Cortical excitability and sleep deprivation: a transcranial magnetic stimulation study

The objective was to assess the changes in cortical excitability after sleep deprivation in normal subjects. Sleep deprivation activates EEG epileptiform activity in an unknown way. Transcranial magnetic stimulation (TMS) can inform on the excitability of the primary motor cortex. Eight healthy subjects (four men and four women) were studied. Transcranial magnetic stimulation (single and paired) was performed by a focal coil over the primary motor cortex, at the "hot spot" for the right first dorsal interosseous muscle. The following motor evoked potential features were measured: (a) active and resting threshold to stimulation; (b) duration of the silent period; (c) amount of intracortical inhibition on paired TMS at the interstimulus intervals of 2 and 3 ms and amount of facilitation at interstimulus intervals of 14 and 16 ms. The whole TMS session was repeated after a sleep deprivation of at least 24 hours. After the sleep deprivation, the threshold to stimulation (in the active and resting muscle), as well as the silent period, did not change significantly. By contrast, the paired stimulus study showed a significant (p<0.05) reduction in both intracortical inhibition and facilitation. Thus, TMS showed that sleep deprivation is associated with changes in inhibition-facilitation balance in the primary motor cortex of normal subjects. These changes might have a link with the background factors of the "activating" effects of sleep deprivation.     

Cortical voluntary activation can be reliably measured in human wrist extensors using transcranial magnetic stimulation.

OBJECTIVE: A twitch interpolation technique using transcranial magnetic stimulation (TMS) was recently developed to measure motor cortical drive to human elbow flexors. Here, we described studies designed to test the applicability and reliability of the technique for the human wrist extensors and to provide new evidence regarding the sensitivity of the technique to inadvertent antagonist activation. METHODS: Study 1: we measured amplitudes of superimposed twitches (SITs) produced by TMS during wrist extension at intensities from rest to maximal voluntary contraction on two occasions (n=9). Study 2: we assessed the impact of inadvertent antagonist activation by TMS on measurement of voluntary activation using a muscle potentiation technique to increase mechanical efficiency of the wrist flexors (n=6). RESULTS: The SITs decreased linearly between 25% and 100% MVC and voluntary activation could be reliably estimated across days (ICC(2,1)=0.963, p<0.001). Prior potentiation of the wrist flexors had little impact on extension SITs and voluntary activation. CONCLUSIONS: TMS allows valid and reliable measurement of voluntary activation of the wrist extensors. SIGNIFICANCE: TMS can be used to assess effects of supraspinal fatigue, pathology and rehabilitation interventions on cortical activation in upper limb muscle groups.     

Cortical inhibition and excitation in abstinent cocaine-dependent patients: a transcranial magnetic stimulation study

Prior transcranial magnetic stimulation studies showed that resting motor threshold is elevated in abstinent cocaine-dependent patients, suggesting a decrease in axonal excitability. In contrast, the increased incidence of seizures and psychosis in this group suggests increased excitability or decreased inhibition. Here, we studied long-interval intracortical facilitation and long-interval intracortical inhibition, paired-pulse transcranial magnetic stimulation measures that are more directly linked to glutamatergic cortical facilitation and GABAergic inhibition, respectively. Ten cocaine-dependent and 10 healthy controls were examined. Resting motor threshold, long-interval intracortical facilitation and long-interval intracortical inhibition were tested from the left motor cortex. The cocaine group showed an elevated resting motor threshold and an increased long-interval intracortical facilitation, whereas long-interval intracortical inhibition was normal. Although the increase in long-interval intracortical facilitation suggests exaggerated cortical glutamatergic excitability, the increase in resting motor threshold may signify a protective mechanism against seizures and psychosis.     

