Testing tDCS against dementia
(Image: Marc Asnin/New Scientist)
LINDA BUSTEED sits nervously as two electrodes wrapped in large, wet sponges are strapped to her head. One electrode grazes the hairline above her left eye while the other sits squarely on her right eyebrow. Wires snake over her head to a small power pack fuelled by a 9-volt battery. Busteed drums her fingers on the table as she anticipates the moment when an electric current will start flowing through her brain.
It sounds like quackery, but it's not. A growing body of evidence suggests that passing a small electric current through your head can have a profound effect on the way your brain works. Called transcranial direct current stimulation (tDCS), the technique has already been shown to boost verbal and motor skills and to improve learning and memory in healthy people - making fully-functioning brains work even better. It is also showing promise as a therapy to cure migraine and speed recovery after a stroke, and may extract more from the withering brains of people with dementia. Some researchers think the technique will eventually yield a commercial device that healthy people could use to boost their brain function at the flick of a switch.
“You could use this to boost your brainpower at the flick of a switch”
Busteed isn't here to test commercial devices, however. The 64-year-old suffers from the degenerative brain disease frontotemporal dementia, which leads to language loss, personality changes and mood swings. There is no treatment.
Busteed is one of 20 patients in a phase II clinical trial led by Eric Wassermann, head of the brain stimulation unit at the US National Institute of Neurological Disorders and Stroke (NINDS) in Bethesda, Maryland. He wants to know whether a 40-minute burst of direct current directed at her left frontal lobe can improve her ability to generate lists of words, a hallmark deficit of her disease. Wassermann's study is double-blind, so he won't know whether Busteed is receiving current or not. Busteed probably won't know either - tDCS is silent and elicits barely a tingle. If she is getting the real thing, Wassermann hopes that the current will "squeeze more out of the sick neurons", enabling Busteed to perform better.
If the trial proves successful, Wassermann would like to develop a brain stimulation device that patients can take home and use whenever they want. He envisages a gizmo about the size of an MP3 player, perhaps incorporated into a hat. "Turn it on and you feel better," he says. "Turn it off and you're back where you started." It sounds too simple to be feasible, but studies from around the world suggest that Wassermann has a good chance of success. "All the scientific literature points in the same direction," says neurologist Leonardo Cohen, chief of the stroke and neurorehabilitation clinic at NINDS. "There must be something to it."
Zapping the brain with electricity to cure various maladies has slipped in and out of vogue over the past two millennia (see "Zaps from the past"). In recent years, however, it has fallen out of favour, superseded by a more powerful non-invasive technique called transcranial magnetic stimulation. TMS works by penetrating the skull not with electricity but with a magnetic field, causing all the neurons in a particular region to fire in concert. After TMS stimulation stops, depending on the frequency of magnetic pulses, this can have the effect of either switching that region on, or turning it off.
TMS has proved exceptionally useful for mapping brain functions and has also been tested as a therapy, but it can be unpredictable and dangerous. Neurons in the brain normally fire asynchronously as they communicate, but TMS can produce a massive synchrony of activity that can propagate through the cortex like a Mexican wave through a stadium. If this happens brain activity shuts down momentarily and causes seizures. Despite an established safety margin for TMS, there is always a remote possibility of triggering a seizure, which means that any treatments have to be monitored by a physician. The bulky nature of the device also makes it difficult to use outside a hospital.
The rediscovery of electrical stimulation began in 1999, when neurologists Walter Paulus and Michael Nitsche of the University of Göttingen in Germany attended a conference at which they heard about an experimental technique combining TMS with direct current stimulation. They went back to their lab intending to try it for themselves, starting with electricity alone. Those first results were "so amazing and encouraging", says Paulus, that they wanted to know more.
In that first experiment, Paulus and Nitsche took a group of healthy volunteers and stimulated their motor cortices with direct current. They found that tDCS increased the neuronal firing rate by up to 40 per cent. Where the effect differed from TMS was that it only affected neurons that were already active - it didn't cause resting neurons to start firing. They also discovered that if they applied tDCS for 3 minutes or more, the effect lingered after the current was switched off, sometimes lasting for several hours. The experiment suggested that tDCS was safe, painless and non-invasive and that the effects on neuronal excitability could potentially have a profound, if temporary, effect on brain function.
Wassermann was intrigued by the impact of tDCS on healthy brains and began laying the groundwork for his own trials. In the past five years, he, the Göttingen team and others have been testing the potential of tDCS, primarily for the brains of healthy volunteers but increasingly as a therapy too.
Administering tDCS is relatively easy. It is essentially a matter of strapping two electrodes to your head, positioning them, adjusting the current to between 1 and 2 milliamps and choosing the right duration.
