[show abstract][hide abstract] ABSTRACT: During the past decade, a large amount of work on transcranial magnetic stimulation (TMS) has been performed, including the development of new paradigms of stimulation, the integration of imaging data, and the coupling of TMS techniques with electroencephalography or neuroimaging. These accumulating data being difficult to synthesize, several French scientific societies commissioned a group of experts to conduct a comprehensive review of the literature on TMS. This text contains all the consensual findings of the expert group on the mechanisms of action, safety rules and indications of TMS, including repetitive TMS (rTMS). TMS sessions have been conducted in thousands of healthy subjects or patients with various neurological or psychiatric diseases, allowing a better assessment of risks associated with this technique. The number of reported side effects is extremely low, the most serious complication being the occurrence of seizures. In most reported seizures, the stimulation parameters did not follow the previously published recommendations (Wassermann, 1998)  and rTMS was associated to medication that could lower the seizure threshold. Recommendations on the safe use of TMS / rTMS were recently updated (Rossi et al., 2009) , establishing new limits for stimulation parameters and fixing the contraindications. The recommendations we propose regarding safety are largely based on this previous report with some modifications. By contrast, the issue of therapeutic indications of rTMS has never been addressed before, the present work being the first attempt of a synthesis and expert consensus on this topic. The use of TMS/rTMS is discussed in the context of chronic pain, movement disorders, stroke, epilepsy, tinnitus and psychiatric disorders. There is already a sufficient level of evidence of published data to retain a therapeutic indication of rTMS in clinical practice (grade A) in chronic neuropathic pain, major depressive episodes, and auditory hallucinations. The number of therapeutic indications of rTMS is expected to increase in coming years, in parallel with the optimisation of stimulation parameters.
[show abstract][hide abstract] ABSTRACT: Sensory inputs from cutaneous and limb receptors are known to influence motor cortex network excitability. Although most recent studies have focused on the inhibitory influences of afferent inputs on arm motor responses evoked by transcranial magnetic stimulation (TMS), facilitatory effects are rarely considered. In the present work, we sought to establish how proprioceptive sensory inputs modulate the excitability of the primary motor cortex region controlling certain hand and wrist muscles. Suprathreshold TMS pulses were preceded either by median nerve stimulation (MNS) or index finger stimulation with interstimulus intervals (ISIs) ranging from 20 to 200 ms (with particular focus on 40-80 ms). Motor-evoked potentials recorded in the abductor pollicis brevis (APB), first dorsalis interosseus and extensor carpi radialis muscles were strongly facilitated (by up to 150%) by MNS with ISIs of around 60 ms, whereas digit stimulation had only a weak effect. When MNS was delivered at the interval that evoked the optimal facilitatory effect, the H-reflex amplitude remained unchanged and APB motor responses evoked with transcranial electric stimulation were not increased as compared with TMS. Afferent-induced facilitation and short-latency intracortical inhibition (SICI) and intracortical facilitation (ICF) mechanisms are likely to interact in cortical circuits, as suggested by the strong facilitation observed when MNS was delivered concurrently with ICF and the reduction of SICI following MNS. We conclude that afferent-induced facilitation is a mechanism which probably involves muscle spindle afferents and should be considered when studying sensorimotor integration mechanisms in healthy and disease situations.
European Journal of Neuroscience 09/2009; 30(3):439-48. · 3.75 Impact Factor
[show abstract][hide abstract] ABSTRACT: Restless legs syndrome (RLS) is characterized by closely interrelated motor and sensory disorders. Two types of involuntary movement can be observed: periodic leg movements during wakefulness (PLMW) and periodic leg movements during sleep (PLMS). Basal ganglia dysfunction in primary RLS has often been suggested. However, clinical observations raise the hypothesis of sensorimotor cortical involvement in RLS symptoms. Here, we explored cortical function via movement-related beta and mu rhythm reactivity.
