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

Abstract

Recent therapeutic human studies testing transcranial direct current stimulation (tDCS) has 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/m(2), 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.

High-Definition Transcranial Direct Current Stimulation Induces Both Acute and Persistent Changes in Broadband Cortical Synchronization: A Simultaneous tDCS–EEG Study

“…Our findings make it difficult to assess the potential of using tDCS specifically for training subjects to use sensorimotor rhythm-based BCIs. However, such effects on cortical excitability could be of use for rehabilitation of neural disorders which exhibit significantly reduced or altered network synchronization in various frequency bands, such as stroke, paralysis, schizophrenia and depression [4], [8], [38]. …”

“…Behavioral studies have since revealed potential therapeutic applications of tDCS for a wide variety of disorders, including Parkinson’s, stroke, depression, schizophrenia, and addiction [3, 4, 8, 9]. EEG recordings following tDCS stimulation periods have revealed changes in resting state oscillatory neural activity, functional connectivity, and event related activity during cognitive tasks.…”

Preconditioning tDCS facilitates subsequent tDCS effect on skill acquisition in older adults

“…After the FORCEtraining with tDCS with the anode placed over M1, using a questionnaire developed by Brunoni et al (2011) andFertonani et al (2010), we asked participants to report the presence and severity (none-mild-moderate-considerable-strong) of feelings of itchiness, tingling, headache, neck pain, scalp pain, burning, warmth/heat, pinching, iron taste, fatigue, concentration difficulties and acute mood changes. In addition, the start (beginning, middle or end of stimulation) and duration (stopped soon, in the middle or towards the end of the stimulation) of these sensations was questioned and participants were asked if the sensations influenced their performance (not at all, a little, considerably, much, very much).…”

Assessing cortical synchronization during transcranial direct current stimulation: A graph-theoretical analysis

“…Experiments in animals (Bindman et al, 1964;Purpura and McMurtry, 1965;Brunoni et al, 2011) and humans (Nitsche and Paulus, 2000) have shown that the use of such currents induces polarity-specific effects that are not strictly restricted to the stimulated site (Stagg et al, 2009;Stagg and Nitsche, 2011;Polania et al, 2011aPolania et al, , 2011bKeeser et al, 2011;Pellicciari et al, 2013). These findings suggest that neuronal mechanisms underlying the described effects should involve synaptic strength changes and possibly the modulation of synaptic connectivity, leading to a viable way to induce changes in excitability (Stagg and Nitsche, 2011) and, therefore, the functionality of specific networks.…”