Decrease In Corticospinal Excitability Research Articles

Modulation of Motor Cortical Inhibition and Facilitation by Touch Sensation from the Glabrous Skin of the Human Hand.

Touch sensation from the glabrous skin of the hand is essential for precisely controlling dexterous movements, yet the neural mechanisms by which tactile inputs influence motor circuits remain largely unexplored. By pairing air-puff tactile stimulation on the hand's glabrous skin with transcranial magnetic stimulation (TMS) over the primary motor cortex (M1), we examined the effects of tactile stimuli from single or multiple fingers on corticospinal excitability and M1's intracortical circuits. Our results showed that when we targeted the hand's first dorsal interosseous (FDI) muscle with TMS, homotopic (index finger) tactile stimulation, regardless of its point (fingertip or base), reduced corticospinal excitability. Conversely, heterotopic (ring finger) tactile stimulation had no such effect. Notably, stimulating all five fingers simultaneously led to a more pronounced decrease in corticospinal excitability than stimulating individual fingers. Furthermore, tactile stimulation significantly increased intracortical facilitation (ICF) and decreased long-interval intracortical inhibition (LICI) but did not affect short-interval intracortical inhibition (SICI). Considering the significant role of the primary somatosensory cortex (S1) in tactile processing, we also examined the effects of downregulating S1 excitability via continuous theta burst stimulation (cTBS) on tactile-motor interactions. Following cTBS, the inhibitory influence of tactile inputs on corticospinal excitability was diminished. Our findings highlight the spatial specificity of tactile inputs in influencing corticospinal excitability. Moreover, we suggest that tactile inputs distinctly modulate M1's excitatory and inhibitory pathways, with S1 being crucial in facilitating tactile-motor integration.

Reward does not modulate corticospinal excitability in anticipation of a Stroop trial.

Action preparation is associated with a transient decrease of corticospinal excitability just before target onset. We have previously shown that the prospect of reward modulates preparatory corticospinal excitability in a Simon task. While the conflict in the Simon task strongly implicates the motor system, it is unknown whether reward prospect modulates preparatory corticospinal excitability in tasks that implicate the motor system less directly. To that effect, we examined reward-modulated preparatory corticospinal excitability in the Stroop task. We administered a rewarded cue-target delay paradigm using Stroop stimuli that afforded a left or right index finger response. Single-pulse transcranial magnetic stimulation was administered over the left primary motor cortex and electromyography was obtained from the right first dorsal interosseous muscle. In line with previous findings, there was a preparatory decrease in corticospinal excitability during the delay period. In contrast to our previous study using the Simon task, preparatory corticospinal excitability was not modulated by reward. Our results indicate that reward-modulated changes in the motor system depend on specific task-demands, possibly related to varying degrees of motor conflict.

Probing the Effect of Block Duration on Corticospinal Excitability during Motor Imagery Performance

Considerable evidence exists related to the behavioral outcomes of motor imagery-based training (MI). Comparatively, there is a relative gap in the literature on how corticospinal excitability, a precursor for experience-dependent plasticity, changes over the course of an MI session, and more specifically if there is an effect of varying the duration of the blocks in which MI is performed. As such, we probed corticospinal excitability during MI, whereby the duration of MI blocks within the session were manipulated yet total exposure to MI was kept constant. Participants performed a total of 24 min of MI of common motor tasks in blocks of 2, 4 or 6 min. Transcranial magnetic stimulation was used to assess corticospinal excitability throughout MI performance. All groups demonstrated increased corticospinal excitability over the session. Owing to a decrease in corticospinal excitability when engaging in 6 min blocks and the variability noted when engaging in 2 min blocks, findings suggest that MI performed in 4 min blocks may be preferable for the generation and maintenance of corticospinal excitability, at least relative to 2 and 6 min blocks. Overall, our findings provide physiological evidence that informs the structure of MI training sessions to optimize their effectiveness.

Do nociceptive stimulation intensity and temporal predictability influence pain-induced corticospinal excitability modulation?

