Effect of paired transcranial magnetic stimulation on the cortical silent period

Objective. To investigate the behaviour of silent period (SP) during paired magnetic cortical stimulation. Background. Paired cortical magnetic stimulation is known to inhibit or facilitate motor evoked potentials (MEPs), but no attention has been paid to its effect on SP. Methods. SP was measured in the contracted first dorsal interosseus muscle after paired cortical stimuli at given interstimulus intervals (ISIs) in eight healthy subjects. Test stimulus intensity was fixed at 110% of resting threshold (RT), while three levels of conditioning stimulus intensities at 40%, 65% and 90% RT were separately employed. We also examined the effect of progressively increasing the test stimulus intensity (120–150 RT) on SP while maintaining stable conditioning stimulus intensity. Results. 65% RT conditioning stimulus shortened the SP at 1–3 ms ISIs with MEP size reduction, and prolonged the SP at 15–20 ms ISIs without affecting MEP size. 90% RT conditioning stimulus showed only SP prolongation, while 40% RT showed only SP shortening at 1 ms ISI. The SP shortening at 2 ms ISI was the most evident with 120% RT test stimulus, but without correlation with the MEP size. The SP prolongation at 15 ms ISI was maximal with 110% RT test stimulus and then almost abolished with 150% RT. The SP shortening at short intervals might be due not only to spinal but also to suprasegmental mechanisms, conceivably mediating cortical excitatory drive to the corticospinal tract. The SP prolongation at intermediate intervals might be due to activation of slowly conducting, intra- or sub-cortical polysynaptic pathways exerting a facilitatory drive on the cortical inhibitory interneurons.     

Modification of the silent period by double transcranial magnetic stimulation.

OBJECTIVES: To study the time course of the changes of the inhibitory network of the human motor system, we investigated the silent period (SP) in 7 healthy subjects by double suprathreshold transcranial magnetic stimulation (TMS). METHODS: SPs and motor evoked potentials (MEPs) were recorded from the voluntarily activated right abductor digiti minimi muscle. Conditioning and test stimuli were delivered with equal intensity, which was set to yield a baseline SP duration of 130 ms by a single pulse, and with various interstimulus intervals (ISIs). In addition, a control experiment with adjustment of the intensity of single stimuli was performed. RESULTS: At ISIs of 20 and 30 ms the test pulse SP duration was prolonged, without increasing the MEP amplitude. The SP duration shortened at longer ISIs and showed a significant depression between ISIs of 60-110 ms. The shortened SP was accompanied by a diminished MEP. The control experiment revealed that the SPs evoked by the adjusted pulses were significantly shorter than the test pulse SPs. CONCLUSIONS: A conditioning stimulus can prolong and shorten the test pulse SP duration at different ISIs. The prolongation is probably cortically generated, whereas the shortening is likely to occur at a cortical and spinal level.     

On the estimation of silent period thresholds in transcranial magnetic stimulation

ObjectiveWe evaluated the induction of corticospinal silent period (SP) using transcranial magnetic stimulation (TMS) at stimulation intensities normalized to resting motor threshold (rMT) or silent period thresholds (SPTs). The aim was to reduce the characteristic inter-individual variation in SP measurements in healthy population to improve the sensitivity of such measurements.MethodsThe cortical representation area of the right hand musculature of 12 healthy subjects was stimulated with navigated TMS with varying stimulating intensities. Subsequently, the individual SPTs for eliciting SPs of 20, 30, and 50 ms in duration were determined from the input–output characteristics.ResultsWhile SPT for 20 and 50 ms SPs differed from rMT, the SPT for 30 ms was similar to rMT. Nevertheless, the inter-individual variation in SP duration was reduced significantly at 120% of SPT30 when compared with SP durations obtained at 120% of rMT.ConclusionsInter-individual variation in the SP duration decreases when applying TMS at stimulation intensities normalized to the individual SPTs instead to the rMT. This makes the SP duration more specific to inhibition and less affected by changes in cortical excitability.SignificanceUse of individual SPTs may improve the sensitivity of the SP measures in studies with inter-individual design.     

