Posts in category: Brain Health, Psychology & Emotional Wellbeing

Stress does more than influence how we feel. It can also change what we remember, particularly when an experience is emotionally intense or personally meaningful. Scientists have long known that cortisol, a hormone released during stressful situations, can strengthen emotional memories. What has been less clear is exactly how this happens inside the brain.

Researchers at Yale University have now uncovered important clues. Their study reveals that cortisol strengthens emotional memories by changing how brain networks involved in emotion and memory function and communicate with one another. The findings offer a deeper understanding of why certain experiences leave such powerful impressions while others quickly fade.

“We all experience stress, and my lab is interested in understanding how stress can be helpful,” said corresponding author Elizabeth Goldfarb, an assistant professor of psychiatry at Yale School of Medicine and of psychology in the Faculty of Arts and Sciences.

The findings were published in the journal Science Advances.

How Stress Hormones Influence Memory

Previous research involving both humans and rodents has shown that stress and cortisol can improve memory for emotional events. Scientists also know that certain brain regions, including the amygdala, play an essential role in this process. The amygdala is particularly important for processing emotions and identifying experiences that may be significant.

However, understanding precisely how cortisol strengthens memories has been challenging. Many brain regions participate in several mental functions, making it difficult to determine whether the hormone is influencing emotional responses, memory formation, or both.

“Forming memories for emotional experiences involves different processes in the brain: first, perceiving an experience as emotional or intense, and second, encoding that experience into long-term memory,” said Goldfarb, who is also a member of Yale’s Wu Tsai Institute, an interdisciplinary research initiative that explores cognition.

The researchers wanted to examine these processes separately to determine how cortisol affects the brain’s ability to recognize emotional significance and preserve an experience as a lasting memory.

Watching the Brain Form Emotional Memories

To investigate, the Yale team conducted an experiment in which participants took a pill containing either hydrocortisone, a form of cortisol, or an inactive placebo. They then viewed a series of pictures while undergoing functional MRI (fMRI) scanning.

This imaging technique measures changes in blood flow and oxygen levels associated with brain activity, allowing researchers to identify which areas of the brain are more active during different tasks.

As participants examined the pictures, they reported their emotional reactions to each image. The following day, researchers tested how well they remembered what they had seen.

Each person completed the experiment twice, once after receiving hydrocortisone and once after receiving the placebo. The study used a double blind design, meaning neither the participants nor the experimenter knew which substance had been administered during a particular session.

This approach allowed the scientists to compare how the same person’s brain responded with and without the additional cortisol.

A Five-Second Look at Brain Network Activity

One of the study’s most important advances came from the way researchers analyzed the brain scans.

Scientists often study a measurement called functional connectivity, which describes how closely activity in different parts of the brain fluctuates together. When two regions show synchronized patterns of activity, it can indicate that they are participating in related processes.

Traditionally, examining these relationships requires several minutes of brain imaging data. The Yale team instead analyzed functional connectivity during individual trials lasting only around five seconds.

Using these brief snapshots, the researchers tested whether patterns of brain activity could predict two different outcomes: how emotionally intense participants found a picture and whether they would remember that picture the following day.

The approach worked for both. By identifying patterns associated with emotional intensity and memory formation separately, the scientists were able to examine how cortisol influenced each network and the interactions between them.

This gave the researchers a more detailed picture of the changing brain activity associated with emotional memory formation.

Cortisol Changes How Brain Networks Work Together

The results revealed two major effects.

First, cortisol improved participants’ ability to remember emotionally significant experiences, confirming what earlier research had suggested.

Second, and more importantly, the hormone strengthened emotional memory through distinct changes in the brain networks responsible for processing emotion and forming memories.

In networks associated with emotion, cortisol produced more consistent patterns of activity and increased their engagement. This suggests that the hormone helped the brain respond more strongly and reliably to the emotional significance of an experience.

In memory networks, cortisol had a different effect. It made their activity patterns more specialized for emotional information, suggesting that the brain was adjusting how it encoded emotionally meaningful experiences.

The hormone also increased coordination between the networks involved in emotion and memory. In other words, cortisol appeared to help these different brain systems work together more effectively when processing experiences that carried emotional weight.

Together, these findings suggest that stress strengthens emotional memories through several interacting brain mechanisms rather than through a single region or process.

Why Emotional Experiences Can Be So Memorable

The results help explain why stress does not necessarily improve memory for everything. Instead, its benefits appear to be selective, making experiences that feel particularly intense or meaningful more likely to be remembered.

The researchers believe this reflects the brain’s ability to adapt to stressful situations by prioritizing information that may be important.

“Stress responses are fundamentally adaptive and can help you form strong memories — but this is specific to experiences that you find to be emotionally intense or meaningful,” Goldfarb said. “This is in part related to your brain increasing engagement of networks that track emotional intensity. So, if you are stressed out and trying to learn something new, it might help to think about exciting elements or strong feelings connected to what you are learning.”

The findings also point to a potentially useful insight about learning. Connecting information to something exciting, personally important, or emotionally engaging could make it easier to remember, particularly during stressful situations.

Rather than simply disrupting memory, stress can sometimes help the brain identify which experiences deserve special attention and strengthen the networks involved in preserving them.

A smile or a frown may reveal more than emotion alone. The faces that capture a child’s attention could provide important clues about their mental health and how depression develops.

New research from Binghamton University, State University of New York, suggests that depression may influence how strongly children focus on emotional expressions such as happy or sad faces. The pattern appears to differ depending on whether a child has a family history of depression.

