The Brain’s Flexibility May Hold the Key to Understanding Mental Illness in a Whole New Way

A healthy brain is not a static organ. It is constantly reorganizing itself, shifting between different networks depending on what you are doing, thinking or feeling at any given moment. That dynamic flexibility, the brain’s ability to fluidly reconfigure its connections in response to changing demands, is one of the most important and least discussed aspects of mental health. And according to a landmark new study published in Nature Communications, disruptions in that flexibility may be at the heart of psychiatric illness in ways that cut across traditional diagnostic categories.

Inside the Research

Researchers at Rutgers University, led by postdoctoral fellow Carrisa Cocuzza, Ph.D., and Avram Holmes, Ph.D., associate professor of psychiatry at Robert Wood Johnson Medical School, studied 219 people, including 134 individuals with psychiatric diagnoses spanning 11 different conditions and 85 people without any psychiatric diagnosis. Participants underwent two types of brain imaging scans: resting state MRI, which captures brain activity when a person is simply lying still, and task-based MRI, which captures how the brain responds while actively performing cognitive tasks. This allowed researchers to examine how brain connectivity patterns shifted across six different cognitive states.

The team also gathered more than 100 behavioral, cognitive and clinical measurements from each participant, which they used to create individualized symptom profiles. Those profiles clustered into four core dimensions of functioning: internalizing symptoms like depression and anxiety, externalizing symptoms like impulsivity and aggression, cognitive functioning, and social and reward processing.

When Flexibility Disappears

The results revealed something striking. People with psychiatric conditions showed significantly reduced flexibility in their brain network dynamics. Rather than fluidly reconfiguring in response to different cognitive demands, their brain networks appeared flattened, less able to shift and adapt across states.

“Their brain networks were less able to shift between different configurations across cognitive states compared to healthy individuals,” Cocuzza explained.

That reduced flexibility was useful for distinguishing between people with and without psychiatric diagnoses. But the most important finding was what happened when the team compared brain dynamics with symptom profiles rather than diagnostic labels. The patterns of brain network flexibility were more strongly linked to individuals’ specific symptom fingerprints than to whether they carried a particular diagnosis at all.

“This work addresses a central challenge in clinical neuroscience, linking changes in brain function to the diverse symptoms experienced across psychiatric disorders,” Holmes noted.

In other words, knowing someone has depression, attention-deficit/hyperactivity disorder (ADHD) or posttraumatic stress disorder tells you less about what is happening in their brain than knowing the specific pattern of symptoms they experience. Two people with the same diagnosis can have very different brain network dynamics, while two people with different diagnoses can look remarkably similar at the neural level.

The investigators also identified a particularly important role for inhibitory cognitive control and interactions between the frontoparietal networks, regions of the brain involved in higher-order thinking, attention and emotional regulation.

A Shift in How We Think About Mental Health

The way mental health conditions are currently diagnosed relies heavily on symptom checklists and categorical labels. You either have depression or you do not. You have ADHD or you do not. But decades of research and clinical experience have shown that this categorical approach misses something important: the enormous variation in how psychiatric conditions manifest in different people, and the significant overlap between conditions that are officially considered distinct.

This study supports a fundamentally different way of thinking about mental health, one that focuses on the biological reality of individual symptom patterns rather than diagnostic boxes.

“The findings indicate that impairments in time-varying brain processes may underlie differences in cognitive and behavioral functioning across individuals,” Holmes said. “By showing that brain network dynamics track symptom variation across diagnostic boundaries, the study supports a shift toward more personalized, biology-informed models of mental health.”

The investigators note that future work will examine how brain network dynamics change over time and in response to treatment, an important next step toward making these insights clinically actionable.