Researchers from the Mark and Mary Stevens Neuroimaging and Informatics Institute ( Stevens INI ) at the Keck School of Medicine of USC will lead a worldwide effort to map how eight common psychiatric disorders affect brain function, supported by a five-year, $3.2 million grant from the National Institutes of Health.
The Global Initiative for Harmonized Functional MRI in Psychiatry will analyze over 94,000 brain scans collected at 257 research sites in 27 countries, from participants ages 4 to 95. The project covers schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, and anorexia nervosa. The investigators say it will be the largest functional MRI study ever conducted, both in the number of people scanned and the number of labs taking part.
“Each of these conditions has been studied mostly on its own, with each group using its own tools,” said Paul M. Thompson, PhD , associate director of the Stevens INI, director of the ENIGMA Consortium, and principal investigator of the project. “When every lab processes its scans the same way, we can finally discover which brain abnormalities are shared across disorders and which are specific. Our new global effort will have enormous power to identify brain signatures that are the most sensitive to each illness, to help us target treatments and predict treatment response.”
Reading the brain at rest
The project relies on resting-state functional MRI, which records brain activity while a person lies quietly in a scanner. The scan tracks small shifts in blood oxygen that rise and fall as brain regions work. When two regions rise and fall in step, like musicians keeping time in an orchestra, researchers consider them functionally connected. Recent work has discovered functional networks involved in attention, rumination, and planning, with a complex pattern of switching and interactions between them that is disturbed in mental illness.
Smaller studies have reported differences in these connection patterns in people with psychiatric conditions, but results have been hard to compare. Labs use different scanners and different analysis steps, and a single study rarely includes enough people to detect subtle effects.
“There is broad agreement that many of the conditions we study in psychiatry share common roots in the brain, yet research on each condition still happens largely in isolation, partly because comparing many diagnoses at once on a large scale is so difficult,” said Frank Hillary, PhD, professor of psychology and neurology at The Pennsylvania State University. “One critical goal of this project is to develop shared methods for studying how brain networks function, so that different areas of psychiatry can be examined side by side to better understand their similarities and differences.”
One method, eight disorders
The effort expands the ENIGMA Consortium , a global network of over 2,500 scientists in 47 countries who conduct some of the largest brain imaging studies of neurological and psychiatric disease. For this project, eight separate international research groups, each focused on one disorder, have agreed to analyze their functional scans with the same standardized processing pipeline, a shared set of software steps that cleans each scan and measures brain connections and dynamic brain changes identically. According to the investigators, it is the first global effort to standardize how functional brain scans are analyzed in psychiatry.
“Until now, a finding in autism and a finding in schizophrenia could come from very different analysis choices, so we couldn’t line them up fairly,” said Clara Moreau, PhD, assistant professor of psychiatry at the Université de Montréal and co-chair of the ENIGMA functional MRI working group. “Agreeing on a targeted multiverse approach, which is used across the world and across disorders, lets us identify distinctive features of these conditions for the first time.”
The size of the combined dataset also opens the door to artificial intelligence methods, which need large amounts of data to learn reliable patterns. The team plans to use these tools to search for markers of illness too subtle for smaller studies to detect.
Testing how disorders group together
Earlier genetic studies suggest these conditions may fall into three families: mood and psychotic disorders, developmental disorders, and compulsive disorders. The researchers will test whether brain function shows the same grouping, which could point to shared biology beneath conditions that are currently diagnosed separately.
The team will also examine how medications such as lithium and antipsychotics relate to differences in brain functional dynamics and connectivity. The project’s broader aims include improving diagnosis, clarifying how these disorders affect the brain, and identifying brain measures that drug trials could use to tell whether a treatment is working. Any such measures would need further testing before they could guide diagnosis or treatment.
“Studies of this size depend on researchers around the world agreeing to share methods and pursue the same questions,” said Arthur W. Toga, PhD , director of the Stevens INI. “By bringing together data from tens of thousands of people across eight conditions, this work could help move psychiatry toward measures grounded in brain biology.”
About the project
The leadership team includes 17 institutions in the United States, Canada, Germany, the Netherlands, Switzerland, France, and Australia. This project is funded by the National Institute of Mental Health, a part of the National Institutes of Health, under award number R01MH142539. Stevens INI researchers on the project include Drs. Christopher R. K. Ching and Katherine Lawrence, and Sophia Thomopoulos (ENIGMA consortium manager).