Can Sound Waves Treat Depression?

A promising new treatment for depression: ultrasound.

Reviewed by Michelle Quirk

Key points

• Up to a third of people with depression do not respond to conventional antidepressant medicines.
• Focused ultrasound monitored with functional MRI imaging may improve depression within 24 hours of treatment.
• Brain ultrasound has been hypothesized to increase brain-derived neurotrophic factor and neurogenesis.

By Mitchell Liester and Bertrand Liang

Depression affects millions of people globally, with pharmacologic therapy a mainstay of treatment. Treatments have also included procedures, such as electroconvulsive therapy (ECT), and more recently deep brain stimulation (DBS) with implanted electrodes. One challenge associated with the use of such treatments is that to access some of the deeper brain structures to treat depression, there is the requirement for neurosurgical intervention. However, recent data from the University of Utah has demonstrated that using sound waves via ultrasound guided by MRI scanning was able to treat depression noninvasively, with results as quickly as 24 hours after stimulation.

Studies have shown a particular part of the brain, the cingulate gyrus, which is in the middle part of the brain, has been associated with severe forms of depression. Experiments have been done that demonstrate stimulation of this area, using surgically implanted electrodes, can treat some cases. The University of Utah group hypothesized utilizing low-intensity sound waves might be able to emulate this deep brain stimulation, allowing a noninvasive treatment to mimic the findings with DBS.

Brain Targets for Depression

Significant work has been done to evaluate areas of the brain associated with depression. While pharmacologic therapy has been successful in treating many forms of depression, the use of new approaches is required to both decrease side effects and to treat more refractory cases. Indeed, there has been significant work evaluating the different areas of the brain that might be targets for DBS to treat depression. Areas including the cingulate gyrus (specifically, the subcallosal cingulate gyrus or SCC), inferior thalamic peduncle, lateral habenular complexes, and rostral cingulate gyrus have all been approached as stimulation targets.

Targeting the cingulate gyrus, specifically the SCC, was one of the first evaluations of DBS in neuropsychiatric disease. In imaging studies, this target has been noted to be involved in treatment-refractory depression. Initial studies showed using implanted electrodes at this region resulted in a 60 percent response after one year, with a 50 percent remission rate that was maintained over several years. Importantly, these treatments have not been associated with adverse events, nor cognitive changes with long-term use. This has led to a number of different approaches being employed to look further at DBS as therapy for depression, with varying techniques and placements for maximizing benefit.

Ultrasound

With the encouraging data using DBS at the SCC, others hypothesized different approaches to attempt to effect similar results with noninvasive means. Interestingly, the mechanism for these approaches has suggested that the release of brain-derived neurotrophic factor (BDNF) is an important component of the effects of DBS. Hence, noting experiments in mice, ultrasound was hypothesized to be a way to increase the release of BDNF, as well as increase neurogenesis, at the SCC. Recent studies have approached other brain areas using targeted ultrasound with preliminary data showing the treatment is safe, with some encouraging efficacy in patients with treatment-resistant depression.

The Utah group sought specifically to address a well-established area of the brain with focused ultrasound. They studied 22 subjects with treatment-resistant depression, in a double-blind fashion (i.e., where investigators and patients were not made aware of whether patients were receiving focused ultrasound or sham treatment). Patients were treated with focused ultrasound monitored with functional MRI imaging. What was intriguing was that in treated patients, SCC neuromodulation was noted with a single 40-minute treatment. Moreover, both mood and depression scores improved significantly; importantly, these findings were noted at 24 hours after treatment.

Future Implications

Pharmacologic therapy has revolutionized the treatment of depression. However, a significant percentage of patients are resistant to antidepressant medications. DBS can alleviate symptoms in some cases. While other approaches to stimulate the brain have shown promise, these are typically invasive and require the implantation of electrodes into the brain. ECT is effective but requires general anesthesia and can be associated with memory loss. The use of focused ultrasound has the advantage of being noninvasive and has been shown to have extraordinarily quick effects: within the first 24 hours, with minimal side effects. The safety of this approach has already been demonstrated when employed to address other neuropsychiatric disorders, from obsessive-compulsive disorder to Parkinson’s disease. As more data arise on the different areas of the brain responsible for these disorders and additional discoveries are made regarding the roles played by BDNF and neuroplasticity, it is anticipated that more treatments may evolve using targeted ultrasound.

Bertrand Liang, MD, Ph.D., is a neurologist and neuroscientist, who has authored four books in the areas of clinical neurology, Buddhism, and management and leadership. Liang is a Diplomate of the American Board of Psychiatry and Neurology, a Fellow of the American Academy of Neurology, and Nominating Member of Sigma Xi, the Research Honor Society.