[Show abstract][Hide abstract] ABSTRACT: A group of European experts was commissioned to establish guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS) from evidence published up until March 2014, regarding pain, movement disorders, stroke, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, consciousness disorders, tinnitus, depression, anxiety disorders, obsessive-compulsive disorder, schizophrenia, craving/addiction, and conversion. Despite unavoidable inhomogeneities, there is a sufficient body of evidence to accept with level A (definite efficacy) the analgesic effect of high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the pain and the antidepressant effect of HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC). A Level B recommendation (probable efficacy) is proposed for the antidepressant effect of low-frequency (LF) rTMS of the right DLPFC, HF-rTMS of the left DLPFC for the negative symptoms of schizophrenia, and LF-rTMS of contralesional M1 in chronic motor stroke. The effects of rTMS in a number of indications reach level C (possible efficacy), including LF-rTMS of the left temporoparietal cortex in tinnitus and auditory hallucinations. It remains to determine how to optimize rTMS protocols and techniques to give them relevance in routine clinical practice. In addition, professionals carrying out rTMS protocols should undergo rigorous training to ensure the quality of the technical realization, guarantee the proper care of patients, and maximize the chances of success. Under these conditions, the therapeutic use of rTMS should be able to develop in the coming years.
Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 06/2014; · 3.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objective of the present study was to investigate the time course of long-interval intracortical inhibition (LICI) and late cortical disinhibition (LCD) as a function of the motor task (index abduction, thumb-index precision grip). Motor-evoked potentials were recorded from the first dorsal interosseus (FDI) muscle of the dominant limb in 13 healthy subjects. We used paired-pulse transcranial magnetic stimulation (TMS) paradigms in which a test pulse was preceded by a suprathreshold priming pulse (130% of the resting motor threshold) with varying interstimulus intervals (ISIs). In each task, double pulses were delivered with ISIs ranging from 30% of the corresponding silent period (SP; ~ 45 ms) to 220% of the SP (~ 330 ms). In both tasks, we found that LICI was followed by LCD (namely a period of increased cortical excitability lasting until ~ 200% of the SP). The time-dependent modulation of LICI and LCD differed in the two tasks; LICI was shorter (i.e. disinhibition occurred earlier) and LCD was more intense during precision grip than during index abduction. Long-interval intracortical inhibition disappeared well before the end of the SP in the precision grip task, suggesting that the mechanisms underlying these two inhibitory phenomena are distinct. Our data suggest that disinhibition might reflect adaptation of neural circuit excitability to the functional requirements of the motor task.
European Journal of Neuroscience 02/2014; · 3.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: High-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) has been shown to reduce akinesia in Parkinson's disease (PD). Given that the processing of sensory afferents is deficient in PD and might be involved in akinesia, we sought to determine whether or not the application of very HF rTMS [intermittent theta-burst stimulation (iTBS) protocol] over the M1 affected sensorimotor integration (SMI) and akinesia. The experiments were carried out in: (i) 11 patients taking their usual dopaminergic treatment ('on-drug'); (ii) eight of the latter patients after withdrawal of dopaminergic treatment ('off-drug'); and (iii) 10 de novo (drug-naive) patients. Sham stimulation was applied in 11 other patients in the 'on-drug' condition. SMI was investigated by conditioning a supra-threshold transcranial magnetic stimulation pulse in the motor region controlling the abductor pollicis brevis with a nerve shock over the median nerve at time intervals corresponding to short- and long-latency afferent inhibition (SAI and LAI) and afferent-induced facilitation (AIF). Akinesia was assessed with a pointing test. In on-drug, off-drug and de novo patients, akinesia in the contralateral arm was lower after iTBS. Sham stimulation had no effect. In on-drug patients (but not other groups), SMI was also influenced by iTBS, with an increase in AIF. No changes in SAI and LAI were observed. Our data suggest that iTBS might improve both akinesia and sensory processing in patients with PD taking levodopa.