Temporal predictability and intensity of an impending nociceptive input both shape pain experience and modulate laser-evoked potentials (LEPs) amplitude. However, it remains unclear whether and how these two factors could influence pain-induced corticospinal excitability modulation. The current study investigated the influence of nociceptive stimulation intensity and temporal predictability on motor-evoked potentials (MEPs) modulation, in parallel to their effect on pain perception and LEPs amplitude. Twenty participants completed electroencephalographic and transcranial magnetic stimulation experiments during which two laser nociceptive stimulation intensities (high and low) were either unpredictably delivered (random delay) or preceded by a fixed-timing cue (fixed delay). The amplitude of the conditioned MEPs was significantly reduced only for the high nociceptive stimulation and was not affected by the temporal predictability of pain (despite the fact that temporal predictability modulated the amplitude of P2 LEP component amplitude). However, a posteriori analyses based on patterns of pain-induced MEPs modulation revealed that participants in which nociceptive stimulation resulted in an increase in corticospinal excitability were more affected by the predictability of pain (i.e. increasing corticospinal excitability even more when pain occurrence was predictable), regardless of the nociceptive stimulation intensity; whereas participants in which nociceptive stimulation resulted in a decrease in corticospinal excitability were sensitive to the intensity of the stimulation but not its predictability. These results suggest a potential influence of cognitive factors such as temporal predictability on the response of the motor system in the presence of pain for some participants, contributing to explain, at least in part, the high variability highlighted in a number of previous studies.

FV 5 Quadri-pulse theta burst stimulation using ultra-high frequency bursts at I-wave periodicity induces direction dependent bi-directional plasticity in human primary motor cortex

Background/Question Long-term potentiation (LTP) and long-term depression (LTD) are forms of cortical plasticity and are considered to be synaptic processes underlying learning and memory. Patterned transcranial magnetic stimulation (TMS) such as theta burst stimulation (TBS) or quadri-pulse stimulation (QPS) can induce LTP-like and LTD-like effects in human primary motor cortex (M1), displayed by an increase or decrease in cortico-spinal excitability. Here, we aimed to test the plasticity-inducing capabilities of a novel protocol that merged TBS and QPS – so called quadri-pulse theta burst stimulation (qTBS) – at interstimulus intervals (ISI) that mimic I-wave periodicity (i.e. 1.5 ms/666 Hz) with an effective anterior-posterior (AP) and posterior-anterior (PA) current flow in the brain. Methods We investigated healthy volunteers (n = 12 per protocol) with 360 bursts of qTBS that was continuously given to M1 (i.e. 1440 full-sine pulses). QTBS consisted of repeated bursts of four biphasic TMS pulses (duration: 160 μ s) separated by ISI of 1.5 ms (666 Hz) and inter-burst intervals of 200 ms. (5 Hz). TMS was applied by a custom-made magnetic stimulator (IMETUM, Munich). Resting motor threshold (rMT), and motor evoked potential (MEP) amplitudes with stimulus intensities to target amplitudes of 1mv (SI1mV) were measured before (Pre) qTBS, directly after (Post1), after 15 min (Post2), after 30 min (Post3) and after 60 min (Post4). Results PA-qTBS at 666 Hz caused a decrease in mean MEP amplitudes, whereas AP-qTBS at 666 Hz induced an increase in mean MEP amplitudes outlasting for approximately 60 min. As expected, baseline data of rMT prior to qTBS differed significantly, with higher thresholds in AP direction. Discussion/Conclusion Continuous qTBS at 666 Hz can induce lasting changes in cortico-spinal excitability. Induced current direction in the brain appears to be relevant when qTBS targets I-wave periodicity, corroborating that high-fidelity spike timing mechanisms are critical for inducing bi-directional plasticity in human M1.