Researchers at the Mood Disorders Institute at Binghamton University study how depression develops in children and adolescents, with particular attention to how family history and emotional experiences may influence vulnerability over time. By identifying these patterns while children are still developing, scientists hope to better understand who may be at greater risk and eventually improve prevention strategies.

“Most of the vulnerabilities that we focus on are still developing during this time period,” said Brandon Gibb, director of the Mood Disorders Institute and SUNY distinguished professor of psychology. “You can catch things as they’re developing, rather than only studying them once they’re already there and pretty stable.”

Following Children’s Attention Over Time

Earlier research has linked depression with greater attention to sad faces. However, those associations have generally been modest, and scientists have not been sure whether biased attention contributes to depression or develops because of it.

The Binghamton study was designed to investigate that question by tracking both depressive symptoms and attention patterns over time. According to the researchers, it is the first study to examine how changes in each may predict later changes in the other among children.

“The real novel piece is that we looked at these transactional relations,” said Kelly Gair, a PhD student at Binghamton and lead author of the paper. “Between attentional biases and depressive symptoms, we looked at the way that they were mutually predicting one another across the time points, which is especially novel and hasn’t been done before.”

The research team, which also included Leslie A. Brick from the University of New Mexico, followed 242 children and their mothers for two years. Participants were assessed every six months.

During each visit, children viewed pairs of faces on a screen. One face showed a neutral expression, while the other displayed an emotion (happy, sad, or angry). Eye tracking technology measured which face held the child’s attention and for how long.

Children in the study looked at faces conveying different emotions onscreen, and eye tracking technology recorded where their attention veered. Photo credit: NimStim Set of Facial Expressions (Tottenham et al., 2009).

Family History Changes the Pattern

The results suggest that increasing depressive symptoms do not affect every child’s attention in the same way. Family history appeared to play an important role.

Among children whose mothers had a history of major depressive disorder, rising depressive symptoms were associated with greater attention to sad faces. In other words, as these children experienced more symptoms themselves, their attention became increasingly drawn toward expressions of sadness.

“For those who are already at risk, the more these children experience depression themselves, the more they lose their ability to pull their attention away from the sad things around them,” Gibb said.

“We know that when you’re depressed, it changes what you pay attention to,” Gair said. “Our results suggest that these changes may be more long-lasting and may differ depending on family history. One thought is that for children of mothers with depression, who are exposed to more facial displays of sadness from interactions with their mom, these types of facial expressions become even more salient when they experience depression themselves, so their attention becomes increasingly stuck on sad expressions.”

Happy Faces May Lose Their Pull

A different pattern emerged among children whose mothers had no history of depression.

When depressive symptoms increased in these children, they did not become more focused on sad expressions. Instead, they paid less attention to happy faces.

“In our lower-risk children, what seems to be happening is that experiences of depression are eroding a protective factor, which is how much they pay attention to happy faces,” Gibb said.

The distinction suggests that depression may alter emotional attention through different pathways depending on a child’s underlying level of familial risk. For some children, sadness may become increasingly difficult to ignore. For others, positive emotional signals may simply become less likely to capture their attention.

Researchers led by the University of Texas at Austin have created a soft wearable patch that improved REM sleep in real-world testing without medication or surgery. Known as NEUSLeeP, the device combines gentle ultrasound stimulation with electrodes that track brain activity as it happens. This allows the patch to influence deep areas of the brain involved in sleep while also monitoring the brain’s response.

“This is the first time we’ve been able to noninvasively target deep brain regions involved in REM sleep, while simultaneously monitoring brain activity,” said Kai Wing “Kevin” Tang, a recent UT biomedical engineering Ph.D. graduate who led the research effort. “Our skin-attached NEUSLeeP patch opens up new possibilities for understanding sleep and treating sleep disorders in home settings,” added Huiliang “Evan” Wang, assistant professor in the Cockrell School of Engineering’s Department of Biomedical Engineering, who supervised Tang’s work and served as the principal investigator (PI) directing the overall project.

Wearable Patch Helps People Reach REM Faster

The researchers tested the technology in a study involving 28 people, with the results published in Nature Communications. On average, participants entered REM sleep 43 minutes sooner and remained in that stage for about 16 minutes longer.

The benefits were observed in both healthy sleepers and participants experiencing some sleep difficulties. Users also described the patch as comfortable and safe, and the study reported minimal adverse effects.

Possible Benefits for Stress and Emotional Health

Among healthy participants, NEUSLeeP stimulation also increased heart rate variability, which is commonly used as an indicator of the body’s ability to respond to stress. Brain imaging revealed changes in circuits associated with emotion, raising the possibility that the technology could support mood regulation and psychological resilience.

“REM sleep is not just about dreaming — it’s about emotional reset and stress adaptation,” explained Gregory Fonzo, assistant professor in the Dell Medical School’s Department of Psychiatry and Behavioral Sciences and one of the project’s co-PIs. “By enhancing REM, we may help people better cope with stress and improve their overall well-being.”

REM sleep disruptions have been associated with depression, anxiety and post-traumatic stress disorder (PTSD). Current approaches to sleep problems, including medication and behavioral therapy, may cause side effects or may not directly address the underlying factors that interfere with REM sleep.

