Low Intensity Focused Ultrasound for Epilepsy- A New Approach to Neuromodulation

Ellen J Bubrick, Nathan J McDannold, Phillip J White, Ellen J Bubrick, Nathan J McDannold, Phillip J White

Abstract

Patients with drug-resistant epilepsy (DRE) who are not surgical candidates have unacceptably few treatment options. Benefits of implanted electrostimulatory devices are still largely palliative, and many patients are not eligible to receive them. A new form of neuromodulation, low intensity focused ultrasound (LIFUS), is rapidly emerging, and has many potential intracranial applications. LIFUS can noninvasively target tissue with a spatial distribution of highly focused acoustic energy that ensures a therapeutic effect only at the geometric focus of the transducer. A growing literature over the past several decades supports the safety of LIFUS and its ability to noninvasively modulate neural tissue in animals and humans by positioning the beam over various brain regions to target motor, sensory, and visual cortices as well as frontal eye fields and even hippocampus. Several preclinical studies have demonstrated the ability of LIFUS to suppress seizures in epilepsy animal models without damaging tissue. Resection after sonication to the antero-mesial lobe showed no pathologic changes in epilepsy patients, and this is currently being trialed in serial treatments to the hippocampus in DRE. Low intensity focused ultrasound is a promising, novel, incisionless, and radiation-free alternative form of neuromodulation being investigated for epilepsy. If proven safe and effective, it could be used to target lateral cortex as well as deep structures without causing damage, and is being studied extensively to treat a wide variety of neurologic and psychiatric disorders including epilepsy.

Keywords: drug-resistant epilepsy; focused; low intensity focused ultrasound; neuromodulation; novel treatments; ultrasound.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

© The Author(s) 2022.