P258 Combining tDCS with prismatic adaptation for non invasive neuromodulation of the motor cortex

Introduction Prismatic adaptation (PA) shifts visual field laterally and induces lateralized deviations of spatial attention. Recently, it has been suggested that prismatic goggles are also able to modulate brain excitability ( Magnani, 2014 ), with cognitive after-effects documented even in tasks not necessarily spatial in nature ( Oliveri, 2013 ). Objectives The aim of the present study was to test whether prisms can modulate motor cortical excitability similarly as anodal transcranial direct current stimulation (tDCS) does; to test whether neuromodulatory effects obtained from tDCS and prismatic goggles could interact and induce homeostatic changes in brain excitability. Materials and methods Twenty-four subjects were submitted to single-pulse transcranial magnetic stimulation (TMS) over the right M1 to measure their Input–Output (IO) curve as a measure of cortical excitability ( Carroll, 2011 ). Assessment was made in three experimental groups: before and after rightward PA; before and after atDCS of the right M1; before and after rightward PA and atDCS of the right M1. Results A significant increase of the steepness of the IO curve slope on the right motor cortex was found following either rightward PA or atDCS; on the other hand, a decrease of the steepness of the IO curve slope was found after the combination of rightward PA and atDCS. Conclusion These findings suggest that PA could be an additional tool to modulate cortical plasticity in motor cortices and that an increase or a decrease in corticospinal excitability depends on the functional state of the M1 before or at the time of conditioning ( Lang, 2004 ).

Relationship between motor corticospinal excitability and ventilatory response during intense exercise.

Effort sense has been suggested to be involved in the hyperventilatory response during intense exercise (IE). However, the mechanism by which effort sense induces an increase in ventilation during IE has not been fully elucidated. The aim of this study was to determine the relationship between effort-mediated ventilatory response and corticospinal excitability of lower limb muscle during IE. Eight subjects performed 3min of cycling exercise at 75-85% of maximum workload twice (IE1st and IE2nd). IE2nd was performed after 60min of resting recovery following 45min of submaximal cycling exercise at the workload corresponding to ventilatory threshold. Vastus lateralis muscle response to transcranial magnetic stimulation of the motor cortex (motor evoked potentials, MEPs), effort sense of legs (ESL, Borg 0-10scale), and ventilatory response were measured during the two IEs. The slope of ventilation (l/min) against CO2 output (l/min) during IE2nd (28.0±5.6) was significantly greater than that (25.1±5.5) during IE1st. Mean ESL during IE was significantly higher in IE2nd (5.25±0.89) than in IE1st (4.67±0.62). Mean MEP (normalized to maximal M-wave) during IE was significantly lower in IE2nd (66±22%) than in IE1st (77±24%). The difference in mean ESL between the two IEs was significantly (p<0.05, r=-0.82) correlated with the difference in mean MEP between the two IEs. The findings suggest that effort-mediated hyperventilatory response to IE may be associated with a decrease in corticospinal excitability of exercising muscle.

Brain State-Dependent Transcranial Magnetic Closed-Loop Stimulation Controlled by Sensorimotor Desynchronization Induces Robust Increase of Corticospinal Excitability.

Desynchronization of sensorimotor rhythmic activity increases instantaneous corticospinal excitability, as indexed by amplitudes of motor-evoked potentials (MEP) elicited by transcranial magnetic stimulation (TMS). The accumulative effect of cortical stimulation in conjunction with sensorimotor desynchronization is, however, unclear. The aim of this study was to investigate the effects of repetitive pairing event-related desynchronization (ERD) with TMS of the precentral gyrus on corticospinal excitability. Closed-loop single-pulse TMS was controlled by beta-band (16-22 Hz) ERD during motor-imagery of finger extension and applied within a brain-computer interface environment in eleven healthy subjects. The same number and pattern of stimuli were applied in a control group of eleven subjects during rest, i.e. independent of ERD. To probe for plasticity resistant to depotentiation, stimulation protocols were followed by a depotentiation task. Brain state-dependent application of approximately 300 TMS pulses during beta-ERD resulted in a significant increase of corticospinal excitability. By contrast, the identical stimulation pattern applied independent of beta-ERD in the control experiment resulted in a decrease of corticospinal excitability. These effects persisted beyond the period of stimulation and the depotentiation task. These results could be instrumental in developing new therapeutic approaches such as the application of closed-loop stimulation in the context of neurorehabilitation.

Corticospinal Excitability in the Hand Muscles is Decreased During Eye Movement with Visual Occlusion.

