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[ARTICLE] Notes on Human Trials of Transcranial Direct Current Stimulation between 1960 and 1998 – Full Text

Background: Transcranial direct current stimulation (tDCS) is investigated to modulate neuronal function including cognitive neuroscience and neuropsychiatric therapies. While cases of human stimulation with rudimentary batteries date back more than 200 years, clinical trials with current controlled stimulation were published intermittently since the 1960s. The modern era of tDCS only started after 1998.

Objectives: To review methods and outcomes of tDCS studies from old literature (between 1960 and 1998) with intention of providing new insight for ongoing tDCS trials and development of tDCS protocols especially for the purpose of treatment.

Methods: Articles were identified through a search in PubMed and through the reference list from its selected articles. We included only non-invasive human studies that provided controlled direct current and were written in English, French, Spanish or Portuguese before the year of 1998, the date in which modern stimulation paradigms were implemented.

Results: Fifteen articles met our criteria. The majority were small-randomized controlled clinical trials that enrolled a mean of approximately 26 subjects (Phase II studies). Most of the studies (around 83%) assessed the role of tDCS in the treatment of psychiatric conditions, in which the main outcomes were measured by means of behavioral scales and clinical observation, but the diagnostic precision and the quality of outcome monitoring, including adverse events, were deficient by modern standards. Compared to modern tDCS dose, the stimulation intensities used (0.1–1 mA) were lower, however as the electrodes were typically smaller (e.g., 1.26 cm2), the average electrode current density (0.2 mA/cm2) was approximately 4× higher. The number of sessions ranged from one to 120 (median 14). Notably, the stimulation session durations of several minutes to 11 h (median 4.5 h) could markedly exceed modern tDCS protocols. Twelve studies out of 15 showed positive results. Only mild side effects were reported, with headache and skin alterations the most common.

Conclusion: Most of the studies identified were for psychiatric indications, especially in patients with depression and/or schizophrenia and majority indicated some positive results. Variability in outcome is noted across trials and within trials across subjects, but overall results were reported as encouraging, and consistent with modern efforts, given some responders and mild side effects. The significant difference with modern dose, low current with smaller electrode size and interestingly much longer stimulation duration may worth considering.

Introduction

Transcranial direct current stimulation (tDCS) consists of applying a weak direct current on the scalp, a portion of which crosses the skull (Datta et al., 2009) and induces cortical changes (Fregni and Pascual-Leone, 2007; Nitsche et al., 2008). The investigation of the application of electricity over the brain dates back to at least 200 years, when Giovanni Aldini (Zaghi et al., 2010) recommended galvanism for patients with deafness, amaurosis and “insanity”, reporting good results with this technique especially when used in patients with “melancholia”. Aldini also used tDCS in patients with symptoms of personality disorders and supposedly reported complete rehabilitation following transcranial administration of electric current (Parent, 2004).

These earliest studies used rudimentary batteries and so were constant voltage, where the resulting current depends on a variable body resistance. Over the 20th century, direct voltage continued to be used but most testing involved pulsed stimulation, starting with basic devices where a mechanical circuit that intermittently connected and broke the circuit between the battery and the subject and evolving to modern current control circuits including Cranial Electrotherapy Stimulation and its variants (Guleyupoglu et al., 2013). Interest in direct current stimulation (or tDCS) resurged with the studies of Priori et al. (1998) and Nitsche and Paulus (2000) that demonstrated weak direct current could change cortical response to Transcranial Magnetic Stimulation, thereby indicating that tDCS could change cortical “excitability”. Testing for clinical and cognitive modification soon followed (Fregni et al., 2005, 2006). Developments and challenges in tDCS research, including applications in the treatment of neuro-psychiatrics disease since 1998 have been reviewed in detailed elsewhere (Brunoni et al., 2012).

