Advertisement

Transcranial Ultrasound (TUS) Effects on Mental States: A Pilot Study

      Abstract

      Background/Objective

      Transcranial ultrasound (TUS) can modulate brain function. To assess possible TUS modulation of mental states, we investigated effects on subjective reports of pain and mood of sub-thermal TUS versus placebo applied to frontal scalp and brain of chronic pain patient volunteers.

      Methods

      With IRB approval and informed consent, subjects with chronic pain completed two visual analog scales for pain (NRS) and mood (VAMS/Global Affect), and their vital signs were recorded 10 min prior to, and 10 min and 40 min following exposure to either subthermal TUS (8 MHz) or placebo (in a double blind crossover study) using the 12L-RS probe of a LOGIQe ultrasound imaging machine (General Electric, USA). A physician, also blinded for TUS versus placebo, applied the probe (with gel) to scalp over posterior frontal cortex, contralateral to maximal pain, for 15 seconds. A second investigator operated the ultrasound machine, randomizing TUS versus placebo. The process was then repeated, applying the opposite modality (TUS or placebo). Results: Subjective reports of Mood/Global Affect were improved 10 min (P = 0.03) and 40 min (P = 0.04) following TUS compared with placebo. NRS pain reports slightly improved following TUS (P = 0.07) at 40 min.

      Conclusion

      We found improvement in subjective mood 10 min and 40 min after TUS compared to placebo. TUS can have safe neurophysiological effects on brain function, and is a promising noninvasive therapy for modulating conscious and unconscious mental states and disorders. We suggest TUS acts via intra-neuronal microtubules, which apparently resonate in TUS megahertz range.

      Keywords

      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'

      References

        • Wassermann E.
        Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the international workshop on the safety of repetitive transcranial magnetic stimulation, June 5–7, 1996.
        Electroencephalography & Clinical Neurophysiology. 1998; 108: 1-16
        • Nekhendzy V.
        • Lemmens H.J.
        • Tingle M.
        • Nekhendzy M.
        • Angst M.S.
        The analgesic and antihyperalgesic effects of transcranial electrostimulation with combined direct and alternating current in healthy volunteers.
        Anesthesia & Analgesia. 2010; 111: 1301-1307
        • Fregni F.
        • Boggio P.S.
        • Lima M.C.
        • Ferreira M.J.
        • Wagner T.
        • Rigonatti S.P.
        • et al.
        A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury.
        Pain. 2006; 122: 197-209
        • Boggio P.S.
        • Fregni F.
        • Valasek C.
        • Ellwood S.
        • Chi R.
        • Gallate J.
        • et al.
        Temporal lobe cortical electrical stimulation during the encoding and retrieval phase reduces false memories.
        PLoS One. 2009; 4: e4959
        • Harvey E.N.
        The effect of high frequency sound waves on heart muscle and other irritable tissues.
        American Journal of Physiology. 1929; 91: 284-290
        • Holscher T.
        • Wilkening W.G.
        • Molkenstruck S.
        • Voit H.
        • Koch C.
        Transcranial sound field characterization.
        Ultrasound in Medicine & Biology. 2008; 34: 973-980
        • Martin E.
        • Jeanmonod D.
        • Morel A.
        • Zadicario E.
        • Werner B.
        High intensity focused ultrasound for non-invasive functional neurosurgery.
        Annals of Neurology. 2009; 66: 858-861
        • Samarbakhsh A.
        • Tuszynski J.A.
        Vibrational dynamics of bio- and nano-filaments in viscous solution subjected to ultrasound: implications for microtubules.
        European Biophysics Journal. 2011; 40: 937-946
        • Bystritsky A.
        • Korb A.S.
        • Douglas P.K.
        • Cohen M.S.
        • Melega W.P.
        • Mulgaonkar A.P.
        • et al.
        A review of low-intensity focused ultrasound pulsation.
        Brain Stimul. 2011; 4: 125-136
        • Gavrilov L.R.
        • Tsirulnikov E.M.
        • Davies I.A.
        Application of focused ultrasound for the stimulation of neural structures.
        Ultrasound in Medicine & Biology. 1996; 22: 179-192
        • Foley J.L.
        • Little J.W.
        • Vaezy S.
        Image-guided high-intensity focused ultrasound for conduction block of peripheral nerves.
        Annals of Biomedical Engineering. 2008; 35: 109-119
        • Velling V.A.
        • Shklyaruk S.P.
        Modulation of the functional state of the brain with the aid of focused ultrasonic action.
        Neuroscience & Behavioral Physiology. 1988; 18: 369-375
        • Tyler W.J.
        • Tufail Y.
        • Finsterwald M.
        • Tauchmann M.L.
        • Olson E.J.
        • Majestic C.
        Remote excitation of neuronal circuits using low-intensity, low-frequency ultrasound.
        PLoS ONE. 2008; 3: e3511
        • Tufail Y.
        • Yoshihiro A.
        • Pati S.
        • Li M.M.
        • Tyler W.J.
        Ultrasonic neuromodulation by brain stimulation with transcranial ultrasound.
        Nature Protocols. 2011; 6: 1453-1470
        • 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: 1267-1275
        • Tufail Y.
        • Matyushov A.
        • Baldwin N.
        • Tauchmann M.L.
        • Georges J.
        • Yoshihiro A.
        • et al.
        Transcranial pulsed ultrasound stimulates intact brain circuits.
        Neuron. 2010; 66: 681-694
        • Bystritsky A.
        • Kerwin L.
        • Feusner J.
        A pilot study of cranial electrotherapy stimulation for generalized anxiety disorder.
        Journal of Clinical Psychiatry. 2008; 69: 412-417
        • Bystritsky A.
        Methods for modifying electrical currents in neuronal circuits.
        (USPTO patent, full-text and image database (AppFT, USPTO). 7,283,861)April, 2002
        • Tsui P.H.
        • Wang S.H.
        • Huang C.C.
        In vitro effects of ultrasound with different energies on the conduction properties of neural tissue.
        Ultrasonics. 2005; 43: 560-565
        • Mihran R.T.
        • Barnes F.S.
        • Wachtel H.
        Temporally-specific modification of myelinated axon excitability in vitro following a single ultrasound pulse.
        Ultrasound in Medicine & Biology. 1990; 16: 297-309
        • Tyler W.J.
        Noninvasive neuromodulation with ultrasound? A continuum mechanics hypothesis.
        Neuroscientist. 2011; 17: 25-36
        • Sachs F.
        Stretch-activated ion channels: what are they?.
        Physiology. 2010; 25: 50-56
        • Fishman S.M.
        • Ballantyne J.C.
        • Rathmell J.P.
        Bonica's management of pain.
        4th ed. Lippincott Williams & Wilkins (LWW), Philadelphia PA2009
        • Baliki M.N.
        • Geha P.Y.
        • Apkarian A.V.
        • Chialvo D.R.
        Beyond feeling: chronic pain hurts the brain, disrupting the default-mode network dynamics.
        Journal of Neuroscience. 2008; 28: 1398-1403
        • Tagliazucchi E.
        • Balenzuela P.
        • Fraiman D.
        • Chialvo D.R.
        Brain resting state is disrupted in chronic pain patients.
        Neuroscience Letters. 2010; 485: 26-31
        • May A.
        Chronic pain may change the structure of the brain.
        Pain. 2009; 137: 7-15
        • Gabis L.
        • Shklar B.
        • Baruch Y.K.
        • Raz R.
        • Gabis E.
        • Geva D.
        Pain reduction using transcranial electrostimulation: a double blind “active placebo” controlled trial.
        Journal of Rehabilitation Medicine. 2009; 41: 256-261
      1. User manual and other documents for the GE LOGIQe device are at: http://apps.gehealthcare.com/servlet/ClientServlet?REQ=Enter+Documentation+Library.

