Paired-pulse Transcranial Magnetic Stimulation Technique Research Articles

Smoking status ameliorates cholinergic impairments in cortical inhibition in patients with schizophrenia

RationaleModulation of cortical excitability, in particular inhibition, is impaired in patients with schizophrenia. Chronic nicotine consumption, which is prevalent in this group, has been shown to alter cortical excitability in healthy individuals and to increase inhibitory activity. Thus, beneficial effects of smoking on impaired cortical excitability in patients with schizophrenia have been proposed, though direct experimental evidence is still lacking. ObjectivesWe aimed to explore the effect of chronic smoking on cortical excitability by comparing smoking and non-smoking patients with schizophrenia. MethodTwenty-six smoking and 19 non-smoking patients diagnosed with schizophrenia were included. Transcranial magnetic stimulation (TMS) applied to the primary motor cortex served as experimental paradigm for measuring corticospinal and intracortical excitability as follows: Resting motor threshold (RMT) and the input/output curve (I/O curve) were obtained to assess corticospinal excitability. Intracortical excitability was explored using paired-pulse TMS techniques (intracortical facilitation (ICF), short-latency intracortical inhibition (SICI) and short-latency afferent inhibition (SAI)). ResultsA significantly stronger inhibition in the cholinergically driven SAI protocol was observed in smokers compared to non-smokers. All other measures did not show significant differences between groups. ConclusionOur results suggest an increased inhibition within cholinergic circuits due to chronic nicotine consumption in schizophrenia. This increase may compensate impaired cholinergic neurotransmission and could explain the high rate of smokers in schizophrenia.

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

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

Regulation of primary motor cortex excitability by repetitive passive finger movement frequency

Somatosensory input induced by passive movement activates primary motor cortex (M1). We applied repetitive passive movement (RPM) of different frequencies to test if modulation of M1 excitability depends on RPM frequency. Twenty-seven healthy subjects participated in this study. Motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) to left M1 were recorded from the right first dorsal interosseous muscle (FDI) to assess corticospinal excitability (experiment 1: n=15), and F-waves were measured from the right FDI as an index of spinal motoneuron excitability (experiment 2: n=15). Passive abduction/adduction of the right index finger was applied for 10min at 0.5, 1.0, 3.0, and 5.0Hz. Both 0.5Hz-RPM and 1.0Hz-RPM decreased MEPs for 2min (p<0.05), and 5.0Hz-RPM decreased MEPs for 15min compared with baseline (p<0.05); however, there was no difference in MEPs after 3.0Hz-RPM. No F-wave changes were observed following any RPM intervention. Based on the results of experiments 1 and 2, we investigated whether RPM modulates cortical inhibitory circuit using the paired-pulse TMS technique (experiment 3: n=12). Short-interval intracortical inhibition (SICI) was measured using paired-pulse TMS (inter-stimulus interval of 3ms) before and after 1.0, 3.0, and 5.0Hz-RPM. Both 1.0 and 5.0Hz-RPM increased SICI compared with baseline (p<0.05). These experiments suggest that M1 excitability decreases after RPM depending on movement frequency, possibly through frequency-dependent enhancement of cortical inhibitory circuit in M1.

Exploring the Evolution of Cortical Excitability Following Acute Stroke

Background. Evolution of changes in intracortical excitability following stroke, particularly in the contralesional hemisphere, is being increasingly recognized in relation to maximizing the potential for functional recovery. Objective. The present study utilized a prospective longitudinal design over a 12-month period from stroke onset, to investigate the evolution of intracortical excitability involving both motor cortices and their relationship to recovery, and whether such changes were influenced by baseline stroke characteristics. Methods. Thirty-one patients with acute unilateral ischemic stroke were recruited from a tertiary hospital stroke unit. Comprehensive clinical assessments and cortical excitability were undertaken at stroke onset using a novel threshold-tracking paired-pulse transcranial magnetic stimulation technique, and repeated at 3-, 6-, and 12-month follow-up in 17 patients who completed the longitudinal assessment. Results. Shortly following stroke, short-interval intracortical inhibition (SICI) was significantly reduced in both lesioned and contralesional hemispheres that correlated with degree of recovery over the subsequent 3 months. Over the follow-up period, ipsilesional SICI remained reduced in all patient groups, while SICI over the contralesional hemisphere remained reduced only in the groups with cortical stroke or more baseline functional impairment. Conclusions. The current study has demonstrated that evolution of intracortical excitability, particularly over the contralesional hemisphere, may vary between patients with differing baseline stroke and clinical characteristics, suggesting that ongoing contralesional network recruitment may be necessary for those patients who have significant disruptions to the integrity of ipsilesional motor pathways. Results from the present series have implications for the development of neuromodulatory brain stimulation protocols to harness and thereby facilitate stroke recovery.

