Transcranial focused ultrasound neuromodulation of the human primary motor cortex

Legon, Wynn; Bansal, Priya; Tyshynsky, Roman; Ai, Leo; Mueller, Jenna L.

doi:10.1101/234666

Cited by 6 publications

(6 citation statements)

References 48 publications

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“…In previous studies, only normal animals and humans with no vision impairment were evaluated (Legon et al, 2018;Di Biase et al, 2019). It was quite recent that tFUS stimulation was tested to evoke neuronal activities of the visual cortices of both normal and blind rats (Lu et al, 2021).…”

Section: Ultrasound Stimulation Of Retina and Visual Cortexmentioning

confidence: 99%

“…Although tFUS has been used to modulate neuronal activity deep in the brain (Tufail et al, 2011;Legon et al, 2014Legon et al, , 2018Di Biase et al, 2019;Lu et al, 2021), these approaches have some limitations such as restricted to low-frequency stimulation, low spatial resolution (>3 mm), and no cell-type selectivity. To overcome these issues, sonogenetics approach was explored (Ibsen et al, 2015).…”

Section: Ultrasound Stimulation Of Retina and Visual Cortexmentioning

confidence: 99%

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Ultrasound stimulation for non-invasive visual prostheses

Badadhe

Roh²,

Lee³

et al. 2022

Front. Cell. Neurosci.

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Globally, it is estimated there are more than 2.2 billion visually impaired people. Visual diseases such as retinitis pigmentosa, age-related macular degeneration, glaucoma, and optic neuritis can cause irreversible profound vision loss. Many groups have investigated different approaches such as microelectronic prostheses, optogenetics, stem cell therapy, and gene therapy to restore vision. However, these methods have some limitations such as invasive implantation surgery and unknown long-term risk of genetic manipulation. In addition to the safety of ultrasound as a medical imaging modality, ultrasound stimulation can be a viable non-invasive alternative approach for the sight restoration because of its ability to non-invasively control neuronal activities. Indeed, recent studies have demonstrated ultrasound stimulation can successfully modulate retinal/brain neuronal activities without causing any damage to the nerve cells. Superior penetration depth and high spatial resolution of focused ultrasound can open a new avenue in neuromodulation researches. This review summarizes the latest research results about neural responses to ultrasound stimulation. Also, this work provides an overview of technical viewpoints in the future design of a miniaturized ultrasound transducer for a non-invasive acoustic visual prosthesis for non-surgical and painless restoration of vision.

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Section: Ultrasound Stimulation Of Retina and Visual Cortexmentioning

confidence: 99%

Section: Ultrasound Stimulation Of Retina and Visual Cortexmentioning

confidence: 99%

Ultrasound stimulation for non-invasive visual prostheses

Badadhe

Roh²,

Lee³

et al. 2022

Front. Cell. Neurosci.

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“…Clearly, there exists tremendous demand for noninvasive neuromodulatory therapies to normalize pathological aberrant firing in cortical [e.g., epilepsy (Chevassus- Au-Louis et al, 1999)] and subcortical [e.g., Parkinson's disease (Galvan and Wichmann, 2008)] brain areas. Output metrics vary, but are commonly tFUS-induced changes in the amplitude of sensory-evoked potentials (SEPs) (Kim et al, 2012;Legon et al, 2014;Chu et al, 2015;Kim et al, 2015;Legon et al, 2018a;Legon et al, 2018b;Darrow et al, 2019), or motor responses (Tufail et al, 2010;Kim et al, 2012;King et al, 2013;Younan et al, 2013;Mehić et al, 2014;Kamimura et al, 2015;Lee et al, 2016). The majority of studies examining effects on the SEPs report reductions in amplitude; these include reduction of somatosensory-evoked potentials in rats (Chu et al, 2015;Darrow et al, 2019) and humans (Legon et al, 2014;2018a), and visually-evoked potentials in rats.…”

Section: Transcranial Focused Ultrasound Brain Studiesmentioning

confidence: 99%

A review of the bioeffects of low-intensity focused ultrasound and the benefits of a cellular approach

Collins

Mesce²

2022

Front. Physiol.

