Changes In Motor Excitability Research Articles

Exploring the links between gut microbiota and excitatory and inhibitory brain processes in alcohol use disorder: A TMS study

While the impact of the gut microbiota on brain and behavior is increasingly recognized, human studies examining this question are still scarce. The primary objective of the current study was to explore the potential relationships between the gut microbiota composition, motor cortical excitability at rest and during inhibitory control, as well as behavioral inhibition, in healthy volunteers and in patients suffering from alcohol use disorder. Motor cortical excitability was examined using a range of transcranial magnetic stimulation (TMS) measures probed at rest, including the recruitment curve, short and long intracortical inhibition, and intracortical facilitation within the primary motor cortex. Moreover, TMS was applied during a choice reaction time task to assess changes in motor excitability associated with inhibitory control. Finally, behavioral inhibition was investigated using a neuropsychological task (anti-saccade). Overall, our results highlight several interesting correlations between microbial composition and brain measures. Hence, higher bacterial diversity, as well as higher relative abundances of UGC-002 and Christensenellaceae R-7 group were correlated with stronger changes in motor excitability associated with inhibitory control. Also, higher abundance of Anaerostipes was associated with higher level of corticospinal excitability. Finally, relative abundances of Bifidobacterium and Faecalibacterium were positively related to performance in the neuropsychological task, suggesting that they might have a positive impact on behavioral inhibition. Although correlation is not causation, the present study suggests that excitatory and inhibitory brain processes might be related to gut microbiota composition.This article is part of the Special Issue on ‘Microbiome & the Brain: Mechanisms & Maladies’.

Transcranial direct current stimulation in stroke – Motor excitability and motor function

ObjectiveTo characterize motor excitability changes and changes of motor performance induced by a single anodal and cathodal transcranial direct current stimulation (tDCS) session in stroke patients. MethodsTwenty subacute stroke patients participated. Motor performance was tested with the Box and Block Test [BBT]. Motor cortex excitability (short interval intracortical inhibition [SICI], intracortical facilitation [ICF], long interval intracortical inhibition [LICI]) was examined by paired pulse transcranial magnetic stimulation before and after a single tDCS session (20 minutes, 1,0 mA). On two different occasions, patients received anodal and cathodal tDCS over the affected hemisphere. TMS recordings were taken from both hands consecutively. ResultsAnodal tDCS significantly reduced SICI without changing ICF or LICI. Cathodal tDCS did not change motor excitability. Both types of tDCS did not alter motor performance. Even prior to anodal tDCS, SICI in the affected hemisphere was lower than in the unaffected hemisphere and was correlated with BBT changes after anodal tDCS. ConclusionsAnodal, but not cathodal tDCS specifically modulated intracortical inhibitory circuits, leading to a disinhibition. SignificanceThe results amplify our knowledge on excitability modulations of tDCS in stroke patients.

Electrophysiological investigation of motor axonal excitability in a mouse model of nerve constriction injury.

Peripheral nerve injuries caused by focal constriction are characterised by local nerve ischaemia, axonal degeneration, demyelination, and neuroinflammation. The aim of this study was to understand temporal changes in the excitability properties of injured motor axons in a mouse model of nerve constriction injury (NCI). The excitability of motor axons following unilateral sciatic NCI was studied in male C57BL/6J mice distal to the site of injury at the acute (6 hours-1 week) and chronic (up to 20 weeks) phases of injury, using threshold tracking. Multiple measures of nerve excitability, including strength-duration properties, threshold electrotonus, current-threshold relationship, and recovery cycle were examined using the automated nerve excitability protocol (TRONDNF). Acutely, injured motor axons developed a pattern of excitability characteristic of ischemic depolarisation. In most cases, the sciatic nerve became transiently inexcitable. When a liminal compound muscle action potential could again be recorded, it had an increase in threshold and latency, compared to both pre-injury baseline and sham-injured groups. These axons showed a greater threshold change in response to hyperpolarising threshold electrotonus and a significant upward shift in the recovery cycle. Mathematical modelling suggested that the changes seen in chronically injured axons involve shortened internodes, reduced myelination, and exposed juxtaparanodal fast K+ conductances. The findings of this study demonstrate long-term changes in motor excitability following NCI (involving alterations in axonal properties and ion channel activity) and are important for understanding the mechanisms of neurapraxic injuries and traumatic mononeuropathies.

