New Noninvasive Device Can Modulate Specific Cell Types in Multiple Diseased Regions of the Brain

[Mij]

A team of biomedical engineers at the Washington University in St. Louis have developed a noninvasive technology that combines a holographic acoustic device with genetic engineering to precisely modulate selected neurons in the multiple diseased regions of the brain. The technology has significant potential to treat human brain diseases, such as Parkinson's disease that involve damage in more than one brain region.

The technology, called AhSonogenetics (Airy-beam holographic sonogenetics) uses a noninvasive, wearable ultrasound device and showed in mouse studies that it is capable of altering genetically selected neurons in the brain. The technology, detailed in a paper published this week in Proceedings of the National Academy of Sciences, builds on several advances from the lab of Hong Chen, an associate professor of biomedical engineering and neurosurgery at Washington University in St. Louis who is the senior author of the study.

LINK

 

[Mij]

The Study: Airy-beam holographic sonogenetics for advancing neuromodulation precision and flexibility, 2024, Zhongtao Hu et al

Significance
Sonogenetics holds promise for noninvasive and cell type–specific neuromodulation using ultrasound, yet its potential has been constrained by existing wearable technologies. We present the development of Airy-beam holographic sonogenetics (AhSonogenetics) and demonstrate its significant capabilities. AhSonogenetics offers superior precision in targeting specific subregions of the brain and unparalleled flexibility to dynamically shift focus across different brain regions in freely moving mice. Furthermore, it is compatible with in vivo optical calcium recordings without cross talk. Importantly, AhSonogenetics enables bilateral stimulation for alleviating motor deficits in mice with Parkinson’s disease, addressing the challenge of simultaneously targeting dysfunction in multiple brain regions. AhSonogenetics represents a multidisciplinary innovation that advances sonogenetic neuromodulation in terms of precision and flexibility.
Abstract
Advancing our understanding of brain function and developing treatments for neurological diseases hinge on the ability to modulate neuronal groups in specific brain areas without invasive techniques. Here, we introduce Airy-beam holographic sonogenetics (AhSonogenetics) as an implant-free, cell type–specific, spatially precise, and flexible neuromodulation approach in freely moving mice. AhSonogenetics utilizes wearable ultrasound devices manufactured using 3D-printed Airy-beam holographic metasurfaces.

These devices are designed to manipulate neurons genetically engineered to express ultrasound-sensitive ion channels, enabling precise modulation of specific neuronal populations. By dynamically steering the focus of Airy beams through ultrasound frequency tuning, AhSonogenetics is capable of modulating neuronal populations within specific subregions of the striatum. One notable feature of AhSonogenetics is its ability to flexibly stimulate either the left or right striatum in a single mouse. This flexibility is achieved by simply switching the acoustic metasurface in the wearable ultrasound device, eliminating the need for multiple implants or interventions. AhSonogentocs also integrates seamlessly with in vivo calcium recording via fiber photometry, showcasing its compatibility with optical modalities without cross talk.

Moreover, AhSonogenetics can generate double foci for bilateral stimulation and alleviate motor deficits in Parkinson’s disease mice. This advancement is significant since many neurological disorders, including Parkinson’s disease, involve dysfunction in multiple brain regions. By enabling precise and flexible cell type–specific neuromodulation without invasive procedures, AhSonogenetics provides a powerful tool for investigating intact neural circuits and offers promising interventions for neurological disorders.

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[Hutan]

Ah, in mice. Actually, in mice genetically engineered to express ultrasound-sensitive ion channels.

If I'm understanding it correctly, it's like adding a switch to neurons, with the switch operated by a sonic signal which can be precise about which bit of the brain they are deployed to. So, an interesting research tool avoiding the need for invasive implants.

 

[alktipping]

totally invasive if ultrasound is altering brain cell function . do they not understand that words have meaning.

 

[SNT Gatchaman]

Interesting idea that ultrasound is "invading" the body, or that anything — drug, psychotherapy — that has an effect is "invasive". I would have defaulted to the standard definition eg US National Cancer Institute —

"A medical procedure that invades (enters) the body, usually by cutting or puncturing the skin or by inserting instruments into the body."

but it's a grey zone and the definition is up for debate. Eg we talk about or invasive or non-invasive mechanical ventilation, but not usually about invasive nasogastric tube insertion or even invasive endoscopy.

What makes a medical intervention invasive? (2024)
Gabriel De Marco; Jannieke Simons; Lisa Forsberg; Thomas Douglas

The classification of medical interventions as either invasive or non-invasive is commonly regarded to be morally important. On the most commonly endorsed account of invasiveness, a medical intervention is invasive if and only if it involves either breaking the skin (‘incision’) or inserting an object into the body (‘insertion’). Building on recent discussions of the concept of invasiveness, we show that this standard account fails to capture three aspects of existing usage of the concept of invasiveness in relation to medical interventions—namely, (1) usage implying that invasiveness comes in degrees, (2) that the invasiveness of an intervention can depend on the characteristics of the salient alternative interventions, and (3) that medical interventions can be invasive in non-physical ways. We then offer the beginnings of a revised account that, we argue, is able to capture a wider range of existing usage. Central to our account is a distinction between two properties: basic invasiveness and threshold invasiveness. We end by assessing what the standard account gets right, and what more needs to be done to complete our schematic account.


Link | PDF (Journal of Medical Ethics) [Open Access]

 

[Creekside]

I don't see how it proposes to treat Parkinson's disease. Are they planning to genetically edit mature human brains to add these acoustic switches?

I do see it as having potential value for understanding the brain. Our present model of brain function is overly simple, so anything that can add to the knowledge of how it actually works is useful. This technique might break a lot of present beliefs of how the brain works and what treatments might be effective.