Study links cognition and brain networks before the first psychotic break

Posted by Danny Bonvissuto on Wednesday, March 5, 2025 in Around the Medical Center, Spring 2025 .

Early detection opens the door for noninvasive intervention for those with treatment-resistant symptoms of psychotic disorders like schizophrenia.

After correlating cognitive impairment and brain network organization in people diagnosed with psychotic disorders, Vanderbilt University Medical Center researchers discovered the same link in those who hadn’t had a first psychotic episode. Their groundbreaking study was published in Biological Psychiatry.

“This link between cognition and brain networks is present even prior to the first psychotic break, suggesting an opportunity for early diagnosis and intervention for the treatment-resistant symptoms of psychotic disorders like schizophrenia and bipolar disorder,” said first author Heather Burrell Ward, MD, director of Neuromodulation Research at VUMC.

Using data from two research consortia — the Human Connectome Project for Early Psychosis and the North American Prodrome Longitudinal Study — plus MRI and cognitive tests, Ward and her team observed that, in individuals with psychotic disorders, cognitive impairment is linked to brain network organization.

After analyzing data from individuals considered at risk for psychotic disorders, but who had not yet had a first psychotic episode, they identified the same brain network-cognition relationship only in those who would eventually develop psychosis.

“There had been a concern that this kind of brain imaging study wasn’t possible at all and that this kind of brain-wide association study linking fMRI signals to cognition/behavior would require thousands of participants to identify reliable findings,” she said. “We hypothesized that this limitation could be overcome with careful choices about cognitive testing and MRI analysis. We were excited to see that not only could our results be replicated, but that we could observe these strong brain network-cognition links in at-risk individuals even before they were diagnosed with psychosis.”

There are no medications to treat cognitive impairment associated with schizophrenia and other psychotic disorders. This impairment is often present by the time an individual has their first psychotic break, making early detection and intervention critical.

Ward is the principal investigator leading an NIH-funded clinical trial testing repetitive transcranial magnetic stimulation (rTMS, a form of noninvasive neuromodulation) for people with psychotic disorders.

“The next step is to test if this brain signature is malleable — that is, can we modulate this circuit with rTMS and improve cognitive performance,” she said.