Methods for extra-low voltage transcranial direct current stimulation: Current and time dependent impedance decreases

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Abstract

Objective

Though tDCS is well tolerated, it is desirable to further limit the voltage applied for additional safety factors and optimized device design. We investigated the minimum voltage required for tDCS using 1.5 and 2.5 mA.

Methods

Impedance data has been collected prior to, during and after 18 tDCS sessions, using 1.5 mA and 2.5 mA tDCS currents and three different test current magnitudes. Data was pooled and tested for differences using t-tests, corrected for multiple comparisons. Average impedance data was fitted into a RLC circuit model with additional double integrator.

Results

We report that the impedance drop during tDCS initiation significantly reduces the voltage compliance required to achieve the target current (14.5 V for 1.5 mA, 18.5 V for 2.5 mA). Data was well approximated by a 4th order linear impedance model.

Conclusion

In addition to indicating the feasibility of reduced voltage tDCS, we propose an extra-low voltage “Limited Total Energy” approach where stimulation is continued at voltage compliance allowing time for impedance to decrease and target current to be reached.

Significance

Reduced-voltage and Limited Total Energy tDCS are viable approaches towards more protective and robust tDCS protocols.

Highlights

Transcranial direct current stimulation is accompanied by a characteristic drop in skin impedance which significantly reduces compliance voltage. ► Skin impedance changes have been investigated experimentally and approximated by a 4th order linear model. ► Reduced-voltage and Limited Total Energy tDCS are viable approaches towards more protective and robust brain stimulation protocols.

Introduction

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that is being evaluated for the treatment of depression, epilepsy, pain, facilitating stroke rehabilitation and further neurological conditions (Hummel et al., 2005, Fregni et al., 2006, Nitsche et al., 2008, Nitsche et al., 2009, Nitsche and Paulus, 2009). During tDCS, a weak constant current is passed across the brain using electrodes placed on the scalp; prolonged passage of current (e.g. >10 min) can lead to lasting changes in neuronal excitability (Nitsche and Paulus, 2000, Nitsche and Paulus, 2001). Most commonly, conductive rubber pads wrapped in saline-soaked sponge pockets are used as tDCS electrodes.

Stimulation protocols for tDCS consist of a fade-in phase in which current is ramped up to the desired intensity (typically <30 s), the main stimulation phase at target intensity (typically 1–2.5 mA, for 10–20 min), and a fade-out phase. The voltage needed to ramp up current and maintain stimulation depends on the impedance across the body and the electrodes. Skin (scalp), skull, CSF, and brain tissue contribute to body impedance, with skin impedance known to change depending on current intensity and density and stimulation duration (Kalia and Guy, 1995, Prausnitz, 1996). Electrode impedance is a function of dynamic electrochemical processes and is also a complex function of stimulation waveform and time (Prausnitz, 1996, Merrill et al., 2005, Minhas et al., 2010). It is precisely because tissue and electrode impedance across subjects and time is highly variable, that current controlled stimulation is used to ensure reproducible delivery of stimulation dose to the brain.

During tDCS, the voltage is therefore adjusted to maintain the desired current level across variable impedances. Poor electrode design and preparation can thus lead to higher voltages being applied. Although current/charge density and total delivered charge are considered the main parameters causing tissue damage and painful sensation (McCreery et al., 1990, Nitsche et al., 2003, Liebetanz et al., 2009), unnecessarily high voltages are also undesirable for several reasons. For example, as electrode voltage increases, additional electrochemical reactions are triggered (Merrill et al., 2005) leading to potentially undesired chemical products and pH changes (Minhas et al., 2010). In addition, with improperly designed stimulation electronics (e.g. using off-label iontophoresis devices), a sudden drop in impedance can lead to a surge in current. Joule heating leading to temperature increases is a function of both current and voltage, though is likely not significant during conventional tDCS or High-Definition tDCS (Datta et al., 2009).

As it may play a role in painful skin sensation and irritation, it seems worthwhile to limit the electrical potential applied to subject’s scalps. Current tDCS devices are limited to output voltages of 20–43 V, independent of current applied (Iontophoresis devices can reach >90 V). Anecdotal evidence suggests that in some subjects the maximum voltage of the stimulator is reached (either software or hardware limited “compliance voltage”) leading to stimulation being aborted. The goal of this short study was to determine lowest possible voltage limits for tDCS devices for 1.5 mA and 2.5 mA target currents using a common electrode design and montage. Experimentally and with a 4th order linear circuit model, we demonstrate that the decrease in impedance produced by the passage of current itself significantly reduces the compliance voltage required. Furthermore, recognizing that reaching and maintaining the target current intensity does not require a strictly controlled (linear) ramp, we develop a “Limited Total Energy” (LTE) approach to tDCS which allows robust extra-low voltage stimulation.

Section snippets

Methods

This study was approved by the IRB of the City College of New York. All seven subjects gave written informed consent.

tDCS was administered for 6 min (30 s ramp-up, 5 min stimulation, 30 s ramp-down) to seven healthy adult subjects, using a custom-designed battery-run circuit (Soterix Medical Inc., NY) which allows free adjustment of maximum output voltage and current magnitude. Current was ramped up and down linearly over 30 s. Two rubber electrodes wrapped in saline soaked sponges, one over the

Results

Impedance across electrodes was monitored before, during, and after tDCS. Pre- and post-tDCS impedance values differed significantly (Fig. 1c). Prior to stimulation the average impedance was 39.4  ± 8.9 (I = 50 μA), 32.1  ± 5.1 (I = 100 μA), and 23.7  ± 4.6 (I = 150–200 μA). As tDCS was initiated, impedance decreased significantly, approaching a minimum value after ∼30 s (corresponding to the ramp up duration where target current is achieved). Average impedance continued to decrease incrementally over

Discussion

Our results indicate that using conventional electrode montages (e.g. C3–SO, C3C4), and appropriate electrode types and preparation (e.g. impedance checks), the voltage limits of clinical tDCS devices can be decreased to values <20 V. Specifically, in a current target specific manner, for 1.5 mA stimulation, output voltage of the device can be limited to 14.5 V, whereas 18.5 V is sufficient for successful stimulation at 2.5 mA target current intensity. Using smaller electrodes (Nitsche et al., 2007

Conflict of Interest

The City University of New York has patent applications on brain stimulation with Christoph Hahn, Justin Rice, Preet Minhas and Marom Bikson as inventors. Marom Bikson is co-founder of Soterix Medical Inc.

References (25)

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These authors contributed equally to this work.

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