Oct 27, 2022
Science
Transcranial Direct Current Stimulation of the Brain
A slightly edited excerpt from Are Electromagnetic Fields Making Me Ill? by Brad Roth
On the November 13, 2020 episode of the reality television show Shark Tank (Season 12, Episode 5), two earnest entrepreneurs, Ken and Allyson Davidov, try to persuade five hard-nosed investors, the “sharks,” to buy into their company. Ken and Allyson sell LIFTiD, a device that applies a weak, steady electrical current to the head. Ken said it’s supposed to improve “productivity, focus, and performance.” Allyson claimed it’s a “smarter way to get a… boost of energy.” Ken called it “the coffee of the future.”
Each shark tried out the apparatus, which required attaching two saline-soaked electrodes to their forehead. When turned on, there were many oohs and aahs. Shark Mark Cuban exclaimed “I feel like I’m being shocked,” shark Kevin O’Leary declared “I feel it in my upper teeth,” and shark Lori Greiner said it was “freaking me out.” Ken explained that LIFTiD is an emerging technology based on transcranial direct current stimulation. He claimed it works by neuroplasticity (changing the electrical structure of the brain) and is backed by 5000 published studies. According to Ken, LIFTiD stimulates the frontal lobe of the brain, and should be applied for 20 minutes a day while doing some activity such as reading a book, studying for an exam, or playing a video game. Ken and Allyson offered the sharks 10% of their company if they would invest $200,000.
Transcranial direct current stimulation (often referred to as tDCS) has been proposed as a treatment for recovery from stroke, for mental illness, and for cognitive enhancement (making you smarter). The goal of many early studies of tDCS was to treat psychiatric disorders such as depression. Investigators claimed that anodal stimulation (using an electrode with a positive voltage) reduced depression, while cathodal stimulation (using a negative voltage) diminished mania. The response to 10 minutes of transcranial direct current stimulation generally lasted for an hour after the current was turned off. The voltage across a cell membrane typically decays in a few thousandths of a second, so tDCS must do more than merely vary the membrane voltage. Instead, longer-lasting changes in the brain structure (plasticity) are required.
Is transcranial direct current stimulation safe? Michael Nitsche and an international team of neurologists have examined tDCS and identified several potential safety hazards (Brain Stimulation, Volume 1, Pages 206–223, 2008).
1. Reactions at the electrode surface can create toxins, but these chemicals are released onto the skin, not into the brain. In addition, usually a saline-soaked sponge is placed between the electrode and the scalp, so the body is not in contact with the toxins at all.
2. In theory, tDCS could excite neurons deep in the brain that control breathing or the heartbeat, but in practice this does not happen.
3. Any metallic object — for example, a metal clip implanted during a previous brain surgery — could distort the electric field produced during tDCS, and patients with such implants should not undergo the procedure.
4. Any electric stimulation could potentially trigger a seizure, so patients with epilepsy should avoid brain stimulation. Fortunately, seizures have not been observed in healthy people.
Despite these possible risks, thousands of patients have undergone tDCS with only a few minor side effects, such as a headache. The technique is considered safe. The risks are low enough, and the technology is simple enough, that do-it-yourselfers have begun building home-made tDCS devices.
Typically, tDCS uses a current of about 1 milliamp. This current comes out of the anode and goes into the cathode. When one milliamp of current is applied through tDCS electrodes, the voltage difference between the cathode and anode is about 9 volts. Therefore, undergoing tDCS is similar to pressing the leads of a nine-volt battery against your head.
How strong of an electric field does transcranial direct current stimulation produce in the brain? To answer this question, Pedro Miranda, a physicist at the University of Lisbon, and his colleagues created a mathematical model (NeuroImage, Volume 70, Pages 48–58, 2013). A realistically-shaped head was divided into five regions: the brain (with its two types of tissue: white matter and grey matter), the cerebrospinal fluid surrounding the brain, the skull, and the scalp. They adopted the finite element method to solve the equation governing the electric field. This method is a computational technique that divides the head into two million volume elements, each having the shape of a tetrahedron (a triangular pyramid). The solution of the equation in each element is simple, but all the elements need to be pieced together, which is a gigantic calculation. The computations took a couple hours, but when complete they provided the electric field distribution in exquisite detail.
