Hopeful Currents

One day last September, 40-year-old Jaime Campbell walked into a brain research laboratory at the University of New Mexico in Albuquerque, where a researcher affixed two sponge-covered electrodes to her head. One was positioned above her left eye, over her brain's prefrontal cortex, and the other was set on the side of her head, over her auditory cortex. With the turn of a dial, a steady two milliamps of direct current coursed through the electrodes for 20 minutes.

Campbell was the first subject in a clinical trial testing whether a technique called transcranial direct current stimulation, or tDCS, could quell her auditory hallucinations; as a schizophrenic, she had heard near-constant background noise—like a tea party, with cups and dishes clanging and people chattering—ever since her illness surfaced at age 15. Drugs had never managed to eliminate it. The trial called for her to undergo two such electric stimulation sessions a day for five days. Vincent Clark, a University of New Mexico psychologist and neuroscientist and one of the study's investigators, was astounded by the results.

"One treatment with tDCS and she was better than she could remember ever being in her entire adult life," Clark says. To their amazement, the noise was dramatically reduced.

Clark's excitement is echoed by many at the frontiers of neuroscience—and not just regarding auditory hallucinations. In recent years, a deluge of studies has been initiated to examine the effects of tDCS and other forms of noninvasive electrical brain stimulation on an assortment of ailments. Depression, migraines, anxiety, chronic pain, obsessive-compulsive disorder, addiction, and tinnitus are all conditions that studies have shown might be helped by a controlled delivery of juice to the noggin. At the University of Pennsylvania, work is underway to find out whether such brain stimulation can improve motor and cognitive impairments following a stroke. Researchers at the University of California, Los Angeles are looking at whether it can help women modulate or increase their sexual desire. And it's not just disorders that are under investigation—scientists are also exploring whether electrical stimulation might help optimize the brain function of healthy people, including souping up memory, creativity, and learning ability.

Researchers insist that their optimism is warranted because it relates to emerging findings about neuroplasticity—that is, the brain's ability to change. Nerve cells communicate with each other by sending electrical signals, and the more signaling activity that's exchanged between nerve cells, the stronger the functional connection between them becomes.

The neural networks created as these connections are formed and dissolved over time underlie our most basic brain functions, like mood regulation and memory. And in the past several years, researchers have begun to understand that disruptions in such networks can also explain mental disorders. Noninvasive brain stimulation technologies are thought to boost or dampen activity in specific brain regions, inducing plasticity and nudging neural networks in a beneficial direction.

If so, scientists project that electrical brain stimulation, because of its capacity for precision, will work where pharmaceutical fixes often fail. "These technologies provide ways to go focally into the brain regions we want to manipulate in ways that medications never could," says Mark George, a psychiatrist and researcher at the Medical University of South Carolina and editor-in-chief of the journal Brain Stimulation.

"With drugs, we use chemical messengers to change connectivity," says Felipe Fregni, a neurologist who directs the Laboratory of Neuromodulation at Harvard University Medical School. "Here it's the same, but we use electrical messengers." Yet apart from a few well studied uses, such as treating depression, much remains to be discovered about effectively wielding the therapeutic powers of electricity. With its potential established, the trick now, Fregni says, "is learning how to use it."

Electroshock Redux

Scientists have toyed with the idea of electricity as a therapeutic agent for centuries. In 47 A.D., a court physician in the Roman Empire treated migraines by applying an electric torpedo fish to sufferers' foreheads, and by the late 18th century, electrical contraptions were being devised in an attempt to cure everything from paralysis and toothache to melancholia and hysteria.

Such approaches didn't get very far until the 1930s, when neurologists and psychiatrists developed electroconvulsive therapy—otherwise known as electroshock or ECT—to treat severe cases of mood disorder. ECT delivers a powerful, seizure-inducing jolt of alternating current to the prefrontal cortex of the brain, and although it has been highly controversial because it can have significant side effects, such as memory loss and other cognitive impairments, it is almost universally acknowledged as effective and still used to treat major depression today.

More recently, developments in electrical brain therapy have presented what might be considered kinder, gentler takes on electroconvulsive therapy. Consider transcranial magnetic stimulation, or TMS, which involves holding a magnetic coil above the head to generate an electric current in a region of the brain below. TMS was originally developed in the 1980s to help map neural functions, but researchers using it little more than a decade later began to notice that it enhanced creativity, mathematical ability, and other cognitive skills. They also began to explore its ability to improve mood, prompting clinical trials and, in 2008, approval from the Food and Drug Administration for use in treating clinical depression. The technique works by stimulating the prefrontal cortex, which is underactive in those with the condition. "We think it's restoring a more correct balance to the whole brain network," says Colleen Loo, a clinical and research psychiatrist at the Black Dog Institute in Australia who studies its use with mood disorders.

