DBS Response to Severe Depression Predicated on Brain Rhythms

In new discoveries, researchers found that a fast and consistent decrease in beta energy at the site of DBS suture implantation was linked with a significant and prolonged reduction in depressive symptoms, according to preliminary research.

Researchers observed that brief stimulation at the time of DBS suture implantation produced a rapid and continuous decrease in beta energy measured at the site of implantation.

The researchers also found that a slower and less-consistent decrease in beta energy over the first 3 months was associated with a shorter time to depressive relapse as compared to those with fast and continuous reductions.

Surgically placed DBS electrodes deliver high-frequency electrical stimulation to key regions of the brain implicated in depression, such as the subgenual cingulate cortex, nucleus accumbens, and ventral capsule/ventral striatum.

This stimulation is intended to alter the activity of these regions to reduce depressive symptoms.

“By patient, the magnitude of the decrease in left beta strength can predict how well they’re doing after a week,” study researcher Helen Mayberg, M.D., director of the Nash Family Foundation for Advanced Circular Therapies at Mount Sinai in New York City, said.

“Patient by patient, the size of the decrease in beta strength, and whether it’s rapid and continuous, versus slower and less steady, is also predictive of who relapses after the period of acute stimulation.”

The research was published online on November 3 in Translational Psychiatry.

Setting appropriate objectives

At the time of bilateral DBS sutures being implanted into the sub-cingulate region (SCC), eight persons with treatment-resistant depression underwent intraoperative electrophysiology recording.

Investigators created patient-specific preoperative models to determine the best target within the SCC for lead implantation.

For the four weeks after surgery, 20 minutes of stimulation was delivered at optimal targets established by the traction device, without any stimulation.

LFPs – electrical communications between neurons deep in the brain – were recorded simultaneously during intraoperative stimulation.

The patient’s depression scores decreased by 45.6% on the 17-item Hamilton Depression Rating Scale (HDRS) after the DBS suture implants, which resulted in an average of 7.8 points.

After establishing the settings on the stimulation device that was most effective at suppressing beta activity for each person, subjects underwent continuous bilateral stimulation for 4 weeks without any changes before being followed clinically for 12 months after surgery.

Investigators noted significant depressive symptom suppression during this time.

However, they also noticed that a continuous and rapid beta suppression was linked with a long time until depressive symptoms returned in comparison to others who experienced a slower and less consistent decrease in beta energy.

The results indicate that the faster and more consistent reduction in beta activity across the SCC is associated with a better antidepressant response after acute stimulation.

This early antidepressant response was linked to a reduction in left hemisphere SCC beta power. The researchers wrote that the connection of symptom improvement with reduced beta-SCC strength indicates that this electrophysiological finding is a “biomarker for treatment improvement.”

This research demonstrates reproducible and consistent changes in brain reading throughout the first minutes of acute stimulation, t provides a roadmap of sorts for how to best use brain reading in clinical practice to enhance treatment response and measure its real-time impact on brain function during the acute stimulus.

Helen Mayberg, M.D. Director of the Nash Family Foundation

The researchers add that the early decrease in depressive symptoms was “partially but not completely” lost during the one-month postoperative fading period.

Furthermore, it is still uncertain whether intracranial stimulation-induced beta strength changes are predictive of a sustained clinical response to chronic DBS therapy for treatment-resistant depression.

But, according to the researchers, chronic SCC DBS at optimal locations as determined by the traction device resulted in an 88% response rate (7 of 8) after 6 months of treatment.

The team suggests that a better understanding of the key beta-related brain networks involved in depression may lead to improved treatment outcomes.

Further research published earlier this year showed that DBS applied to one part of the brain might help reduce depressive symptoms by triggering the release of another neurotransmitter – dopamine, which is linked with increased motivation and goal-oriented behavior.

Closer to reality in mental health

“This line of work takes psychiatry one step closer to precision,” said Shaheen E. Lakhan, MD, Ph.D., a neurologist in Newton, Massachusetts. Medscape Medical News.

“Outside medicine, many ailments have measurable biomarkers that indicate whether the disease is present or worsening. There’s hemoglobin A1c for diagnosing diabetes, urine tests for urinary tract infections.

But psychiatry has not had this until recently with the advent of functional neuroimaging.”

The research was funded by the US National Institutes of Health, the Department of Defense, and industry (Uniformed Services University; St Jude Medical). The study authors report no relevant financial relationships.

“Over the last several decades, DBS for people with advanced Parkinson’s disease has produced an intriguing occurrence: their sadness typically subsides and their mood improves.

Researchers have attempted to determine whether this is simply a reduction in motor symptoms of Parkinson’s disease or whether Deep brain stimulation directly impacts mood.

To everyone’s surprise, a specific subset of neurons within the ventral capsule/ventral striatum (VC/VS)–a subcortical brain region involved in motivation, pleasure, and reward–seems to play a role.”

This study now shows that the beta rhythm, a signal deep in the brain that traditional EEG can’t pick up, “predicted who would later benefit from DBS at the time of transplant,” according to Dr. Lakhan.

“This is absolutely essential not just for predicting response to DBS for depression, but also for targeting this potential biomarker of treatment success more broadly, for other psychiatric disorders.”

The researchers indicated that this finding could help determine whether early-phase clinical trials can be held with a simple 10-minute EEG test instead of the more invasive DBS electrode implantation.

The study was conducted by scientists from Mass General Hospital (MGH), Brigham and Women’s Hospital, and the VA Boston Healthcare System, all in Massachusetts, Emory University School of Medicine in Atlanta, Stanford University, Palo Alto, California, and the New York State Psychiatric Institute.

“Lakhan thought that ‘other treatment trials, for example, with medicines or non-invasive digital neurostimulation and modification (DiNaMo), might utilize this biomarker to improve development and maximize effect one day for a certain person,’” according to the report.

“These signals are deep in the brain now, but it’s possible that even something as simple as a wearable EEG, with electrodes placed on the scalp instead of invasive DBS implants, could help make these signals accessible to anyone.”