The current is very weak and most people feel nothing, except in some cases a "slight tingle or itch", says Wassermann. The human head is a poor conductor, he adds, estimating that at least 50 per cent of the current is lost, shunted across the skin as it follows the path of least resistance to the other electrode. But measurements of neural activity prove that some current does pass through the brain.
What exactly is happening is unknown, but experiments with humans and animals, as well as recordings from individual neurons, suggest that it can either increase the activity of neurons that are already firing, or damp it down, depending on the direction of the current and how the neurons are aligned.
Neurons in the cerebral cortex tend to be arranged with their information-gathering dendrites pointing outwards, towards the scalp, and their information-transmitting axons projecting inwards. When the positively charged tDCS electrode is close to the dendrites, the current causes active neurons to fire more frequently. The negative electrode does the opposite. So if you know the region of the cortex you want to target, you can zap it with one of the electrodes to either stimulate it or inhibit it. Of course, the area under the second electrode is experiencing the opposite effect. "This bothers me to no end," admits Wassermann. But he says that if you place the second electrode just above an eye, it is distanced from the brain by bone and sinus.
The overall effect of tDCS, says Cohen, is to make the excited area work more effectively. "It's like giving a small cup of coffee to a relatively focal part of your brain - the one that you know will be engaged in the performance of certain tasks," he says. "The one you need to do the task better."
So far so good, but does this trickle of charge have any effect on cognitive performance? In 2003, Paulus's team produced evidence that it does (Journal of Cognitive Neuroscience, vol 15, p 619).
The researchers asked volunteers to press keys in response to instructions on the computer screen. What the volunteers didn't know was that the sequence of keystrokes followed a subtle but predictable pattern. With stimulatory tDCS applied to their primary motor cortices, the volunteers learned the sequence significantly faster than normal. Stimulating different brain areas or applying inhibitory or "sham" tDCS had no effect.
Paulus and colleagues have since gone on to produce more positive results. Plying the left prefrontal cortex with stimulatory tDCS, for example, boosts performance on a different test of learning and memory. They showed volunteers combinations of squares, circles, triangles and diamonds and asked them to guess whether that combination was "sunny" or "rainy". At first the task is baffling, but eventually, by trial and error, volunteers discover hidden rules and start scoring higher than chance. According to the researchers, volunteers who received tDCS stimulation got the gist significantly faster.
It's not just stimulatory tDCS that can give your brain a boost. Last year Andrea Antal, a member of Paulus's team, reported that inhibitory tDCS can work too. She used tDCS to inhibit activity in a region of the visual cortex called V5, which helps perceive movement. The result was improved performance on a visual tracking task in which the subject had to follow a dot on the computer screen that could come from one of four directions.
"At first we were utterly surprised that inhibitory tDCS makes something better - it should be worse," says Antal. However, she says, the task is very complicated and produces a lot of neural activation and noise. Perhaps tDCS improves the signal to noise ratio.
The Göttingen team isn't the only one with success stories. Last year researchers at Beth Israel Deaconess Medical Center in Boston, Massachusetts, showed that working memory, the sort used to memorise facts or lists of words, can be improved with stimulatory tDCS. "It's a bit like increasing the amount of RAM available," says team leader Alvaro Pascual-Leone.
Wassermann himself tested tDCS on the left prefrontal cortex of 103 volunteers and saw a 20 per cent improvement in their ability to generate lists of words beginning with a given letter. A handful of people even noticed the difference. "They didn't say 'I feel like superman', but they did notice that they were performing better," says Wassermann. Taken together, he says, these results suggest that tDCS really can be used to boost brainpower beyond its normal limits.
It is also showing promise as a therapy. Antal is testing inhibitory tDCS for migraine and the associated sensations of flashing lights, strange colours and blurred vision, known as auras. She says that while tDCS does not work for all types of migraine, in many people it reduces pain and stops the auras.
Cohen, meanwhile, has tested the technique on stroke patients. He stresses that he has tried it on less than 40 people so far, and that up to now the results are only proof of principle. Still, from what he has seen he thinks that tDCS in combination with rehab could help some patients regain movements that would help them do things such as eat, turn pages and grasp small objects. "The most important point is that the magnitude of improvements correlates with increases in the excitability of neurons," he says. "This suggests cause and effect."
Overall, it seems that tDCS has real promise, though many questions remain. Key among those is the full range of brain functions that could be enhanced. Wassermann speculates that almost any brain function associated with a specific, localised region of the cerebral cortex is potentially amenable to tDCS. Anything buried deeper in the brain, however, is probably not accessible except via dangerously strong currents.