Cortical excitability in schizophrenia. Studies using transcranial magnetic stimulation

Abnormalities in brain plasticity, including abnormal information processing by disturbed cortical inhibition and facilitation in schizophrenia, have been described several times in the past. Transcranial magnetic stimulation (TMS) provides a neurophysiological technique for the measurement of cortical excitability, especially of the motoneural system. With TMS it is possible to explore important aspects of the pathophysiological mechanisms underlying schizophrenia using recently developed paradigms (paired pulse method, cortical silent period). This review summarizes the results of available diagnostic TMS studies in schizophrenia. Studies investigating the efficacy of therapeutic repetitive magnetic stimulation in patients with treatment resistant hallucinations or predominantly negative symptoms were not considered. The reviewed studies support the assumption of reduced cortical inhibition, probably caused by GABAergic deficit, in schizophrenia. Factors influencing the study results, the limitations of this promising technique in schizophrenia, and further research options are discussed.     

Cortical voluntary activation of the human knee extensors can be reliably estimated using transcranial magnetic stimulation

The objective of this study was to determine if a transcranial magnetic stimulation (TMS) method of quantifying the degree to which the motor cortex drives the muscles during voluntary efforts can be reliably applied to the human knee extensors. Although the technique for estimating “cortical” voluntary activation (VA) is valid and reliable for elbow flexors and wrist extensors, evidence that it can be applied to muscles of the lower limb is necessary if twitch interpolation with TMS is to be widely used in research or clinical practice. Eight subjects completed two identical test sessions involving brief isometric knee extensions at forces ranging from rest to maximal voluntary contraction (MVC). Electromyographic (EMG) responses to TMS of the motor cortex and electrical stimulation of the femoral nerve were recorded from the rectus femoris (RF) and biceps femoris (BF) muscles, and knee extension twitch forces evoked by stimulation were measured. The amplitude of TMS‐evoked twitch forces decreased linearly between 25% and 100% MVC (r² > 0.9), and produced reliable estimations of resting twitch and VA (ICC_2,1 > 0.85). The reliability and size of cortical measures of VA were comparable to those derived from motor nerve stimulation when the resting twitches were estimated on the basis of as few as three TMS trials. Thus, TMS measures of VA may provide a reliable and valid tool in studies investigating central fatigue due to exercise and neurological deficits in neural drive in the lower limbs. © 2008 Wiley Periodicals, Inc. Muscle Nerve 2008     

Cortical involvement in myopathies: Insights from transcranial magnetic stimulation

Objective

There is increasing evidence that an involvement of central nervous system (CNS) can occur in several myopathies. Transcranial magnetic stimulation (TMS) may represent a valuable tool for investigating important neurophysiological and pathophysiological aspects of cortical involvement in neuromuscular disorders. In this review paper we aimed to perform a systematic search of the studies employing TMS techniques in subjects suffering from myopathies.

Motor recovery following stroke: a transcranial magnetic stimulation study.

OBJECTIVES: To verify the usefulness of early recording of motor evoked potentials (MEPs) in predicting motor outcome after stroke and to investigate the neural mechanisms underlying functional recovery following stroke. METHODS: We performed a comparative analysis of the behaviour of motor responses evoked by transcranial magnetic stimulation (TMS) of the ipsilateral and contralateral motor cortex in the affected and unaffected thenar muscles of 21 consecutive patients with acute stroke. RESULTS: According to the behaviour of MEPs in the affected muscles, patients could be divided into 3 groups: (a) 10 subjects with absent responses to TMS of both the damaged and undamaged hemisphere, whose motor recovery was poor and related to the size of MEPs on the normal side; (b) 5 subjects with larger MEPs upon TMS of the ipsilateral (undamaged) than of the contralateral (damaged) cortex, whose good recovery possibly resulted from the emergence of ipsilateral pathways; (c) 6 subjects with larger MEPs in the affected than in the unaffected muscles, whose good recovery was possibly subserved by alternative circuits taking over cortical deafferentation. CONCLUSIONS: Early MEP recording in acute stroke provides useful information on the clinical prognosis and the different mechanisms of motor recovery.     

Motor control in simple bimanual movements: a transcranial magnetic stimulation and reaction time study.

