Associative plasticity in surround inhibition circuits in human motor cortex

Surround inhibition is a physiological mechanism that is hypothesised to improve contrast between signals in the central nervous system. In the human motor system, motor surround inhibition (mSI) can be assessed using transcranial magnetic stimulation (TMS). We evaluated whether it is possible to modulate mSI, using a paradigm able to induce plastic effects in primary motor cortex (M1). Fifteen healthy volunteers participated in the experiments. To assess mSI, we delivered single pulses at rest and at the onset of a right thumb abduction. TMS pulses over abductor digiti minimi (ADM; surround muscle) hotspot were delivered when EMG activity in right abductor pollicis brevis (APB; active muscle) > 100 μV was detected. Paired associative stimulation (PAS) was delivered using peripheral median nerve electric stimulation and TMS over APB M1 area at an interstimulus interval of 21.5 ms for the real PAS (PAS21.5) and 100 ms for the sham PAS (PAS100). To verify the effect of PAS21.5 on mSI we collected 20 MEPs from ADM at rest and during APB movements before (T0) and 5 (T1), 15 (T2) and 30 (T3) minutes after PAS21.5. mSI from APB to ADM was present at baseline. PAS21.5 increased the amount of mSI compared with baseline whereas there was no effect after PAS100. Our results suggest that mSI is an adaptable phenomenon depending on prior experience.     

Dopamine agonists restore cortical plasticity in patients with idiopathic restless legs syndrome

In the present work, we aimed at assessing whether patients with idiopathic restless legs syndrome (RLS) showed alterations of sensory‐motor plasticity, an indirect probe for motor learning, within the motor cortex (M1). Previous findings suggest that learning in human M1 occurs through LTP‐like mechanisms. To test our hypothesis, we employed the paired associative stimulation (PAS) protocol by transcranial magnetic stimulation (TMS), which is able to induce LTP‐like effects in the motor cortex of normal subjects. Twelve patients with idiopathic RLS and 10 age‐ and sex‐matched control subjects were recruited. PAS protocol consisted of 0.05 Hz electrical median nerve stimulation (90 stimuli), paired with 0.05 Hz TMS (90 stimuli) over the hot spot for stimulating the abductor pollicis brevis (APB) muscle given 25 milliseconds after the onset of the electrical stimulus. Corticospinal excitability recorded in APB muscle, as indexed by MEP obtained after single stimulus, was tested before and up to 30 minutes after PAS protocol. Eight of 12 patients were studied before and after 4 weeks of dopaminergic treatment. PAS protocol increased significantly corticospinal excitability as long as 30 minutes in healthy subjects. On the contrary, PAS protocol did not change the amplitude of MEPs in patients with idiopathic RLS without treatment. PAS associative plasticity was restored after 4 weeks of dopaminergic treatment. Our data demonstrated that associative sensory‐motor plasticity, an indirect probe for motor learning, is impaired in idiopathic RLS patients but may be reverted to normal after dopaminergic treatment. © 2008 Movement Disorder Society     

Modulation of corticospinal excitability by paired associative stimulation: Reproducibility of effects and intraindividual reliability

OBJECTIVE: Electrical stimulation of the median nerve followed by a magnetic pulse on the primary motor cortex (M1) is effective to cause an increase in the amplitude of motor evoked potential (MEP) registered in the target muscle with the interstimulus interval (ISI) at 25ms (paired associative stimulation, PAS). The aim of this study is to evaluate the reproducibility of PAS with ISI 25 (PAS25), assessed in two separate sessions. Intraindividual reliability of TMS measures was also evaluated. METHODS: Motor threshold of abductor pollicis brevis (APB), assessed at rest, and MEP amplitude of APB and abductor digiti minimi (ADM) were assessed before and after PAS25 in 18 healthy volunteers (nine males and nine females). RESULTS: Data showed a significant increase of MEP amplitude in the target muscle (APB) after PAS25 and a reproducibility of group effect in the two sessions, as assessed by ANOVA, but a lack of intraindividual reliability, as assessed by intraclass correlation coefficients (ICC). CONCLUSIONS: The results underline the reproducibility of mean effects and the need to be careful when comparing the same subject on different days. SIGNIFICANCE: Electrical stimulation of the median nerve followed by a magnetic pulse delivered on M1 after 25ms causes a reproducible increase in MEP amplitude, without showing an acceptable intraindividual reliability.     

