Event-related desynchronization and excitability of the ipsilateral motor cortex during simple self-paced finger movements.

OBJECTIVE: To study the time course of oscillatory EEG activity and corticospinal excitability of the ipsilateral primary motor cortex (iM1) during self-paced phasic extension movements of fingers II-V. METHODS: We designed an experiment in which cortical activation, measured by spectral-power analysis of 28-channel EEG, and cortical excitability, measured by transcranial magnetic stimulation (TMS), were assessed during phasic self-paced extensions of the right fingers II-V in 28 right-handed subjects. TMS was delivered to iM1 0-1500 ms after movement onset. RESULTS: Ipsilateral event-related desynchronization (ERD) during finger movement was paralleled by increased cortical excitability of iM1 from 0-200 ms after movement onset and by increased intracortical facilitation (ICF) without changes in intracortical inhibition (ICI) or peripheral measures (F waves). TMS during periods of post-movement event-related synchronization (ERS) revealed no significant changes in cortical excitability in iM1. CONCLUSIONS: Our findings indicate that motor cortical ERD ipsilateral to the movement is associated with increased corticospinal excitability, while ERS is coupled with its removal. These data are compatible with the concept that iM1 contributes actively to motor control. No evidence for inhibitory modulation of iM1 was detected in association with self-paced phasic finger movements. SIGNIFICANCE: Understanding the physiological role of iM1 in motor control.     

Cabergoline reverses cortical hyperexcitability in patients with restless legs syndrome

OBJECTIVE: To reverse the profile of abnormal intracortical excitability in patients with restless legs syndrome (RLS) by administering the dopaminergic agonist cabergoline. METHODS: The effects of this drug on motor cortex excitability were examined with a range of transcranial magnetic stimulation (TMS) protocols before and after administration of cabergoline over a period of 4 weeks in 14 patients with RLS and in 15 healthy volunteers. Measures of cortical excitability included central motor conduction time; resting and active motor threshold to TMS; duration of the cortical silent period; short latency intracortical inhibition (SICI) and intracortical facilitation using a paired-pulse TMS technique. RESULTS: Short latency intracortical inhibition was significantly reduced in RLS patients compared with the controls and this abnormal profile was reversed by treatment with cabergoline; the other TMS parameters did not differ significantly from the controls and remained unaffected after treatment with cabergoline. Cabergoline had no effect on cortical excitability of the normal subjects. CONCLUSIONS: As dopaminergic drugs are known to increase SICI, our findings suggest that RLS may be caused by a central nervous system dopaminergic dysfunction. This study demonstrates that the cortical hyperexcitability of RLS is reversed by cabergoline, and provides physiological evidence that this dopamine agonist may be a potentially efficacious option for the treatment of RLS.     

Increased cortical excitability after selective REM sleep deprivation in healthy humans: A transcranial magnetic stimulation study

BackgroundREM sleep has antiepileptogenic properties whereas, its loss is known to have a proconvulsive role. However, the mechanisms underlying the proepileptogenic effects of REM sleep deprivation are yet not fully understood. The aim of our study was to evaluate the effects of selective REM sleep deprivation (SRD) on cortical excitability in healthy subjects by means of transcranial magnetic stimulation (TMS).MethodsTen normal subjects underwent three TMS sessions: (1) in baseline condition (BL), (2) after SRD by awakening them at each REM sleep onset and (3) after non-rapid eye movement sleep awakenings (NREM-A) as control for potential non-specific effects of interruptions. The TMS investigation included two protocols: (a) the evaluation of motor evoked potentials (MEPs) and silent period (SP) parameters, recorded in response to single pulse magnetic stimulation; (b) the evaluation of the time course of intracortical motor activity tested with paired-pulse TMS applied at inter-stimulus intervals of 1–10 ms.ResultsAfter SRD the principal finding observed using single pulse TMS was a significant reduction in the duration of SP whereas, a reduction of intracortical inhibition was found, using the paired-pulse TMS. TMS parameters did not show significant changes after NREM-A with respect to BL.ConclusionsSRD may influence cortical excitability with a reduction of inhibitory intracortical mechanisms, thus supporting the proconvulsant role of REM loss.     

