Have you ever heard the expression that bad things happen in threes?

While this concept is generally regarded as a superstition, there is a ring of truth to it for individuals with schizophrenia, who frequently suffer from three distinct sets of problems.

The first type, known as positive symptoms, occur when individuals start to display new behaviors such as hallucinations of confusion as a result of the disorder.

Will Coon, PhD

The second type, negative symptoms, occur when schizophrenic individuals stop performing or displaying certain behaviors or emotions. These symptoms may manifest as withdrawal, depression or a lack of emotion.

The third type, cognitive deficits, result in difficulties with learning and memory retention, and can be some of the most debilitating when it comes to day-to-day functioning, according to Will Coon, PhD, a postdoctoral research fellow in the laboratory of Dara S. Manoach, PhD, at the Martinos Center for Biomedical Imaging.

Only about 20% of individuals with schizophrenia whose symptoms are well managed can work because of the cognitive deficits they experience, Coon explains.

Coon is part of a research team at the Manoach Lab that is investigating the connection between sleep and psychiatric disorders such as schizophrenia, with the hope of finding new treatments.

The Connections Between Sleep and Memory

It has long been known that sleep plays a crucial role in forming and consolidating memories, Coon says. “But when you compare the sleep of a healthy person to a person with schizophrenia who is clinically stable, there aren’t many differences on the surface. Their sleep is no more or less interrupted than that of a healthy individual.”

However, when the team looked deeper into the brain activity during sleep, they found a dramatic difference. Individuals with schizophrenia experienced a much lower number of sleep spindles than healthy individuals.

Named after the spindle-like shapes they make on EEG readouts, sleep spindles are short bursts of brain activity that occur during light sleep. The spindles typically appear simultaneously across different areas of the cortex—the part of the brain responsible for memory consolidation and deep thought.

Discovering this disparity led to a compelling question for the research team: Could increasing the production of sleep spindles help in treating the cognitive symptoms of schizophrenia?

Searching for Solutions

To test this theory, team’s first approach was to increase the production of sleep spindles in study participants with schizophrenia by giving them a common sleep drug. While the production of sleep spindles went up, the participants did not show a commensurate improvement on learning and memory tests.

This lead the team to try a second approach that seeks to use non-invasive electrical stimulation to both increase the overall number of sleep spindles produced and coordinate their production across different areas of the cortex.

“It is this synchronous communication—where the spindles are all oscillating together at the same time—that’s what allows them to connect to each other and integrate different aspects of memory and previous experiences and consolidate them in a stable and retrievable way,” Coon says.

The new approach is similar to how a conductor leads an orchestra. If each musician is playing at a different speed, the piece will fall apart. Simply adding more musicians to the mix won’t help if the coordination is not there. “You want the tempo to be the same so they are playing a symphony instead of individual riffs.”

Next Steps

More research needs to be done to see if this approach will translate into an effective treatment. But the good news is that the technology is inexpensive, accessible and non-invasive. The stimulation can be applied by wearing a headband of electrodes during sleep.

“I think the most exciting thing about this work is it’s at the forefront of what everyone’s been talking about in neuroscience for the past five years now—this kind of interdisciplinary approach, Coon says.  Here I am a basic neuroscience researcher, and I’m getting to work on technologies and studies that may have a clinical impact.”

Getting the Complete Picture

The unique collaborative atmosphere of Mass General—where researchers, clinicians and patients can work together to develop new treatments—has also helped to move the project forward, Coon says.

“It’s really seeing the entire process—from the concept, to the testing of the hypothesis, to the implementation of a translational approach and generating ideas for what might be an effective therapy that could help a lot of people.

“To see it all in one place is rare, and I think it’s absolutely unique to this institution.”