Corticospinal excitability in the hand muscles decreases during smooth pursuit eye movement. The present study tested a hypothesis that the decrease in corticospinal excitability in the hand muscles at rest during eye movement is not caused by visual feedback but caused by motor commands to the eye muscles. Healthy men (M age = 28.4 yr., SD = 5.2) moved their eyes to the right with visual occlusion (dark goggles) while their arms and hands remained at rest. The motor-evoked potential in the hand muscles was suppressed by 19% in the third quarter of the eye-movement period, supporting a view that motor commands to the eye muscles are the cause of the decrease in corticospinal excitability in the hand muscles. The amount of the suppression was not significantly different among the muscles, indicating that modulation of corticospinal excitability in one muscle induced by eye movement is not dependent on whether eye movement direction and the direction of finger movement when the muscle contracts are identical. Thus, the finding failed to support a hypothetical view that motor commands to the eye muscles concomittantly produce motor commands to the hand muscles. Moreover, the amount of the suppression was not significantly different between the forearm positions, indicating that the suppression was not affected by proprioception of the forearm muscles when visual feedback is absent.

Adaptive Motor Imagery: A Multimodal Study of Immobilization-Induced Brain Plasticity

The consequences of losing the ability to move a limb are traumatic. One approach that examines the impact of pathological limb nonuse on the brain involves temporary immobilization of a healthy limb. Here, we investigated immobilization-induced plasticity in the motor imagery (MI) circuitry during hand immobilization. We assessed these changes with a multimodal paradigm, using functional magnetic resonance imaging (fMRI) to measure neural activation, magnetoencephalography (MEG) to track neuronal oscillatory dynamics, and transcranial magnetic stimulation (TMS) to assess corticospinal excitability. fMRI results show a significant decrease in neural activation for MI of the constrained hand, localized to sensorimotor areas contralateral to the immobilized hand. MEG results show a significant decrease in beta desynchronization and faster resynchronization in sensorimotor areas contralateral to the immobilized hand. TMS results show a significant increase in resting motor threshold in motor cortex contralateral to the constrained hand, suggesting a decrease in corticospinal excitability in the projections to the constrained hand. These results demonstrate a direct and rapid effect of immobilization on MI processes of the constrained hand, suggesting that limb nonuse may not only affect motor execution, as evidenced by previous studies, but also MI. These findings have important implications for the effectiveness of therapeutic approaches that use MI as a rehabilitation tool to ameliorate the negative effects of limb nonuse.

Effects of short-term training combining strength and balance exercises on maximal strength and upright standing steadiness in elderly adults

This study investigated the effects of two training programmes of 6weeks combining strength and balance exercises in different proportions. One training programme [n=10; 71.4 (6.3) years] consisted mainly of strength exercises (ST) and the other programme [n=8; 71.4 (6.4) years] included a majority of balance exercises (BT). Maximal strength of lower leg muscles and centre of pressure (CoP) steadiness during upright stance in various sensory conditions were measured before and after training. The input–output relation of motor evoked potential (MEP) induced by transcranial magnetic stimulation and H reflex was also assessed in soleus during upright standing. The maximal strength of the ankle plantar flexor muscles increased after training programmes (p<0.001) with a trend for greater gain in ST (+35.7%) compared with BT (+20.8%, p=0.055). The gain in strength was positively correlated with the increase in voluntary activation (p<0.001). Both training programmes decreased maximal amplitude and mean fluctuations of CoP displacements recorded in the backward–forward direction when standing on a foam mat (p<0.05) but not on a rigid surface. The electromyographic activity of the ankle plantar flexor muscles during upright standing decreased (p<0.05) after training but not for the tibialis anterior. Results obtained for H reflex and MEP input–output relations suggest an increased efficacy of Ia afferents to activate low-threshold motor neurones and a decrease in corticospinal excitability after training. This study indicates that short-term training combining strength and balance exercises increases maximal strength and induces change in the neural control of lower leg muscles during upright standing.

Balancing the excitability of M1 circuitry during movement observation without overt replication.