Enhancing Motor Brain Activity Improves Memory for Action Language: A tDCS Study.

The embodied cognition approach to linguistic meaning posits that action language understanding is grounded in sensory-motor systems. However, evidence that the human motor cortex is necessary for action language memory is meager. To address this issue, in two groups of healthy individuals, we perturbed the left primary motor cortex (M1) by means of either anodal or cathodal transcranial direct current stimulation (tDCS), before participants had to memorize lists of manual action and attentional sentences. In each group, participants received sham and active tDCS in two separate sessions. Following anodal tDCS (a-tDCS), participants improved the recall of action sentences compared with sham tDCS. No similar effects were detected following cathodal tDCS (c-tDCS). Both a-tDCS and c-tDCS induced variable changes in motor excitability, as measured by motor-evoked potentials induced by transcranial magnetic stimulation. Remarkably, across groups, action-specific memory improvements were positively predicted by changes in motor excitability. We provide evidence that excitatory modulation of the motor cortex selectively improves performance in a task requiring comprehension and memory of action sentences. These findings indicate that M1 is necessary for accurate processing of linguistic meanings and thus provide causal evidence that high-order cognitive functions are grounded in the human motor system.

Temporal Profile and Limb-specificity of Phasic Pain-Evoked Changes in Motor Excitability

A fundamental function of nociception is to trigger defensive motor responses to threatening events. Here, we explored the effects of phasic pain on the motor excitability of ipsilateral and contralateral arms. We reasoned that the occurrence of a short-lasting nociceptive stimulus should result in a specific modulation of motor excitability for muscles involved in the withdrawal of the stimulated limb. This was assessed using transcranial magnetic stimulation (TMS) of the left and right primary motor cortex to elicit motor-evoked potentials (MEPs) in three flexor and two extensor muscles of both arms. To assess the time-course of nociception-motor interactions, TMS pulses were triggered 50–2000 ms after delivering short-lasting nociceptive laser stimuli to the left or right hand. We made three main observations. First, nociceptive stimuli induced an early-latency (100 ms) enhancement of MEPs in flexor muscles of the stimulated hand. Considering its latency, this modulation is likely consequent to nociceptive-motor interactions at spinal level. This early and lateralized enhancement was followed by a later (150–400 ms) MEP reduction in extensor muscles of the stimulated hand and flexor muscles of both hands, predominant at the stimulated hand. Finally, we observed a long-lasting (600–2000 ms) MEP enhancement in muscles of the non-stimulated hand. These later effects of the nociceptive stimulus could reflect nociception-motor interactions occurring at cortical level.

TDCS changes in motor excitability are specific to orientation of current flow

BackgroundMeasurements and models of current flow in the brain during transcranial Direct Current Stimulation (tDCS) indicate stimulation of regions in-between electrodes. Moreover, the folded cortex results in local fluctuations in current flow intensity and direction, and animal studies suggest current flow direction relative to cortical columns determines response to tDCS. MethodsHere we test this idea by using Transcranial Magnetic Stimulation Motor Evoked Potentials (TMS-MEP) to measure changes in corticospinal excitability following tDCS applied with electrodes aligned orthogonal (across) or parallel to M1 in the central sulcus. ResultsCurrent flow models predicted that the orthogonal electrode montage produces consistently oriented current across the hand region of M1 that flows along cortical columns, while the parallel electrode montage produces non-uniform current directions across the M1 cortical surface. We find that orthogonal, but not parallel, orientated tDCS modulates TMS-MEPs. We also show modulation is sensitive to the orientation of the TMS coil (PA or AP), which is thought to select different afferent pathways to M1. ConclusionsOur results are consistent with tDCS producing directionally specific neuromodulation in brain regions in-between electrodes, but shows nuanced changes in excitability that are presumably current direction relative to column and axon pathway specific. We suggest that the direction of current flow through cortical target regions should be considered for targeting and dose-control of tDCS.