Twelve patients with idiopathic, primary RLS were investigated and compared with 10 healthy subjects. In the patient group, we analyzed event-related beta and mu (de)synchronization (ERD/S) for PLMS and PLMW during a suggested immobilization test (SIT). An ERD/S analysis was also performed in patients and controls during self-paced right ankle dorsal flexion at 8:30 PM (i.e., the symptomatic period for patients) and 8:30 AM (the asymptomatic period).
Before PLMS, there was no ERD. Intense ERS was recorded after PLMS. As with voluntary movement, cortical ERD was always observed before PLMW. After PLMW, ERS had a diffuse scalp distribution. Furthermore, the ERS and ERD amplitudes and durations for voluntary movement were greater during the symptomatic period than during the asymptomatic period and in comparison with healthy controls, who presented an evening decrease in these parameters. Patients and controls had similar ERD and ERS patterns in the morning.
On the basis of a rhythm reactivity study, we conclude that the symptoms of RLS are related to cortical sensorimotor dysfunction.
Sleep Medicine 06/2009; 10(10):1090-6. · 3.49 Impact Factor
[show abstract][hide abstract] ABSTRACT: The objective of this study was to characterize the effects of various parameters (notably the frequency and intensity) of repetitive transcranial magnetic stimulation (rTMS) applied over the primary motor (M1) and premotor (PMC) cortices on the excitability of the first dorsalis interosseus (FDI) corticospinal pathway. To this end, we applied a comprehensive input-output analysis after fitting the experimental results to a sigmoidal function. Twenty-six healthy subjects participated in the experiments. Repetitive TMS was applied either over M1 or PMC at 1 Hz (LF) for 30 min (1,800 pulses) or at 20 Hz (HF) for 20 min (1,600 pulses). In the HF condition, the TMS intensity was set to 90% (HF(90)) of the FDI's resting motor threshold (RMT). In the LF condition, the TMS intensity was set to either 90% (LF(90)) or 115% (LF(115)) of the RMT. The FDI input/output (I/O) curve was measured on both sides of the body before rTMS (the Pre session) and then during two Post sessions. For each subject, the I/O curves (i.e., the integral of the FDI motor-evoked potential (MEP) vs. stimulus intensity) were fitted using a Boltzmann sigmoidal function. The graph's maximum slope, S (50) and plateau value were then compared between Pre and Post sessions. LF(115) over M1 increased the slope of the FDI I/O curve but did not change the S (50) and plateau value. This also suggested an increase in the RMT. HF(90) led to a more complex effect, with an increase in the slope and a decrease in the S (50) and plateau value. We did not see a cross effect on the homologous FDI corticospinal pathway, and only PMC LF(90) had an effect on ipsilateral corticospinal excitability. Our results suggest that rTMS may exert a more complex influence on cortical network excitability than is usually reported (i.e. simple inhibitory or facilitatory effects). Analysis of the fitted stimulus response curve indicates a dichotomous influence of both low- and high-frequency rTMS on M1 cortical excitability; this may reflect intermingled effects on excitatory and inhibitory cortical networks.
Experimental Brain Research 03/2008; 187(2):207-17. · 2.22 Impact Factor
[show abstract][hide abstract] ABSTRACT: To examine the effects of a 30 min, 1 Hz subthreshold rTMS in a case of cortical tremor which is caused by hyperexcitability of sensorimotor cortex.
Stimulation was applied over primary and, in a second time, over premotor cortex (M1 and PMC, respectively). Tremor was monitored by accelerometers placed on the index fingers of hands outstretched, before and several times after rTMS. Each rTMS session consisted of 1800 pulses delivered at 1 Hz with an intensity of 90% of resting motor threshold.
PMC but not M1 stimulation led to a decrease of the postural tremor (90% decrease of acceleration total spectral power). This functional benefit was associated to normalization of electrophysiologic parameters (short-interval intracortical inhibition and cortical silent period duration). Moreover, when stimulating PMC during two daily sessions, improvement of the tremor was longer than one day stimulation and this benefit was associated with functional improvement.