Posture-related modulation of cortical excitability in the tibialis anterior muscle in humans

Corticospinal excitability in the lower leg muscles is enhanced during standing as compared to other postures. In the present study, we investigated how the excitability of intracortical circuits that control the tibialis anterior muscle (TA) is modulated during standing. Short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were assessed by the paired-pulse transcranial magnetic stimulation technique during standing (STD) and sitting (SIT) with a comparable background activity level in both the soleus and the TA muscle. The results demonstrated that SICI was less effective during STD than during SIT, whereas ICF was more effective during STD than during SIT. These findings suggest that the excitabilities of these cortical neural circuits are modulated depending on posture. A decrease in SICI and an increase in ICF may reflect subliminal enhancement of the cortical excitability in the TA muscle during standing as compared with that during sitting.

Cortical excitability in smoking and not smoking individuals with and without nicotine

Activation of nicotinic acetylcholine receptors has a major neuromodulatory impact on central nervous system function. Beyond acute activation, chronic nicotine intake has long-lasting effects on cortical excitability in animal experiments, caused by receptor up- or down-regulation. Knowledge about the impact of nicotine on cortical excitability in humans, however, is limited. We therefore aimed to explore the effect of nicotine intake on cortical excitability in healthy human smokers and non-smokers. The primary motor cortex served as model, and cortical excitability was monitored via transcranial magnetic stimulation (TMS). Corticospinal excitability and intracortical excitability were recorded before and after application of nicotine patch in both groups. Corticospinal excitability was explored by motor threshold and input/output curve (I/O curve), and intracortical excitability was explored by means of paired-pulse TMS techniques (intracortical facilitation (ICF), short-latency intracortical inhibition (SICI), I-wave facilitation and short-latency afferent inhibition (SAI)). The results show that smokers during nicotine withdrawal display increased corticospinal excitability with regard to the I/O curve (TMS intensity 150% of resting motor threshold) compared to non-smokers and furthermore enhanced SAI and diminished ICF at the intracortical circuit level. After administration of nicotine, intracortical facilitation in smokers increased, while in non-smokers, inhibition (SICI, SAI) was enhanced. Our results show that chronic nicotine consumption in smokers alters cortical excitability independent from acute nicotine consumption and that acute nicotine has different effects on motor cortical excitability in both groups.

Neural mechanisms underlying the changes in ipsilateral primary motor cortex excitability during unilateral rhythmic muscle contraction

The aim of this study was to investigate the neural mechanisms underlying the changes in the ipsilateral primary motor cortex (ipsi-M1) excitability induced during the unilateral rhythmic muscle contraction of the first dorsal interosseous (FDI) (rhythmic contraction) muscle with three different frequencies of auditory cues (1, 2, and 3Hz). The effect of different frequencies of unilateral rhythmic contraction on changes in the ipsi-M1 excitability was assessed using a single-pulse transcranial magnetic stimulation (TMS) technique when subjects were performing the unilateral rhythmic contractions according to each auditory cue frequency. After that, the changes in short intracortical inhibition (SICI)/facilitation (ICF), long intracortical inhibition (LICI) within the ipsi-M1, and interhemispheric inhibition (IHI), as well as dorsal premotor cortex to M1 (PMd–M1), and dorsolateral prefrontal cortex to M1 (DLPFC-M1) connectivity from the contralateral hemisphere to the ipsi-M1 were assessed using paired-pulse TMS techniques. The motor evoked potentials (MEP) induced in the right FDI were recorded. In the results, the ipsi-M1 excitability induced in response to single-pulse TMS was significantly decreased in the 2Hz conditions, compared with the 1Hz and 3Hz conditions. Furthermore, PMd–M1 connectivity and LICI were significantly modulated depending on the frequency of the unilateral rhythmic contraction. In contrast, the changes in the SICI, ICF, IHI, and DLPFC–M1 were not directly associated with the rhythm frequency. These results suggest that PMd–M1 connectivity and LICI within the ipsi-M1 are likely to preferentially operate to modulate ipsi-M1 excitability during the performance of unilateral rhythmic contraction with different frequencies.

