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Brain radio: Switching nerve circuit’s firing frequency radically alters alertness levels in animal models

brain radioIt's a kick to consider that a part of the brain could act like a radio, with different stations operating at different frequencies, playing different kinds of music and variously attracting or repelling different “listening audiences.” A new study by Stanford neuroscientist Jin Hyung Lee, PhD, and her colleagues has isolated a brain circuit linking just such a "transmission station" in the midbrain to various "listener" regions in the forebrain.

The findings have clear therapeutic potential. In a news release about the research, I wrote:

In a case study published in 2007, [researchers] demonstrated that electrically stimulating the central portion of the thalamus — a deep-brain relay station routing inputs from the senses to myriad cognitive-processing centers throughout the cerebral cortex — could restore consciousness in a patient who’d been in a minimally conscious state for six years.

“But there was no way to know how it worked,” Lee told me.

Now, in a set of experiments published in eLife, she and her associates have used precisely targeted stimulation and recording techniques to show that forcing a set of nerve cells in the central thalamus to fire at 40 or 100 times a minute induces a state of arousal: Rats that were fast asleep wake up and start roving around and exploring their environments. Switch the same nerve cells to a firing frequency of 10 times a minute, and the same rats immediately go into a state of deep unconsciousness more akin to a coma or a petit mal seizure (a transient state of behavioral arrest) than to restful sleep.

In addition to these behavioral effects, forcing those central-thalamic nerve cells to fire at different rates causes distinct structures elsewhere in the brain to rev up or slack off. In a sense, firing at 100 times a minute was like blasting heavy-metal music - some forebrain regions leapt into the mosh pit, some ran for cover - while 10 times a minute (the easy-listenin' channel?) variously appealed to or turned off different brain areas.

You can't do that with a drug.

Much progress has been made in treating patients with neurogenic disease with drugs that affect the levels of, or substitutes for, signalling chemicals in the brain known as neurotransmitters. But drugs, once they've reached the brain, go pretty much wherever the blood takes them. They sometimes trip off, or shut down, circuits that aren't relevant to the problem, resulting in unintended side effects.

Plus, there's no obvious way for drugs to cause a particular brain circuit to reliably fire at a particular frequency.

But there's a way to do that. It's called deep-brain stimulation. DBS devices, implanted into specific spots in the brain and emitting intermittent bursts of electrical signals, have proven effective at eliminating tremors due to Parkinson's disease and at ameliorating psychiatric conditions from depression to obsessive-compulsive disorder.

The new findings highlight DBS's potential for yet another therapeutic goal: restoring consciousness in minimally conscious patients.

Previously: New way to watch what stem cells transplanted into the brain do once they get there, Stanford conducts first U.S. implantation of deep-brain-stimulation device that monitors, records brain activity and Positive results in deep-brain-stimulation trial for epilepsy
Photo by Hartwig HKD

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