OBJECTIVE: Simple reaction time (RT) can be influenced by transcranial magnetic stimulation (TMS) to the motor cortex. Since TMS differentially affects RT of ipsilateral and contralateral muscles a combined RT and TMS investigation sheds light on cortical motor control of bimanual movements. METHODS: Ten normal subjects and one subject with congenital mirror movements (MM) were investigated with a RT paradigm in which they had to move one or both hands in response to a visual go-signal. Suprathreshold TMS was applied to the motor cortex ipsilateral or contralateral to the moving hand at various interstimulus intervals (ISIs) after presentation of the go-signal. EMG recordings from the thenar muscles of both hands were used to determine the RT. RESULTS: TMS applied to the ipsilateral motor cortex shortened RT when TMS was delivered simultaneously with the go-signal. With increasing ISI between TMS and go-signal the RT was progressively delayed. This delay was more pronounced if TMS was applied contralateral to the moving hand. When normal subjects performed bimanual movements the TMS-induced changes in RT were essentially the same as if they had used the hand in an unimanual task. In the subject with MM, TMS given at the time of the go-signal facilitated both the voluntary and the MM. With increasing ISI, however, RT for voluntary movements and MM increased in parallel. CONCLUSIONS: Ipsilateral TMS affects the timing of hand movements to the same extent regardless of whether the hand is engaged in an unimanual or a bimanual movement. It can be concluded, therefore, that in normal subjects simple bimanual movements are controlled by each motor cortex independently. The results obtained in the subject with MM are consistent with the hypothesis that mirror movements originate from uncrossed corticospinal fibres. The alternative hypothesis that a deficit in transcallosal inhibition leads to MM in the contralateral motor cortex is not compatible with the presented data, because TMS applied to the motor cortex ipsilateral to a voluntary moved hand affected voluntary movements and MM to the same extent.     

Cortical silent period in the tongue induced by transcranial magnetic stimulation.

Cortical silent period (SP) of the limb muscles is thought to reflect the cortical excitability. However, the lingual SP has not been examined precisely even in normal subjects. We investigated SP in the tongue induced by transcranial magnetic stimulation (TMS) in 18 controls. Surface electrodes were placed on the lingual dorsum using a bipolar technique. A round coil (13.5 cm in outer diameter) connected with Magstim 200 stimulator was placed on the motor cortex of the tongue, and the intensity of the stimulation was increased stepwise to maximum. SP was detected in all subjects especially at the contralateral side to the stimulated side, without contamination of peripheral SP. The duration of SP depended on the stimulus intensity, while the degrees of muscle contraction did not influence SP. SP of the tongue showed similar characteristics to that of limb muscles. This suggests that SP of lingual muscles can be clinically useful for the evaluation of corticobulbar excitability.     

Visual and motor cortex excitability: a transcranial magnetic stimulation study.

OBJECTIVES: Phosphene thresholds (PTs) to transcranial magnetic stimulation over the occipital cortex and motor thresholds (MTs) have been used increasingly as measures of the excitability of the visual and motor cortex. MT has been utilized as a guide to the excitability of other, non-motor cortical areas such as dorsolateral prefrontal cortex. The aims of this study were to compare the PTs to MTs; to assess their stability across sessions; and to investigate their relation to MTs. METHODS: PTs and MTs were determined using focal transcranial magnetic stimulation over the visual and motor cortex. RESULTS: PTs were shown to be significantly higher than MTs. Both PTs and MTs were stable across sessions. No correlation between PTs and MTs could be established. CONCLUSIONS: Phosphene threshold is a stable parameter of the visual cortex excitability. MTs were not related to the excitability of non-motor cortical areas.     

Cortical plasticity and motor activity studied with transcranial magnetic stimulation

For decades cortical representations of the parts of the body have been considered to be unchangeable. This view has changed radically during the past 20 years using new tools designed to study plasticity in the adult human brain. Transcranial magnetic stimulation (TMS) is a valuable non-invasive technique for exploring the ability of the motor cortex to change during motor skill acquisition. Results obtained with TMS in neurological patients as well as in normal subjects demonstrate that cortical plasticity is a necessity for correct adaptation to the continuously changing environment. Topographical reorganization of the motor cortex depends on the types of movements performed by the subjects. During simple training, the cortical representation is enlarged, and it returns to its initial size when the task is overlearned. These transient modifications characterize simple motor training. Motor skills in which coordination of distal and proximal muscles, precision of the task and spatio-temporal constraints are associated, has a different impact on cortical reorganization. We propose that years of practice of a complex motor skill induces a new cortical topography that must be interpreted as structural plasticity which provides the capacity to execute a plastic behaviour instead of a stereotypical movement. We review the neuronal mechanisms underlying plasticity in different types of movement. We stress new emerging notions, such as overlap of cortical maps, and system dynamics at single neuron and network levels, to explain the reorganization of movement representations that encode motor skill. Dendritic arborizations as functional computing elements, newly generated neurons in adult brain, and plastic architectures of cortical networks operating as distributed functional modules are new hypotheses for structural plasticity.     