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.     

Pallidal stimulation modifies after-effects of paired associative stimulation on motor cortex excitability in primary generalised dystonia

OBJECTIVE: To determine the effect of globus pallidus internus (GPi) deep brain stimulation (DBS) on motor cortex plasticity in patients with primary generalised dystonia. METHODS: We studied 10 patients with primary generalised dystonia (5 DYT1+, 5 idiopathic, 5 female, mean age 42) following GPi DBS and 10 healthy subjects. Motor cortex plasticity was assessed using transcranial magnetic stimulation (TMS) paired associative stimulation (PAS) of motor cortex and median nerve, a method which has been shown in healthy subjects to produce LTP-like effects. Thresholds and TMS intensity to produce a resting motor evoked potential (MEP) of 1 mV were determined. Resting MEP amplitude and stimulus response curves were recorded before and after PAS. Patients were recorded ON and OFF DBS in separate sessions. RESULTS: The mean TMS intensity to produce a resting MEP of 1 mV was 54% of maximum stimulator output when OFF and 52% ON DBS. Fifteen minutes after PAS the resting MEP amplitude increased in patients OFF DBS and in control subjects whereas it decreased in patients ON DBS. Similarly, after PAS, the mean amplitude of the stimulus response curve increased OFF DBS, but this effect was abolished with DBS ON. Furthermore, patients who had the largest clinical response to chronic DBS also had the largest difference in the effect of PAS with DBS ON vs. OFF. CONCLUSIONS: After PAS, patients with primary generalised dystonia showed a similar pattern of increased motor cortex excitability as healthy subjects when GPi DBS was OFF but not with GPi DBS ON. These results suggest that GPi DBS may reduce LTP-like motor cortex plasticity, which could contribute to its mechanism of action in dystonia.     

Lateralization of unimanual and bimanual motor imagery

Most studies of motor imagery have examined motor cortex function during imagery of dominant hand movement. The aim of this study was to examine the modulation of excitability in the dominant and non-dominant corticomotor pathways during kinesthetic motor imagery of unimanual and bimanual movement. Transcranial magnetic stimulation (TMS) was applied over the contralateral motor cortex (M1) to elicit motor-evoked potentials (MEPs) in the abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles of each hand, in two separate sessions. Transcutaneous electrical stimuli were also delivered to the median nerve at each wrist, to elicit F-waves from APB. Fifteen right-handed volunteers imagined unimanual and bimanual phasic thumb movements, paced with a 1-Hz auditory metronome. Stimuli were delivered at rest, and either 50 ms before (ON phase), or 450 ms after (OFF phase), the metronome beeps. Significant MEP amplitude facilitation occurred only in right APB, during the ON phase of motor imagery of the right hand and both hands. Significant temporal modulation of right APB MEP amplitude was observed during motor imagery of right, left and bimanual performance. F-wave persistence and amplitude were unaffected by imagery. These results demonstrate that the motor imagery is lateralized to the left (dominant) hemisphere, which is engaged by imagery of each hand separately, and bimanual imagery. This finding has implications for the use of motor imagery in rehabilitation.     

Effects of Two Weeks of Cerebellar Theta Burst Stimulation in Cervical Dystonia Patients

Dystonia is generally regarded as a disorder of the basal ganglia and their efferent connections to the thalamus and brainstem, but an important role of cerebellar-thalamo-cortical (CTC) circuits in the pathophysiology of dystonia has been invoked. Here in a sham controlled trial, we tested the effects of two-weeks of cerebellar continuous theta burst stimulation (cTBS) in a sample of cervical dystonia (CD) patients. Clinical evaluations were performed by administering the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). We used TMS to measure the inhibitory connectivity between the cerebellum and the contralateral motor cortex (cerebellar brain inhibition [CBI]), and the excitability of the contralateral primary motor cortex assessing intracortical inhibition (SICI), intracortical facilitation (ICF) and cortical silent period (CSP). Paired associative stimulation (PAS) was tested to evaluate the level and the topographical specificity of cortical plasticity, which is abnormally enhanced and non-focal in CD patients. Two weeks of cerebellar stimulation resulted in a small but significant clinical improvement as measured by the TWSTRS of approximately 15%. Cerebellar stimulation modified the CBI circuits and reduced the heterotopic PAS potentiation, leading to a normal pattern of topographic specific induced plasticity. These data provide novel evidence CTC circuits could be a potential target to partially control some dystonic symptoms in patients with cervical dystonia.     

