My Q and A With Patrick Fuller on How Neuroscience Can Unlock Sleep's Mysteries

Patrick Fuller is a neuroscientist at Harvard Medical School's esteemed Division of Sleep Medicine. In answer to my questions, he shared his insights on the importance of good sleep hygiene, how our brain's clock is connected to our overall well-being, and the problem with sleeping pills.
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Patrick Fuller is a neuroscientist at Harvard Medical School's esteemed Division of Sleep Medicine. In answer to my questions, he shared his insights on the importance of good sleep hygiene, how our brain's clock is connected to our overall well-being, and the problem with sleeping pills.

What have you found in your research on the "neurocircuit basis" that supports sleep?

In specific reference to our recent work on the brainstem slow-wave-sleep promoter "center," we showed that this region of the brain is first connected (synaptically) to an important wake-promoting region of the brainstem that in turn is connected with important wake-promoting circuitry of the forebrain, which itself connects to the cerebral cortex. Essentially, we provided a circuit "wiring diagram" by which activation of brainstem sleep-promoting neurons might produce "whole brain" sleep. The reason I emphasize the word "neurocircuit" in our work is because I believe that in order to understand how the brain accomplishes virtually anything, one must first understand the functional cellular and synaptic "scaffolding" from which brain phenomena emerge.

Tell me about how circadian regulation affects our sleep and wakeful consciousness.

So it all starts (and ends!) with a little biological clock in our brain. The so-called "master" circadian clock is actually a collection of neurons located in a small region of the hypothalamus, itself a very small structure. (In humans, the hypothalamus is about the size of an almond.) This clock is remarkable for many reasons, perhaps most notably that no other region of the brain can assume its function if/when it is damaged. The clock's fundamental role is to keep us "synchronized" with the Earth's light-dark cycle as well as keep our body's internal rhythms synchronized with one another. And we now know that proper external and internal synchronization is fundamental to our physical and mental well-being. A great example of what happens when your internal rhythms become transiently desynchronized with the environment, as well as with one another, is jet lag disorder, which results in symptoms of fatigue, loss of appetite, insomnia, irritability, gastrointestinal disruption, cognitive impairment and general malaise. When individuals experience more long-term disruption or desychronization, such as occurs in certain occupational settings including shift work, long-haul airline pilots, astronauts, or because of a circadian rhythm sleep disorder, the physical consequences may reach far beyond just feeling "crummy" (see jet lag above), as these individuals are at increased risk of developing cardiovascular disease, metabolic diseases like diabetes and obesity and even cancer. Indeed, it would not be an exaggeration to say that our brain's clock is an inescapable and all-pervading biological consideration when it comes to our health and well-being.

It probably comes as no surprise to learn that the circadian clock also controls the sleep-wake cycle (rhythm). As is self-evident, we sleep at night and wake during the day, at least for those of us working a normal (i.e., not shift or night) schedule. And the circadian clock plays a very important role in determining the timing at which we wake up and fall to sleep. The clock also plays an important role in helping us stay awake during the latter part of the day as well as in keeping us asleep for the entire night. In other words, the clock, at different times of day, provides either a wake-promoting or sleep-promoting influence on the brain and body. And going back to the example of jet lag, these properties of the clock are a contributing factor to why one feels so crummy after a long plane flight -- your clock is trying to put your brain and body to sleep (or keep them awake) at the "wrong time." And the situation is of course made worse by the fact that your clock is also confused by the change in timing of the external light-dark cycle.

You were profiled in a New York magazine article titled "Has a Harvard neurologist found the cure for insomnia?" Describe what you discovered and what it means for sleep.

Well, I'd say that a bit of journalistic liberty was taken with that title. We (and I stress we) did not discover a cure for anything. What we, and my postdoctoral fellow, Dr. Christelle Anaclet, in particular, "discovered" was that the brainstem contains a locus of neurons that actually trigger, and possibly maintain, deep "slow-wave" sleep, and its electroencephalographic correlate, cortical slow-wave activity. We showed that we could rapidly trigger deep sleep in mice by "remotely" activating a certain type of neuron in this brain region, as well as prevent entry into deep sleep by inhibiting these same cells. Our findings, therefore, have potential implications for treating sleep disorders, such as insomnia, by providing a new (potential) structural/cellular target for rational drug design or the development of other therapeutic modalities.

What would you say to those who view sleeping pills as the answer to insomnia and other sleep difficulties?

In the interest of full disclosure, I should start off by saying that I think our society is a bit overly reliant on pills (of all types), and that I am, generally speaking, not a big fan of taking pills for all ills, so my answer to your question could be construed as biased. At the same time, I do think the judicious prescription and usage of sleeping pills or hypnotics/sedatives can serve a very medically valuable purpose and are a godsend for people with bona fide sleeping disorders, such as insomnia. To be sure, insomnia is a major health condition, and patients with insomnia often experience a major decrease in quality of life. Where you get into trouble is with the diagnosis of insomnia, which is actually a complex clinical task and something I don't feel can be conclusively made without a full psychiatric/medical and EEG (performed in sleep lab) workup. Self-diagnosed insomnia or the provision of prescriptions for sleeping pills by well-intentioned but not fully informed physicians remains a problem, at least in my view. This perspective is underscored by the fact that patients with primary insomnia (i.e., insomnia that is not associated with any other identifiable medical condition), account for only about 15 percent of all insomnia patients seen at sleep clinics. And as alluded to above, the diagnosis issue is complicated by the fact that insomnia is often a symptom of (or is comorbid with), and not the cause of, many disorders, neuropsychiatric conditions in particular. Insomnia, for example, is a common symptom of anxiety disorders. In this instance, providing sleep pills for anxiety-induced insomnia might be considered akin to treating a fever with a fever-reducing agent but not addressing the underlying infection driving the fever. (I do acknowledge that treating sleeping/waking symptoms can, in some cases, help resolve the primary medical issue as well.) The other problem with many sleeping pills is the documented side effects, something I consider to be a bit of an elephant in the room. And this is because some of the FDA-approved -- and widely prescribed -- sleeping pills can have side effects that are, to put it mildly, "undesirable," including sleepwalking, sleep eating, hallucinations and sexual parasomnias. Many users also report that these drugs make them feel like they are hungover following the drug-induced sleep. In sum, my answer to your question remains overly simplistic, but I would reiterate that it is important to keep in mind that treating sleep disorders, including insomnia, can be a complex task, in particular because sleep disorders are frequently comorbid with other challenging-to-treat disorders.

I think the key to good sleep, in the absence of pathology, is for people to practice good "sleep hygiene." This would include adopting and maintaining a specific time to rise and go to sleep, getting seven to eight hours of sleep every night, avoiding stimulants after the early afternoon and keeping alcohol consumption in the evening to a minimum. If insomnia persists in spite of good sleep hygiene, and psychiatric (anxiety, PTSD, depression, major life stressors, etc.) and other (cardiovascular disease, substance abuse, sleep disorders such as sleep apnea or restless legs syndrome, etc.) issues have been ruled out, then primary insomnia may be the correct clinical diagnosis, and limited use of sleeping pills, such as eszopiclone or other so-called "Z-drugs," would be justified.

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