Abstract
Brain-machine interfaces (BMIs) are one of the key motivating applications for the BRAIN Initiative’s drive to develop
innovative technologies for large-scale recording of neural activity, benefiting not only BMI, but many other neuroscience
studies. The most advanced techniques for neural recording and BMIs are currently invasive, causing local damage to living
brain tissue, limiting their applications in human neuroscience research and BMI. On the other hand, noninvasive techniques
typically offer relatively low spatial resolution and sensitivity. A minimally invasive BMI would bridge the gap between
these extremes, opening a new avenue for neuroscience research and neuroprosthetics. Recently, functional ultrasound (fUS)
imaging was introduced as a breakthrough technology for large-scale recording of neural activity – providing highly
sensitive imaging of activity-dependent changes in blood flow with a spatiotemporal resolution of ~100 µm and 100 ms at
several-cm depth. Importantly, fUS can record from outside the brain and protective dura mater tissue, vastly expanding its
potential use in neuroscience applications and BMIs alike. While fUS is a hemodynamic technique, its excellent
spatiotemporal performance and single-trial sensitivity offer a substantially closer connection to the underlying neuronal
signals than achievable with other hemodynamic methods such as fMRI.
In this project, we will push the boundaries of fUS as a technology for large-scale recording of neural activity by developing
a fUS-based minimally invasive BMI. This proposal is based on preliminary data acquired by the collaborating investigators
showing that ultrafast fUS imaging of the posterior parietal cortex in non-human primates (NHP) provides sufficient
information to predict planned movements from single trial fUS recordings. These remarkable findings suggest that it may
be possible to use fUS as the basis for a minimally invasive BMI that is implanted in the skull and does not penetrate the
dura or brain tissue.
Turning this potential into reality requires several fundamental advances in fUS neural imaging technology, which will
greatly enhance the utility of this large-scale neural imaging technique across neuroscience applications. These advances
include (1) maximizing the speed, data processing and information content extracted from fUS to enable a high-
performance, real-time acute BMI; (2) developing a surgically implantable fUS technology for chronic, longitudinal
minimally invasive recording of neural activity from a specific brain region; and (3) extending the fUS technology from 2D
to 3D to facilitate applications requiring real-time imaging of large brain volumes. This proposal is enabled by two key
innovations made by the co-PIs: the invention of fUS by Tanter, and the discovery by the collaborative team of Andersen,
Shapiro and Tanter that fUS signals contain information that can be used for BMI. In addition, several new innovations are
introduced through the proposed work including techniques to acquire and process fUS data in real time, advances in fUS
hardware and surgical techniques for chronic implantation, and advances to enable wide-field and sparse real-time 3D
imaging. If successful, this project will significantly advance the capabilities of fUS as a widely useful technology for rapid,
sensitive, large-scale neural imaging and enable minimally invasive BMI.