Effective Parameters for Ultrasound-Induced In Vivo Neurostimulation

King, Randy L.; Brown, Julian; Newsome, William T.; Pauly, Kim Butts

doi:10.1016/j.ultrasmedbio.2012.09.009

Cited by 426 publications

(500 citation statements)

References 40 publications

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“…Compared to emerging ultrasonic neuromodulation techniques in which ultrasound directly activates or inhibits brain regions or releases local neuromodulatory compounds [48][49][50][51][52][53][54][55] , ATAC does not require an ultrasound transducer to be mounted on the subject during modulation. After transduction and expression of chemogenetic receptors in a genetically defined subset of cells at the FUS-targeted site, neuromodulation is conveniently controlled using an orally bioavailable drug.…”

Section: Discussionmentioning

confidence: 99%

Acoustically targeted chemogenetics for the non-invasive control of neural circuits

et al. 2018

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Neurological and psychiatric diseases often involve the dysfunction of specific neural circuits in particular regions of the brain. Existing treatments, including drugs and implantable brain stimulators, aim to modulate the activity of these circuits, but are typically not cell type-specific, lack spatial targeting or require invasive procedures. Here, we introduce an approach to modulating neural circuits noninvasively with spatial, cell-type and temporal specificity. This approach, called acoustically targeted chemogenetics, or ATAC, uses transient ultrasonic opening of the blood brain barrier to transduce neurons at specific locations in the brain with virally-encoded engineered G-protein-coupled receptors, which subsequently respond to systemically administered bio-inert compounds to activate or inhibit the activity of these neurons. We demonstrate this concept in mice by using ATAC to noninvasively modify and subsequently activate or inhibit excitatory neurons within the hippocampus, showing that this enables pharmacological control of memory formation. This technology allows a brief, noninvasive procedure to make one or more specific brain regions capable of being selectively modulated using orally bioavailable compounds, thereby overcoming some of the key limitations of conventional brain therapies.

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Section: Discussionmentioning

confidence: 99%

Acoustically targeted chemogenetics for the non-invasive control of neural circuits

et al. 2018

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“…Recent advances in US hardware, medical imaging, and computer modeling have allowed for greatly increased efficacy in delivering US pulses through the intact skull, and even utilization of the skull's curvature to reduce US beam attenuation within the brain ( fig. 1 ) [Clement and Hynynen, 2002;Clement, 2004;Clement et al, 2005;White et al, 2006;King et al, 2013].…”

Section: Ultrasonic Wave Propagation In Tissuementioning

confidence: 99%

“…It is important to note that while this focusing effect is beneficial, the skull composition still causes a degree of acoustic scattering and US wave attenuation as a result of acoustic impedance mismatches between the scalp, skull, and cortical surface, which must be compensated for in order to maintain a high spatiotemporal resolution [Ziskin, 1993;Hynynen and Jolesz, 1998;Clement and Hynynen, 2002;Clement, 2004;King et al, 2013].…”

Section: Ultrasonic Wave Propagation In Tissuementioning

confidence: 99%

“…Currently, there is no clear indication of which technique may be more efficacious for NM, though it is likely that it is target specific, and further complicated by the depth of a tissue structure, the homogeneity of intervening tissue before the target, and the prevalence of mechanosensitive elements of the target cell type itself [Kim et al, 2012]. With regard to neural tissues specifically, both continuous-wave and pulsed-wave US have been found to be effective in modulating neural activity [King et al, 2013]. Current work is building off of these studies and utilizing enhanced technological advances for elucidation of how cells and tissue mechanistically respond to ultrasonic stimulation.…”

Section: Continuous Wave Versus Pulsed-wave Usmentioning

confidence: 99%

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The Body Acoustic: Ultrasonic Neuromodulation for Translational Medicine

Ventre

Koppes

2016

Cells Tissues Organs

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For the greater part of the last century, ultrasound (US) has seen widespread use in applications ranging from materials science to medicine. The history of US in medicine has also seen promising success in clinical diagnostics and regenerative medicine. Recent studies have shown that US is able to manipulate the nervous system, leading toward potential treatment for various neuropathological conditions, a phenomenon known as ultrasonic neuromodulation (NM). Ultrasonic NM is a promising alternative to pharmaceuticals and surgery, due to high spatiotemporal resolution combined with the potentially noninvasive means of application. Current advances have made progress in establishing effective dosage limits, waveform parameters, and stimulus regimes in order to achieve desired effects in a variety of tissue and cell types. However, to date there has been limited systematic analysis of the complex variables involved in creating a therapeutic US stimulation regime specifically tailored to the nervous system. Without a fundamental understanding of the effects of US on neural tissue, including the surrounding bone, musculature, and vasculature, the safety and efficacy of US as an NM tool is yet to be determined. Advances in imaging technology and focusing hardware highlight new avenues for potential clinical applications for therapeutic ultrasonic stimulation. US may be an alternative to electrical and magnetic means of NM for targets in the central nervous system as well as in the peripheral and autonomic nervous systems. This review provides a historical perspective on the past, present, and future of US as a translational therapeutic.

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“…Recently, ultrasonic brain stimulation has emerged as a novel noninvasive brain stimulation modality showing improved penetration and spatial resolution over existing noninvasive brain stimulation methods. Not only animal experiments but also recent experiments on human subjects have shown the promising capabilities of ultrasound as a novel neuro-modulation modality [2][3][4][5][6][7][8][9].…”

mentioning

confidence: 99%

Development of a Wearable Robotic Positioning System for Noninvasive Transcranial Focused Ultrasound Stimulation

Kim

Lee

2016

IEEE/ASME Trans. Mechatron.

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Transcranial ultrasound neuromodulation has been attracting more and more interest from researchers as a novel modality for brain stimulation. Typical manual positioning for brain stimulation requires the patient to sit still during stimulation for extended periods and readily loses its positioning accuracy if the patient moves. To address these problems of inconvenience and inaccuracy, we proposed a robotic positioning system for targeted ultrasound brain stimulation. The proposed device automatically moves the ultrasound transducer to a desired position and orientation, enabling far more accurate and comfortable automatic positioning of the transducer than when using traditional manual positioning. The device was developed as a wearable design because it eliminates the necessity for troublesome motion compensation for the user's unintentional movements. Parallel and serial mechanisms were combined and a torque optimization method was proposed so as to obtain a lightweight design and to implement a sufficient number of degrees of freedom of motion.Index Terms-Noninvasive brain stimulation and treatment, robotic positioning system, transcranial magnetic stimulation, and ultrasound stimulation. T T J J J J T x x q J J J J

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Effective Parameters for Ultrasound-Induced In Vivo Neurostimulation

Cited by 426 publications

References 40 publications

Acoustically targeted chemogenetics for the non-invasive control of neural circuits

Acoustically targeted chemogenetics for the non-invasive control of neural circuits

The Body Acoustic: Ultrasonic Neuromodulation for Translational Medicine

Development of a Wearable Robotic Positioning System for Noninvasive Transcranial Focused Ultrasound Stimulation

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