Patterns of motor control reorganization in a patient with mirror movements.

OBJECTIVE: To explore motor control reorganization in a 40-year-old, left-handed patient with perinatally acquired mirror movements. METHODS: We performed simultaneous bilateral recordings of motor evoked potentials (MEPs) following focal transcranial magnetic stimulation (fTMS) and of central silent period (cSP) during unilateral voluntary contraction in abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles. RESULTS: For both muscles the MEP study showed bilateral fast-conducting corticospinal projections from the right undamaged hemisphere, and residual contralateral projections from the left hemisphere. The cSP findings differed in the two muscles: the mirror phenomenon was bilateral in the ADM, but present only on the right side in the APB muscles; the mirror activity of right ADM and APB muscles was inhibited only by fTMS of the ipsilateral right motor cortex; the mirror phenomenon in the left ADM muscle was inhibited only by fTMS of the contralateral right motor cortex. CONCLUSIONS: Mirror movements of right APB and ADM muscles were sustained by the ipsilateral connections from the undamaged motor cortex, while the mirror phenomenon in the left ADM muscle could be explained by hypothesizing a bilateral activation of motor cortices. This previously unreported electrophysiological picture demonstrates that different patterns of motor control may realize after perinatal cerebral lesions, even in different distal muscles of the same patient.     

Impaired modulation of motor cortex excitability by homonymous and heteronymous muscle afferents in focal hand dystonia.

A decrease of heteronymous median nerve-evoked inhibition of corticospinal projections to forearm extensor muscles was reported in a group of 10 dystonic patients by Bertolasi and colleagues in 2003. Here we tested the excitability of corticomotoneuronal connections to both wrist extensor (ECR) and flexor (FCR) muscles after conditioning stimulation of median and also radial nerve at rest in a group of 25 patients with focal hand dystonia compared to 20 healthy subjects. We also investigated the effect of the wrist dystonic posture, either in flexion or in extension, on the afferent modulation of ECR and FCR motor evolved potentials (MEPs). The heteronymous (median-induced) but also homonymous (radial-induced) inhibitions (interstimuli intervals 13-21 ms) of ECR MEP size observed in healthy subjects were decreased in patients. In addition, homonymous (median-induced) facilitation of FCR MEP size was also decreased in patients while heteronymous inhibition (radial-induced) was not. Neither the involvement of the target muscle in the dystonic posture nor the origin of the afferent volley (from a dystonic muscle) influenced the degree of impairment of afferent modulation of the MEP. These findings support the view that a global abnormal somatosensory coupling in focal hand dystonia may contribute to an inadequate motor command to wrist muscles.     

Different short-term modulation of cortical motor output to distal and proximal upper-limb muscles during painful sensory nerve stimulation

The pattern of upper-limb muscle activation following painful stimulation has not been clarified in detail. We investigated the short-term inhibitory and excitatory effects of painful electrical digital stimulation on the motoneuron pools of distal and proximal upper-limb muscles. Transcranial magnetic stimulation (TMS) was used as test stimulus, and painful digital nerve stimulation as conditioning stimulus for motor evoked potential (MEP) recordings over the abductor digiti minimi (ADM), abductor pollicis brevis (APB), biceps brachii (BB), and deltoid muscles. Inhibition of the conditioned MEP response was most prominent in the distal muscles, whereas BB and deltoid muscles were only weakly inhibited. The mean MEP response over APB decreased with painful cutaneous stimuli, showing maximum inhibition (by 82%) at interstimulus intervals (ISIs) of 50 ms. Inhibition in the ADM was maximal (49%) but less pronounced at an ISI of 40 ms. The BB and deltoid muscles showed inhibition by 25% and 29%, respectively. Significant facilitation was present in BB and deltoid muscles by 43% and 41% at an ISI of 100 ms, but not in the smaller hand muscles. The observed pattern of upper-limb muscle activation corresponds to the protective withdrawal reflex and the neuronal basis of the observed short-term modulation of motor activity is compatible with a spinal or brainstem pathway.     

