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Ever since the physician Scribonius Largus slapped an electric torpedo fish on the forehead of a headache sufferer in the early days of the Roman empire, electricity has been pursued as a cure for a seemingly endless variety of ailments–by serious scientists and profiteering quacks alike. The latest chapter in this long and colorful history (see sidebar below) involves something called transcranial direct current stimulation, in which a small electric current is delivered to the brain through electrodes placed on the head.
In the last few years this method of electrical brain stimulation has caught the attention of scientists at some of the world's leading universities. They think it has potential for treating disorders like depression and chronic pain, helping people recover faster from strokes, and even enhancing learning, memory, and creativity in healthy people. And, as I write in this month's print issue of WIRED, this research–and the largely enthusiastic media coverage it's inspired–has convinced a small, but growing community of ordinary people to try zapping their own brains in hopes of boosting their brainpower and enhancing their psychological wellbeing.
Many researchers trace the current wave of interest in brain stimulation to a study published in 2000 by two German scientists, Michael Nitsche and Walter Paulus. At the time, Nitsche says, they were looking for ways to regulate the excitability of neurons in specific brain regions to help people with epilepsy and other disorders. During their search, Nitsche came across some older studies on direct current stimulation, and they decided to give it a try.
The results were encouraging. Depending on the set up, a small current delivered via two saline-soaked sponges could either enhance or dampen activity in particular parts of the brain for several minutes, Nitsche and Paulus reported in what's become a landmark paper for research on transcranial direct current stimulation (tDCS).
The experiments were done with healthy volunteers, and Nitsche and Paulus were cautious in their interpretation. More work would be needed to figure out how tDCS works and whether its effects would last long enough to be useful as a treatment, they wrote. Nitsche, who has a reputation as a careful and methodical scientist, has focused his efforts since then on understanding exactly what tDCS does to the brain. Meanwhile, other researchers focused their efforts on investigating its potential to boost cognition and treat brain disorders.
It's not hard to understand why. "We spend, together, about a third of a trillion dollars a year on pharmaceuticals," said Vincent Clark a neuroscientist at the University of New Mexico, speaking at a conference on tDCS hosted by the University of California, Davis in September. Pharmaceutical companies spend about $5 billion to develop a single new drug and bring it to market, Clark said, and yet many people aren't well served by the drugs that are available. (He might have added that the staggering costs and difficulty of developing new drugs for brain disorders has prompted several major pharmaceutical companies to cut their neuroscience R&D programs in recent years).
A shocking history
Electricity has been a colorful recurring character in the history of medicine. In the first century AD, the Roman physician Scribonius Largus applied electric torpedo fish to patients’ bodies to treat headaches, gout and even hemorrhoids. In the 1700s, Italian physicist and physician Luigi Galvani argued that "animal electricity" was the animating life force, and in a sense he was right: Our muscles and nerves depend on the flow of electrically charged ions. But his work also inspired macabre attempts to reanimate the recently deceased with electric shocks – a likely inspiration for Mary Shelly's Frankenstein.
Jump ahead to the early 20th century, and the spread of electric power in America renewed popular interest in bodily betterment through electricity. Electrified belts, with attachments for the nether regions, promised to renew masculine vigor and sold by the hundreds of thousands. So too did the Elec-Treat Mechanical Heart, a handheld stimulator that promised to cure everything from neuralgia to pleurisy before its inventor became the first person prosecuted by the US government for making bogus medical claims in 1938.
The electrotherapy that lurks most ominously in our collective memory, however, is electroconvulsive therapy, and in particular its brutal portrayal in the 1975 film One Flew Over the Cuckoo's Nest. ECT pumps so much electricity into the brain that neurons can't stop firing. It causes seizures. Although it can be, and is, used humanely to reboot the brain of someone in the grip of severe depression, the stigma has been hard to shake. Advocates of tDCS like to point out that the 1 to 2 milliamps of current involved is about a thousand times less than what's used in ECT, and less than what's needed to light a typical LED.
"We need other solutions," Clark said.
And for a growing number of researchers, this type of brain stimulation looks like an interesting alternative. Several teams are investigating tDCS in combination with traditional rehabilitation to help stroke patients recover speech and movement faster. The idea is that the electric therapy may make the brain more plastic and better able to compensate for damaged connections.
A group at Harvard has found promise for treating depression and chronic pain. In a study published last year with Brazilian collaborators, for example, they found that tDCS was as effective as a common antidepressant drug, sertaline (Zoloft), at reducing symptoms of depression. Combining brain stimulation with the drug was more effective than either one alone. Other researchers are looking into using it to reduce the irritating ringing perceived by people with tinnitus or curb food cravings in people with certain eating disorders. Hundreds of studies have been published, and scores of clinical trials are underway or in the works.