This study shows that 1 Hz rTMS over premotor cortex can improve cortical tremor.
These results raise the interest of the motor cortical stimulation as a possible therapeutic target for treatment of action tremor.
[show abstract][hide abstract] ABSTRACT: This study used TMS mapping to investigate the motor representation of the abductor pollicis brevis (APB) muscles in a group of patients with focal epilepsy originating in central or pre-central region.
Eight epileptic patients and eight control subjects participated in the study. The coil was moved in 1.5-cm steps along a grid drawn on the subject's skull over the motor cortex of both hemispheres. At each site, six APB motor responses (evoked by TMS at 1.2 times the resting motor threshold) were recorded and averaged. The peak-to-peak amplitude was measured and plotted against the mediolateral and anteroposterior coil positions. The area of each APB muscle representation was measured and the position of the optimal point was calculated.
The resting motor threshold was increased bilaterally in epileptic patients. The maps were distorted in most patients (but not in control subjects), as evidenced by an off-centre optimal point. Interhemispheric differences in APB map areas were greater in patients than in control subjects. However, whether these increases in map area were on the epileptic side or on healthy side depended on the given subject.
The changes in APB representation observed in epileptic patients demonstrate that reorganization occurs within the motor cortex. The heterogeneity of the present results is probably related to different locations of the epileptogenic and/or lesional areas and to a variety of compensatory phenomena that may occur, notably with respect to the disease duration.
Epilepsy Research 08/2007; 75(2-3):197-205. · 2.24 Impact Factor
[show abstract][hide abstract] ABSTRACT: Dystonia is characterized by sustained muscle contraction, which frequently causes repetitive, twisting movements or abnormal posture. The precise pathophysiological mechanisms of dystonia are still unknown. Several studies did demonstrate that, although motor cortex hyperexcitability appears to be responsible for abnormal co-contraction and overflow to adjacent muscles, plasticity mechanisms and integrative sensorimotor processing are also likely to be involved in this condition. Current dystonia treatments are based on oral medication, injection of botulinum toxin and, in a low proportion of cases, bi-pallidal deep brain stimulation. However, treatment outcome is generally disappointing. A few researchers have reported the application of repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex or the premotor cortex, with the goal of decreasing motor cortex hyperexcitability. This article reviews all studies using this technique in dystonia and discusses rTMS therapeutic impact and its possible mechanisms of action in this indication. Currently, the premotor cortex seems to be the best target for rTMS in dystonia. Rather than merely reducing the hyperexcitability of the primary motor cortex, this technique's clinical benefit seems to result from modifications in plasticity and restoration of sensorimotor integration. The corollary technique for chronic rTMS is electrical cortical stimulation. Even though this new therapeutic tool may have therapeutic promise, more studies are required to confirm it. In particular, we need to broaden our knowledge of rTMS impact on the various forms of dystonia and to optimize target localization.
[show abstract][hide abstract] ABSTRACT: This study examines the effect of high-level skilled behaviour on motor cortex representations of upper extremity muscles of ten sportswomen. We used transcranial magnetic stimulation to map proximal medial deltoid and distal extensor carpi radialis muscle representations on both hemispheres during low-level voluntary contraction. We compared cortical representation areas between two groups of subjects and between hemispheres within subjects. The first group comprised five elite volleyball attackers and the second group five runners. Four stimuli were delivered on multiple scalp sites (1.5 cm apart) to induce motor-evoked potentials recorded by surface EMG. Maps were described in terms of excitable scalp positions and of motor-evoked potentials. We observed differences in map areas between the two groups. Volleyball players had larger cortical representations of the proximal medial deltoid muscle than runners. Furthermore, the volleyball players had larger map areas for dominant muscles compared with non-dominant muscles. There was no difference, however, in map area for either muscle between the dominant and non-dominant arm in the runner group. Our results show that heavy training in a specific skill induces an expansion of proximal muscle representation in the contralateral primary motor cortex. This enlarged map area for proximal muscle is accompanied by an increase in the overlapping of proximal and distal muscle representations. This could reflect the fact that motor learning of co-ordinated movement involves a common control of both muscles. This reorganization supports the hypothesis of a cortical plasticity driven by activity.