Motor imagery of phasic thumb abduction temporally and spatially modulates corticospinal excitability.

OBJECTIVE: To explore the spatial and temporal characteristics of the modulation of corticospinal and segmental excitability during actual and imagined movement of a single digit. METHODS: Using transcranial magnetic stimulation (TMS), motor evoked potentials (MEPs) were evoked in abductor pollicis brevis (APB) and abductor digiti minimi (ADM) of the dominant hand in 8 subjects, while they either rested, isometrically contracted their thenar muscles in time with a 1 Hz metronome, or imagined doing so. Magnetic stimuli were delivered during the 'on' and 'off' phases of the real and imagined movements. F waves were also recorded from APB and ADM under rest and motor imagery conditions. RESULTS: It was found that both motor imagery and actual movement produced a muscle-specific, temporally modulated increase in corticospinal excitability during the task. The evidence of F-wave modulation was inconclusive. CONCLUSIONS: These results lend further support to the notion that actual movement and motor imagery modulate corticospinal excitability in a similar manner, primarily at the supraspinal level. SIGNIFICANCE: Motor imagery and actual movement appear to modulate motor cortex excitability with a similar degree of spatial and temporal resolution, which supports the use of motor imagery in the rehabilitation of motor function.     

Short latency afferent inhibition and facilitation in patients with writer's cramp.

Patients with writer's cramp (WC) show abnormalities of sensorimotor integration possibly contributing to their motor deficit. We studied sensorimotor integration by determining short-latency afferent inhibition (SAI) in 12 WC patients and 10 age-matched healthy controls. A conditioning electrical median nerve stimulus was followed 14 to 36 msec later by transcranial magnetic stimulation of the contralateral primary motor cortex, and motor evoked potentials (MEP) were recorded from the relaxed or contracting abductor pollicis brevis muscle (APB). SAI was normal in WC but during APB relaxation SAI was followed by abnormal MEP facilitation, which was absent during APB contraction and in the controls. These findings suggest that somatosensory short-latency inhibitory input into the primary motor cortex is normal in WC, whereas a later excitatory input, which very likely reflects the long-latency reflex II, is exaggerated.     

Nonspecific facilitation of responses to transcranial magnetic stimulation.

We examined the effect of facial muscle contraction and eye movements on motor evoked potentials (MEPs) from the abductor pollicis brevis muscle (APB) evoked by transcranial magnetic stimulation (TMS). The hypothesis was that activity of large cortical regions (face) influences the excitability of spinal motoneurons via cortical or subcortical pathways. MEPs were recorded in 12 healthy subjects during the following conditions: (1) rest; (2) facial muscle contraction; (3) eye movements; (4) 10% precontraction of the target muscle; and (5) simultaneous target muscle precontraction and facial muscle contraction. In 9 subjects, spinal motoneuron excitability was assessed by measurements of F waves during the same facilitation maneuvers. Activation of eye and facial muscles clearly facilitated MEPs from the APB. The facilitation of MEP size during nonspecific maneuvers was almost similar to that obtained by target muscle precontraction, whereas shortening of latencies was significantly smaller. The occurrence and amplitude of F waves increased in parallel with MEP size during specific and nonspecific facilitation, pointing to spinal motoneuronal threshold changes as a potential facilitatory mechanism by facial and eye muscle activation. The different MEP latencies during specific and nonspecific facilitation were not explained by different spinal motoneuron excitability, but raise the possibility that supraspinal mechanisms contributed to nonspecific facilitation.     