Utilizing Transcranial Magnetic Stimulation to Study the Human Neuromuscular System

Transcranial magnetic stimulation (TMS) has been in use for more than 20 years, and has grown exponentially in popularity over the past decade. While the use of TMS has expanded to the study of many systems and processes during this time, the original application and perhaps one of the most common uses of TMS involves studying the physiology, plasticity and function of the human neuromuscular system. Single pulse TMS applied to the motor cortex excites pyramidal neurons transsynaptically (Figure 1) and results in a measurable electromyographic response that can be used to study and evaluate the integrity and excitability of the corticospinal tract in humans. Additionally, recent advances in magnetic stimulation now allows for partitioning of cortical versus spinal excitability. For example, paired-pulse TMS can be used to assess intracortical facilitatory and inhibitory properties by combining a conditioning stimulus and a test stimulus at different interstimulus intervals. In this video article we will demonstrate the methodological and technical aspects of these techniques. Specifically, we will demonstrate single-pulse and paired-pulse TMS techniques as applied to the flexor carpi radialis (FCR) muscle as well as the erector spinae (ES) musculature. Our laboratory studies the FCR muscle as it is of interest to our research on the effects of wrist-hand cast immobilization on reduced muscle performance, and we study the ES muscles due to these muscles clinical relevance as it relates to low back pain. With this stated, we should note that TMS has been used to study many muscles of the hand, arm and legs, and should iterate that our demonstrations in the FCR and ES muscle groups are only selected examples of TMS being used to study the human neuromuscular system.

Reduced interhemispheric inhibition in mild cognitive impairment

In mild cognitive impairment (MCI), the corpus callosum is known to be affected structurally. We evaluated callosal function by interhemispheric inhibition (IHI) using transcranial magnetic stimulation (TMS) in MCI patients. We investigated 12 amnestic MCI patients and 16 healthy age-matched control subjects. The IHI was studied with a paired-pulse TMS technique. The conditioning TMS was given over the right primary motor cortex (M1) and the test TMS over the left M1. Motor evoked potentials were recorded from the relaxed first dorsal interosseous muscle. We also studied other motor cortical circuit functions; short-latency afferent inhibition (SAI), short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). Both the amount of IHI and SAI were significantly reduced in MCI patients as compared with control subjects, whereas SICI or ICF did not differ between them. The degree of IHI significantly correlated with neither the mini-mental state examination score nor the degree of SAI. Our results suggest that transcallosal connection between bilateral M1 is primarily involved in MCI, regardless of SAI dysfunction.

Motor skill training induces changes in the excitability of the leg cortical area in healthy humans

Training-induced changes in cortical excitability may play an important role in rehabilitation of gait ability in patients with neurological disorders. In this study, we investigated the effect of a 32-min period of motor skill, non-skill and passive training involving the ankle muscles on leg motor cortical excitability in healthy humans. Transcranial magnetic stimulation (TMS) at a range of intensities was applied to obtain a recruitment curve of the motor evoked potentials (MEPs) in the tibialis anterior (TA) muscle before and after training. We also explored the effect of training on inhibitory and facilitatory cortical circuits by using a paired-pulse TMS technique at intervals of 2.5 ms (short-interval intracortical inhibition, SICI) and 8 ms (intracortical facilitation, ICF). During motor skill training, subjects were instructed to make a cursor follow a series of target lines on a computer screen by performing voluntary ankle dorsi- and plantarflexion movements. Non-skill and passive training consisted of repeated voluntary and assisted dorsi- and plantarflexion movements, respectively. Recruitment curves increased significantly after 32 min of motor skill training but not after non-skill and passive training, suggesting that only skill motor training increases motor cortical excitability. Motor skill training was not accompanied by any changes in the recruitment curves of TA MEPs evoked by transcranial electrical stimulation, suggesting that the increased MEPs to TMS was likely caused by changes in excitability at a cortical site. SICI was decreased after 32 min of motor skill training but no changes were observed in ICF. We conclude that similar plastic changes as have previously been reported for the hand motor following motor skill training may also be observed for the leg motor area. The observed plastic changes appeared to be related to the degree of difficulty in the motor task, and may be of relevance for rehabilitation of gait disorders.