Modulation of motor cortex excitability by paired peripheral and transcranial magnetic stimulation

Objective

Repetitive application of peripheral electrical stimuli paired with transcranial magnetic stimulation (rTMS) of M1 cortex at low frequency, known as paired associative stimulation (PAS), is an effective method to induce motor cortex plasticity in humans. Here we investigated the effects of repetitive peripheral magnetic stimulation (rPMS) combined with low frequency rTMS (‘magnetic-PAS’) on intracortical and corticospinal excitability and whether those changes were widespread or circumscribed to the cortical area controlling the stimulated muscle.

The effect of transcranial direct current stimulation on motor sequence learning and upper limb function after stroke

Objective

To assess the impact of electrode arrangement on the efficacy of tDCS in stroke survivors and determine whether changes in transcallosal inhibition (TCI) underlie improvements.

Correlation between disability and transcranial magnetic stimulation abnormalities in patients with multiple sclerosis

Multiple sclerosis (MS) is an idiopathic inflammatory demyelinating disorder of the central nervous system. Clinical evaluation, MRI, cerebrospinal fluid testing and evoked potentials (EP) are among the available methods utilized for disease diagnosis and monitoring. To date, no surrogate markers have been established to assess disease evolution and progression. The aim of this study is to assess motor evoked potentials (MEP) of MS patients by transcranial magnetic stimulation (TMS) and investigate the possible correlations between TMS abnormalities and disability in the patient group, which includes a subgroup with no apparent pyramidal tract dysfunction. A total of 131 clinically definite MS patients were included in the study. Motor responses to TMS stimulation were recorded. Absent values, decreases in amplitude, prolongation of latency and central motor conduction time (CMCT) were considered as abnormal. A total of 109 (83%) patients displayed abnormal MEP amplitude, 68 (52%) displayed MEP latency, and 64 (49%) displayed CMCT abnormalities. Abnormal CMCT, latency and amplitude results were correlated with Expanded Disability Status Scale scores (p < 0.001). Our results indicate that TMS-EP in MS patients is correlated with disability, and that these findings may support the role of EPs in predicting disability even in subclinical presentations.     

Short-term reliability of transcranial magnetic stimulation motor maps in upper limb amputees

The aim of this study was to verify the short-term reliability of transcranial magnetic stimulation (TMS) parameters for a damaged stump muscle in upper-limb amputees (n = 6). The motor threshold, response latency and map center of gravity in the mediolateral plane showed good reliability, whereas the map volume measure was less stable. The stability of most TMS measures across time supports the use of TMS in studying cortical plasticity in amputees.     

磁刺激运动诱发电位技术对急性脊髓炎患者预后的影响

目的探讨磁刺激运动诱发电位（MEP）对急性脊髓炎患者预后评估的意义。方法对36例根据病史、体征、脑脊液、磁共振临床确诊的急性脊髓炎患者于发病2周内进行磁刺激运动诱发电位检查,记录检查结果,并于12周后复查。正常对照组为30例健康者。结果急性脊髓炎患者MEP异常形式主要表现为锥体束传导阻滞、潜伏期延长、波幅降低。12周后复查显示,锥体束传导阻滞患者预后较差;而锥体束传导延迟、波幅降低患者预后良好。结论磁刺激运动诱发电位不仅能判断疾病的严重程度,而且对判断预后提供帮助;磁刺激运动诱发电位显示锥体束传导延迟和波幅降低者预后较好,锥体束传导阻滞者预后较差。     

Improvement of motor performance and modulation of cortical excitability by repetitive transcranial magnetic stimulation of the motor cortex in Parkinson's disease.

