High Resolution Modulation of Brain Circuit Activity by Pulsed Ultrasound

Brain Circuit Stimulation by Pulsed Ultrasound

About a decade ago we found that low-intensity pulsed ultrasound is capable of directly stimulating voltage-gated sodium and calcium transients, action potentials, and synaptic transmission using in vitro hippocampal preparations as illustrated above (PLoS One, 2008). Based on these observations, we hypothesized the mechanical (non-thermal) bioeffects of pulsed ultrasound exerted actions on neuronal membranes and ion channels to non-invasively stimulate or modulate brain circuit activity (see Neuromechanobiology); Neuroscientist, 2011; Nature Reviews Neuroscience, 2012). We subsequently provided the first evidence that transcranial pulsed ultrasound is capable of non-invasively stimulating intact cortical and hippocampal circuits of mice without causing tissue heating or cellular damage (Neuron, 2010; Nature Protocols, 2011). Since then our basic observations have been replicated in numerous in vitro and in vivo models including humans.

Adapted from Nature Neuroscience, 2014

We spent many years investigating and characterizing the safety of pulsed ultrasound for neuromodulation before providing the first neurophysiological and psychophysical demonstrations that transcranial focused ultrasound (FUS) can noninvasively modulate human brain activity as shown above (Nature Neuroscience, 2014; Brain Stimulation, 2014). 


Spatial Resolution of Focused Ultrasound for Neuromodulation

Perhaps one of the biggest advantages of ultrasonic neuromodulation is the spatial resolution it can confer. As shown above, tFUS at 0.5 MHz yields a lateral spatial resolution in human cortex of about 5 mm compared to the centimeter plus resolutions offered by other commonly used methods such as tDCS and TMS.

When transmission across a skull is not required, high-frequency ultrasound (> 1 MHz) can be used to achieve spatial resolutions approaching single cell scales. For example, retinal circuits have been modulated with 90 micron resolution using 43 MHz focused ultrasound (Menz et al, 2014). Advances in phased array transducers, including those using acoustic hyper-lenses or metamaterials, combined with improved phase distortion algorithms and enhanced beam forming techniques will enable more precise control of neural activity at even higher spatial resolutions than can currently be achieved.

The development of ultrasound transducers specifically designed to interface with neural circuits will enable the modulation of brain activity using mechanobiological interfaces that may provide advantages over conventional electronic and state-of-the-art bioelectronic methods.  


Deep-brain Modulation by Focused Ultrasound

 
 

For the past couple years we have been working to establish best approaches for modulating deep-brain function. As we continue investigating mechanisms of action and applications of ultrasonic neuromodulation, our present translational work is aimed at regulating limbic function using transcranial focused ultrasound. 


Peripheral Stimulation by Pulsed Ultrasound

Adapted from PLoS One, 2012

In addition to our work on direct brain circuit modulation by transcranial focused ultrasound, we have investigated the utility of pulsed ultrasound in peripheral circuit modulation. Here we provided neurophysiological evidence that pulsed ultrasound can differentially activate peripheral nerve circuits in humans as shown above (PLoS One, 2012). We are interested in using pulsed ultrasound to modulate peripheral nerve activity for a variety of clinical and non-clinical applications including human-machine interfaces.