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Precision Deep Brain Stimulation Shows Initial Promise for Severe Depression

Posted on by Dr. Francis Collins

Caption: Implanted deep brain stimulation with one lead (blue) in the amygdala, and the other lead (red) in the ventral capsule/ventral striatum. Credit: Ken Probst, University of California, San Francisco

For many people struggling with depression, antidepressants and talk therapy can help to provide relief. But for some, the treatments don’t help nearly enough. I’m happy to share some early groundbreaking research in alleviating treatment-resistant depression in a whole new way: implanting a pacemaker-like device capable of delivering therapeutic electrical impulses deep into the brain, aiming for the spot where they can reset the depression circuit.

What’s so groundbreaking about the latest approach—so far, performed in just one patient—is that the electrodes didn’t simply deliver constant electrical stimulation. The system could recognize the specific pattern of brain activity associated with the patient’s depressive symptoms and deliver electrical impulses to the brain circuit where it could provide the most relief.

While much more study is needed, this precision approach to deep brain stimulation (DBS) therapy offered immediate improvement to the patient, a 36-year-old woman who’d suffered from treatment-resistant major depressive disorder since childhood. Her improvement has lasted now for more than a year.

This precision approach to DBS has its origins in clinical research supported through NIH’s Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative. A team, led by Edward Chang, a neurosurgeon at the University of California San Francisco’s (UCSF) Epilepsy Center, discovered while performing DBS that the low mood in some patients with epilepsy before surgery was associated with stronger activity in a “subnetwork” deep within the brain’s neural circuitry. The subnetwork involved crosstalk between the brain’s amygdala, which mediates fear and other emotions, and the hippocampus, which aids in memory.

Researchers led by Andrew Krystal, UCSF, Weill Institute for Neurosciences, attempted in the latest work to translate this valuable lead into improved care for depression. Their results were published recently in the journal Nature Medicine [1].

Krystal and colleagues, including Chang and Katherine Scangos, who is the first author of the new study, began by mapping patterns of brain activity in the patient that was associated with the onset of her low moods. They then customized an FDA-approved DBS device to respond only when it recognized those specific patterns. Called NeuroPace® RNS®, the device includes a small neurostimulator and measures about 6 by 3 centimeters, allowing it to be fully implanted inside a person’s skull. There, it continuously monitors brain activity and can deliver electrical stimulation via two leads, as shown in the image above [2].

Researchers found they could detect and predict high symptom severity best in the amygdala, as previously reported. The next question was where the electrical stimulation would best relieve those troubling brain patterns and associated symptoms. They discovered that stimulation in the brain’s ventral capsule/ventral striatum, part of the brain’s circuitry for decision-making and reward-related behavior, led to the most consistent and sustained improvements. Based on these findings, the team devised an on-demand and immediate DBS therapy that was unique to the patient’s condition.

It will be important to learn whether this precision approach to DBS is broadly effective for managing treatment-resistant depression and perhaps other psychiatric conditions. It will take much more study and time before such an approach to treating depression can become more widely available. Also, it is not yet clear just how much it would cost. But these remarkable new findings certainly point the way toward a promising new approach that will hopefully one day bring another treatment option for those in need of relief from severe depression.


[1] Closed-loop neuromodulation in an individual with treatment-resistant depression. Scangos KW, Khambhati AN, Daly PM, Makhoul GS, Sugrue LP, Zamanian H, Liu TX, Rao VR, Sellers KK, Dawes HE, Starr PA, Krystal AD, Chang EF. Nat Med. 2021 Oct;27(10):1696-1700

[2] The NeuroPace® RNS® System for responsive neurostimulation, NIH BRAIN Initiative.


Depression (National Institute of Mental Health/NIH)

Deep Brain Stimulation for Parkinson’s Disease and other Movement Disorders (National Institute of Neurological Disorders and Stroke/NIH)

Andrew Krystal (University of California San Francisco)

Katherine Scangos (UCSF)

Edward Chang (UCSF)

NIH Support: National Institute of Neurological Disorders and Stroke


  • Alice E says:

    This is astounding! Depression has been my life along with being completely compliant with therapy and medications. Nevertheless, I would gladly volunteer to be of any help in developing lasting and truly therapeutic results for others like me with Major Depression. Both my Mother and daughter are bi-polar with Mother (now deceased) probably schizophrenic as well. My daughter is non-compliant and self-medicates, so she probably wouldn’t be interested or even accept the probability that this innovative treatment might help her. Please, if possible, consider me as a potential volunteer for the study and, at least, keep me up to date with results and further trials. Thanks very much.

