Stimulation of brain's "depression switch" offers rapid, sustained relief
The past decade of research into deep brain stimulation (DBS), in which implanted electrodes are used to target specific brain regions with electrical impulses, has brought to light its potential to tackle a variety of neurological disorders. Depression is one where the technology is beginning to show real promise, and a new study has uncovered valuable details on how it induces anti-depressive effects, offering scientists a novel biomarker via which they can work to optimize the approach.
A number of studies in the past few years have driven home the potential of DBS to alleviate symptoms of depression, from improving mood in moderate to severe sufferers, to providing fast-acting and long-lasting relief in patients resistant to treatment. Despite these kinds of exciting results, there are blanks to fill in when it comes to how exactly DBS alters brain function, and what signs we might look out for to see if it is having the desired effect.
Led by scientists at Mount Sinai Hospital, this new study sought to dig into the mechanisms through which DBS can induce rapid and reproducible effects in subjects suffering from treatment-resistant depression. The experiments saw eight patients implanted with electrodes in a region of the brain called the subcallosal cingulate, known to play a major role in depression, with stimulation then applied over the course of one hour.
The scientists recorded the electrophysiological activity and with the help of a machine learning algorithm, monitored the electrical signals between neurons deep in the brain. This revealed a rapid and consistent change in brain state through a decrease in beta power at the site of stimulation, with these immediate changes correlating with a significant decline in depression scores even one week later.
“What we found was that within minutes of stimulation inside the operating room, there was a change in the beta brain rhythm," says co-first author Allison C. Waters. "Patients who showed larger changes then experienced greater relief from their depression in the week after surgery. The beta rhythm is conventionally associated with the brain's determination of whether to stop or keep going with a course of action, which is why neurologists target beta with DBS to treat disorders of movement. We haven't had a clear signal to target with DBS for depression, but now we can speculate as to how the beta signal might function in this context: a release of the brake that generates fatigue and slowness, or interrupting a habitual cycle of negative self-focused thought."
This identification of an objective biomarker by which scientists can track the efficacy of DBS in tackling depression is a key stepping stone in the effort to optimize the approach, and bring it to life as a clinical treatment. The pursuit of such biomarkers applies to other fields of DBS research, too, with another study this week not just identifying specific biomarkers associated with cognitive deficits, but demonstrating how implants might respond in real-time to improve mental function.
With regard to depression, the study offers evidence that the brain state changes that occur almost immediately after DBS is instigated can be used as an objective biomarker, and that the benefits last long outside the operating room. The trials monitoring these biomarkers are ongoing, with Phase II trials now recruiting new subjects as the scientists continue working to improve the lives of depression sufferers.
“We generally think of depression treatment as taking weeks to months to show stable and meaningful changes in core clinical features of the illness,” said study leader Helen S. Mayberg. “This study shows reproducible and consistent changes in a brain readout over the first minutes of optimized stimulation in the operating room in individual patients. This provides new mechanistic understanding of the 'depression switch' that moves a patient from a state of sustained mental pain and immobility to relief and the renewed capacity to move and engage.”
The research was published in the journal Translational Psychiatry.
Source: Mount Sinai