Exercise-induced changes of motor excitability with and without sensory block

To explore interactions between the sensory and motor system, we investigated motor excitability changes following a motor exercise with and without an anesthetic block of cutaneous inputs overlying the target muscle. Transcranial magnetic stimulation (TMS) with a focal coil was applied to determine motor output maps, intracortical inhibition (ICI) and intracortical facilitation (ICF) of the first dorsal interosseous muscle (FDI) on both sides. Twelve subjects performed phasic right index finger adductions (frequency: 0.333 Hz) for 30 min. TMS measurements were performed before and after the motor task (Experiment 1). In Experiment 2, median and radial nerve were blocked with Ropivacaine injections at the right wrist prior to the motor exercise. TMS was applied before and after induction of anesthesia and after exercise. In Experiment 3, the same anesthetic block was applied and TMS was performed before and after induction of anesthesia and after additional 30 min of rest. In Experiment 1, right FDI motor output area was enlarged, its center of gravity moved posteriorly, and ICI was reduced after the exercise. In Experiment 2, anesthesia was associated with a shrinkage of right FDI motor output area. After exercise, right FDI motor output area enlarged again but was still significantly smaller than pre-anesthesia. In both experiments, TMS results of left FDI remained unchanged. In Experiment 3, the anesthesia-induced decrease of right FDI motor output area remained unchanged after the period of rest. We conclude that a simple motor task enhanced the cortical representation of the target muscle and reduced intracortical inhibition. An impairment of cutaneous afferents decreased the cortical representation of the target muscle. The decrease of motor excitability induced by the sensory deficit could only partially be reversed by the motor exercise.     

Transcranial magnetic stimulation in sleep fragmentation: a model to better understand sleep disorders

ObjectiveTo investigate practice-dependent plasticity and cortical inhibition/excitability in good sleepers after a night of sleep fragmentation (SF), by means of transcranial magnetic stimulation (TMS).MethodsIn basal condition (BC), after a full night of spontaneous sleep, and in fragmented condition (FC), after a fragmented night of sleep, motor evoked potential (MEP) amplitude, motor threshold (MT), silent period (SP), and intracortical inhibition were assessed. In both conditions subjects performed, also, a bimanual motor task: MEPs were recorded before and after exercise, and after rest. We evaluated the presence of post-exercise facilitation and delayed facilitation. Subjects reported their alertness level (Stanford Sleepiness Scale–SSS).ResultsMT and SSS were significantly increased in SF. Instead, no significant differences for MEP amplitude or SP or intracortical inhibition were found. In both conditions post-exercise facilitation and delayed facilitation were present.ConclusionSF produces disruption of nocturnal sleep and increases daytime sleepiness. Confirmatory features of this clinical behaviour could be that in FC we observed a significant increase in SSS and in MT. SF was unable to modify cortical inhibition\excitability and\or to influence plasticity-related parameters. These results seem inconsistent with some of TMS alterations observed in sleep deprivation (SD) and restless legs syndrome (RLS). We suggest that SD and SF represent different phenomena that can depend on various networks acting on motor cortex. We speculate that alterations in cortical excitability found in RLS are intrinsically related to the underlying disease itself and are not instead directly associated with the SF present in RLS.     

Intravenous clomipramine decreases excitability of human motor cortex. A study with paired magnetic stimulation

Several recent reports suggest the possibility of monitoring pharmacological effects on brain excitability through transcranial magnetic stimulation (TMS). In these studies, paired magnetic stimulation has been used in normal subjects and on patients who were taking different antiepileptic drugs. The aim of our study was to investigate motor area excitability on depressed patients after intravenous administration of a single dose of clomipramine, a tricyclic antidepressant. Motor cortex excitability was studied by single and paired transcranial magnetic stimulation (TMS) before and after 4, 8 and 24 h from intravenous administration of 25 mg of clomipramine. Cortical excitability was measured using different TMS parameters: motor threshold (MT), motor evoked potential (MEP) amplitude, duration of cortical silent period (CSP), intracortical inhibition (ICI) and intracortical facilitation (ICF). Spinal excitability and peripheral nerve conduction was measured by F response and M wave. A temporary but significant increase of motor threshold and intracortical inhibition and a decrease of intracortical facilitation were observed 4 h following drug administration. MEP amplitude, cortical silent period, F response and M wave were not significantly affected by drug injection. Our findings suggest that a single intravenous dose of clomipramine can exert a significant but transitory suppression of motor cortex excitability in depressed patients. TMS represents a useful research tool in assessing the effects of motor cortical excitability of neuropsychiatric drugs used in psychiatric disease.     

