Extended Multiple-Field High-Definition transcranial direct current stimulation (HD-tDCS) is well tolerated and safe in healthy adults

Abstract

Background: High definition transcranial direct current stimulation (HD-tDCS) has been administered over single brain regions for small numbers of sessions. Safety, feasibility and tolerability of HD-tDCS over multiple brain regions, multiple daily stimulations and long periods are not established.

Objective: We studied safety, feasibility and tolerability of daily HD-tDCS over 2-4 brain regions for 20 sessions in healthy adults.

Methods: Five healthy adults underwent physical and neurological examination, electrocardiogram (EKG), electroencephalogram (EEG) and cognitive screening (ImpACT) before, during and after HD-tDCS. Four networks (left/right temporoparietal and frontal) were stimulated in sequence (20 min each) using HD-tDCS in 20 daily sessions. Sessions 1-10 included sequential stimulation of both temporoparietal networks, sessions 11-15 stimulations of 4 networks and sessions 16-20 two daily stimulation cycles of 4 networks/cycle (1.5 mA/network). Side effects, ImpACT scores and EEG power spectrum were compared before and after HD-tDCS.

Results: All subjects completed the trial. Adverse events were tingling, transient redness at the stimulation site, perception of continuing stimulation after end of session and one self-resolving headache. EEG power spectrum showed decreased delta power in frontal areas several days after HD-tDCS. While at the group level ImpACT scores did not differ before and after stimulations, we found a trend for correlation between decreased EEG delta power and individual improvements in ImpACT scores after HD-tDCS.

Conclusion: Prolonged, repeat daily stimulation of multiple brain regions using HD-tDCS is feasible and safe in healthy adults. Preliminary EEG results suggest that HD-tDCS may induce long lasting changes in excitability in the brain.

Keywords: HD-tDCS; adverse events; feasibility; safety; tolerability.

Fig 1. Diagram of HD-tDCS stimulation protocol and timing of ancillary studies

A: left temporoparietal network; B: right temporoparietal network; C: left frontal network; D: right frontal network.

Fig 2. Diagram of stimulation principle and outline of the HD-tDCS stimulation session design. There were four networks applied as noted on the diagram

Networks were stimulated sequentially in the sequence left temporoparietal (20 min), right temporoparietal (20 min), left frontal (20 min), right frontal (20 min). Total duration of one full HD-tDCS cycle was 80 min. Only 1 daily cycle was applied in sessions 1–15, and 2 daily cycles in sessions 16–20.

Fig 3

ImpACT scores before and after 20 sessions of HD-tDCS, applied as outlined in figure 1 and table 1. Columns depict mean scores ± SD in n=5 participants. No statistically significant differences were detected when before and after treatment scores were compared using Student’s t-test.

Fig 4. EEG power topographies

Upper panel: Changes in EEG delta power after HD-tDCS treatment. From left to right: average referenced EEG delta power topographies before (EEG #1) and after (EEG #4) HD-tDCS, differences between the two, and SPM and SNPM T maps. T maps are thresholded for display at uncorrected p<0.05. A rainbow color scale is used for SWA, and a hot color scale for T values. Lower panel: Correlation between changes in EEG delta power and improvements in ImpACT scores after HD-tDCS. From left to right: slope of multiple regression between changes in EEG delta power and improvements in ImpACT scores; SPM and SNPM T maps; and distribution plot for the statistical peaks of correlation analysis. T maps are thresholded for display at uncorrected p<0.05. A rainbow color scale is used for regression slope values, and a hot color scale for T values.