Transcranial Ultrasound

Enhancing Mindfulness Training

SEMA lab at the Center for Consciousness Studies is happy to announce a new crowdfunding campaign.  Help SEMA lab fund a brain imaging and neurostimulation experiment targeting the Default Mode Network - a central area that may be involved in mindfulness training.  

SEMA Lab - CCS-UA

Dr. Jay Sanguinetti, Co-Director of SEMA Lab and Associate Director of the Center for Consciousness Studies -  

https://semalab.arizona.edu/

Jay Lacoste Sanguinetti is the associate director of the Center for Consciousness Studies and a research assistant professor in the College of Social and Behavioral Sciences. Sanguinetti specializes in psychophysiological measures (EEG, fMRI, eye-tracking) of visual perception, emotion, and mindfulness meditation. His current research includes using noninvasive brain stimulation to enhance cognition and well-being. Sanguinetti recently co-launched the Sonication Enhanced Mindful Awareness (SEMA) lab to develop accelerated mindfulness protocols for therapeutic interventions to treat addiction, chronic pain, and depression.

SEMA lab is focused on accelerating mindfulness training with ultrasound (or other technologies).
At the SEMA Lab (Sonication Enhanced Mindful Awareness),    we seek to solve a common obstacle faced when applying mindfulness practice to clinical populations: Mindfulness meditation is sometimes simply too difficult for those that could benefit the most from it.
Mindfulness has been shown to improve outcomes for a whole host of disorders, such as  chronic pain, depressionanxietyeating disordersaddiction… the list goes on. Despite its effectiveness, compliance with mindfulness protocols in clinical populations tends to be low, perhaps due to the immense effort and time it takes to start seeing benefits of the practice. This is an unfortunate paradox keeping these populations from experiencing the life-changing effects the practice can have: In essence, mindfulness can free someone of their disorder, but the disorder keeps them from committing to the practice.
How do we solve this problem? With SEMA, we can make mindfulness more rewarding at the beginning of the practice, so that the practitioner continues to apply meditation training. With this approach, the barriers to commitment and consistent practice become lessened, and the practitioner is free to explore the life-changing effects that mindfulness has to offer.
How can we make mindfulness more rewarding? We’re using a new form of noninvasive brain stimulation called transcranial ultrasound (TUS).  TUS uses low-intensity ultrasound to safely and reversibly modulate brain activity and is quickly gaining traction as a tool for neuroscience.  When we ultrasound a part of the brain, we call that “sonicating” the brain.  TUS can be focused, allowing us to sonicate relatively specific parts of the brain.  We are aiming the ultrasound to a part of the brain that we think should help enhance the acquisition of meditation skills (like equanimity, concentration, and sensory clarity) and participants will receive sonication while they meditate.  Thus, we are not seeking to replace meditation — participants will still have to do the hard work.  But we hope this paradigm will help them learn the meditation techniques quicker and benefit from the practice sooner.
This research is in the early stages.  So far, we have run pilot experiments that have been encouraging, but we must do more to validate these results.  In SEMA lab at the University of Arizona, we are currently launching several experiments to examine the efficacy and safety of the sonication enhanced mindfulness.  We will be submitting these results to peer-reviewed journals as soon as the experiments are completed.  Check back soon for updates.
 Sema Lab 1 pager.pdf.    Jay Sanguinetti - TEDx       Shinzen Young - podcast  
Transcranial Ultrasound Stimulation
Ultrasound consists of megahertz mechanical vibrations, and is widely used for medical imaging. As microtubules have megahertz vibrations, we have been studying ultrasound effects on the brain, delivered non-invasively from the scalp – ‘transcranial ultrasound’ (‘TUS’). We performed the first clinical trial of transcranial ultrasound (TUS) on mental states on human volunteers, finding that 15 seconds of sub-thermal 8 MHz ultrasound applied at the fronto-temporal scalp resulted in 40 minutes of mood improvement compared with placebo.
With the discovery of coherent megahertz vibrations in microtubules (2012, Anirban Bandyopadhyay group in Japan), Hameroff proposed that low intensity, non-invasive megahertz vibrations – ultrasound  –  to the brain could therapeutically stimulate microtubule resonance and polymerization, and improve mental and cognitive states. He and UA Anesthesiology colleagues performed and published the first clinical trial showing mood enhancement by non-invasive transcranial ultrasound (‘TUS’) in human volunteers in 2013 in Brain Stimulation. Now collaborating with Psychology professor John JB Allen, Jay Sanguinetti, and, in the College of Medicine, Bellal Joseph (Surgery), Rich Amini (Emergency Medicine), and Todd Vanderah (Pharmacology), and with funding from the Penrose Institute, the group is planning TUS clinical studies for Alzheimer’s