OBJECTIVE: To assess the effects of focal motor cortex stimulation on motor performance and cortical excitability in patients with Parkinson's disease (PD). METHODS: Repetitive transcranial magnetic stimulation (rTMS) was performed on the left motor cortical area corresponding to the right hand in 12 'off-drug' patients with PD. The effects of subthreshold rTMS applied at 0.5 Hz (600 pulses) or at 10 Hz (2000 pulses) using a 'real' or a 'sham' coil were compared to those obtained by a single dose of l-dopa. The assessment included a clinical evaluation by the Unified Parkinson's Disease Rating Scale and timed motor tasks, and a neurophysiological evaluation of cortical excitability by single- and paired-pulse TMS techniques. RESULTS: 'Real' rTMS at 10 or 0.5 Hz, but not 'sham' stimulation, improved motor performance. High-frequency rTMS decreased rigidity and bradykinesia in the upper limb contralateral to the stimulation, while low-frequency rTMS reduced upper limb rigidity bilaterally and improved walking. Concomitantly, 10 Hz rTMS increased intracortical facilitation, while 0.5 Hz rTMS restored intracortical inhibition. CONCLUSIONS: Low- and high-frequency rTMS of the primary motor cortex lead to significant but differential changes in patients with PD both on clinical and electrophysiological grounds. The effects on cortical excitability were opposite to previous observations made in healthy subjects, suggesting a reversed balance of cortical excitability in patients with PD compared to normals. However, the underlying mechanisms of these changes remain to determine, as well as the relationship with clinical presentation and response to l-dopa therapy. SIGNIFICANCE: The present study gives some clues to appraise the role of the primary motor cortex in PD. Clinical improvement induced by rTMS was too short-lasting to consider therapeutic application, but these results support the perspective of the primary motor cortex as a possible target for neuromodulation in PD.     

Decreased cortical excitability during motor imagery after disuse of an upper limb in humans

OBJECTIVE: The present study investigated the effect of joint immobilization on corticomotoneuronal excitability to only intracortical input from a hierarchical level above the primary motor cortex. METHODS: Motor evoked potentials (MEPs) and H-reflexes in the flexor carpi radialis muscle were elicited from 8 orthopedic patients with splints and 8 healthy volunteers. Each patient was examined on the day of splint removal (disuse stage) and 2 months after that day (recovery stage). Both potentials were recorded under 3 conditions: at rest, while imagining motor movement (during motor imagery), and during 10% of maximum voluntary contraction (10% MVC). RESULTS: In the patient group, the amplitude of surface electromyography during voluntary maximum wrist flexion was lower at the disuse stage than at the recovery stage, although the supra-maximum M-wave amplitude did not change between stages. Compared to both the patient group at the recovery stage and the control group, patients at the disuse stage recorded significantly lower MEPs, but only during motor imagery. In contrast, the H-reflex amplitudes were not significantly changed under any of the 3 conditions for both patients and control. CONCLUSIONS: The present results indicated a strict parallelism between motor execution (the reduction of electromyography during mvc after immobilization) and motor imagery (the reduction of MEP-amps after immobilization). This parallelism suggests that a functional reorganization or decreased excitability in the cerebral cortex area involved in executing movement likely decreases the motor capability to produce voluntary muscular output after immobilization.     

Quantification of the corticospinal silent period evoked via transcranial magnetic stimulation

A magnetic pulse to the cortex during a muscle contraction produces a motor evoked potential (MEP) followed by electrical quiescence before activity resumes that is indicative of corticospinal inhibition and commonly referred to as the corticospinal slient period (SP). The purpose of the present study was to determine the effect of stimulus intensity and quantification method on the between-visit variability of the SP in healthy individuals. On two occasions we recorded the SP from 9 humans at 3 stimulus intensities (10, 20 and 30% above active motor threshold [AMT]) and quantified the SP based on 8 common criteria. We evaluated the effect of stimulus intensity on reliability by using the limits of agreement, and this analysis revealed that the lower stimulus intensities (10 and 20% AMT) exhibited heteroscedasticity, which indicates the amount of random error increases as the silent period increases. The 30% AMT intensity was homoscedastic. We used both visual and mathematical approaches to quantify the SP, and observed that the between-visit coefficient of variation (CV) was less for the visual methods, and that the CV was reduced when the SP onset was earliest in the temporal occurrence of events (i.e. MEP onset to EMG return CV=12%). Inter-rater reliability for the visual analyses were high (r=0.91-0.99). These results suggest that SPs evoked with a stimulus intensity >or=30% AMT and quantified visually by defining the start of the SP at stimulus delivery or the start of the MEP be utilized to decrease the between visit variability.     

