This Brain Goes to 11—And Won’t Shut Up!

Question: Why can’t people with insomnia get to sleep despite having large sleep debts?

Shelby Harris: Well, the actual function of the brain, not so sure yet.  There’s a lot of different theories about it, but when you talk about psychologically in your brain, a lot of people with insomnia, though not all, report that they can’t turn their minds off.  So, it’s not every patient that I see, but I’d say a good 70% to 80% of the patients when they go to bed it’s like a stereo is playing at an 11 or 12 and they can’t turn it down, at all.  So it makes it very hard for their body to down regulate to be able to go to bed at night.  And in those patients they tend to then be more awake at nights, they’ll toss and turn, they’ll think more, they get frustrated.  And when that starts to happen, you really don’t sleep even more because you’re making your body tense and your mind is getting more and more active.  

And you said, “sleep debt” so, in general, there are patients with insomnia who – many patients with insomnia will actually over report the lack of sleep that they are getting.  They are still having insomnia, but it’s seems worse to them than actually it is.  So, if they say they’re sleep deprived, they haven’t slept at all in three days; if we actually take them into a lab, most of the time we actually do see they’re sleeping on and off here and there.  There might be little episodes of micro-sleeps or naps during the day, but they’re actually getting a little bit of sleep.  

And we’ve looked at sleep diaries of patients with insomnia, and they’ll say that they don’t sleep for one or two days.  And the body actually has a natural function, after about the third day to start catching up and you get a little bit more sleep the third night.  And that’s usually what I tell my patients.  When they start worrying about not sleeping, I’ll say, “Say the mantra to myself; if I don’t sleep tonight, I’ll likely sleep tomorrow, and if not tomorrow then definitely the third” because our body has a way of naturally catching up. 

Question: How can we treat insomnia?

Shelby Harris: So there’s a few different ways that we treat insomnia.  The first thing that we always do is we look at the cause.  So, more times than not, but not every time, it can be linked to a medical problem, such as menopause, cancer, chronic pain, it can be linked to anxiety and depression.  Those are the more common causes.  There are some patients who just have insomnia and they’ve had it since they were a kid and we don’t quite know why.  So when we look at the cause, we definitely want to treat whatever else is going on, but insomnia often because it becomes its own diagnosis and that requires its own treatment.  So if somebody has chronic pain, we want to manage the pain, but we still want to treat the insomnia separately.  So what we’ll tend to do in our sleep lab is we’ll do a thorough evaluation and we usually have myself, who is a Psychologist and a Sleep Behavioral Sleep Specialist, I treat the patients first.  So we try not using medications initially, and we use something called **** behavioral therapy for insomnia.  This changes behaviors people do in bed, none of the tossing and turning.  I’ll work on patient’s thoughts about sleep, “So I must get eight hours of sleep tonight or I won’t sleep tomorrow.”  That sometimes – or “I won’t function tomorrow.”  That sometimes makes it very difficult for you to sleep at night.  We’ll work on relaxation strategies and also changing the times you go to bed will actually make them sleep a little bit less for a few nights so their body’s natural sleep drive starts to kick in.  That is very effective in about 60% to 70% of patients who do it, four to eight sessions, not even every week; it works for 60% to 70% of patients.  The rates are just a good as all the medication that are out there, and the rates are actually better in the long term.  

The other option we have are medication treatments.  So you’ll have the treatments such as Ambien, Lunesta, Sonata, and we’ll also have Rozerem and for some patients we use Benzodiazopine/Clonazepam.  Things like that to help with anxiety.  Those are another option that we’ll use.  Sometimes we’ll use them in combination with behavioral, sometimes alone.  It really depends upon the patient. 

For many with insomnia, their minds are like stereos at maximum volume with no off switch.

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Yale scientists restore brain function to 32 clinically dead pigs

Researchers hope the technology will further our understanding of the brain, but lawmakers may not be ready for the ethical challenges.

Still from John Stephenson's 1999 rendition of Animal Farm.
Surprising Science
  • Researchers at the Yale School of Medicine successfully restored some functions to pig brains that had been dead for hours.
  • They hope the technology will advance our understanding of the brain, potentially developing new treatments for debilitating diseases and disorders.
  • The research raises many ethical questions and puts to the test our current understanding of death.

The image of an undead brain coming back to live again is the stuff of science fiction. Not just any science fiction, specifically B-grade sci fi. What instantly springs to mind is the black-and-white horrors of films like Fiend Without a Face. Bad acting. Plastic monstrosities. Visible strings. And a spinal cord that, for some reason, is also a tentacle?