European Journal of Neuroscience 06/2012; 36(5):2669-78. · 3.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Step initiation is associated with anticipatory postural adjustments (APAs) that vary according to the speed of the first step. When step initiation is elicited by a "go" signal (i.e. in a reaction time task), the presentation of an unpredictable, intense, acoustic startling stimulus (engaging a subcortical mechanism) simultaneously with or just before the imperative "go" signal is able to trigger early-phase APAs. The aim of the present study was to better understand the mechanisms underlying APAs during step initiation. We hypothesized that the early release of APAs by low-intensity, non-startling stimuli delivered long before an imperative "go" signal indicates the involvement of several different mechanisms in triggering APAs (and not just acoustic reflexes triggering brainstem structures). Fifteen healthy subjects were asked to respond to an imperative visual "go" signal by initiating a step with their right leg. A brief, binaural 40, 80 or 115 dB auditory stimulus was given 1.4 s before the "go" signal. Participants were instructed not to respond to the auditory stimulus. The centre of pressure trajectory and the electromyographic activity of the orbicularis oculi, sternocleidomastoid and tibialis anterior muscles were recorded. All three intensities of the auditory stimulus were able to evoke low-amplitude, short APAs without subsequent step execution. The louder the stimulus, the more frequent the elicitation. Depending on the intensity of the stimulus, APAs prior to step initiation can be triggered without the evocation of a startle response or an acoustic blink. Greater reaction times for these APAs were observed for non-startling stimuli. This observation suggested the involvement of pathways that did not involve the brainstem as a "prime mover".
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to determine whether task-dependent differences in corticospinal pathway excitability occur in going from isolated contractions of the index finger to its coordinated activity with the thumb. Focal transcranial magnetic stimulation (TMS) was used to measure input-output (I/O) curves--a measure of corticospinal pathway excitability--of the contralateral first dorsal interosseus (FDI) muscle in 21 healthy subjects performing two isometric motor tasks: index abduction and precision grip. The level of FDI electromyographic (EMG) activity was kept constant across tasks. The amplitude of the FDI motor evoked potentials (MEPs) and the duration of FDI silent period (SP) were plotted against TMS stimulus intensity and fitted, respectively, to a Boltzmann sigmoidal function. The plateau level of the FDI MEP amplitude I/O curve increased by an average of 40% during the precision grip compared with index abduction. Likewise, the steepness of the curve, as measured by the value of the maximum slope, increased by nearly 70%. By contrast, all I/O curve parameters [plateau, stimulus intensity required to obtain 50% of maximum response (S(50)), and slope] of SP duration were similar between the two tasks. Short- and long-latency intracortical inhibitions (SICI and LICI, respectively) were also measured in each task. Both measures of inhibition decreased during precision grip compared with the isolated contraction. The results demonstrate that the motor cortical circuits controlling index and thumb muscles become functionally coupled when the muscles are used synergistically and this may be due, at least in part, to a decrease of intracortical inhibition and an increase of recurrent excitation.
Journal of Neurophysiology 12/2011; 107(5):1522-9. · 3.04 Impact Factor
[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: Sensorimotor performance declines with normal aging. The present study explored age-related changes in sensorimotor integration by conditioning a supra-threshold transcranial magnetic stimulation pulse with a peripheral nerve shock at different interstimulus intervals. Cortical motor threshold of the abductor pollicis brevis muscle, intracortical inhibition and facilitation were measured. We also assessed the influence of median nerve stimulation on motor cortex excitability at intervals which evoked short- and long-latency afferent inhibition (SAI and LAI, respectively) and afferent-induced facilitation (AIF). We observed a marked decrease of the long latency influence of proprioceptive inputs on M1 excitability in the elderly, with the loss of AIF and LAI. The SAI, motor thresholds and intracortical inhibition and facilitation were not age-related. Decreased sensorimotor performance with aging appears to be associated with a decrease in the influence of proprioceptive inputs on motor cortex excitability at longer intervals (probably via higher order cortical areas).
[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. · 3.67 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. · 3.10 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. · 2.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Visually determining what is reachable in peripersonal space requires information about the egocentric location of objects but also information about the possibilities of action with the body, which are context dependent. The aim of the present study was to test the role of motor representations in the visual perception of peripersonal space.
Seven healthy participants underwent a TMS study while performing a right-left decision (control) task or perceptually judging whether a visual target was reachable or not with their right hand. An actual grasping movement task was also included. Single pulse TMS was delivered 80% of the trials on the left motor and premotor cortex and on a control site (the temporo-occipital area), at 90% of the resting motor threshold and at different SOA conditions (50ms, 100ms, 200ms or 300ms).
Results showed a facilitation effect of the TMS on reaction times in all tasks, whatever the site stimulated and until 200ms after stimulus presentation. However, the facilitation effect was on average 34ms lower when stimulating the motor cortex in the perceptual judgement task, especially for stimuli located at the boundary of peripersonal space.
This study provides the first evidence that brain motor area participate in the visual determination of what is reachable. We discuss how motor representations may feed the perceptual system with information about possible interactions with nearby objects and thus may contribute to the perception of the boundary of peripersonal space.
PLoS ONE 02/2008; 3(8):e2862. · 3.53 Impact Factor
[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. · 2.19 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.