Timing and specificity of early changes in motor excitability during movement observation.

Motor resonance is typically considered a modulation of motor activity during action observation, which mirrors the pattern of muscle activation occurring during execution of the observed action. There is preliminary evidence that motor activity accompanying action observation comprises two stages: an initial non-specific modulation, followed by a later change in excitability that is specific to the muscles involved in the action. We built on this previous work, with the aims of (1) clarifying the time-course of muscle specificity during action observation and (2) establishing whether modulation at each time point reflects significant changes (facilitation or suppression) from baseline. Motor-evoked potentials were elicited in two muscles-the first dorsal interosseous (FDI) and abductor digiti minimi (ADM)-while participants watched stimuli showing index or little finger abduction. Our results provide partial support for previous findings of muscle-specific modulation after, but not before, 200 ms. Interestingly, however, this was shown only by facilitation of the FDI during index finger observation; there was no significant facilitation of the ADM when little finger movement was observed. Furthermore, we found no facilitation of corticospinal excitability (specific or non-specific) at time points earlier than 200 ms (100-150 ms). We discuss these results in the context of previous work showing a non-specific increase in excitability at 90 ms during action observation. Together, these findings suggest a fast and short-lived facilitation of corticospinal excitability that occurs at around 60-90 ms and ends by 100-150 ms.

Discrimination of speech and non-speech sounds following theta-burst stimulation of the motor cortex.

Perceiving speech engages parts of the motor system involved in speech production. The role of the motor cortex in speech perception has been demonstrated using low-frequency repetitive transcranial magnetic stimulation (rTMS) to suppress motor excitability in the lip representation and disrupt discrimination of lip-articulated speech sounds (Möttönen and Watkins, 2009). Another form of rTMS, continuous theta-burst stimulation (cTBS), can produce longer-lasting disruptive effects following a brief train of stimulation. We investigated the effects of cTBS on motor excitability and discrimination of speech and non-speech sounds. cTBS was applied for 40 s over either the hand or the lip representation of motor cortex. Motor-evoked potentials recorded from the lip and hand muscles in response to single pulses of TMS revealed no measurable change in motor excitability due to cTBS. This failure to replicate previous findings may reflect the unreliability of measurements of motor excitability related to inter-individual variability. We also measured the effects of cTBS on a listener’s ability to discriminate: (1) lip-articulated speech sounds from sounds not articulated by the lips (“ba” vs. “da”); (2) two speech sounds not articulated by the lips (“ga” vs. “da”); and (3) non-speech sounds produced by the hands (“claps” vs. “clicks”). Discrimination of lip-articulated speech sounds was impaired between 20 and 35 min after cTBS over the lip motor representation. Specifically, discrimination of across-category ba–da sounds presented with an 800-ms inter-stimulus interval was reduced to chance level performance. This effect was absent for speech sounds that do not require the lips for articulation and non-speech sounds. Stimulation over the hand motor representation did not affect discrimination of speech or non-speech sounds. These findings show that stimulation of the lip motor representation disrupts discrimination of speech sounds in an articulatory feature-specific way.

Eating tools in hand activate the brain systems for eating action: A transcranial magnetic stimulation study

There is increasing neuroimaging evidence suggesting that visually presented tools automatically activate the human sensorimotor system coding learned motor actions relevant to the visual stimuli. Such crossmodal activation may reflect a general functional property of the human motor memory and thus can be operating in other, non-limb effector organs, such as the orofacial system involved in eating. In the present study, we predicted that somatosensory signals produced by eating tools in hand covertly activate the neuromuscular systems involved in eating action. In Experiments 1 and 2, we measured motor evoked response (MEP) of the masseter muscle in normal humans to examine the possible impact of tools in hand (chopsticks and scissors) on the neuromuscular systems during the observation of food stimuli. We found that eating tools (chopsticks) enhanced the masseter MEPs more greatly than other tools (scissors) during the visual recognition of food, although this covert change in motor excitability was not detectable at the behavioral level. In Experiment 3, we further observed that chopsticks overall increased MEPs more greatly than scissors and this tool-driven increase of MEPs was greater when participants viewed food stimuli than when they viewed non-food stimuli. A joint analysis of the three experiments confirmed a significant impact of eating tools on the masseter MEPs during food recognition. Taken together, these results suggest that eating tools in hand exert a category-specific impact on the neuromuscular system for eating.