Future Trials for Insomnia, Depression and PTSD

The team plans to conduct larger studies to verify the initial results and evaluate whether NEUSLeeP could help people with PTSD, depression and chronic insomnia. The researchers also see potential uses in home sleep monitoring, neuroscience research and personalized sleep treatments.

“Our vision is a future where patients with mental health disorders can optimize their sleep with a noninvasive and safe treatment,” said Vincent Mysliwiec, M.D., a professor at UT Health San Antonio, a leading expert in sleep disorders, and another co-PI on the project. “This technology could help millions of people get the restorative sleep they need.”

Nightmares can be one of the most distressing symptoms of post-traumatic stress disorder (PTSD), a condition that may develop after a person experiences a disaster, serious accident, violence, combat, or another severe trauma. During sleep, people with PTSD may feel as though they are living through the event again in vivid detail. These repeated episodes can cause severe sleep loss and make some people afraid to go to bed.

Available medications often provide limited relief from trauma-related nightmares. Researchers at Charité — Universitätsmedizin Berlin therefore examined whether a prescription drug containing THC, one of the active compounds found in cannabis, could help. The findings, published in Nature Medicine, showed that more than half of the participants responded to the treatment. More than one-third said their nightmares disappeared completely.

Why PTSD Nightmares Are So Difficult to Treat

The effects of a terrifying or life-threatening experience can continue long after the immediate danger has passed. In post-traumatic stress disorder (PTSD), the brain has difficulty processing overwhelming events. The memories may be stored in a way that makes them return involuntarily and without conscious control.

This can happen during the day and at night. While sleeping, people with PTSD may repeatedly relive the trauma until they wake in panic. Antidepressants and medications that lower blood pressure are among the treatments sometimes used, but their effectiveness is limited. They also often do little to relieve the nightmares themselves. Germany has not yet approved a medication specifically for trauma-related nightmares.

Prof. Stefan Röpke studies trauma-related disorders at the Department of Psychiatry and Neurosciences on the Benjamin Franklin Campus of Charité. While exploring possible new treatments, he and his team, working with additional research partners, turned their attention to tetrahydrocannabinol, commonly known as THC. It is the primary psychoactive compound in cannabis.

THC interacts with the body’s endocannabinoid system, which helps regulate sleep, stress, and the way emotional memories are processed. Stefan Röpke explains: “There is evidence suggesting that during REM sleep — the intense dream phases in which the brain processes experiences and regulates emotions — THC reduces dream activity and thereby alleviates nocturnal stress responses.”

Testing Dronabinol for PTSD Nightmares

Cannabis-based medicines are already used in pain treatment, especially when standard therapies do not work well enough or cause intolerable side effects. In Germany, access became easier after the so-called “Cannabis for medical purposes” law went into effect in 2017. The legislation expanded the medical and scientific use of cannabinoids derived from plants or produced synthetically.

For the study, the researchers used Dronabinol, a prescription medication containing THC obtained directly from the cannabis plant and administered as drops. They wanted to find out whether the drug could safely reduce nightmares linked to PTSD.

More than 170 people with post-traumatic stress disorder and frequent, severe nightmares took part. For ten weeks, participants received either Dronabinol or a cannabis-flavored placebo that looked identical. They took the drops each evening before going to bed.

Neither the participants nor the healthcare professionals knew who received the medication and who received the placebo. This double-blind, placebo-controlled design is considered the gold standard for testing medical treatments.

Nightmares Declined More With THC Treatment

At the end of the ten weeks, nightmare severity had fallen significantly more in the Dronabinol group than in the placebo group. On a scale ranging from zero to eight, the average nightmare burden dropped by 3.7 points among participants taking Dronabinol. The placebo group experienced an average decrease of 2.2 points. For the people affected, the difference was clearly noticeable.

“More than a third of the patients treated with Dronabinol reported that they no longer experienced any nightmares after ten weeks. Another 21 percent reported that their nightmare burden had been at least halved,” as Stefan Röpke stated. “And about five out of six patients in the dronabinol group felt their health had markedly improved.”

No Severe Side Effects or Signs of Dependence

The cannabinoid appeared to act specifically on nightmares and sleep rather than on every aspect of PTSD. The researchers could not conclusively show that it reduced the overall severity of post-traumatic stress disorder or any accompanying depression.

Even so, most participants experienced meaningful relief. By interrupting the repeated nighttime reliving of trauma, the treatment allowed many of them to sleep more peacefully.

No severe side effects were reported. Mild and moderate effects, including dizziness, headaches, and increased appetite, occurred more frequently among those receiving Dronabinol. The researchers also found no withdrawal symptoms after participants stopped taking the evening doses at the end of the study.

Future studies will examine whether the treatment remains safe and effective when used for longer periods. Researchers also want to determine whether patients may gradually develop tolerance to the drug.

Scientists at Mount Sinai have identified three important brain connections associated with long-term improvement in patients receiving deep brain stimulation (DBS) for severe depression that has not responded to conventional treatments. The discovery could help researchers make this experimental therapy more precise and effective.

Published October 1 in the American Journal of Psychiatry, the research examined the largest group of patients assembled across multiple independent cohorts to date who had received subcallosal cingulate deep brain stimulation (SCC DBS) for treatment-resistant depression.

The researchers found that lasting improvements were consistently associated with electrical stimulation reaching three specific white matter pathways: the cingulum bundle, forceps minor, and medial uncinate fasciculus/ventral amygdalofugal pathways.

