iTMS ISI, with the greatest facilitation for ISIs at 4 and 5 ms with PA TMS, and 4 ms with AP TMS. Maximum SICF at baseline (irrespective of ISI) was associated with increased iTMS response, but only for PA stimulation. These results suggest that modifying iTMS parameters targeting late I-waves can influence M1 plasticity. They also suggest that maximum SICF may be a means by which responders to iTMS targeting the late I-waves could be identified.

Modeling motor-evoked potentials from neural field simulations of transcranial magnetic stimulation

ObjectiveTo develop a population-based biophysical model of motor-evoked potentials (MEPs) following transcranial magnetic stimulation (TMS). MethodsWe combined an existing MEP model with population-based cortical modeling. Layer 2/3 excitatory and inhibitory neural populations, modeled with neural-field theory, are stimulated with TMS and feed layer 5 corticospinal neurons, which also couple directly but weakly to the TMS pulse. The layer 5 output controls mean motoneuron responses, which generate a series of single motor-unit action potentials that are summed to estimate a MEP. ResultsA MEP waveform was generated comparable to those observed experimentally. The model captured TMS phenomena including a sigmoidal input–output curve, common paired pulse effects (short interval intracortical inhibition, intracortical facilitation, long interval intracortical inhibition) including responses to pharmacological interventions, and a cortical silent period. Changes in MEP amplitude following theta burst paradigms were observed including variability in outcome direction. ConclusionsThe model reproduces effects seen in common TMS paradigms. SignificanceThe model allows population-based modeling of changes in cortical dynamics due to TMS protocols to be assessed in terms of changes in MEPs, thus allowing a clear comparison between population-based modeling predictions and typical experimental outcome measures.

Decreased neuroplasticity in minor burn injury survivors compared to non-injured adults: A pilot study in burn injury survivors aged 45 years and older

ObjectiveNeuroplasticity is the capacity of the brain to change or adapt with experience: brain changes occur with use, disuse, and injury. Repetitive transcranial magnetic stimulation (rTMS) can be used to induce neuroplasticity in the human brain. Here, we examined rTMS-induced neuroplasticity in the primary motor cortex in burns survivors and controls without injury, and whether neuroplasticity is associated with functional recovery in burns survivors. MethodsSixteen burn injury survivors (total body surface area of burn injury <15%) and 13 non-injured control participants were tested. Repetitive TMS (specifically, spaced continuous theta-burst stimulation[cTBS]) was applied to induce neuroplasticity 6 and 12 weeks after injury in burn survivors and in two sessions separated by 6 weeks in controls. Motor evoked potentials (MEPs) elicited by single-pulse TMS were measured before and after rTMS to measure neuroplasticity. Burns survivors completed a functional assessment 12 weeks after injury. ResultsNon-injured controls showed decreased MEP amplitude 15−30 min after spaced cTBS in both experimental sessions. Burn survivors showed a smaller change in MEP amplitude after spaced cTBS compared to controls 6 weeks after burn injury but no difference compared to controls 12 weeks after burn injury. In burn survivors, there was a significant positive association between general health outcome (Short-Form Health Survey) and the change in MEP amplitude after spaced cTBS 12 weeks after injury (r=.73, p = .01). ConclusionsThe current findings suggest that burn survivors have a reduced capacity for neuroplasticity early in the recovery period (6 weeks after injury), which normalizes later in the recovery period (12 weeks after injury). Furthermore, the results provide preliminary evidence to suggest that burn survivors with normalized neuroplasticity 12 weeks after injury recover faster after burn injury.

Gait-combined transcranial alternating current stimulation modulates cortical control of muscle activities during gait.

Non-invasive brain stimulation has been of interest as a therapeutic tool to modulate cortical excitability. However, there is little evidence that oscillatory brain stimulation can modulate the cortical control of muscle activities during gait, which can be assessed using coherence analysis of paired surface electromyographic (EMG) recordings. This study aimed to investigate the effects of gait-combined transcranial alternating current stimulation (tACS) at the gait cycle frequency on the cortical control of muscle activities during gait using EMG-EMG coherence analysis. Fourteen healthy young adults participated in this study. All participants underwent 2 test conditions (real tACS and sham stimulation over the leg area of the primary motor cortex during 10-min treadmill walking). The average peak-to-peak amplitudes of the motor evoked potentials (MEPs) from the tibialis anterior (TA) and lateral gastrocnemius muscles in the sitting position and EMG-EMG coherences in the TA muscle, triceps surae muscles, quadriceps muscles, and hamstring muscles during gait were measured before and after stimulation. Entrainment effect was significantly higher during real tACS than during sham stimulation. After real tACS, the MEP amplitude and beta band (13-33Hz) coherence area increased in the TA muscle. The change in MEP amplitude from the TA muscle was positively correlated with the change in beta band coherence area in the TA muscle. Gait-combined tACS can modulate the strength of descending neural drive to TA motoneurons during gait. This suggests that oscillatory brain stimulation is a useful therapeutic tool to modulate the cortical control of muscle activities during gait.

