Transcranial DC Stimulation Coupled With TENS for the Treatment of Chronic Pain A Preliminary Study

Objective: Based on evidence showing that electrical stimulation of the nervous system is an effective method to decrease chronic neurogenic pain, we aimed to investigate whether the combination of 2 methods of electrical stimulation-a method of peripheral stimulation [transcutaneous electrical nerve stimulation (TENS)] and a method of noninvasive brain stimulation (transcranial direct current stimulation (tDCS)]-induces greater pain reduction as compared with tDCS alone and sham stimulation. Methods: We performed a preliminary, randomized, sham-controlled, crossover, clinical study in which 8 patients were randomized to receive active tDCS/active TENS (""tDCS/TENS"" group), active tDCS/sham TENS (""tDCS"" group), and sham tDCS/sham TENS (""sham"" group) stimulation. Assessments were performed immediately before and after each condition by a blinded rater. Results: The results showed that there was a significant difference in pain reduction across the conditions Of stimulation (P = 0.006). Post hoc tests showed significant pain reduction as compared with baseline after the tDCS/TENS condition [reduction by 36.5% (+/- 10.7), P = 0.004] and the tDCS condition [reduction by 15.5% (+/- 4.9), P = 0.014], but not after sham stimulation (P = 0.35). In addition, tDCS/TENS induced greater pain reduction than tDCS (P = 0.02). Conclusions: The results of this pilot study suggest that the combination of TENS with tDCS has a superior effect compared with tDCS alone.

Prefrontal cortex modulation using transcranial DC stimulation reduces alcohol craving: A double-blind, sham-controlled study

Background: Functional neuroimaging studies have shown that specific brain areas are associated with alcohol craving including the dorsolateral prefrontal cortex (DLPFC). We tested whether modulation of DLPFC using transcranial direct current stimulation (tDCS) could alter alcohol craving in patients with alcohol dependence while being exposed to alcohol cues. Methods: We performed a randomized sham-controlled study in which 13 subjects received sham and active bilateral tDCS delivered to DLPFC (anodal left/cathodal right and anodal right/cathodal left). For sham stimulation, the electrodes were placed at the same positions as in active stimulation; however, the stimulator was turned off after 30 s of stimulation. Subjects were presented videos depicting alcohol consumption to increase alcohol craving. Results: Our results showed that both anodal left/cathodal right and anodal right/cathodal left significantly decreased alcohol craving compared to sham stimulation (p < 0.0001). In addition, we found that following treatment, craving could not be further increased by alcohol cues. Conclusions: Our findings showed that tDCS treatment to DLPFC can reduce alcohol craving. These findings extend the results of previous studies using noninvasive brain stimulation to reduce craving in humans. Given the relatively rapid suppressive effect of tDCS and the highly fluctuating nature of alcohol craving, this technique may prove to be a valuable treatment strategy within the clinical setting. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

Anodal transcranial direct current stimulation of the motor cortex increases cortical voluntary activation and neural plasticity

INTRODUCTION: We examined the cumulative effect of 4 consecutive bouts of non-invasive brain stimulation on corticospinal plasticity and motor performance, and whether these responses were influenced by the brain-derived neurotrophic factor (BDNF) polymorphism.

METHODS: In a randomized double-blinded cross-over design, changes in strength and indices of corticospinal plasticity were analyzed in 14 adults who were exposed to 4 consecutive sessions of anodal and sham transcranial direct current stimulation (tDCS). Participants also undertook a blood sample for BDNF genotyping (N=13).

RESULTS: We observed a significant increase in isometric wrist flexor strength with transcranial magnetic stimulation revealing increased corticospinal excitability, decreased silent period duration, and increased cortical voluntary activation compared to sham tDCS.

DISCUSSION: The results show that 4 consecutive sessions of anodal tDCS increased cortical voluntary activation manifested as an improvement in strength. Induction of corticospinal plasticity appears to be influenced by the BDNF polymorphism.