Handedness is mainly associated with an asymmetry of corticospinal excitability and not of transcallosal inhibition

Objective The study aims to compare transcallosal inhibition (TI), as assessed by the paired-pulse transcranial magnetic stimulation (TMS) technique, in a sample of right-handed subjects (RH) and left-handed subjects (LH). Motor thresholds (MTs) and motor evoked potential (MEP) amplitudes were also measured in the two groups, as an index of corticospinal activity. Methods Thirty-two normal subjects (16 RH and 16 LH) were recorded with a paired-pulse TMS paradigm (intensity of both pulses=120% of MT). The inter-stimulus intervals (ISIs) were 2, 4, 6, 8, 10, 12, 14, 16, 18, and 20 ms for both motor cortices, and MEP responses were recorded from the abductor digiti minimi muscles. Results Both groups showed a clear TI centred around the 12 ms ISI, but no difference was found as a function of handedness or of hemisphere. On the other hand, the two groups differed in terms of corticospinal activity, since the hand motor dominant hemisphere had lower MTs than the non-dominant one in LH, and larger MEP amplitudes for the right hand were found in RH. Conclusions Results point to a functional asymmetry of the motor cortex on the hand-dominant versus the non-dominant hemisphere, while handedness does not seem associated with functional differences in callosal inhibition, as measured by the inter-hemispheric paired-pulse TMS technique.

Altered cortical excitability in obsessive-compulsive disorder.

To assess cortical inhibitory and excitatory mechanisms in obsessive-compulsive disorder (OCD). Transcranial magnetic stimulation (TMS) studies have found decreased neuronal inhibition and a reduced cortical silent period in the primary motor area in Tourette's syndrome, focal dystonia, and other disorders believed to involve dysfunction of subcortical structures, including the basal ganglia. Dysfunction of the basal ganglia and linked regions also has been implicated in OCD, which has significant clinical and familial overlap with tic disorders. We applied the TMS techniques previously used in Tourette's syndrome to a group of 16 OCD patients (seven unmedicated) and 11 age-matched healthy volunteers extensively screened for psychopathology. Measures of motor cortex excitability included resting and active motor threshold, cortical silent period duration, and intracortical inhibition and facilitation using a paired-pulse TMS technique with a subthreshold conditioning stimulus. Similar to recent findings in Tourette's syndrome and focal dystonia, this study reports significantly decreased intracortical inhibition (ICI) relative to the volunteers at interstimulus intervals from 2 to 5 msec. We also found decreased active and resting motor evoked potential threshold in the OCD patients, another indication of increased cortical excitability. Neither abnormality appeared medication related. The decreases in ICI and motor threshold were greatest in OCD patients with comorbid tics, but remained significant in patients without tics. The data suggest abnormal cortical excitability in obsessive-compulsive disorder. These findings are congruent with the hypothesis that Tourette's syndrome and obsessive-compulsive disorder (OCD) are analogous disorders with overlapping dysfunction in corticobasal circuits. Patients with tic-related OCD may have more abnormal motor cortex excitability than OCD patients without tics.

Transcranial Magnetic Stimulation as a Probe and Potential Treatment in Obsessive-Compulsive Disorder

Transcranial magnetic stimulation (TMS), a relatively noninvasive probe of cortical function, permits new kinds of explorations of relationships between regional brain activity and symptomatology in obsessive-compulsive disorder (OCD). In TMS, a pulsed magnetic field affects activity in cerebral cortex underlying an electromagnetic coil placed on the scalp. Results of exploratory studies suggest that the single- or paired-pulse TMS techniques, and the newer repetitive method (rTMS), in which trains of stimuli are delivered at a given frequency, are potentially useful probes of cortical mechanisms involved in psychopathologic conditions, as in studies of motor, sensory, and cognitive physiology. For example, single-pulse TMS of motor cortex can produce muscle potentials or movement. Higher-frequency repetitive stimulation (rTMS) of occipital cortex can produce phosphenes or visual extinction, stimulation of Broca's area results in word-finding difficulties or speech arrest, and rTMS of prefrontal cortex affects verbal recall and other cognitive functions. Prefrontal rTMS can alter mood in healthy individuals. Both open and controlled clinical studies suggest that single-pulse TMS, and rTMS, may have antidepressant effects. Although the cerebral cortex is the only human brain structure subject to direct magnetic stimulation with current technology, TMS may influence activity in subcortical sites via their functional relationships with cortical areas. The effects of TMS on cortical excitability may depend on a combination of factors including coil design, stimulus frequency and intensity, and possibly the functional state of the cortex before stimulation.