Muscle length: A new feature to investigate neural control of lengthening contractions.

Muscle length: A new feature to investigate neural control of lengthening contractions.

Transcranial Static Magnetic Field Stimulation of the Motor Cortex in Children.

BackgroundNon-invasive neuromodulation is an emerging therapy for children with early brain injury but is difficult to apply to preschoolers when windows of developmental plasticity are optimal. Transcranial static magnetic field stimulation (tSMS) decreases primary motor cortex (M1) excitability in adults but effects on the developing brain are unstudied.Objective/HypothesisWe aimed to determine the effects of tSMS on cortical excitability and motor learning in healthy children. We hypothesized that tSMS over right M1 would reduce cortical excitability and inhibit contralateral motor learning.MethodsThis randomized, sham-controlled, double-blinded, three-arm, cross-over trial enrolled 24 healthy children aged 10–18 years. Transcranial Magnetic Stimulation (TMS) assessed cortical excitability via motor-evoked potential (MEP) amplitude and paired pulse measures. Motor learning was assessed via the Purdue Pegboard Test (PPT). A tSMS magnet (677 Newtons) or sham was held over left or right M1 for 30 min while participants trained the non-dominant hand. A linear mixed effect model was used to examine intervention effects.ResultsAll 72 tSMS sessions were well tolerated without serious adverse effects. Neither cortical excitability as measured by MEPs nor paired-pulse intracortical neurophysiology was altered by tSMS. Possible behavioral effects included contralateral tSMS inhibiting early motor learning (p < 0.01) and ipsilateral tSMS facilitating later stages of motor learning (p < 0.01) in the trained non-dominant hand.ConclusiontSMS is feasible in pediatric populations. Unlike adults, tSMS did not produce measurable changes in MEP amplitude. Possible effects of M1 tSMS on motor learning require further study. Our findings support further exploration of tSMS neuromodulation in young children with cerebral palsy.

Muscle-specific modulation of indirect inputs to primary motor cortex during action observation.

Single-pulse transcranial magnetic stimulation (spTMS) studies report that movement observation facilitates corticospinal excitability in primary motor cortex (M1) in a muscle-specific manner. However, motor evoked potentials (MEPs) elicited by spTMS are known to reflect the summation of several descending volleys in corticospinal neurons which are evoked via mono- and polysynaptic inputs (so-called indirect waves or I-waves). It is unclear which of these components contribute to the muscle-specific modulation of M1 during action observation. The interactions between different I-waves are reflected in the facilitatory peaks elicited with a short-intracortical facilitation (SICF) protocol when two pulses are sent to M1 at precise intervals (i.e., 1.3, 2.5 or 4.1ms). Here, we explored the modulation of early and late SICF peaks during action observation by measuring highly specific MEP amplitude changes measured in two muscles (index, FDI and little finger, ADM) while participants observed two different actions (precision and whole-hand grip). Our results demonstrate that both early (1.3ms) and late (2.5 and 4.1ms) SICF peaks are modulated in the context of movement observation. However, only the second peak (ISI 2.5ms) was significantly associated with the muscle-specific modulation of corticospinal excitability as measured with spTMS. This late SICF peak is believed to reflect the activity cortico-cortical pathways involved in the facilitation of muscle-specific representations in M1. Thus, our findings suggest that movement observation leads to widespread activation of different neural circuits within M1, including those mediating cortico-cortical communication.

Bradykinesia in Alzheimer’s disease and its neurophysiological substrates

ObjectiveAlzheimer’s disease is primarily characterized by cognitive decline; recent studies, however, emphasize the occurrence of motor impairment in this condition. Here, we investigate whether motor impairment, objectively evaluated with kinematic techniques, correlates with neurophysiological measures of the primary motor cortex in Alzheimer’s disease. MethodsTwenty patients and 20 healthy subjects were enrolled. Repetitive finger tapping was assessed by means of a motion analysis system. Primary motor cortex excitability was assessed by recording the input/output curve of the motor-evoked potentials and using a conditioning-test paradigm for the assessment of short-interval intracortical inhibition and short-latency afferent inhibition. Plasticity-like mechanisms were indexed according to changes in motor-evoked potential amplitude induced by the intermittent theta-burst stimulation. ResultsPatients displayed slowness and altered rhythm during finger tapping. Movement slowness correlated with reduced short-latency afferent inhibition in patients, thus suggesting that degeneration of the cholinergic system may also be involved in motor impairment in Alzheimer’s disease. Moreover, altered movement rhythm in patients correlated with worse scores in the Frontal Assessment Battery. ConclusionThis study provides new information on the pathophysiology of altered voluntary movements in Alzheimer’s disease. SignificanceThe study results suggest that a cortical cholinergic deficit may underlie movement slowness in Alzheimer’s disease.