Electrophysiological correlates of motor conversion disorder

In patients with a functional (psychogenic) paresis, motor conduction tests are, by definition, normal. We investigated whether these patients exhibit an abnormal motor excitability. Four female patients with a functional paresis of the left upper extremity were studied using transcranial magnetic stimulation (TMS). We investigated motor thresholds, intracortical inhibition and intracortical facilitation at rest. Corticospinal excitability was evaluated by single pulse TMS during rest and during imagination of tonic index finger adductions. Data obtained from the affected first dorsal interosseous muscle were compared with the unaffected hand and with a healthy age‐matched control group. Three patients demonstrated a flaccid paresis, one patient had a psychogenic dystonia. Motor thresholds, short interval intracortical inhibition and intracortical facilitation recorded from the affected side were normal. In healthy subjects, movement imagination produced an increase of corticospinal excitability. In the patients, motor imagery with the affected index finger resulted in a decrease of corticospinal excitability compared to rest, being significantly different from the unaffected side and from the control group. We suggest that suppression of corticospinal excitability during movement imagination is an electrophysiological correlate of the patients' inability to move voluntarily and provides some insight into the pathophysiology of this disorder. © 2008 Movement Disorder Society     

Motor cortex excitability in chronic fatigue syndrome.

OBJECTIVE: To use transcranial magnetic stimulation (TMS) to define motor cortical excitability in chronic fatigue syndrome (CFS) subjects during a repetitive, bilateral finger movement task. METHODS: A total of 14 CFS patients were tested and compared with 14 age-matched healthy control subjects. TMS of the motor cortex (5% above threshold) was used to elicit motor evoked potentials (MEPs). Subjects performed regular (3-4/s) repetitive bilateral opening-closing movements of the index finger onto the thumb. MEPs of the first dorsal interosseus (FDI) were measured before, immediately following exercise periods of 30, 60 and 90 s, and after 15 min of rest. RESULTS: Performance, defined by rate of movement, was significantly slower in CFS subjects (3.5/s) than in controls (4. 0/s) independent of the hand measured. The rate, however, was not significantly affected by the exercise duration for either group. The threshold of TMS to evoke MEPs from the FDI muscle was significantly higher in CFS than in control subjects, independent of the hemisphere tested. A transient post-exercise facilitation of MEP amplitudes immediately after the exercise periods was present in controls independent of the hemisphere tested, but was absent in CFS subjects. A delayed facilitation of MEPs after 15-30 min of rest was restricted to the non-dominant hemisphere in controls; delayed facilitation was absent in CFS subjects. CONCLUSIONS: Individuals with CFS do not show the normal fluctuations of motor cortical excitability that accompany and follow non-fatiguing repetitive bimanual finger movements.     

Neurophysiological study of corticomotor pathways in restless legs syndrome.

OBJECTIVE: To test the variations in cerebral motor excitability in patients with primary restless legs syndrome (RLS) by using electrophysiological techniques. In RLS patients periodic legs movements (PLMs) in sleep and wake have been described and it is hypothesised that PLMs result from a sleep-related disinhibition of descending central motor inhibitory pathways. Moreover, in primary RLS, these modifications are still debated. METHODS: In 15 patients with primary RLS, transcranial magnetic stimulation (TMS) was carried out using several paradigms, particularly paired pulse TMS with short interstimulus intervals (ISI) in abductor digiti minimi (ADM) and tibialis anterior (TA) muscles. RESULTS: Short ISI paired TMS showed a significant decrease in inhibition and increase in facilitation in ADM muscles. This result was even more evident in TA muscles of patients as compared to the controls and these modifications were more evident in the limbs which were more affected by PLM. Moreover, intracortical (corticocortical) inhibition (ICI) and intracortical facilitation (ICF) unchanged their biphasic time course. CONCLUSIONS: In our study the changes in short paired-pulse ICI and ICF revealed the presence of an altered excitability of central motor pathways, with good correlation with asymmetric distribution of symptoms.     