These findings strengthen the case for using detailed maps of the brain’s connections to determine exactly where electrodes should be implanted, rather than choosing their positions based primarily on anatomical landmarks. Known as connectome-based targeting, this strategy has already helped shape the ongoing Abbott TRANSCEND clinical trial, a randomized, controlled study that uses individualized brain connectivity maps to guide SCC DBS treatment.

“This study underscores the importance of individualized surgical targeting for achieving optimal outcomes with deep brain stimulation for depression,” said Helen Mayberg, MD, Mount Sinai Professor in Neurotherapeutics and founding Director of the Nash Family Center for Advanced Circuit Therapeutics at the Icahn School of Medicine at Mount Sinai. “In any randomized controlled trial of a neuromodulation treatment, precise lead placement and confirmation that the intended brain target has been engaged are essential first steps. We still have much to learn about which patients are most likely to benefit from stimulation of this particular target, but developing imaging-based signatures that can match patients to their optimal treatment remains a central goal of our research.”

How Deep Brain Stimulation Targets Severe Depression

For people with treatment-resistant depression, standard therapies have failed to provide adequate relief. Researchers are investigating deep brain stimulation as a possible treatment for individuals living with severe, persistent symptoms.

The procedure involves surgically placing electrodes inside the brain to deliver controlled electrical signals to circuits involved in depression. However, positioning the electrodes correctly remains one of the greatest challenges.

Electrical stimulation does not simply affect the brain tissue closest to an implanted electrode. It can also influence larger networks through the white matter pathways that connect different brain regions. As a result, two patients with electrodes implanted in nearly identical locations may experience very different outcomes depending on which connections are actually stimulated.

Earlier research from Mount Sinai and Emory University helped establish the importance of these networks. In studies published between 2014 and 2023 in Biological Psychiatry, Molecular Psychiatry, and Nature, the teams identified white matter pathways associated with successful SCC DBS treatment and developed a method for planning electrode placement using brain connectivity maps.

The latest investigation sought to determine whether those connections were also important in patients treated at other research centers. Scientists also wanted to understand whether differences in the pathways reached by stimulation could help account for patients who did not benefit.

Three Brain Connections Linked to Lasting Improvement

To investigate, the researchers examined information from several clinical studies, including the BROADEN trial and a patient cohort at the University of Toronto, where SCC DBS was originally developed.

They used computer models of the electrical fields generated by implanted electrodes alongside maps of brain connectivity. This allowed them to estimate which pathways received stimulation and compare those patterns across different patient groups.

The results showed a consistent relationship between sustained improvement and stimulation of the cingulum bundle, forceps minor, and medial uncinate fasciculus/ventral amygdalofugal pathways.

One finding was especially notable. Across the study sites, patients who had not responded to treatment after two years showed a lack of stimulation engagement with the left cingulum bundle.

The researchers did not investigate whether moving electrodes to reach this pathway would improve those patients’ symptoms. Nevertheless, the pattern offers a possible explanation for why apparently similar electrode placements can produce different results. An electrode might be positioned in the correct general region but still fail to activate all the connections associated with lasting improvement.

“This study addresses an important question in DBS: not simply which area of the brain to stimulate, but which connections within that area need to be engaged,” said Brian Kopell, MD, Director of the Center for Neuromodulation at Mount Sinai. “For a network disorder such as depression, millimeters can determine whether stimulation reaches the pathways we intend to modulate. Identifying and reproducibly engaging those pathways gives us a more precise surgical target and a framework for understanding why otherwise similar electrode placements may produce different clinical outcomes.”

Toward More Personalized Depression Treatments

Although reaching these three pathways appears important, the researchers emphasize that electrode placement alone is unlikely to determine whether a patient improves.

The investigation concentrated on identifying the brain connections that should receive stimulation. Additional studies are needed to determine which individuals are most likely to benefit from SCC DBS and how electrical stimulation should be adjusted as treatment continues.

There were also limitations to the brain imaging data. Individual diffusion MRI scans, which can provide information about a person’s white matter connections, were not available for every participant. Consequently, much of the analysis used generalized maps of brain connectivity rather than maps created specifically for each patient.

For the Emory patient group, the researchers were able to compare results obtained from generalized connectivity maps with those based on individual diffusion imaging. Both approaches produced consistent findings, providing further support for the importance of the identified pathways. However, more research is needed to establish the value of patient-specific imaging.

Future investigations will explore whether additional brain imaging measurements, including white matter integrity and functional connectivity, can help identify suitable patients, improve electrode placement, and guide treatment settings.

“Our findings show precisely engaging these white matter pathways is a critical first step toward sustained response,” said Ki Sueng Choi, PhD, Associate Professor, Imaging Core Leader at the Center for Advanced Circuit Therapeutics at Mount Sinai, and corresponding author of the study. “The next step is to characterize abnormal functional and structural brain states along these pathways to build more detailed models for setting patient-specific stimulation parameters, including amplitude, frequency, and pulse width, for precision medicine.”

By combining increasingly detailed brain maps with personalized stimulation settings, scientists hope to better understand why some people experience lasting relief while others do not. The findings represent another step toward developing more targeted treatments for severe depression, although further clinical research is necessary to establish how much these approaches can improve outcomes.

Most of the brain’s roughly 100 billion neurons are produced before birth. However, the small number of new neurons that continue to form in the adult hippocampus may play an important role in protecting against depression, according to new research from Columbia University Vagelos College of Physicians and Surgeons.

