Neuromodulation

Focused ultrasound can stimulate or suppress neural activity, depending on the parameters of the energy applied to neural tissue.

The mechanical effects of focused ultrasound are thought to dominate this mechanism1-4, however, there is evidence of neuromodulation during various brain treatments at temperatures below the thermal ablation threshold5.
Neuromodulatory effects could potentially enable a range of therapeutic benefits including:

  • verifying targets in the brain prior to ablative procedures;
  • suppressing epileptic seizures or symptoms of psychiatric disorders; and
  • temporarily blocking nerves to treat pain;

Studies have shown that the mechanical effects of pulsed focused ultrasound can reversibly decrease the functionality of targeted neurons2. This allows for the temporary blocking of neural signals from targeted locations within the brain or spinal/peripheral nerves. Such techniques hold promise in the treatment of epilepsy or chronic pain2,6.
Conversely, pulsed focused ultrasound can be used to stimulate targeted neurons7. Ultrasound energy with specific pulse parameters can trigger the activation and propagation of neural signals that could stimulate precise areas of the brain. This would enable the possibility of mapping neural networks and enhancing our understanding of the brain8,9.

Finally, the thermal effects of focused ultrasound can also be used to induce neuromodulation. When brain tissue is raised to a slightly elevated temperature—lower than that required for thermal ablation—neural signals may be temporarily suppressed in that area5. This technique can be used to confirm the target in the brain during neurological treatments (e.g. essential tremor) before delivering the therapeutic dose of ultrasound energy to create a permanent lesion.

Suggested content:

Webinar: Transient Ultrasonic Modulation of the Brain: from remote palpation to action potential triggering by Jean Francois Aubry, PhD (August 12, 2015)

Webinar: Focused Ultrasound for the Treatment of Central Nervous System Diseases by Elisa Konofagou, PhD (May 6, 2015)

Focused Ultrasound Foundation Neuromodulation Workshop Summary/White Paper

References:

[1] Wahab RA, Choi M, Liu Y, Krauthamer V, Zderic V, Myers MR. Mechanical bioeffects of pulsed high intensity focused ultrasound on a simple neural model. Med. Phys. 2012;39:4274–83.

[2] W. J. Tyler, Y. Tufail, M. Finsterwald, M. L. Tauchmann, E. J. Olson, and C. Majestic, “Remote excitation of neuronal circuits using low-intensity, low-frequency ultrasound.,” PLoS ONE, vol. 3, no. 10, Oct. 2008. 

[3] Plaksin M, Shoham S, Kimmel E. Intramembrane Cavitation as a Predictive Bio-Piezoelectric Mechanism for Ultrasonic Brain Stimulation. Phys. Rev. X. 2014;4:011004.

[4] Deffieux T, Younan Y, Wattiez N, Tanter M, Pouget P, Aubry J-F. Low-intensity focused ultrasound modulates monkey visuomotor behavior. Curr. Biol. CB. 2013;23:2430–3.

[5] Elias WJ, Huss D, Voss T, Loomba J, Khaled M, Zadicario E, et al. A Pilot Study of Focused Ultrasound Thalamotomy for Essential Tremor. N. Engl. J. Med. 2013;369:640–8

[6] S.-S. Yoo, H. Kim, B.-K. Min, E. Franck, and S. Park, “Transcranial focused ultrasound to the thalamus alters anesthesia time in rats.,” Neuroreport, vol. 22, no. 15, pp. 783–787, Oct. 2011. 

[7] Younan Y, Deffieux T, Larrat B, Fink M, Tanter M, Aubry J-F. Influence of the pressure field distribution in transcranial ultrasonic neurostimulation. Med. Phys. 2013;40:082902.

[8] Tufail Y, Yoshihiro A, Pati S, Li MM, Tyler WJ. Ultrasonic neuromodulation by brain stimulation with transcranial ultrasound. Nat. Protoc. 2011;6:1453–70.

[9] Yoo S-S, Bystritsky A, Lee J-H, Zhang Y, Fischer K, Min B-K, et al. Focused ultrasound modulates region-specific brain activity. NeuroImage. 2011;56:1267–75.

Click here for additional references from PubMed. 

Video courtesy of InSightec.