Using mice as an animal model, we are investigating the possibility that fetal ultrasound exposure in utero has contributed to the observed dramatic increase in the number of cases of autism. A leading hypothesis suggests that autism may arise through a combination of genetic predisposition and exposure to certain environmental factors during a vulnerable period of neuro-development in utero. To test this hypothesis we exposed mice to diagnostic ultrasound in utero during a specific developmental time window to check for possible post-birth induction of autistic-like behavior and neuro-anatomy. Specifically, we exposed anesthetized pregnant mice to ultrasound for 30 minutes on embryonic day 12. When mice pups were three weeks of age, we used a variety of behavioral tests to assay for autistic-like characteristics. Additionally, we performed histology on the mouse brains, analyzing them for neuroanatomical characteristics of autism. Our published results show significant social behavioral differences between ultrasound-exposed and sham-exposed mice. Also, preliminary analysis of the brains found decreased minicolumnar width and variability in the ultrasound-exposed group relative to the sham-exposed group. Both the behavioral and neuroanatomical results are consistent with the hypothesis that diagnostic ultrasound exposure in utero represents a potential risk factor for autism. Future research will target study of possible bio-physical mechanisms that may underlie our observations. Specifically, we intend to tag newborn cortical neurons via injection of BrdU in an attempt to quantify ultrasound’s effect on the migration of these neurons, anticipating a relationship between dose of ultrasound and extent of disruption of the cortical layers within the brains of ultrasound-exposed mice.

Transcranial ultrasound can alter brain function transiently and nondestructively, offering a new tool to study brain function and inform future therapies. Previous research on neuromodulation implemented pulsed low frequency (250–700 kHz) ultrasound with spatial peak temporal average intensities (ISPTA) of 0.1–10 W/cm2. That work used transducers that either insonified relatively large volumes of mouse brain (several mL) with relatively low frequency ultrasound and produced bilateral motor responses, or relatively small volumes of brain (on the order of 0.06 mL) with relatively high frequency ultrasound that produced unilateral motor responses. Our work seeks to increase anatomical specificity to neuromodulation with modulated focused ultrasound (mFU). Here, ‘modulated’ means modifying a focused 2-MHz carrier signal dynamically with a 500-kHz signal as in vibro-acoustography, thereby creating a low frequency, but small volume (approximately 0.015 mL) source of neuromodulation. Application of transcranial mFU to lightly anesthetized mice produced various motor movements with high spatial selectivity (on the order of 1 mm) that scaled with the temporal average ultrasound intensity. Alone, mFU and focused ultrasound (FUS) each induced motor activity, including unilateral motions, though anatomical location and type of motion varied. Of interest is the exploration of potential research and clinical applications for targeted, transcranial neuromodulation created by modulated focused ultrasound, especially mFU’s ability to produce compact sources of ultrasound at the very low frequencies (10–100s of Hertz) that are commensurate with the natural frequencies of the brain. Currently, I am working to incorporate mFU with electroencephalography (EEG) to aid researchers and clinicians in localizing neural activity. Theoretically, the vibro-acoustography paradigm allows a small volume of neural tissue to be tagged with a specific difference frequency; EEG will determine the origin of this signal.