Sertraline vs. ELectrical Current Therapy for Treating Depression Clinical Trial - SELECT TDCS: Design, rationale and objectives

Background: Despite significant advancements in psychopharmacology, treating major depressive disorder (MDD) is still a challenge considering the efficacy, tolerability, safety, and economical costs of most antidepressant drugs. One approach that has been increasingly investigated is modulation of cortical activity with tools of non-invasive brain stimulation - such as transcranial magnetic stimulation and transcranial direct current stimulation (tDCS). Due to its profile, tDCS seems to be a safe and affordable approach. Methods and design: The SELECT TDCS trial aims to compare sertraline vs. tDCS in a double-blinded, randomized, factorial trial enrolling 120 participants to be allocated to four groups to receive sertraline + tDCS, sertraline, tDCS or placebo. Eligibility criteria are moderate-to-severe unipolar depression (Hamilton Depression Rating Scale >17) not currently on sertraline treatment. Treatment will last 6 weeks and the primary outcome is depression change in the Montgomery-Asberg Depression Rating Score (MADRS). Potential biological markers that mediate response, such as BDNF serum levels, Val66Met BDNF polymorphism, and heart rate variability will also be examined. A neuropsychological battery with a focus on executive functioning will be administered. Discussion: With this design we will be able to investigate whether tDCS is more effective than placebo in a sample of patients free of antidepressants and in addition, we will be able to secondarily compare the effect sizes of sertraline vs. tDCS and also the comparison between tDCS and combination of tDCS and sertraline. (C) 2010 Elsevier Inc. All rights reserved.

Facilitative effects of bi-hemispheric tDCS in cognitive deficits of Parkinson Disease patients

Parkinson’s disease (PD) is a progressive neurodegenerative disorder, primarily characterized by motor symptoms such as tremor, rigidity, bradykinesia, stiffness, slowness and impaired equilibrium. Although the motor symptoms have been the focus in PD, slight cognitive deficits are commonly found in non-demented and non-depressed PD patients, even in early stages of the disease, which have been linked to the subsequent development of pathological dementia. Thus, strongly reducing the quality of life (QoL). Both levodopa therapy and deep brain stimulation (DBS) have yield controversial results concerning the cognitive symptoms amelioration in PD patients. That does not seems to be the case with transcranial direct current stimulation (tDCS), although better stimulation parameters are needed. Therefore we hypothesize that simultaneously delivering cathodal tDCS (or ctDCS), over the right prefrontal cortex delivered with anodal tDCS (or atDCS) to left prefrontal cortex could be potentially beneficial for PD patients, either by mechanisms of homeostatic plasticity and by increases in the extracellular dopamine levels over the striatum.

Studio degli effetti della stimolazione transcranica a corrente diretta (tdcs) sui potenziali evocati visivi steady state

I potenziali evocati visivi steady state (ssVEPs) consistono in una perturbazione dell’attività elettrica cerebrale spontanea e insorgono in presenza di stimoli visivi come luci monocromatiche modulate sinusoidalmente. Nel tracciato EEG si instaurano oscillazioni di piccola ampiezza ad una frequenza pari a quella dello stimolo. L’analisi nel dominio delle frequenze permette di mettere in evidenza queste oscillazioni che si presentano con un picco ben distinto in corrispondenza della frequenza dello stimolo. L’obiettivo di questo lavoro è quello di capire se la stimolazione transcranica in corrente continua (tDCS) ha degli effetti a breve e a medio termine sui SSVEPs. Si è studiato gli effetti della stimolazione anodica utilizzando un montaggio di stimolazione extra-cefalico (anodo posizionato su Oz e catodo sul braccio destro). L’esperimento prevede il flickering a 3 frequenze di interesse (12, 15, 20 Hz) di 3 quadrati colorati (rosso e giallo) su sfondo nero. Sono state quindi messe a confronto 4 condizioni operative: baseline, stimolazione sham, stimolazione anodica, condizione Post Anodica.L’esperimento è stato sottoposto a 6 soggetti di età tra i 21 e i 51 anni. Il segnale è stato acquisito da due canali bipolari localizzati nella regione occipitale (O1-PO7 e O2-PO8). È stato effettuato un filtraggio tra 3-60 Hz e a 50 Hz. Si sono stimate le PSD normalizzate rispetto alla condizione di riposo in baseline e le potenze nell’intorno della frequenze di interesse (12,15,20 Hz). I dati chiaramente artefattuali sono stati scartati mediante un’analisi esplorativa. Da qui è stato deciso di non includere nella statistica la stimolazione anodica. L’analisi statistica considera tre aspetti: effetto stimolazione, effetto frequenza ed effetto colore. In alcune configurazioni la stimolazione post anodica si è rivelata significativamente differente con ranghi medi delle colonne inferiori alle altre stimolazioni. Non ci sono differenze significative tra le frequenze. Il colore giallo è risultato significativamente maggiore al colore rosso.

