Homeostatic plasticity in human motor cortex demonstrated by two consecutive sessions of paired associative stimulation

Long-term potentiation (LTP) and long-term depression (LTD) underlie most models of learning and memory, but neural activity would grow or shrink in an uncontrolled manner, if not guarded by stabilizing mechanisms. The Bienenstock-Cooper-Munro (BCM) rule proposes a sliding threshold for LTP/LTD induction: LTP induction becomes more difficult if neural activity was high previously. Here we tested if this form of homeostatic plasticity applies to the human motor cortex (M1) in vivo by examining the interactions between two consecutive sessions of paired associative stimulation (PAS). PAS consisted of repeated pairs of electrical stimulation of the right median nerve followed by transcranial magnetic stimulation of the left M1. The first PAS session employed an interstimulus interval equalling the individual N20-latency of the median nerve somatosensory-evoked cortical potential plus 2 ms, N20-latency minus 5 ms, or a random alternation between these intervals, to induce an LTP-like increase in motor-evoked potential (MEP) amplitudes in the right abductor pollicis brevis muscle (PAS(LTP)), an LTD-like decrease (PAS(LTD)), or no change (PAS(Control)), respectively. The second PAS session 30 min later was always PAS(LTP). It induced an moderate LTP-like effect if conditioned by PAS(Control), which increased if conditioned by PAS(LTD), but decreased if conditioned by PAS(LTP). Effects on MEP amplitude induced by the second PAS session exhibited a negative linear correlation with those in the first PAS session. Because the two PAS sessions activate identical neuronal circuits, we conclude that 'homosynaptic-like' homeostatic mechanisms in accord with the BCM rule contribute to regulating plasticity in human M1.     

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.     

Plasticity of motor threshold and motor-evoked potential amplitude – A model of intrinsic and synaptic plasticity in human motor cortex?

BackgroundNeuronal plasticity is the physiological correlate of learning and memory. In animal experiments, synaptic (i.e. long-term potentiation (LTP) and depression (LTD)) and intrinsic plasticity are distinguished. In human motor cortex, cortical plasticity can be demonstrated using transcranial magnetic stimulation (TMS). Changes in motor-evoked potential (MEP) amplitudes most likely represent synaptic plasticity and are thus termed LTP-like and LTD-like plasticity.Objective/hypothesisWe investigated the role of changes of motor threshold and their relation to changes of MEP amplitudes.MethodsWe induced plasticity by paired associative stimulation (PAS) with 25 ms or 10 ms inter-stimulus interval or by motor practice (MP) in 64 healthy subjects aged 18–31 years (median 24.0).ResultsWe observed changes of MEP amplitudes and motor threshold after PAS[25], PAS[10] and MP. In all three protocols, long-term individual changes in MEP amplitude were inversely correlated to changes in motor threshold (PAS[25]: P = .003, n = 36; PAS[10]: P = .038, n = 19; MP: P = .041, n = 19).ConclusionWe conclude that changes of MEP amplitudes and MT represent two indices of motor cortex plasticity. Whereas increases and decreases in MEP amplitude are assumed to represent LTP-like or LTD-like synaptic plasticity of motor cortex output neurons, changes of MT may be considered as a correlate of intrinsic plasticity.     

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     

Age dependence of primary motor cortex plasticity induced by paired associative stimulation.

OBJECTIVE: The increase of elderly population prompted growing research for the understanding of cerebral phenomena sustaining learning abilities, with inclusion of long-term potentiation (LTP)-like plasticity phenomena. Aim of the present study was to characterize LTP-like plasticity dependence on age and gender. METHODS: A LTP-like primary motor cortex plasticity inducing a potentiation of the motor evoked potential (MEP) to focal transcranial magnetic stimulation as a consequence of a paired associative stimulation (PAS) was induced in a 50 healthy subject cohort, equally distributed for gender and age groups (25 young subjects, mean age+/-SD=29.8+/-4.5 years; elderly 61.1+/-4.1 years). RESULTS: Resting motor thresholds' excitability level increased in the elderly group, the basal MEP did not depend on gender or age. The PAS-induced primary motor cortex (M1) plastic excitability modulation was similar in young females and males, while it decreased with age in females only. CONCLUSIONS: A reduction of the PAS-induced M1 plasticity in females after menopause was documented, possibly due to an impairment of intracortical excitatory network activity. SIGNIFICANCE: A LTP-like plasticity dependence on age was found in female only, suggesting caution in interpreting behavioural studies on learning abilities in dependence on age.     

