New Trial Uses Precision Radiation to ‘Retune’ Brain for Depression

SAN CARLOS, Calif. – January 13, 2026 – For the millions of people worldwide trapped in the grip of treatment-resistant depression (TRD), hope can be a scarce commodity. After cycling through multiple medications and therapies with little to no relief, patients and clinicians are left searching for new options to combat a condition that affects an estimated 30% of all individuals with major depressive disorder. Now, a pioneering clinical trial is exploring a radically new approach: using focused, low-dose radiation not to destroy tissue, but to subtly modulate the dysfunctional brain circuits at the heart of severe depression.

ZAP Surgical Systems, Inc., a leader in non-invasive robotic brain surgery, has announced a landmark research collaboration with top medical institutions in Beijing to investigate this novel therapy. The study, formally launched in December 2025, will use the company’s ZAP-X Gyroscopic Radiosurgery platform to deliver what it calls “precision radiomodulation” in a first-in-human effort to treat TRD. It represents a cautious but significant step into a new frontier of psychiatric care, moving beyond pharmacology and toward the direct, non-invasive tuning of the brain’s own complex wiring.

A New Frontier in Neuromodulation

The scientific foundation for the trial rests on decades of neuroimaging research that has identified a key hub in the brain’s mood regulation network: the subgenual anterior cingulate cortex (sgACC). In patients with severe depression, this small, deep-seated structure is often found to be persistently hyperactive, contributing to the relentless negative emotional states that define the illness. Modulating this hyperactivity has become a primary goal for advanced depression therapies.

Invasive procedures like deep brain stimulation (DBS) have already validated the sgACC as a therapeutic target by surgically implanting electrodes to deliver electrical impulses directly to the region. While effective for some, DBS involves significant surgical risks, permanent hardware, and considerable patient burden. This new study proposes a different path.

Instead of surgery, the trial will use the ZAP-X system to deliver stereotactic radiotherapy—highly focused beams of radiation—to the sgACC. Crucially, the approach is non-ablative. Unlike traditional radiosurgery for tumors, which uses high-dose radiation to destroy cells, this method employs a much lower dose. The goal is not tissue destruction but radiomodulation: inducing localized biological and metabolic changes to calm the overactive circuit without causing neuronal death or damage.

“Treatment-resistant depression remains one of the most challenging conditions in psychiatry, with many patients failing to benefit from existing therapies,” said Dr. Gang Wang, President and Professor of Psychiatry at Beijing Anding Hospital and the study’s Principal Investigator. “This study represents a cautious but important step toward exploring whether ultra-precise, low-dose radiomodulation of the subgenual anterior cingulate cortex can safely influence dysfunctional mood circuits without tissue destruction.”

Precision Beyond Oncology

At the center of this research is the ZAP-X platform, a system purpose-built for sub-millimeter accuracy. Originally designed for treating brain tumors, its unique gyroscopic design allows radiation beams to be delivered from thousands of angles, shaping the dose precisely to the target while sparing surrounding healthy tissue. This capability is what makes the leap from oncology to psychiatry theoretically possible.

For ZAP Surgical, this trial marks a strategic expansion beyond its established market. The company, founded by Stanford neurosurgeon Dr. John R. Adler, is actively pioneering the use of its technology for functional disorders, including addiction and obesity, in addition to depression. This diversification could open vast new markets for a technology once confined to cancer care.

“This study reflects a careful, scientifically grounded exploration of how ultra-precise, non-invasive radiosurgery may be used to modulate dysfunctional brain circuits,” said Dr. Adler, who also serves as the company’s CEO. “ZAP-X was purpose-built for precision, and this research represents an important step toward responsibly expanding its potential beyond traditional oncologic applications.”

The outpatient procedure requires no anesthesia and is completed in a single session, positioning it as a potentially lower-risk and more accessible alternative to invasive neuromodulation techniques.

A Cautious Step into a New Clinical Realm

The “Precision Radiomodulation Therapy Project for Depression” is designed with deliberate caution. The interventional, single-blind trial will enroll approximately nine participants with confirmed TRD across three cohorts, with each group receiving a different dose of radiation (15 Gy, 20 Gy, or 25 Gy). This dose-escalation design is a standard safety measure, allowing investigators to carefully assess tolerability and identify a potential therapeutic window.

Registered on ClinicalTrials.gov under identifier NCT07274917, the study has received full Institutional Review Board (IRB) approval, ensuring it adheres to international ethical standards for human research. The primary measure of success will be a change in scores on the Montgomery-Åsberg Depression Rating Scale (MADRS), a standard clinical tool for assessing the severity of depression, at four weeks after the single treatment session. Researchers will also track secondary outcomes, including cognitive function and neuroimaging changes, for up to 12 weeks. Enrollment is expected to begin in early 2026 under the leadership of Dr. Wang and Dr. Longsheng Pan, a leading neurosurgeon at the Chinese PLA General Hospital 301.

Balancing Innovation with Patient Safety

While the prospect of a non-invasive, single-session treatment for severe depression is compelling, the approach ventures into uncharted territory, raising important questions about safety. Using radiation to alter brain function for a non-fatal psychiatric condition requires a high degree of certainty about the risk-benefit profile.

The core premise is that the low radiation doses will be safe and non-destructive, but the long-term effects of even low-dose radiation on sensitive neural tissue are not yet fully understood. Potential risks, though theoretical at these dose levels, include subtle cognitive changes over time or a very small, long-term increase in the risk of secondary malignancies. The safety data from ZAP-X’s use in ablating tumors cannot be directly extrapolated to this new, modulatory application.

The study’s architects are acutely aware of these considerations, embedding rigorous monitoring protocols into the trial. By starting with a small number of patients and carefully escalating the dose, the research team aims to build a foundational base of safety and efficacy data. The results of this carefully monitored study will be eagerly awaited by clinicians and patients alike, potentially signaling a new direction for treating one of modern medicine's most intractable illnesses.