Transcranial direct current stimulation (tDCS) is an established technique to modulate cortical excitability1,2. It has been used as an investigative tool in neuroscience due to its effects on cortical plasticity, easy operation, and safe profile. One area that tDCS has been showing encouraging results is pain alleviation 3-5.
Transcranial direct current stimulation (tDCS) is a technique that has been intensively investigated in the past decade as this method offers a non-invasive and safe alternative to change cortical excitability2. The effects of one session of tDCS can last for several minutes, and its effects depend on polarity of stimulation, such as that cathodal stimulation induces a decrease in cortical excitability, and anodal stimulation induces an increase in cortical excitability that may last beyond the duration of stimulation6. These effects have been explored in cognitive neuroscience and also clinically in a variety of neuropsychiatric disorders – especially when applied over several consecutive sessions4. One area that has been attracting attention of neuroscientists and clinicians is the use of tDCS for modulation of pain-related neural networks3,5. Modulation of two main cortical areas in pain research has been explored: primary motor cortex and dorsolateral prefrontal cortex7. Due to the critical role of electrode montage, in this article, we show different alternatives for electrode placement for tDCS clinical trials on pain; discussing advantages and disadvantages of each method of stimulation.
1. Materials
In this guide we illustrate the most typical tDCS set-up for pain management: using conductive rubber electrodes, pocket type perforated sponges, both placed on the head, with no topical anesthetic.
2. Measurements
3. Skin Preparation
4. Position electrodes
5. Start tDCS
6. After the procedure
7. Representative Results:
With proper setup, the tDCS device should display that either current is flowing during active tDCS situation, or the device should display sham mode when running a sham stimulation procedure (Figure 10).
Of note, even with the device indicating that current is flowing through the system, current might actually being shunted through the skin. In order to avoid this effect, it is recommended to have sufficient distance between electrodes. According to modeling studies we recommend that to be of at least 8cm when using 5x7cm electrodes17.
Furthermore, it is recommended to consult computer head models14 and neurophysiological studies. These additional steps would ensure that a specific montage is associated with significant changes in cortical excitability in the area that is being investigated.
Representative for anodal stimulation is an increase of brain excitability, whereas cathodal stimulation leads to a reduction of the cortical excitability. Robust evidence for this has been revealed in trials targeting the primary motor cortex (Figure 6).
The variation of the electrode size leads to a variation of focal effects. With a decrease of the diameter of the electrode, a more focal stimulation can be achieved. This can be proven by using TMS over the motor cortex. On the other hand by increasing electrode size it is possible to have a functionally ineffective electrode (Figure 8).
With session duration of 20 minutes or more and with multiple sessions over consecutive days, the after-effects of tDCS will last longer. Example for this is the treatment of pain syndromes.
One important point is the location of the reference electrode. If an extracephalic position is chosen, investigator should be aware of current distribution as the reference electrode might displace the peak of induced current and modify the effects of tDCS.
Figure 1. Materials
Figure 2: Vertex Position. Cortical areas marked according to the 10/20 system.
Figure 3: Nasion and Inion Position
Figure 4: Motor cortex Position. Cortical areas marked according to the 10/20 system.
Figure 5: DLPFC Position. DLPFC= dorsolateral prefrontal cortex. Cortical areas marked according to the 10/20 system.
Figure 6: Change in cortical excitability due to current polarity and tDCS montage. Table: Induced effects of tDC stimulation on the size of the motor evoked potential (MEP), assessed by transcranial magnetic stimulation (TMS). MEP amplitudes after stimulation are given in percent of MEP without stimulation. Note that only the motor cortex (M1) – contralateral supra-orbital (Fp2) montage setting leads to a significant increase of MEP size after anodal and a decrease of MEP amplitude after cathodal stimulation. There are no significant effects on MEP amplitude in other tDCS montages. Figure: Electrode Placements6 (modified from Nitsche 2000).
Figure 7: Electrode Sizes
Figure 8: Decreasing the size of the electrode leads to a more focally effect of tDCS. Muscle-evoked potential (MEP) amplitude sizes of the abductor digiti minimi (ADM) and of the first dorsal interosseus muscle (FDI) during anodal or cathodal tDCS. Using the condition of a 35 cm2 electrode, anodal and cathodal tDCS influence the MEP amplitude size of the ADM and the FDI to a similar extent. At this montage, both hand muscle representation areas are located underneath the stimulating electrode. In the case of a smaller electrode, which is only placed over the representational area of the ADM, the effects of MEP amplitude changes of the cortical FDI representation are not reproducible (see yellow column)18 (modified from Nitsche 2007).
Figure 9: Tissue-depended current density. Current densities calculated in different tissues. Magnitude of current density is dependent on the conductivity of tissue. Note that approximately 10% of current density reaches the Gray Matter19 (modified from Wagner 2007a).
Figure 10: Different stimulation conditions: active vs. sham. Some tDCS devices provide set ups for active and sham condition. Usually applicable stimulation is indicated with a light signal.
