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      Dosage Considerations for Transcranial Direct Current Stimulation in Children: A Computational Modeling Study

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          Abstract

          Transcranial direct current stimulation (tDCS) is being widely investigated in adults as a therapeutic modality for brain disorders involving abnormal cortical excitability or disordered network activity. Interest is also growing in studying tDCS in children. Limited empirical studies in children suggest that tDCS is well tolerated and may have a similar safety profile as in adults. However, in electrotherapy as in pharmacotherapy, dose selection in children requires special attention, and simple extrapolation from adult studies may be inadequate. Critical aspects of dose adjustment include 1) differences in neurophysiology and disease, and 2) variation in brain electric fields for a specified dose due to gross anatomical differences between children and adults. In this study, we used high-resolution MRI derived finite element modeling simulations of two healthy children, ages 8 years and 12 years, and three healthy adults with varying head size to compare differences in electric field intensity and distribution. Multiple conventional and high-definition tDCS montages were tested. Our results suggest that on average, children will be exposed to higher peak electrical fields for a given applied current intensity than adults, but there is likely to be overlap between adults with smaller head size and children. In addition, exposure is montage specific. Variations in peak electrical fields were seen between the two pediatric models, despite comparable head size, suggesting that the relationship between neuroanatomic factors and bioavailable current dose is not trivial. In conclusion, caution is advised in using higher tDCS doses in children until 1) further modeling studies in a larger group shed light on the range of exposure possible by applied dose and age and 2) further studies correlate bioavailable dose estimates from modeling studies with empirically tested physiologic effects, such as modulation of motor evoked potentials after stimulation.

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          Most cited references23

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          Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation.

          In this paper we demonstrate in the intact human the possibility of a non-invasive modulation of motor cortex excitability by the application of weak direct current through the scalp. Excitability changes of up to 40 %, revealed by transcranial magnetic stimulation, were accomplished and lasted for several minutes after the end of current stimulation. Excitation could be achieved selectively by anodal stimulation, and inhibition by cathodal stimulation. By varying the current intensity and duration, the strength and duration of the after-effects could be controlled. The effects were probably induced by modification of membrane polarisation. Functional alterations related to post-tetanic potentiation, short-term potentiation and processes similar to postexcitatory central inhibition are the likely candidates for the excitability changes after the end of stimulation. Transcranial electrical stimulation using weak current may thus be a promising tool to modulate cerebral excitability in a non-invasive, painless, reversible, selective and focal way.
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            Optimized multi-electrode stimulation increases focality and intensity at target.

            Transcranial direct current stimulation (tDCS) provides a non-invasive tool to elicit neuromodulation by delivering current through electrodes placed on the scalp. The present clinical paradigm uses two relatively large electrodes to inject current through the head resulting in electric fields that are broadly distributed over large regions of the brain. In this paper, we present a method that uses multiple small electrodes (i.e. 1.2 cm diameter) and systematically optimize the applied currents to achieve effective and targeted stimulation while ensuring safety of stimulation. We found a fundamental trade-off between achievable intensity (at the target) and focality, and algorithms to optimize both measures are presented. When compared with large pad-electrodes (approximated here by a set of small electrodes covering 25 cm(2)), the proposed approach achieves electric fields which exhibit simultaneously greater focality (80% improvement) and higher target intensity (98% improvement) at cortical targets using the same total current applied. These improvements illustrate the previously unrecognized and non-trivial dependence of the optimal electrode configuration on the desired electric field orientation and the maximum total current (due to safety). Similarly, by exploiting idiosyncratic details of brain anatomy, the optimization approach significantly improves upon prior un-optimized approaches using small electrodes. The analysis also reveals the optimal use of conventional bipolar montages: maximally intense tangential fields are attained with the two electrodes placed at a considerable distance from the target along the direction of the desired field; when radial fields are desired, the maximum-intensity configuration consists of an electrode placed directly over the target with a distant return electrode. To summarize, if a target location and stimulation orientation can be defined by the clinician, then the proposed technique is superior in terms of both focality and intensity as compared to previous solutions and is thus expected to translate into improved patient safety and increased clinical efficacy.
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              Inter-Individual Variation during Transcranial Direct Current Stimulation and Normalization of Dose Using MRI-Derived Computational Models

              Background: Transcranial Direct Current Stimulation (tDCS) is a non-invasive, versatile, and safe neuromodulation technology under investigation for the treatment of neuropsychiatric disorders, adjunct to rehabilitation, and cognitive enhancement in healthy adults. Despite promising results, there is variability in responsiveness. One potential source of variability is the intensity of current delivered to the brain which is a function of both the operator controlled tDCS dose (electrode montage and total applied current) and subject specific anatomy. We are interested in both the scale of this variability across anatomical typical adults and methods to normalize inter-individual variation by customizing tDCS dose. Computational FEM simulations are a standard technique to predict brain current flow during tDCS and can be based on subject specific anatomical MRI. Objective: To investigate this variability, we modeled multiple tDCS montages across three adults (ages 34–41, one female). Results: Conventional pad stimulation led to diffuse modulation with maximum current flow between the pads across all subjects. There was high current flow directly under the pad for one subject while the location of peak induced cortical current flow was variable. The High-Definition tDCS montage led to current flow restricted to within the ring perimeter across all subjects. The current flow profile across all subjects and montages was influenced by details in cortical gyri/sulci. Conclusion: This data suggests that subject specific modeling can facilitate consistent and more efficacious tDCS.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                27 September 2013
                : 8
                : 9
                : e76112
                Affiliations
                [1 ]Children’s Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
                [2 ] The City College of the City University of New York, New York, New York, United States of America
                [3 ]Center for Cognitive Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
                Cardiff University, United Kingdom
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: SKK AJW PM MB. Performed the experiments: SKK AJW PM ARR MB. Analyzed the data: SKK AJW PM ARR MB. Wrote the manuscript: SKK AJW PM CG MB.

                Article
                PONE-D-13-19181
                10.1371/journal.pone.0076112
                3785412
                24086698
                aa9d629a-1113-481b-aa3c-82f3827eeadb
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 9 May 2013
                : 21 August 2013
                Funding
                This work was supported by Clayton’s Hope Foundation and National Institutes of Health, National Institute of Neurological Disorders and Stroke K12NS049453 (SK Kessler). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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