Transcranial direct-current stimulation

Transcranial direct current stimulation (tDCS) is a form of neurostimulation which uses constant, low current delivered directly to the brain area of interest via small electrodes. tDCS was originally developed to help patients with brain injuries such as strokes. Tests on healthy adults demonstrated that tDCS can increase cognitive performance on a variety of tasks, depending on the area of the brain being stimulated. tDCS has been utilized to enhance language and mathematical ability, attention span, problem solving, memory, and coordination.

Discovery
The basic design of tDCS, using direct current (DC) to stimulate the area of interest, has been around for over 100 years. There were a number of rudimentary experiments completed before the 19th century using this technique that tested animal and human electricity. Luigi Galvani and Alessandro Volta were two such researchers that utilized the technology of tDCS in their explorations of the source of animal cell electricity. It was due to these initial studies that tDCS was first brought into the clinical scene. In 1804, Aldini started a study in which he used the technique of direct current stimulation and was successful in improving the mood of melancholy patients.

Transition into modern scientific research
There was a brief rise of interest in transcranial direct current stimulation in the 1960s when studies by the researcher Albert proved that the stimulation could affect brain function by changing the cortical excitability. He also discovered that positive and negative stimulation had different effects on the cortical excitability. Although these findings were important in the use of tDCS in therapy, research in this area was again dropped as drug therapy proved to be a more profitable method of therapy.

It wasn’t until recently that interest in tDCS was reignited. This time, the rediscovery was fueled by an increase of interest and understanding of basic brain functioning, therapeutic application, as well as new brain stimulation and brain imaging techniques such as TMS and fMRI. Now, Transcranial direct current stimulation is beginning to be used more frequently as a brain stimulation technique because safety protocol has shown that tDCS is extremely safe for human use.

Operation
Transcranial direct current stimulation works by sending constant, low direct current through the electrodes. When these electrodes are placed in the region of interest, the current induces intracerebral current flow. This current flow then either increases or decreases the neuronal excitability in the specific area being stimulated based on which type of stimulation is being used. This change of neuronal excitability leads to alteration of brain function, which can be used in various therapies as well as to provide more information about the functioning of the human brain.

Parts
Transcranial direct current stimulation is a relatively simple technique and traditional devices contain only a few parts. These include two electrodes and a battery powered device that delivers constant current. Control software can also be used in experiments that require multiple sessions with differing stimulation types such that neither the person receiving the stimulation nor the person administering the stimulation knows which type is currently being administered. Each device has an anodal electrode and a cathodal electrode. The anodal electrode is the positively charged electrode and the cathodal electrode is the negatively charged electrode. The conventional current flows from the anode through the skull and brain to the cathode, creating a circuit. The device that delivers the current has controls that set the current as well as the duration of stimulation.

In modern devices such as the ones used for MtCS, multiple electrodes can be used, and their individual currents controlled. Such devices use small, EEG-like gelled electrodes (unlike traditional devices, which use large, sponge electrodes soaked in saline).

Set up
To set up the tDCS device, the electrodes and the skin need to be prepared. This ensures a strong connection between the skin and the electrode. The careful placement of the electrodes is crucial to successful tDCS technique. The electrode pads come in various sizes with benefits to each size. A smaller sized electrode achieves a more focused stimulation of a site while a larger electrode ensures that the entirety of the region of interest is being stimulated. If the electrode is placed incorrectly, a different site or more sites than intended may be stimulated resulting in faulty results. One of the electrodes is placed over the region of interest and the other electrode, the reference electrode, is placed in another location in order to complete the circuit. This reference electrode is usually placed on the neck or shoulder of the opposite side of the body than the region of interest. Since the region of interest may be small, it is often useful to locate this region before placing the electrode by using a brain imaging technique such as fMRI or PET. Once the electrodes are placed correctly, the stimulation can be started. Many devices have a built-in capability that allows the current to be "ramped up" or increased gradually until the necessary current is reached. This decreases the amount of stimulation effects felt by the person receiving the tDCS. After the stimulation has been started, the current will continue for the amount of time set on the device and then will automatically be shut off. Recently a new approach has been introduced where instead of using two large pads, multiple (more than two) smaller sized gel electrodes are used to target specific cortical structures. This new approach is called High Definition tDCS (HD-tDCS). In a pilot study, HD-tDCS was found to have greater and longer lasting motor cortex excitability changes than sponge tDCS.

