Study: Brain Stimulation Can Be Individualized to Treat Depression

The most common treatment for depression often includes some mix of therapy and medication. But a new study offers a promising potential solution when traditional therapies don't seem to be doing the trick. "Targeted neuromodulation," according to a new preliminary study, could offer another, more individualized, option.

Neuromodulation is nothing new: it consists of sending electrical impulses to the brain and has been found to relieve symptoms of depression for decades, particularly in people whose depression does not respond to existing therapies. However, the novel aspect of the study lies in its personalization. Instead of sending electrical impulses to the entire brain, researchers targeted specific brain regions based on past patterns, hence the name "targeted modulation."

“Prior attempts to develop neuromodulation for depression have always applied stimulation in the same site in all patients, and on a regular schedule that fails to specifically target the pathological brain state," Katherine Scangos, MD, PhD, lead study author and assistant professor of psychiatry at the University of California, said in a press release. "We know depression affects different people in very different ways, but the idea of mapping out individualized sites for neuromodulation that match a patient’s particular symptoms had not been well explored.”

This study "really gets as near as you could get to circuit-level areas of the brain," Irving Reti, MBBS, a research psychiatrist at Johns Hopkins University in Maryland not involved with the study, tells Verywell. Even though personalized neuropsychiatry is still in its infancy, Reti, who is also the director of the Electroconvulsive Therapy (ECT) Service at Johns Hopkins Hospital, says this study and its technology are "taking things to the next level."

Researchers from the University of California San Francisco's Dolby Family Center for Mood Disorders and Weill Institute for Neurosciences published their findings in the journal Nature Medicine on January 18.

The Research

In one severely depressed patient, researchers mapped brain regions and how they responded to mild stimulation through stereo-EEG for ten days.

They then matched each stimulated area with a perceived effect, depending on the emotional state an individual was in. For example, sending electrical impulses to certain sites helped alleviate depression symptoms, such as anxiety, low energy, and anhedonia—the inability to feel pleasure.

The patient this technique was used on is a 36-year-old woman who has been dealing with "severe treatment-resistant depression since childhood," hampering her ability to work or even drive. When stimulated in one region, she reported "tingles of pleasure," and in another, "neutral alertness…less cotton and cobwebs," according to the press release.

However, stimulation can have different effects depending on what state the patient is in. For example, stimulating one area when the patient feels anxious can lead to calm feelings, but led to drowsiness when the patient was already feeling more low-energy.

Duration of stimulation, as well as the duration of perceived relief, pose additional variables. Still, researchers found that it was possible to alleviate depression symptoms for hours. At the close of the 10-day trial, the patient experienced "temporary remission lasting six weeks."

After six weeks, researchers surgically implanted a neuromodulatory device called the NeuroPace Responsive Neurostimulation (RNS) System. The device is already used in individuals with epilepsy and works by detecting and stopping seizures before they occur through targeted neuromodulation. This time, it will work in the same way, but on brain patterns that indicate a depressive episode.

The patient reported that she can't tell when the device is stimulating her brain, which helps it realize its ultimate goal. “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," Scangos explained in the press release.

This is the initial study of a five-year clinical trial that seeks to evaluate this personalized neuromodulation on a larger scale. Researchers will implant the same device in 12 patients with major depression who have not responded to any other therapies. By learning how patients with depression and their brains specifically respond to modulation, researchers can program devices to send stimulation in real-time.

How Is It Different From "Electroshock" Therapy?

"Targeted neuromodulation" might seem similar to the century-old term "electroshock therapy," now known as electroconvulsive therapy (ECT)—which Reti says many of his patients and their families might "recoil" from at first mention.

"It's about destigmatizing mental illness, and especially ECT," Reti says, making reference to the mental images many have of what ECT is, influenced by movies and historical accounts.

Nowadays, ECT is administered with muscle relaxants, minimizing patients' movement during the seizure. Also, people tend to come in for more than one treatment, given that it works overtime.

Still, ECT can lead to memory loss, which has led researchers to try new, non-convulsive brain stimulation treatments, such as Transcranial Magnetic Stimulation (TMS), Deep Brain Stimulation (DBS), and now, the personalized neuromodulation highlighted in this recent study.

Reti says that ECT is notable for its rapidity. "The thing that is extraordinary about ECT that you don't see with other psychiatric treatments is that very ill patients often get better very quickly," Reti says. "It's quite remarkable to see them turn around…sometimes after just three treatments."

"It's a good area to be educating the public about...to help destigmatize illness and treatment," Reti adds. "The more education, the better."