European Journal of Neuroscience 02/2005; 21(1):259-66. · 3.75 Impact Factor
[show abstract][hide abstract] ABSTRACT: Experiments were done on nine cats anaesthetized with pentobarbitone to determine whether motor cortical zones controlling
antagonistic muscles are synaptically interconnected. Motor cortical zones controlling wrist flexors, or extensors, were identified
by microstimulation and intramuscular electromyographic recordings (microstimulation: 11 pulses at 333 pulses/s, current 10–40
μA). The position of each zone of interest was marked by a small ink spot on the surface of the cortex and on a scaled drawing
of the cortical surface (cruciate region). Following the identification of wrist flexor and extensor zones the anterograde
tracer biocytin was injected into one, or two, wrist extensor zones at three depths (400, 800 and 1500 μm) from the cortical
surface. A small injection of horseradish peroxidase (HRP) – producing a dark brown spot of approximately 300–500 μm – was
made in layer II–III of one or more wrist flexor zones. Similar HRP injections were made in the deep layers of wrist extensor
zones that were not labelled by biocytin. The HRP injections served to mark the position of potential targets of biocytin-labelled
fibres. In some experiments the biocytin was injected into a wrist flexor zone and HRP was deposited in one or more wrist
extensor zones. Biocytin-labelled fibres (blue) were found throughout the expanse of the forelimb representation zone, as
has been previously reported. More specifically, in all animals biocytin-labelled fibres were found in identified cortical
zones controlling the same muscle(s) as well as in zones controlling an antagonist(s). Club-like swellings, indicative of
synaptic boutons, were observed on these fibres. The density of labelled fibres was greater in the upper cortical layers (II–III),
but a large number of terminals were also present in the lower cortical layers (V–VI). We conclude that there exist intracortical
circuits linking motor cortical zones controlling antagonistic muscles. Elucidating the nature and function of these circuits
is likely to be important for understanding the mode of operation of the motor cortex.
Experimental Brain Research 04/1998; 120(2):223-232. · 2.22 Impact Factor
[show abstract][hide abstract] ABSTRACT: Ten subjects made rapid, simultaneous movements of jaw (elevation or lowering) and right foot (ankle flexion or extension) in two experimental situations: (1) in response to an external signal (reaction-time situation), and (2) in a self-paced situation. We calculated the mean time intervals between the onsets of electromyographic (EMG) activity of agonist muscles (tibialis anterior or gastrocnemius lateralis compared with masseter or digastricus pars anterior) and those between the onsets of movement acceleration at each joint. Despite the fact that subjects reported simultaneous jaw-foot movements, there was always a short time interval between the two movements as between the agonist EMG activities. When the subjects were asked to perform a jaw elevation movement simultaneously with an ankle movement (flexion or extension), the sign of the time interval was dependent on the situation of movement initiation. In the reaction-time situation, the jaw motor activity preceded that of the ankle, whereas the reverse temporal order was observed in the self-paced situation. This is consistent with a previous hypothesis suggesting that the simultaneity of two motor actions is centrally established through two separate central processes: reactive or predictive. When subjects tried to perform simultaneous jaw lowering and foot flexion or extension movements, the strict temporal order observed when considering jaw elevation and ankle movements disappeared. The jaw motor activity generally preceded that of ankle in the reactive situation, but, depending on the subjects, it preceded or followed the ankle motor activity during self-paced movements. It is likely that the specific spindle supply of jaw muscles accounts for these results. Indeed, the jaw depressor muscles, in contrast to the elevators, lack muscle spindles. Our results suggest that the kinesthetic inputs used by the upper central nervous system to synchronize two rapid voluntary movements are mainly those from spindles located in the muscles that accelerate the movement, suggesting a strong alpha-gamma linkage.
