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How to turn electricity into a brain drug

A jolt of electricity can act as a drug when just the right amount of it is delivered to just the right part of the brain.

"We often try to correct a problem occurring in some tiny part of the brain's complicated circuitry by administering a drug," Stanford neuroscientist Josef Parvizi, MD, PhD, told me during an interview about a new study published in Neuron. "However, instead of reaching the cells you want to target, much or most of the drug may wind up in the skin, bone, muscle, liver and elsewhere, not to mention brain cells you don't want to target."

That can cause all kinds of side effects.

Meanwhile, devices delivering therapeutic doses of electricity to specific points within the brain are in wide use. Such devices are increasingly prescribed to counter the tremors of Parkinson's disease and are approved for some patients with obsessive-compulsive disorder. Similar devices are undergoing clinical testing for other conditions, including depression, epilepsy and Tourette syndrome, Parvizi said.

In a news release about the study, Parvizi said he's optimistic -- mostly:

Electrical brain stimulation, targeting only a specific malfunctioning brain circuit, has immense potential to change medical practice. But figuring out just how much current will be effective without recruiting unwanted brain circuitry and inducing side effects has been largely guesswork.

Parvizi and a colleague, former postdoctoral scholar Jon Winawer, PhD (now at New York University), set out to establish a dose-response curve for electricity applied to the brain, analogous to the curves pharmacologists routinely plot for drugs so physicians can confidently provide the right amount to patients.

Parvizi, a practicing neurologist who directs Stanford's Human Intracranial Cognitive Electrophysiology Program, recruited four adult patients who were under his evaluation to determine the point of origin of their recurring, drug-refractory (drugs don't help) epileptic seizures. In this procedure, a portion of the skull is temporarily removed and a grid of electrodes is placed on the brain's surface in order to record seizure activity and pinpoint the spot in the brain where it begins.

Parvizi and Winawer showed the four volunteers geometric forms moving across a computer screen while they stared at the center of the screen, and used brain-imaging techniques to record neural activity induced by this visual stimulation in a brain-surface region called the primary visual cortex. This allowed the researchers to construct "maps" linking various points in each patient's visual field to a corresponding location in that patient's primary visual cortex.

Then Parvizi used the electrodes positioned on the study volunteers' brain surfaces to induce, rather than record, brain activity by delivering defined, safe amounts of current to selected points on the primary visual cortex. When he did so, volunteers reported (as expected) seeing visual hallucinations in the part of their visual field corresponding to the part of the primary visual cortex being stimulated.

The bigger the electrical "dose," the larger the experienced visual hallucination. From this, the investigators could infer how much brain tissue in the primary visual cortex a given dose had stimulated.

The resulting dose-response relationship can be put to work in clinical trials of electrical brain stimulation.

Previously: Circuit breaker: One Stanford scientist and his quest to control epileptic seizures, The brain makes its own Valium: Built-in seizure brake?, Light-switch seizure control? In a bright new study, researchers show how and Possible trigger for childhood seizures identified
Photo by Michael Coghlan

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