Transcranial stimulation of the developing brain: A plea for extreme caution

Davis, NJ (2014) Transcranial stimulation of the developing brain: A plea for extreme caution. Frontiers in Human Neuroscience, 8 (AUG). ISSN 1662-5161

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Abstract

Transcranial stimulation can be used to modulate the activity of the brain. Recent developments in our understanding of technologies such as transcranial magnetic or electrical stimulation have afforded reasonable grounds for optimism that techniques such as TMS or tDCS might be effective treatments for neurally-mediated disorders. Researchers have demonstrated encouraging benefits of TMS and tDCS in treating conditions such as tinnitus (Burger et al., 2011), depression (Arul-Anandam and Loo, 2009), and stroke (Nowak et al., 2010). Collectively these techniques are often referred to as “non-invasive brain stimulation” (NIBS), although I would argue that this term is not appropriate since in all cases energy is being transferred across the skull (Davis and van Koningsbruggen, 2013), and the use of this term may be misleading to the general public who are not aware of the documented risks associated with these procedures. More recently it has been suggested that brain stimulation be used to treat neurological disorders in pediatric cases. A recent review by Vicario and Nitsche (2013a) identified a number of opportunities and challenges for the use of brain stimulation in children. Here I offer a plea for calm and for caution. The ethical stakes in clinical and research procedures with children are high enough that a conservative approach is warranted. Many of the ethical issues, relevant both to adult and child participants, have been touched on by other authors (e.g., Cohen Kadosh et al., 2012; Krause and Cohen Kadosh, 2013); however this paper will focus on the gaps in our knowledge that affect our ability to assess risk in translating brain stimulation procedures to pediatric cases. There are a number of known risks associated with brain stimulation. Mild side-effects may include scalp tenderness, headache or dizziness, which are typically associated with the mechanism of delivery or with being immobilized in a chair or frame, and which may be under-reported (Brunoni et al., 2011). More serious effects may include seizure, mood changes or induction of hyper- or hypo-mania. However, the risk of seizure is low, at around 0.1% of adult cases and around 0.2% of pediatric reports, although these figures may not reflect unreported off-label use of the techniques (Rossi et al., 2009). These more serious symptoms are largely associated with people who already possess a degree of susceptibility, such as people with a history of epilepsy (Davis et al., 2013). Adult brain stimulation is thought be reasonably safe when used within defined limits (see below), however here I wish to focus on a number of factors that complicate the translation of TMS and tDCS protocols to pediatric cases. I will focus on the key unknowns in brain stimulation research: 1. The unknown effects of stimulation; 2. The unknown side-effects of stimulation; 3. The lack of clear dosing guidelines; 4. The lack of translational studies from adults to children. I will set out these “known unknowns” in translating our knowledge about TMS and tDCS effects to clinical pediatric applications, and touch on the practical and ethical barriers to their widespread usage.