Experimental Brain Research 03/1998; 119(1):58-64. · 2.22 Impact Factor
[show abstract][hide abstract] ABSTRACT: Experiments were done to determine whether the strength of reciprocal inhibition from ankle flexors to extensors can be controlled independently of the level of ongoing motor activity in a task-dependent manner. In this paper we use the term reciprocal inhibition in the functional sense--inhibition of the antagonist(s) during activity of the agonist(s)--without reference to specific neural pathways that may be involved. The strength of reciprocal inhibition of the soleus alpha-motoneurons was determined by measuring the amplitude of the H reflex during voluntary, postural, and locomotor tasks requiring activity of the ankle flexor tibialis anterior (TA). Differences in the strength of reciprocal inhibition between tasks were determined from plots of the soleus H reflex amplitude versus the mean value of the TA electromyogram (EMG). Additionally, in tasks involving movement, the correlation between the H reflex amplitude and the joint kinematics was calculated. In most subjects (15 of 22) the soleus H reflex decreased approximately linearly with increasing tonic voluntary contractions of the TA. The H reflex also decreased approximately linearly with the TA EMG activity when subjects where asked to lean backward. There were no statistical differences between the regression lines obtained in these tasks. In some subjects (7 of 22), however, the H reflex amplitude was independent of the level of TA EMG activity, except for a sudden drop at high levels of TA activity (approximately 60-80% of maximum voluntary contraction). The type of relation between the soleus H reflex and the TA EMG activity in these tasks was not correlated with the maximum H reflex to maximum M wave (Hmax/Mmax) ratio measured during quiet standing. In marked contrast, during the swing phase of walking--over the same range of TA EMG activity as during the tonic voluntary contraction task--the H reflex was reduced to zero in most subjects (24 of 31). In seven subjects the H reflex during the swing phase was reduced to some 5% of the value during quiet standing. The same result was found when subjects were asked to produce a stepping movement with one leg (OLS) in response to an auditory "go" signal. Additionally, in the OLS task it was possible to examine the behavior of the H reflex during the reaction time and thus to evaluate the relative contribution of central commands versus movement-related afferent activity to the inhibition of the soleus H reflex. In 11 of 12 subjects the H reflex attained its minimum value before either the onset of EMG activity or movement of any of the leg joints. It is significant that the H reflex was most powerfully inhibited during the swing phase of walking and the closely related OLS task. The H reflex was also measured during isolated ankle dorsiflexion movements. The subjects were asked to track a target displayed on a computer screen with dorsiflexion movements of the ankle. The trajectory of the target was the same as that of the ankle during the swing phase of walking. The soleus H reflexes were intermediate in size between the values obtained in the tonic contraction task and the walking or OLS tasks. A negative, but weak, correlation (r2 < 0.68) between the soleus H reflex and the TA EMG was found in 3 of 10 subjects. Furthermore, there was no correlation between the H reflex amplitude and the ankle angular displacement or angular velocity. In this task, as in the OLS task, the H reflex began to decrease during the reaction time before the onset of TA EMG activity. We conclude that the strength of reciprocal inhibition of the soleus alpha-motoneuron pool can thus be controlled independently of the level of motor activity in the ankle flexors. The strength of the inhibition of the antagonist(s) depends on the task, and for each task the strength of the inhibition is not necessarily proportional to the level of motor activity in the agonist(s). (ABSTRACT TRUNCATED)
