Advertisement

Frequency Dependence of Ultrasound Neurostimulation in the Mouse Brain

      Abstract

      Ultrasound neuromodulation holds promise as a non-invasive technique for neuromodulation of the central nervous system. However, much remains to be determined about how the technique can be transformed into a useful technology, including the effect of ultrasound frequency. Previous studies have demonstrated neuromodulation in vivo using frequencies <1 MHz, with a trend toward improved efficacy with lower frequency. However, using higher frequencies could offer improved ultrasound spatial resolution. We investigate the ultrasound neuromodulation effects in mice at various frequencies both below and above 1 MHz. We find that frequencies up to 2.9 MHz can still be effective for generating motor responses, but we also confirm that as frequency increases, sonications require significantly more intensity to achieve equivalent efficacy. We argue that our results provide evidence that favors either a particle displacement or a cavitation-based mechanism for the phenomenon of ultrasound neuromodulation.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Ultrasound in Medicine and Biology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Apfel R.E.
        • Holland C.K.
        Gauging the likelihood of cavitation from short-pulse, low-duty cycle diagnostic ultrasound.
        Ultrasound Med Biol. 1991; 17: 179-185
        • Bader K.B.
        • Holland C.K.
        Gauging the likelihood of stable cavitation from ultrasound contrast agents.
        Phys Med Biol. 2013; 58: 127-144
        • Bystritsky A.
        • Korb A.S.
        • Douglas P.K.
        • Cohen M.S.
        • Melega W.P.
        • Mulgaonkar A.P.
        • Desalles A.
        • Min B.K.
        • Yoo S.S.
        A review of low-intensity focused ultrasound pulsation.
        Brain Stimul. 2011; 4: 125-136
        • 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: 2430-2433
        • Doherty J.
        • Trahey G.
        • Nightingale K.
        • Palmeri M.
        Acoustic radiation force elasticity imaging in diagnostic ultrasound.
        IEEE Trans Ultrason Ferroelectr Freq Control. 2013; 60: 685-701
        • Duck F.A.
        Acoustic properties of tissue at ultrasonic frequencies.
        in: Duck F.A. Physical properties of tissue. A comprehensive reference book. Academic Press, London1990: 73-135
        • Elder S.A.
        Cavitation microstreaming.
        J Acoust Soc Am. 1959; 31: 54
        • Fenno L.
        • Yizhar O.
        • Deisseroth K.
        The development and application of optogenetics.
        Annu Rev Neurosci. 2011; 34: 389-412
        • Fry F.J.
        • Ades H.W.
        • Fry W.J.
        Production of reversible changes in the central nervous system by ultrasound.
        Science. 1958; 127: 83-84
        • Fry W.J.
        • Mosberg W.H.
        • Barnard J.W.
        • Fry F.J.
        Production of focal destructive lesions in the central nervous system with ultrasound.
        J Neurosurg. 1954; 11: 471-478
        • Gavrilov L.R.
        • Gersuni G.V.
        • Ilyinsky O.B.
        • Sirotyuk M.G.
        • Tsirulnikov E.M.
        • Shchekanov E.E.
        The effect of focused ultrasound on the skin and deep nerve structures of man and animal.
        Prog Brain Res. 1976; 43: 279-292
        • Goss S.A.
        • Frizzell L.A.
        • Dunn F.
        Ultrasonic absorption and attenuation in mammalian tissues.
        Ultrasound Med Biol. 1979; 5: 181-186
        • Heureaux J.
        • Chen D.
        • Murray V.L.
        • Deng C.X.
        • Liu A.P.
        Activation of a bacterial mechanosensitive channel in mammalian cells by cytoskeletal stress.
        Cell Mol Bioeng. 2014; 7: 307-319
        • Hynynen K.
        The threshold for thermally significant cavitation in dog's thigh muscle in vivo.
        Ultrasound Med Biol. 1991; 17: 157-169
      1. International Commission on Radiation Units and Measurements. Tissue Substitutes, Phantoms and Computation Modelling in Medical Ultrasound. Bethesda, MD, 1998.