Peer-Reviewed Publications 
Sanguinetti Joseph L., Hameroff Stuart, Smith Ezra E., Sato Tomokazu, Daft Chris M. W., Tyler William J., Allen John J. B.  Transcranial Focused Ultrasound to the Right Prefrontal Cortex Improves Mood and Alters Functional Connectivity in Humans, Frontiers in Human Neuroscience, 2020 Feb 28.    https://doi.org/10.3389/fnhum.2020.00052
ABSTRACT
Transcranial focused ultrasound (tFUS) is an emerging method for non-invasive neuromodulation akin to transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). tFUS offers several advantages over electromagnetic methods including high spatial resolution and the ability to reach deep brain targets. Here we describe two experiments assessing whether tFUS could modulate mood in healthy human volunteers by targeting the right inferior frontal gyrus (rIFG), an area implicated in mood and emotional regulation. In a randomized, placebo-controlled, double-blind study, participants received 30 s of 500 kHz tFUS or a placebo control. Visual Analog Mood Scales (VAMS) assessed mood four times within an hour (baseline and three times after tFUS). Participants who received tFUS reported an overall increase in Global Affect (GA), an aggregate score from the VAMS scale, indicating a positive shift in mood. Experiment 2 examined resting-state functional (FC) connectivity using functional magnetic resonance imaging (fMRI) following 2 min of 500 kHz tFUS at the rIFG. As in Experiment 1, tFUS enhanced self-reported mood states and also decreased FC in resting state networks related to emotion and mood regulation. These results suggest that tFUS can be used to modulate mood and emotional regulation networks in the prefrontal cortex.

Presentations and Videos

Videos

Workshop 3 -  CONSCIOUSNESS AND ULTRASONIC NEUROMODULATION. Jay Sanguinetti,  University of Arizona; Alexander Bystritsky, UCLA;  Martin Monti,  UCLA (R); Seung-Schik Yoo, Harvard University  (R).  The Science of Consciousness Conference, Tucson, AZ. April 18-22, 2022.  2022 TSC-CCS YouTube Channel  

Ep130: Awakened Scientist - Dr Jay Sanguinetti 2 

In this interview I am once again joined by Dr Jay Sanguinetti, Research Professor at the University of Arizona, Assistant Director at the ...YouTube · Guru Viking · Jan 14, 2022

https://www.youtube.com/watch?v=h88ggJ1Lolo


Neuro Technologies to Enhance Cognition

Jay is a scientist in Tucson, AZ. He was trained in philosophy, neuroscience, and cognitive psychology, and completed his Ph.D. at the ...YouTube · Infinite Loops · Dec 9, 2021. www.youtube.com › watch


ARE OUR BRAINS WIRED FOR COMPASSION? 
The Science Behind Caring for OthersSBS - Downtown Lecture Series - Tucson,  Jay Lacoste Sanguinetti, October 13, 2021   WATCH NOW
Our brains appear wired to respond to the suffering of others. In fact, our reward circuits fire when we alleviate suffering. The emerging neuroscience of compassion has begun to reveal our innate need to care for others and how this ability has helped us survive. But the story does not end there. Cultivating compassion through training practices like meditation activates brain circuits related to positive emotion, reduces stress, and leads to overall well-being.  In this talk, Jay Lacoste Sanguinetti, associate director of the Center for Consciousness Studies, will explore the fascinating new science of compassion and how intentional cultivation of this important ability may have wide-ranging impacts on our individual and societal health.

Simulation #781 Dr. Jay Sanguinetti 

www.youtube.com › watch

Dr. Jay Sanguinetti is a Research Assistant Professor at the University of Arizona and Assistant Director to the Center for Consciousness ...YouTube · Simulation · Aug 25, 2021


Hacking enlightenment: can ultrasound help you transcend ...

www.youtube.com › watch

Can technology improve the way we meditate? At the University of Arizona, Dr Jay Sanguinetti and master meditator Shinzen Young are using .. The Guardian · June 29, 2021.  The Guardian newspaper feature on SEMA lab 

https://youtu.be/spukj-4sYS0


Ultrasonic Neuromodulation and Transcendence
Awakened Futures Summit 2020.  Shinzen Young and Jay Sanguinetti, May 20, 2020; Shinzen Young and Jay Sanguinetti | Awakened Futures ...

YouTube · Consciousness Hacking.    

View all


Dr. Jay Sanguinetti - YouTube

www.youtube.com › watch

Dr. Jay Sanguinetti. 706 views May 19, 2020 Enhancing Well-being and Mindfulness Via ... TEDx Talks. TEDx Talks. 