This historical note aims to explore earlier data on human trial using current controlled stimulation (tDCS) before 1998 with the goal of informing ongoing understanding and development of tDCS protocols. As expected, we found variability in the quality of trial design, data collection and reporting in these earlier studies. Nonetheless, many clinical findings are broadly consistent with modern efforts, including some encouraging results but also variability across subjects. We also describe a significant difference in dose with lower current, smaller electrodes and much longer durations (up to 11 h) than used in modern tDCS.

Figure 2. Summary of study parameters on human trials using transcranial direct current stimulation (tDCS) in old literature (from 1960 to 1998). Models of commonly used montages of tDCS in early studies (A); red: anode electrode(s), blue: cathode electrode(s). Total number of subjects in each group of patients participating in studies using aforementioned montages (B.1) and leading countries conducting tDCS studies in early stage with number of published articles (B.2).

Continue —> Frontiers | Notes on Human Trials of Transcranial Direct Current Stimulation between 1960 and 1998 | Frontiers in Human Neuroscience

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[WEB SITE] tDCS – A Therapy For The Future? – Brain Blogger

Transcranial direct current stimulation (tDCS) is a non-invasive, painless brain stimulation method which uses electrical currents to modulate neuronal activity in specific parts of the brain. A constant, low intensity current is delivered through small electrodes attached to the scalp in order to either increase or reduce neuronal activity.

This is clearly a trending topic: although interest in tDCS dates back to the 1960s, a search in PubMed reveals that more than half of the articles on tDCS were published in the last two years.

Despite numerous studies on different applications for tDCS, its use is still not generally accepted in the clinical setting; tDCS is not an FDA-approved therapy, remaining mostly an experimental method. Although tDCS has been tested on numerous conditions such as depression, anxiety, schizophrenia, Parkinson’s disease, Alzheimer’s disease, chronic pain, fibromyalgia, and stroke, its efficacy is still largely inconclusive.

Many studies applying tDCS have already been published in 2015, as well as a few reviews analyzing its efficacy for different conditions. By gathering the available information for the application of tDSC in a specific context, reviews are particularly useful, allowing researchers to sort through all the conflicting data. And these have actually shown some promising applications for tDSC.

Learning and Memory

There have been claims that tDCS can enhance cognition in healthy adult populations, especially working memory and language production, spiking the interest in tDCS as a neuroenhancement tool.

tDCS seems to act as a neuromodulatory technique, inducing a long-term enhancement or reduction of signal transmission between neurons. By strengthening or weakening neuronal connections, it may facilitate learning and memory formation, as well as neural plasticity that contributes to functional recovery after stroke, for example.

However, a review on the effects of a single-session of tDCS showed that it did not have a significant effect on a variety of cognitive function such as language, episodic memory, working memory or mental arithmetic, just to name a few. Nevertheless, it did not exclude the possibility that tDCS may be effective after multiple sessions.

There are in fact many reports from studies in healthy subjects stating that tDCS enhances verbal performance and learning, improving such outcomes as verbal speed, fluency, and amount of verbal learning. These language enhancement outcomes could potentially be quite useful in treating language deficits associated with different pathological conditions. In fact, tDCS has been used to enhance treatment efficacy in post-stroke aphasia rehabilitation and the results seem promising, with tDCS being effective in increasing language skills despite a high variety of stimulation parameters and patient characteristics.

Language enhancement can also be applied to a word reading context. Repeated tDCS application to adults with developmental dyslexia has been shown to significantly improve reading speed and fluency.

Reports supporting a positive effect on memory enhancement can also be found. Different studies have demonstrated an improvement in working memory and episodic memory in healthy subjects, with an increase in accuracy and in response time. But again, the evidences are still considered insufficient for a clinical application.

These memory enhancement effects could be quite useful in both Alzheimer’s and Parkinson’s disease, and in post-stroke rehabilitation. Again, some promising outcomes in these pathologies have been reported, but there are still conflicting results.

Continue–> tDCS – A Therapy For The Future? | Brain Blogger.

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