Although observation of a movement increases the excitability of the motor system of the observer, it does not induce a motor replica. What is the mechanism for replica suppression? We performed a series of experiments, involving a total of 66 healthy humans, to explore the excitability of different M1 circuits and the spinal cord during observation of simple movements. Several strategies were used. In the first and second experimental blocks, we used several delay times from movement onset to evaluate the time-course modulation of the cortico-spinal excitability (CSE), and its potential dependency on the duration of the movement observed; in order to do this single pulse transcranial magnetic stimulation (TMS) over M1 was used. In subsequent experiments, at selected delay times from movement-onset, we probed the excitability of the cortico-spinal circuits using three different approaches: (i) electric cervicomedullary stimulation (CMS), to test spinal excitability, (ii) paired-pulse TMS over M1, to evaluate the cortical inhibitory-excitatory balance (short intracortical inhibition (SICI) and intracortical facilitation (ICF)], and (iii) continuous theta-burst stimulation (cTBS), to modulate the excitability of M1 cortical circuits. We observed a stereotyped response in the modulation of CSE. At 500 ms after movement-onset the ICF was increased; although the most clear-cut effect was a decrease of CSE. The compensatory mechanism was not explained by changes in SICI, but by M1-intracortical circuits targeted by cTBS. Meanwhile, the spinal cord maintained the elevated level of excitability induced when expecting to observe movements, potentially useful to facilitate any required response to the movement observed.

Effects of vitamin D supplementation on neuroplasticity in older adults: a double-blinded, placebo-controlled randomised trial.

Vitamin D can improve muscle function and reduce falls, but whether it can strengthen neural connections within the brain and nervous system is not known. This 10-week randomised controlled trial indicates that treatment with 2,000 IU/day vitamin D3 does not significantly alter neuroplasticity relative to placebo in older adults. The purpose of this study was to examine the effects of vitamin D supplementation on neuroplasticity, serum brain-derived neurotrophic factor (BDNF) and muscle strength and function in older adults. This was a 10-week double-blinded, placebo-controlled randomised trial in which 26 older adults with 25-hydroxyvitamin D [25OHD] concentrations 25-60 nmol/L were randomised to 2,000 IU/day vitamin D3 or matched placebo. Single- and paired-pulse transcranial magnetic stimulation applied over the motor cortex was used to assess changes in motor-evoked potentials (MEPs) and short-interval intracortical inhibition (SICI), as measures of corticospinal excitability and inhibition respectively, by recording electromyography (EMG) responses to stimulation from the wrist extensors. Changes in muscle strength, stair climbing power, gait (timed-up-and-go), dynamic balance (four square step test), serum 25(OH)D and BDNF concentrations were also measured. After 10 weeks, mean 25(OH)D levels increased from 46 to 81 nmol/L in the vitamin D group with no change in the placebo group. The vitamin D group experienced a significant 8-11% increase in muscle strength and a reduction in cortical excitability (MEP amplitude) and SICI relative to baseline (all P < 0.05), but these changes were not significantly different from placebo. There was no effect of vitamin D on muscle power, function or BDNF. Daily supplementation with 2,000 IU vitamin D3 for 10 weeks had no significant effect on neuroplasticity compared to placebo, but the finding that vitamin D treatment alone was associated with a decrease in corticospinal excitability and intracortical inhibition warrants further investigation as this suggests that it may improve the efficacy of neural transmission within the corticospinal pathway.

Effects of being imitated on motor responses evoked by pain observation: exerting control determines action tendencies when perceiving pain in others.

Brain-imaging research has shown that experiencing pain oneself and perceiving pain in others lead to a similar pattern of activation, suggesting that the latter is based on internal simulation of the observed pain. Further evidence for this idea stems from transcranial magnetic stimulation measuring corticospinal excitability (CSE). It has been demonstrated that our motor cortex is involved whenever we observe another person receiving painful stimulation to the hand (Avenanti et al., 2005). However, both decreases and increases of CSE have been described during pain observation, so the exact nature of these CSE changes has remained unclear so far. In the present study, we hypothesized that CSE changes are determined by the control that the observer has over the hand that receives painful stimulation. To test this hypothesis, we manipulated the control over the observed hand using a paradigm in which participants' movements are being imitated by a hand on screen-giving them full control over the hand-or not. Consistent with previous results, we evidenced a decrease in CSE when participants experienced no control over the hand that received painful stimulation. In contrast, inducing control resulted in an increase in CSE. We conclude that exerting control over the observed hand leads to a completely altered action tendency. Whereas an anesthetic response is typically observed in the absence of control, increasing control induces motor facilitation reminiscent of preparation of an avoidance response.