Modulation of preparatory volitional motor cortical activity by paired associative transcranial magnetic stimulation

Paired associative transcranial magnetic stimulation (PAS) has been shown to induce long‐term potentiation (LTP)‐like or long‐term depression (LTD)‐like change in excitability of human primary motor cortex (M1), as probed by motor evoked potential (MEP) amplitude. In contrast, little is known about PAS effects on volitional motor cortical activity. In 10 healthy subjects, movement related cortical potentials (MRCP) were recorded to index volitional motor cortical activity during preparation of simple thumb abduction (prime mover: abductor pollicis brevis, APB) or wrist extension movements (prime mover: extensor carpi radialis, ECR). PAS_LTP increased, PAS_LTD decreased, and PAS_control did not change MEP_APB, while MEP_ECR, not targeted by PAS, remained unchanged in all PAS conditions. PAS_LTP decreased MRCP negativity during the late Bereitschaftspotential (?500 to 0 ms before movement onset), only in the APB task, and predominantly over central scalp electrodes contralateral to the thumb movements. This effect correlated negatively with the PAS_LTP induced increase in MEP_APB. PAS_LTD and PAS_control did not affect MRCP amplitude. Findings indicate a specific interference of PAS with preparatory volitional motor cortical activity, suggestive of a net result caused by increased M1 excitability and disrupted effective connectivity between premotor areas and M1. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Corticospinal excitability in patients with secondary dystonia due to focal lesions of the basal ganglia and thalamus

ObjectiveTo investigate the possible correlations between clinico-radiological features and pathophysiological mechanisms in patients with dystonia secondary to focal brain lesions.MethodsSingle and paired-pulse transcranial magnetic stimulation was used to assess corticospinal excitability in 10 patients (4 females; mean age 61) and a group of normal controls. Active threshold, latency and amplitude of motor evoked potentials (MEPs), silent period (SP) duration and short-interval intracortical inhibition (SICI) were evaluated.ResultsPatients with lesions involving the putamen and caudate presented with dystonic postures at rest. TMS assessment in these subjects showed increased MEP amplitude on the affected side and a bilateral decrease of SP duration and SICI. When the lesion spared the putamen and caudate, mainly involving the thalamus, the clinical picture was dominated by slow repetitive involuntary movements and tremor. In the affected side of these subjects the MEP amplitude was reduced and the MEP threshold was increased.ConclusionsWhen putamen and caudate were lesioned, the patients presented with dystonic postures at rest; furthermore the patients showed changes of corticospinal excitability in comparison to both healthy subjects and other dystonic patients.SignificanceThere are correlations between type of dystonia, site of the lesion and neurophysiological findings.     

Paired-associative stimulation can modulate muscle fatigue induced motor cortex excitability changes

The aim of this study was to examine whether the changes of the motor cortex excitability induced by muscle fatigue could be affected by prior or subsequent intervention protocol supposed to induce opposing excitability changes. For this purpose we used paired associative stimulation (PAS) method, where peripheral nerve stimuli were associated with transcranial magnetic stimulation (TMS) of the motor cortex at a fixed interstimulus interval of 25 ms. The PAS protocol used is known to produce a long lasting, long-term potentiation (LTP) like change of cortical plasticity manifested by significant increase in motor evoked potentials (MEPs) amplitude. In this study, we confirmed significant MEP size reduction following fatigue, which had been already reported in the literature. When PAS was applied either immediately before or after muscle fatigue protocol, the excitability changes were largely occluded and MEP sizes remained close to baseline levels. However, in spite of the effects on cortical excitability, conditioning with PAS did not cause any change in target fatigue measure, the endurance point, which remained the same as when fatiguing protocol was applied alone. The present results demonstrate that fatigue-related changes in cortical excitability can be modulated by either prior or subsequent excitability promoting activity. They also suggest that muscle fatigue associated changes in motor cortical excitability probably represent non-specific activity-related plasticity, rather than a direct expression of the so-called central fatigue.     

Changes in motor cortex excitability during ipsilateral hand muscle activation in humans.

OBJECTIVES: To test whether unilateral hand muscle activation involves changes in ipsilateral primary motor cortex (M1) excitability. METHODS: Single- and paired-pulse transcranial magnetic stimulation (TMS) of the right hemisphere was used to evoke motor evoked potentials (MEPs) from the resting left abductor pollicis brevis (APB) in 9 normal volunteers. We monitored changes in motor threshold (MT), MEP recruitment, intracortical inhibition (ICI) and intracortical facilitation (ICF) while the ipsilateral right APB was either at rest or voluntarily activated. Spinal motoneuron excitability was assessed using F-wave recording procedures. RESULTS: Voluntary muscle activation of the ipsilateral APB significantly facilitated the MEPs and F-waves recorded from the contralateral APB. Facilitation was observed with muscle activation >50% of the maximum voluntary force and with stimulus intensities >20% above the individual resting motor threshold. Intracortical inhibition significantly decreased in the ipsilateral M , while there was no significant change in intracortical facilitation during this maneuver. CONCLUSIONS: Unilateral hand muscle activation changes the excitability of homotopic hand muscle representations in both the ipsilateral M1 and the contralateral spinal cord. While the large proportion of MEP facilitation most likely occurred at a spinal level, involvement of the ipsilateral hemisphere may have contributed to the enlargement of magnetic responses.     

