Transcranial Direct Current Stimulation research line.
ECP application documentation.
Prof. Dr. Alexander Sack, Maastricht, 21-04-2017
In this document we outline the following:
· Description of Brain Stimulation Technique
· Safety and Comfort
· Experimental Procedures and Limitations
· Additional Safety Information and Procedures
Introduction
Transcranial direct current stimulation (tDCS) is an established, safe, and comfortable brain stimulation method for clinical and research applications, inducing temporary effects on regional brain excitability. There are no known consistent side- or after-effects. The most often reported noticeable effect in participants is a ‘tingling’ sensation of the skin during stimulation, which is not uncomfortable and lasts only a few tens of seconds at the onset of stimulation. There are industry standards of measurement parameters which will be followed as outlined below.
Description of Brain Stimulation Technique
TDCS is a non-invasive form of transcranial electric stimulation focusing on neuro-modulation rather than actual neuro-stimulation. Several applications, using the same equipment and physical principles, are subsumed under the proposed method. These are
1) Transcranial direct current stimulation (tDCS)
2) Sinusoidal transcranial direct current stimulation (stDCS)
3) Transcranial alternating current stimulation (tACS)
4) Transcranial random-noise stimulation (tRNS)
Safety considerations and potential side effects have not been shown to be different between these various applications, and besides the equipment they share many characteristics in terms of experimental design, procedures, and participant comfort. We therefore first explain the basic, common methodology behind tDCS application, before we outline the differences (for a more detailed technical description of tDCS and its specific sub-forms see Paulus et al., 2011).
tDCS
TDCS involves a battery, connected to two or more electrode patches (see image to the right). One of these patches serves as the reference electrode, the other serves as the stimulating electrode. A low-intensity electrical current flows between the electrode patches. If the current flows from the stimulating (here colored ‘red’) electrode patch to the reference electrode (‘blue’), we speak of ‘anodal stimulation’. If the current flows from the reference to the stimulating electrode (‘blue to red’), we speak of ‘cathodal stimulation’. By changing the baseline membrane potential of neurons underlying the stimulating electrode, these neurons are more (in the case of anodal stimulation) or less (in the case of cathodal stimulation) excitable than usual. This effect lasts during the stimulation period, and for some time afterwards, depending on stimulation duration. As we will never stimulate for periods longer than 40 mins, the maximum duration of effects (lasting excitability modulation) will not exceed 90 to 120 minutes.
stDCS
In sinusoidal tDCS, the current flowing between the electrode patches is not constant, but increases and decreases in intensity in a repeating sinusoidal (wave-like) pattern. Depending on the frequency of this pattern, brain oscillations used by the brain to communicate (measured often by electroencephalography, EEG), can be stimulated - if the stDCS frequency is similar to the brain oscillation frequency - or inhibited - if the stDCS frequency is different from the brain oscillation frequency. This method thus allows an investigation of brain oscillations and their role in perception and cognition, rather than only the role of a stimulated brain region.
tACS
In transcranial alternating current stimulation, the situation and goals are similar. The difference is that, instead of changing current intensity with a particular frequency, the direction of current flow (anodal versus cathodal, see above) changes back and forth with a particular frequency. This appears to have similar effects to stDCS, although probably stronger. Therefore, tACS is often used instead of stDCS.
tRNS
In transcranial random noise stimulation, the current flow direction and current intensity also changes over time, yet not in any fixed frequency. Rather, the frequency of the changing current intensity/direction varies randomly over time. This is a way to disturb the ongoing neuronal processing by disrupting not one brain oscillation frequency band in a specific brain region, but al. Therefore, it becomes more difficult for the region to engage in organized spatiotemporal activities. This thus creates somehow an online, direct ‘virtual lesion’ of the stimulated brain region.
Safety and Comfort
Safety
tDCS and its various applications have been pioneered and applied in human volunteers as early as about 1800 (Paulus et al., 2011). The method should, theoretically, not have any adverse effects, since it merely affects the membrane potentials of brain cells. These membrane potentials are also changed by the brain itself and constitute how the brain communicates. TDCS uses the same bio-physiological principles, but controlled ‘from the outside’ by the experimenter. Therefore, no damage, permanent changes, or – generally speaking – theoretical risk of any kind to the brain can occur using this method.