 YouTube · USC Center for Mindfulness Science · May 19, 2020

USC Center for Mindfulness Science invited Dr. Sanguinetti to give a 45-minute lecture on our research.

LINK ?


Accelerating Mindfulness Training 
Hosted at Stanford. Jay Sanguinetti, PhD Adjunct Professor, University of Arizona, Research Assistant Professor, BrainMind Summit   Apr 7, 2020

Simulation #408 
www.youtube.com › watch
Dr. Jay Sanguinetti is a Research Scientist at the University of Arizona focused ... Allen's TEDx Talk ▻ http://bit.ly/AllenTEDx Allen's IG ...May 21, 2019

Brain Photobiomodulation and Meditation    
Lecture - Dr. Jay Sanguinetti   Vielight Inc  Mar 4, 2019

www.youtube.com › watch


Hacking enlightenment: can ultrasound help you transcend reality?
YouTube · The Guardian

https://www.youtube.com/watch?v=spukj-4sYS0

Dr. Jay Sanguinetti leads a non-invasive neuromodulation based meditation workshop in Big Sky, Montana, as part of the Big Sky Ideas ...

Date


A Technoboost for Meditation
 Jay Sanguinetti, Feb 8, 2019   TEDx Talks - TEDxBigSky

A Technoboost for Meditation | Jay Sanguinetti | TEDxBigSky


Catch the Wave - Ultrasonic Neuromodulation and Higher
The Transformative Technology Conference   Jay Sanguinetti, Nov 21, 2018

Ultrasound Waves Applied to the Brain Can Alter Patients' Moods 

JAY SANGUINETTI, PHD ·  Jay Sanguinetti · TEDx Talks · Jul 18, 2013

https://www.jaysanguinetti.com/transcranial-ultrasound

 

 

Presentations cont.
Hameroff, S (with JJB Allen and JSanguinetti.) Depart. of Psychology, University of Arizona) ‘Transcranial ultrasound (‘TUS’) effects on mood and memory in human volunteers’ Presentation, 2nd International Brain Stimulation Conference, Barcelona, Spain, Mar 5-8, 2017
Hameroff, Stuart. Google Sci-Foo, Invited Speaker, 2016
a) Lightning talk – ‘Good vibrations – Tuning the brain with transcranial ultrasound’ Invited Speaker
b) ‘Quantum physics and consciousness’ (session on the future of physics with Max Tegmark and Nobel laureate Frank Wilczek), Google Campus, Mountain View, California, July 22-24, 2016.
U. Raman, S. Parker, C. Duffield S. Ghosh, SR Hameroff; Ultrasound promotes neurite outgrowth-Implications for TBI Neuroscience, Nov 18, 2014. 
http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=dce66052-114c-45af-91ba-eb3ed7734750&cKey=239fddd0-588b-4f3b-870b-cdae8ed35987&mKey=%7b54C85D94-6D69-4B09-AFAA-502C0E680CA7%7d#
Hameroff, Stuart.  ‘Transcranial Ultrasound (TUS) Stimulation at the Scalp Vertex Increases Self-Ratings on a Buddhist-Based Nonattachment Scale’ Brain Stimulation, Concurrent Speaker with Michael Goldstein, JL Sanguinetti; WJ Tyler, JJB Allen, The Science of Consciousness, Tucson, Arizona, April 23, 2014. p. 114 abstract 115

http://www.consciousness.arizona.edu/documents/FinalCCS_BOOKofAbstracts_2014-2.pdf

Hameroff, Stuart.  ‘Low-Intensity Ultrasound Promotes Neurite Outgrowth in Cultured Cortical Neurons’ Brain Stimulation, Concurrent Speaker with Uma Raman, Sara Parker, Chris Duffield, Sourav Ghosh, The Science of Consciousness, Tucson, Arizona, April 23, 2014. p. 130 abstract 146

http://www.consciousness.arizona.edu/documents/FinalCCS_BOOKofAbstracts_2014-2.pdf

Hameroff, Stuart. ‘Ultrasound Vibrations Stabilize Microtubules In Vitro’  Brain Stimulation, Concurrent Speaker with Saatviki Gupta, Nandita Gupta; Arun Kumar Gupta, The Science of Consciousness, Tucson, Arizona, April 23, 2014. p. 202 abstract 284

http://www.consciousness.arizona.edu/documents/FinalCCS_BOOKofAbstracts_2014-2.pdf

