https://med.stanford.edu/news/all-news/2023/05/depression-reverse-brain-signals.html Skip to Content Skip to Local Navigation Skip to Global Navigation Stanford Medicine News Center Site Nav Menu * See us on facebook * See us on twitter * See us on youtube * See us on linkedin * See us on instagram Stanford Medicine Explore Stanford Medicine * Health Care + Find a doctor + Adult-care doctor + Pediatrician or pediatric specialist + Obstetrician + Clinics & Services + Adult care + Pediatric care + Obstetrics + Clinical trials + Locations + Stanford Health Care + Stanford Children's Health + Emergency Department + Dial 911 in the event of a medical emergency Explore Health Care Learn how we are healing patients through science & compassion Back * Research + Basic science departments + Clinical science departments + Institutes + Research centers + See full directory + Research Resources + Research administration + Academic profiles + Clinical trials + Funding opportunities + See all + Professional Training + Postdoctoral scholars + Clinical research fellows Research News Stanford team stimulates neurons to induce particular perceptions in mice's minds Stanford team stimulates neurons to induce particular perceptions in mice's minds Explore Research Learn how we are fueling innovation Back * Education + MD program + PA Programs + PhD programs + Masters programs + Continuing Medical Education + Postdoctoral scholars + Residencies & fellowships + High School & Undergraduate Programs + See all + Education Resources + Academic profiles + School Administration + Basic science departments + Clinical science departments + Alumni services + Faculty resources + Diversity programs + Lane Library + Student resources Education News Students from far and near begin medical studies at Stanford Students from far and near begin medical studies at Stanford Explore Education Learn how we empower tomorrow's leaders Back * Give Support Stanford Medicine + Support teaching, research, and patient care. + Ways to give + Why giving matters + Make a gift online Support Children's Health + Support Lucile Packard Children's Hospital Stanford and child and maternal health + Ways to give + How your gift helps + Make an online gift Back * About + About us + News + Contacts + Maps & directions + Leadership + Vision + Diversity + Global health + Community engagement + Events + How you can help Stanford School of Medicine Stanford Health Care Stanford Children's Health Back * Site Search Submit Search Query Toggle Dropdown MenuMenu * Scope Blog * Stanford Medicine Magazine * Of Note * COVID-19 Updates * Topics Topics Administration Aging Big Data Biochemistry Bioengineering Cancer Cardiovascular Health Chemical Biology Chronic Disease COVID-19 Developmental Biology Education Genetics Global Health Health Policy Hearing Imaging Immunology Infectious Disease Mental Health Neuroscience Nutrition Obituaries Pain Patient Care Pediatrics Precision Health Preventive Medicine Sleep Stem Cells Surgery Technology Transplantation Urology Women's Health [ ] Search Stanford Medicine News 2023 Reversing brain signals treats depression Story Researchers treat depression by reversing brain signals traveling the wrong way share A new study led by Stanford Medicine researchers is the first to reveal how magnetic stimulation treats severe depression: by correcting the abnormal flow of brain signals. May 15, 2023 - By Nina Bai Brains Brain images from a patient with major depression before (left) and after treatment with Stanford neuromodulation therapy, which restores the normal timing of activity in the anterior cingulate cortex. Nolan Williams Lab Powerful magnetic pulses applied to the scalp to stimulate the brain can bring fast relief to many severely depressed patients for whom standard treatments have failed. Yet it's been a mystery exactly how transcranial magnetic stimulation, as the treatment is known, changes the brain to dissipate depression. Now, research led by Stanford Medicine scientists has found that the treatment works by reversing the direction of abnormal brain signals. The findings also suggest that backward streams of neural activity between key areas of the brain could be used as a biomarker to help diagnose depression. "The leading hypothesis has been that TMS could change the flow of neural activity in the brain," said Anish Mitra, MD, PhD, a postdoctoral fellow in psychiatry and behavioral sciences. "But to be honest, I was pretty skeptical. I wanted to test it." Mitra had just the tool to do it. As a graduate student at Washington University in Saint Louis, in the lab of Mark Raichle, MD, he developed a mathematical tool to analyze functional magnetic resonance imaging, or fMRI -- commonly used to locate active areas in the brain. The new analysis used minute differences in timing between the activation of different areas to also reveal the direction of that activity. In the new study, published May 15 in the Proceedings of the National Academy of Sciences, Mitra and Raichle teamed up with Nolan Williams, MD, associate professor of psychiatry and behavioral sciences, whose team has advanced the use of magneticstimulation, personalized to each patient's brain anatomy, to treat profound depression. The FDA-cleared treatment, known as Stanford neuromodulation therapy, incorporates advanced imaging technologies to guide stimulation with high-dose patterns of magnetic pulses that can modify brain activity related to major depression. Compared with traditional TMS, which requires daily sessions over several weeks or months, SNT works on an accelerated timeline of 10 sessions each day for just five days. "This was the perfect test to see if TMS has the ability to change the way that signals flow through the brain," said Mitra, who is lead author of the study. "If this doesn't do it, nothing will." Raichle and Williams are senior authors of the study. Mitra Anish Mitra Timing is everything The researchers recruited 33 patients who had been diagnosed with treatment-resistant major depressive disorder. Twenty-three received SNT treatment, and 10 received a sham treatment that mimicked SNT but without magnetic