      2. Jolesz F.A. Hynynen K.H. MRI-guided focused ultrasound surgery. Informa Healthcare USA, Inc., New York2008
        • Kim H.
        • Chiu A.
        • Lee S.D.
        • Fischer K.
        • Yoo S.-S.
        Focused ultrasound-mediated non-invasive brain stimulation: Examination of sonication parameters.
        Brain Stimul. 2014; 7: 748-756
        • Kim H.
        • Park M.Y.
        • Lee S.D.
        • Lee W.
        • Chiu A.
        • Yoo S.-S.
        Suppression of EEG visual-evoked potentials in rats through neuromodulatory focused ultrasound.
        Neuroreport. 2015; 26: 211-215
        • Kim H.
        • Taghados S.J.
        • Fischer K.
        • Maeng L.S.
        • Park S.
        • Yoo S.S.
        Noninvasive transcranial stimulation of rat abducens nerve by focused ultrasound.
        Ultrasound Med Biol. 2012; 38: 1568-1575
        • King R.L.
        • Brown J.R.
        • Newsome W.T.
        • Pauly K.B.
        Effective parameters for ultrasound-induced in vivo neurostimulation.
        Ultrasound Med Biol. 2013; 39: 312-331
        • King R.L.
        • Brown J.R.
        • Pauly K.B.
        Localization of ultrasound-unduced in vivo neurostimulation in the mouse model.
        Ultrasound Med Biol. 2014; 40: 1-11
        • Lee W.
        • Kim H.
        • Jung Y.
        • Song I.-U.
        • Chung Y.A.
        • Yoo S.S.
        Image-guided transcranial focused ultrasound stimulates human primary somatosensory cortex.
        Sci Rep. 2015; 5: 8743
        • Lee W.
        • Lee S.D.
        • Park M.Y.
        • Foley L.
        • Purcell-Estabrook E.
        • Kim H.
        • Fischer K.
        • Maeng L.S.
        • Yoo S.S.
        Image-guided focused ultrasound-mediated regional brain stimulation in sheep.
        Ultrasound Med Biol. 2016; 42: 459-470
        • Legon W.
        • Sato T.F.
        • Opitz A.
        • Mueller J.
        • Barbour A.
        • Williams A.
        • Tyler W.J.
        Transcranial focused ultrasound modulates the activity of primary somatosensory cortex in humans.
        Nat Neurosci. 2014; 17: 322-329
        • McDannold N.
        • Maier S.E.
        Magnetic resonance acoustic radiation force imaging.
        Med Phys. 2008; 35: 3748-3758
        • Mehić E.
        • Xu J.M.
        • Caler C.J.
        • Coulson N.K.
        • Moritz C.T.
        • Mourad P.D.
        Increased anatomical specificity of neuromodulation via modulated focused ultrasound.
        PLoS One. 2014; 9: e86939
        • Menz M.
        • Nikoozadeh A.
        • Khuri-Yakub P.
        • Baccus S.
        Origins of ultrasound neural stimulation in the retina.
        (2013 Neurosci Meet Plan) Society for Neuroscience, San Diego, CA2013: 218 (11)
        • Menz M.D.
        • Oralkan O.
        • Khuri-Yakub P.T.
        • Baccus S.A.
        Precise neural stimulation in the retina using focused ultrasound.
        J Neurosci. 2013; 33: 4550-4560
        • Mihran R.T.
        • Barnes F.S.
        • Wachtel H.
        Temporally-specific modification of myelinated axon excitability in vitro following a single ultrasound pulse.
        Ultrasound Med Biol. 1990; 16: 297-309
        • Min B.K.
        • Bystritsky A.
        • Jung K.I.
        • Fischer K.
        • Zhang Y.
        • Maeng L.S.
        • Park S.I.
        • Chung Y.A.
        • Jolesz F.A.
        • Yoo S.S.