Due to electrical stimulation of the skin, participants with various forms of skin diseases (e.g. Psoriasis, Eczema) could experience irritation of the skin during and/or after stimulation. This would not lead to lasting discomfort or damage, yet participants with skin damage or diseases or other types of complaints will not be tested in our lab. A screening form (see below) will include exclusion criteria to ensure this. Furthermore, electrodes are covered by saline-solution-soaked sponges in order to avoid any electrochemical reactions at the electrode-tissue-interface (for further explanation see Nitsche et al., 2008).
Aside from the theoretical considerations regarding safety issues using tDCS, it is important to consider the practical experiences made in the field. Since the inception of tDCS, hundreds if not thousands of participants were tested, and recent reviews have taken inventory of the side effects and participant experiences. For instance, Poreisz and colleagues (2007) systematically summarized the side effects of 567 tDCS sessions over motor and non-motor cortical areas (occipital, temporal, parietal) including 102 participants (75.5% healthy participants, 8.8% migraine patients, 5.9% post-stroke patients and 9.8% tinnitus patients). During tDCS a mild tingling sensation was the most commonly reported side effect (70.6%), moderate fatigue was felt by 35.3% of the participants, whereas a light itching sensation under the stimulation electrodes occurred in 30.4% of cases. After tDCS headache (11.8%), nausea (2.9%) and insomnia (0.98%) were reported, but fairly infrequently. Even when assuming that all these reports of side effects were directly related to the brain stimulation experiment, they seem to be mild, rare, and temporary. As Nitsche and colleagues (2008) point out, tDCS is a non-invasive brain stimulation method “with no serious side effects, except for a slight itching under
the electrode, and seldom-occurring headache, fatigue, and nausea” (page reference) as long as the applied currents do not exceed a maximum stimulation intensity of 2 milliampere (mA) and the stimulation duration 1 hour – the framework in which also we will operate (see below). Based on the application of tDCS on approximately 2000 – 3000 participants from all over the world, no side effects other than mentioned were ever reported.
Comfort
Also in terms of comfort, tDCS has few side effects. The occasionally reported ‘tingling’ of the skin at stimulation onset is generally not considered unpleasant, is mild, and automatically fades after a few tens of seconds, even if the stimulation continues for minutes up to tens of minutes. In fact, tDCS procedures are suitable to ‘single-blind’ or even ‘double-blind’ experiments, because a control condition is often implemented as follows: in the control (sham stimulation) condition, the brain stimulation procedure is started the same way as in the experimental (real stimulation) condition. Yet, after 30 seconds, the device is turned off, and because the tingling sensation (if at all present) will already have receded, participants do not notice that their brains are not stimulated. This is how little subjective impact the methodology has on the volunteers.
Experimental Procedures and Limitations
Prior to the Experiment
Even though up to this day there are no known risk factors to tDCS, we will take the safest possible route and, therefore, screen participants for risk factors to other brain stimulation methods employed in our lab (i.e. Transcranial magnetic stimulation, TMS). To ensure maximum safety and minimization of all types of risk, we will employ the same procedures with regards to 1) participant screening, 2) participant treatment, and 3) certification of experimenters as we do for TMS.
1) Participant screening
In the appendix to the ECP proposal at hand, our participant screening form is provided. The exclusion criteria we apply are overly strict for tDCS, yet we implement them, nevertheless, to allow for one consistent participant base for both TMS and tDCS experiments. Briefly, participants will be excluded if they:
- have any (substantial history of) skin disease or irritation.
- are currently (or in the last 24 hours) taking medication, or consumed (hard or soft) drugs (max. 2 units of alcohol in the preceding 24 hours).
- currently suffer from headache or sleep deprivation.
- have (1st-degree relatives with) epilepsy or a history of seizures.
- have been diagnosed with neurological or psychiatric disorders.
2) Participant treatment
Participant will receive the ‘participant information’ as documented in the appendix, after adaptation of this document for the experiment at hand. They will receive ample time to review this information, will be informed about the contact information of the responsible researcher and of an independent physician - in case they experience adverse effects or have remaining questions after the experimental session(s). Further, they will be given the opportunity to ask questions at any time before and during the experiment. Upon requesting written informed consent (see appendix), the experimenter will emphasize that participants can quit the experiment at any time without giving a reason and that in such case they will still receive compensation for their spent time.
