At the Icahn School of Medicine at Mount Sinai, researchers have mapped a pattern that feels deeply familiar to anyone who's lived with depression: a brain trapped in a loop, cycling through the same difficult states over and over. The discovery, published in Nature Communications, offers new language for that experience of feeling stuck—and points toward more targeted ways to break free.
For decades, depression research focused on whether certain brain regions were more or less active in people with the condition. The Mount Sinai team, led by Yael Jacob and Ülgen Kilic, took a different approach. They examined not static activity levels, but the brain's movement—how it transitions between different patterns of neural activity over time. Using advanced resting-state functional magnetic resonance imaging combined with diffusion tractography (a technique that maps the brain's structural connections), they modeled what they call the brain's "energy landscape," a framework that shows how easily or difficultly the brain can shift from one state to another.
The findings reveal something counterintuitive. "One of the most intriguing findings was that these brain states were not necessarily stronger," Kilic explained. Instead, certain maladaptive brain states appeared more frequently but lasted for shorter periods—and crucially, the brain found them harder to escape. The researchers observed asymmetries in the brain's energy landscape: some transitions were easier to enter than to exit, and people with depression more often followed energetically demanding pathways even when lower-energy alternatives existed. This isn't about strength of brain activity. It's about entrapment.
The pattern mirrors what patients have long reported. "Many patients describe depression as feeling stuck in negative patterns of thought, mood and behavior," Jacob said. "Our findings suggest that this experience of being 'stuck' may reflect measurable changes in the brain's underlying dynamics." The work reframes depression not as a problem of isolated brain regions failing, but as a dynamical systems challenge—the brain caught in repeating loops among maladaptive states.
This shift in understanding opens new clinical doors. The researchers suggest their framework could help explain how existing interventions work: transcranial magnetic stimulation, deep brain stimulation, antidepressant medications, ketamine, and psychedelics all influence the brain's energy landscape and state transitions. If the problem is a brain trapped in difficult patterns, then interventions can be viewed as tools to help the brain shift out of those loops.
"In principle, this work could help researchers model how much input the brain may need, where stimulation should occur and when interventions may be most effective," Jacob said. The goal is moving beyond treating depression as a static condition toward more precise, biologically informed approaches tailored to how an individual brain becomes and stays entrapped.
The team's next steps involve testing whether similar dynamics appear in other psychiatric disorders and whether these patterns change with treatment or predict recovery. They're building a map of the brain's geometry of suffering—and charting paths toward freedom.