        Focused ultrasound-mediated suppression of chemically-induced acute epileptic EEG activity.
        BMC Neurosci. 2011; 12: 23
        • Nyborg W.L.
        Heat generation by ultrasound in a relaxing medium.
        J Acoust Soc Am. 1981; 70: 310
        • Pennes H.H.
        Analysis of tissue and arterial blood temperatures in the resting human forearm.
        J Appl Physiol. 1948; 1: 93-122
        • Plaksin M.
        • Shoham S.
        • Kimmel E.
        Intramembrane cavitation as a predictive bio-piezoelectric mechanism for ultrasonic brain stimulation.
        Phys Rev X. 2014; 4: 1-10
        • Prieto M.L.
        • Oralkan Ö.
        • Khuri-Yakub B.T.
        • Maduke M.C.
        Dynamic response of model lipid membranes to ultrasonic radiation force.
        PLoS One. 2013; 8: e77115
        • Tennant K.A.
        • Adkins D.L.
        • Donlan N.A.
        • Asay A.L.
        • Thomas N.
        • Kleim J.A.
        • Jones T.A.
        The organization of the forelimb representation of the C57 BL/6 mouse motor cortex as defined by intracortical microstimulation and cytoarchitecture.
        Cereb Cortex. 2011; 21: 865-876
        • ter Haar G.R.
        • Daniels S.
        Evidence for ultrasonically induced cavitation in vivo.
        Phys Med Biol. 1981; 26: 1145-1149
        • Tufail Y.
        • Matyushov A.
        • Baldwin N.
        • Tauchmann M.L.
        • Georges J.
        • Yoshihiro A.
        • Tillery S.I.H.
        • Tyler W.J.
        Transcranial pulsed ultrasound stimulates intact brain circuits.
        Neuron. 2010; 66: 681-694
        • Tyler W.J.
        Noninvasive neuromodulation with ultrasound? A continuum mechanics hypothesis.
        Neuroscientist. 2011; 17: 25-36
        • Vyas U.
        • Kaye E.
        • Pauly K.B.
        Transcranial phase aberration correction using beam simulations and MR-ARFI.
        Med Phys. 2014; 41: 032901
        • Wagner T.
        • Valero-Cabre A.
        • Pascual-Leone A.
        Noninvasive human brain stimulation.
        Annu Rev Biomed Eng. 2007; 9: 527-565
        • Wahab R.A.
        • Choi M.
        • Liu Y.
        • Krauthamer V.
        • Zderic V.
        • Myers M.R.
        Mechanical bioeffects of pulsed high intensity focused ultrasound on a simple neural model.
        Med Phys. 2012; 39: 4274-4283
        • Wang T.R.
        • Dallapiazza R.
        • Elias W.J.
        Neurological applications of transcranial high intensity focused ultrasound.
        Int J Hyperthermia. 2015; 00: 1-7
        • Wright C.J.
        • Rothwell J.
        • Saffari N.
        Ultrasonic stimulation of peripheral nervous tissue: An investigation into mechanisms.
        J Phys. 2015; 581: 1-12
        • Yoo S.S.
        • Bystritsky A.
        • Lee J.H.
        • Zhang Y.
        • Fischer K.
        • Min B.K.
        • McDannold N.J.
        • Pascual-Leone A.
        • Jolesz F.A.
        Focused ultrasound modulates region-specific brain activity.
        Neuroimage. 2011; 56: 1267-1275
        • 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
        • Zhang Y.
        • Chen K.
        • Sloan S.A.
        • Bennett M.L.
        • Scholze A.R.
        • O'Keeffe S.
        • Phatnani H.P.
        • Guarnieri P.
        • Caneda C.
        • Ruderisch N.
        • Deng S.
        • Liddelow S.A.
        • Zhang C.
        • Daneman R.
        • Maniatis T.
        • Barres B.A.
        • Wu J.Q.
        An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex.
        J Neurosci. 2014; 34: 11929-11947