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By Sara Bottome

In 2019, roughly 7.8% of adults and 15.7% of adolescents in the United States experienced at least one major depressive episode. While psychotherapy, exercise, and antidepressants can help alleviate depression symptoms for most people struggling with mild to moderate depression, some with major depressive disorder (MDD) are resistant to these treatments

Electroconvulsive therapy, which causes intentional seizures that jolt the brain, is one of the most common and effective treatments for those with resistant severe depression. The therapy was first used in the 1930s; although electroconvulsive therapy generally remains the most effective, many other approaches utilizing electricity to stimulate the brain have been developed since then.

One of the most promising electrical therapy approaches is deep-brain stimulation. The first clinical attempts to use this method involved inserting wires into a specific region of the patient’s brain and applying a constant high frequency. This particular approach, which applies a constant stimulation to one region of the brain, is known as open-loop stimulation. The results were mixed; the non-stop full stimulation lifted some out of depression, but not all, and a large clinical trial held in 2017 failed to show any significant positive results from the treatment. 

Luckily, researchers knew where to turn next; many believed that deep-brain stimulation could be improved with the development of a more targeted approach using closed-loop instead of open-loop stimulation. 

The development of closed-loop therapy capable of targeting an individual patient’s depressive symptoms seemed far off in 2017. However, researchers from the University of California, San Francisco have recently reached this goal with their implementation of closed-loop therapy using a deep-brain sensing and stimulation device on a 36-year old woman, Sarah, with treatment-resistant depression, as outlined in a Nature Medicine paper published on October 4th, 2021.

The device, which was implanted into Sarah’s brain, is capable of recognizing the emittance of a particular brain signal that can be used as a biomarker, signaling the onset of depressive symptoms. In Sarah’s case, the UCSF researchers were able to connect the emittance of a gamma wave in her amygdala, a brain region known to be involved in emotions, with the onset of her depressive symptoms. Having detected this signal, the device electrically stimulates a specific (pre-determined) part of the brain, which intervenes and alleviates the patient’s depression symptoms when needed. In Sarah’s case, the UCSF researchers found that stimulation of the right ventral capsule/ventral striatum (VC/VS) “led to consistent, sustained and dose-dependent improvement of symptoms.” 

Sarah receives the electrical jolts of stimulation about 300 times in a day, and having had the device implanted for over a year, her description of its effects is that “as time has gone on, it’s been this virtuous cycle, a spiral upwards,” Sarah said. “Everything has gotten easier and easier and easier.” The group that designed and implanted the device in Sarah’s brain is now developing similar devices for the brains of a few more patients with treatment-resistant depression.

Although the single device in Sarah’s brain has proved successful thus far, the complexity of the sophisticated imaging and machine learning technology used by the UCSF researchers to design the device makes it difficult to implement the approach on a large scale. Nonetheless, the results of the research help illuminate the workings of depression and how deep-brain stimulation can be used and advanced to treat depression, and potentially other mood disorders and addiction.