Effects of deep brain stimulation on the primary motor cortex: Insights from transcranial magnetic stimulation studies

Deep brain stimulation (DBS) implanted in different basal ganglia nuclei regulates the dysfunctional neuronal circuits and improves symptoms in movement disorders. However, the understanding of the neurophysiological mechanism of DBS is at an early stage. Transcranial magnetic stimulation (TMS) can be used safely in movement disorder patients with DBS, and can shed light on how DBS works. DBS at a therapeutic setting normalizes the abnormal motor cortical excitability measured with motor evoked potentials (MEP) produced by primary motor cortical TMS. Abnormal intracortical circuits in the motor cortex tested with paired-pulse TMS paradigm also show normalization with DBS. These changes are accompanied with improvements in symptoms after chronic DBS. Single-pulse DBS produces cortical evoked potentials recorded by electroencephalography at specific latencies and modulates motor cortical excitability at certain time intervals measured with MEP. Combination of basal ganglia DBS with motor cortical TMS at stimulus intervals consistent with the latency of cortical evoked potentials delivered in a repetitive mode produces plastic changes in the primary motor cortex. TMS can be used to examine the effects of open and closed loop DBS. Patterned DBS and TMS delivered in a repetitive mode may be developed as a new therapeutic method for movement disorder patients.     

Direct comparison of cortical excitability to transcranial magnetic stimulation in obstructive sleep apnea syndrome and restless legs syndrome

ObjectiveChanges to transcranial magnetic stimulation (TMS) have been reported in obstructive sleep apnea syndrome (OSAS) and restless legs syndrome (RLS), although no direct comparison study is available. The aim of this new investigation is to assess and compare cortical excitability of OSAS and RLS patients using the same methodology and under the same experimental conditions.MethodsFourteen patients with OSAS and 12 with RLS were compared to 14 age-matched controls. All patients were untreated and had a severe degree of disease. Resting motor threshold (rMT), cortical silent period (CSP) and motor evoked potentials MEPs, as well as intracortical inhibition (ICI) and facilitation at interstimulus interval (ISI) of 3 and 10 ms, respectively, were explored from the right first dorsal interosseous muscle, during wakefulness.ResultsrMT was higher in OSAS than in RLS and controls. CSP was shorter in RLS only when compared to apneic patients, whereas it was similar between OSAS and controls. OSAS subjects exhibited slightly prolonged central motor conductivity, whereas MEP amplitude was smaller in both patient groups. The ICI ratio at ISI of 3 ms was decreased in RLS patients only.ConclusionsDistinct changes of responses at TMS were found, probably connected with the different neurophysiological substrates underlying OSAS and RLS and could not be interpreted as a mere reflection of the effects of sleep architecture alteration. TMS can be considered an additional tool for the understanding of clinical and pathophysiological aspects of sleep disorders, and possibly for the evaluation of the effect of therapy.     

Effects of citalopram on the excitability of the human motor cortex: a paired magnetic stimulation study

Several recent reports suggest the possibility of monitoring pharmacological effects on brain excitability through transcranial magnetic stimulation (TMS). Different drugs have been studied using paired magnetic stimulation in normal subjects and patients. In particular, it has been suggested that antidepressant drugs may have an appreciable effect on motor excitability. The aim of the present study was to investigate motor area excitability in normal subjects after oral administration of a single dose of citalopram, a selective serotonin reuptake inhibitor (SSRI) antidepressant. Motor cortex excitability was studied by single and paired transcranial magnetic stimulation before and 2.5 and 36 (t1/2=36 h) h after oral administration of 30 mg of citalopram. Cortical excitability was measured using different transcranial magnetic stimulation parameters: motor threshold (MT), motor-evoked potential (MEP) amplitude and latency, motor recruitment, duration of cortical silent period (CSP), intracortical inhibition and intracortical facilitation. Spinal excitability and peripheral nerve conduction were measured by F response and M wave. Temporary but significant increases in motor threshold, motor-evoked potentials, silent period and intracortical inhibition were observed 2.5 h after drug administration, without any significant changes in motor-evoked potential amplitude and latency and spinal excitability parameters. Our findings suggest that a single oral dose of citalopram can induce significant but transitory suppression of motor cortex excitability in normal subjects.     

Reduced excitability of the motor cortex in untreated patients with de novo idiopathic "grand mal" seizures.