Another new technique is Multichannel or Multifocal transcranial current stimulation (MtCS) in which multiple, individually controlled electrodes are used to target multiple cortical regions simultaneously using tDCS, tACS or tRNS. The idea is to use advanced modeling tools such as the ones described in (Miranda et al., 2013) to simulate the resulting electric fields in the brain and, based on this, optimize montage locations and currents. See for a tutorial on how to use such devices for stimulation and EEG recording.

Types of stimulation
There are three different types of stimulation: anodal, cathodal, and sham. The anodal stimulation is positive (V+) stimulation that increases the neuronal excitability of the area being stimulated. Cathodal (V-) stimulation decreases the neuronal excitability of the area being stimulated. Cathodal stimulation can treat psychological disorders that are caused by the hyper-activity of an area of the brain. Sham stimulation is used as a control in experiments. Sham stimulation emits a brief current but then remains off for the remainder of the stimulation time. With sham stimulation, the person receiving the tDCS does not know that they are not receiving prolonged stimulation. By comparing the results in subjects exposed to sham stimulation with the results of subjects exposed to anodal or cathodal stimulation, researchers can see how much of an effect is caused by the current stimulation, rather than by the placebo effect.

Effects on brain
One of the most important aspects of tDCS is its ability to achieve cortical changes even after the stimulation is ended. The duration of this change depends on the length of stimulation as well as the intensity of stimulation. The effects of stimulation increase as the duration of stimulation increases or the strength of the current increases. The way that the stimulation changes brain function is either by causing the neuron’s resting membrane potential to depolarize or hyperpolarize. When positive stimulation (anodal tDCS) is delivered, the current causes a depolarization of the resting membrane potential, which increases neuronal excitability and allows for more spontaneous cell firing. When negative stimulation (cathodal tDCS) is delivered, the current causes a hyperpolarization of the resting membrane potential. This decreases neuron excitability due to the decreased spontaneous cell firing.

Neuroplasticity refers to the ability of the brain to change throughout life based on experiences. The way that transcranial direct current stimulation functions could be due to the plasticity concepts of long term potentiation (LTP) and long term depression (LTD) since the two share some basic similarities. Long term potentiation is the strengthening between two neurons while long term depression is the weakening between two neurons. These effects are achieved mainly through an alteration of synaptic transmission ability. LTP enhances transmission and LTD hinders transmission. Likewise, tDCS stimulation involves the alteration of synaptic transmission ability through modifications of intracellular cAMP and calcium levels. Also, both LTP, LTD, and the effects of tDCS are protein synthesis dependent. It is for these reasons that LTP and LTD are proposed mechanisms of the function of tDCS.

TMS
Transcranial direct current stimulation is a relatively unconventional method of stimulating the brain. While this method is gaining interest, the most commonly used method of brain stimulation is transcranial magnetic stimulation (TMS). This technique of brain stimulation utilizes an electric coil held above the region of interest on the scalp that uses rapidly changing magnetic fields to induce small electrical currents in the brain. There are two types of TMS: repetitive TMS and single pulse TMS. Both are used in research therapy but effects lasting longer than the stimulation period are only observed in repetitive TMS. Similar to tDCS, an increase or decrease in neuronal activity can be achieved using this technique, but the method of how this is induced is very different. Transcranial direct current stimulation has the two different directions of current that cause the different effects. Increased neuronal activity is induced in repetitive TMS by using a higher frequency and decreased neuronal activity is induced by using a lower frequency.

Both TMS and tDCS are painless and considered safe for human use. However TMS is more expensive, difficult to sham, and may need a trained coil holder while tDCS is relatively easy to apply. Transcranial magnetic stimulation causes the neuron’s action potentials to fire, resulting in a stronger effect. Since tDCS only causes increased spontaneous cell firing, it does not have as big as an effect. One benefit of tDCS when compared to TMS is that due to the smaller effect, there is a much smaller chance of causing seizures in the person receiving the stimulation.