  • Janet says:

    While this is good news it angers me because you are dangling a carrot in front of desperate people. My son is gone. He took his life because antidepressants took away his humanity. What good do you think you are doing by announcing this then withholding any hope that it is available to anyone who would be willing to be a volunteer NOW!! All of you in your ivory towers have no clue what detrimental effects some medications have on patients. Helping those with mental illness is last on the list of those in government or the healthcare arena. Making money comes first. As you stated we don’t know the cost yet. That says it all.
    How about making it available now to those who are planning to take their lives. Otherwise keep it to yourself.

  • Dave Gaines says:

    Pretty fascinating stuff.

  • Theresa says:

    Dr. Collins
    Please consider making DBS available for Brain Injured people too. Since my accident in 1989, I’ve only been surviving depression’s assaults.

    Pills and procedures have all failed to lessen depressions powers. I’m still trapped in a shrinking black box.

    I began slipping into the seasonal “why bother”
    Until reading how DBS helped free that woman from her dark place.

    Thank you

  • hndidar says:

    This is pretty informative, thanks.

  • davidson says:

    Depression kills us, day by day.

  • Lisa O'CONNOR says:

    First, would like to thank the researchers, as well as physicians who work so tirelessly. Although if it wasn’t for individuals whose passion was to truly help make a difference and improving other’s quality of life, we might never know how completely grateful others are for a better quality of life. So grateful for these innovative therapies!

  • Paul T. says:

    When and where will this ever be available. We have a son who is rather desperate after years of meds. Thanks for any updates.

  • Carrie S. says:

    I also would like to thank all researchers for their tireless work on all illnesses. I do not have clinical depression, but have many loved-ones that are affected, so I do understand how horrible it is, and it depresses me that way. I am hopeful that the trend is towards more focus on mental illness. I truly believe it is the root of almost all illness. I see this brain implant discovery as the future of helping people with all kinds of behavior disorders, hopefully better than drugs with less side effects. I applaud the medical community for all they have done to help their fellow man.

  • Stephen Baudanza says:

    Dr Edward Chang , Andrew Krystal, A most intriguing article indeed. I too have suffered with severe depression and anxiety for 35 yrs.. Please add me to the list of volunteers for your research program. At the very least keep me posted on updates to this wonderful breakthrough.

  • Fahmida P. says:

    Depression is a curse. If we overcome it, we will lead a peaceful life. Good luck with the research.

  • Zuccheri Gianni says:

    These are extraordinary technologies that nevertheless require a delicate practical path.

    A less invasive solution:
    look for algorithms that predict through, some monitored parameters, the influences derived from the intestinal brain.

    It would perhaps be a more convenient and effective solution for less dramatic cases of depressive illness.
    Specific blood chemistry dosages or other signals to be included in a validated summation for probability diagnostic schemes, could result in drug and suffering savings.

    There are numerous studies that deal with the influence of the intestine on anxiety and depression, examples :
    Review J Neurosci Res
    . 2019 Oct;97(10):1223-1241. doi: 10.1002/jnr.24476. Epub 2019 May 29.

    “The role of inflammation and the gut microbiome in depression and anxiety”
    Jason M Peirce , Karina Alviña
    J Nutr Biochem. 2022 Jan;99:108854. doi: 10.1016/j.jnutbio.2021.108854. Epub 2021 Sep 14.

    “Consumption of 85% cocoa dark chocolate improves mood in association with gut microbial changes in healthy adults: a randomized controlled trial”
    Ji-Hee Shin , Chong-Su Kim , Lina Cha , Sojeong Kim , Seokoh Lee , Suyeon Chae , Woo Young Chun , Dong-Mi Shin

  • Zuccheri Gianni says:

    We become saddened to read the sufferings of those with these health problems; but at the same time, while we push ourselves to find solutions, we also ask ourselves why such disturbances of the mind that condition human existence arise.

    A spontaneous reflection:
    Nature prepares survival mechanisms that allow us to resist in various extreme conditions.

    The question:
    Is depression a survival mechanism under certain conditions or a planning error of the mental structure?
    Perhaps both answers are valid:
    If Nature allows a certain number of individuals with a severe health problem to appear in the population, at the same time these people in certain conditions are at an advantage over those who are not affected.

    In summary: the living conditions and the environment in which we find ourselves make our body more or less efficient (example: beta Thalassemia and Malaria ).

    Humanity throughout history has faced and faces famines, infections and pains of all kinds. Probably under conditions of lack of food and rest or exposure to intense painful stimuli, certain constitutions survived better than others.
    Paradoxically, the problems arise when the prohibitive conditions cease and this leads to a change in the Network of the neurological structures of physical pain.
    Used to walking barefoot on a pebble beach, you produce endorphins, which will stop when you go back to wearing comfortable shoes

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