Cortical excitability in cryptogenic localization-related epilepsy: interictal transcranial magnetic stimulation studies

PURPOSE: To assess whether single-and paired-pulse transcranial magnetic stimulation (TMS) can measure the interictal brain excitability of medicated patients with cryptogenic localization related epilepsy (CLE). Changes in the balance between excitation and inhibition are the core phenomena in focal epileptogenesis. TMS can assess this balance in the primary motor cortex. METHODS: We selected 18 patients with CLE and similar clinical features in whom we located the epileptogenic area reliably, with 11 age-and sex-matched healthy controls. For both motor cortices, we determined the threshold to TMS, the duration of the cortical silent period, and the corticocortical inhibition and facilitation curve. RESULTS: TMS was safe. The more antiepileptic drugs (AEDs) taken by the patients, the higher their threshold to TMS. The silent period duration failed to show significant changes. On paired TMS, a cluster analysis identified a homogeneous subgroup of patients (n = 7) who showed a significantly defective corticocortical inhibition and excess facilitation. With respect to the epileptogenic area, the phenomenon was bilateral in four of these patients, ipsilateral in two, and contralateral in one. The phenomenon was independent of AEDs and many other clinical variables. However, this patient group had a higher seizure frequency and a higher proportion of electroencephalograms (EEGs) showing interictal generalized epileptic discharges than the rest of the patients. CONCLUSION: Paired TMS provided a valuable pathophysiologic insight into the interictal excitatory state of the cortex in CLE. This method can potentially supply useful prognostic clinical information.     

Relative suppression of magical thinking: a transcranial magnetic stimulation study

The tendency to perceive meaning in noise (apophenia) has been linked to "magical thinking" (MT), a distinctive form of thinking associated with a range of normal cognitive styles, anomalous perceptual experiences and frank psychosis. Important aspects of MT include the propensity to imbue meaning or causality to events that might otherwise be considered coincidental. Structures in the lateral temporal lobes have been hypothesised to be involved in both the clinical and nonclinical aspects of MT. Accordingly, in this study we used single-pulse transcranial magnetic stimulation (TMS) to stimulate either the left or right lateral temporal areas, or the vertex, of 12 healthy participants (balanced for similar levels of MT, delusional ideation and temporal lobe disturbance) while they were required to indicate if they had "detected" pictures, claimed to be present by the experimenters, in visual noise. Relative to the vertex, TMS inhibition of the left lateral temporal area produced significant reduced tendency to report meaningful information, suggesting that left lateral temporal activation may be more important in MT and therefore producing and supporting anomalous beliefs and experiences. The effect cannot simply be explained by TMS induced cognitive slowing as reaction times were not affected.     

Hemispheric asymmetry in cortical control of memory-guided saccades. A transcranial magnetic stimulation study

