Critical Steps

Aspects to be checked prior to starting the procedure

Before starting the stimulation, researchers should make sure that the participant has no contraindications for HD-tDCS. Table 1 lists some important considerations to be taken into account and summarizes the most important contraindications, including presence of metallic implants or devices in the head, severe brain injuries or significant skin lesions. The researcher should inspect for presence of the latter within the 4x1-ring perimeter while preparing for electrode placement. We do not recommend application of the technique if such lesions exist. This is important as, though skin lesions have not been reported when using the HD electrodes and casings shown in this article, skin damage has been reported after delivery of several consecutive sessions of conventional tDCS 3, particularly if performed over a period of 14 days 25.

The presence of metallic implants or defects in the skull or brain parenchyma can significantly modify current flow 17,26 and result in stimulation of cortical regions other than those intended. For safety reasons, stimulation should be avoided in patients with implanted medical devices. Relative contraindications include presence of epilepsy or history of a stroke, unless the study is specifically focused on studying these conditions. HD-tDCS should be avoided in pregnant women due to lack of data on safety.

It is of utmost importance to check the polarity of the cables when connecting the 4x1 Multichannel Stimulation Adapter to the conventional tDCS device. Failure to do so may result in delivering the wrong type of stimulation to the participant. Make sure that the cable labeled as "Center", which may often be red, is plugged to the correct terminal (anode or cathode).

The operator should also visually inspect the Ag/AgCl sintered ring electrodes for evidence of deposition of electrolysis products before each use and replace them if indicated. After each active stimulation session, products of electrochemical reactions tend to build up on the rough surface on the bottom of the electrodes. For this reason, it is recommended that each electrode be located in the center of the 4x1 configuration for two active stimulation sessions only. Subsequently, it can be rotated and used as one of the return electrodes. Once each of the five electrodes in a set has served as the center electrode twice, it is recommended to use a new set of electrodes. It is straightforward to label each electrode and record the number of uses in order to rotate them in a coordinated manner. In addition to tolerability, the (limited) rotation of electrodes is also intended to avoid a high-impedance case where current will not be divided equally across the four return electrodes. The operator is responsible for checking contact quality prior to the stimulation (as explained in Steps 5.12 to 5.14), and ensuring that no abnormally high resistance values are observed.

It might occur that participants move their heads excessively or inadvertently pull the cables and dislodge or break them. For this reason, it is advisable to loop each cable around its plastic casing and to tape the 4x1 adapter output cable to a surface (i.e. the chair or the participant's clothes).

If desired, it may be possible to add topical anesthetics to the scalp in order to prevent potentially uncomfortable sensations and to enhance blinding of participants in the study. However, it should be kept in mind that, although skin burns have not been reported with HD-tDCS, there could be a small theoretical risk for this adverse effect and the use of topical anesthetics might prevent participants from reporting it during the stimulation. In this demonstration, as well as in our previous studies, we have not used topical anesthetics as any discomfort is generally reported as mild.

As mentioned above, in order to have optimal results it is very important to prevent the electrical gel from spreading beyond the limits of the plastic casing. Otherwise, current might shunt from one electrode to another.

Important considerations during the stimulation

Unless this is required as part of study design, the subject should not be sleeping, reading or otherwise distracted during the stimulation session. This is important as it has been reported that intense cognitive effort, boredom or sleeping, muscle activation and other activities leading to changes in cortical excitability can result in altered and opposed effects of conventional tDCS 27.

Upon initiation of the stimulation, and in order to prevent side effects from sudden start of current flow, the device automatically ramps current up and down over a period of thirty seconds. For similar reasons, do not switch between "Pass" and "Scan" modes while the conventional tDCS device is generating current. It is always advisable to periodically ask subjects whether they feel comfortable with the procedure in order to make sure that the stimulation is proceeding safely.

Stimulation in susceptible populations, including pediatric patients, may require dose adjustment.

Practical aspects after the procedure

In order to collect further evidence on safety and to monitor HD-tDCS effects, we recommend using an adverse effects questionnaire such as the one depicted in Table 3, which should be delivered to participants following each session. Make sure to screen for the presence of the most common adverse effects associated with HD-tDCS, such as discomfort, tingling, itching and burning sensations. Furthermore, the meaningfulness of these data can be improved by also asking for quantitative subjective scores. This can be achieved by having a numeric scale for patients to report the intensity or severity of the adverse effects, for instance from 1 to 5 or from 1 to 10. It is also important to deliver the side effect questionnaire after each sham session. This allows for comparing the frequency of adverse effects associated with both active and sham stimulation. For conventional tDCS, some side effects have been reported to be even more frequent in the sham group 24, headache being one example.

Possible modifications

For 4x1 HD-tDCS, stimulation protocols may be designed involving different target locations, current polarity and intensity, and radius of the ring. As a general rule, increasing 4x1 ring diameter will increase the depth of penetration and maximum intensity under the ring 28. Conversely, reducing ring radius increases focality but decreases induced brain electric field. Therefore, further investigation of optimal dose per indication is warranted.

Although this article is focused on 4x1-ring HD-tDCS, other electrode deployments can also be used, such as 4x2 and 3x3 (dual strip), among others. Though HD-tDCS offers many options for customization, the methods for positioning and preparing electrodes, as described here, should be followed along with using only hardware and accessories that have specifically been tested for this purpose. This includes paying special attention to HD plastic casing design, gel, and electrodes. For example, electrodes other than Ag/AgCl sintered ring have also been tested in order to deliver DC, such as Ag pellet, Ag/AgCl pellet, Ag/AgCl disc and rubber pellet 9. However, both Ag and rubber pellet electrodes induced changes in pH, and increases in temperature and electrode potential were reported for all electrodes except for Ag/AgCl ring and disc. Therefore, it appears that Ag/AgCl ring electrodes may be an effective and safer approach. In the future, modifications of the approach described in this paper may also be used to deliver interventions such as transcranial alternating current stimulation.

Limitations

At this point, the role of 4x1-ring HD-tDCS polarity on cortical excitability remains unclear. Though neurophysiological studies have reported that both 1.0 mA and 2.0 mA of anodal 4x1-ring HD-tDCS led to increases in cortical excitability among healthy subjects 13,14, a wider body of evidence specifically addressing HD-tDCS studies is needed before any generalization can be made. In addition, it is noteworthy that the effects of cortical excitability modulation using 4x1-ring HD-tDCS may be time-dependent, reaching their peak several minutes after the end of the stimulation and not immediately after it 14,16. Therefore, sequential assessments over different time points following the intervention may be needed in order to obtain accurate results.