Effects of paired associated stimulation with different stimulation position on motor cortex excitability and upper limb motor function in patients with cerebral infarction

ObjectiveTo investigate the effects of paired associated stimulation (PAS) with different stimulation position on motor cortex excitability and upper limb motor function in patients with cerebral infarction.MethodA total of 120 volunteers with cerebral infarction were randomly divided into four groups. Based on conventional rehabilitation treatment, the PAS stimulation group was given the corresponding position of PAS treatment once a day for 28 consecutive days. The MEP amplitude and RMT of both hemispheres were assessed before and after treatment, and a simple upper limb Function Examination Scale (STEF) score, simplified upper limb Fugl–Meyer score (FMA), and improved Barthel Index (MBI) were used to assess upper limb motor function in the four groups.ResultsFollowing PAS, the MEP amplitude decreased, and the RMT of abductor pollicis brevis (APB) increased on the contralesional side, while the MEP amplitude increased and the RMT of APB decreased on the ipsilesional side. After 28 consecutive days the scores of STEF, FMA, and MBI in the bilateral stimulation group were significantly better than those in the ipsilesional stimulation group and the contralesional stimulation group, but there was no significant difference in the scores of STEF, FMA, and MBI between the ipsilesional stimulation group and the contralesional stimulation group.ConclusionThe excitability of the motor cortex can be changed when the contralesional side or the ipsilesional side was given the corresponding PAS stimulation, while the bilateral PAS stimulation can more easily cause a change of excitability of the motor cortex, resulting in better recovery of the upper limb function.     

Effect of intensive motor training with repetitive transcranial magnetic stimulation on upper limb motor function in chronic post-stroke patients with severe upper limb motor impairment

Background Intensive motor training with low-frequency repetitive transcranial magnetic stimulation (rTMS) has efficacy as a therapeutic method for motor dysfunction of the affected upper limb in patients with mild to moderate stroke. However, it is not clear whether this combination therapy has the same effect in chronic post-stroke patients with severe upper limb motor impairment.

Objectives The aim of this study was to test the treatment effects of intensive motor training with low-frequency rTMS in chronic post-stroke patients with severe upper limb motor impairment.

Methods A convenience sample of 26 chronic post-stroke patients with severe upper limb motor impairment participated in this study with the non-randomized, non-controlled clinical trial. All subjects were hospitalized to receive intensive motor training with low-frequency rTMS. During 2 weeks in which Sundays were excluded, a total of 24 sessions (2 sessions per day) of the intervention were conducted. The Fugl–Meyer Assessment (FMA) and Wolf Motor Function Test (WMFT) were used to assess motor impairment and function of the affected upper limb, respectively, before and after intervention. Paired t-test was used to analyze the effects of the intervention.

Results The FMA total score and WMFT log performance time significantly improved from before to after intervention (FMA: 12.6–18.0; WMFT: 3.6–3.3, p < 0.001).

Conclusions The present results suggest that intensive motor training with low-frequency rTMS could improve motor impairment in chronic post-stroke patients with severe upper limb motor impairment and contribute to the expansion of the application range of this combination therapy.     

Motor cortex inhibition is not impaired in patients with Alzheimer's disease: evidence from paired transcranial magnetic stimulation

Motor cortex excitability was studied by transcranial magnetic stimulation (TMS) in 17 patients with Alzheimer’s disease (AD). Resting and active thresholds for TMS were significantly reduced in AD patients compared to young and aged healthy subjects. The maximum amplitude of the motor response evoked by TMS was also significantly increased in AD patients. We have tested if these changes are related to a modification of the short-lasting intracortical inhibition of the motor cortex by paired conditioning-test TMS. We found no significant differences between AD patients and aged healthy subjects even if there is a slight but significant difference between aged and young normal subjects. We conclude that the modification of excitability of the motor cortex does not result from an impaired intracortical inhibition.     