Analisi delle potenzialita della tDCS applicata allo studio e alla riabilitazione dei processi cognitivi

L’estrema importanza degli aspetti neurologici che riguardano la vita dell’uomo, unitamente all’elevato grado di invalidità che le malattie del sistema nervoso sono in grado di provocare, ha portato nel corso del tempo gli studiosi a sviluppare metodologie di intervento sempre più accurate e specifiche nel tentativo di far fronte a queste complesse situazioni. Il sempre più frequente ricorso alle cure farmacologiche e alla psicoterapia ha saputo ben presto però sollevare numerose perplessità in merito all’efficacia di tali approcci. È a partire da questi presupposti che è stato possibile portare avanti nuovi studi sulla tDCS, un particolare tipo di apparecchiatura biomedicale basata sul concetto di elettrostimolazione cerebrale. Questo lavoro si propone di descrivere la capacità della tDCS di intervenire direttamente sui meccanismi che comunemente si verificano all’interno del cervello umano tramite il rilascio di corrente, nonché i numerosi miglioramenti che sono stati rilevati in seguito al suo utilizzo su soggetti umani. Si propone inoltre di mettere in evidenza le grandi potenzialità che essa è in grado di manifestare relativamente ai processi cognitivi, partendo dagli aspetti che riguardano il linguaggio, passando attraverso quelli propri della memoria e della conoscenza, fino ad arrivare a rivestire un ruolo di primo piano anche all’interno delle sfaccettature tipiche degli stati umorali.

tDCS: Stimolazione transcranica a corrente continua in ambiente sperimentale e clinico

Poiché i processi propri del sistema nervoso assumono una funzione fondamentale nello svolgimento della vita stessa, nel corso del tempo si è cercato di indagare e spiegare questi fenomeni. Non solo infatti il suo ruolo è di primaria importanza, ma le malattie che lo colpiscono sono altamente invalidanti. Nell’ultimo decennio, al fine di far luce su questi aspetti profondamente caratterizzanti la vita dell’uomo, hanno avuto luogo diversi studi aventi come strumento d’esame la stimolazione transcranica a corrente continua. In particolare questo lavoro si propone di analizzare gli ambiti di interesse dell’applicazione della tDCS, soffermandosi sulla capacità che ha questa metodica di indagare i meccanismi propri del cervello e di proporre terapie adeguate qualora questi meccanismi fossero malfunzionanti. L’utilizzo di questa stimolazione transcranica unitamente ai più moderni metodi di neuroimaging permette di costruire, o quanto meno cercare di delineare, un modello delle strutture di base dei processi cognitivi, quali ad esempio il linguaggio, la memoria e gli stati di vigilanza. A partire da questi primi promettenti studi, la tDCS è in grado di spostare le proprie ricerche nell’ambito clinico, proponendo interessanti e innovative terapie per le malattie che colpiscono il cervello. Nonostante patologie quali il morbo di Parkinson, l’Alzheimer, la dislessia ed l’afasia colpiscano una grande percentuale della popolazione non si è ancora oggi in grado di garantire ai pazienti dei trattamenti validi. E’ in questo frangente che la tDCS assume un ruolo di primaria importanza: essa si presenta infatti come una tecnica alternativa alle classiche cure farmacologie e allo stesso tempo non invasiva, sicura e competitiva sui costi.

Effects of transcranial direct current stimulation (tDCS) on behaviour and electrophysiology of language production

Excitatory anodal transcranial direct current stimulation (A-tDCS) over the left dorsal prefrontal cortex (DPFC) has been shown to improve language production. The present study examined neurophysiological underpinnings of this effect. In a single-blinded within-subject design, we traced effects of A-tDCS compared to sham stimulation over the left DPFC using electrophysiological and behavioural correlates during overt picture naming. Online effects were examined during A-tDCS by employing the semantic interference (SI-)Effect – a marker that denotes the functional integrity of the language system. The behavioural SI-Effect was found to be reduced, whereas the electrophysiological SI-Effect was enhanced over left compared to right temporal scalp-electrode sites. This modulation is suggested to reflect a superior tuning of neural responses within language-related generators. After -(offline) effects of A-tDCS were detected in the delta frequency band, a marker of neural inhibition. After A-tDCS there was a reduction in delta activity during picture naming and the resting state, interpreted to indicate neural disinhibition. Together, these findings demonstrate electrophysiological modulations induced by A-tDCS of the left DPFC. They suggest that A-tDCS is capable of enhancing neural processes during and after application. The present functional and oscillatory neural markers could detect positive effects of prefrontal A-tDCS, which could be of use in the neuro-rehabilitation of frontal language functions.