Subsequent research has shown that TMS may also help alleviate migraines, post-traumatic stress disorder, epilepsy and other conditions. Yet it's hardly perfect: Only a third of severely depressed patients experience remission after TMS therapy, and only 50 percent benefit from it at all. What's more, most psychiatrists don't have access to pricey TMS machines, so people must travel to special locations for the treatment and may have to foot bills of up to $10,000 or more since insurance often doesn't cover it. As a result, the adoption of the technology has been modest.

Some of the drawbacks of TMS may be remedied by tDCS, a relative newcomer in the field. Delivered through a small, portable device that costs just a few hundred dollars, one might think of tDCS as TMS's younger sibling—it's about a decade behind in development and employs a much weaker direct current, equivalent to the strength of a 9-volt battery, and so has a subtler effect. Rather than forcing nerve cells into action, the technique merely nudges their firing potential. "It's more like neural encouragement," says Roy Hamilton, a neurologist at the University of Pennsylvania who studies the effects of both techniques on stroke recovery.

As with TMS, depression has so far been the best studied and most promising use of tDCS, in part because researchers have a good sense of where to direct the stimulation. That uniformity of practice has allowed data to pile up. It seems to help up to half of those with clinical depression for whom drugs have been unsuccessful. But in trials for other conditions—hundreds are underway—protocols have been less consistent and subjects fewer in number. Clark's schizophrenia study, for example, is one of more than a dozen trying to replicate a promising French study from 2012 in which tDCS reduced auditory hallucinations by about 30 percent in 30 people with schizophrenia.

Despite its still experimental status, enthusiasm about tDCS abounds, and wider clinical availability may be on the horizon: Two companies now conducting clinical trials are hoping the FDA will approve the release of medical-grade tDCS devices in the coming year.

Along with tDCS and TMS, another treatment, known as cranial electrotherapy stimulation, or CES, has a growing foothold. Originally called electrosleep and developed in the 1950s to treat insomnia, CES delivers pulses of low-level alternating current through electrodes placed at the temples, at a tiny fraction of the strength of electroconvulsive therapy. Several CES devices received FDA approval in the 1980s and 1990s for the treatment of insomnia, depression, anxiety, and pain. The approach received a boost last year when the FDA withdrew a requirement that it undergo more stringent regulation, and today it is the only electrical brain stimulation device sold directly to consumers.

Charles Fisher is the president of the company that makes the Fisher Wallace Stimulator, one of a small handful of CES devices on the market, and he states that doctors using his product report a positive success rate of about 75 percent. But published studies are limited. A recent trial of the stimulator, financed by Fisher's company and conducted by psychiatrists at Mount Sinai Beth Israel Medical Center in New York, showed solid promise for its effect on bipolar depression, although the study involved only 16 patients. Igor Galynker, the study's primary investigator, says it's tough to parse results from so few subjects, but he believes that the device is effective and now uses it in his practice. "My clinical impression is that there is a subgroup of people who clearly benefit," Galynker says.

On the whole, however, researchers have not embraced CES and caution that it hasn't been tested as rigorously as other techniques. And the fact that users may line it up incorrectly on their heads or ramp the current up and down makes it tough to evaluate in a nonclinical context. "I'm sure it works, but you need to refine the optimal parameters," Fregni says.

Determining how best to use experimental types of electrical brain stimulation begs for more investigation, in part because nearly limitless variables are involved. "For each form, there might be hundreds or thousands or ultimately millions of ways to apply it," Clark says. The size and placement of electrodes, the amplitude and duration of current, to say nothing of combinations of different stimulation techniques—all of this is ripe for testing, he says. "It's as if each one is a slightly different type of medication, and each medication is unique." The only thing to do is to keep going, he adds. "And don't discount anything until you know that it doesn't work."

Power Play

A guide to juicing up the brain

Transcranial Magnetic Stimulation (TMS)

TMS uses electromagnetic pulses delivered through a metal coil positioned over the scalp to generate localized current in the brain area below. This current is strong enough to cause nerve cells in the region to fire; when the coil is placed over the motor cortex, recipients see one of their thumbs twitch.

Transcranial Direct Current Stimulation (tDCS)

The fastest-growing area of interest in noninvasive brain stimulation, tDCS uses just one to two milliamps of direct current, about as much as is generated by a 9-volt battery. The current delivered by tDCS simply raises or lowers the so-called resting potential of nerve cells, thus modulating how much stimulation they will need to fire.

Cranial Electrotherapy Stimulation (CES)

Developed in the 1950s to fight insomnia, CES devices are currently the only ones sold directly to consumers. CES works on the same principle as electroconvulsive therapy (ECT) but at one-one-thousandth the strength, delivering low levels of pulsed alternating current through electrodes placed just above the temples.

On the Horizon

Recent research has brewed up an acronym stew of new techniques coming down the pike. Some are novel twists on existing technologies—for example, TMS that penetrates deeper into the brain, and a type of high-definition (HD) tDCS that delivers more precise stimulation. New approaches also under investigation include transcranial alternating current stimulation (tACS), transcranial random noise stimulation (tRNS), and transcranial pulsed ultrasound (TPU).