Hameroff, Stuart.  ‘Transcranial Ultrasound (TUS) Stimulation at the Scalp Vertex Increases Self-Ratings on a Buddhist-Based Nonattachment Scale’ Brain Stimulation, Concurrent Speaker with Michael Goldstein, JL Sanguinetti; WJ Tyler, JJB Allen, The Science of Consciousness, Tucson, Arizona, April 23, 2014. p. 114 abstract 115

http://www.consciousness.arizona.edu/documents/FinalCCS_BOOKofAbstracts_2014-2.pdf

Sanguinetti JL, Smith E, Allen John JB, and Hameroff S. (2014). “Human Brain Stimulation with Transcranial Ultrasound: Potential Applications for Mental Health.” Bio electromagnetic and Subtle Energy Medicine, 2nd edition, CRC Press, pp 355-360, 13-08-2014.
Transcranial Ultrasound for Brain Stimulation: Effects on Mood, J. L. Sanguinetti, Ezra E. Smith, Lauritz Dieckman, John Vanuk, Stuart Hameroff, John J. B. Allen- poster 2013 
http://apsychoserver.psychofizz.psych.arizona.edu/JJBAReprints/SPR2013/Sanguinetti_Smith_Dieckman_Vanuk_Hameroff_Allen_SPR_2013.pdf

Transcranial Ultrasound for Brain Stimulation: Effects on Mood
J. L. Sanguinetti, Ezra E. Smith, Lauritz Dieckman, John Vanuk, Stuart Hameroff, John J. B. Allen- poster 2013 

http://apsychoserver.psychofizz.psych.arizona.edu/JJBAReprints/SPR2013/Sanguinetti_Smith_Dieckman_Vanuk_Hameroff_Allen_SPR_2013.pdf

Ultrasound Research at CCS: An Overview
Peer Reviewed - Research Publications:
Transcranial Focused Ultrasound to the Right Prefrontal Cortex Improves Mood and Alters Functional Connectivity in Humans. Sanguinetti JL.,  Hameroff S., Smith EE., Sato T., Daft CM.,Tyler William J., Allen JJB, Frontiers in Human Neuroscience 28 February 2020   www.frontiersin.org › articles › fnhum.2020.00052 › full     
Human Brain Stimulation with Transcranial Ultrasound: Potential Applications for Mental Health. Sanguinetti JL, Smith E, Allen John JB, Hameroff S,  Bio electromagnetic and Subtle Energy Medicine, 2nd edition, CRC Press, pp 355-360, 13-08, 2014.  https://experts.arizona.edu/en/publications/human-brain-stimulation-with-transcranial-ultrasound-potential-ap
Increased Excitability Induced in the Primary Motor Cortex by Transcranial Ultrasound Stimulation. Benjamin C. Gibson, Joseph L. Sanguinetti, Bashar W. Badran, Alfred B. Yu, Evan P. Klein, Christopher C. Abbott, Jeffrey T. Hansberger, and Vincent P. Clark, Front. Neurol., 28 Nov.          2018   https://www.frontiersin.org/articles/10.3389/fneur.2018.01007/full
Ref to: Sanguinetti JL, Smith E, Allen J, Hameroff S.  Human brain stimulation with transcranial ultrasound. In Bioelectromagnetic and Subtle Energy Medicine Motor Cortex by Transcranial Ultrasound Stimulation 2014.  https://pdfs.semanticscholar.org/f3be/acc5c0e187b5ff744a6aeeb33c55f1f4907f.pdf
Transcranial ultrasound (TUS) effects on mental states: A pilot study. Hameroff S, Trakas M, Duffield C, Annabi E, Gerace MB, Boyle P, Lucas A, Amos Q, Buadu A, and Badal JJ.  Brain Stimulation Received 21 November 2011; received in revised form 19 February 2012; accepted 6 May 2012. published online 30 May 2012. Brain Stimul. 2013 May;6(3):409-15  https://www.ncbi.nlm.nih.gov/pubmed/22664271

 

