Noninvasive Modulation of the Subcallosal Cingulate and Depression With Focused Ultrasonic Waves

Area of Science:

• Neuroscience
• Neuromodulation
• Psychiatry

Background:

• Excessive subcallosal cingulate cortex (SCC) activity is linked to severe depression.
• Surgical SCC stimulation alleviates depression, but noninvasive methods lack deep-target precision.
• A novel noninvasive approach using low-intensity focused ultrasound to modulate the SCC was developed.

Purpose of the Study:

• To assess the efficacy of noninvasive ultrasonic stimulation of the SCC in patients with treatment-resistant depression.
• To evaluate the ability of focused ultrasound to selectively target and modulate deep brain structures like the SCC.
• To investigate the impact of SCC neuromodulation on mood and depression severity.

Main Methods:

• A randomized, double-blind, sham-controlled study involving 22 individuals with treatment-resistant depression.
• Concurrent functional magnetic resonance imaging (fMRI) was used to quantify target engagement during ultrasonic stimulation of the bilateral SCC.
• Mood state and depression severity were assessed using the Sadness subscale of the Positive and Negative Affect Schedule and the 6-item Hamilton Depression Rating Scale.

Main Results:

• fMRI confirmed a target-specific decrease in SCC activity during real stimulation (p = .028).
• Neuromodulation at the individual participant level was detectable in 7 of 16 participants with a single 10-minute scan (p < .05).
• Real SCC stimulation led to greater improvements in mood and depression scores compared to sham stimulation (p < .05).

Conclusions:

• Ultrasonic stimulation effectively modulates SCC activity and rapidly reduces depressive symptoms in a pilot study.
• Noninvasive, selective targeting of deep brain areas opens new avenues for circuit-directed therapeutics.
• This technology offers potential for analyzing deep-brain circuit function in humans noninvasively.