By Tammy Awtry. Mentored and edited by Michael Chorost.
At the annual American Association for the Advancement of Science conference held virtually in February 2022, Helen Mayberg, M.D., discussed the three markers her lab developed to monitor and define recovery in patients who have been successfully treated for treatment-resistant depression with deep brain stimulation (DBS).
Treatment-resistant depression is a debilitating disorder affecting one-third of adults suffering from major depression. As the name implies, traditional therapies provide no relief. However, deep brain stimulation (DBS) has had tremendous success in reversing the symptoms associated with treatment-resistant depression. However, what does it mean to be well?
Mayberg argued that there is no way to monitor if patients are truly on the path to a full recovery without a definition of wellness. Once recovery has been defined, these markers can monitor how patients are doing and what treatment modifications may be necessary. Researchers and doctors will then be able to determine if a patient is in temporary distress or on the brink of a relapse. They will also be able to classify if a patient has achieved sustained recovery or are still in the short-term season of instability.
“As we think about the application of invasive neuromodulation to this almost nebulous and ethereal problem,” Mayberg says, “we have to reduce it down to elements that might be tractable and measurable.”
Mayberg’s lab at the Icahn School of Medicine at Mount Sinai has defined three markers to monitor dynamic metrics to distinguish successful short- and long-term treatment.
The first marker of wellness is the metaphorical “switch” that is flipped within a minute of a patient receiving DBS for the first time. The patient immediately feels a profound difference and relief from symptoms. This behavioral change was correlated with an electrophysiological shift in the subcallosal cingulate (SCC), where stimulation occurs. The SCC is a bundle of white matter that acts as a connecting highway between several brain regions and has been implicated in regulating negative mood states.
When the “switch” is flipped, a decrease in beta activity in the left SCC is seen, which is clinically meaningful because patients with depression almost always have more beta activity in the brain. The magnitude of the decrease was directly related to how well the patients were doing a week later without any further stimulation. However, this decrease could not predict how well the patients were doing six months later.
This led the lab to investigate the development of a second marker, which measured long-term, stable recovery effects. A comparison of patients receiving continuous DBS at the one-month mark and when they were considered well (after six months) showed that although the results were still left beta-dominant, it is a different effect than seen immediately after the “switch” was flipped. Here it was an increase in beta-activity. Gamma-activity, which is usually decreased in depression, was also increased.
“Actually,” Mayberg explained, “depression isn’t a mood disorder. It is a movement disorder.” The SCC has projections to the supplementary motor cortex, which is involved in controlling movement. When the initial “switch” is flipped in the operating room, Mayberg’s patients feel the negative emotions turn off and feel like moving. As Mayberg described it, “The initial decrease in beta-activity is no accident.” A person who is not ill will move away from a negative stimulus; movement is the reaction to the stimulus. Depressed patients want to move, but it is as if they are paralyzed. The initial stimulation gives the patients the ability to move. The late effect of this return to normalcy was that beta-activity could return to a new state of increased activity.
In addition to using brain activity as a marker, the lab also wanted to identify a non-invasive third marker for wellness. They determined that long-term recovery could be measured by analyzing facial features. A comparison of video interviews of patients before stimulation and after six months of continuous treatment showed a marked and measurable difference in facial movements across various features. It is not simply a result of the patients smiling more. They have increased movements of the eyes and forehead.
These three biometric markers can be used to individualize treatments. The data can be used to develop closed-loop neuromodulation systems or as a monitoring system to inform decisions about dose adjustments. They can also determine if sufficient brain adaptations have been achieved so that rehabilitation can begin to further support the patient’s recovery process. As Mayberg states, “We are about getting people back to ground zero.”
Tammy Awtry is a graduate student with Johns Hopkins University working on a Masters in Science Writing. She has previously earned a B.S. in Chemistry and Ph.D. in Neuroscience. She is the mom of three pretty awesome teenagers in Colorado. Email her at drawtry24@gmail.com.