And it's not just people with medical problems who may stand to benefit. The military has investigated using tDCS to accelerate training for of fighter jet pilots and intelligence analysts. Researchers at Oxford have claimed it can make people better at learning math. Australian researchers say it can foster creative insight.
The list goes on and on. Remarkably, no serious side effects have been reported (although at least one study has suggested that benefits in one type of cognitive performance may come at the cost of another).
The symposium at UC Davis was attended by many researchers who think tDCS has a lot of potential. But it wasn't hard to detect some cautionary undertones.
Marom Bikson is a biomedical engineer at the City College of New York whose lab has been using computer models and slices of rat brains to investigate the physiological mechanisms of tDCS. Bikson is very enthusiastic about the therapeutic potential of brain stimulation, but his talk in Davis highlighted some significant unknowns about the physiological mechanisms.
The one or two milliamps of current typically used in tDCS isn't enough to make neurons fire. Instead, it seems to put them in an altered physiological state that makes them more or less likely to fire (depending on how the current flows) and more or less prone to rewire their connections with one another.
How that would cause therapeutic effects in the brain isn't exactly clear.
The way it’s often described in the scientific as well as the DIY community, is that the desirable effects from tDCS come from putting a positive electrode over some part of the brain you want to stimulate and perhaps a negative electrode over some part that you want to inhibit. But that's far too simplistic, Bikson said.
For one thing, cognitive functions like memory or math don't map neatly onto individual brain regions. For another, his modeling suggests that the amount of current flowing to a given part of the brain depends critically on the geometry of the whole set up. That means that the exact position of the electrodes and even variations in the bumps and grooves on the surface of the brain can make a big difference in how much current goes where.
His lab has developed a method called HD tDCS that uses four or more electrodes and computer models of current flow to tailor the stimulation far more precisely than what's possible with the two electrodes typically used in research studies (and virtually all DIY projects). Bikson has started a company, Soterix, to develop this technology.
A stronger dose of caution came from Vincent Walsh, a cognitive neuroscientist at University College London. Walsh did something I'd never seen in 12 years of attending scientific conferences as a journalist: He started his talk by pointing out the flaws in a study from his own lab, a 2010 study that suggested tDCS could improve mathematical learning. Walsh argued that other research studies have suffered from similar problems, ranging from inadequate control experiments, to guesswork about which parts of the brain were being excited and inhibited, to unanswered questions about whether the modest effects reported in most lab studies have any real-world relevance.
At one point he threw up a partial list of almost 20 conditions and cognitive skills that have been improved by tDCS according to published studies – everything from migraines to moral decision making.
"Something's got to give," he said. "It cannot all be true."
Walsh may have overstated his case a bit for dramatic effect, but he's making good points, Bikson told me at the reception after the symposium. The field needs to mature and move toward bigger, more carefully controlled studies, he said. Michael Nitsche stood nearby, nodding his head in agreement. "We have lots of pilot studies suggesting it could be useful for many diseases, but whether this translates to clinical reality is difficult to say," Nitsche said. "What we need now is a new phase of studies that aim to optimize the stimulation and produce strong, long-lasting effects."
As an example of where the field should be headed, Bikson points to a randomized controlled clinical trial underway in Brazil. He is collaborating with Andre Brunoni of the University of São Paulo, who will enroll 240 patients with depression. The study will compare tDCS head to head against Escitalopram (Lexapro) to see if tDCS is more effective and has fewer side effects then drug treatment. It may be the largest test yet for tDCS in a clinical population.
Just as the scientists are taking stock of what they do and don't know about tDCS and refining their experiments, the DIY community seems to be enthusiastically forging ahead. Driven by frustration with pills that don't adequately manage their depression or chronic pain, or by the desire to be sharper and more focused, ordinary people taking the science out of the lab and into their lives.
They're able to do it, in part, because the scientific literature is becoming more accessible than ever, and online forums like blogs and reddit are providing new ways for likeminded people to find each other and share information. It helps that a tDCS device is relatively cheap and easy to purchase or assemble.
The DIY movement makes some scientists uneasy.
"You could absolutely hurt yourself with this," Bikson said. People might crank up the current, for example, based on the notion that if 2 milliamps is good, 20 must be great (wrong!). Some self-experimenters are already playing around with current that alternates or randomly fluctuates between positive and negative. That's like popping a pill when you don't know what it is, Bikson says: "Changing the current or waveform is the same as changing the chemical composition of a drug—it's just not the same thing anymore.”
University labs and clinical trials have safeguards in place to protect people, he points out. Experiments are subject to ethical review. Outside the lab, there’s none of that.
Of course he and his colleagues want ordinary people to benefit from their work. And they're reluctant to tell people what they should or shouldn't do to their own bodies and minds. But they also believe they should have a role in the process.
Instead, the citizens are seizing the science for themselves–whether it's ready or not.
