Gaining a clearer picture of how injury, illness reshape the brain
A blow to the head unleashes a complex cascade of events. Cables in the brain’s transmission system stretch and disconnect. Nerve cell communication breaks down. Blood vessels rupture.
There were over 200,000 hospitalizations in the United States related to traumatic brain injury (TBI) in 2019, according to the Centers for Disease Control and Prevention. But only in the past two decades have researchers begun to understand precisely how those events impact thinking, behavior, and function.
That’s thanks to advancements in imaging equipment and techniques, says Neil Harris, PhD, professor-in-residence in the Department of Neurology at the David Geffen School of Medicine at UCLA, who has 25 years of experience studying brain injury in animal models.
“In vivo imaging is a very powerful technique, because not only does it allow you multiple shots on goal, but we can look at disease progression without having to harvest the tissue of an animal,” Dr. Harris says. “We’re using the very same imaging techniques to study animals as the ones clinicians use on patients, and so, it’s much easier to translate findings from animal to human.”
In clinical research, improvements in techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) have given scientists access to unprecedented amounts of brain connectivity information, or how various regions work together in both healthy and damaged brains.
But having access to so much real-time information can be a challenge in itself, says Roger Woods, MD, a professor in the Department of Neurology at UCLA and director of the Ahmanson-Lovelace Brain Mapping Center. Unlike, say, genomics studies, in which a researcher can perform multiple tests on a patient’s tumor, imaging requires a person’s real-time participation.
“We could have a patient in the MRI scanner 8 hours per day, every day for a week, and still have more to learn about the specifics of their brain connectivity. Obviously, that’s not practical or cost-effective,” says Dr. Woods. “The challenge is to distill out the information that really matters for clinical purposes. That’s the challenge the field is still trying to work through.”
Exploring unique methods
Dr. Harris and Dr. Woods are among a large and diverse group of research scientists at UCLA Health who are using imaging to gain deeper insights into the intricate, mysterious system that is the human brain.
In Dr. Harris’s lab, a primary research focus is uncovering how rehabilitative interventions after traumatic brain injury could be adapted to improve brain connectivity and clinical outcomes.
To start to answer these questions, Dr. Harris and his team are imaging rodent models of brain injury while they are resting and during tasks. This method, he says, provides an “unbiased approach” to monitor brain circuitry.
Another method the research group is exploring is functional ultrasound imaging which, unlike MRI, allows the laboratory’s researchers to monitor changes in brain connectivity directly through the skull in a freely moving rodent while it is performing a cognitive task. The technology is new and still being developed, says Dr. Harris, but already has led the team to discover interesting changes in brain connectivity after just a single concussion.
DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) is one of the other technologies that Dr. Harris is employing in his lab to study brain function after injury. The technology uses designer receptors introduced into cells — in this case, in the brain — through viral vectors. The researchers are then able to remotely activate and study distinct areas of the brain to test for their effect on improving outcome with rehabilitation therapy.
The ultimate goal of his lab, Dr. Harris says, is to determine biomarkers that can predict how the brain might respond to certain interventions — both pharmaceutical and rehabilitation — in order to find the most useful therapeutic approaches.
“There’s no magic bullet, but I think understanding brain function will lead to new interventions that, in combination with physical therapy, will modulate the brain to improve outcomes.”
Treating psychiatric disorders
In UCLA’s Brain Mapping Center, Dr. Woods has joined a number of studies using imaging to investigate the underpinnings and potential therapies for various psychiatric disorders, including depression.
In a study published last month in Nature Scientific Reports, for example, Dr. Woods and a group of researchers led by Katherine Narr, PhD, an associate professor-in-residence in the Department of Neurology at UCLA, showed with MRI that a non-invasive brain stimulation method led to structural brain changes in patients with major depression.
Major depression is one of the most common mental disorders in the United States, with an estimated 21 million adults experiencing at least one major depressive episode in 2020, according to the National Institutes of Health.
Transcranial direct current stimulation (tDCS) delivers low electrical currents to the scalp to modulate the excitability of neurons. Some research suggests that tDCS may improve symptoms in psychiatric disorders, like depression, “and it can have effects that are persistent even after the current is no longer being applied,” Dr. Woods says.
However, there have been mixed results from clinical trials, underscoring the need for researchers to demonstrate evidence of changes in brain connectivity.
Analyzing longitudinal structural MRI data from a randomized, double-blind, clinical trial of patients with depression, the UCLA Health research team found that the therapy induced significant increases in gray matter in the patients. Depression has been shown to lower levels of gray matter, which is found on the outer layer of the brain and is essential to proper brain function.
“We’re thinking about this kind of treatment in a number of psychiatric diseases — as a way identify and modify a certain brain circuit by changing its excitability,” Dr. Woods says.
The strength in brain imaging research at UCLA Health, he adds, lies within the diversity of its researchers.
“One of things that has always been appealing about brain imaging is that it is so collaborative between so many specialists across many different disciplines,” Dr. Woods says. “UCLA capitalizes on the strength of our neurology, psychiatry, and neurosurgery divisions.”
Lauren Ingeno is the author of this article.