Transcranial Focused Ultrasound Stimulation for Neuroscience — Method Summary
Summary #02. Brain stimulation and imaging methods #1.
“Transcranial Focused Ultrasound (tFUS) and Transcranial Unfocused Ultrasound (tUS) Neuromodulation: From Theoretical Principles to Stimulation Practices”
With this review I start the series of articles on state-of-the-art brain stimulation and imaging methods that show hope for application in next-generation brain-computer interface device 😇
🧐 At a glance:
Neuroscience research and application is based on physical methods to record and manipulate brain activity. The review proposed by authors covers the mechanisms, problems and applications of recently proposed method of non-invasive, spatially and temporally selective brain modulation method — transcranial focused ultrasound stimulation (tFUS)
paper — https://www.frontiersin.org/articles/10.3389/fneur.2019.00549/full
⌛️Prerequisites:
I suggest to get familiar with these concepts before reading the review:
- Neural cells, neuronal membrane (this is definitely needed to understand anything I am going to talk about next)
- Neuroscience methods: fMRI, EEG, transcranial magnetic stimulation (TMS)
🚀 Motivation:
We can now record the brain activity, interpret it and extract useful information fairly well. If we further wish to engineer a bidirectional brain communication device, we should develop a means of focused brain stimulation. Ideally, it should convey information directly into the brain or modulate its activity in a predictable way. Non-invasive methods, such as transcranial electrical/magnetic stimulation stimulate superficial layers in a non-specific way, while optogenetics is invasive, requires genome editing and is not portable. In this review a recently developed method of non-invasive focused ultrasound stimulation is broken down into pieces.
🔍 Main Ideas:
1) How tFUS works
Multiple ultrasound sources emit signals which interfere at the point of focus, selectively affecting a small brain region. Modern algorithms can make the precise calculation of focus point possible taking into account skull acoustic properties.
Main mechanisms of sound modulation of electrical activity of the neural cells:
1. Mechanical stretching of membrane causing capacitive current
2. Activation of mechanoreceptors changing membrane permeability for different ions
Thus its mechanic forces transforming the neuronal membrane to cause electrical changes, which constitute brain activity.
2) Potential problems
- Heating (ultrasound conveys energy which dissipates in brain tissue)
- Formation of cavities (mechanical pressure)
These lead to local tissue damage. The good thing is, the stimulation parameters can be adjusted to avoid these issues.
3) tFUS features:
😃 Non-invasive — does not require surgery
😃 Allows targeting deeper structures
🙁 Non-cell type specific — affects all cells in a region of focus
🙄 Modulatory — changes the population activity (affects information flows but does not convey information itself) — can cause excitation or inhibition (but not information transfer)
🙂 Spatial resolution <1cm
🙂 Time resolution <1 sec, effects can last up to 2 hours
😃 Portable and affordable device
4) Experimental insights:
- Focused ultrasound can facilitate targeted drug delivery! “FUS in combination with microbubbles administered intravenously can open the blood-brain barrier, in a targeted, non-invasive, safe, and reversible manner”
- tFUS modulates EEG oscillatory dynamics and affects individual components of somatosensory evoked potentials — this suggests it alters sensory stimulus processing
- tFUS in somatosensory cortex caused sensations and in visual cortex — phosphenes (similar to TMS)
- tFUS affects BOLD (fMRI) responses both in cortical and deeper structures
- Appliying tFUS to right prefrontal cortex altered mood and influenced functional connectivity (study)
📈 Possibility for development:
In combination with optogenetics it was shown possible to develop proteins that are sensitive to ultrasound frequencies, thus making it possible to cell-specific manipulation of brain activity (sonogenetics)
📝 My Notes:
- Particularly excited about possible sonogenetic approach: this overcomes both optogenetics pitfalls (invasive) and tFUS (non-specific) allowing for precise information tranfer in the brain
- tFUS resembles TMS a lot (modulatory, non cell-type specific), although it has two advantages: stimulation of deeper structures and more spatial specificity. I’d say it’s next step in non-invasive neuromodulation!
- tFUS certainly has scientific value for capturing causal interactions in different brain regions. It again resembles TMS in this fashion, but now we can stimulate amygdala or insular cortex revealing more important information about brain dynamical behavior.
🐎 Further reading:
Original ultrasound focusing method article (2001)
Applications of FUS in neurology (Nature Reviews Neurology)
Next time I will try to learn more about novel brain recording method: functional ultrasound imaging
🔥 Also, I will surely try to break down various optogenetic methods and their modern variations that show promise for true non-invasive brain communication device!
This review was made in collaboration with Alexander Kovalev. He focuses on neural networks and their application in brain-computer interfaces.