Journal of Neurophysiology 07/1997; 78(1):429-38. · 3.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: Experiments were done to determine the form of the input-output relation (i.e. stimulus intensity vs response amplitude) of the corticospinal pathway of the first dorsal interosseous and the tibialis anterior, respectively. Our purpose was to determine from these quantitative relations which input-output parameters would be useful measures in studies dealing with motor cortical task dependence. The motor cortex was excited by focal transcranial magnetic stimuli and the evoked motor response were recorded with surface electromyographic electrodes. In some experiments the discharge probability of single motor units in response to magnetic stimuli of increasing intensity was determined from intramuscular recordings. For both muscles the form of the input-output relation was sigmoidal. The steepness of the relation increased, up to 4-7 times the value at rest, with increasing tonic background activity. The threshold decreased, but only slightly, with increasing tonic background activity. The minimum value of the threshold was reached at activation levels of about 10-20% of the maximum tonic effort, whereas the steepness of the relation reached its maximum at higher activation levels, typically about 30-40% of the maximum tonic effort. These observations imply that these two input-output parameters of the corticospinal pathway - one reflecting the bias level (threshold) and the other the gain (slope) - are determined by different neural mechanisms. The plateau level of the sigmoidal input-output relation was not influenced by the background activation level, except that in some subjects (4/9) it could not be reached when no background motor activity was present. This was probably due, for the most part, to limitation of the maximum stimulator output. Additionally, this finding may reflect a change in the intrinsic excitability of the motor cortex in going from rest to activity, or that convergent inputs from different descending and afferent systems are required for maximal activation of motoneuron pools. Thus, the threshold, steepness and plateau level characterize the input-output parameters of the human corticospinal pathway for a given level of motor activity. In contrast to the nonlinear input-output relation of the corticospinal pathway as whole, which includes the motoneuron pool and any spinal interneuronal relays, the discharge probability of all single motor units was a linearly increasing function of the stimulus strength (r> or =0.9, P<0.01). Thus, the sigmoidal input-output relation of the corticospinal pathway, as a whole, is not due to the input-output properties of single motoneurons. The possible neural mechanisms which underlie the shape and parameters of the input-output relation as well as the methodological implications of the results are considered.
Experimental Brain Research 05/1997; 114(2):329-38. · 2.22 Impact Factor
[show abstract][hide abstract] ABSTRACT: The authors present several examples taken from their own work of
changes in the input-output properties of neural circuits of the spinal
cord and of the corticospinal pathway during a variety of natural motor
tasks. The point is made that modulations of the effectiveness, or
intensity of action, of these pathways depend on the motor task being
executed, occur automatically, and serve to adapt the motor system to
the biomechanical exigencies of the task. The authors also suggest that
the control signals involved in reflex modulation are an intrinsic
feature of the motor commands
Engineering in Medicine and Biology Society, 1995., IEEE 17th Annual Conference; 10/1995
[show abstract][hide abstract] ABSTRACT: The jaw movement kinematics in relation to the EMG activity of two antagonistic jaw muscles (the masseter and the digastricus pars anterior) were examined in healthy subjects and patients with Friedreich's disease. Dysarthria and ataxia are the main characteristics of this disease. Jaw movement was monitored with a magnetometer system, and bipolar surface electrodes were used to record EMG activity. Unidirectional opening, unidirectional closing and opening-closing movements of the mandible were performed in a simple reaction time situation. The data were compared with those for normal control subjects. The kinematic and electromyographic characteristics were: (a) prolonged total movement duration resulting from increased acceleration and deceleration durations; (b) decreased maximum velocity, and a secondary peak in the velocity profile; (c) tonic EMG activity in muscles supposedly at rest; (d) prolonged EMG bursts. Premotor reaction time was also increased. These characteristics are similar to those, previously described, of limb movements in subjects with cerebellar dysfunctions and suggest that the alterations of jaw movement in Friedreich's ataxia could be due to a deficit in cerebellar control.
Electroencephalography and Clinical Neurophysiology 03/1995; 97(1):29-35.