Testing the involvement of the prefrontal cortex in lucid dreaming: A tDCS study

Recent studies suggest that lucid dreaming (awareness of dreaming while dreaming) might be associated with increased brain activity over frontal regions during rapid eye movement (REM) sleep. By applying transcranial direct current stimulation (tDCS), we aimed to manipulate the activation of the dorsolateral prefrontal cortex (DLPFC) during REM sleep to induce lucid dreaming. Nineteen participants spent three consecutive nights in a sleep laboratory. On the second and third nights they randomly received either 1 mA tDCS for 10 min or sham stimulation during each REM period starting with the second one. According to the participants' self-ratings, tDCS over the DLPFC during REM sleep increased lucidity in dreams. The effects, however, were not strong and found only in frequent lucid dreamers. While this indicates some preliminary support for the involvement of the DLPFC in lucid dreaming, further research, controlling for indirect effects of stimulation and including other brain regions, is needed.

Cathodal HD-tDCS on the right V5 improves motion perception in humans

Brain lesions in the visual associative cortex are known to impair visual perception, i.e., the capacity to correctly perceive different aspects of the visual world, such as motion, color, or shapes. Visual perception can be influenced by non-invasive brain stimulation such as transcranial direct current stimulation (tDCS). In a recently developed technique called high definition (HD) tDCS, small HD-electrodes are used instead of the sponge electrodes in the conventional approach. This is believed to achieve high focality and precision over the target area. In this paper we tested the effects of cathodal and anodal HD-tDCS over the right V5 on motion and shape perception in a single blind, within-subject, sham controlled, cross-over trial. The purpose of the study was to prove the high focality of the stimulation only over the target area. Twenty one healthy volunteers received 20 min of 2 mA cathodal, anodal and sham stimulation over the right V5 and their performance on a visual test was recorded. The results showed significant improvement in motion perception in the left hemifield after cathodal HD-tDCS, but not in shape perception. Sham and anodal HD-tDCS did not affect performance. The specific effect of influencing performance of visual tasks by modulating the excitability of the neurons in the visual cortex might be explained by the complexity of perceptual information needed for the tasks. This provokes a "noisy" activation state of the encoding neuronal patterns. We speculate that in this case cathodal HD-tDCS may focus the correct perception by decreasing global excitation and thus diminishing the "noise" below threshold.

Effetti della tDCS sui pattern ERS/ERD indotti da immaginazione motoria: stato dell'arte

I sistemi BCI EEG-based sono un mezzo di comunicazione diretto tra il cervello e un dispositivo esterno il quale riceve comandi direttamente da segnali derivanti dall'attività elettrica cerebrale. Le features più utilizzate per controllare questi dispositivi sono i ritmi sensorimotori, ossia i ritmi mu e beta (8-30 Hz). Questi ritmi hanno la particolare proprietà di essere modulati durante l'immaginazione di un movimento generando così delle desincronizzazioni e delle sincronizzazioni evento correlate, ERD e ERS rispettavamente. Tuttavia i destinatari di tali sistemi BCI sono pazienti con delle compromissioni corticali e non sono sempre in grado di generare dei pattern ERD/ERS stabili. Per questo motivo, negli ultimi anni, è stato proposto l'uso di tecniche di stimolazione cerebrale non invasiva, come la tDCS, da abbinare al training BCI. In questo lavoro ci si è focalizzati sugli effetti della tDCS sugli ERD ed ERS neuronali indotti da immaginazione motoria attraverso un'analisi dei contributi presenti in letteratura. In particolare, sono stati analizzati due aspetti, ossia: i) lo studio delle modificazioni di ERD ed ERS durante (online) o in seguito (offline) a tDCS e ii) eventuali cambiamenti in termini di performance/controllo del sistema BCI da parte del soggetto sottoposto alla seduta di training e tDCS. Le ricerche effettuate tramite studi offline o online o con entrambe le modalità, hanno portato a risultati contrastanti e nuovi studi sarebbero necessari per chiarire meglio i meccanismi cerebrali che sottendono alla modulazione di ERD ed ERS indotta dalla tDCS. Si è infine provato ad ipotizzare un protocollo sperimentale per chiarire alcuni di questi aspetti.