Non-invasive brain stimulation techniques aimed at mental and neurological conditions include transcranial magnetic stimulation (TMS) for depression, and transcranial direct current (electrical) stimulation (tDCS), shown to improve memory. Transcranial ultrasound stimulation (TUS) has also shown promise.
Mood disorders, Alzheimer’s disease, traumatic brain injury (TBI) and post-traumatic stress disorders (PTSD) are enormous problems for those afflicted, their families, caregivers and society in general. Current treatments for these disorders are modestly effective at best, and new, more effective and inexpensive approaches are needed. A major hurdle in treatment is the lack of understanding in mainstream approaches as to how the brain works normally, how mood, cognition, memory and consciousness derive from synaptic computation among neurons. However evidence now suggests mental states may depend, to some extent at least, on vibrations, e.g. sound wave solitons in neuronal membranes, and megahertz (‘MHz’, 106 to 107 Hz) resonances in microtubule networks inside neurons. In TBI and Alzheimer’s disease, microtubules are disrupted and release ‘tau’, a microtubule-associated protein. Under normal circumstances, microtubules are directly responsible for neuronal and synaptic growth, repair and plasticity.
Ultrasound (US) consists of mechanical oscillations, e.g. in MHz. ‘Transcranial ultrasound’ (‘TUS’) passes low intensity, sub-thermal US through the skull into the brain, safely and painlessly. In clinical trials, TUS improves human mood and cognition, and in lab studies megahertz stimulation promotes microtubule assembly. We propose to determine safety and efficacy of inexpensive and potentially portable TUS technology for improving recovery from TBI, Alzheimer’s disease.
Hypothesis or Objective: High intensity US can heat, cavitate and ablate kidney stones, brain tumors and other tissue. Mid-intensity US (‘diathermy’) causes mild heating, useful for musculoskeletal problems. Low intensity, ‘sub-thermal’ US (<720 mW/cm2 by FDA guidelines) excites peripheral neurons,4 and promotes their regeneration after injury. Applied at the scalp, low intensity TUS is FDA-approved for brain imaging, though supplanted by CT, MRI etc. TUS is still used to image brains of newborn babies through boneless fontanelles, and can be focused anywhere in the adult brain. WJ Tyler and others first showed low intensity TUS caused behavioral and electrophysiological changes in animals, and more recently cognitive enhancement in humans.
In the first TUS study on human mental states,11 our group showed that 15 seconds of 8 MHz TUS to fronto-temporal cortex from temporal scalp at 150 mW/cm2 resulted in 40 minutes of improved mood compared to sham exposure. Further studies12 have shown optimal mood improvement with 2 MHz TUS for 30 seconds to right fronto-temporal cortex. In some cases, vertex stimulation (targeting cingulate cortex) resulted in uncontrolled laughter, “out of body” experiences and feelings of being “more in the moment”. High frequency (gamma synchrony) EEG was increased near the TUS stimulation site.
Regarding cellular and molecular level mechanisms, Tyler suggested TUS promotes vibrations in a mechanical continuum of extracellular, intra-membrane and intra-neuronal structures. Among these are microtubules, self-assembling polymers of tubulin, the brain’s most prevalent protein. TUS might act by tuning or enhancing endogenous microtubule megahertz resonances.
Cellular damage in TBI is attributed to biochemical cascades, apoptosis, inflammation, free radicals, glutamate excitotoxicity, blood brain barrier breakdown, axon shearing, and cytoskeletal disruption. Regardless, neuronal recovery and synaptic formation require microtubule-dependent extension of axonal and dendritic ‘neurites’. TUS may stimulate neuronal repair (e.g. for TBI) and memory turnover (PTSD). TUS warrants clinical trials for TBI, Alzheimer’s disease and PTSD.
Research Strategy
Our previous TUS studies have used a clinical GE Logiq US imaging device, and the U+ single transducer TUS headset from Thync, Tyler’s company (formerly NeuroTrek). Both devices are limited in range of MHz frequencies for testing. We are collaborating with Sterling Cooley (Berkeley Ultrasound, Berkeley, California) who has developed a TUS device called the NeuroResonator 1 (NR1) which we tested and calibrated in October, 2014. Proposed modifications will upgrade to the battery-powered NeuroResonator 2 (‘NR2’) with multiple US piezo transducer/emitters with various lead placements, each emitter controlled individually, able to be aimed at particular brain areas, driven synchronously, sequentially, in any combination and/or pulse modulated, e.g. by music. The NR2 will be calibrated, tested, and reviewed and approved by our Bioengineering and Institutional Review Board. Stimulation sites will be selected based on injured brain area, right fronto-temporal and other areas. We plan pilot studies commencing early spring 2015 and will search for optimal techniques. With the NR2 fitting in an EEG cap, we will also study TUS effects on simultaneous EEG.
References cited
Heimburg T, Jackson AD. On soliton propagation in biomembranes and nerves  Proc. Natl. Acad. Sci. U.S.A. 2005, 102 (2): 9790

