Dr. Helen Mayberg, MD is a professor and neurologist at Mount Sinai in New York City. She has gained a reputation as an authority in the study and treatment of depression. Focusing at the circuit level on the etiology of depression, Dr. Mayberg formulated a novel theory of the systemic dysfunctions involved in depression. Her work showed how many disparate areas of the brain interact with each other in depression, eventually discovering evidence pointing toward a region of the brain, Brodmann Area 25 (BA25), whose (dys)function is of central importance in the condition. This area’s activity was demonstrated to be connected to the experience of extreme negative affect. In the context of the brain as a whole, BA25 represents a good candidate for a network hub that coordinates the different regions involved in bringing about the unhealthy mental states associated with major depression.
Having uncovered the central role of BA 25, Dr. Mayberg subsequently turned to the goal of translating her discovery into an effective therapeutic. This is something which is sorely needed, depression being one of the most significant causes of morbidity and lost productivity throughout the world. Dr. Mayberg moved forward on the hypothesis that if BA 25 was an important coordinating region in depression-related pathological states, modulating its activity may have an overall salutary effect on mental health. This modulation can be achieved by the use of Deep Brain Stimulation, wherein a pacemaker-like device is surgically implanted deep within the brain in order to deliver electrical current to precisely alter the activity of a tiny target region of the brain. DBS is an effective treatment for the neural degeneration associated with Parkinson’s Disease, but it also represents a promising topic of research in the development of therapeutics for a wide variety of psychiatric and neurological conditions. Dr. Mayberg and her collaborators thus became pioneers in the use of DBS in depression; beginning nearly two decades ago, the team began to successfully treat depressed patients who had previously failed to respond to many other treatments. DBS remains an important emerging technology in the alleviation of depression, with more research coming out every year.
One of Dr. Mayberg’s more recent publications, published in April of 2017 in the Nature journal Molecular Psychiatry, focused on a connectomic approach to precisely target the placement of DBS devices in interventions for depression. Before surgery, the researchers used high-resolution MRI scans to perform Diffusion Tensor Imaging (DTI), an imaging method that can reveal the connections (white matter fiber tracts) between different areas of the brain in three dimensions. Using a technique called Determinisic Tractography, they used these images to determine the strength of the connections between those regions identified as pathological in depression, including those networked together with BA 25. The image included here (Figure 2 from the paper) provides a visual representation of these connections: the panel on the left is a global view of the four main fiber bundles that converge on BA 25 which are important in the mechanism of successful DBS treatment, and on the right a view of one patient’s network connections (tractography) is depicted. They used this connectomic knowledge to tailor the placement of DBS contacts within the subcallossal cingulate gyrus (a region which includes BA 25). After surgery and the initiation of DBS treatment, they performed further tractography to identify connectomic changes associated with the therapeutic and further tailor future patient’s surgeries. Overall they achieved a positive response in 9 out of 11 patients after one year, 6 being in remission. This study represents a significant step forward in the refinement of DBS into a precise and effective treatment for a devastating disease.
Zarek Siegel is a first-year PhD student working in Eric Halgren’s research group.