The Clinical Neuroscience of Sleep and Insomnia

Recent developments in neuroscience suggest that sleep disorders, such as insomnia, are tied to the dysregulation of the sleep-wake switching system. This research was discussed here at the annual meeting of the American Psychiatric Association (APA).

Input from the prefrontal cortex and limbic system can in turn influence the occurrence and emotional tone associated with sleep and wakefulness. “There is a biological timing system that influences the overall tone and timing of sleep and awakeness,” said Daniel J. Buysse, MD, Professor of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States. “You cannot just will yourself to sleep.”

Buysse presented the case of a 40-year-old woman, “Kathy,” who had just lost her teaching job and who was going through a divorce and custody battle over her two children. She complained of difficulty falling asleep and staying asleep. As a consequence, she said, she had cognitive difficulties, problems concentrating and focusing, feelings of fatigue, and lack of energy. She would have a few bad nights generally followed by a few good nights’ sleep, but sleep was always worse after experiencing upsetting events. A sleep evaluation found that she had a long-term tendency toward sleep problems and had tried various over-the-counter methods to get desired sleep.

Buysse asked the audience of psychiatrists which aspect of Kathy’s presentation was most likely related to a decreased homeostatic sleep drive. Thirty-nine percent thought she was possibly napping during the day and ruining her chance of a full night’s sleep.

“Daytime symptoms associated with insomnia, all seen in Kathy’s case,” Buysse said, “fall into three areas: mood disturbance, cognitive difficulties, and difficulty focusing with fatigue.”

While a sleep lab may show that a person is sleeping, people with insomnia conversely feel they are simultaneously awakened during sleep. “To their brain, it’s day,” he said, explaining the implications of the sleep-wake switching system for insomnia.” Buysse said to tell patients with insomnia not to sleep during the day “because if you nap during the day, you’re not going to have enough sleep drive to get to sleep at night.” It was also suggested that patients get up at the same time every day so they receive enough light as the circadian system requires it.

There can be lesions of perifornical orexin (another name for hypocretin, a chemical secreted in the hypothalamus that regulates the sleep-wake cycle) neurons that produce unstable sleep-wake states with frequent wake-sleep transitions.

In rat studies, when their cages are swapped out, the rats have reduced sleep due to stress. This stress-induced insomnia may produce a “flickering” of the sleep-wake switch. There are actually simultaneous sleep and wake centres on at the same time when the rat is stressed. In human populations, however, asking someone how they sleep may be better than objective tests since the flickering tests cannot be accomplished with a routine psychiatric practice, Buysse said.

There are certain areas of the brain that do not shut off in insomniacs when compared to good sleepers. Areas in the cingulum remain active in sleep; the brains are not shutting off effectively. “People with insomnia have high EEG frequencies and more brain activity than good sleepers; their brains are going even when they’re asleep,” noted Buysse who also pointed out that insomniacs have a reduced sleep drive overall. There is also more measurable cortisol in primary insomnia patients than in healthy control subjects when cortisol, a stress hormone, is measured during the night. “Insomniacs increase cortisol and arousal at night.”

Buysse suggested that psychiatrists ask patients how they feel “right now,” rather than asking how they have felt over the past week. He suggested developing a rating scale for concentration, mood, energy, alertness and overall feelings. Assess patients four times a day for seven days for alert cognition, negative mood, positive mood, sleepiness and fatigue. “Good sleepers feel much more alert in the morning than insomniacs who catch up only at the very, very end of the day,” said Buysse, who added that insomniacs are more alert at the end of the day.

Back to Kathy. Buysse again asked the gathered psychiatrists which aspect of Kathy’s presentation is most likely related to a decreased homeostatic sleep drive and this time some 64% correctly said her sleeping late and daytime napping were associated with worse sleep outcome.

[Presentation title: Making Every Sheep Count: Evidence-Based Approaches to Treating Insomnia. Abstract 578]

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