Differential contributions of the mIPS and PMd in the movement planning of reaches investigated through HD-tDCS

To reach for a target, we must formulate a movement plan - a difference vector of the target position with respect to the starting hand position. While it is known that the medial part of the intraparietal sulcus (mIPS) and the dorsal premotor (PMd) activity reflects aspects of a kinematic plan for a reaching movement, it is unclear whether or how the two regions may differ. We investigated the functional roles of the mIPS and PMd in the planning of reaching movements using high definition transcranial direct current stimulation (HD-tDCS) and examined changes in horizontal endpoint error when participants were subjected to anodal and cathodal stimulation. The left mIPS and PMd were functionally localized with fMRI in each participant using an interleaved center-out pointing and saccade task and mapped onto the scalp using Brainsight. We adopted a randomized, single-blind design and applied anodal and cathodal stimulation (2mA for 20 min; 3cm radius 4x1 electrode placement) during 4 separate visits scheduled at least a week apart. Each participant performed 250 baseline, stimulation, and post-stimulation memory-guided reaches starting from one of two initial hand positions (IHPs) to one of 4 briefly flashed targets (20 cm distant, 5 cm apart horizontally) while fixating on a straight-ahead cross located at the target line. Separate 2-way repeated measures ANOVAs of horizontal endpoint error difference after cathodal tDCS at each stimulation site revealed a significant IHP by target position interaction effect at the left mIPS, and significant IHP and target main effects at the left PMd. Behaviorally, these effects corresponded to IHP-dependent contractions after cathodal mIPS tDCS and IHP-independent contractions after cathodal PMd tDCS. These results suggest that the movement vector is not yet formed at the input level of mIPS, but is encoded at the input of PMd. These results also indicate that tDCS is a viable, useful method in investigating movement planning properties through temporary perturbations of the system.

Tecniche di stimolazione transcranica: TMS e tDCS a confronto

Nel corso degli ultimi decenni si è assistito a un aumento di malattie e disturbi che colpiscono il sistema nervoso,specialmente il cervello. Si è dunque resa necessaria la ricerca e l'analisi di tecniche di stimolazione transcranica a fini sperimentali, clinici e di diagnosi. Tra queste spiccano per la loro versatilità la TMS e la tDCS, le quali hanno già trovato e possono ancora trovare la loro applicazione in numerosi ambiti anche molto differenti tra loro, tra cui quello motorio, verbale, della memoria o per disturbi neurodegenerativi. L'analisi approfondita delle loro applicazioni può non solo portare a meglio comprendere i limiti che le due tecniche hanno al giorno d'oggi e quindi portare a un miglioramento delle stesse, ma anche ad una comprensione più accurata del funzionamento del sistema nervoso, tutt'ora ancora alquanto oscuro nella sua complessità. Infine, confrontando le due tecniche si può meglio definire anche quali possano essere gli ambiti in cui l'una e l'altra sono più vantaggiose o possano dare contributi più incisivi.

Améliorer la douleur et le sommeil chez les aînés souffrant de douleur chronique à l’aide de la stimulation transcrânienne par courant direct (tDCS)

Résumé : Introduction: La douleur chronique et les problèmes de sommeil ont un impact significatif sur la qualité de vie. La prévalence de ces deux conditions augmente substantiellement avec l’âge. L’objectif de cette étude était d’évaluer la faisabilité d’une étude randomisée, contrôlée par placebo et de recueillir des données sur l’efficacité de la stimulation transcrânienne par courant direct (tDCS) pour réduire la douleur et améliorer le sommeil chez des aînés souffrant de douleur chronique d’origines musculo-squelettique. Méthodes: Quatorze patients souffrant de douleur chronique et de problèmes de sommeil ont reçu cinq séances quotidiennes consécutives de tDCS anodique appliquée au cortex moteur primaire (2 mA, 20 minutes) ou cinq séances de tDCS simulée de manière randomisée. L’intensité de la douleur était mesurée avec une échelle visuelle analogue et les paramètres de sommeil avec l’actigraphie. Pendant toute la durée de l’étude, des journaux de bord de douleur et de sommeil étaient aussi utilisés afin de mesurer l'effet de la tDCS sur la douleur et le sommeil du quotidien des participants. Résultats: Les résultats indiquent que la tDCS réelle engendre une analgésie de 59 %, alors que la tDCS simulée ne réduit pas la douleur (p < 0,05). Par contre, aucun changement n’a été observé au niveau des paramètres de sommeil (tous les p ≥ 0,18). Conclusion: Il appert que cinq séances de tDCS anodique appliquée au niveau du cortex moteur primaire seraient efficaces pour réduire la douleur des aînés souffrant de douleur chronique, mais pas pour améliorer leur sommeil. De futures études seront nécessaires afin de déterminer si d’autres paramètres de stimulation pourraient avoir un impact sur le sommeil et si ces résultats peuvent être reproduits en utilisant un plus grand nombre de patients.

