Translational research in transcranial direct current stimulation (tDCS): a systematic review of studies in animals

Andre Russowsky Brunoni, Felipe Fregni 3  and Rosana Lima Pagano 4
  • 1 Department of Neurosciences and Behavior, Institute of Psychology, University of São Paulo, Cidade Universitária, 05508-000 Butantã, São Paulo, Brazil
  • 2 University Hospital, University of São Paulo, Brazil
  • 3 Laboratory of Neuromodulation, Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
  • 4 Laboratory of Neuromodulation and Experimental Pain, Hospital Sírio-Libanês, São Paulo 01308-050, Brazil

Abstract

Recent therapeutic human studies testing transcranial direct current stimulation (tDCS) have shown promising results, although many questions remain unanswered. Translational research with experimental animals is an appropriate framework for investigating its mechanisms of action that are still undetermined. Nevertheless, animal and human studies are often discordant. Our aim was to review tDCS animal studies, examining and comparing their main findings with human studies. We performed a systematic review in Medline and other databases, screening for animal studies in vivo that delivered tDCS. Studies in vitro and using other neuromodulatory techniques were excluded. We extracted data according to Animal Research: Reporting In Vivo Experiments (ARRIVE) guidelines for reporting in vivo animal research. Thus, we collected data on sample characteristics (size, gender, weight and specimen) and methodology (experimental procedures, experimental animals, housing and husbandry, as well as analysis). We also collected data on methods for delivering tDCS (location, size, current and current density of electrodes and electrode montage), experimental effects (polarity-, intensity- and after-effects) and safety. Only 12 of 48 potentially eligible studies met our inclusion criteria and were reviewed. Quality assessment reporting was only moderate and studies were heterogeneous regarding tDCS montage methodology, position of active and reference electrodes, and current density used. Nonetheless, almost all studies demonstrated that tDCS had positive immediate and long-lasting effects. Vis-à-vis human trials, animal studies applied higher current densities (34.2 vs. 0.4 A/m2, respectively), preferred extra-cephalic positions for reference electrodes (60% vs. 10%, respectively) and used electrodes with different sizes more often. Potential implications for translational tDCS research are discussed.

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Reviews in the Neurosciences provides a forum for reviews, critical evaluations and theoretical treatment of selective topics in the neurosciences. The journal provides an authoritative reference work for those interested in the structure and functions of the nervous system at all levels of analysis, including the genetic, molecular, cellular, behavioral, cognitive and clinical neurosciences.

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