stimulation. They compared data from these patients with that of 85 healthy controls without depression. When they analyzed fMRI data across the whole brain, one connection stood out. In the normal brain, the anterior insula, a region that integrates bodily sensations, sends signals to a region that governs emotions, the anterior cingulate cortex. "You could think of it as the anterior cingulate cortex receiving this information about the body -- like heart rate or temperature -- and then deciding how to feel on the basis of all these signals," Mitra said. In three-quarters of the participants with depression, however, the typical flow of activity was reversed: The anterior cingulate cortex sent signals to the anterior insula. The more severe the depression, the higher the proportion of signals that traveled the wrong way. "What we saw is that who's the sender and who's the receiver in the relationship seems to really matter in terms of whether someone is depressed," Mitra said. "It's almost as if you'd already decided how you were going to feel, and then everything you were sensing was filtered through that," he said. "The mood has become primary." "That's consistent with how a lot of psychiatrists see depression," he added. "Even things that are quite joyful to a patient normally are suddenly not bringing them any pleasure." When depressed patients were treated with SNT, the flow of neural activity shifted to the normal direction within a week, coinciding with a lifting of their depression. Those with the most severe depression -- and the most misdirected brain signals -- were the most likely to benefit from the treatment. "We're able to undo the spatio-temporal abnormality so that people's brains look like those of normal, healthy controls," Williams said. Williams Nolan Williams A biomarker for depression A challenge of treating depression has been the lack of insight into its biological mechanisms. If a patient has a fever, there are various tests -- for a bacterial or viral infection, for example -- that could determine the appropriate treatment. But for a patient with depression, there are no analogous tests. "This is the first time in psychiatry where this particular change in a biology -- the flow of signals between these two brain regions -- predicts the change in clinical symptoms," Williams said. Not everyone with depression has this abnormal flow of neural activity, and it may be rare in less severe cases of depression, Williams said, but it could serve as an important biomarker for triaging treatment for the disorder. "The fMRI data that allows precision treatment with SNT can be used both as a biomarker for depression and a method of personalized targeting to treat its underlying cause," he said. "When we get a person with severe depression, we can look for this biomarker to decide how likely they are to respond well to SNT treatment," Mitra said. "Behavioral conditions like depression have been difficult to capture with imaging because, unlike an obvious brain lesion, they deal with the subtlety of relationships between various parts of the brain," said Raichle, who has studied brain imaging for more than four decades. "It's incredibly promising that the technology now is approaching the complexity of the problems we're trying to understand. The researchers plan to replicate the study in a larger group of patients. They also hope others will adopt their analytic technique to uncover more clues about the direction of brain activity hidden in fMRI data. "As long as you have good clean fMRI data, you can study this property of the signals," Mitra said. The study was funded by a Brain and Behavior Research Foundation Young Investigator Award, the NIMH Biobehavioral Research Awards for Innovative New Scientists award (grant R01 5R01MH122754-02), Charles R. Schwab, the David and Amanda Chao Fund II, the Amy Roth PhD Fund, the Neuromodulation Research Fund, the Lehman Family, the Still Charitable Trust, the Marshall and Dee Ann Payne Fund, the Gordie Brookstone Fund, the Mellam Family Foundation, and the Baszucki Brain Research Fund. * Nina Bai Nina Bai Nina Bai is a science writer in the Office of Communications. Email her at nina.bai@stanford.edu. Media Contacts * Nina Bai Tel 650-724-2763 nina.bai@stanford.edu About Stanford Medicine Stanford Medicine is an integrated academic health system comprising the Stanford School of Medicine and adult and pediatric health care delivery systems. Together, they harness the full potential of biomedicine through collaborative research, education and clinical care for patients. For more information, please visit med.stanford.edu. Related News * Experimental depression treatment is nearly 80% effective in controlled study October 28, 2021 Experimental depression treatment is nearly 80% effective in controlled study In a double-blind controlled study, high doses of magnetic brain stimulation, given on an accelerated timeline and individually targeted, caused remission in 79% of trial participants with severe depression. * April 6, 2020 Stanford researchers devise treatment that relieved depression in 90% of participants in small study Topics * Neurology & Neurosurgery * Depression * Psychiatry & Mental Health * Medical Research * Stanford Medicine * All Topics Stanford Medicine Magazine 2023 ISSUE 1 Real-world health How social factors make or break us Stanford Medicine Magazine: Real-World Health Stanford Medicine Magazine: Real-World Health News Center News Center Office of Communications For Journalists For Faculty & Staff School Policies Contacts News Sources Scope Blog Stanford Medicine Magazine Stanford Health Care Newsroom Stanford Children's Health Newsroom Stanford School of Medicine About Contact Maps & Directions Careers Basic Science Departments Clinical Science Departments Academic Programs Vision Find People Visit Stanford Search Clinical Trials Give a Gift (c)2023 Stanford Medicine * Privacy Policy * Terms of Use * See us on Facebook * See us on Twitter * Stanford University * Stanford School of Medicine * Stanford Health Care * Stanford Children's Health * Stanford Health Care Tri-Valley * Stanford Medicine Partners