Motor excitability changes during action observation in stroke patients

To explore whether stroke patients exhibit increases in motor excitability during action observation, whether differences exist between the affected and non-affected sides, and between pure motor strokes and predominantly sensory strokes. In 18 patients (10 pure motor strokes, 8 predominantly sensory strokes, < 6 months after the stroke) transcranial magnetic stimulation was used to test motor excitability while the patients viewed a video showing a hand performing pinch grips. Transcranial magnetic stimulation pulses were applied at 120% of the individual motor threshold at rest, as obtained from the affected hemisphere. Recordings were taken simultaneously from the first dorsal interosseous muscle of both hands. Motor performance was evaluated with the Box and Block Test. Transcranial magnetic stimulation-evoked muscle responses obtained from the affected and the unaffected sides were significantly higher during action observation than during rest (p = 0.024 and p = 0.004, respectively). This effect was significantly stronger when measuring the same hand as the one viewed in the video (p = 0.019). No difference was found between motor and sensory strokes. In 11 patients there was an action observation-associated increase in the amplitudes of motor evoked potentials in the affected side. In 15 patients there was an action observation-associated increase in motor evoked potentials amplitudes in the unaffected side. The results are potentially relevant for the use of action observation as a treatment strategy.

Electrophysiological correlates of disobedience and feigning-like behaviour in motor imagery

ObjectiveTo explore motor excitability changes induced by disobedience and feigning-like behaviour. MethodsHealthy subjects participated in motor imagery tasks. They imagined either a maximum muscle relaxation (condition 1) or a pinch grip (condition 2). In other trials, they were instructed to disobey the command to imagine a pinch grip. Instead, they should either imagine a maximum muscle relaxation (condition 3) or think of something else which they could choose freely (condition 4). Transcranial magnetic stimulation was used to explore motor excitability during the different tasks. Motor evoked potential amplitudes were expressed as percentage of the task-free control condition (condition 5). ResultsImagination of a pinch grip enhanced motor excitability, imagery of maximum muscle relaxation reduced motor excitability below the level of the control condition. In conditions 3 and 4, motor excitability was lower than in condition 2. However, motor excitability in condition 3 was higher than in condition 1. ConclusionsHealthy subjects successfully disobeyed the motor imagery command but failed to maintain the down-regulation of motor excitability when trying to imagine maximum muscle relaxation. SignificanceThe results help to interpret the down-regulation of motor excitability found in patients with motor conversion disorder.

Interhemispheric Balance in Parkinson's Disease: A Transcranial Magnetic Stimulation Study

BackgroundParkinson's disease (PD) is characterized by various changes in motor excitability. ObjectiveTo examine through Transcranial Magnetic Stimulation (TMS) cortical excitability, specifically addressing interhemispheric connections in PD. MethodsNineteen PD patients with a predominant involvement of the left hemibody (7 females, age 61.7 years,) and 13 controls (6 females, age 61.5 years) entered the study. Patients were subdivided into two groups (early and advanced) according to the time from PD diagnosis. Participants underwent evaluation of Resting Motor Threshold (RMT) and ipsilateral Silent Period (iSP), induced by suprathreshold TMS on the ipsilateral-M1, measured as suppression of voluntary EMG activity. Mirror Movements (MM) were EMG-recorded and scored, in three upper limb muscles, during unilateral voluntary hand movement. Patients were studied at baseline (OFF drug) and after acute levodopa challenge (ON). ResultsPD patients showed a general reduction in RMT vs controls (P < 0.01 for right and left hemisphere) in both drug conditions. Early PD had a significantly lower RMT over the right vs the left hemisphere (P = 0.027); this difference was no longer significant after levodopa. In early PD patients, MM were mainly observed in the right arm during voluntary activation of the left, more affected side both in OFF (P = 0.033) and in ON (P = 0.046). In PD, RMT of the left, less affected M1 was significantly correlated with the right lateralized motor score (P = 0.011; Spearman's coefficient = −0.585), as well as with disease duration. In PD patients, a shorter (P = 0.039) and smaller (P = 0.037) iSP was detected when the stimulus was applied to the worse M1 (right) compared with the contralateral side. This asymmetry was significant only OFF drug. In the PD group iSP-duration from the right, less affected APB was negatively correlated with the MM recorded from the same side during the voluntary movement of the worse side (Spearman's coefficient = −0.498; P = 0.035). ConclusionsIncreased cortical motor excitability in PD, consistent with previous findings, is more evident in the worse hemisphere, particularly in early PD. Asymmetric motor involvement is also associated with excessive involuntary mirroring and defective interhemispheric inhibition, both unfavoring the more affected side. Altogether, these findings suggest that asymmetric motor involvement in PD, particularly in the earlier phases of the disease, affects the interhemispheric balance of cortical excitability, movement lateralization and transcallosal inhibition.

