Recent work published by my colleagues and I showed that diagnostic ultrasound, applied directly over the visual cortex of human participants, increased the likelihood that they would observe visual effects while looking at a visual target, with that likelihood increasing over the course of the experiment. However due to a lack of EEG data, it is impossible to know the biophysical mechanisms and neural pathways that generate the observed effects on brain function. To better understand the full effect and mechanism of our initial findings, I helped develop a surgical protocol for a mouse model allowing for the collection of EEG data while exposing the animal to a combination of light and diagnostic ultrasound stimuli. EEG data was collected from 5 mice using a stimulus paradigm that we believed would increase the rodent's susceptibility to light stimulus. I utilized Matlab for processing, visualization, and statistical analysis of the data to determine the effects and hypothesize potential biophysical mechanisms of the stimuli. My analysis focused on determining whether the ultrasound stimulus successfully increased the susceptibility of the visual cortex, and which brain frequency bands were modulated by the stimulation.

Hydrocephalus is a condition in which the cerebrospinal fluid (CSF) accumulates in the brain, increasing pressure inside the skull. A common method of treatment in pediatric patients is the placement of a shunt inside the fluid-filled ventricle of the brain. Overtime, shunts will become obstructed, fail to work, and require brain surgery and reimplantation of a new shunt. We will apply a intense focus ultrasound to send a pulse through the catheters obstructed by astrocyte tissue cultures in a three-dimensional model for shunt failure. When the method has been refined, we plan to apply ultrasound on catheters clogged from cerebrospinal fluid (CSF) that will be obtained from shunt replacement surgeries performed at Seattle Children’s hospital. Our aim is to improve the flow rate through the catheter, thus providing a less invasive method for shunt clearing in pediatric patients with hydrocephalus.

 Iaccarino et al exposed one hour of light flickering at 40Hz to awake 5XFAD Alzheimer's Disease (AD) mouse models, consequently generating action potentials at 40 Hz and activating mircoglia. Consequent colocalization of microglia with Aß plaque actuely and clearing of Aß plaque after seven days was observed, but only in the visual cortex. We hypothesized transcranially delivered, near diagnostic ultrasound (tnDU) can replicate the results of Iaccarino et al but throughout its area of application, thus not limited to the visual cortex. We exposed sedated 5XFAD mice to tnDU at 40Hz with 400microsecond-long pulses for one hour, targeting one hemisphere of brain centered on its hippocampus. Chronic studies targeted comparable brain in each hemisphere for one hour/day for five days. Histology and EEG recoding revealed acute application of tnDU activated more microglia that colocalized with Aß plaque, relative to the contralateral hemisphere of treated brain with brain activation at 40Hz. Chronic application reduced their Aß plaque burden by nearly half relative to paired sham animals. Our results compare to those of Iaccarino et al but throughout the area of ultrasound-exposed brain. Our results also compare to those achieved by medications that target Aß for a substantially shorter period of time. The proximity of our ultrasound protocol to those shown as safe for non-human primates and humans may motivate its rapid translation to human studies.