Key Points
- Researchers at the University of Texas at Austin investigated the use of low-intensity focused ultrasound neuromodulation for a variety of mental health disorders.
- The team first evaluated target engagement of the left amygdala and then continued with daily treatment in 24 participants.
The research team led by Greg Fonzo, PhD, assistant professor of Psychiatry and Behavioral Sciences and co-director of the Charmaine and Gordon McGill Center for Psychedelic Research and Therapy at the University of Texas at Austin’s Dell Medical School, has been investigating the use of low-intensity focused ultrasound neuromodulation for mood, anxiety, and trauma-related disorders (MATRDs). Earlier this year, the team published positive results from their clinical trial using the BrainSonix Pulsar 1002 system under neuronavigation.
In the first phase of the project, a total of 47 participants – 25 patients plus 22 healthy controls (HCs) – participated in a double-blind, sham-controlled clinical trial (NCT05228964) by undergoing transcranial focused ultrasound and functional MRI scans. The researchers successfully targeted the left amygdala, which is known to be hyperactive in mood and anxiety disorders. The results from the targeting portion of the clinical trial revealed that active treatment (vs. sham) to the amygdala modulated the brain circuitry.
The team then continued with an unblinded, single-arm clinical trial in 25 patients with various mental health disorders, including major depression, bipolar I or II, generalized anxiety, post-traumatic stress, social anxiety, or panic disorder. After amygdala targeting was confirmed, 24 of the 25 patients continued on with daily repetitive transcranial focused ultrasound (rtFUS). Out of the 24 participants, 21 (88%) completed all 15 rtFUS treatment sessions, which were scheduled once daily for three weeks. The rtFUS parameters included a 10-Hz pulse repetition frequency at a 5% duty cycle with a 5-millisecond pulse width. The average pulse intensity was 14.4 watts/cm2.
The primary outcome measures were rate of treatment completion and treatment response as measured by the Mood and Anxiety Symptom Questionnaire General Distress (MASQ-GD) subscale score and change in amygdala reactivity to emotional faces. The team also administered a large number of secondary response scales. MASQ-GD scores, which were all 19 or higher at screening, were collected at the start of each odd-numbered rtFUS session.
The study produced the following outcomes:
- As compared with sham, the active treatment reduced left amygdala blood oxygenation level–dependent signal and produced patient-related differences in hippocampal and insular responses.
- The repetitive treatments were well-tolerated with no serious adverse events.
- The primary outcome was met, and the treatment led to significant reductions in MASQ-GD scores (p = 0.001, Cohen’s d = 0.77).
- Amygdala activation to emotional stimuli was also significantly reduced.
“Participants showed marked improvements across a range of symptoms after just three weeks of daily treatments,” said Dr. Fonzo in the University of Texas at Austin press release. “What makes this approach revolutionary is that it’s the first time we’ve been able to directly modulate deep brain activity in patients without invasive procedures or medications. For decades, the amygdala has been a target of interest, but access has required either brain surgery or indirect approaches through cortical stimulation. Focused ultrasound neuromodulation opens a new frontier in psychiatric treatment, potentially offering relief to patients who have not responded to traditional therapies.”
In summary, this research study provided initial evidence that focused ultrasound can safely modulate amygdala function in patients with MATRDs. These findings warrant the conduction of double-blind, randomized controlled trials.
When asked about his future research, Dr. Fonzo said, “Next steps include the confirmation of similar neurobiological and clinical benefits in a uniform diagnostic sample and future randomized clinical trials to confirm efficacy. Additional work is underway to examine potential therapeutic effects in alcohol and substance-use disorders, explore methods to optimize energy delivery and parameters for maximal therapeutic benefit, and employ focused ultrasound as an experimental tool to probe psychological constructs of relevance to MATRDs that are mediated by subcortical structures (e.g., emotional learning and memory).”
This study was funded by the One Mind – Baszucki Brain Research Fund. Investigators also acknowledged various individual funding sources.
See Molecular Psychiatry (Open Access)
See the University of Texas Press Release
See media coverage in Neuroscience News, Medical Xpress, Discover Magazine, SciTechDaily, Technology Networks, Brain & Behavior, and PsyPost
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