When one milliamp of current is applied through a scalp electrode, the largest electric field in the brain was calculated to be less than 0.5 V/m. The threshold for excitation of a neuron in the brain is about 10 V/m. This means transcranial direct current stimulation produces a voltage across the cell membrane with a strength about one twentieth of that needed to excite a neuron. Electric fields in the brain as weak as about 0.1 V/m could, under ideal conditions, modify the rate of spontaneous neural activity (Journal of Neuroscience, Volume 23, Pages 7255–7261, 2003). Something similar to this must be occurring if tDCS is truly affecting the brain.
In 2009, I wrote an editorial in the journal Clinical Neurophysiology about another of Miranda’s articles (Volume 120, Pages 1037–1038). The editorial identified the smallness of the electric field as an unresolved problem when trying to interpret tDCS experiments. I concluded that “Miranda et al.’s impressive calculations provide valuable insight into the electric field distribution induced during transcranial direct current stimulation. This same kind of meticulous modeling is required to determine how the neuron responds to the electric field.” This conclusion remains true today.
One vexing topic in tDCS is the placebo, which is crucial for a clinical trial. If a medication is being tested, the placebo is a sugar pill with the same size, shape, color, and taste as that of the drug. A placebo for transcranial direct current stimulation is difficult to design, because the electric field it produces in the brain is about a hundred times smaller than the electric field in the scalp. Most of the current follows the path of least resistance, which is through the skin and highly conducting scalp (that is, transcutaneous) rather than through the poorly conducting skull (transcranial). The relatively strong electric field in the scalp (often greater than 10 V/m) can excite pain receptors, peripheral nerves, and skeletal muscle. The titillation and annoyance resulting from stimulation of the scalp is presumably what caused the investors on Shark Tank to react with oohs and aahs when they tried out LIFTiD.
Luuk van Boekholdt, a graduate student at the Katholieke Universiteit Leuven in Belgium, and his coworkers analyzed this issue (Molecular Psychiatry, Volume 26, Pages 456–461, 2021). They noted that the usual sham (placebo) stimulation occurs by attaching the electrodes to the scalp and going through the same procedure as the patients receiving real stimulation, except the stimulus current is not turned on. That eliminates the weak electric field in the brain, which is presumably causing the clinical response, but also eliminates the titillation and annoyance caused by the stronger electric field in the scalp. Van Boekholdt postulates that two mechanisms exist that may be responsible for any tDCS clinical outcome: transcranial excitation of the brain and transcutaneous excitation of the scalp. Scalp stimulation could trigger behaviors, such as arousal and vigilance, that might be responsible for clinical outcomes such as treatment of depression or improvement in memory.
Van Boekholdt et al. suggest alternative sham experiments that investigators could take advantage of during tDCS to improve their research. They propose applying an anesthetic cream to the scalp to deaden any perception of scalp stimulation (the cream would need to be applied to patients receiving either real or pretend stimulation). Another control could be putting the electrodes on some other part of the body, rather than the head. For instance, electrodes on the abdomen would provide a transcutaneous sensation, but would not produce an electric field in the head. This might be effective if patients are not aware that tDCS is supposed to work by stimulating the brain. All these placebos have their own drawbacks. Designing the ideal placebo is the Achilles heel of clinical trials using electrical stimulation.
Ken and Allyson Davidov might have a difficult time marketing LIFTiD if it turns out that the mechanism has nothing to do with exciting the brain. As shark Mark Cuban said as he rejected their pitch for investment, Ken and Allyson “tried to sell science without using science.” His conclusion might be more prescient than he realized. The science behind transcranial direct current stimulation is unclear. There are enough positive studies that we cannot reject it out of hand, but there are enough questions that we cannot accept it as an established therapy.