Other types of stimulation
Variants related to tDCS in include tACS and tRNS, a group of technologies commonly referred to as tCS. One other technique of electrical stimulation that has been used is called transcranial electrical stimulation, or TES. TES also functions by inducing neuronal change via electrical currents. TES, unlike tDCS, causes the resting neurons to fire and can be painful to the person receiving the stimulation, so this method is no longer frequently used.

Safety
When applied following established safety protocols, transcranial direct current stimulation is widely regarded as a safe method of brain stimulation, causing no apparent short-term harm. Safety protocols limit the current, duration, and frequency of stimulation, thereby limiting the effects and risk.

Safety protocol
There has been much work done in the last 10 years to develop a safety protocol for administering transcranial direct current stimulation. Many studies have been conducted to determine the optimal time of stimulation and current used as well as steps to take in order to reduce or eliminate the side effects felt by the person receiving the stimulation. These standards are still not entirely set and continue to expand as more research is done. Currently, the accepted maximum current for human use is 2 mA and usually 1 mA or less is used. The device itself has a maximum current setting that while above what is suggested to use, it is still within a range in which no harm is done to the person receiving the stimulation.

Studies have been completed to determine the current density at which overt brain damage occurs in rats. It was found that in cathodal stimulation, a current density of 142.9 A/m2 delivering a charge density of 52400 C/m2 or higher caused a brain lesion in the rat. This is over two orders of magnitude from what is currently being used.

There is no strict limitation on the duration of stimulation set at this point but a stimulation time of 20 minutes is considered the ideal time. The longer the stimulation duration, the longer the observed effects of the stimulation persist once the stimulation has ended. A stimulation length of 10 minutes results in observed effects lasting for up to an hour.

It is generally encouraged to wait at least 48 hours to a week before repeating the stimulation. Also, it is advised to warn the person receiving the stimulation of the possible after effects of the tDCS stimulation.

Side effects of stimulation
There are a few minor side effects that can be felt by the person while receiving the stimulation, and most of these can be controlled by correct set up of the device. These side effects include skin irritation, a phosphene at the start of stimulation, nausea, headache, dizziness, and itching under the electrode. Nausea most commonly occurs when the electrodes are placed above the mastoid, which are used for stimulation of the vestibular system. A phosphene is a brief flash of light and this effect can occur if an electrode is placed near to the eye. A recent study of over 500 subjects using the currently accepted protocol reported only a slight skin irritation and a phosphene as side effects.

There are several ways to reduce the skin irritation felt during stimulation. One of the most important methods of preventing skin irritation is by preparing the electrodes with saline solution and the skin with electrode cream thoroughly. Also, ramping up the current can reduce the irritation. This is done by slowly increasing the current until the desired current is reached.

Risks
There are no known risks of tDCS at this time, but since this technique of stimulation is still being explored, safety precautions should be observed. The set protocols must be followed to ensure correct use of the device. Also, it is not advised to administer this stimulation to people susceptible to seizures, such as people with epilepsy. Although seizures do not seem to be a risk for healthy individuals, those with a tendency towards seizures may react differently. As more is discovered about the use of tDCS, the safety standards may change, making it important to remain familiar with the most currently updated safety protocol.

Clinical
Clinical therapy using tDCS may be the most promising application of this technique. There have been therapeutic effects shown in clinical trials involving Parkinson's disease, tinnitus, fibromyalgia, and post-stroke motor deficits. In a recent study, stroke patients with speech difficulties displayed great improvement through a tDCS based therapy, with the improvement lasting past the one week retest. Stimulation therapy could also be developed into effective therapy for various psychiatric disorders such as depression,    anxiety disorders, and schizophrenia. Some researchers are investigating potential applications such as the improvement of focus and concentration.

Psychological
The majority of psychological studies involving tDCS focus on the expansion of knowledge about a certain region of the brain or a certain psychological phenomenon. For example, much work is done on the ability and specifics of working memory. Many of these studies stimulate a particular region of the brain and then observe the effects of the stimulation in some type of cognitive task.