Rachel Smith, Ph.D., is collaborating with researchers across UAB on the two-year project, which will focus on the intracranial neural networks responsible for major depressive symptoms in epilepsy patients.
Photographer: Lexi CoonRachel Smith, Ph.D., received a 2024 NARSAD Young Investigator grant from the Brain and Behavior Research Foundation that could create new insights into what takes place inside the brains of clinically depressed patients.
Smith, an assistant professor in the University of Alabama at Birmingham’s School of Engineering, is collaborating with researchers from UAB’s Departments of Psychiatry, Neurology and Psychology on the two-year project, which will focus on the intracranial neural networks responsible for major depressive symptoms in epilepsy patients.
“Research into mental health disorders, such as anxiety, depression, schizophrenia, OCD, etc., typically focus on the disorder directly,” Smith said. “It often doesn’t branch out into disorders such as epilepsy where they often co-occur. Our study is unique because, by focusing on patients with epilepsy who also have depression, we will have access to tools in the brain that we wouldn’t have in a broader sample of depression patients.”
It is estimated that more than 30 percent of epilepsy patients suffer from depression — and some estimates go as high as 80 percent. That overlap creates a ready-made cohort of subjects who can supply data through intracranial EEG electrodes that are already routinely used in studies of epilepsy.
“Even though the conditions can be independent of one another, these tools that we use to treat epilepsy will allow us to collect data that could lead to a better understanding of what is happening in these highly specific neural networks of depressed patients,” Smith said.
Smith’s study comes at a time of increased interest in the use of electrical stimulation to treat psychiatric disorders such as treatment-resistant depression. Scientists have seen some early success using deep-brain stimulation therapy for movement disorders and obesity disorders. However, when used to treat patients suffering from TRD, DBS has been inconsistent, at best.
The reason DBS works in some patients and not in others, Smith says, is an incomplete understanding of the heterogeneous brain networks that regulate mood. “These networks are unique to each patient,” Smith said. “They have been investigated using noninvasive neural imaging modalities with some success, but these modalities have low temporal resolution.”
Accessing the brain
To get a clearer understanding of what is happening in the brains of patients with TRD, Smith says, scientists will need to literally get inside the heads of patients.
“By placing electrodes inside the brain through intracranial EEG, we can access the specific neuronal circuits that give rise to depressive symptoms,” Smith said. “The problem is that we can only currently test this in patients with epilepsy where intracranial EEG is part of routine clinical care, and this technique does not yet apply to the broader TRD community.”
That is where Smith and her team of UAB researchers come in. Since arriving at UAB in 2022, Smith has received multiple grants to fund research into epilepsy. During her research, she and her collaborators have established a protocol for performing single-pulse electrical stimulation in epilepsy patients to define pathological effective (directed) connectivity and to identify hyperexcitable areas in the epileptogenic network that can serve as potential neuromodulation targets.
Laying a foundation for future research
Since January 2023, Smith’s team has collected data using SPES from 18 epilepsy patients. With the funding from the BBRF, her team plans to grow that cohort to 30 patients. “Our overarching goal is to use SPES to both map depression effective connectivity networks in epilepsy patients and infer biomarkers for neuromodulation strategies for TRD,” Smith said.
Collaborating on the project with Smith are Matthew Macaluso, D.O., from the Department of Psychiatry; Benjamin Cox, M.D., from the Department of Neurology; and Adam Goodman, Ph.D., from the Department of Psychology.
“Ideally, this will be a first step,” Smith said. “We hope this project will lay the groundwork for several future research directions that are likely to be funded by the NIH, NSF and Department of Defense. As we discover which neural features best reflect the depression burden in epilepsy patients, we can develop specific stimulation strategies to modulate these features.”