To study the temporal organisation of memory-guided saccade control we used single-pulse transcranial magnetic stimulation (TMS) over the left posterior parietal (PPC) and prefrontal cortex (PFC) in eight healthy subjects. TMS was applied either following presentation of a visual target, i.e. 160, 260, and 360 ms after the flashed point, or during the period of memorisation, i.e. between 700 and 1500 ms, or finally 100 ms after extinguishing of the central fixation point (i.e. 2100 ms after the target presentation). Latency of memory-guided saccades and the percentage of error in amplitude (PEA) was measured and compared with results without stimulation.TMS over the left PPC 100 ms after the extinguishing of the central fixation point significantly increased memory-guided saccade latency bilaterally. Furthermore, stimulation over the left PFC had a significant effect on the PEA of contralateral memory-guided saccades when applied during the period of memorisation, i.e. between 700 and 1500 ms.In a previous study using identical methodology [13: Müri RM, Vermersch SI, Rivaud S, Gaymard B, Pierrot-Deseilligny C. Effects of single-pulse transcranial magnetic stimulation over the prefrontal and posterior parietal cortices during memory-guided saccades in humans. Journal of Neurophysiology 1996;76:2102-2106], we found that TMS over the right PPC increased the contralateral PEA when applied 260 ms after the flash, the effects on saccade latency after right PPC stimulation or on the PEA after right PFC stimulation being similar to those observed here. Taken together, these results show that (1) a hemispheric asymmetry in the preparation of memory-guided saccade amplitude during the early phase of sensorimotor integration exists, (2) memory-guided saccade triggering is controlled by PPC on both sides, and (3) PFC on both sides are involved in spatial working memory performance.     

Measurement of voluntary activation of the back muscles using transcranial magnetic stimulation

ObjectiveTwitch interpolation using transcranial magnetic stimulation (TMS) has recently been used to measure the level of drive from the motor cortex to contracting muscles of the upper and lower limbs, termed voluntary activation. It has yet to be used to assess voluntary activation in trunk muscles. The aim of this study was to assess the feasibility of using TMS to measure voluntary activation in back muscles.MethodsSixteen healthy subjects performed a series of brief maximal and submaximal isometric contractions of the back extensors during which TMS was delivered to the motor cortex. The evoked (superimposed) twitch was measured using dynamometry and simultaneous surface electromyographic (EMG) recordings were taken from the left and right erector spinae at vertebral level T12. Voluntary activation was derived using the expression: (1-superimposed twitch amplitude/resting twitch amplitude) × 100. The resting twitch amplitude was estimated by extrapolation of the linear correlation between voluntary torque and superimposed twitch amplitude to zero torque.ResultsThe relationship between superimposed twitch size and voluntary contraction strength for contraction strengths of 50–100% MVC was linear but regression revealed variability between subjects. When data were included from those subjects with a good linear regression fit a strong linear relationship was found for the group means between voluntary contraction strength and voluntary activation (r² = 1) and superimposed twitch size (r² = 0.99) for contraction strengths of 50–100% MVC. Voluntary activation was found to be less than maximal (67.71 ± 5.22%) during maximal efforts. Time-to-peak amplitude decreased linearly with increasing voluntary torque. The amplitudes of the motor evoked potentials (MEPs) increased with increasing voluntary torque.ConclusionsTwitch interpolation using TMS can be used to quantify voluntary activation in back extensors. The results of this study reveal that neural drive to the back extensors during strong contractions is submaximal.SignificanceThe assessment of voluntary activation of the back muscles may aid our understanding of the mechanisms of alteration in control of these muscles implicated in chronic low back pain.     

Cortical excitability in juvenile myoclonic epileptic patients and their asymptomatic siblings: A transcranial magnetic stimulation study

In this study, we aimed to evaluate motor cortical excitability changes in patients with juvenile myoclonic epilepsy (JME) and their asymptomatic siblings (AS) using single-pulse transcranial magnetic stimulation (spTMS). 21 patients with JME and their 21 AS were compared to 20 healthy controls. All of JME patients were receiving antiepileptic therapy and their seizures were well controlled. Firstly, standard EEG examinations and then TMS studies were performed. Resting motor threshold (RMT), motor evoked potential (MEP) amplitudes, the durations of central motor conduction time (CMCT) and cortical silent period (CSP) were measured. After TMS studies, EEG recordings were repeated in an hour to evaluate any effect of TMS study on EEG. There were no significant differences between the first and second EEG recordings. No seizures were recorded during and after the TMS study. RMT was found higher in JME patients than AS and normal controls. There were no significant differences between cortical MEP amplitudes and MEP amplitude/CMAP (compound muscle action potential) amplitude ratio in all three groups. CMCT duration was shorter in JME patients than AS. CSP durations of JME patients were found to be longer than controls. In AS, CSP durations were also found to be longer than controls but this difference was not found statistically significant. Our results suggested that although high MT may be related to antiepileptic therapy, the prolongation of CSP duration may reflect impairment of supraspinal and/or intracortical inhibitory mechanism in JME. To eliminate the drug effect, further studies are needed in newly diagnosed JME patients without medication and large series of their asymptomatic siblings.     

