Estimulació magnètica transcranial en la rehabilitació de l'afàsia

En el present treball de revisió es valoren els resultats de deu assaigs en pacients afàsics en que s'ha utilitzat l'estimulació magnètica transcranial, amb o sense rehabilitació del llenguatge associada, i s'ha mesurat l'efectivitat d'aquesta tècnica per generar canvis què facilitin una millor recuperació de l'afàsia.

The neural processes generating visual phenomenal consciousness: ERP and neuronavigated brain stimulation studies

One of the greatest conundrums to the contemporary science is the relation between consciousness and brain activity, and one of the specifi c questions is how neural activity can generate vivid subjective experiences. Studies focusing on visual consciousness have become essential in solving the empirical questions of consciousness. Th e main aim of this thesis is to clarify the relation between visual consciousness and the neural and electrophysiological processes of the brain. By applying electroencephalography and functional magnetic resonance image-guided transcranial magnetic stimulation (TMS), we investigated the links between conscious perception and attention, the temporal evolution of visual consciousness during stimulus processing, the causal roles of primary visual cortex (V1), visual area 2 (V2) and lateral occipital cortex (LO) in the generation of visual consciousness and also the methodological issues concerning the accuracy of targeting TMS to V1. Th e results showed that the fi rst eff ects of visual consciousness on electrophysiological responses (about 140 ms aft er the stimulus-onset) appeared earlier than the eff ects of selective attention, and also in the unattended condition, suggesting that visual consciousness and selective attention are two independent phenomena which have distinct underlying neural mechanisms. In addition, while it is well known that V1 is necessary for visual awareness, the results of the present thesis suggest that also the abutting visual area V2 is a prerequisite for conscious perception. In our studies, the activation in V2 was necessary for the conscious perception of change in contrast for a shorter period of time than in the case of more detailed conscious perception. We also found that TMS in LO suppressed the conscious perception of object shape when TMS was delivered in two distinct time windows, the latter corresponding with the timing of the ERPs related to the conscious perception of coherent object shape. Th e result supports the view that LO is crucial in conscious perception of object coherency and is likely to be directly involved in the generation of visual consciousness. Furthermore, we found that visual sensations, or phosphenes, elicited by the TMS of V1 were brighter than identically induced phosphenes arising from V2. Th ese fi ndings demonstrate that V1 contributes more to the generation of the sensation of brightness than does V2. Th e results also suggest that top-down activation from V2 to V1 is probably associated with phosphene generation. The results of the methodological study imply that when a commonly used landmark (2 cm above the inion) is used in targeting TMS to V1, the TMS-induced electric fi eld is likely to be highest in dorsal V2. When V1 was targeted according to the individual retinotopic data, the electric fi eld was highest in V1 only in half of the participants. Th is result suggests that if the objective is to study the role of V1 with TMS methodology, at least functional maps of V1 and V2 should be applied with computational model of the TMS-induced electric fi eld in V1 and V2. Finally, the results of this thesis imply that diff erent features of attention contribute diff erently to visual consciousness, and thus, the theoretical model which is built up of the relationship between visual consciousness and attention should acknowledge these diff erences. Future studies should also explore the possibility that visual consciousness consists of several processing stages, each of which have their distinct underlying neural mechanisms.

Excitabilité du système miroir : une étude de stimulation magnétique transcrânienne sur le chant et le langage