      2. FDA approval document for the LOGIQe (including for cephalic imaging) is available at: http://www.accessdata.fda.gov/cdrh_docs/pdf9/K091374.pdf.

        • Barnett S.B.
        Intracranial temperature elevation from diagnostic ultrasound.
        Ultrasound in Medicine & Biology. 2001; 277: 883-888
        • Aaslid R.
        • Markwalder T.-M.
        • Nornes H.
        Noninvasive transcranial Doppler ultrasound recording of flow velocity in basal cerebral arteries.
        Journal of Neurosurgery. 1982; 57: 769-774
        • Wijnhoud A.D.
        • Franckena M.
        • van der Lugt A.
        • Koudstaal P.J.
        • Dippel E.D.
        Inadequate acoustical temporal bone window in patients with a transient ischemic attack or minor stroke: role of skull thickness and bone density.
        Ultrasound in Medicine & Biology. 2008; 34: 923-929
        • Halsey J.H.
        Effect of emitted power on waveform intensity in transcranial Doppler.
        Stroke. 1990; 21: 1573-1578
        • Hartrick C.T.
        • Kovan J.P.
        • Shapiro S.
        The numeric rating scale for clinical pain measurement: a ratio measure.
        Pain Practice. 2003; : 310-316
        • Stern R.A.
        • Arruda J.E.
        • Hooper C.R.
        • Wolfner G.
        Visual analogue mood scales to measure internal mood state in neurologically impaired patients: description and initial validity evidence.
        Aphasiology. 1997; 11: 59-71
        • Craddock T.J.A.
        • Tuszynski J.A.
        • Chopra D.
        • Casey N.
        • Goldstein L.E.
        • Hameroff S.R.
        • et al.
        The zinc dyshomeostasis hypothesis of Alzheimer's disease.
        PLoS One. 2012; 7: e33552
        • Hameroff S.
        • Watt R.C.
        Information processing in microtubules.
        Journal of Theoretical Biology. 1982; 98: 549-561
        • Hameroff S.
        Quantum computation in brain microtubules? The Penrose-Hameroff “Orch OR” model of consciousness.
        Philosophical Transactions Royal Society London (A). 1998; 356: 1869-1896
        • Hameroff S.
        • Craddock T.
        • Tuszynski J.
        “Memory bytes” – molecular match for CaMKII phosphorylation encoding of microtubule lattices.
        Journal of Integrative Neuroscience. 2010; 9: 253-267
        • Craddock T.J.
        • Tuszynski J.
        • Hameroff S.
        Cytoskeletal signaling: is molecular memory encoded in microtubule lattices by CaMKII phosphorylation?.
        PLoS Computational Biology. 2012; 8: e1002421
        • Pokorný J.
        • Hasek J.
        • Jelínek F.
        • Saroch J.
        • Palan B.
        Electromagnetic activity of yeast cells in the M phase.
        Electro & Magnetobiology. 2001; 20: 371-396
        • Pokorný J.
        Excitation of vibration in microtubules in living cells.
        Bioelectrochemistry. 2004; 63: 321-326
      3. Sahu S, Hirata K, Fujita D, Ghosh S, Bandyopadhyay A. Radio-frequency-induced ultrafast assembly of microtubules and their length-independent electronic properties. Nature Materials, in press.