But like any good science fiction, it's only a matter of time before some manner of it seeps into our reality. This week's Nature published the findings of researchers who managed to restore function to pigs' brains that were clinically dead. At least, what we once thought of as dead.

What's dead may never die, it seems

The researchers did not hail from House Greyjoy — "What is dead may never die" — but came largely from the Yale School of Medicine. They connected 32 pig brains to a system called BrainEx. BrainEx is an artificial perfusion system — that is, a system that takes over the functions normally regulated by the organ. The pigs had been killed four hours earlier at a U.S. Department of Agriculture slaughterhouse; their brains completely removed from the skulls.

BrainEx pumped an experiment solution into the brain that essentially mimic blood flow. It brought oxygen and nutrients to the tissues, giving brain cells the resources to begin many normal functions. The cells began consuming and metabolizing sugars. The brains' immune systems kicked in. Neuron samples could carry an electrical signal. Some brain cells even responded to drugs.

The researchers have managed to keep some brains alive for up to 36 hours, and currently do not know if BrainEx can have sustained the brains longer. "It is conceivable we are just preventing the inevitable, and the brain won't be able to recover," said Nenad Sestan, Yale neuroscientist and the lead researcher.

As a control, other brains received either a fake solution or no solution at all. None revived brain activity and deteriorated as normal.

The researchers hope the technology can enhance our ability to study the brain and its cellular functions. One of the main avenues of such studies would be brain disorders and diseases. This could point the way to developing new of treatments for the likes of brain injuries, Alzheimer's, Huntington's, and neurodegenerative conditions.

"This is an extraordinary and very promising breakthrough for neuroscience. It immediately offers a much better model for studying the human brain, which is extraordinarily important, given the vast amount of human suffering from diseases of the mind [and] brain," Nita Farahany, the bioethicists at the Duke University School of Law who wrote the study's commentary, told National Geographic.

An ethical gray matter

Before anyone gets an Island of Dr. Moreau vibe, it's worth noting that the brains did not approach neural activity anywhere near consciousness.

The BrainEx solution contained chemicals that prevented neurons from firing. To be extra cautious, the researchers also monitored the brains for any such activity and were prepared to administer an anesthetic should they have seen signs of consciousness.

Even so, the research signals a massive debate to come regarding medical ethics and our definition of death.

Most countries define death, clinically speaking, as the irreversible loss of brain or circulatory function. This definition was already at odds with some folk- and value-centric understandings, but where do we go if it becomes possible to reverse clinical death with artificial perfusion?

"This is wild," Jonathan Moreno, a bioethicist at the University of Pennsylvania, told the New York Times. "If ever there was an issue that merited big public deliberation on the ethics of science and medicine, this is one."

One possible consequence involves organ donations. Some European countries require emergency responders to use a process that preserves organs when they cannot resuscitate a person. They continue to pump blood throughout the body, but use a "thoracic aortic occlusion balloon" to prevent that blood from reaching the brain.

The system is already controversial because it raises concerns about what caused the patient's death. But what happens when brain death becomes readily reversible? Stuart Younger, a bioethicist at Case Western Reserve University, told Nature that if BrainEx were to become widely available, it could shrink the pool of eligible donors.

"There's a potential conflict here between the interests of potential donors — who might not even be donors — and people who are waiting for organs," he said.

It will be a while before such experiments go anywhere near human subjects. A more immediate ethical question relates to how such experiments harm animal subjects.

Ethical review boards evaluate research protocols and can reject any that causes undue pain, suffering, or distress. Since dead animals feel no pain, suffer no trauma, they are typically approved as subjects. But how do such boards make a judgement regarding the suffering of a "cellularly active" brain? The distress of a partially alive brain?

The dilemma is unprecedented.

Setting new boundaries

Another science fiction story that comes to mind when discussing this story is, of course, Frankenstein. As Farahany told National Geographic: "It is definitely has [sic] a good science-fiction element to it, and it is restoring cellular function where we previously thought impossible. But to have Frankenstein, you need some degree of consciousness, some 'there' there. [The researchers] did not recover any form of consciousness in this study, and it is still unclear if we ever could. But we are one step closer to that possibility."

She's right. The researchers undertook their research for the betterment of humanity, and we may one day reap some unimaginable medical benefits from it. The ethical questions, however, remain as unsettling as the stories they remind us of.

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