Modulation of human corticospinal excitability by paired associative stimulation

Paired Associative Stimulation (PAS) has come to prominence as a potential therapeutic intervention for the treatment of brain injury/disease, and as an experimental method with which to investigate Hebbian principles of neural plasticity in humans. Prototypically, a single electrical stimulus is directed to a peripheral nerve in advance of transcranial magnetic stimulation (TMS) delivered to the contralateral primary motor cortex (M1). Repeated pairing of the stimuli (i.e., association) over an extended period may increase or decrease the excitability of corticospinal projections from M1, in manner that depends on the interstimulus interval (ISI). It has been suggested that these effects represent a form of associative long-term potentiation (LTP) and depression (LTD) that bears resemblance to spike-timing dependent plasticity (STDP) as it has been elaborated in animal models. With a large body of empirical evidence having emerged since the cardinal features of PAS were first described, and in light of the variations from the original protocols that have been implemented, it is opportune to consider whether the phenomenology of PAS remains consistent with the characteristic features that were initially disclosed. This assessment necessarily has bearing upon interpretation of the effects of PAS in relation to the specific cellular pathways that are putatively engaged, including those that adhere to the rules of STDP. The balance of evidence suggests that the mechanisms that contribute to the LTP- and LTD-type responses to PAS differ depending on the precise nature of the induction protocol that is used. In addition to emphasizing the requirement for additional explanatory models, in the present analysis we highlight the key features of the PAS phenomenology that require interpretation.

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.

Does the longer application of anodal-transcranial direct current stimulaton increase corticomotor excitability further? A pilot study

Introduction: Anodal transcranial direct current stimulation (a-tDCS) of the primary motor cortex (M1) has been shown to be effective in increasing corticomotor excitability.
　
Methods: We investigated whether longer applications of a-tDCS coincide with greater increases in corticomotor excitability compared to shorter application of a-tDCS. Ten right-handed healthy participants received one session of a-tDCS (1mA current) with shorter (10 min) and longer (10+10 min) stimulation durations applied to the left M1 of extensor carpi radialis muscle (ECR). Corticomotor excitability following application of a-tDCS was assessed at rest with transcranial magnetic stimulation (TMS) elicited motor evoked potentials (MEP) and compared with baseline data for each participant.
　
Results: MEP amplitudes were increased following 10 min of a-tDCS by 67% (p = 0.001) with a further increase (32%) after the second 10 min of a-tDCS (p = 0.005). MEP amplitudes remained elevated at 15 min post stimulation compared to baseline values by 65% (p = 0.02).
　
Discussion: The results demonstrate that longer application of a-tDCS within the recommended safety limits, increases corticomotor excitability with after effects of up to 15 minutes post stimulation.

Noninvasive stimulation of the temporoparietal junction: a systematic review

Imaging and lesion studies have suggested numerous roles for the temporoparietal junction (TPJ), for example in attention and neglect, social cognition, and self/other processing. These studies cannot establish causal relationships, and the importance and relevance of (and interrelationships between) proposed roles remain controversial. This review examined studies that use noninvasive transcranial stimulation (NTS) to explore TPJ function. Of 459 studies identified, 40 met selection criteria. The strengths and weaknesses of NTS-relevant parameters used are discussed, and methodological improvements suggested. These include the need for careful selection of stimulation sites and experimental tasks, and use of neuronavigation and concurrent functional activity measures. Without such improvements, overlapping and discrete functions of the TPJ will be difficult to disentangle. Nevertheless, the contributions of these studies to theoretical models of TPJ function are discussed, and the clinical relevance of TPJ stimulation explored. Some evidence exists for TPJ stimulation in the treatment of auditory hallucinations, tinnitus, and depersonalisation disorder. Further examination of the TPJ in conditions such as autism spectrum disorder is also warranted.

Low-frequency brain stimulation to the left dorsolateral prefrontal cortex increases the negative impact of social exclusion among those high in personal distress

The dorsolateral prefrontal cortex (DLPFC) is thought to play a key role in the cognitive control of emotion and has therefore, unsurprisingly, been implicated in the regulation of physical pain perception. This brain region may also influence the experience of social pain, which has been shown to activate similar neural networks as seen in response to physical pain. Here, we applied sham or active low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC, previously shown to exert bilateral effects in pain perception, in healthy participants. Following stimulation, participants played the “Cyberball Task”; an online ball-tossing game in which the subject participant is included or excluded. Compared to sham, rTMS did not modulate behavioural response to social exclusion. However, within the active rTMS group only, greater trait personal distress was related to enhanced negative outcomes to social exclusion. These results add further support to the notion that the effect of brain stimulation is not homogenous across individuals, and indicates the need to consider baseline individual differences when assessing response to brain stimulation. This seems particularly relevant in social neuroscience investigations, where trait factors may have a meaningful effect.

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.