Material |
TDCS device |
9V Battery (2x) |
Two rubber head bands |
Two conductive rubber electrodes |
Two sponge electrodes |
Cables |
NaCl solution |
Measurement Tape |
Table 1. Materials
Anode Electrode Positioning | Cathode Electrode Positioning | Observations | Caveats |
Primary Motor cortex (M1) | Supra-Orbital | This is the most used montage. It has been proven that the cortical excitability can be changed up to 40%6 (Figure 6). Anodal stimulation results in neuronal depolarisation and increasing neuronal excitability while cathodal stimulation has opposite results6. | Only one motor cortex is stimulated – might be a problem for bilateral pain syndromes. Also the confounding effect of the supra-orbital electrode needs to be considered. |
Primary Motor cortex (M1) | Primary Motor cortex | – Interesting approach when there is a bi-hemispheric imbalance between motor cortices (such as in stroke) – Can be used with two anodal stimulation electrodes (see sixth row), where cathodal electrode is placed in the supraorbital area for instance. |
Electrodes might be too close to each other- issue of shunting. A decrease of the area of the electrodes will increase the degree of shunting along the skin 19 Therefore shunting might be related not only to electrode positioning but also to electrode size. The relative resistance of the tissues is dependent upon the electrode position and size- the overall resistance on which the current flows is dependent upon the electrode properties19. |
Dorsolateral Prefrontal Cortex (DLPFC) | Supra-Orbital | Most used for DLPFC stimulation – positive results for treatment of depression20 and also chronic pain3. | Only unilateral DLPFC stimulation situation is possible with this montage. |
Dorsolateral Prefrontal Cortex | Dorsolateral Prefrontal Cortex | – Interesting approach when there is a bi-hemispheric imbalance. – Can be used for a two anodal stimulation situation (see sixth row), where cathodal electrode is placed in the supraorbital area for instance. |
Electrodes might be too close to each other- issue of shunting 19. (Please see second row, fourth column). |
Occipital | Vertex | Interesting active control for chronic pain trials or for modulation of visual cortex. | When used as active control, reference electrodes are placed in different locations- problem of comparability between intra- and inter- experimental approaches. |
Two anodal electrodes, e.g. both Motor cortices | Supra-Orbital | Simultaneous change in cortical excitability | Transcallosal inhibition might add a confounding factor21 |
One electrode over a cortical target, e.g. Primary Motor cortex (M1) | Extra-Cranial | Avoid the confounding effect of two electrodes with opposite polarities in the brain7. | Depending on intended target, current distribution might not be optimal and therefore induce ineffective stimulation22 |
Table 2. Electrode Positioning7
Note: It is possible that the differences between various electrode positions might be the activation of different neuronal populations due to different electrical field orientations.
Critical Steps:
Aspects to be checked prior to starting procedure:
During both- active or sham- tDCS always ask whether subject still feels comfortable and is able to continue procedure.
Possible modifications:
Rationale for using tDCS in chronic pain:
The fact that multiple therapeutic pharmacological modalities provide only modest relief for chronic pain patients raises the possibility that the cause for the persistence of this debilitating disorder may lie within plastic changes in pain related neural networks. Interestingly, modulation of cortical activity can be achieved non-invasively by tDCS, as described earlier, which has been reported to produce lasting therapeutic effects in chronic pain due to changes in cortical plasticity.
Clinical effect of tDCS in chronic pain:
It has been shown that tDCS applied to the motor cortex changes the local cortical excitability (Figure 6)6. More precisely, anodal stimulation results in an increase of neuronal excitability, whereas cathodal stimulation has opposite results6. Indeed, anodal tDCS application over M1 leads to a greater improvement in visual analogue scale (VAS) pain ratings than sham tDCS. This therapeutic effect on pain following M1 stimulation, although transient, was reproduced in several groups of patients with neuropathic pain syndromes like trigeminal neuralgia, poststroke pain syndrome31, back pain and fibromyalgia32. Interestingly, clinical trials in neuropathic pain, due to spinal cord injury, stimulation of the motor cortex by tDCS showed pain improvement and cumulative analgesic effect that lasted two weeks after the stimulation. There is also evidence of its analgesic effect in fibromyalgia patients33 that is still significant after three weeks of follow-up for anodal tDCS of the M1 compared with sham stimulation, and as well as stimulation of the DLPFC33. Although the effects of anodal tDCS over DLFPC for pain improvement have not been explored extensively, it was shown it can be used to modulate pain thresholds in healthy subjects34. Nevertheless, stimulation of this brain area is a reliable technique for enhancing working memory 10, increasing performance on memory tasks in Alzheimer disease9 and reducing cue-provoked smoking craving significantly35 for instance; therefore it is also conceivable that this might be a useful strategy to modulate affective-emotional cognitive networks associated with pain processing in patients with chronic pain.
The authors have nothing to disclose.
DaSilva AF received funding support from CTSA high-tech funding grant, University of Michigan to complete this review. Volz MS is funded by a grant scholarship from Stiftung Charité.