La perception de mouvements est associée à une augmentation de l’excitabilité du cortex moteur humain. Ce système appelé « miroir » sous-tendrait notre habileté à comprendre les gestes posés par une tierce personne puisqu’il est impliqué dans la reconnaissance, la compréhension et l’imitation de ces gestes. Dans cette étude, nous examinons de quelle façon ce système miroir s’implique et se latéralise dans la perception du chant et de la parole. Une stimulation magnétique transcrânienne (TMS) à impulsion unique a été appliquée sur la représentation de la bouche du cortex moteur de 11 participants. La réponse motrice engendrée a été mesurée sous la forme de potentiels évoqués moteurs (PÉMs), enregistrés à partir du muscle de la bouche. Ceux-ci ont été comparés lors de la perception de chant et de parole, dans chaque hémisphère cérébral. Afin d’examiner l’activation de ce système moteur dans le temps, les impulsions de la TMS ont été envoyées aléatoirement à l’intérieur de 7 fenêtres temporelles (500-3500 ms). Les stimuli pour la tâche de perception du chant correspondaient à des vidéos de 4 secondes dans lesquelles une chanteuse produisait un intervalle ascendant de deux notes que les participants devaient juger comme correspondant ou non à un intervalle écrit. Pour la tâche de perception de la parole, les participants regardaient des vidéos de 4 secondes montrant une personne expliquant un proverbe et devaient juger si cette explication correspondait bien à un proverbe écrit. Les résultats de cette étude montrent que les amplitudes des PÉMs recueillis dans la tâche de perception de chant étaient plus grandes après stimulation de l’hémisphère droit que de l’hémisphère gauche, surtout lorsque l’impulsion était envoyée entre 1000 et 1500 ms. Aucun effet significatif n’est ressorti de la condition de perception de la parole. Ces résultats suggèrent que le système miroir de l’hémisphère droit s’active davantage après une présentation motrice audio-visuelle, en comparaison de l’hémisphère gauche.

Impact d’une sieste sur plasticité cérébrale induite par stimulation magnétique transcrânienne

Chez l’humain, différents protocoles de stimulation magnétique transcrânienne répétée (SMTr) peuvent être utilisés afin de manipuler expérimentalement la plasticité cérébrale au niveau du cortex moteur primaire (M1). Ces techniques ont permis de mieux comprendre le rôle du sommeil dans la régulation de la plasticité cérébrale. Récemment, une étude a montré que lorsqu’une première session de stimulation SMTr au niveau de M1 est suivie d’une nuit de sommeil, l’induction subséquente de la plasticité par une deuxième session SMTr est augmentée. La présente étude a investigué si ce type de métaplasticité pouvait également bénéficier d’une sieste diurne. Quatorze sujets en santé ont reçu deux sessions de intermittent theta burst stimulation (iTBS) connue pour son effet facilitateur sur l’excitabilité corticale. Les sessions de stimulation étaient séparées par une sieste de 90 minutes ou par une période équivalente d’éveil. L’excitabilité corticale était quantifiée en terme d’amplitude des potentiels évoqués moteurs (PEM) mesurés avant et après chaque session de iTBS. Les résultats montrent que la iTBS n’est pas parvenue à augmenter de manière robuste l’amplitude des PEMs lors de la première session de stimulation. Lors de la deuxième session de stimulation, la iTBS a produit des changements plastiques variables et ce peu importe si les sujets ont dormi ou pas. Les effets de la iTBS sur l’excitabilité corticale étaient marqués par une importante variabilité inter et intra-individuelle dont les possibles causes sont discutées.

Effets de la stimulation magnétique transcrânienne dans la maladie de Parkinson avec déficits cognitifs légers

Beaucoup de patients atteints de la maladie de Parkinson (MP) peuvent souffrir de troubles cognitifs dès les étapes initiales de la maladie et jusqu’à 80% d’entre eux vont développer une démence. Des altérations fonctionnelles au niveau du cortex préfrontal dorsolatéral (CPFDL), possiblement en relation avec le noyau caudé, seraient à l’origine de certains de ces déficits cognitifs. Des résultats antérieurs de notre groupe ont montré une augmentation de l’activité et de la connectivité dans la boucle cortico-striatale cognitive suite à la stimulation magnétique transcrânienne (SMT) utilisant des paramètres « theta burst » intermittent (iTBS) sur le CPFDL gauche. Pour cette étude, 24 patients atteints de la MP avec des troubles cognitifs ont été séparées en 2 groupes : le groupe iTBS active (N=15) et le groupe sham (stimulation simulée, N=9). Une batterie neuropsychologique détaillée évaluant cinq domaines cognitifs (attention, fonctions exécutives, langage, mémoire et habiletés visuo-spatiales) a été administrée lors des jours 1, 8, 17 et 37. Le protocole iTBS a été appliqué sur le CPFDL gauche durant les jours 2, 4 et 7. Les scores z ont été calculés pour chaque domaine cognitif et pour la cognition globale. Les résultats ont montré une augmentation significative de la cognition globale jusqu’à 10 jours suivant l’iTBS active, particulièrement au niveau de l’attention, des fonctions exécutives et des habiletés visuo-spatiales. Cet effet sur la cognition globale n’est pas répliqué dans le groupe sham. Ces résultats suggèrent donc que l’iTBS peut moduler la performance cognitive chez les patients atteints de MP avec des déficits cognitifs.