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This review article highlights the historical developments and current state of knowledge of an important neuromodulation technology: low-intensity focused ultrasound. Because compelling studies have shown that focused ultrasound can modulate neuronal activity non-invasively, especially in deep brain structures with high spatial specificity, there has been a renewed interest in attempting to understand the specific bioeffects of focused ultrasound at the cellular level. Such information is needed to facilitate the safe and effective use of focused ultrasound to treat a number of brain and nervous system disorders in humans. Unfortunately, to date, there appears to be no singular biological mechanism to account for the actions of focused ultrasound, and it is becoming increasingly clear that different types of nerve cells will respond to focused ultrasound differentially based on the complement of their ion channels, other membrane biophysical properties, and arrangement of synaptic connections. Furthermore, neurons are apparently not equally susceptible to the mechanical, thermal and cavitation-related consequences of focused ultrasound application—to complicate matters further, many studies often use distinctly different focused ultrasound stimulus parameters to achieve a reliable response in neural activity. In this review, we consider the benefits of studying more experimentally tractable invertebrate preparations, with an emphasis on the medicinal leech, where neurons can be studied as unique individual cells and be synaptically isolated from the indirect effects of focused ultrasound stimulation on mechanosensitive afferents. In the leech, we have concluded that heat is the primary effector of focused ultrasound neuromodulation, especially on motoneurons in which we observed a focused ultrasound-mediated blockade of action potentials. We discuss that the mechanical bioeffects of focused ultrasound, which are frequently described in the literature, are less reliably achieved as compared to thermal ones, and that observations ascribed to mechanical responses may be confounded by activation of synaptically-coupled sensory structures or artifacts associated with electrode resonance. Ultimately, both the mechanical and thermal components of focused ultrasound have significant potential to contribute to the sculpting of specific neural outcomes. Because focused ultrasound can generate significant modulation at a temperature <5°C, which is believed to be safe for moderate durations, we support the idea that focused ultrasound should be considered as a thermal neuromodulation technology for clinical use, especially targeting neural pathways in the peripheral nervous system.

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“…tFUS showed to be able to target both cortical and deeper brain regions. It allowed to stimulate human primary and secondary somatosensory cortex (Lee et al, 2016;Legon et al, 2018) eliciting different tactile sensations in different regions of the hand (Legon et al, 2014;Lee et al, 2015). In the study of (Lee et al, 2015), tFUS evoked transient somatic sensations on the hand and/or the fingers of 11 out of 12 healthy subjects.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the effects of focused ultrasound stimulation on the central nervous system through a multiscale simulation approach

Scarpelli

Stefano

Cordella

et al. 2022

Front. Bioeng. Biotechnol.

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The lack of sensory feedback represents one of the main drawbacks of commercial upper limb prosthesis. Transcranial Focused Ultrasound Stimulation (tFUS) seems to be a valid non-invasive technique for restoring sensory feedback allowing to deliver acoustic energy to cortical sensory areas with high spatial resolution and depth penetration. This paper aims at studying in simulation the use of tFUS on cortical sensory areas to evaluate its effects in terms of latency ad firing rate of the cells response, for understanding if these parameters influence the safety and the efficacy of the stimulation. In this paper, in order to study the propagation of the ultrasound wave from the transducer to the cortical cells, a multiscale approach was implemented by building a macroscopic model, which estimates the pressure profile in a simplified 2D human head geometry, and coupling it with the SONIC microscale model, that describes the electrical behaviour of a cortical neuron. The influence of the stimulation parameters and of the skull thickness on the latency and the firing rate are evaluated and the obtained behaviour is linked to the sensory response obtained on human subjects. Results have shown that slight changes in the transducer position should not affect the efficacy of the stimulation; however, high skull thickness leads to lower cells activation. These results will be useful for evaluating safety and effectiveness of tFUS for sensory feedback in closed-loop prosthetic systems.

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Transcranial focused ultrasound neuromodulation of the human primary motor cortex

Cited by 6 publications

References 48 publications

Ultrasound stimulation for non-invasive visual prostheses

Ultrasound stimulation for non-invasive visual prostheses

A review of the bioeffects of low-intensity focused ultrasound and the benefits of a cellular approach

Evaluation of the effects of focused ultrasound stimulation on the central nervous system through a multiscale simulation approach

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