The findings provide the first evidence that neurogenesis, the process of producing new neurons, stalls in the brains of adults with major depressive disorder. Researchers also identified molecular programs involved in controlling this process, offering potential clues for developing new treatments.

“Historically, depression was thought to be a disease of neurotransmitter deficiency, especially serotonin, but we now think that depression stems from multiple issues that affect our neurons’ ability to adapt to stress and changing environments,” says Maura Dupont, professor of psychiatry, who led the research.

“Without the ability to create new neurons, people with depression may not have the resilience to effectively adapt to the environment.”

How New Neurons May Shape Memory and Emotion

The researchers focused on the hippocampus, a brain region that plays a major role in episodic memory and emotional responses to the environment. It is also one of the few areas of the adult brain that continues to generate new neurons.

Although the hippocampus is not the only brain region involved in depression, its influence over both memory and emotion has made it an important area of study. Researchers believe changes there may contribute to the tendency of people with depression to interpret experiences more negatively.

“The hippocampus is important for our ability to distinguish between similar but different memories and separate the emotional connotation of past memories and current events,” Dupont says.

This ability is known as pattern separation. When it becomes impaired, individual memories and the emotions attached to them may become less distinct, allowing separate experiences to blend together.

“You may be out with a friend for lunch, but she’s tired and doesn’t talk much. With intact pattern separation, you remember this as a unique event. With impaired pattern separation, it becomes mixed with previous memories of feeling rejected, leading you to think, ‘They’re upset with me’,” Dupont explains. “And I see this a lot in my patients, where they can only retrieve negative information from their memories.”

Research in mice has shown that adult neurogenesis is necessary for pattern separation. A recent study involving patients with brain tumors, in whom neurogenesis was eliminated by radiation therapy directed at the hippocampus, suggests that the same relationship may exist in humans.

“It’s important to emphasize that we do not yet know the complete mechanism, particularly in humans, but the newborn neurons seem to enhance pattern separation because they are especially responsive to new experiences and can be incorporated into new memory circuits more easily, allowing new memories to be stored separately from the old ones,” Dupont says. “Turning neurogenesis back on may be a way to treat depression in some people by rewiring their hippocampus circuit.”

Depression Affects More Than New Neuron Growth

The researchers found that the changes linked to depression extended well beyond neurogenesis. New neuron formation operates within a larger hippocampal circuit that stores episodic memories along with their emotional significance, and molecular disruptions appeared throughout that system.

The affected genes included those involved in building new connections between neurons, supporting communication among brain cells, supplying cellular energy, and moving materials within cells.

The trisynaptic circuit, the hippocampus’s primary pathway for establishing new emotional memories, also displayed evidence of inflammation and cellular stress in people with depression.

To identify these changes, researchers studied nearly half a million brain cells collected from people with depression and control subjects shortly after each donor’s death.

Using an array of recently developed techniques, the team measured the activity of every gene within individual cells and examined whether cellular proteins had been altered. This enormous dataset allowed researchers to see what individual cells were doing and determine exactly where affected cells were located within the hippocampal circuit.

Genes, Environment, and the Biology of Depression

The analysis revealed altered activity in several genes whose genetic variants have previously been associated with major depression.

Other disrupted genes showed epigenetic changes that may reflect the influence of environmental factors. Epigenetic mechanisms can adjust how strongly genes are turned on or off without altering the underlying DNA sequence.

“These are like dimmer switches that control how active genes are, and they are affected by life experiences such as stress, learning, aging, chemicals, etc.,” Dupont says.

The diversity of molecular changes may also help explain why depression can look so different from one person to another.

“Overall, the wide range of effects we found could reflect different pathogenetic mechanisms, perhaps indicating that depression is not just one disease,” she adds.

Researchers still have only a limited understanding of depression’s underlying biology, according to Dupont. By defining the disorder more precisely at the cellular and molecular levels, studies like this one could eventually provide new targets for treatment.

Toward Molecular Subtypes of Depression

Dupont and her colleagues hope that depression could eventually be classified according to its molecular characteristics, much as cancer increasingly is today.

“We want to reclassify depression based on its molecular features, similar to what has been done in cancer,” Dupont says. “Classifying cancers based on their cellular characteristics, not their locations, has led to new and improved treatments. We hope the same will be true for depression and other psychiatric or brain diseases.”

Two people diagnosed with depression can experience vastly different symptoms. One might struggle with persistent anxiety and repetitive negative thoughts, while another may experience trauma related symptoms or substance abuse. But do these differences also appear in the way their brains function?

Researchers at the University of Helsinki investigated this question and uncovered a striking finding: people with the same depression diagnosis can have dramatically different patterns of brain activity. In some cases, communication between brain regions was unusually strong, while in others, it was weaker than normal.

Depression is a major global health concern. According to the World Health Organization (WHO, 2025), approximately 332 million (5.2%) adults worldwide are affected. In Finland, depression is the leading individual cause of both extended sick leave and disability pensions.

Brain Study Reveals Five Distinct Depression Profiles

To investigate the biological differences associated with depression, researchers examined brain activity in 263 people diagnosed with major depressive disorder and 75 healthy participants who served as a comparison group.

The analysis revealed five distinct groups based on differences in functional connectivity, a measure of how closely activity in different brain regions is coordinated. When two regions show synchronized activity, it suggests they are working together as part of a larger brain network. However, stronger connectivity does not necessarily mean the brain is functioning better.