Combination of noninvasive brain stimulation with pharmacotherapy

Noninvasive brain stimulation (NIBS) techniques are being increasingly investigated as a therapeutic approach for neuropsychiatric disorders. One method is to combine NIBS with pharmacotherapy to enhance the clinical effects or avoid an increase in drug dosages to decrease the incidence of side effects. However, few studies to date have investigated the relative and combined efficacy of NIBS with pharmacotherapy. Based on a literature review of previous studies and meta-analyses for major depression, we identified four randomized, controlled trials that tested the combination of NIBS with a new drug and two trials that directly compared NIBS versus pharmacotherapy. There was no study designed to address the relative efficacy of each intervention against placebo and against combined therapy. We discuss the methods and rationale of NIBS-pharmacotherapy trials, addressing some methodological aspects, including factorial design, recruitment, blinding, blinding assessment, placebo effect and quantitative aspects, such as power analysis, statistics and interaction effects. Our review of the methodology underlying NIBS-drug trials provides insights for the further clinical research development of NIBS in major depression.

Cumulative priming effects of cortical stimulation on smoking cue-induced craving

Smoking cue-provoked craving is an intricate behavior associated with strong changes in neural networks. Craving is one of the main reasons subjects continue to smoke; therefore interventions that can modify activity in neural networks associated with craving can be useful tools in future research investigating novel treatments for smoking cessation. The goal of this study was to use a neuromodulatory technique associated with a powerful effect on spontaneous neuronal firing - transcranial direct current stimulation (tDCS) - to modify cue-provoked smoking craving. Based on preliminary data showing that craving can be modified after a single tDCS session, here we investigated the effects of repeated tDCS sessions on craving behavior. Twenty-seven subjects were randomized to receive sham or active tDCS (anodal tDCS of the left DLPFC). Our results show a significant cumulative effect of tDCS on modifying smoking cue-provoked craving. In fact, in the group of active stimulation, smoking cues had an opposite effect on craving after stimulation - it decreased craving - as compared to sham stimulation in which there was a small decrease or increase on craving. In addition, during these 5 days of stimulation there was a small but significant decrease in the number of cigarettes smoked in the active as compared to sham tDCS group. Our findings extend the results of our previous study as they confirm the notion that tDCS has a specific effect on craving behavior and that the effects of several sessions can increase the magnitude of its effect. These results open avenues for the exploration of this method as a therapeutic alternative for smoking cessation and also as a mean to change stimulus-induced behavior. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Non-invasive brain stimulation for the management of arterial hypertension

The neural control of the cardiovascular system is a complex process that involves many structures at different levels of nervous system. Several cortical areas are involved in the control of systemic blood pressure, such as the sensorimotor cortex, the medial prefrontal cortex and the insular cortex. Non-invasive brain stimulation techniques - repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) - induce sustained and prolonged functional changes of the human cerebral cortex. rTMS and tDCS has led to positive results in the treatment of some neurological and psychiatric disorders. Because experiments in animals show that cortical modulation can be an effective method to regulate the cardiovascular system, non-invasive brain stimulation might be a novel tool in the therapeutics of human arterial hypertension. We here review the experimental evidence that non-invasive brain stimulation can influence the autonomic nervous system and discuss the hypothesis that focal modulation of cortical excitability by rTMS or tDCS can influence sympathetic outflow and, eventually, blood pressure, thus providing a novel therapeutic tool for human arterial hypertension. (C) 2009 Published by Elsevier Ltd.