Independent experts are somewhat divided. "Whether low DC current can produce cognitive effects is an open question but I wouldn't rule it out," says Ralph Hoffman, professor of psychiatry at Yale University. "The physiology is plausible. It doesn't sound nutty." Dominique Durand, director of the neural engineering centre at Case Western Reserve University in Cleveland, Ohio, is less impressed. "I think it is pushing it because this is not selective," he says. "It basically stimulates a large part of the brain."
The biggest unknown, however, is whether tDCS will be more than a flash in the pan. "What we are most concerned about is that it will work a couple of times and then won't work again," says Wassermann. Just as you can become habituated to a strong smell if you are exposed to it for a long time, it is possible that a brain region exposed to a direct current more than once or twice in a short space of time will get used to it. If habituation does occur, says Wassermann, the technique is useless. "If this can't do something for somebody then forget it. It just becomes a funny phenomenon."
Wassermann and other researchers, however, are satisfied that at the very least tDCS is safe. What is more, the device itself is tantalisingly simple and would be cheap and easy to make. "It's comfortable, easy and inexpensive, and it seems to work," says Cohen. Adds Wassermann: "Anyone with the know-how could go to an electronics store, buy the components and build one." If tDCS proves its worth, he is interested in developing a commercial device. He points out that you can already buy headgear that claims to cure insomnia, anxiety and depression by stimulating your brain with alternating current, even though there is scant evidence that it works. Imagine the potential for a brain stimulator that really does the business.
So if the day comes when you can buy a battery-powered thinking cap, what use might it be? One possibility is that it could help you learn new, improved skills. The results with motor learning and visual tracking, for example, might translate into a better tennis game or improved piano playing. "And if you can enhance motor learning with tDCS then it might help you learn something else," agrees Wassermann. It's conceivable that enhanced learning and verbal skills could make it easier to learn a second language or expand your vocabulary, says Cohen. Students might even be able to raise their game by giving themselves a blast of tDCS before class.
Another possibility, says Wassermann, is using tDCS to boost your alertness. Researchers funded by the US military have already expressed interest in developing that side of the technology for pilots (New Scientist, 18 February, p 34). "Fighter pilots land on aircraft carriers at the worst times of night after working long hours," says Wassermann. "Suppose you have this device in your helmet, you could flick it on before landing and get much more alertness."
It sounds too good to be true, and it may turn out to be. But if tDCS lives up to its promise perhaps all you'll need to boost your brainpower is a 9-volt battery, a couple of wires and some pieces of wet sponge. Now there's an electrifying thought.
From issue 2547 of New Scientist magazine, 15 April 2006, page 34
Psychiatry's Shocking New Tools
By Samuel K. Moore
Psychiatrists are beginning to look at an even simpler technology than transcranial magnetic stimulation to fight depression. "It's like hooking the patient up to a car battery," jokes Sachdev. "But with safety features," his colleague Colleen Loo, a senior research fellow, hastily adds. Crude or not, it's a pretty accurate description of an experimental technique called, or tDCS. Basically, it subjects the front half of the brain to a minutes-long 1-mA direct current once a day for several weeks "
TECHNICAL ILLUSTRATION: BRYAN CHRISTIE
: A device drives a small direct current through the front part of a patient's brain. Though the stimulation is done only for minutes a day over a period of weeks, it appears to alter the activity of neurons in the long term.
The simplicity of tDCS makes it sound almost suspicious, and indeed its origins stretch back into the murk of 19th-century quackery. But the principle of how tDCS seems to work in the brain is roughly the same as that of rTMS. They both seek to make neurons in the prefrontal cortex, the decision-making part of the brain, more excitable, that is, more likely to propagate a signal from neuron to neuron. In tDCS's case a small current, delivered via electrodes on the temples, biases brain cells, making them more likely to emit a spike of voltage, says Alvaro Pascual-Leone, associate professor of neurology studying tDCS at Harvard University, in Cambridge, Mass. The effect, studies have shown, lasts long after the current is turned off.
The concept and technology are so simple, in fact, that Pascual-Leone and his colleagues suggested in The British Journal of Psychiatry that tDCS be used in the developing world as a first-line treatment for depression instead of rather expensive antidepressant drugs. But Sachdev thinks this is a terrible idea. "We need to know a lot more about tDCS before it is accepted as an effective treatment and must await the results of many ongoing trials," he wrote in a rebuttal. "In the meantime, depressed patients in the developing world should be dissuaded from unplugging their car batteries and clamping them on their foreheads."
Pascual-Leone says he has results showing tDCS fought treatment-resistant depression as well as rTMS did in experiments done at the University of São Paulo School of Medicine, in Brazil, but at press time the study had not yet been published in a peer-reviewed journal....
The animation shows the activation of a corticospinal axon with transcranial electrical stimulation. The membrane potential is illustrated with colors: hot colors show the action potential. The time span of the animation is 600 microseconds. Stimulus is illustrated with the red and blue color of the electrodes.