“What was particularly interesting was the contrasting patterns of brain activity found under the umbrella of the same depression diagnoses. In some individuals, the functional connectivity between brain regions was stronger than usual, while in others it was weaker,” says Director Satu Palva of the Neuroscience Center, University of Helsinki.

These differences were also associated with particular symptoms. Participants in one group showed especially strong connections between brain regions, along with more pronounced substance abuse problems. Another group displayed weaker connections and a greater prominence of post-traumatic stress disorder (PTSD) symptoms.

The contrasting results could help explain why earlier studies examining the brains of people with depression have sometimes reached conflicting conclusions. If researchers study different combinations of patients, they may observe very different patterns, even though everyone involved has received the same diagnosis.

The findings add to growing evidence that depression may not have a single, consistent biological signature. Instead, the condition could involve several distinct patterns of brain function.

The Five Brain Patterns Linked to Depression

The researchers classified participants with depression into five groups based on how strongly different brain areas communicated and the frequencies at which their activity was coordinated.

Each group had a characteristic pattern of brain connectivity and associated symptoms:

Group 1: Strong connectivity and severe symptoms

Participants generally showed relatively strong connections between brain regions. This profile was associated with more severe symptoms across several areas, including depression, anxiety, rumination, and reduced ability to function in daily life. Rumination refers to repeatedly dwelling on distressing thoughts, worries, or negative experiences.

Group 2: Weaker connectivity and milder depression

This group was characterized by relatively weak communication between brain regions. Compared with the other groups, participants generally experienced milder symptoms.

Group 3: Widespread weak connectivity and trauma symptoms

People in this group showed reduced connectivity across substantial portions of the brain. Symptoms associated with post-traumatic stress disorder (PTSD) were particularly prominent.

Group 4: Mixed connectivity and multiple challenges

This profile combined unusually strong connections in some brain regions with weaker connections in others. Participants tended to experience more severe depression, greater substance abuse problems, and lower overall well-being.

Group 5: The strongest connectivity and substance abuse symptoms

Participants in the fifth group had the strongest connections between brain regions of any group identified in the study. Substance abuse was a particularly prominent issue, while trauma related symptoms were less pronounced than in the other groups.

Importantly, all five groups also showed differences from the healthy participants. These distinctions extended beyond whether brain connections were strong or weak. The groups also differed in which brain regions were involved and the frequencies at which their activity was synchronized.

Together, the patterns suggest that people diagnosed with depression may experience substantially different changes in how their brain networks operate.

Measuring Brain Activity With Millisecond Precision

To capture these differences, the scientists used magnetoencephalography (MEG), a brain imaging technique that detects extremely faint magnetic fields produced by electrical activity in the brain.

Unlike methods that track slower changes associated with brain activity, MEG can follow electrical signals as they unfold over extremely short periods. This makes it particularly useful for investigating the timing and coordination of communication between brain regions.

Using MEG, the researchers recorded brain activity in all 263 participants with depression and the 75 healthy control subjects.

“MEG enabled us to monitor electrical brain activity with millisecond precision, helping us get closer to what actually happens in the brain at any given moment. Previously, depression phenotypes have been studied using methods with slower responses,” Palva notes.

This high level of temporal precision allowed the team to examine rapid changes in brain activity that might be difficult to distinguish using slower measurement techniques.

By studying these fast signals, the researchers were able to identify differences not only in the strength of connectivity but also in the frequencies at which brain regions appeared to work together.

Could Brain Activity Lead to More Personalized Depression Treatments?

The discovery raises an important possibility for the future of mental health care: treatments might eventually be selected partly according to a person’s individual pattern of brain activity.

Today, finding an effective depression treatment can involve trying different medications or therapies and evaluating how well each works. Because patients can respond differently to the same treatment, identifying the most suitable approach is not always straightforward.

Brain activity measurements could eventually provide additional information to help guide these decisions. However, the researchers emphasize that their findings are not yet ready for clinical use.

“We’re not yet at the point where brain measurements can be used to choose the right treatment for patients, but the study does show one possible route,” Palva says.

A major long-term goal is to better understand how particular symptoms relate to the way brain networks function. Connecting these biological patterns with patients’ experiences could help researchers develop more precise ways to identify and characterize depression.

Eventually, such knowledge might allow doctors to determine which therapies are most likely to help individual patients, potentially reducing the amount of trial and error involved in treatment.

For now, the five brain profiles offer a different way to understand depression. Rather than assuming that one diagnosis corresponds to one underlying pattern of brain activity, the findings suggest that depression can involve markedly different biological changes, sometimes even in opposite directions.

Northwestern scientists have identified, for the first time, a specific group of neurons — cells in the brain — that appear to contribute to anxiety caused by cannabinoid drugs, particularly when those drugs are combined with stressful conditions. Cannabinoids are a category of substances that includes THC, the main psychoactive ingredient in cannabis.

To investigate how cannabinoids influence fear and anxiety, researchers exposed mice to a threatening smell derived from fox urine. Before encountering the odor, the animals were given either a placebo or a synthetic cannabinoid drug.

Mice that received the cannabinoid froze more frequently and spent less time exploring the predator scent. Researchers traced these anxiety related behaviors to increased activity in a small population of brain cells known as somatostatin neurons. These neurons are located in the central amygdala, an area of the brain involved in processing fear and stress.

When the researchers genetically silenced the somatostatin neurons, the mice that received the cannabinoid became less likely to avoid the predator odor. The result suggested that these cells play an important role in producing the anxious response.