3) Certification of Experimenters
Only “Certified Users” will be allowed to administer non-invasive brain stimulation (TMS & tDCS) in the laboratories at FPN and Oxfordlaan 55. User certification is granted to FPN employees on the following basis/requirements:
- They must have followed the theoretical and practical ‘certified user course’ on non-invasive brain stimulation techniques. This consists of a seminar organized by the TMS group of the CN department under supervision of Dr. Alexander Sack, and minimally 5 session of hands-on experience with TMS/tDCS under the supervision of an already certified TMS/tDCS user.
- They must have demonstrated under supervision of a certified user conceptual and practical knowledge of TMS/tDCS, and proficiency in both practical TMS/tDCS administration and participant treatment, independently.
- For further information on the Certified User training see appendix.
The Experimental Session
1) Participant arrives in the lab: the certified user (CU) welcomes him/her
2) Participant is given the “participant information”, a standard document adapted to the specifics of the experiment at hand. He/she is given ample time to review it.
3) After the participant red the information, the CU emphasizes relevant information in the participant information (contact information of researchers and independent physician), and asks if there are any remaining questions.
4) The CU demonstrates the tDCS device and electrode patches and explains the procedure (outlined below). The CU then also explains the conditions, tasks, and parameters of the experimental session at hand (how long will it take, what will the participant need to do, if possible without biasing results: what is the research question and relevance of the project?).
5) The participant fills out the ‘pre-experimental check’ form (see appendix), which is a second participant screening form filled out in each measurement session in order to make sure that the information given in the screening form is still relevant and no acute changes have occurred.
6) Participant provides written informed consent.
7) The participant is seated in a chair in front of the stimulus computer. The stimulating and reference electrode patches are dipped in a saline solution (to ensure conductance of the direct current).
8) The electrode patches are applied to the head of the participant, the reference electrode either on the forehead (see image above) or on a mastoid behind the ears. The location(s) of the stimulation electrode patch(es) depend on the brain region under investigation, and can include frontal, parietal, temporal, and occipital regions.
9) The direct current stimulation will be administered, and the CU ensures that the participant is comfortable.
10) The participant performs a behavioral, perceptual, or cognitive task, during and/or after the stimulation.
11) At the end of the session, the participant will be compensated with either ‘proefpersoonpunten’ (1 point per hour of participation) or IRIS-cheques (10€ per hour). The CU will make sure that no adverse effects were experienced, and will encourage participants to establish contact if any adverse effects occur after the experimental session.
12) During any tDCS session a first-aider or so-called ‘bedrijfshulpverlener’ (someone trained in dealing with emergency situations) will always be on call.
Limitations
Additional Methodology
In the proposed research line, the tDCS procedures may be combined with the following additional measurements;
- behavioral and psychophysical measurements
- Eyetracking measurements using the Eyelink system (this requires no hardware on the body of the participant - only a camera positioned near the stimulus monitor - and provides no additional strain to participants)
- EMG measurements: electrodes may be attached to muscles in the hand or wrist area to measure muscular activity
- TMS: up to 5 pulses of TMS may be applied to stimulated or other brain regions, not during, but potentially after the administration of tDCS to modulate cortical excitability. The TMS pulses can be used to directly probe excitability of a brain region. Any application of this kind of TMS would not fall under the approval of tDCS currently under consideration, but would fall under an approval (to be requested separately) of TMS experimentation.
Stimuli and Tasks
Only sensory stimuli are presented to participants, before, during, or after tDCS. These stimuli would not be emotionally disturbing, or perceptually uncomfortable. The most ethically sensitive stimuli would potentially be still images of negative emotional expressions on faces (e.g. to test recognition of facial expressions, including faces looking scared, sad, disgusted or angry).
Only perceptual, cognitive, or behavioral tasks are employed that do not disturb or cause stress to participants. Cognitive tasks will include attention paradigms and numerical paradigms, perceptual tasks will include visual and/or auditory target detection, discrimination, or subjective ratings of visibility, behavioral tasks will include motor responses.