Modern imaging has given researchers vast new understandings of how the complex circuitry of the brain works and goes awry.

But much remains unknown.

Some illnesses, such as schizophrenia and personality disorders, especially frustrate scientists — and illustrate the difficulty of understanding the labyrinth of mental illnesses.

“This is where we’ve made the least progress, quite frankly,” said Dr. Mark George, director of MUSC’s Center for Advanced Imaging Research and its Brain Stimulation Laboratory.

Schizophrenia, actually a complex group of disorders, appears to be caused by brainwide circuitry problems. They usually emerge in the late teens when the brain embarks on a massive rewiring project.

The dilemma: How do you target treatments to correct global brain dysfunctions?

Once researchers figure that out, treatments could develop for all kinds of other brainwide neurological problems.

“That would be the holy grail,” George said.

A dominant theory is that schizophrenia occurs in-utero during brain formation and causes a fundamental problem with brain organization. Then, for reasons researchers don’t understand, behaviors emerge during the brain rewiring project in the teens and into early adulthood.

“It’s something about the blossoming of the brain at that time that makes behaviors emerge in patients at high risk,” George said.

Schizophrenia also seems to appear more frequently in teens who use drugs, especially heavy amounts of marijuana, he said.

Then comes an entire group of mental illnesses that stump researchers — personality disorders.

“We really don’t understand those at all,” George said.

Are they even “diseases?” George questions the underlying notion that a person can have a disease of the personality or temperament. At what point is a major personality deviance, such as anti-social behavior, a diagnosable medical condition?

Plus, personality disorders often occur in people who experienced unstable early lives. Are they reacting to those experiences, or is there a physical dysfunction in the brain?

“It is harder to see, harder to diagnose,” George conceded.