Depression can be a crippling condition for those who suffer from it. Researchers have developed a variety of ways to manage its symptoms, but the results are different for everyone. Experts recommend an individualized treatment plan to help people manage their symptoms in the most appropriate way.
Now, a team of scientists from the University of California San Francisco (UCSF) is taking that to the next level. The researchers developed a system for customized neurostimulation based on a person’s current mood that could be used to eliminate depression symptoms altogether. Their approach builds on previous research done in the area of targeted neuromodulation.
So far, the team has only demonstrated its approach in one patient. However, the results are promising and the researchers plan on conducting a larger trial in the days to come. The research was recently published in the journal Nature Medicine.
The brain is a complex network of electrical pulses that dictate what we think, feel, and do. Much like a pacemaker modulates the electrical signals of the heart, specialized probes can be used to change the electrical signals in the brain.
In a press release, UCSF professor Dr. Katherine Scangos said, “The brain, like the heart, is an electrical organ, and there is a growing acceptance in the field that the faulty brain networks that cause depression – just like epilepsy or Parkinson’s disease – could be shifted into a healthier state by targeted stimulation.”
This isn’t the first time that researchers have tried to use neuromodulation to treat depression. Previous attempts, however, always worked with the same part of the brain during each session. The UCSF team wanted to explore what happened by modulating different parts of the brain based on a person’s current mood.
Study co-author Dr. Andrew Krystal says, “We’ve developed a framework for how to go about personalizing treatment in a single individual, showing that the distinctive effects of stimulating different brain areas are reproducible, long-lasting, and state-dependent.”
How it Works
The approach used by the UCSF team is novel but relies on previous research in many ways. To determine if its system was effective, the team enlisted the held of one patient with severe, long-term treatment-resistant depression. The 36-year-old woman spent 10 days with the research team at UCSF’s Helen Diller Medical Center.
During that time, the researchers mapped how electrical stimulation in different areas of the brain affected its signals. They used an approach called stereo-EEG to monitor the patient’s brain via 10 intracranial electrode leads.
Interestingly, the team found that stimulating several distinct brain sites for 90 seconds reliably produced a positive emotional state. Researchers used clinical scales to assess the patient’s depression symptoms and severity throughout the 10-day period.
In all, the researchers explored three sites, honing in on each one with longer sessions lasting three to ten minutes to try and create longer-lasting relief.
The team found that the patient’s current emotional state at the time of treatment had a lot to do with how she responded. When the patient felt anxiety during the stimulation, she reported feeling calmer afterward. When she was feeling tired, she said that the stimulation made her feel even more drowsy. Although the effects weren’t identical across all three regions, they changed depending on how the patient felt at the time.
While there is still plenty of work to do regarding this technology, the original patient’s words are striking. Following the trial period, she said, “I’ve tried literally everything, and for the first few days I was a little worried that this wasn’t going to work. But then when they found the right spot, it was like the Pillsbury Doughboy when he gets poked in the tummy and has that involuntary giggle.”
“I hadn’t really laughed at anything for maybe five years, but I suddenly felt a genuine sense of glee and happiness, and the world went from shades of dark gray to just—grinning,” the patient added.
Those words are inspiring for those looking to escape from the symptoms of their depression. For the researchers, they were highly motivating.
Over the course of the study, the researchers found that they could generate long-term symptom relief by tailoring the stimulation to the patient’s mood. Ultimately, she experienced a remission of six weeks following the 10-day period.
Krystal says, “The fact that we could eliminate this patient’s symptoms for hours with just a few minutes of targeted stimulation was remarkable to see. It emphasizes that even the most severe depression is a brain circuit disease that may just need a targeted nudge back into a healthy state.”
More to Come
Sadly, the patient’s depression symptoms did return after the six-week remission. That wasn’t entirely unexpected. It also gave the researchers a chance to move to the next phase of the trial.
They implanted a device called the NeuroPace RNS System in her brain. It was originally designed for people with epilepsy. When a patient is about to have a seizure, the device detects brain patterns which indicate it and applies targeted stimulation to cancel them out. This effectively prevents the seizure from happening.
In this case, the device detects when the patient is heading towards a highly depressed state and can intervene in real-time. It applies undetectable levels of targeted neurostimulation at just the right moment.
Scangos says, “The idea is that keeping neural circuit activity functioning along the correct track, the pathways that support pathological negative thought processes in depression can be unlearned.”
Since having the NeuroPace device implanted in June, the UCSF patient says that her depression symptoms have almost completely gone away. She says, “I can’t tell exactly when the device turns on, but I generally feel more of a sense of clarity, an ability to look at my emotions rationally and apply the tools that I’ve worked on through psychotherapy, and that is so far from where I was before.”
Next, the patient will undergo two additional six-week periods, one with the device turned on and one with it turned off, to monitor for placebo effects.
More research will be needed before this approach can safely be prescribed to patients outside of a trial setting. The team is planning to include 12 participants in its so-called PRESIDIO trial in the days to come.
Pending the results, targeted, timely neuromodulation could become a viable option for those battling depression. In the meantime, it provides hope for those looking for a solution.