Aftereffects of Intermittent Theta-Burst Stimulation in Adjacent, Non-Target Muscles

To assess motor cortex neurophysiology, including the mechanisms of neuroplasticity, transcranial magnetic stimulation (TMS) is typically applied to the motor “hotspot”— the optimal site for inducing a twitch in a given target muscle. It is known that the effects of suprathreshold repetitive TMS (rTMS) spread along functional connections beyond the specific cortical stimulation target, and yet, it is unknown whether the aftereffects of subthreshold intermittent theta-burst stimulation (iTBS), an ultra-high frequency patterned rTMS protocol, extend beyond the targeted muscle.We investigated whether and to what extent iTBS induces changes in the cortical output to other intrinsic hand muscles with adjacent cortical representation to the target. Sixteen healthy adults underwent neuronavigated TMS-iTBS targeting the first dorsal interosseus (FDI) hotspot. Proportion of motor evoked potentials (MEPs) at the resting motor threshold (RMT), baseline MEP amplitude, and iTBS-induced changes in MEP amplitude were compared between FDI, abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles. MEP amplitudes recorded from the three muscles at RMT and suprathreshold intensities indicated the chosen hotspots were relatively selective for FDI. Nevertheless, iTBS induced significant facilitation of MEPs recorded from both FDI and APB, but not ADM. Surprisingly, the MEP modulation was greater in APB, even when controlling for the baseline MEP amplitude. These results indicate that iTBS modulation of cortico-spinal excitability extends beyond the representation of the targeted muscle. Results have implications both for how iTBS may be used in clinical treatment and for the safety guidelines for the application of iTBS.

The effect of combined transcranial direct current stimulation and peripheral nerve electrical stimulation on corticospinal excitability.

Transcranial direct current stimulation (tDCS) and peripheral nerve electrical stimulation (PES) can change corticospinal excitability. tDCS can be used to non-invasively modulate the cerebral cortex’s excitability by applying weak current to an electrode attached to the head, and the effect varies with the electrode’s polarity. Previous studies have reported the effect of combined tDCS and PES on corticospinal excitability; when compared to single stimulation, combined stimulation increases cortical excitability. In contrast, another study reported that the effect of tDCS is attenuated by PES; hence, there is no consensus opinion on the effect on combined stimulation. Therefore, this study aimed to clarify the effect of combined tDCS and PES on corticospinal excitability. In Experiment 1, the combined stimulation of anodal tDCS and PES (anodal tDCS + PES) was performed, and in Experiment 2, a combined stimulation with PES, after cathodal tDCS (PES after cathodal tDCS), was performed using a homeostatic metaplasticity theoretical model. In Experiment 1, anodal tDCS produced a significant increase from baseline in motor-evoked potential (MEP) amplitude 10 min after stimulation, but no significant changes in MEP amplitude were observed with PES or the anodal tDCS + PES condition. Experiment 2 showed a significant decrease in MEP amplitude immediately after cathodal tDCS, and a significant increase in MEP amplitude 15 min after PES, but no significant change in MEP amplitude was observed with sequential PES following cathodal tDCS. In conclusion, our data indicate that PES with anodal tDCS suppressed the effect of tDCS. Also, PES after cathodal tDCS did not induce homeostatic metaplasticity and increase corticospinal excitability.

Increased Excitability Induced in the Primary Motor Cortex by Transcranial Ultrasound Stimulation.

Background: Transcranial Ultrasound Stimulation (tUS) is an emerging technique that uses ultrasonic waves to noninvasively modulate brain activity. As with other forms of non-invasive brain stimulation (NIBS), tUS may be useful for altering cortical excitability and neuroplasticity for a variety of research and clinical applications. The effects of tUS on cortical excitability are still unclear, and further complications arise from the wide parameter space offered by various types of devices, transducer arrangements, and stimulation protocols. Diagnostic ultrasound imaging devices are safe, commonly available systems that may be useful for tUS. However, the feasibility of modifying brain activity with diagnostic tUS is currently unknown.Objective: We aimed to examine the effects of a commercial diagnostic tUS device using an imaging protocol on cortical excitability. We hypothesized that imaging tUS applied to motor cortex could induce changes in cortical excitability as measured using a transcranial magnetic stimulation (TMS) motor evoked potential (MEP) paradigm.Methods: Forty-three subjects were assigned to receive either verum (n = 21) or sham (n = 22) diagnostic tUS in a single-blind design. Baseline motor cortex excitability was measured using MEPs elicited by TMS. Diagnostic tUS was subsequently administered to the same cortical area for 2 min, immediately followed by repeated post-stimulation MEPs recorded up to 16 min post-stimulation.Results: Verum tUS increased excitability in the motor cortex (from baseline) by 33.7% immediately following tUS (p = 0.009), and 32.4% (p = 0.047) 6 min later, with excitability no longer significantly different from baseline by 11 min post-stimulation. By contrast, subjects receiving sham tUS showed no significant changes in MEP amplitude.Conclusion: These findings demonstrate that tUS delivered via a commercially available diagnostic imaging ultrasound system transiently increases excitability in the motor cortex as measured by MEPs. Diagnostic tUS devices are currently used for internal imaging in many health care settings, and the present results suggest that these same devices may also offer a promising tool for noninvasively modulating activity in the central nervous system. Further studies exploring the use of diagnostic imaging devices for neuromodulation are warranted.