Focused Ultrasound of the Right Amygdala for Potentially Treating Anxiety

INSTITUTION: MUSC Brain Stimulation Division/Psychiatry (With UCLA, MGH)

PROJECT LEADERS: MUSC – Drs. Mark George, Bashar Badran, Xingbao Li

PROJECT DURATION: 2 years

Transcranial focused pulsed ultrasound (tFUS) is a promising new noninvasive brain stimulation method for probing the neural correlates of consciousness. tFUS uses ultrasonic sound waves that can safely pass through the skull and focused to stimulate deep brain regions. In earlier work we pioneered administering tFUS to the thalamus, a brain region highly involved in pain perception, to reduce pain perception. In our current, ongoing double-blind, multi-institution study we are testing whether 4 sessions of tFUS administered to the right amygdala has the ability to reduce anxiety symptoms in adults with generalized anxiety disorder.

Broader Impact:

If tFUS delivered to the amygdala reveals anti-anxiety effects in this small initial clinical trial, this would set the stage for larger studies and potentially FDA approval of a new treatment. With respect to consciousness studies, the more we understand how to use tFUS to modify regional brain activity and behavior, the better we can use it in future studies to probe the brain basis of consciousness.

Publications:

• Badran, B. W., et al. (2020). "Sonication of the anterior thalamus with MRI-Guided transcranial focused ultrasound (tFUS) alters pain thresholds in healthy adults: A double-blind, sham-controlled study." Brain Stimul 13(6): 1805-1812.

  BACKGROUND: Transcranial focused ultrasound (tFUS) is a noninvasive brain stimulation method that may modulate deep brain structures. This study investigates whether sonication of the right anterior thalamus would modulate thermal pain thresholds in healthy individuals. METHODS: We enrolled 19 healthy individuals in this three-visit, double-blind, sham-controlled, crossover trial. Participants first underwent a structural MRI scan used solely for tFUS targeting. They then attended two identical experimental tFUS visits (counterbalanced by condition) at least one week apart. Within the MRI scanner, participants received two, 10-min sessions of either active or sham tFUS spread 10 min apart targeting the right anterior thalamus [fundamental frequency: 650 kHz, Pulse repetition frequency: 10 Hz, Pulse Width: 5 ms, Duty Cycle: 5%, Sonication Duration: 30s, Inter-Sonication Interval: 30 s, Number of Sonications: 10, ISPTA.0 995 mW/cm2, ISPTA.3 719 mW/cm2, Peak rarefactional pressure 0.72 MPa]. The primary outcome measure was quantitative sensory thresholding (QST), measuring sensory, pain, and tolerance thresholds to a thermal stimulus applied to the left forearm before and after right anterior thalamic tFUS. RESULTS: The right anterior thalamus was accurately sonicated in 17 of the 19 subjects. Thermal pain sensitivity was significantly attenuated after active tFUS. The pre-post x active-sham interaction was significant (F(1,245.95) = 4.03, p = .046). This interaction indicates that in the sham stimulation condition, thermal pain thresholds decreased 1.08 degrees C (SE = 0.28) pre-post session, but only decreased .51 degrees C (SE = 0.30) pre-post session in the active stimulation group. CONCLUSIONS: Two 10-min sessions of anterior thalamic tFUS induces antinociceptive effects in healthy individuals. Future studies should optimize the parameter space, dose and duration of this effect which may lead to multi-session tFUS interventions for pain disorders.

• Caulfield, K. A. and M. S. George (2018). "The Future of Brain Stimulation Treatments." Psychiatr Clin North Am 41(3): 515-533.

  Trends in brain stimulation include becoming less invasive, more focal, and more durable with less toxicity. Several of the more interesting new potentially disruptive technologies that are just making their way through basic and sometimes clinical research studies include low-intensity focused ultrasound and temporally interfering electric fields. It is possible, and even likely, that noninvasive brain stimulation may become the dominant form of brain treatments over the next 20 years. The future of brain stimulation therapeutics is bright.