Temporal dispersion of cortically evoked single motor unit potentials in ALS

Peristimulus time histograms (PSTHs) can be used to investigate corticomotoneuronal dysfunction in amyotrophic lateral sclerosis (ALS). The most characteristic change is temporal dispersion of the primary peak. We recorded PSTHs in the extensor digitorum communis with voluntary motor units activation (standard PSTHs) or at rest (non-activated PSTHs). Standard PSTHs were recorded in 29 motor units of 12 healthy control subjects and 12 sporadic ALS patients. Double primary peaks were seen in three motor units of two healthy control subjects and 10 motor units from five ALS patients. The number of subpeaks was up to three in most of the normal motor units as well as in the earlier component of double primary peaks. The subpeaks were smaller and less discernible in the later component of double primary peaks. Non-activated PSTHs of ALS patients demonstrated similar decomposition of subpeaks in the motor units with significantly increased variability of latency. Similar findings in the standard PSTHs and non-activated PSTHs suggest that the abnormalities seen in ALS are independent of the membrane potential of the spinal motoneuron and therefore supraspinal in origin. The decomposed additional later component may indicate activation of slow conducting corticospinal tracts.     

Computer-based model of epidural motor cortex stimulation: Effects of electrode position and geometry on activation of cortical neurons

Objective

The aim of this study was to determine the effects of electrode placement, geometry, and polarity during epidural cortical stimulation (ECS) on thresholds for direct activation of cortical neurons.

Methods

We used a computational model of epidural electrical stimulation of the motor cortex coupled to compartmental models of cortical neurons.

Results

Thresholds varied with stimulation polarity and neuron position, and neurons deep within the sulci had much larger thresholds than those on the crowns or lips of the gyri. Axons were more excitable than cell bodies or dendrites. Delivering stimulation with the lead placed above or perpendicular to the sulci resulted in substantial stimulation of the gyri adjacent to the target gyrus. Electrode diameter and inter-electrode spacing influenced thresholds and affected the spread of activation in the cortex.

Conclusions

Electrode placement, geometry, and polarity during ECS influence excitation properties of cortical neurons substantially.

Significance

Epidural leads have varying geometries, and in clinical studies of ECS the placement of the lead has been inconsistent. These results provide an improved understanding of the effects of electrode placement, geometry, and polarity on the outcome of ECS and can facilitate the rational implantation and programming of ECS systems.     

Therapeutic applications of repetitive transcranial magnetic stimulation (rTMS) in movement disorders: A review

Repetitive transcranial magnetic stimulation (rTMS) is emerging as a valuable adjunctive therapeutic modality in movement disorders. It is a non-invasive technique of repeated stimulation of the cerebral cortex by a train of magnetic pulses. The therapeutic effect of rTMS was first noted in depression. Later several researchers have investigated the role of rTMS in various movement disorders, notably Parkinson's disease, dystonia, Tourette's syndrome etc. The rTMS protocols used in these studies vary widely, lacks uniformity and often the results are not consistent. The optimal rTMS parameters for each disorder are yet to be established. This review discusses the current knowledge on the therapeutic applications of rTMS in various movement disorders.     

Abnormal response of motor cortex to photic stimulation in idiopathic generalized epilepsy