A Physiological Signal That Prevents Motor Skill Improvements during Consolidation

Different memories follow different processing pathways. For example, some motor skill memories are enhanced over wakefulness, whereas others are instead enhanced over sleep. The processing pathway that a motor skill memory follows may be determined by functional changes within motor circuits. We tested this idea using transcranial magnetic stimulation to measure corticospinal excitability at 6, 21, 36, 96, and 126 min after participants learnt tasks that either were or were not enhanced over wakefulness. There was no change in corticospinal excitability after learning a motor skill that was subsequently enhanced; whereas, there was a substantial transient decrease in corticospinal excitability after learning a motor skill that was not enhanced. In subsequent experiments, we abolished the decrease in corticospinal excitability by applying theta burst stimulation to either the dorsolateral prefrontal or primary motor cortex, and induced motor skill improvements during consolidation. The motor skill improvements in each experiment were correlated with the corticospinal excitability after learning. Together, these experiments suggest that corticospinal excitability changes act as a physiological signal, which prevents improvements from developing over wakefulness, and so when this signal is abolished improvements are induced. Our observations show that the human brain can actively prevent the processing of memories, and provides insights into the mechanisms that control the fate of memories.

Brain-Derived Neurotrophic Factor – A Major Player in Stimulation-Induced Homeostatic Metaplasticity of Human Motor Cortex?

Repetitive transcranial magnetic stimulation (rTMS) of the human motor hand area (M1HAND) can induce lasting changes in corticospinal excitability as indexed by a change in amplitude of the motor-evoked potential. The plasticity-inducing effects of rTMS in M1HAND show substantial inter-individual variability which has been partially attributed to the val66met polymorphism in the brain-derived neurotrophic factor (BDNF) gene. Here we used theta burst stimulation (TBS) to examine whether the BDNF val66met genotype can be used to predict the expression of TBS-induced homeostatic metaplasticity in human M1HAND. TBS is a patterned rTMS protocol with intermittent TBS (iTBS) usually inducing a lasting increase and continuous TBS (cTBS) a lasting decrease in corticospinal excitability. In three separate sessions, healthy val66met (n = 12) and val66val (n = 17) carriers received neuronavigated cTBS followed by cTBS (n = 27), cTBS followed by iTBS (n = 29), and iTBS followed by iTBS (n = 28). Participants and examiner were blinded to the genotype at the time of examination. As expected, the first TBS intervention induced a decrease (cTBS) and increase (iTBS) in corticospinal excitability, respectively, at the same time priming the after effects caused by the second TBS intervention in a homeostatic fashion. Critically, val66met carriers and val66val carriers showed very similar response patterns to cTBS and iTBS regardless of the order of TBS interventions. Since none of the observed TBS effects was modulated by the BDNF val66met polymorphism, our results do not support the notion that the BDNF val66met genotype is a major player with regard to TBS-induced plasticity and metaplasticity in the human M1HAND.

The effect of advance information about the sequence of a to-be-signaled motor response on corticospinal excitability during the foreperiod

We investigated the effect of advance information about the sequence of a to-be-signaled motor response on corticospinal excitability during the foreperiod in healthy humans. Advance information about the sequence of a to-be-signaled motor response was provided by a precue signal 600 ms before a response signal during a warned choice reaction task. The precue signal indicated the sequence of one of three to-be-signaled motor responses: simple, repetitive, or sequential motor responses. The amplitude of the motor-evoked potential (MEP) decreased significantly 100 ms before the response signal in both the first dorsal interosseous (FDI) and abductor pollicis brevis (APB) muscles, but a significant decrease was present only in the APB muscle 300 ms before the response signal. The decrease in the MEP amplitude 100 ms before the response signal induced by the precue signal indicating the repetitive motor response was significantly smaller than that induced by the precue signal indicating the simple or sequential motor response in the FDI muscle, and was significantly smaller than that induced by the precue signal indicating the sequential motor response in the APB muscle. The decrease in corticospinal excitability in the middle foreperiod is larger when the advance information about a to-be-signaled motor response is unrelated to the muscle tested, and the decrease in the late foreperiod is affected by advance information about the sequence of a to-be-signaled motor response.