Jaw-opening reflex and corticobulbar motor excitability changes during quiet sleep in non-human primates.

To test the hypothesis that the reflex and corticobulbar motor excitability of jaw muscles is reduced during sleep. Polysomnographic recordings in the electrophysiological study. University sleep research laboratories. The reflex and corticobulbar motor excitability of jaw muscles was determined during the quiet awake state (QW) and quiet sleep (QS) in monkeys (n = 4). During QS sleep, compared to QW periods, both tongue stimulation-evoked jaw-opening reflex peak and root mean square amplitudes were significantly decreased with stimulations at 2-3.5 × thresholds (P < 0.001). The jaw-opening reflex latency during sleep was also significantly longer than during QW. Intracortical microstimulation (ICMS) within the cortical masticatory area induced rhythmic jaw movements at a stable threshold (≤ 60 μA) during QW; but during QS, ICMS failed to induce any rhythmic jaw movements at the maximum ICMS intensity used, although sustained jaw-opening movements were evoked at significantly increased threshold (P < 0.001) in one of the monkeys. Similarly, during QW, ICMS within face primary motor cortex induced orofacial twitches at a stable threshold (≤ 35 μA), but the ICMS thresholds were elevated during QS. Soon after the animal awoke, rhythmic jaw movements and orofacial twitches could be evoked at thresholds similar to those before QS. The results suggest that the excitability of reflex and corticobulbar-evoked activity in the jaw motor system is depressed during QS.

Poststroke and Brain Injury Rehabilitation Treatment Strategies

In the June, July, and August issues of the Journal, we introduced the first three parts of a four-issue special series focused on innovative, physiologic treatments for stroke and traumatic brain injury.1–3 These disorders are leading causes of adult disability in the United States, accounting for tremendous personal, social, and financial costs for survivors, caregivers, and society. In the June issue, Hillis has provided an up-to-date review on how physiologic treatments may optimize poststroke aphasia recovery.4 Choi et al.5 and Buxbaum et al.6 have presented data in the July issue relevant to poststroke spatial neglect treatment. The August issue has focused on pharmaceutical treatment of acquired adynamic speech and disordered consciousness.7,8 In this issue, we consider how rehabilitative strategies can be refined and developed further. In rehabilitation science, it is absolutely critical that we move from basic discovery—new, potentially promising neurorehabilitation interventions—toward large-scale, systematic clinical studies and beyond, to their optimal application. Even within our own field, intermediate-stage studies are criticized because they do not use randomized controlled or meta-analytic methodology. However, phase III research planning is neither appropriate nor desirable when a treatment hypothesis is being refined, and its feasibility and optimal setting are being explored.9 This issue presents two papers on combined treatment strategies for poststroke hemiparesis, an area emerging from observational reports into systematic group studies. Malcolm et al.10 added repetitive transcranial magnetic stimulation to a modified protocol for constraint-induced therapy. Although constraint-induced therapy seems to have resulted in motor improvement, adjuvant repetitive transcranial magnetic stimulation induced changes in motor excitability in treated patients without an associated, clinically evident treatment effect. Their results suggest that the relationship between physiologic parameters and functional improvement needs clarification, as do optimal parameters for designing constraint-induced therapy to produce functional gains across individuals. Levy et al.11 examined a combination of botulinum toxin A injections, evidence-based exercise therapy, and constraint-induced movement therapy in hemiparetic patients with spasticity, and motor function insufficient for constraint-induced movement therapy candidacy by standard criteria. Motor ability improved with toxin and exercise therapy, but in the four patients who became eligible, gains made with subsequent constraint-induced movement therapy unfortunately receded as spasticity returned. A larger-scale investigation of constraint-induced movement therapy in stroke survivors with very low motor functional ability, after administering botulinum toxin A/exercise treatment, may now be indicated. We are grateful for the opportunity to bring Journal readers the four-issue special series on brain injury rehabilitation. We hope these articles stimulate a continuing dialogue in the rehabilitation science community and aid in developing more studies to complete and strengthen our translational continuum.

