FOCUS_Sleep High-tech nightcap: Researchers use more than 100 electrodes to record the electrical currents on the surface of the head while a subject sleeps. This brain activity is used to generate a sleep profile. 32 MaxPlanckResearch 4 | 16 When the Brain Switches to Standby People who haven’t gotten enough sleep often see the world as a fairly sad place. If their tiredness lasts for weeks or even months, their dark mood may become chronic and develop into depression. Conversely, depression is frequently also associated with severe sleep disorders. Axel Steiger and his team at the Max Planck Institute of Psychiatry in Munich are studying the connection between disturbed sleep and depression. To do this, they measure human brain activity in the sleep lab. TEXT CATARINA PIETSCHMANN Photo: Denise Vernillo FOCUS_Sleep 1 Wakefulness 2 Non-REM sleep 3 REM sleep EMG EEG Delta Theta Beta & Gamma EEG spectrum 0 10 20 30 40 50 60 70 0 10 20 30 40 50 60 70 0 10 20 30 40 50 60 70 Frequency (Hertz) Frequency (Hertz) Frequency (Hertz) Top Measuring mouse sleep: While awake (column 1 ), mice move around a lot, so their muscles are more frequently active. The graph shows the electrical signals from their neck muscles (electromyograph; top). The neurons in their brain fire in different rhythms and across a broad range of frequencies (middle and bottom). In non-REM sleep (column 2), the skeletal muscles become inactive (top). Brain activity oscillates with high amplitudes but low frequency (delta waves; middle and bottom). In REM sleep (column 3), the muscle tones are almost flat (top) and theta rhythms predominate in the brain (middle and bottom). Opposite page In the sleep lab of the Max Planck Institute of Psychiatry, Michael Czisch records the subject’s brain activity in an MRI scanner. This device makes the activity of the sleeping brain visible to scientists. tress at work, relationship is- Sleep Medicine at the Max Planck Insti- al environment for his research. He and sues or moving to another tute of Psychiatry in Munich. his team study the connection between city can literally rob people of The long-standing clinic, which fo- sleep patterns and nocturnal hormone their sleep. According to the cuses on stress-related complaints such release in depression. While the volun- Robert Koch Institute, one as depression, sleep disorders and anx- teers spend a night in the sleep lab, the outS of every three German citizens has iety, was founded by Emil Kraepelin in scientists measure the electrical impuls- suffered from a sleep disorder at some 1917 as the German Research Institute es of their brain and muscles, record stage in their life. In most cases, sleep for Psychiatry, and became a member their eye movements and regularly take patterns return to normal once the of the Kaiser Wilhelm Society in 1924. small blood samples to assess the levels stressful event or issue has passed. How- It contains five wards with a total of of certain hormones. ever, when such symptoms persist for 120 beds, a day clinic, a number of spe- The researchers then use the wave weeks or months, it is important to cial outpatient clinics and several re- patterns from the electroencephalo- consult a doctor. search institutions, all under one roof. gram (EEG) along with the other mea- Poor sleep can have physical or surements to extrapolate the sequence mental causes. “Disturbed sleep can be SNOOZING IN THE NAME of the different sleep stages, also both a cause and a consequence of de- OF SCIENCE known as the sleep profile, or hypno- pression – in other words, it is both a gram. This is a step-like diagram con- symptom and a risk factor. It leads to a Patients can voluntarily choose to take sisting of several phases: At the start of huge increase in the risk of depression,” part in scientific studies – for Steiger, the night, the subject gradually falls explains Axel Steiger, Senior Physician who has led the Sleep Endocrinology into a deeper sleep, and the amplitude and Head of the Outpatient Clinic for Research Group since 1991, it is an ide- of the EEG waves increases as this oc- Graphic: D. Kumar & M. Kimura (2014) 34 MaxPlanckResearch 4 | 16 curs. The EEG amplitude is low when continual stream of data down the characterized by increased blood pres- the subject is awake or in REM sleep, wires to a computer. This allows the re- sure and pulse, while the skeletal mus- and high during deep sleep, the lowest searchers to look into the cerebral cor- cles remain fully relaxed. Four, five or rung on the ladder. tex and even deeper parts, such as the sometimes even six or more cycles of The Institute also uses high-density limbic system, the seat of the emotions. deep sleep and REM sleep per night are EEG (HD-EEG), the newest