“The results of this study could explain why a good trip can turn bad pretty quickly if people consume too much cannabis or the situation they are in turns stressful or scary,” said study senior author Dr. Sachin Patel, chair of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine.

The study was published on Oct. 2 in Nature Communications.

Tracking the Brain During a Threat

Patel and his colleagues gave mice several different doses of the synthetic cannabinoid and measured their reactions to the predator odor. The researchers recorded how much time the animals spent near the scent and whether they responded by freezing or fleeing.

At the same time, the team monitored activity inside the brain by implanting a small microscope into the mice’s brain.

Researchers also studied brain tissue to determine how cannabinoids changed communication between neurons. Their experiments showed that the drug weakened a natural brain mechanism that normally acts as a “brake” on somatostatin neurons. With that restraint reduced, the neurons became more active.

“Higher doses of cannabinoids and environmental stress worked together to synergistically release the ‘brake’ on the central amygdala, which in turn drove excessive anxiety,” Patel explained.

Why Cannabis and Anxiety Matter

Cannabis use in the U.S. has steadily increased in recent years. At the same time, emergency department visits involving adverse effects from the drug have also risen.

Previous studies have found an association between cannabis use and a higher long term risk of anxiety. Anxiety and mood disorders are also on the rise globally.

“Understanding how cannabis affects brain function to generate its psychoactive effects could ultimately reveal new ways to counteract negative consequences should they arise in some people,” Patel said.

The researchers believe the findings may also have relevance beyond cannabis related side effects. Patel said the same neurons could potentially represent a broader target for understanding or reducing anxiety.

“Suppressing the activity of somatostatin neurons in the central amygdala could represent a final pathway for reducing anxiety symptoms, not just in the context of cannabis side effects,” he explained.

A new approach to treating post-traumatic stress disorder (PTSD) has received FDA clearance, offering a personalized alternative for people who have not found sufficient relief through existing treatments. Developed by California-based Wave Neuroscience in collaboration with researchers at the Texas A&M Health Institute of Biosciences and Technology, the technology uses brain activity measurements to guide targeted magnetic stimulation.

Early clinical trial findings have been encouraging. According to Wave Neuroscience, patients experienced a 52% reduction in PTSD symptoms, while 68% achieved remission. The full findings are still being prepared for public release, but researchers believe the technology could significantly expand treatment options for millions of people.

The need for more effective PTSD care is substantial. In the United States, approximately 17.5 veterans die by suicide each day, and about 7% of veterans receive a PTSD diagnosis annually.

PTSD can develop after traumatic experiences such as military combat, serious accidents, natural disasters, or violence. An estimated 6% of Americans will experience PTSD during their lifetime, with higher rates among women and veterans.

Why Current PTSD Treatments Are Not Enough

Since PTSD was formally recognized as a diagnosis in 1980, treatment has largely centered on psychotherapy and medications known as selective serotonin reuptake inhibitors (SSRIs), including sertraline and fluoxetine.

Although these approaches can help, many patients continue to experience symptoms despite receiving treatment.

A 2020 review of PTSD medications found that patients reported improvements ranging from 6.8 to 10.1 points on symptom assessments. However, remission rates reached only 10.9% at most.

Wave Neuroscience reported substantially stronger preliminary outcomes in its clinical trial. Erik Won, DO, the company’s chief medical officer, described the results as a major advance over previously reported medication outcomes.

“In comparison to that study, our FDA trial reported a 52% reduction in symptoms, so more than a four-fold increase in efficacy,” Won said. “And more importantly, we saw 68% remission in our clinical trial. So, it’s really a quantum change, an inflection point in what we can offer to patients. From a clinical care perspective, that’s really meaningful.”

These findings are promising, although the results come from different studies and should not be interpreted as a direct comparison of treatment effectiveness.

How Personalized Brain Stimulation Works

The newly cleared system uses Magnetic e-Resonance Therapy (MeRT), a technology that combines measurements of brain activity with targeted magnetic stimulation.

First, an electroencephalogram (EEG) records the brain’s electrical signals. This information helps guide a personalized treatment plan using transcranial magnetic stimulation, or TMS.

During TMS, a coil positioned against the scalp delivers magnetic pulses that stimulate brain activity. The technique has already been used for other psychiatric conditions, including treatment-resistant depression.

What distinguishes MeRT is its use of an AI-assisted algorithm to customize stimulation protocols based on each patient’s brain activity rather than relying on a standardized approach.

“Transcranial magnetic stimulation, or TMS, was previously FDA cleared for treatment-resistant depression,” Won said. “By adding an augmented AI derived multivariate algorithm, we were able to personalize protocols that received FDA clearance for post-traumatic stress disorder, which should open up market access to about 13 million people who may be struggling with PTSD.”

Dr. Kenneth S. Ramos, a physician-scientist at Texas A&M Health with extensive experience in precision medicine, helped guide the research.

His work focuses on adapting medical care to the characteristics of individual patients instead of assuming that everyone will respond to the same treatment.

“Most clinical interventions for the treatment of PTSD do not work very well,” Ramos said. “So, this is a huge area where identifying interventions that could hopefully add quality of life to the people impacted by this disorder would be tremendously impactful.”

Wave Neuroscience CEO Fred Walke said Ramos was a natural fit for the project because of his expertise in personalized medicine.

Targeting PTSD With Greater Precision

Conventional TMS generally follows treatment protocols that are less individualized. MeRT builds on the same underlying technology but adjusts treatment according to the patient’s specific brain activity.

