Transcranial Direct Current Stimulation: Comparison
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Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique considered to be safe, tolerable, and acceptable to use in adults.

  • tDCS
  • children
  • safety
  • tolerability
  • brain stimulation
  • systematic review
  • adolescents

1. Introduction

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique considered to be safe, tolerable, and acceptable to use in adults [1][2][3][4][5][6][7][8]. However, it is minimally researched and still controversial in pediatrics [9]. tDCS utilizes a direct, low-amplitude electrical current to enhance or depress cell membrane excitability [10]. The interest around tDCS is driven by its potential to induce neuroplastic changes and potentially aid in the treatment or management of mood disorders such as depression [11], memory deficits and motor control in Parkinson’s diseases [12], memory deterioration in Alzheimer’s diseases and dementia [13], impairments in attention-deficit/hyperactivity disorder (ADHD) [14], reduction of pain in chronic pain conditions [15], and expediting stroke recovery [16]. With the mounting experimental evidence for tDCS use in adults, interest in the application of tDCS in children is growing considerably [7][17]. Rivera-Urbina et al. [17] highlighted evidence for pediatric tDCS in epilepsy, autism, dyslexia, ADHD, and other psychiatric disorders such as depression and schizophrenia. This is further supported by the review from Lee et al. [18] which presented evidence for overall interest and efficacy of tDCS in child and adolescent psychiatric disorders. Despite the growing evidence, there is still a degree of uncertainty regarding tDCS use in children. Such reservations are primarily centered on the present lack of evidence for the short- and long-term safety and tolerability of tDCS in the developing brain.

2. Discussion of Current Trends

2.1 The Safety of Remote and At-Home tDCS

Recent trends in tDCS research have focused on at-home use. Indeed, multiple studies have found good compliance and outcomes using an at-home tDCS approach [19][20][21]. Although this raises some obvious safety concerns, Charvet et al. [22] and Knotkova et al. [23] have published practical guidelines for at home or remotely supervised tDCS use. These are admirable steps forward and will help researchers and clinicians safely implement tDCS at home. This is particularly important in the current climate of COVID-19. A recent guideline was published by Bikson et al. [24] to outline the necessity and importance of safely implementing and continuing tDCS and TMS treatments during the pandemic. That being said, the biggest risks associated with tDCS are not likely to occur in clinical trials or clinical applications, but rather among consumers pursuing self-prescribed at-home tDCS. If used improperly, tDCS may cause burns and potentially other unforeseen adverse events.

At the moment, consumer tDCS devices are readily available for less than $200 via ecommerce websites such as Amazon; and consumer reviews seem to indicate that it is in demand. A quick YouTube search of at-home tDCS will reveal videos with tens of thousands of views further attesting to consumer interest and demand. Even parents of children with ADHD have expressed their desire to pursue tDCS treatment [8]. Despite expert panels [25], these devices are available for sale without any governing authority or regulation. Aside from the warranted safety concerns, this poses a serious healthcare dilemma. At the moment, tDCS is not a readily available treatment option in most hospitals or outpatient treatment centres, but it is available for unregulated consumer purchase online. This means that individuals who desire tDCS treatment will primarily have to pursue it on their own without the guidance of a medical professional. It would seem that the adoption of tDCS into community medicine would help to ensure the safety of those pursuing tDCS as a treatment option. Therefore, there is a consistent onus on researchers to disseminate evidence into community medicine and to educate clinicians on how to properly implement tDCS into their practice. It is evident that when used properly tDCS has the capability of being a safe and effective medical intervention; there is no reason why patients should have to put themselves at risk by pursuing this treatment on their own through consumer devices.

2.2. Dose Optimization

Another recent trend in tDCS research is dosage, such as individualized amperage and electrode montage based on MRI, EEG, or TMS [11][26][27][28][29][30][31][32][33]. This research has revealed that tDCS, much like medication, dosage and titration can be optimized based on individual characteristics such as age and weight, but also skull and brain morphology. Arguably, individualized tDCS protocols should radically improve treatment efficacy and subsequently safety. If individualized, tDCS is considered the highest level of safety precaution, then consumer-prescribed tDCS would be the least. In the present review, five studies used methods to individualize tDCS, such as Auvichayapat [34] placing the electrode over the epileptogenic focus, or Rich [35] using the TMS motor hot spot and MEP threshold. Although the other many studies to dat have not individualized their tDCS protocols, they collectively provided sound evidence for the general safety of tDCS at multiple relevant brain regions such as the DLPFC, STG, and M1. Overall, it is clear that the optimal stimulation target site for tDCS is totally dependent on the desired clinical outcomes and the subject specific characteristics. That said, a few things can definitely be agreed upon: in stroke or neuromotor studies, and epilepsy studies, individualization of stimulation parameters, especially location, is the gold standard. This is true in adults and it holds true in youth.