Impairment of sensory-motor plasticity in mild Alzheimer’s disease

BackgroundPrimary motor cortex (M1) is relatively spared in the early stages of Alzheimer’s disease (AD).ObjectiveAim of the present study was to investigate whether abnormal M1 synaptic plasticity is present at an early stage of AD. We employed an electrophysiological protocol, named rapid paired associative stimulation (rPAS), involving repetitive transcranial magnetic stimulation (rTMS) paired with electrical stimulation of the contralateral median nerve, that modifies corticospinal excitability and short latency afferent inhibition (SAI).MethodsWe studied 10 patients with a diagnosis of probable mild AD according to the Mini Mental State Examination score (minimum 21) and 14 age-matched control subjects. Motor evoked potentials (MEP) amplitudes and short-afferent inhibition (SAI) were measured at baseline before and for up to 60 min after 5Hz-rPAS in abductor pollicis brevis (APB). rPAS consisted of 600 pairs of transcranial magnetic stimuli, at a rate of 5 Hz for 2 min, coupled with electrical median nerve stimulation preceding TMS over the contralateral M1 at an inter-stimulus interval of 25 ms.ResultsBaseline SAI was significantly reduced in AD patients. In the control subjects rPAS induced a significant increase in MEP amplitudes and a decrease of SAI in the APB muscle persistently for up to 1 h. Conversely 5Hz-rPAS did not induce any significant changes in MEP amplitudes and SAI in mild AD patients.ConclusionsSensory-motor plasticity is impaired in the motor cortex of AD at an early stage of the disease.     

Plasticity of the motor cortex in Parkinson's disease patients on and off therapy.

We used the paired associative stimulation (PAS) technique to investigate associative plasticity of the sensorimotor cortex in 16 Parkinson's disease (PD) patients off and on therapy and in 10 age-matched controls. After PAS, motor evoked potential (MEP) amplitudes increased more and the cortical silent period showed a reduced prolongation in patients off therapy than in controls. These changes lasted for at least 30 minutes. In addition, MEP amplitudes increased in a less focal manner in patients off therapy than in controls. After patients received dopaminergic therapy, these abnormalities normalized. The abnormal responsiveness of sensorimotor cortex neurons to PAS in PD patients off therapy probably reflects disordered plasticity within the motor cortex.     

Impact of coil position and electrophysiological monitoring on determination of motor thresholds to transcranial magnetic stimulation.

OBJECTIVE: We compared motor and movement thresholds to transcranial magnetic stimulation (TMS) in healthy subjects and investigated the effect of different coil positions on thresholds and MEP (motor-evoked potential) amplitudes. METHODS: The abductor pollicis brevis (APB) 'hot spot' and a standard scalp position were stimulated. APB resting motor threshold (APB MEP-MT) defined by the '5/10' electrophysiological method was compared with movement threshold (MOV-MT), defined by visualization of movements. Additionally, APB MEP-MTs were evaluated with the '3/6 method,' and MEPs were recorded at a stimulation intensity of 120% APB MEP-MT at each position. RESULTS: APB MEP-MTs were significantly lower by stimulation of the 'hot spot' than of the standard position, and significantly lower than MOV-MTs (n=15). There were no significant differences between the '3/6' and the '5/10' methods, or between APB MEP amplitudes by stimulating each position at 120% APB MEP-MT. CONCLUSIONS: Coil position and electrophysiological monitoring influenced motor threshold determinations. Performing 6 instead of 10 trials did not produce different threshold measurements. Adjustment of intensity according to APB MEP-MT at the stimulated position did not influence APB MEP amplitudes. SIGNIFICANCE: Standardization of stimulation positions, nomenclature and criteria for threshold measurements should be considered in design and comparison of TMS protocols.