Repetitive transcranial magnetic stimulation as treatment of poststroke depression: a preliminary study.

BACKGROUND: Depression has a significant impact on poststroke recovery and mortality. There are a proportion of patients with poststroke depression (PSD) who do not respond to antidepressants. Repetitive Transcranial Magnetic Stimulation (rTMS) might be a safe and effective alternative in these refractory cases. METHODS: We conducted a randomized, parallel, double-blind study of active versus sham left prefrontal rTMS in patients with refractory PSD. After discontinuing antidepressants, patients were randomly assigned to receive 10 sessions of active (10 Hz, 110% of the motor threshold, 20 trains of 5 seconds duration) or sham left prefrontal rTMS. Efficacy measures included HAM-D scores, response and remission rates. Patients completed a neuropsychological battery at baseline and after completing the protocol. RESULTS: When compared with sham stimulation, 10 sessions of active rTMS of the left dorsolateral prefrontal cortex were associated with a significant reduction of depressive symptoms. This reduction was not influenced by patient's age, type or location of stroke, volume of left frontal leukoaraiosis or by the distance of the stimulating coil to the prefrontal cortex. However, there was a significant positive correlation between the percentage of reduction of Ham-D scores and frontal gray and white matter volumes. There were no significant changes in cognitive functioning between the active and the sham stimulation groups. In addition, there were few and mild adverse effects that were equally distributed among groups. CONCLUSIONS: Taken together, these preliminary findings suggest that rTMS may be an effective and safe treatment alternative for patients with refractory depression and stroke.     

Motor and phosphene thresholds: a transcranial magnetic stimulation correlation study

Objective: To investigate the stability of visual phosphene thresholds and to assess whether they correlate with motor thresholds. Background: Currently, motor threshold is used as an index of cortical sensitivity so that in transcranial magnetic stimulation (TMS) experiments, intensity can be set at a given percentage of this value. It is not known whether this is a reasonable index of cortical sensitivity in non-motor and hence whether it should be used in experiments where other cortical areas are targeted. Previous studies have indicated that phosphene threshold might be a suitable alternative in TMS studies of the visual system. Method: Using single pulse TMS visual phosphene and motor thresholds were measured in 15 subjects. Both thresholds were retested in seven of these subjects a week later. Result: Visual phosphene thresholds, though stable within subjects across the two sessions, showed greater variability than motor thresholds. There was no correlation between the two measures. Conclusion: TMS motor thresholds cannot be assumed to be a guide to visual cortex excitability and by extension are probably an inappropriate guide to the cortical excitability of other non-motor areas of the brain. Phosphene thresholds are proposed as a potential standard for inter-individual comparison in visual TMS experiments.     

Semantic factors influence multisensory pairing: a transcranial magnetic stimulation study

It is traditionally assumed that temporal and spatial factors determine whether information provided by different sensory modalities is combined in a single percept. However, neuropsychological reports of selective damage to audio-visual integration and recent neurophysiological results suggest that semantic factors related to the content of the stimuli could also play a role. As a means of extending evidence provided by neuropsychological dissociations we set up a direct comparison of two kinds of audio-visual pairs with different semantic properties and used transcranial magnetic stimulation (TMS). We investigated the selective impact of TMS on two kinds of audio-visual pairings presented under identical spatio-temporal conditions (face-voice and tone-shape pairings). Our results show that TMS applied over the left posterior parietal cortex at 200 ms disrupted audio-visual integration for the tone-shape pairings but not for the face-voice ones. Our data are consistent with neuropsychological findings and indicate that besides the well-known dimensions of spatial and temporal contiguity, content is an important determinant of audio-visual integration. Our study also illustrates the usefulness of TMS for addressing the role of semantic factors in multi-sensory perception