2.3. Pediatric tDCS Safety Timeline

tDCS really started gaining traction in adults in the late 1990s and early 2000s. It took approximately one decade for this knowledge to successfully transfer to adolescents and children. In 2011 Mattai et al. [36] published what appears to be the first clinical application of tDCS in youth; and rightfully so, it had an emphasis on safety and tolerability. Now, 10 years after Mattai’s initial publication, the potential for tDCS in pediatric neurology and neuropsychiatry is starting to be realized and accepted [8]. From 2011 to 2021, several hundred papers have been published about tDCS in children. However, only a limited number evaluated and reported safety outcomes. Mattai actually had a relatively small sample size of 12, but their mostly adolescent subjects were exposed to a total of 125 active tDCS sessions. Two years later, Auvichayapat et al. [34] published an epilepsy study (n = 36) but each subject only received a single session of tDCS. Also in 2013, Andrade et al. [37] conducted a study with 140 active sessions in 14 children with neurodevelopmental issues. Notably, Andrade’s sample has the youngest mean age (7.57) of all the studies we reviewed (not including an infant case study). This was less than half the average age of Mattai’s sample from two years previous (16.37). Andrade’s sample was also the only one that underwent 30 minutes tDCS sessions. Sample size and number of sessions in these safety trials continued to grow until they peaked with Gomez [38] in 2017, with 15 subjects receiving a total of 300 active sessions.

The knowledge progression seen from Gillick 2014 to the present also significantly advanced evidence of the safety and tolerability of pediatric tDCS. Gillick and her lab are responsible for 1/3 of the included studies. The studies began in 2014 [39], with only a single subject and a single 10 min session; and then in 2015 [40], with 11 subjects also receiving only a single 10 min session. Then in 2018 and 2019, Gillick was senior author with Rich [35] and Nemanich [41] as leads, respectively. From Rich in 2018, we saw an increase in duration of sessions from 10 to 20 min, and number of sessions from 1 to 10 for 8 subjects. Then in 2019, Nemanich provided an even larger sample of 20 subjects each receiving 10 sessions of 20 min each. Nemanich’s trial also included the largest sample of 100 sham tDCS sessions, to date. These four studies had perhaps the most consistent reporting of side effects and adverse events considering they were all published under the seniority of Gillick.

At the same time as Gillick, Kirton’s laboratory also provided significant advancements in pediatric tDCS in neurotypical controls [42][43] as well as stroke [44]. The contributions from Kirton were all rigorously controlled and saw a similar scientific progression as Gillick such as increased number of sessions and additional control arms. Also similar to Gillick, all of the papers from Kirton’s supervision maintained rather consistent reporting styles making them easier to synthesize and interpret. The methodology of Kirton’s papers also included routine tolerability side effect questionnaires, often TMS motor mapping, and occasionally other assessments like vital signs and cognitive evaluations. That being said, the reported results from Kirton [42][43][44] tended to focus on the efficacy of tDCS and less on changes in objective safety measures like neuroimaging.

In the 10 years spanning all of the reviewed trials, the expected and experienced side effects have consistently remained only mild sensations of itching, tingling, burning, or pain. That being said, the distinction between sensations such as itching, tingling, burning, or pain on the scalp are not well defined and therefore responses may be biased by the frame of the question. This is why many of the side effect questionnaires employed today ask specifically about each individual sensation. On that note, it was surprising that other potential sensory side effects related to vision or hearing were scarcely investigated. In addition to using a consistent side effect questionnaire, future researchers should also consider defining their desired clinical outcomes and clear criteria for stopping protocol. Studies using neuroimaging as a marker of safety in terms of detecting abnormal function after tDCS should clearly define what they consider abnormal (i.e., the type of signature, the number of standard deviations required to be abnormal). The same should be indicated for cognitive, psychiatric, motor, and other outcomes specific to the authors’ hypotheses. This would really improve the level of interpretability and aggregation of the safety results across the literature.

 

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