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Personalizing Neuromodulation for Neuropsychiatric Disorders

Neuromodulation, or brain stimulation, has emerged as a viable treatment option for neuropsychiatric disease, augmenting existing treatments such as drug-based and psychological therapies. At the Peter O’Donnell Jr. Brain Institute, UT Southwestern researchers are utilizing their knowledge to build infrastructure for personalized neuromodulatory therapies to treat patients with depression, obsessive compulsive disorder, psychosis, and anxiety.

According to William T. Dauer, M.D., the inaugural Director of the Peter O’Donnell Jr. Brain Institute and a Professor of Neurology and Neuroscience at UT Southwestern, the evolution of electrical and magnetic brain stimulation technologies has led to the creation of high-tech stimulation devices and more precise imaging. These advances have opened the door to understanding the complex neural pathways that contribute to neuropsychiatric disease and are helping clinicians target these diseased brain circuits.

A UT Southwestern team of surgeons and researchers is now on the cusp of delivering personalized stimulation treatment, which tailors therapy to an individual’s unique characteristics, including their clinical history, symptoms, brain anatomy, and biology, and living environment.

The O’Donnell Brain Institute has over 7,000 square feet of “dry lab” space dedicated to brain circuitry-related research where physician-scientists, neurosurgeons, ioinformaticians, electrical and biomedical engineers, psychiatrists, and theoretical neuroscientists are working together to advance these interventions.

“We believe that personalizing strategies tailored to the specific brain anatomy of each patient will significantly enhance the success of deep brain stimulation for treatment-resistant depression.”

Nader Pouratian, M.D., Ph.D.
Professor and Chair of the Department of Neurological Surgery


Evolving Applications

Modern neuromodulatory interventions include both invasive and noninvasive approaches such as deep brain stimulation (DBS) and responsive neurostimulation (RNS), which enable targeting of specific brain structures.

Building on pioneering depth electrode research, DBS was first applied to movement disorders in the late 1990s. Recent work is exploring its utility in conditions such as treatment-resistant depression, obsessive compulsive disorder, schizophrenia, eating disorders, and chronic pain.

Due to recent technological progress, implantable neuromodulation devices are now more precise, reliable, durable, and biocompatible. Furthermore, substantial leaps in MRI technology, such as diffusion tensor tractography, and optimization of electroencephalogram (EEG) data have yielded a wealth of knowledge about how neuronal circuits operate and interact in these disorders.

By utilizing these technologies, UT Southwestern researchers are examining electrode recordings from patients who have undergone DBS surgery. Moreover, they are noninvasively measuring brain electrical activity through EEG, working to decipher how different amplitudes, frequencies, bandwidths, and polarities of brain waves affect the excitation of nerves.

Pilot Studies Test Efficacy in Treatment-Resistant Depression

Under the direction of Nader Pouratian, M.D., Ph.D., Professor and Chair of the Department of Neurological Surgery, UT Southwestern researchers are leading two clinical trials exploring the utility of DBS in treatment-resistant depression.

The first (NCT03952962) is utilizing MRI tractography to determine the most effective treatment site within an area of the brain termed the subcallosal cingulate (SCC) for stimulation. The trial is enrolling 12 patients and is designed to identify personalized targets to guide neuromodulation programming and therapy. “We believe that personalizing strategies tailored to the specific brain anatomy of each patient will significantly enhance the success of DBS for treatment-resistant depression,” Dr. Pouratian says.

The second study (NCT03437928) is examining the simultaneous stimulation of two regions of the brain: the ventral capsule/ventral striatum and the SCC. Since each target area connects to different parts of the depression network, the trial will examine the effects of separate or combined stimulation in a cohort of six patients.

“This trial is unique because the team will implant temporary recording electrodes to map the biosignatures of depression to both improve treatment and learn more about how depression affects brain circuits,” Dr. Pouratian explains.

Pathway to Clinical Care
At present, an array of neuromodulatory treatments – both invasive and noninvasive alike – are under investigation for use in neuropsychiatric conditions. “The enduring interest in techniques such as DBS speaks to their potential as a treatment with longer-term impact,” Dr. Pouratian says. “DBS also has the ability to target deeper brain areas that are largely inaccessible to noninvasive methods.”

Though the O’Donnell Brain Institute’s umbrella of research spans from basic to translational science, neuromodulation is particularly beneficial in that it caters to the patient’s urgent clinical needs.

“My basic science colleagues are doing important work to understand the pathophysiology of depression, while my clinically based colleagues are eager to explore the neuromodulatory options newly becoming available to help patients forge healthy paths forward,” Dr. Dauer says. “It’s an exciting time to be working in this field.”

William T. Dauer, M.D., is Professor of Neurology and Neuroscience and the inaugural Director of the Peter O’Donnell Jr. Brain Institute. His research focuses on the molecular basis of dystonia and mechanisms of neurodegeneration in Parkinson’s disease.

Nader Pouratian, M.D., Ph.D., is Professor and Chair of the Department of Neurological Surgery. His research focuses on developing brain-mapping techniques to improve the precision and targeting of neurosurgical procedures.