OBJECTIVES: Transcranial magnetic stimulation (TMS) was used to investigate motor cortex excitability, intracortical excitatory, and inhibitory pathways in 18 patients having experienced a first "grand mal" seizure within 48 hours of the electrophysiological test. All had normal brain MRI, and were free of any treatment, drug, or alcohol misuse. Results were compared with those of 35 age matched normal volunteers. METHODS: The following parameters of responses to TMS were measured: motor thresholds at rest and with voluntary contraction, amplitudes of responses, cortical silent periods, and responses to paired pulse stimulation with interstimulus intervals of 1 to 20 ms. RESULTS: In patients, there were significantly increased motor thresholds with normal amplitudes of motor evoked potentials (MEPs), suggesting decreased cortical excitability. Cortical silent periods were not significantly different from those of normal subjects. Paired TMS with short interstimulus intervals (1-5 ms) induced normal inhibition of test MEPs, suggesting preserved function of GABAergic intracortical inhibitory interneurons. On the contrary, the subsequent period of MEP facilitation found in normal subjects (ISIs of 6-20 ms) was markedly reduced in patients. This suggests the existence of abnormally prolonged intracortical inhibition or deficient intracortical excitation. In nine patients retested 2 to 4 weeks after the initial seizure, these abnormalities persisted, although to a lesser extent. CONCLUSION: The present findings together with abnormally high motor thresholds could represent protective mechanisms against the spread or recurrence of seizures.     

Changes of cortical excitability after dopaminergic treatment in restless legs syndrome

ObjectiveDopaminergic pathways are most likely involved in the pathophysiology of restless legs syndrome (RLS). In previous investigations, an alteration of cortical excitability was suggested to be related to a dopaminergic dysfunction in RLS. The purpose of our study was to compare practice-dependent plasticity in RLS patients before and after a month of dopaminergic treatment.MethodsSingle-pulse transcranial magnetic stimulation (TMS) was used to define motor evoked potential (MEP) amplitude, motor threshold, and silent period (SP) as well. Subjects performed three exercise blocks (bimanual motor task). MEP amplitude, registered immediately after each exercise block and after a rest period, was compared to baseline. The time course of intra-cortical inhibition was tested using paired-pulse TMS at short inter-stimulus intervals. For the single-pulse TMS procedures, we enrolled 12 patients affected by primary RLS and 12 normal subjects. For the paired-pulse TMS procedures, only six patients underwent the examination. RLS patients underwent the examination in both pre- and post-dopaminergic treatment conditions.ResultsIn RLS patients MEP amplitude increased after the rest period only in the post-treatment condition, showing a delayed facilitation. After exercise, MEP amplitude increased, but not enough to be significant, showing a positive trend but not a clear-cut post-exercise facilitation. In the pre-treatment condition instead, MEP amplitude did not change either after rest period or after exercise.RLS patients showed a marked increase of the central motor inhibition, assessed by using paired-pulse TMS at short inter-stimulus intervals after pramipexole treatment. On the contrary, the duration of the SP did not change compared to the pre-treatment condition.ConclusionsIn RLS patients after dopaminergic treatment, the main finding was the changing of MEP amplitude after rest following a motor task. Since dopaminergic treatment can reverse delayed facilitation in RLS, we hypothesized that cortical plasticity related to dopaminergic systems may play a crucial role in RLS pathophysiology.     

Modulation of cortical excitability and interhemispheric inhibition prior to rhythmic unimanual contractions

The objective of this study was to investigate premotor modulation of motor cortical excitability between rhythmic unimanual finger contractions. Applying TMS at rest prior to an anticipated contraction provides a measure of cortical excitability that reflects premotor modulatory drive and is uncontaminated by the alterations in spinal and cortical excitability that occur during muscle activation. We hypothesized that premotor structures contribute to unimanual movement through the modulation of intracortical and interhemispheric inhibitory circuits within the primary motor cortex and that this premotor modulation would be evident at rest between contractions. Thus, we used transcranial magnetic stimulation (TMS) to assess short interval intracortical inhibition (SICI) and interhemispheric inhibition (IHI) in a 500-ms epoch prior to a planned contraction of the right FDI in 10 participants (21.4±1.9 years). These measures of inhibition were made in three different states: (1) at complete rest (with no plan to contract), (2) at rest between rhythmic contractions, and (3) during low level contractions. Cortical excitability was enhanced prior to a contraction and during a contraction compared to at rest (F((2,18))=758.3, p<0.001). IHI was also increased prior to a contraction compared to at rest and during a contraction while SICI was only reduced during a contraction (F((2,38))=30.3, p<0.001).We used this pre-contraction protocol to investigate the cortical mechanisms of unimanual control. However, this protocol would be a useful tool to investigate any neuromuscular adaptation that may occur as a result of altered premotor modulation of cortical excitability, such as neuromuscular fatigue, training and movement disorders.     

