Electrical activity in the brain is a direct correlate to neuronal activity. Existing technology can record electrical activity on a millisecond scales through invasive placement of electrodes within the brain or non- invasively, using subdermal electrodes. Such recordings can be used to study brain function, diagnose diseases of the brain or to directly control external machinery (a.k.a. Brain Computer Interface or BCI). Currently, the low fidelity, sensitivity, poor spatial resolution, and susceptibility to noise limits the use of subdermal EEG. We propose to increase the anatomical specificity of EEG by using another non-invasive method, pulsed focused ultrasound (pFU) stimulation, to add a unique electrophysiological marker or tag to the focal electrophysiological activity within a small volume of brain (<<1mm^3). Our recent work shows that we can induce a measurable EEG signal above physiological frequencies through transcranial pFU stimulation of rat brain with a pulse repetition frequency at 1.05 kHz. We call this unique high-frequency EEG signal induced by pFU an ?acoustic beacon?, hypothesizing that it arises from only the volume of brain insonified by pFU. We directly measured brain activity within a frequency band (3-40 Hz) that we also observed via amplitude-demodulation of the acoustic beacon. These results suggest that pFU can tag focal regions within the brain, allowing reconstruction of brain activity within that focus through analysis of EEG signals. However, unresolved issues include definitive detection of known and focal endogenous brain signals via analysis of the acoustic beacon, whose production does not alter endogenous brain activity. We propose to resolve these issues by testing the following hypothesis: pFU applied to brain transcranially can encode focal brain activity in a manner detectable via EEG and without altering focal brain function. We will induce visually evoked potentials (VEPs) via pulsed light application to the exposed eye of anesthetized mice, with the exact anatomical location of stimulated cortex documented via fMRI. We will apply pFU with a variety of parameter values (carrier frequency, pulse duration, spatial peak pulse-average intensity) to the site of stimulated brain then away from the site, while recording subdermal EEG. We will analyze the resulting acoustic beacon signal measured by EEG to detect the light induced low-frequency visually evoked potentials. We anticipate that the acoustic beacon encodes the VEPs if and only if the pFU focus overlaps with the activated portion of visual cortex. If successful, future work may one day allow recording of electrical activity non-invasively from anywhere within the brain, including simultaneously from several locations, at millisecond time scales and with millimeter spatial resolution. Additionally, non-invasive BCIs with unsurpassed accuracy will be made possible by this technique, as it would allow placement of a virtual probe anywhere on the brain. Finally, appropriate pFU protocols can modulate brain activity, opening the possibility of using pFU plus EEG to create a closed-loop BCI system through pFU protocols that can monitor and, separately, alter brain function.
Towards deep brain monitoring with superficial EEG sensors plus neuromodulatory focused ultrasound This project will test whether a novel combination of ultrasound and electroencephalography (EEG) can be used to detect brain activity with precise spatial resolution, which is not possible with EEG alone. We propose to test our new technique in mice, where we use stimulation of the whisker and, separately, the optic nerve, to create well-defined local brain activity as our test signal.