The axon is activated directly at a deep bend at a location corresponding to the fiber entering the midbrain. The propagating action potential initiated nearer surface is blocked due collision.
See details in 'Veikko Suihko (1998): Modeling direct activation of corticospinal axons using transcranial electrical stimulation. Electroencephalography and clinical Neurophysiology, 109, 238-244.'
Imagine you have a headache. Or you're too fried to face a busy workload. Rather than taking aspirin or coffee, you put a small device the size of an iPod to the back of your head and push a button to revitalize your brain. Sound futuristic? It may not be many years away.
Scientists have scrutinized the human brain for thousands of years, but with the use of electricity and magnets, medical researchers are getting closer to identifying the areas -- and creating the tools -- that stimulate and repair the mysterious organ.
Eric Wassermann, a neurologist and chief of the Brain Stimulation Unit at the National Institute of Neurological Disorders and Stroke (NINDS), has come closest to creating an inexpensive, painless "thinking cap." The device runs on electrical currents, known as transcranial direct current stimulation. His studies have shown that tDCS can boost verbal skills in healthy people by as much as 20 percent.
In one study, volunteers were asked to recall and say as many words that begin with a particular letter as possible, then passed a tiny (2-milliamp) current through electrodes attached to their foreheads. The volunteers were quizzed again using a different letter with the current on and were able to come up with 20 percent more words. The only side effect so far has been itching or tingling on the scalp.
Wassermann can't pinpoint exactly what is happening, but he thinks tDCS lets the prefrontal cortex, the brain part associated with verbal memory, transmit signals more easily. Any function associated with a specific region of the cerebral cortex (the outer edges of the brain) is potentially within tDCS's reach. The goal is to make the targeted area work more effectively, like giving it a small cup of coffee.
"It doesn't cause neurons to fire on their own -- it needs to have some drive on them to do so," says Wassermann. "It's a little like treating specific nerve cells locally with a drug, so it could be a very helpful way of boosting brain function in people with brain disorders and injuries."
Even though he is focusing on tDCS for more heavy-duty problems like head injuries and dementia, Wassermann does not rule out a thinking cap that any healthy person could use to boost brainpower with the flick of a switch. The device is already simple and easy to make, he says. "Anyone with the know-how could go to an electronics store, buy the components, and build one. It's simply a 9-volt battery, a couple of wires, and some pieces of wet sponge. The question now is, what part of the brain do you stimulate, and how can it actually help you? That's what we're still trying to learn."
Neurologists are also using electricity to try to treat various brain disorders, from Parkinson's disease to headaches. As early as 45 BC, a Roman court physician named Scribonius Largus noted that the application of live torpedo fish, a type of electric ray, to patients' foreheads cured headaches. Greek physician and philosopher Galen noted the same findings a century later.
The modern version of Largus's and Galen's fish involves magnetic pulses in an up-and-coming treatment known as transcranial magnetic stimulation. Techniques are still being refined, but researchers know that by placing a TMS device on different areas of the head, they can make fingers twitch or freeze speech in mid-sentence. Doctors treating depression aim the magnets at the prefrontal cortex, while those treating migraine headaches go toward the nerve centers in the back of the head.
"There's evidence that migraines start with electrical hyperexcitability in the brain's cortex," says Yousef Mohammad, a neurologist at the Ohio State University Medical Center, who has found evidence that a TMS device placed against the back of the head can prevent migraine pain. "Our theory is that if we can break that with two pulses of an electromagnetic field, we can abort a headache before it starts." Mohammad is working with a medical company to research a portable TMS device the size of a hair dryer, and recently launched a bigger study nationwide.
Wassermann has also tested TMS by using himself as a guinea pig. He had a fellow researcher target his brain's speech centers by zapping him while speaking, which stopped him in mid-sentence -- a feeling he calls "indescribable."
So next time you feel frazzled or foggy, think of strapping on a catchy-looking gadget and gently jolting your way to rejuvenation. Now, that's an electrifying thought.
For a more complete roundup of the clinical research into the new device-based therapies, see Brain Stimulation in Psychiatric Treatment, edited by Sarah H. Lisanby, Washington, D.C., American Psychiatric Publishing (2004).
A Neuronetics executive teaches you how to design a transcranial magnetic stimulator in "Designing Transcranial Magnetic Stimulation Systems," by K. Davey and M. Riehl, IEEE Transactions on Magnetics, March 2005, pp. 1142–48.
More details of vagus nerve stimulators are laid out in "Vagus Nerve Stimulation for the Treatment of Depression," by Dorin Panescu, IEEE Engineering in Medicine and Biology Magazine, November–December 2005, pp. 68–72.