Motor cortex dysfunction revealed by cortical excitability studies in Parkinson's disease: influence of antiparkinsonian treatment and cortical stimulation.

Single or paired pulse paradigms of transcranial magnetic stimulation (TMS) provide several parameters to test motor cortex excitability, such as motor threshold (MT), motor evoked potential (MEP) amplitude, electromyographic silent period to cortical stimulation (CSP) and intracortical facilitation (ICF) or inhibition (ICI). Various changes in TMS parameters, revealing motor cortex dysfunction, were found in patients with Parkinson's disease (PD). For instance, low MT and increased MEP size disclosed an enhanced corticospinal motor output at rest, while reduced ICF and failure of MEP size increase during contraction suggested defective facilitatory cortical inputs, particularly for movement execution. Inhibitory cortical pathways were also found less excitable at rest (reduced ICI) and sometimes during contraction (shortened CSP). By restoring cortical inhibition, dopaminergic drugs and deep brain stimulation probably overcome the difficulty to focus neuronal activity onto the appropriate network required for a specific motor task. The application of repetitive TMS trains over motor cortical areas also showed some effect on cortical excitability, opening perspectives to consider the motor cortex as a target for therapeutic neuromodulation in PD. However, systematic studies of cortical excitability remained to be performed in large series of patients with PD, taking into account disease stage, clinical symptoms and medication influence.     

Transient motor evoked potential suppression following a complex sensorimotor task.

OBJECTIVE: To investigate the mechanism involved in the transient suppression of the response to transcranial magnetic stimulation (TMS) following repeated performance of a complex sensorimotor training task (ST). METHODS: A total of 19 healthy subjects participated in 4 experiments, all involving performance of the grooved pegboard test (GPT). The experiments investigated the effect of the ST on corticospinal and intracortical excitability, spinal excitability and maximal pinch grip force. RESULTS: Motor evoked potential amplitude decreased significantly following the ST in both muscles tested and this was associated, but not correlated, with a decrease in the time taken to perform the GPT. There was no change in intracortical inhibition or facilitation (tested at interstimulus intervals of 3 and 10 ms, respectively). M wave amplitude was unchanged, as were F wave amplitude, latency and persistence and there was no evidence of muscle fatigue. CONCLUSIONS: The reduction in corticospinal excitability was short lasting (<10 min) and was not accompanied by changes at the spinal or peripheral level, suggesting that other intracortical circuits may be involved. SIGNIFICANCE: Repeated performance of motor tasks can result in both short- and long-term modulation of motor cortical excitability. However, the relationship between changes in corticospinal excitability and motor performance is complex and critically dependent upon task type and duration.     

Motor system excitability in patients with restless legs syndrome

In 18 patients with idiopathic restless legs syndrome (RLS), intracortical inhibition by paired transcranial magnetic stimulation (TMS) was significantly reduced for both foot and hand muscles, suggesting that the entire motor cortex is disinhibited in RLS. Decreased intracortical facilitation in the foot muscle but not in the hand muscle may be due to subliminal activation of the symptomatic lower limbs. Motor excitability measurements of single TMS were not altered. These results support a subcortical origin of RLS.     

Assessment of cortical excitability using threshold tracking techniques

Conventional paired-pulse transcranial magnetic stimulation (TMS) techniques of assessing cortical excitability are limited by fluctuations in the motor evoked potential (MEP) amplitude. The aim of the present study was to determine the feasibility of threshold tracking TMS for assessing cortical excitability in a clinical setting and to establish normative data. Studies were undertaken in 26 healthy controls, tracking the MEP response from abductor pollicis brevis. Short-interval intracortical inhibition (SICI) occurred up to an interstimulus interval (ISI) of 7-10 ms, with two distinct peaks evident, at ISIs of < or =1 and 3 ms, followed by intracortical facilitation to an ISI of 30 ms. Long-interval intracortical inhibition (LICI) occurred at ISIs of 50-300 ms, peaking at 150 ms. The present study has confirmed the effectiveness of the threshold tracking TMS technique in reliably and reproducibly measuring cortical excitability. Simultaneous assessment of upper and lower motor neuronal function with threshold tracking techniques may help to determine the site of disease onset and patterns of progression in neurodegenerative diseases.