http://www.pnas.org/content/102/28/9790.full

Sahu S, Ghosh S, Ghosh B, Aswani K, Hirata K, Fujita D, Bandyopadhyay A.   Atomic water channel controlling remarkable properties of a single brain microtubule: correlating single protein to its supramolecular assembly. Biosens Bioelectron. 2013 Sep 15;47:141-8. doi: 10.1016/j.bios.2013.02.050. Epub 2013 Mar 15.   http://www.ncbi.nlm.nih.gov/pubmed/23567633
Sahu S, Ghosh S, Hirata K, Fujita D, Bandyopahyay A.  Multi-level memory-switching properties of a single brain microtubule. Applied Physics Letters (Impact Factor: 3.79). 03/2013; 102(12). DOI: 10.1063/1.4793995

http://link.aip.org/link/doi/10.1063/1.4793995?ver=pdfcov

Harvey EN, The effect of high frequency sound waves on heart muscle and other irritable tissues.  American Journal of Physiology, 91. 1929 December 1, pp. 284–290

http://ajplegacy.physiology.org/content/91/1/284.full-text.pdf+html

Raso, VVM, Barbieri CH, Mazzer N, Fazan VPS. Can therapeutic ultrasound influence the regener ation of peripheral nerves?  Journal of Neuroscience Methods, v. 142, n.1, p. 185-192, 2005. DOI: 10.1016/j.jneumeth.2004.08.016

http://www.sciencedirect.com/science/article/pii/S0165027004003097

Park SC, Oh SH, Seo TB, Namgung U, Kim JM, Lee JH.  Ultrasound-stimulated peripheral nerve regeneration within asymmetrically porous PLGA/Pluronic F127 nerve guide conduit.   J Biomed Mater Res B Appl Biomater. 2010 Aug;94(2):359-66. doi: 10.1002/jbm.b.31659.

http://www.ncbi.nlm.nih.gov/pubmed/20552617

Tyler WJ, Tufail Y, Finsterwald M, Tauchmann ML, Olson EJ, et al.Remote Excitation of Neuronal Circuits Using Low-Intensity, Low-Frequency Ultrasound. PLoS ONE 2008. 3(10): e3511. doi:10.1371/journal.pone.0003511

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0003511

Pearse A. Keane, Adnan Tufail, Praveen J. Patel. Management of Neovascular Age-Related Macular Degeneration in Clinical Practice: Initiation, Maintenance, and Discontinuation of Therapy, J Ophthalmol. 2011; 2011: 752543. Published online 2011 November 22. doi: 10.1155/2011/752543 PMCID: PMC3228281 
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3228281/ 
Yoo SS, Bystritsky A, Lee JH, Zhang Y, Fischer K,  Min BK, McDannold NJ, Pascual-Leone A,  Jolesz FA.  Focused ultrasound modulates region-specific brain activity. Neuroimage. 2011 Jun 1; 56(3):1267-75. Doi: 10.1016/j.neuroimage.2011.02.058. Epub2011 Feb 24.   

http://www.ncbi.nlm.nih.gov/pubmed/21354315

Legon W, Sato TF, Opitz A, Mueller J, Barbour A, Williams A, Tyler WJ. Transcranial focused ultrasound modulates the activity of primary somatosensory cortex in humans, Nature Neuroscience 2014 Jan 12.         17, 322-329 doi:10.1038/nn.3620 

http://www.nature.com/neuro/journal/v17/n2/full/nn.3620.html

Hameroff S, Trakas M, Duffield C, Annabi E, Gerace MB, Boyle P, Lucas A, Amos Q, Buadu A, Badal JJ. Transcranial ultrasound (TUS) effects on mental states: a pilot study, Brain Stimul. 2013 May;6(3):409-15. doi: 10.1016/j.brs.2012.05.002. Epub 2012 May 29.

http://www.ncbi.nlm.nih.gov/pubmed/22664271

Tyler WJ, Ultrasound for Neuromodulation? A Continuum Mechanics Hypothesis. The Neuroscientist 17(1), 2011, 25-36.

http://www.public.asu.edu/~wtyler/lab/Curriculum%20Vitae_files/tyler2010neurosnts.pdf

Raman, U, Gupta S, Parker S , Gupta N, Gupta AK, Duffield C, Ghosh S, Hameroff S.   Low-intensity ultrasound (US) stabilizes microtubules and promotes neurite outgrowth.  2014.  
Ultrasound promotes neurite outgrowth-Implications for TBI – Nov 18, 2014,  U.Raman, S.Parker, C.Duffield, S.Ghosh, *S. R. Hameroff 

http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=dce66052-114c-45af-91ba-eb3ed7734750&cKey=239fddd0-588b-4f3b-870b-cdae8ed35987&mKey=%7b54C85D94-6D69-4B09-AFAA-502C0E680CA7%7d

