An Eye on Shut-Eye

by Rabiya S. Tuma

July, 2005

Functional brain imaging is thought to be one of the most important discoveries in sleep research in the past 100 years. Researchers are using it to look at what happens in the whole brain during sleep, both in healthy individuals and in people who suffer sleep disturbances such as depression, sleep apnea, and insomnia.

Before brain imaging techniques developed, researchers relied on electroencephalograms, or EEGs, to learn about the different stages of sleep. EEGs detect the electrical activity in the brain through electrodes placed on a patient's scalp. The technique measures general patterns of brain activity, such as the speed of neural spikes, but is not sensitive enough to distinguish activity in different brain regions or in the deeper structures of the brain, below the cortex.

In the past, traces from an electroencephalogram, left, provided information about the stages of sleep. That method has been upstaged by functional magnetic resonance imaging, above, which provides a comparison of sensory processing during wakefulness, shown in the scan on the left, and light sleep. Sound signals are transmitted to the auditory cortex during wakefulness, as indicated by increased neural activity, but not during sleep.  Credits:  Hannah Gal / Photo Researchers, Inc.;  Czisch et al., 2004.

Scientists know how sounds are processed in the brain when someone hears something while they are awake, with neural signals passing from the auditory nerve to the thalamus and then to the primary cortex, where the signals are processed. To find out what happens when someone is sleeping and hears a noise, Thomas Pollmächer, a lead investigator at the Max Planck Institute of Psychiatry in Munich, and colleagues are using functional magnetic resonance imaging, or fMRI, and EEG.

For these experiments, a volunteer lies in the MRI scanner with electrodes on his or her head. When the volunteer falls asleep, the researchers play a sound repeatedly. Significantly, the scientists do not detect activation in the thalamus or auditory cortex. The researchers interpret this lack of a strong signal to mean that the brain is actually trying to repress outside stimuli, as if trying to maintain sleep and prevent waking.

During rapid-eye movement sleep, or REM, during which most dreaming occurs, the group has observed a similar pattern in which the auditory cortex is quiet.

"The brain functions in a closed mode," Pollmächer says. "It tries to exclude external sensory information and reinforce internal signals."

That observation agrees with experimental data showing that sleep is important for reinforcing memories. While a person sleeps, the brain reviews the tasks or events of the day, storing them more securely than if the brain processed them only at the moment they occurred.

Meanwhile, Eric Nofzinger and colleagues at the Western Psychiatric Institute and Clinic in Pittsburgh are examining what regions of the brain are active during sleep in healthy and depressed volunteers and are helping to explain why patients with depression have a hard time sleeping.

In these experiments, volunteers sleep in a normal bedroom setting, with EEG electrodes attached and an intravenous (IV) needle in their arms. When volunteers reach a specified stage of sleep, the scientists inject a solution of radioactive glucose through the IV. They then wake the volunteers and put them in a positron emission tomography, or PET, scanner. Because the glucose goes to the cells that are most active, the team can see what regions of the brain were in use when they injected the solution.

During REM sleep depressed patients have an overactive limbic system, which controls emotions. "It's like they have a raw nerve, which is too easily overstimulated," Nofzinger says.

The team has started to look at what happens in patients who are depressed but receiving treatment. Nofzinger says they have preliminary results in these patients, and that although it is too early to draw conclusions, there are undoubtedly differences between untreated and treated patients.

Sleep is key to restoring an individual's brain power. If scientists can find out what healthy sleep looks like and what happens when it is disrupted-as occurs in depression-they may be able to correct it.

One striking observation, Pollmächer says, is what happens when his team uses EEG to see what is going on in a patient who complains about severe sleep disturbances: "The EEGs are almost non-remarkable. It could be that by looking at deeper regions [with imaging techniques] we will be able to understand why people perceive their sleep is so bad."