Mapping brain health
Brain imaging metadata helps advance mental health research and treatment
By Claire Kowalick
While most people focus on what they see during brain imaging, Peter Fox, MD, director of the Research Imaging Institute at The University of Texas Health Science Center at San Antonio, will tell you that the real value is in the mathematics and quantitative assessments behind those pictures.
Fox has worked for decades to understand the brain and its interconnected processes and networks of disease. As Fox explained, the brain is an information processing engine. It takes in information through our senses, synthesizing it to compute our experience of the world, interpreting the events unfolding around us, making plans and executing actions through neuronal signals to the muscles and other organs.
Just as scientists and engineers express many complex processes with network models, the brain is best understood as a multiscale hierarchy of networks. Diseases can be modeled as disruptions of these healthy networks.
Instead of specializing in any one disorder, Fox focuses on mathematical approaches that can be applied to normal brain functions and to a host of mental, neurological and development disorders.
In the 1980s, Fox introduced a system for standardizing brain imaging analyses and later created a way to share the data created by this strategy online. BrainMap, the standardized strategy he introduced decades ago, has been used by tens of thousands of published studies. Today, BrainMap shares published brain-imaging data from more than 250,000 research study participants’ scans. This is critical, since for conditions like mental health disorders, analysis of data on a massive scale is essential.
How it works
Data from a published work is inputted in a standardized way, created by Fox, and expressed in coordinates of x, y and z to pinpoint locations in the brain. Standardization means information from all over the world is mergeable into this treasure trove of data.
Fox explains that brain effects in psychiatric disorders are subtle and may hardly be visible with one person’s information. However, when there are data and metadata from 50 studies of 50 patients each and 50 controls, the disease effects come into focus.
At this point, there is no psychiatric disorder that can be diagnosed through imaging, and the neurobiology of mental health disorders is not well understood. Meta-analysis is the only way to get reliable results when associating specific brain areas with mental health disorders.
“We take those massive meta-analytic models to characterize disorders, to design new treatments for them and test them out through clinical trials,” Fox said.
Current research is exploring what cognitive areas to focus treatment on, the strength of connections within the networks, and how treatment administered in easier-to-reach areas of the brain affects the deeper regions of the brain.
Potential for targeted therapies
The imaging bank is also used to support work in interventional psychiatry treatments like transcranial magnetic stimulation, or TMS. During TMS treatment, a device is placed near a person’s head and magnetic impulses are strategically delivered to target specific portions of the brain.
“In neuromodulation, we’ve shown that when you stimulate one area, it spreads through the whole network,” Fox said.
A first-of-its-kind tool created by Fox’s lab and currently in the process of FDA approval is a robotic-driven, MRI-informed TMS system that promises unprecedented gains in therapeutic precision and personalization.
With his system, MRI brain modeling is completed for each individual and mapped to a model of the condition the person is experiencing. The model is used to compute the optimal pose for the robotic arm to deliver treatment. For each day’s treatments, the patient is precisely registered to their treatment plan. The robot then solves the path and applies the TMS treatment at a precision within one millimeter.
“This approach is more precise than anything that is being done elsewhere,” Fox said.
The BrainMap database makes it possible to catalog data from thousands of images and compare them to see what they have in common. Models are then adapted for each subject and modified frequently to create personalized, targeted treatments.
“We are at that level of trying to discover what the underlying mechanisms are and how we might want to treat them,” Fox said.
Through the power of large numbers, Fox and his team are making novel discoveries and using them to create highly precise treatments based on models of neurological function and disease networks.
“We take those massive metaanalytic models to characterize disorders, to design new treatments for them and test them out through clinical trials..”
-Peter Fox, MD, director of the Research Imaging Institute
Impacts for future treatments
In addition to his own research endeavors, Fox mentors and assists other UT Health San Antonio scientists in the use of brain mapping to expand knowledge in a variety of fields.
According to Sudha Seshadri, MD, director of the health science center’s Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, the support from the Research Imaging Institute is critical to the success of clinical trials on Alzheimer’s, dementia and other conditions. Seshadri said the institute, directed by Fox, is one of the main reasons she decided to come to UT Health San Antonio.
“Over the past six years, the Research Imaging Institute and Biggs Institute have grown together to attract outstanding faculty, initiate new ventures and attract over $40 million in research funding driven by our research imaging capabilities built over the years by Dr. Fox,” said Seshadri.
Melissa Martinez, MD, a professor of psychiatry and behavioral sciences, works closely with Fox in the use of repetitive transcranial magnetic stimulation (rTMS) for her patients with treatment-resistant depression. Fox invented an rTMS system that uses brain mapping for extremely precise treatment. The imaging-guided, robotically delivered rTMS at Fox’s lab is being considered for treatment of other conditions including post-traumatic stress disorder (PTSD) and smoking cessation.
John Moring, PhD, assistant research professor in the Department of Psychiatry and Behavioral Sciences, knew that to get to the neurological root of connections between tinnitus and PTSD, he needed training in brain mapping. Fox served as Moring’s mentor during his career-development training in neuroimaging. Moring said that because of Fox’s superior tutelage, he was able to conduct coordinate-based meta-analyses that highlight potential connections between the two conditions.
Globally, the surge in brain-mapping research seen today owes much to Fox’s leadership and the groundbreaking BrainMap initiative that he pioneered. His framework now enables the seamless collection and integration of brain data from researchers worldwide, fueling advancements that were once thought impossible and uncovering connections within the brain previously unimagined — offering new insights into these complex functions.
Fox’s work has not only revolutionized neuroscience, but also has catalyzed a shift in how neurological and mental health research is approached, laying the foundation for a future where the diagnosis and treatment of these conditions will be redefined.
Activation Maps
Activation maps show how brain regions are interacting while participants are “at rest” during a functional MRI scan. These images, from a study conducted by John Moring, PhD, provide a view of the brain’s resting-state network among a sample of 35 participants, including 24 with tinnitus only and 11 with both tinnitus and post-traumatic stress disorder. These images show several overlapping regions of the brain that are active in both tinnitus and PTSD. Current and future work by Moring will determine if treatments for one disorder could be effective for both disorders. These networks align with a previous study that included approximately 30,000 participants using the BrainMap database created by Peter Fox, PhD.