Transcranial ultrasound (‘TUS’) – an optimal non-invasive brain-machine interface via microtubules?  Society for Neuroscience, SR Hameroff, JL Sanguinetti, C Duffield, U Raman, S Ghosh,S Parker, QD Amos, JJB Allen, November 14, 2013, Brain Stimulation Journal 

http://www.brainstimjrnl.com/article/S1935-861X%2812%2900084-8/abstract

Sanguinetti JL, Smith EE, Dieckman L, Vanuk J, Hameroff S, Allen JJB , Noninvasive Transcranial Ultrasound for Brain Stimulation: Effects on Mood in a Pilot Study, Psychophysiology 50, S36-S36 Psychophysiology 51, S42-S42. 2013 Abstract.

https://scholar.google.com/citations?user=-5FNEp0AAAAJ&hl=en&oi=sra#d=gs_md_cita-d&u=%2Fcitations%3Fview_op%3Dview_citation%26hl%3Den%26user%3D-5FNEp0AAAAJ%26citation_for_view%3D-5FNEp0AAAAJ%3AUeHWp8X0CEIC%26tzom%3D420

Additional Media

Good vibrations: Mediating mood through brain ultrasound – Researchers have developed a novel technique to affect mood through ultrasound vibrations applied to the brain. Their findings could potentially lead to new treatments for psychological and full story, Science Daily, July 18, 2013

https://www.sciencedaily.com/releases/2013/07/130718161525.htm


Non-invasive brain stimulation techniques aimed at mental and neurological conditions include transcranial magnetic stimulation (TMS) for depression, and transcranial direct current (electrical) May 15, 2013, Science Daily...full story
https://www.sciencedaily.com/releases/2013/05/130515094825.htm

Mediating Mood Through Brain Ultrasound, UA News, July 16, 2013
http://uanews.org/story/good-vibrations-mediating-mood-through-brain-ultrasound

 


continued: 

Medically, research into therapies for mental and cognitive disorders should include testbeds for quantum optical effects in microtubules. 

  1. Quantum optical pharmacology laboratory, testing effects of potential drug molecules on microtubule superradiance, quantum optics and electronic cloud dipoles. Also effects of ultrasound, and terahertz radiation. In addition to microtubules, we will study organic molecules including polyaromatic hydrocarbons, and other molecules from extraterrestrial sources through collaborations with Dante Lauretta.  

  2. CCS pioneered brain ultrasound therapy. When Anirban discovered megahertz and other frequencies in microtubules, I wondered whether ultrasound (megahertz mechanical vibrations) into the brain may be beneficial. It turned out to be safe and painless in reasonable exposure, and we performed and published the first clinical trial of transcranial ultrasound (TUS) on chronic pain and mood (Hameroff et al, 2013). I later worked with Jay Sanguinetti and John Allen in psychology on TUS (Sanguinetti et al, 2020), and hope to continue and expand clinical trials of TUS, e.g. for dementia, TBI, depression, anxiety, PTSD and addiction 

  3. https://semalab.arizona.edu/&nbsp;

 

First Trial

2 photos

Stuart Hameroff administers TUS to a volunteer

 
Stuart Hameroff and colleagues performed the first clinical trial of trancranial ultrasound (TUS) on mental states, finding improved mood after 15 seconds of sub-thermal 8 MHz ultrasound compared with placebo applied at the temporal skull. Another project is being planned numerous colleagues including, UA professor of psychology John Allen and postdoc Jay Sanguineti for mood, cognition and psychological and neurological disorders (including post-operative cognitive dysfunction) and others, tba.

Microtubules within brain neurons are thought to resonate at megahertz frequencies, precisely where ultrasound acts. We hope to enhance mood, and treat various neurological disorders by stimulating brain microtubule dynamics through TUS.

Two subsequent TUS studies done in collaboration with UA professor of psychology John Allen and post-doc Jay Sanguinetti have shown similar mood improvement from brief, sub-thermal TUS. These studies are currently being written up for publication.

Jay Sanguinetti administers brain ultrasound during a clinical trial.

Non-invasive brain stimulation techniques aimed at mental and neurological conditions include transcranial magnetic stimulation (TMS) for depression, and transcranial direct current (electrical) stimulation (tDCS), shown to improve memory. Transcranial ultrasound stimulation (TUS) has also shown promise.

Mood disorders, Alzheimer’s disease, traumatic brain injury (TBI) and post-traumatic stress disorders (PTSD) are enormous problems for those afflicted, their families, caregivers and society in general. Current treatments for these disorders are modestly effective at best, and new, more effective and inexpensive approaches are needed. A major hurdle in treatment is the lack of understanding in mainstream approaches as to how the brain works normally, how mood, cognition, memory and consciousness derive from synaptic computation among neurons. However evidence now suggests mental states may depend, to some extent at least, on vibrations, e.g. sound wave solitons in neuronal membranes, and megahertz (‘MHz’, 106 to 107 Hz) resonances in microtubule networks inside neurons. In TBI and Alzheimer’s disease, microtubules are disrupted and release ‘tau’, a microtubule-associated protein. Under normal circumstances, microtubules are directly responsible for neuronal and synaptic growth, repair and plasticity.