Clinical trial design in non-invasive brain stimulation psychiatric research

Major depressive disorder (MDD) trials - investigating either non-pharmacological or pharmacological interventions - have shown mixed results. Many reasons explain this heterogeneity, but one that stands out is the trial design due to specific challenges in the field. We aimed therefore to review the methodology of non-invasive brain stimulation (NIBS) trials and provide a framework to improve clinical trial design. We performed a systematic review for randomized, controlled MDD trials whose intervention was transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) in MEDLINE and other databases from April 2002 to April 2008. We created an unstructured checklist based on CONSORT guidelines to extract items such as power analysis, sham method, blinding assessment, allocation concealment, operational criteria used for MDD, definition of refractory depression and primary study hypotheses. Thirty-one studies were included. We found that the main methodological issues can be divided in to three groups: (1) issues related to phase II/small trials, (2) issues related to MDD trials and, (3) specific issues of NIBS studies. Taken together, they can threaten study validity and lead to inconclusive results. Feasible solutions include: estimating the sample size a priori; measuring the degree of refractoriness of the subjects; specifying the primary hypothesis and statistical tests; controlling predictor variables through stratification randomization methods or using strict eligibility criteria; adjusting the study design to the target population; using adaptive designs and exploring NIBS efficacy employing biological markers. In conclusion, our study summarizes the main methodological issues of NIBS trials and proposes a number of alternatives to manage them. Copyright (C) 2011 John Wiley & Sons, Ltd.

Into the Island: A new technique of non-invasive cortical stimulation of the insula

Study aim. - We describe a new neuronavigation-guided technique to target the posterior-superior insula (PSI) using a cooled-double-cone coil for deep cortical stimulation. Introduction. - Despite the analgesic effects brought about by repetitive transcranial magnetic stimulation (TMS) to the primary motor and prefrontal cortices, a significant proportion of patients remain symptomatic. This encouraged the search for new targets that may provide stronger pain relief. There is growing evidence that the posterior insula is implicated in the integration of painful stimuli in different pain syndromes and in homeostatic thermal integration. Methods. - The primary motor cortex representation of the lower leg was used to calculate the motor threshold and thus, estimate the intensity of PSI stimulation. Results. - Seven healthy volunteers were stimulated at 10 Hz to the right PSI and showed subjective changes in cold perception. The technique was safe and well tolerated. Conclusions. - The right posterior-superior insula is worth being considered in future studies as a possible target for rTMS stimulation in chronic pain patients. (c) 2012 Elsevier Masson SAS. All rights reserved.

Theta Burst Stimulation Over the Right Broca's Homologue Induces Improvement of Naming in Aphasic Patients

Improvements of language production in aphasic patients have been reported following repeated 1-Hz transcranial magnetic stimulation over the nondamaged right hemisphere. Most studies examined aphasic patients in the chronic phase. The effect of transcranial magnetic stimulation application in acute or subacute patients has not been systematically studied. We aimed to evaluate whether continuous theta burst stimulation, an inhibitory protocol with a shorter application time than the common 1-Hz protocol, is able to improve naming performance in aphasic patients in different poststroke phases.

Theta burst stimulation reduces disability during the activities of daily living in spatial neglect

Left-sided spatial neglect is a common neurological syndrome following right-hemispheric stroke. The presence of spatial neglect is a powerful predictor of poor rehabilitation outcome. In one influential account of spatial neglect, interhemispheric inhibition is impaired and leads to a pathological hyperactivity in the contralesional hemisphere, resulting in a biased attentional allocation towards the right hemifield. Inhibitory transcranial magnetic stimulation can reduce the hyperactivity of the contralesional, intact hemisphere and thereby improve spatial neglect symptoms. However, it is not known whether this improvement is also relevant to the activities of daily living during spontaneous behaviour. The primary aim of the present study was to investigate whether the repeated application of continuous theta burst stimulation trains could ameliorate spatial neglect on a quantitative measure of the activities of daily living during spontaneous behaviour. We applied the Catherine Bergego Scale, a standardized observation questionnaire that can validly and reliably detect the presence and severity of spatial neglect during the activities of daily living. Eight trains of continuous theta burst stimulation were applied over two consecutive days on the contralesional, left posterior parietal cortex in patients suffering from subacute left spatial neglect, in a randomized, double-blind, sham-controlled design, which also included a control group of neglect patients without stimulation. The results showed a 37% improvement in the spontaneous everyday behaviour of the neglect patients after the repeated application of continuous theta burst stimulation. Remarkably, the improvement persisted for at least 3 weeks after stimulation. The amelioration of spatial neglect symptoms in the activities of daily living was also generally accompanied by significantly better performance in the neuropsychological tests. No significant amelioration in symptoms was observed after sham stimulation or in the control group without stimulation. These results provide Class I evidence that continuous theta burst stimulation is a viable add-on therapy in neglect rehabilitation that facilitates recovery of normal everyday behaviour.