Transcranial direct current stimulation does not modulate motor cortex excitability in patients with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive disease caused by the degeneration of upper and lower motor neurons. The etiology of ALS is unclear, but there is evidence that loss of cortical inhibition could be related to motor neuron degeneration. We sought to determine whether cathodal transcranial direct current stimulation (tDCS) can reduce cortical excitability in patients with ALS. Three sessions of cathodal tDCS, lasting 7, 11, or 15 minutes, were performed in 10 patients and 10 healthy controls. Corticospinal excitability was measured before and after the tDCS. Cathodal tDCS induced a consistent decrease in corticospinal excitability in healthy controls, but not in ALS patients. The failure of tDCS to produce an excitability shift in the patients supports the potential diagnostic value of tDCS as a marker of upper motor neuron involvement. However, variation in corticospinal excitability measurements both inter- and intraindividually will limit its usefulness.

Alteration of cortical excitability in patients with fibromyalgia

We assessed cortical excitability and intracortical modulation systematically, by transcranial magnetic stimulation (TMS) of the motor cortex, in patients with fibromyalgia. In total 46 female patients with fibromyalgia and 21 normal female subjects, matched for age, were included in this study. TMS was applied to the hand motor area of both hemispheres and motor evoked potentials (MEPs) were recorded for the first interosseous muscle of the contralateral hand. Single-pulse stimulation was used for measurements of the rest motor threshold (RMT) and suprathreshold MEP. Paired-pulse stimulation was used to assess short intracortical inhibition (SICI) and intracortical facilitation (ICF). Putative correlations were sought between changes in electrophysiological parameters and major clinical features of fibromyalgia, such as pain, fatigue, anxiety, depression and catastrophizing. The RMT on both sides was significantly increased in patients with fibromyalgia and suprathreshold MEP was significantly decreased bilaterally. However, these alterations, suggesting a global decrease in corticospinal excitability, were not correlated with clinical features. Patients with fibromyalgia also had lower ICF and SICI on both sides, than controls, these lower values being correlated with fatigue, catastrophizing and depression. These neurophysiological alterations were not linked to medication, as similar changes were observed in patients with or without psychotropic treatment. In conclusion, fibromyalgia is associated with deficits in intracortical modulation involving both GABAergic and glutamatergic mechanisms, possibly related to certain aspects of the pathophysiology of this chronic pain syndrome. Our data add to the growing body of evidence for objective and quantifiable changes in brain function in fibromyalgia.

Impaired modulation of corticospinal excitability following subthreshold rTMS in focal hand dystonia

Previous studies have demonstrated that subthreshold 1 Hz repetitive transcranial magnetic stimulation (rTMS) causes a decrease in corticospinal excitability in neurologically normal subjects. The effects of subthreshold 1 Hz rTMS upon corticospinal excitability and intracortical inhibition in subjects with focal hand dystonia (FHD) is not yet clear. The purpose of this study was to examine the effects of low intensity 1 Hz rTMS upon these variables in control and FHD subjects. We recorded electromyographic (EMG) from the first dorsal interosseous (FDI) muscle of the dominant hands of seven control subjects, and seven affected hands of five FHD subjects. We used single and paired pulse TMS to examine motor evoked potential (MEP) amplitude, short interval intracortical inhibition (ICI) and silent period duration before, during and after 20 min of low intensity 1 Hz rTMS. MEP amplitude decreased significantly over the course of the rTMS in control subjects, but did not change in FHD subjects. Silent period duration was significantly longer in control subjects after rTMS, but there was no change in FHD subjects. There was no significant change in ICI after rTMS in either subject group, despite the rTMS intensity being set to preferentially activate intracortical inhibitory networks. This suggests that low intensity 1 Hz rTMS may have limited application in the normalisation of inhibitory function in FHD.