Loss of topographic specificity of LTD-like plasticity is a trait marker in focal dystonia

In focal hand dystonia, long-term potentiation (LTP) and depression (LTD)-like neuronal plasticity, as assessed by paired associative stimulation (PAS) targeting the hand-associated motor cortex, is enhanced and the topographic organization of plasticity is lost. However, if any of these abnormalities alone is sufficient to cause focal dystonia (FD) remains unknown. Ten patients with cervical dystonia (CD), 9 with blepharospasm (BS) and 16 age- and sex-matched controls were examined. PAS was performed by combining repetitively electric stimulation of the median nerve with subsequent transcranial magnetic stimulation of the contralateral motor cortex at 21.5ms (PAS21.5) and 10ms (PAS10). Corticospinal excitability was indexed by the magnitude of motor evoked potentials (MEPs) recorded from abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles. In controls, MEP size of the homotopically conditioned APB increased after PAS21.5 whereas the MEP size of the heterotopically conditioned ADM remained stable. PAS10 led to a decrease of MEP size of the APB and to an increase of the heterotopic ADM. In contrast, after PAS21.5 and PAS10 in CD and BS MEP size increased and decreased, respectively, in both muscles. The magnitude of excitability changes, however, did not differ between dystonic patients and healthy controls. In FD the topographic organization of PAS21.5 and PAS10-induced plasticity is deranged in cortical areas not involved in the control of the dystonic body part. Somatotopical disorganization of plasticity may represent an endophenotypic trait in FD but may not be sufficient to generate a dystonic phenotype. Development of a dystonic phenotype may require that the gain of plasticity is additionally enhanced. This article is part of a Special Issue entitled "Advances in dystonia".     

A local signature of LTP- and LTD-like plasticity in human NREM sleep

Paired associative stimulation (PAS) repeatedly pairs electrical nerve stimulation with transcranial magnetic stimulation of the contralateral motor hand area (M1(HAND)). Depending on the interstimulus interval, PAS can induce a long-term potentiation (LTP)-like facilitation or long-term depression (LTD)-like suppression of cortical excitability. In three experimental sessions, 12 awake men received PAS of the right median nerve and left M1(HAND) in the evening before sleep. To optimize the timing of paired stimulation in M1(HAND), the interstimulus interval of PAS was adjusted to the individual N20-latency of the somatosensory evoked potential to induce LTP-like effects (PAS(N20+2ms)), LTD-like effects (PAS(N20-5ms)), or no timing-dependent after-effects (PAS(control)). Motor-evoked potentials (MEPs) showed high interindividual variations in the conditioning effects of PAS(N20+2ms) and PAS(N20-5ms) on cortical excitability. However, PAS(control) allowed us to adjust for any unspecific stimulation effects and the MEP increase after PAS(N20+2ms) differed significantly from the MEP decrease after PAS(N20-5ms). PAS(N20+2ms) and PAS(N20-5ms) also had a differential effect on regional expression of slow waves and slow spindle activity during the first hour of subsequent non-rapid eye movement (NREM) sleep. At the electrode sites overlying the conditioned M1(HAND) and the adjacent premotor cortex, local expression of slow spindle activity was significantly correlated with interindividual differences in the efficacy of PAS(N20+2ms) and PAS(N20-5ms) to potentiate or suppress cortical excitability. This correlation indicates that PAS shapes the local regulation of slow sleep spindles during subsequent NREM sleep.     

Relation of Brain Stimulation Induced Changes in MEP Amplitude and BOLD Signal

BackgroundNon-invasive human brain stimulation can induce long-term plasticity reflected by changes in putative markers of synaptic activation, such as the motor evoked potential (MEP) amplitude elicited by transcranial magnetic stimulation or the task-dependent blood oxygenation level-dependent (BOLD) signal measured by functional magnetic resonance imaging.ObjectiveTo study the relationship between brain stimulation induced changes in MEP amplitude and BOLD signal.MethodsPaired associative stimulation of the hand area of the left primary somatosensory cortex (S1-PAS) was applied in 15 healthy subjects to induce excitability change in the adjacent primary motor cortex (M1) [Kriváneková et al. 2011, Eur J Neurosci 34:1292-1300]. Before and after S1-PAS, MEP amplitude in a right hand muscle, and the BOLD signal during a right hand motor or somatosensory activation task were measured.ResultsS1-PAS resulted in substantial individual MEP and BOLD signal changes, but these changes did not correlate in M1 or S1.ConclusionsFindings indicate that MEP amplitude and BOLD signal within the tested M1 reflect physiologically distinct aspects of synaptic excitability change. Therefore, it is suggested that MEP amplitude and BOLD signal are complementary rather than interchangeable markers of synaptic excitability.     