Motor Strokes

The purpose of this research was to investigate the impact of lesion location on motor excitability and motor performance. We studied patients with pure motor strokes in 4 different brain areas: motor cortex lesions (n=7), striatocapsular lesions (n=13), lacunar lesions of the internal capsule (n=13), and paramedian pontine lesions (n=10). Motor performance tests included the 9-hole-peg test and grip strength recordings. Motor excitability was determined by transcranial magnetic stimulation. Motor thresholds, stimulus-response curves, silent periods, motor cortical inhibition, and facilitation were investigated. The 4 groups were clinically similar but showed major differences in motor excitability. Only motor cortex lesions had a loss of intracortical inhibition in the affected hemisphere. In the internal capsule lesion group and the pontine lesion group, stimulus-response curves were depressed on the affected side. All of the subcortical lesions showed a prolongation of the silent period in the paretic side. Motor thresholds were predominantly elevated in the lesioned hemisphere of patients with internal capsule or pontine lesions. Motor performance was correlated with silent period duration in internal capsule lesions and with motor thresholds in internal capsule and pontine lesions. Motor cortex lesions exhibited deficient inhibitory properties. In contrast, subcortical lesions displayed an enhancement of inhibition. Internal capsule and pontine lesions affecting the corticospinal tract on different levels particularly impaired neuronal recruitment. Our results suggest that the lesion location determines a specific pattern of motor excitability changes.

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

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

Acute Remapping within the Motor System Induced by Low-Frequency Repetitive Transcranial Magnetic Stimulation

Repetitive transcranial magnetic stimulation (rTMS) of human primary motor cortex (M1) changes cortical excitability at the site of stimulation and at distant sites without affecting simple motor performance. The aim of this study was to explore how rTMS changes regional excitability and how the motor system compensates for these changes. Using functional brain imaging, activation was mapped at rest and during freely selected finger movements after 30 min of 1 Hz rTMS. rTMS increased synaptic activity in the stimulated left M1 and induced widespread changes in activity throughout areas engaged by the task. In particular, movement-related activity in the premotor cortex of the nonstimulated hemisphere increased after 1 Hz rTMS. Analyses of effective connectivity confirmed that the stimulated part of M1 became less responsive to input from premotor and mesial motor areas. Conversely, after rTMS our results were consistent with increased coupling between an inferomedial portion of left M1 and anterior motor areas. These results are important for three reasons. First, they show changes in motor excitability to central inputs from other cortical areas (as opposed to peripheral or exogenous inputs used in previous studies). Second, they suggest that maintenance of task performance may involve activation of premotor areas contralateral to the site of rTMS, similar to that seen in stroke patients. Third, changes in motor activations at the site of rTMS suggest an rTMS-induced remodeling of motor representations during movement. This remapping may provide a neural substrate for acute compensatory plasticity of the motor system in response to focal lesions such as stroke.

