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Scientists have discovered a "signature" in brain activity that could explain why some severely brain injured patients awake from a minimally conscious state as result of sleep aid drugs and other medication. This is according to a study published in the journal eLife.
The research team led by investigators from Weill Cornell Medical College in New York, say their findings could help predict whether other patients suffering from "similarly harbor reserve capacity" may respond to sleep drugs or other approaches.
The researchers began their study after finding that three patients who suffered severe brain damage "awoke" from minimal cognitive capacity after using a sleep drug called Ambien, also known as zolpidem.
All three patients were brain damaged in different ways. One suffered a fall, another suffered a brain aneurism while another almost drowned after a car accident.
Using electroencephalography (EEG) to monitor the patients' brain waves when using Ambien, the researchers found that although their brains were damaged in different ways, they all demonstrated the same low frequency waves in their readings.
In detail, these brain waves were found to be most active in the frontal cortex - a region known to be very dependent on other brain structures in order to be active, mostly the central thalamus and the striatum.
These two areas work together to support a variety of functions, including short-term memory, reward, motivation, attention, alertness and sleep.
The investigators hypothesize that the way Ambien works in the brain is similar to how an anesthesia drug works. It "briefly triggers a fast wave of excitation in the brain before causing sleep." They say this is a phenomenon known as "paradoxical excitation."
The investigators explain that in healthy people who use Ambien, it produces sedation and causes them to sleep. But in those who suffer severe brain damage, it activates the brain further following its activation of the "sleeping" cells, causing the patients to become more awake.
Explaining this theory further, Dr. Nicholas Schiff, professor of neurology and neuroscience and professor of public health at Weill Cornell Medical College says:
"What we think is happening in these patients is that the initial excitation produced by Ambien turns on a specific circuit. The drug creates the opportunity for the brain to effectively catch a ride on this initial wave of excitation, and turn itself back on."
He adds that the circuit turned on by the Ambien, which he refers to as the "mesocircuit," links the "cortical" areas of the brain to the central thalamus and the striatum.
Because the neurons in the central thalamus are strongly connected to other areas of the brain, "damage in one part of the brain or another will affect the thalamus, which is key to consciousness. Neurons in the striatum will only fire if there is a lot of electrical input coming to them quickly," says Dr. Schiff.
However, the researchers found that in the study participants, the "misocircuit" deactivates once the effects of Ambien have worn off. This means that regular use of the drug is needed to maintain optimum results.
Dr. Schiff notes that one patient in the study who suffered brain damage from almost drowning has seen significant reductions in tremors and spasticity through using Ambien regularly at mealtimes. He is now able to use objects, such as a spoon, and is alert and able to communicate.
He adds that another patient is now able to "reliably move from minimally conscious to the mid-range of what is called a confusional state - a more alert status, but not full consciousness."
From these results, Dr. Schiff notes that "use of Ambien offers a step in the right direction, but certainly not a cure."
The researchers say the patients' EEG patterns found in the study suggest they have a "recruitable reserve" of functions in critical areas of the brain that Ambien is able to tap into in order to "switch on" the brain.
From this, Dr. Schiff says they hope to be able to screen other patients with EEG in order to determine if they also have these recruitable reserves.
And the investigators note that although some patients with severe brain damage may not respond to Ambien due to the targeting of very specific brain receptors, other drugs could potentially have the same effects.
They point to two drugs called amantadine and L-Dopa. Both provide the brain with extra dopamine and previous studies have shown them to have similar effects on improving the function of patients who are severely brain damaged.
Dr. Schiff adds:
"Now that we have uncovered important insight into fundamental mechanisms underlying the dramatic and rare response of some severely brain-injured patients to Ambien, we hope to systematically explore ways to achieve such kick-starts in other patients - that is our goal."
Medical News Today recently reported on a study suggesting that brain abnormalities as a result of concussion are visible months after injury.
Written by Honor Whiteman
Copyright: Medical News Today
Not to be reproduced without the permission of Medical News Today.
Common resting brain dynamics indicate a possible mechanism underlying zolpidem response in severe brain injury, DOI: http://dx.doi.org/10.7554/eLife.01157, Shawniqua T Williams, Mary M Conte, Andrew M Goldfine, Quentin Noirhomme, Olivia Gosseries, Marie Thonnard, Bradley Beattie, Jennifer Hersh, Douglas I Katz, Jonathan D Victor, Steven Laureys, Nicholas D Schiff, published in eLife, 19 November 2013. Open access
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19 Apr. 2014. <http://www.medicalnewstoday.com/articles/269231>
Whiteman, H. (2013, November 23). "Sleep drugs 'awake' brain damaged patients with 'signature' activity." Medical News Today. Retrieved from
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