Supplementary motor area plays a causal role in automatic inhibition of motor responses

BackgroundThe masked-priming paradigm is used to test unconscious inhibitory processes of the brain. A tendency towards responses that are incompatible with the prime, designated as negative compatibility effect (NCE), emerges when the perception of a priming visual stimulus is “masked” afterwards. This effect presumably stems from a subliminal inhibitory process against the masked-prime. Prior lesions as well as activation studies suggest a key role of SMA in this effect.ObjectiveThis study was conducted to elucidate a causal role of SMA in the subliminal response inhibition represented by the NCE.MethodsUsing a repeated-measures pre–post design with a group of healthy people, physiological measures (resting and active motor thresholds and motor evoked potential (MEP) amplitude) and behavioral ones (choice reaction time (CRT), positive compatibility effect (PCE) and NCE) were obtained before and after three quadripulse stimulation (QPS), namely sham, M1-QPS, and SMA-QPS, on different days. CRT and PCE served as indices for different aspects of motor execution.ResultsMotor thresholds were not altered after any QPS, although the M1-QPS increased MEP amplitude. Neither CRT nor PCE was altered significantly after QPS protocols. NCE was abolished after the SMA-QPS.ConclusionsAbolished NCE after the SMA-QPS in the absence of MEP changes suggests that (1) SMA plays a cardinal role in the NCE, and (2) the network involved in NCE is different from that of MEP generation.     

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.     

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.     

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

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

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.     

A new temporal window for inducing depressant associative plasticity in human primary motor cortex

ObjectiveSpike-timing dependent plasticity (STDP) usually refers to synaptic plasticity induced by near-synchronous activation of neuronal input and neuronal firing. However, some models of STDP predict effects that deviate from this tight temporal synchrony. We aimed to characterise the induction of STDP using paired associative stimulation (PAS) when the pre-synaptic input arrives in primary motor cortex (M1) at (i) intermediate intervals (50–80 ms; PAS₅₀,..PAS₈₀) before the post-synaptic neuron is activated and (ii) long intervals (100–450 ms; PAS_?100,..PAS_?450) after the post-synaptic neuron is activated. PAS at near-synchronicity (PAS₂₅) was applied for comparison.MethodsTo characterise the physiological effects of the different PAS protocols, we examined short- and long-interval intra-cortical inhibition; intra-cortical facilitation and short- and long-latency afferent inhibition, in addition to recording MEPs in 45 healthy individuals.ResultsMEP amplitude was reduced at PAS intervals between ?250 and ?450 ms, increased with PAS₂₅, and unaltered at the remaining intervals. There was no change in intra-cortical inhibitory or facilitatory circuits following any PAS protocol.ConclusionsThese findings provide evidence of a previously unreported temporal window in which PAS induces a depression of corticospinal excitability in human M1.SignificanceEstablishing new temporal rules for STDP broadens its applicability for therapeutic usage in future.     

Effect of Consecutive Application of Paired Associative Stimulation on Motor Recovery in a Rat Stroke Model: A Preliminary Study

This study investigated the changes in motor evoked potential (MEP) amplitude and motor behavior index when paired associative stimulation (PAS), a conjoint stimulation of a peripheral nerve and the motor cortex, was applied in a rat stroke model. The PAS was applied to 19 rats and sham stimulation was applied to 15 rats. One part of PAS consisted of peripheral electrical stimulation of the soleus muscle and the other part was transcranial magnetic stimulation of the motor cortex. The stimulation was repeated for 30 min with a frequency of 0.05 Hz. Five sessions of PAS were applied over 5 consecutive days. The motor behavior index was higher in the PAS group than in the sham stimulation group at 7 d after ischemic brain injury. There was no lasting difference between the PAS animals and the sham stimulation group in MEP amplitude although MEP amplitude was increased immediately after PAS. MEP amplitude can be increased by the PAS paradigm in rats as well as in humans and PAS has potential therapeutic value for motor recovery after brain injury.     

Effect of consecutive application of paired associative stimulation on motor recovery in a rat stroke model: a preliminary study

This study investigated the changes in motor evoked potential (MEP) amplitude and motor behavior index when paired associative stimulation (PAS), a conjoint stimulation of a peripheral nerve and the motor cortex, was applied in a rat stroke model. The PAS was applied to 19 rats and sham stimulation was applied to 15 rats. One part of PAS consisted of peripheral electrical stimulation of the soleus muscle and the other part was transcranial magnetic stimulation of the motor cortex. The stimulation was repeated for 30 min with a frequency of 0.05 Hz. Five sessions of PAS were applied over 5 consecutive days. The motor behavior index was higher in the PAS group than in the sham stimulation group at 7 d after ischemic brain injury. There was no lasting difference between the PAS animals and the sham stimulation group in MEP amplitude although MEP amplitude was increased immediately after PAS. MEP amplitude can be increased by the PAS paradigm in rats as well as in humans and PAS has potential therapeutic value for motor recovery after brain injury.     