Ramos emphasized that even small biological differences between people can have major implications for medical care. Humans are approximately 99.9% genetically alike, yet the remaining 0.1% contributes to differences that can influence how individuals respond to treatment.

By accounting for these differences and tailoring stimulation to each person’s brain, researchers observed substantial reductions in PTSD symptom severity.

Ramos illustrated the distinction with an analogy involving a leaking roof.

He likened conventional TMS to covering a leak with a tarp to manage its effects. MeRT, in contrast, aims to provide a more targeted solution, comparable to identifying and replacing the damaged shingles responsible for the problem.

The broader goal is to move beyond treating patients with standardized protocols and toward interventions guided by measurable biological information.

From Breakthrough Designation to FDA Clearance

The regulatory process reached an important milestone in 2024, when MeRT received an FDA Breakthrough Device designation.

Dr. Rick Silva, executive director of clinical trials at the Texas A&M Health Institute of Biosciences and Technology, explained that the designation helps promising technologies move through regulatory review more efficiently.

It does not eliminate scientific or medical requirements. Instead, it can streamline communication and reduce administrative delays while preserving the standards needed for FDA clearance.

Silva said the progress was particularly meaningful because the project began during the COVID-19 pandemic and advanced through the regulatory process unusually quickly.

According to Silva, medical device development and clinical evaluation can often take around 10 years before clearance is obtained. This project completed the relevant process in just over two years.

He credited the experience and dedication of the Wave Neuroscience team with helping make that accelerated progress possible.

“I’ve been involved in probably close to 1,000 projects in academic medical centers over the years at varying degrees of depth and detail,” Silva said. “Patients are why I do what I do. It’s hard, and the failure rate is high, and it’s a lot of work. But when you get to a point where something is going to benefit patients, it’s very professionally gratifying and personally gratifying in many ways as well.”

A New Drug-Free Option for PTSD Patients

Dr. Israel Liberzon, distinguished professor of psychiatry and behavioral sciences at the Texas A&M Naresh K. Vashisht College of Medicine, served as the study’s lead psychiatrist and PTSD specialist.

He believes the clearance represents an important expansion of the available treatments for PTSD.

According to Liberzon, MeRT will become the only FDA-cleared nonmedication treatment specifically for PTSD once it reaches patients.

“Right now, the FDA has approved only two medications for PTSD,” Liberzon said. “It doesn’t mean that only two of them are used, but both are SSRIs. This is the first time that in addition to the medication, we have a non-medication option. There is psychotherapy that people use for PTSD, but psychotherapies require a lot of effort. People must participate actively, and many drop out because it’s too anxiety provoking. So now we have a unique alternative.”

In the clinical trial, participants received five treatment sessions each week over a period of five to six weeks.

Researchers reported that the improvements appeared to persist after the treatment sessions ended, suggesting the benefits may extend beyond the active therapy period.

For patients who struggle with medication side effects or find psychotherapy difficult to complete, a treatment based on personalized brain stimulation could provide another option.

“People living with PTSD have been left with trial-and-error treatment, medications and their side effects, and limited outcomes—even when treated by the most dedicated and experienced physicians,” Won said. “Wave’s FDA clearance signals a fundamentally different future: one in which PTSD can be objectively evaluated, precisely treated and meaningfully healed.”

Won also believes the technology could eventually be adapted to other psychiatric conditions, including depression and anxiety.

Could Personalized Brain Therapy Transform Mental Healthcare?

Dr. Leslie S. Prichep, chief scientific officer at Wave Neuroscience, sees the FDA clearance as an important step toward treatment decisions guided by objective measurements of brain function.

“The FDA clearance of the MeRT System reflects decades of scientific research using electrophysiological biomarkers in identifying abnormal brain activity profiles and guiding personalized intervention strategies,” Prichep said. “We believe this represents an important advancement toward a more objective, data-informed model of mental healthcare.”

Walke believes that giving patients clearer information about their brain activity could also help change public attitudes toward mental illness.

He compared the idea to treating a broken bone with a cast. By making mental health conditions easier to understand through measurable physical information, the company hopes to reduce stigma and help patients better understand their experiences.

“One of the goals of the company is to create a platform for mental healthcare that uses objective imagery to help patients understand why they’re experiencing life the way that they are,” Walke said. “That insight, compounded with proven technologies, promises incredibly high efficacy when personalized.”

An important next step will be ensuring that patients can actually obtain the treatment. Wave Neuroscience and Texas A&M Health are working with other stakeholders to expand availability and make the therapy more affordable through insurance coverage.

“Our hope is that this research and technology can be a catalyst for more widespread development and innovation of more effective, personalized and precision-guided treatments,” Won said. “This is proof positive that population-scale personalized medicine is not just an aspirational goal but is an achievable reality today.”

The project combines years of work across medicine, neuroscience, clinical research, and technology, all directed toward improving the lives of people affected by PTSD.

For Ramos, the opportunity to help veterans carries particular significance because of Texas A&M’s longstanding involvement in military and veteran initiatives.

“Texas A&M has a very rich history of military and veteran priorities,” Ramos said. “It’s a no-brainer that Texas A&M faculty would be interested in and supportive of an initiative that hopefully would bring positive solutions to a big problem. And anything we could do to help alleviate that problem is going to go a long way towards making a difference in the individual’s life as well as the people who are close to them. I feel very fortunate that we at Texas A&M were meaningfully involved in this project.”