First prize central motor excitability changes after spinal manipulation: A transcranial magnetic stimulation study

Background: The physiologic mechanism by which spinal manipulation may reduce pain and muscular spasm is not fully understood. One such mechanistic theory proposed is that spinal manipulation may intervene in the cycle of pain and spasm by affecting the resting excitability of the motoneuron pool in the spinal cord. Previous data from our laboratory indicate that spinal manipulation leads to attenuation of the excitability of the motor neuron pool when assessed by means of peripheral nerve Ia-afferent stimulation (Hoffmann reflex). Objective: The purpose of this study was to determine the effects of lumbar spinal manipulation on the excitability of the motor neuron pool as assessed by means of transcranial magnetic stimulation. Methods: Motor-evoked potentials were recorded subsequent to transcranial magnetic stimulation. The motor-evoked potential peak-to-peak amplitudes in the right gastrocnemius muscle of healthy voulunteers (n = 24) were measured before and after homolateral L5-S1 spinal manipulation (experimental group) or side-posture positioning with no manipulative thrust applied (control group). Immediately after the group-specific procedure, and again at 5 and 10 minutes after the procedure, 10 motor-evoked potential responses were measured at a rate of 0.05 Hz. An optical tracking system (OptoTRAK, Northern Digital Inc, Waterloo, Canada [<0.10 mm root-mean-square]) was used to monitor the 3-dimensional (3-D) position and orientation of the transcranial magnetic stimulation coil, in real time, for each trial. Results: The amplitudes of the motor-evoked potentials were significantly facilitated from 20 to 60 seconds relative to the prebaseline value after L5-S1 spinal manipulation, without a concomitant change after the positioning (control) procedure. Conclusions: When motor neuron pool excitability is measured directly by central corticospinal activation with transcranial magnetic stimulation techniques, a transient but significant facilitation occurs as a consequence of spinal manipulation. Thus, a basic neurophysiologic response to spinal manipulation is central motor facilitation.

Cortical excitability in patients after loading doses of lamotrigine: a study with magnetic brain stimulation.

Transcranial magnetic stimulation (TMS) of the brain allows the pharmacologic effects of anti-convulsant drugs (AEDs) on the excitability of motor corticospinal pathways to be evaluated in patients with epilepsy and normal subjects. However, no study has yet documented the changes in motor excitability in patients treated with lamotrigine (LTG). We aimed to study the effects of loading doses of LTG on TMS recordings in patients with epilepsy at the beginning of their treatment. We investigated single-pulse TMS in six patients with complex partial seizures. The TMS recordings were performed in five sessions before and during 5 weeks of treatment. Motor threshold, motor-evoked potential (MEP) amplitude, cortical silent period, and peripheral conduction velocity were used as parameters of evaluation. LTG was started with a dosage of 25 mg/day until a daily maintenance dosage of 200 mg/day was reached. The motor threshold activation of thenar muscles was significantly increased by LTG after 2 weeks of treatment and was increased in a parallel way to the loading dose of the drug at week 3 and 5 of treatment. The MEP size recorded from the thenar muscles did not show significant changes at high- or low-intensity stimulation. The cortical silent period remained unchanged at low- and high-intensity stimulation. The absolute latency of MEPs after cortical and cervical stimulation was unchanged, as was the central motor conduction time. Our study documents that loading doses of LTG, administered as monotherapy, progressively increases patients' motor thresholds over short periods.

Transcranial magnetic stimulation in partial epilepsy: drug-induced changes of motor excitability.

Single-pulse transcranial magnetic stimulation (s-TMS) with recording of motor evoked potentials (MEPs) from thenar muscles of both hands was performed on 84 patients with cryptogenic partial epilepsy and 50 healthy controls. We analyzed the cortical latency (CL), central conduction time (CCT), and threshold intensity (TI) required to elicit liminal MEPs at rest. In the patients, CL and CCT were normal, but TI was significantly higher than in the controls. Of the 84 patients, 65 were taking one or more antiepileptic drugs and 19 were untreated. The untreated patients had a significantly lower TI than the treated patients. In the treated patients, the TI increase paralleled the number of drugs taken. Additionally, in 2 subgroups of patients undergoing major modifications of antiepileptic treatment, TI dropped after partial withdrawal of medication and increased following the commencement of therapy. The results suggest that anticonvulsants depress the excitability of human motor pathways in epileptic subjects.