Excitability Profile of Motor Evoked Potentials and Silent Periods

The aim of this study was to confirm the excitability profile of human cortical circuits on the motor evoked potential (MEP) and the silent period (SP) after paired transcranial magnetic stimulation (TMS) with variable interstimulus intervals (ISI), and to compare the time courses of MEP and SP after paired TMS at variable ISIs. MEPs were elicited at the hypothenar muscles at rest, and during tonic muscle contraction by applying paired TMS to the motor cortex. The authors measured the MEP amplitude during rest and the duration of SP during tonic muscle contraction at various ISIs. The response to paired stimuli was inhibited by an ISI of 1–5 ms and facilitated by an ISI of 10–20 ms. The SP at an ISI of 1–5 ms was shorter than that at the single suprathreshold stimulus, but the SP at an ISI of 15–25 ms was longer than this. A significant correlation was observed between the MEP amplitude and the duration of SP at ISIs of 1–20 ms and for a CS of 80% of threshold. These results may provide useful data for the study of the function of cortical excitability in disease states and suggest that the neural circuits underlying MEP and SP differ partly.     

Altered plasticity of the human motor cortex in Parkinson's disease

Interventional paired associative stimulation (IPAS) to the contralateral peripheral nerve and cerebral cortex can enhance the primary motor cortex (M1) excitability with two synchronously arriving inputs. This study investigated whether dopamine contributed to the associative long-term potentiation-like effect in the M1 in Parkinson's disease (PD) patients. Eighteen right-handed PD patients and 11 right-handed age-matched healthy volunteers were studied. All patients were studied after 12 hours off medication with levodopa replacement (PD-off). Ten patients were also evaluated after medication (PD-on). The IPAS comprised a single electric stimulus to the right median nerve at the wrist and subsequent transcranial magnetic stimulation of the left M1 with an interstimulus interval of 25 milliseconds (240 paired stimuli every 5 seconds for 20 minutes). The motor-evoked potential amplitude in the right abductor pollicis brevis muscle was increased by IPAS in healthy volunteers, but not in PD patients. IPAS did not affect the motor-evoked potential amplitude in the left abductor pollicis brevis. The ratio of the motor-evoked potential amplitude before and after IPAS in PD-off patients increased after dopamine replacement. Thus, dopamine might modulate cortical plasticity in the human M1, which could be related to higher order motor control, including motor learning.     

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.     

AAEM minimonograph #35: Clinical experience with transcranial magnetic stimulation

We elicited motor evoked potentials (MEPs) using transcortical magnetic stimulation in 150 control subjects aged 14 to 85 years and 275 patients with a variety of diseases. There were no significant side effects. Cortex-to-target muscle latencies measured 20.2 +/- 1.6 ms (thenar), 14.2 +/- 1.7 ms (extensor digitorum communis), 9.4 +/- 1.7 ms (biceps), and 27.2 +/- 2.9 ms (tibialis anterior). Central motor delay between the cortex and the C-7 and L-5 measured 6.7 +/- 1.2 ms and 13.1 +/- 3.8 ms, respectively. Mean spinal cord motor conduction velocity measured 65.4 m/s. MEP amplitude expressed as a percentage of the maximum M wave was never less than 20% of the M wave. A value of less than 10% is considered abnormal. MEP latency increases linearly with age and central motor delay is longer in older subjects. Compound muscle action potentials and absolute MEP amplitudes decreased linearly with age. In multiple sclerosis (MS), MEP latency and central delay were often very prolonged. The MEP was more sensitive than the SEP in MS. In amyotrophic lateral sclerosis, MEP latencies were only modestly prolonged; the characteristic abnormality was reduced amplitude. When pseudobulbar features predominated MEPs were often absent. The MEP was of normal latency in Parkinson's disease, but age-related amplitude was often increased. MEP latency and amplitude were normal in Huntington's disease. Abnormal MEPs persisted several months after stroke despite good functional recovery. The MEP could be used to advantage to demonstrate proximal conduction slowing and block in demyelinating neuropathies. In plexopathy, ability to elicit an MEP several days after onset of paresis was good evidence of neuronal continuity in motor fibers.