Ultrasound (US) consists of mechanical oscillations, e.g. in MHz. ‘Transcranial ultrasound’ (‘TUS’) passes low intensity, sub-thermal US through the skull into the brain, safely and painlessly. In clinical trials, TUS improves human mood and cognition, and in lab studies megahertz stimulation promotes microtubule assembly. We propose to determine safety and efficacy of inexpensive and potentially portable TUS technology for improving recovery from TBI, Alzheimer’s disease.

Hypothesis or Objective: High intensity US can heat, cavitate and ablate kidney stones, brain tumors and other tissue. Mid-intensity US (‘diathermy’) causes mild heating, useful for musculoskeletal problems. Low intensity, ‘sub-thermal’ US (<720 mW/cm2 by FDA guidelines) excites peripheral neurons,4 and promotes their regeneration after injury. Applied at the scalp, low intensity TUS is FDA-approved for brain imaging, though supplanted by CT, MRI etc. TUS is still used to image brains of newborn babies through boneless fontanelles, and can be focused anywhere in the adult brain. WJ Tyler and others first showed low intensity TUS caused behavioral and electrophysiological changes in animals, and more recently cognitive enhancement in humans.

In the first TUS study on human mental states,11 our group showed that 15 seconds of 8 MHz TUS to fronto-temporal cortex from temporal scalp at 150 mW/cm2 resulted in 40 minutes of improved mood compared to sham exposure. Further studies12 have shown optimal mood improvement with 2 MHz TUS for 30 seconds to right fronto-temporal cortex. In some cases, vertex stimulation (targeting cingulate cortex) resulted in uncontrolled laughter, “out of body” experiences and feelings of being “more in the moment”. High frequency (gamma synchrony) EEG was increased near the TUS stimulation site.

Regarding cellular and molecular level mechanisms, Tyler suggested TUS promotes vibrations in a mechanical continuum of extracellular, intra-membrane and intra-neuronal structures. Among these are microtubules, self-assembling polymers of tubulin, the brain’s most prevalent protein. TUS might act by tuning or enhancing endogenous microtubule megahertz resonances.

Cellular damage in TBI is attributed to biochemical cascades, apoptosis, inflammation, free radicals, glutamate excitotoxicity, blood brain barrier breakdown, axon shearing, and cytoskeletal disruption. Regardless, neuronal recovery and synaptic formation require microtubule-dependent extension of axonal and dendritic ‘neurites’. TUS may stimulate neuronal repair (e.g. for TBI) and memory turnover (PTSD). TUS warrants clinical trials for TBI, Alzheimer’s disease and PTSD.

Research Strategy

Our previous TUS studies have used a clinical GE Logiq US imaging device, and the U+ single transducer TUS headset from Thync, Tyler’s company (formerly NeuroTrek). Both devices are limited in range of MHz frequencies for testing. We are collaborating with Sterling Cooley (Berkeley Ultrasound, Berkeley, California) who has developed a TUS device called the NeuroResonator 1 (NR1) which we tested and calibrated in October, 2014. Proposed modifications will upgrade to the battery-powered NeuroResonator 2 (‘NR2’) with multiple US piezo transducer/emitters with various lead placements, each emitter controlled individually, able to be aimed at particular brain areas, driven synchronously, sequentially, in any combination and/or pulse modulated, e.g. by music. The NR2 will be calibrated, tested, and reviewed and approved by our Bioengineering and Institutional Review Board. Stimulation sites will be selected based on injured brain area, right fronto-temporal and other areas. We plan pilot studies commencing early spring 2015 and will search for optimal techniques. With the NR2 fitting in an EEG cap, we will also study TUS effects on simultaneous EEG.

Press/Media 

Good vibrations: Mediating mood through brain ultrasound – Researchers have developed a novel technique to affect mood through ultrasound vibrations applied to the brain. Their findings could potentially lead to new treatments for psychological and …full story, Science Daily, July 18, 2013

Mediating Mood Through Brain Ultrasound, UA News, July 16, 2013


Non-invasive brain stimulation techniques aimed at mental and neurological conditions include transcranial magnetic stimulation (TMS) for depression, and transcranial direct current (electrical) May 15, 2013, Science Daily...full story