Limits to tDCS effects in language:failures to modulate word production in healthy participants with frontal or temporal tDCS

Transcranial direct current stimulation (tDCS) is a method of non-invasive brain stimulation widely used to modulate cognitive functions. Recent studies, however, suggests that effects are unreliable, small and often non-significant at least when stimulation is applied in a single session to healthy individuals. We examined the effects of frontal and temporal lobe anodal tDCS on naming and reading tasks and considered possible interactions with linguistic activation and selection mechanisms as well possible interactions with item difficulty and participant individual variability. Across four separate experiments (N, Exp 1A = 18; 1B = 20; 1C = 18; 2 = 17), we failed to find any difference between real and sham stimulation. Moreover, we found no evidence of significant effects limited to particular conditions (i.e., those requiring suppression of semantic interference), to a subset of participants or to longer RTs. Our findings sound a cautionary note on using tDCS as a means to modulate cognitive performance. Consistent effects of tDCS may be difficult to demonstrate in healthy participants in reading and naming tasks, and be limited to cases of pathological neurophysiology and/or to the use of learning paradigms.

Neuromodulation approaches for the treatment of major depression: challenges and recommendations from a working group meeting

The use of neuromodulation as a treatment for major depressive disorder (MDD) has recently attracted renewed interest due to development of other non-pharmacological therapies besides electroconvulsive therapy (ECT) such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). METHOD: We convened a working group of researchers to discuss the updates and key challenges of neuromodulation use for the treatment of MDD. RESULTS: The state-of-art of neuromodulation techniques was reviewed and discussed in four sections: [1] epidemiology and pathophysiology of MDD; [2] a comprehensive overview of the neuromodulation techniques; [3] using neuromodulation techniques in MDD associated with non-psychiatric conditions; [4] the main challenges of neuromodulation research and alternatives to overcome them. DISCUSSION: ECT is the first-line treatment for severe depression. TMS and tDCS are strategies with a relative benign profile of side effects; however, while TMS effects are comparable to antidepressant drugs for treating MDD; further research is needed to establish the role of tDCS. DBS and VNS are invasive strategies with a possible role in treatment-resistant depression. In summary, MDD is a chronic and incapacitating condition with a high prevalence; therefore clinicians should consider all the treatment options including invasive and non-invasive neuromodulation approaches.

Polarity-Dependent Transcranial Direct Current Stimulation Effects on Central Auditory Processing

Given the polarity dependent effects of transcranial direct current stimulation (tDCS) in facilitating or inhibiting neuronal processing, and tDCS effects on pitch perception, we tested the effects of tDCS on temporal aspects of auditory processing. We aimed to change baseline activity of the auditory cortex using tDCS as to modulate temporal aspects of auditory processing in healthy subjects without hearing impairment. Eleven subjects received 2mA bilateral anodal, cathodal and sham tDCS over auditory cortex in a randomized and counterbalanced order. Subjects were evaluated by the Random Gap Detection Test (RGDT), a test measuring temporal processing abilities in the auditory domain, before and during the stimulation. Statistical analysis revealed a significant interaction effect of time vs. tDCS condition for 4000 Hz and for clicks. Post-hoc tests showed significant differences according to stimulation polarity on RGDT performance: anodal improved 22.5% and cathodal decreased 54.5% subjects' performance, as compared to baseline. For clicks, anodal also increased performance in 29.4% when compared to baseline. tDCS presented polarity-dependent effects on the activity of the auditory cortex, which results in a positive or negative impact in a temporal resolution task performance. These results encourage further studies exploring tDCS in central auditory processing disorders.