Background: Intermittent photic stimulation (IPS) shortens the cortical silent period (CSP) elicited by transcranial magnetic stimulation (TMS) over the primary motor hand area (M1_HAND). This response is absent in healthy individuals with a photoparoxysmal response (PPR). Here we combined TMS of the M1_HAND with IPS to examine whether patients with idiopathic generalized epilepsy (IGE) exhibit an abnormal cortical response pattern to IPS. Methods: In 13 PPR‐positive and 12 PPR‐negative patients with IGE and in 13 PPR‐negative healthy controls, we used focal TMS to the M1_HAND to study how cortical excitability is changed by concurrent IPS at 50 Hz. Results: IPS at 50 Hz reduced the duration of the CSP in healthy PPR‐negative individuals, whereas IPS had no effect on the CSP in PPR‐positive and PPR‐negative patients with generalized epilepsy. The failure of IPS to shorten the CSP was independent of antiepileptic medication. Single‐pulse or paired‐pulse TMS only without concurrent IPS showed a higher motor threshold in PPR‐positive patients with epilepsy, presumably caused by antiepileptic medication. No additional differences in cortical excitability were found among groups. Conclusions: Because the CSP is mediated by intracortical GABAergic mechanisms, our results indicate that IGEs are associated with an altered responsiveness of GABAergic inhibitory circuits in the M1_HAND. This electrophysiological trait is independent of photosensitivity. Excitability changes at the cortical or thalamic level may mediate this abnormal cortical response pattern in patients with IGE.     

Effects of anodal transcranial direct current stimulation over lower limb primary motor cortex on motor learning in healthy individuals

Transcranial direct current stimulation (tDCS) is a neuromodulatory technique which alters motor functions in healthy humans and in neurological patients. Most studies so far investigated the effects of tDCS on mechanisms underlying improvements in upper limb performance. To investigate the effect of anodal tDCS over the lower limb motor cortex (M1) on lower limb motor learning in healthy volunteers, we conducted a randomized, single‐blind and sham‐controlled study. Thirty‐three (25.81 ± 3.85, 14 female) volunteers were included, and received anodal or sham tDCS over the left M1 (M1‐tDCS); 0.0625 mA/cm² anodal tDCS was applied for 15 min during performance of a visuo‐motor task (VMT) with the right leg. Motor learning was monitored for performance speed and accuracy based on electromyographic recordings. We also investigated the influence of electrode size and baseline responsivity to transcranial magnetic stimulation (TMS) on the stimulation effects. Relative to baseline measures, only M1‐tDCS applied with small electrodes and in volunteers with high baseline sensitivity to TMS significantly improved VMT performance. The computational analysis showed that the small anode was more specific to the targeted leg motor cortex volume when compared to the large anode. We conclude that anodal M1‐tDCS modulates VMT performance in healthy subjects. As these effects critically depend on sensitivity to TMS and electrode size, future studies should investigate the effects of intensified tDCS and/or model‐based different electrode positions in low‐sensitivity TMS individuals.     

Pregabalin exerts oppositional effects on different inhibitory circuits in human motor cortex: a double-blind, placebo-controlled transcranial magnetic stimulation study

PURPOSE: To explore acute effects of pregabalin (PGB) on human motor cortex excitability with transcranial magnetic stimulation (TMS). METHODS: PGB, 600 mg/day, was orally administered in 19 healthy subjects twice daily in a randomized, double-blind, placebo-controlled crossover design. Several measures of motor cortex excitability were tested with single- and paired-pulse TMS. RESULTS: Mean short-interval intracortical inhibition (SICI) was reduced after PGB (74 +/- 7% of unconditioned response) compared with placebo (60 +/- 6% of unconditioned response). In contrast, mean long-interval intracortical inhibition (LICI) was increased by PGB (26 +/- 4% of unconditioned response) compared with placebo (45 +/- 8% of unconditioned response), and mean cortical silent period (CSP) showed an increase from 139 +/- 8 ms or 145 +/- 8 ms after placebo to 162 +/- 7 ms or 161 +/- 10 ms after PGB. Motor thresholds, intracortical facilitation, and corticospinal excitability were unaffected. CONCLUSIONS: The observed excitability changes with oppositional effects on SICI and LICI or CSP suggest gamma-aminobutyric acid (GABA)B-receptor activation. They are markedly distinct from those induced by gabapentin, although both PGB and gabapentin are thought to mediate their function by binding to the alpha2-delta subunit of voltage-gated calcium channels. Conversely, the TMS profile of PGB shows striking similarities with the pattern evoked by the GABA-reuptake inhibitor tiagabine.