Repetitive TMS over the human oculomotor cortex: comparison of 1-Hz and theta burst stimulation

The aim of the study was to compare the effect duration of two different protocols of repetitive transcranial magnetic stimulation (rTMS) on saccade triggering. In four experiments, two regions (right frontal eye field (FEF) and vertex) were stimulated using a 1-Hz and a theta burst protocol (three 30Hz pulses repeated at intervals of 100ms). The same number of TMS pulses (600 pulses) was applied with stimulation strength of 80% of the resting motor threshold for hand muscles. Following stimulation the subjects repeatedly performed an oculomotor task using a modified overlap paradigm, and saccade latencies were measured over a period of 60min. The results show that both 1-Hz and theta burst stimulation had inhibitory effects on saccade triggering when applied over the FEF, but not over the vertex. One-hertz rTMS significantly increased saccade latencies over a period of about 8min. After theta burst rTMS, this effect lasted up to 30min. Furthermore, the decay of rTMS effects was protocol-specific: After 1-Hz stimulation, saccade latencies returned to a baseline level much faster than after theta burst stimulation. We speculate that these time course differences represent distinct physiological mechanisms of how TMS interacts with brain function.

Interhemispheric balance of overt attention: a theta burst stimulation study

Interhemispheric imbalance is discussed as a pathophysiological mechanism in visuospatial neglect. It is suggested that after a lesion of the right hemisphere the mutual transcallosal inhibition is impaired, resulting in an increased activity of the left hemisphere. We investigated the interhemispheric balance of attention in healthy subjects by using a free visual exploration task and by interfering with the neural activity of the posterior parietal cortex (PPC) of either hemisphere using an inhibitory transcranial magnetic stimulation routine with theta burst stimulation (TBS). Subjects explored colour photographs of real-life scenes presented on a computer screen under four conditions: (i) without TBS; (ii) after TBS over the right PPC; (iii) after TBS over the left PPC; and (iv) after TBS over the right PPC and, after the first half of the task, over the left PPC. Eye movements were measured, and distribution of mean cumulative fixation duration over screen halves was analyzed. TBS over the right PPC resulted in a significant rightward shift of mean cumulative fixation duration of approximately 30 min. The shift could be reversed when a subsequent train of TBS was applied over the left PPC. However, left PPC stimulation alone had no significant effect on visual exploration behaviour. The present study shows that the effect of TBS on the PPC depends on which hemisphere is stimulated and on the state of the contralateral homologue area. These findings are in accordance with the predictions of the interhemispheric rivalry model in neglect.

One session of repeated parietal theta burst stimulation trains induces long-lasting improvement of visual neglect

BACKGROUND AND PURPOSE: Visual neglect is a frequent disability in stroke and adversely affects mobility, discharge destination, and length of hospital stay. It is assumed that its severity is enhanced by a released interhemispheric inhibition from the unaffected toward the affected hemisphere. Continuous theta burst transcranial magnetic stimulation (TBS) is a new inhibitory brain stimulation protocol which has the potential to induce behavioral effects outlasting stimulation. We aimed to test whether parietal TBS over the unaffected hemisphere can induce a long-lasting improvement of visual neglect by reducing the interhemispheric inhibition. METHODS: Eleven patients with left-sided visual neglect attributable to right hemispheric stroke were tested in a visual perception task. To evaluate the specificity of the TBS effect, 3 conditions were tested: 2 TBS trains over the left contralesional posterior parietal cortex, 2 trains of sham stimulation over the contralesional posterior parietal cortex, and a control condition without any intervention. To evaluate the lifetime of repeated trains of TBS in 1 session, 4 trains were applied over the contralesional posterior parietal cortex. RESULTS: Two TBS trains significantly increased the number of perceived left visual targets for up to 8 hours as compared to baseline. No significant improvement was found with sham stimulation or in the control condition without any intervention. The application of 4 TBS trains significantly increased the number of perceived left targets up to 32 hours. CONCLUSIONS: The new approach of repeating TBS at the same day may be promising for therapy of neglect.