technology Schematic representations of the typical. Deep sleep is a component of in this area, to evaluate brain activity. hypnogram show clear differences be- non-REM sleep. In healthy young peo- Subjects wear a kind of “nightcap” fit- tween REM (rapid eye movement) ple, it is most pronounced at the start ted to the head with 118 fine electrodes sleep, when dreaming typically occurs, of the night and occurs only rarely or – normally there are ten. While they and non-REM sleep. REM sleep appears not at all in the early morning. slumber in the soundproof room, their as a stage below the waking state but Directly after falling asleep, most brain, facial muscles and heart send a clearly above that of deep sleep. It is people sleep especially deeply for about LEARNING WHILE ASLEEP While asleep, the body is at rest only on the outside, be- sleep for up to 17 hours a day. This is due to the enormous cause sleep is an active process: metabolism is running at growth and maturing processes that occur in the brain full speed, particularly in terms of growth and regenera- during this time. Never again do humans learn so much as tion, detoxification and tissue repair. Some parts of the in the first weeks and months of life. Three- to five-year- brain are also highly active, processing the stimuli that the olds can manage on 10 to 13 hours, while seven to eight brain absorbed during the day, separating important infor- hours is generally enough for 18- to 78-year-olds. The sleep- mation from irrelevant details, and moving memories from wake cycle also changes. Adults generally sleep only at short-term to long-term storage. That’s why good sleep night and for a single stretch, while newborns take a num- promotes good memory. ber of shorter sleeps over the course of a day. By the age of The need for sleep decreases continuously during the one, most children already sleep through the night, and course of a lifetime. In the first three months of life, infants their daytime sleep decreases noticeably. Graphic: D. Kumar & M. Kimura (2014) Photo: Denise Vernillo 4 | 16 MaxPlanckResearch 35 Axel Steiger has devoted nearly his entire leasing hormone (CRH). In the event Kimura, head of the Sleep and Teleme- research life to sleep. Among other things, of an infection, for example, CRH in- try Core Unit in the Institute, used ro- he is Head of the Outpatient Clinic for Sleep directly stimulates the release of corti- dent models in which specific genes Medicine at the Max Planck Institute of Psychiatry. There, various disorders are sol in the adrenal glands. The cortisol were intentionally switched off or acti- diagnosed and treated, such as nighttime then activates the immune system. vated in order to study their exact func- sleep and movement disorders, unusual sleep The same thing happens in the event tion. Animals that have been stressed behaviors (such as sleepwalking), and night of exam stress or a heated argument. for extended periods, as well as those terrors and nightmares. Once the situation has passed, the that have been genetically modified so stress hormones come back into bal- that their brains produce more CRH 90 minutes. This is followed by the ance. At this stage, the cortisol already than usual, fell faster and more fre- first REM period. “Depressed patients, circulating slows CRH release and quently into a REM episode when on the other hand, progress to REM hence its own production. asleep. This makes them the ideal ani- sleep faster, sometimes after just ten mal models for depression. minutes,” says Steiger. In addition, the HORMONE INTERACTION But are there really depressed mice? first REM period is generally longer in AS A FOCUS OF RESEARCH “Of course we don’t know whether these patients. they really feel like human patients, If we compare patterns of hormone “We believe that this feedback mecha- but their sleep phenotype is certainly secretion with sleep profiles, it is nota- nism is dysfunctional in patients with similar to that of depressed patients,” ble that less growth hormone is re- depression, probably because the corti- says Kimura. In the “forced swim” test, leased in depressed patients than in sol receptors in the brain that stop the for example, whereas healthy mice healthy subjects. The cortisol values are release of the hormone in healthy indi- swim around and try to struggle also different, climbing much higher in viduals are faulty,” explains Steiger. through longer, “depressed” mice give many patients, especially in the second When depression subsides, the cortisol up sooner. And although mice gener- half of the night. levels initially fall, while the sleep pat- ally wake more frequently and seldom Cortisol is an important stress hor- tern remains disturbed for a time.