References

    1. Ryvlin P, Rheims S, Hirsch LJ, Sokolov A, Jehi L. Neuromodulation in epilepsy: state-of-the-art approved therapies. Epilepsy Curr. 2021;20(12):1038-1047.
    1. Fregni F, Otachi PTM, Do Valle A, et al. A randomized clinical trial of repetitive transcranial magnetic stimulation in patients with refractory epilepsy. Ann Neurol. 2006;60(4):447-455.
    1. Bystritsky A, Korb AS, Douglas PK, et al. A review of low-intensity focused ultrasound pulsation. Brain Stimul. 2011;4(3):125-136.
    1. Leinenga G, Langton C, Nisbet R, Götz J. Ultrasound treatment of neurological diseases - current and emerging applications. Nat Rev Neurol. 2016;12(3):161-174.
    1. Elias WJ, Lipsman N, Ondo WG, et al. A randomized trial of focused ultrasound thalamotomy for essential tremor. N Engl J Med. 2016;375(8):730-739.
    1. Lee W, Kim H-C, Jung Y, et al. Transcranial focused ultrasound stimulation of human primary visual cortex. Sci Rep. 2016;6:34026.
    1. Lee W, Kim S, Kim B, et al. Non-invasive transmission of sensorimotor information in humans using an EEG/focused ultrasound brain-to-brain interface. PLoS One. 2017;12(6):e0178476.
    1. Gavrilov LR. Use of focused ultrasound for stimulation of nerve structures. Ultrasonics. 1984;22(3):132-138.
    1. Legon W, Sato TF, Opitz A, et al. Transcranial focused ultrasound modulates the activity of primary somatosensory cortex in humans. Nat Neurosci. 2014;17(2):322-329.
    1. Mueller J, Legon W, Opitz A, Sato TF, Tyler WJ. Transcranial focused ultrasound modulates intrinsic and evoked EEG dynamics. Brain Stimul. 2014;7(6):900-908.
    1. Leo A, Mueller JK, Grant A, Eryaman Y, Wynn L. Transcranial focused ultrasound for BOLD fMRI signal modulation in humans. Annu Int Conf IEEE Eng Med Biol Soc. 2016;2016:1758-1761.
    1. Lee W, Kim H, Jung Y, Song I-U, Chung YA, Yoo S-S. Image-guided transcranial focused ultrasound stimulates human primary somatosensory cortex. Sci Rep. 2015;5:8743.
    1. Lee W, Chung YA, Jung Y, Song I-U, Yoo S-S. Simultaneous acoustic stimulation of human primary and secondary somatosensory cortices using transcranial focused ultrasound. BMC Neurosci. 2016;17(1):68.
    1. Dallapiazza RF, Timbie KF, Holmberg S, et al. Noninvasive neuromodulation and thalamic mapping with low-intensity focused ultrasound. J Neurosurg. 2018;128(3):875-884.
    1. King RL, Brown JR, Newsome WT, Pauly KB. Effective parameters for ultrasound-induced in vivo neurostimulation. Ultrasound Med Biol. 2013;39(2):312-331.
    1. Tufail Y, Matyushov A, Baldwin N, et al. Transcranial pulsed ultrasound stimulates intact brain circuits. Neuron. 2010;66(5):681-694.
    1. Wattiez N, Constans C, Deffieux T, et al. Transcranial ultrasonic stimulation modulates single-neuron discharge in macaques performing an antisaccade task. Brain Stimul. 2017;10(6):1024-1031.
    1. Yoo S-S, Bystritsky A, Lee J-H, et al. Focused ultrasound modulates region-specific brain activity. Neuroimage. 2011;56(3):1267-1275.
    1. Yuan Y, Yan J, Ma Z, Li X. Noninvasive focused ultrasound stimulation can modulate phase-amplitude coupling between neuronal oscillations in the rat hippocampus. Front Neurosci. 2016;10:348.
    1. Kim H, Chiu A, Lee SD, Fischer K, Yoo S-S. Focused ultrasound-mediated non-invasive brain stimulation: examination of sonication parameters. Brain Stimul. 2014;7(5):748-756.
    1. King RL, Brown JR, Pauly KB. Localization of ultrasound-induced in vivo neurostimulation in the mouse model. Ultrasound Med Biol. 2014;40(7):1512-1522.
    1. Kim H, Park MY, Lee SD, Lee W, Chiu A, Yoo S-S. Suppression of EEG visual-evoked potentials in rats through neuromodulatory focused ultrasound. Neuroreport. 2015;26(4):211-215.
    1. Kim H-C, Lee W, Kunes J, et al. Transcranial focused ultrasound modulates cortical and thalamic motor activity in awake sheep. Sci Rep. 2021;11(1):19274.
    1. Deffieux T, Younan Y, Wattiez N, Tanter M, Pouget P, Aubry J-F. Low-intensity focused ultrasound modulates monkey visuomotor behavior. Curr Biol. 2013;23(23):2430-2433.
    1. Yang P-F, Phipps MA, Newton AT, et al. Neuromodulation of sensory networks in monkey brain by focused ultrasound with MRI guidance and detection. Sci Rep. 2018;8(1):7993.
    1. Downs ME, Teichert T, Buch A, et al. Toward a cognitive neural prosthesis using focused ultrasound. Front Neurosci. 2017;11:607.
    1. Chen S-G, Tsai C-H, Lin C-J, et al. Transcranial focused ultrasound pulsation suppresses pentylenetetrazol induced epilepsy in vivo. Brain Stimul. 2020;13(1):35-46.
    1. Hakimova H, Kim S, Chu K, Lee SK, Jeong B, Jeon D. Ultrasound stimulation inhibits recurrent seizures and improves behavioral outcome in an experimental model of mesial temporal lobe epilepsy. Epilepsy Behav. 2015;49:26-32.
    1. Min B-K, Bystritsky A, Jung K-I, et al. Focused ultrasound-mediated suppression of chemically-induced acute epileptic EEG activity. BMC Neurosci. 2011;12:23.
    1. Yoo SS, Jung K, Zhang Y, McDannold N, Bystritsky A, Jolesz F. Non-invasive suppression of animal-model chronic epilepsy using image-guided focused ultrasound. Proc Int Soc Magnet Reson Med. 2010;18:105-111.
    1. Legon W, Ai L, Bansal P, Mueller JK. Neuromodulation with single-element transcranial focused ultrasound in human thalamus. Hum Brain Mapp. 2018;39(5):1995-2006.
    1. Monti MM, Schnakers C, Korb AS, Bystritsky A, Vespa PM. Non-invasive ultrasonic thalamic stimulation in disorders of consciousness after severe brain injury: a first-in-man report. Brain Stimul. 2016;9(6):940-941.
    1. Zeng K, Darmani G, Fomenko A, et al. Induction of human motor cortex plasticity by theta burst transcranial ultrasound stimulation. Ann Neurol. 2022;91(2):238-252. doi:10.1002/ana.26294.
    1. Fomenko A, Neudorfer C, Dallapiazza RF, Kalia SK, Lozano AM. Low-intensity ultrasound neuromodulation: an overview of mechanisms and emerging human applications. Brain Stimul. 2018;11(6):1209-1217.
    1. Stern JM, Spivak NM, Becerra SA, et al. Safety of focused ultrasound neuromodulation in humans with temporal lobe epilepsy. Brain Stimul. 2021;14(4):1022-1031.
    1. Loo CK, McFarquhar TF, Mitchell PB. A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression. Int J Neuropsychopharmacol. 2008;11(1):131-147.
    1. Brinker ST, Preiswerk F, White PJ, Mariano TY, McDannold NJ, Bubrick EJ. Focused Ultrasound Platform for Investigating Therapeutic Neuromodulation Across the Human Hippocampus. Ultrasound Med Biol. 2020;46(5):1270-1274.
    1. Darmani G, Bergmann TO, Butts Pauly K, et al. Non-invasive transcranial ultrasound stimulation for neuromodulation. Clin Neurophysiol. 2022;135:51-73.
    1. Clement GT, Hynynen K. Correlation of ultrasound phase with physical skull properties. Ultrasound Med Biol. 2002;28(5):617-624.
    1. Aubry J-F, Tanter M, Pernot M, Thomas J-L, Fink M. Experimental demonstration of noninvasive transskull adaptive focusing based on prior computed tomography scans. J Acoust Soc Am. 2003;113(1):84-93.
    1. Riis TS, Webb TD, Kubanek J. Acoustic properties across the human skull. Ultrasonics. 2022;119:106591.
    1. Lee CC, Chou CC, Hsiao FJ, et al. Pilot study of focused ultrasound for drug‐resistant epilepsy. Epilepsia. 2022;63(1):162-175.
    1. Sarica C, Fomenko A, Nankoo J-F, et al. Toward focused ultrasound neuromodulation in deep brain stimulator implanted patients: ex-vivo thermal, kinetic and targeting feasibility assessment. Brain Stimul. 2022;15(2):376-379.
    1. Mainprize T, Lipsman N, Huang Y, et al. Blood-brain barrier opening in primary brain tumors with non-invasive MR-guided focused ultrasound: a clinical safety and feasibility study. Sci Rep. 2019;9(1):321.
    1. Lipsman N, Meng Y, Bethune AJ, et al. Blood-brain barrier opening in Alzheimer’s disease using MR-guided focused ultrasound. Nat Commun. 2018;9(1):2336.
    1. Zhang Y, Zhou H, Qu H, et al. Effects of non-invasive, targeted, neuronal lesions on seizures in a mouse model of temporal lobe epilepsy. Ultrasound Med Biol. 2020;46(5):1224-1234.

Source: PubMed

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