Detection and characterization of motor activity in behaving infants through the use of novel ultrasonic brain imaging technology

Abstract Recent advances in neuroimaging technology have significantly contributed to a better understanding of brain organization, and the development and application of more efficient clinical programs. However, inherent limitations to the existing techniques make large-scale imaging of neural activity with high spatiotemporal resolution and specificity in young populations challenging (1). Functional magnetic resonance imaging (fMRI) is predominantly performed on sleeping infants to minimize motion-related artifacts and avoid exposure to certain stimuli in the novel scanner environment (e.g., loud noise). Techniques that can be used in awake infants, such as electroencephalography (EEG), magnetoencephalography (MEG) and functional near-infrared spectroscopy (fNIRS) are more suited to study cognitive (non-motor) developmental mechanisms. A recent review study from our team revealed high level of exclusion rates associated with technical limitations in pediatric neuroimaging explaining the limited neuroimaging motor-related studies in infants (less than 5%). Functional ultrasound imaging (fUSI) is a novel technology that provides a unique combination of spatial coverage (depth up to 8 cm), unprecedented spatiotemporal resolution (100 μm, up to 10 ms) and compatibility with freely moving subjects (2). While most fUSI studies have been conducted in rodents (2-5), one of the most exciting aspects of this technology is its ability to scale to larger organisms, including monkeys (6, 7), adult humans (8), and sleeping infants (9, 10). Although fUSI typically requires thinned skull surgery or trepanation to enable the penetration of the ultrasound waves, in infants, fUSI images can be acquired non-invasively through the fontanels. The first proof-of-concept application of fUSI in neonates opened a new avenue for studying the brain in infancy (9, 10). However, this study was performed on sleeping infants, limiting the type of behavioral paradigms that can be used to explore neural correlates of motor development. Here, we take the next major leap in functional neuroimaging by extending fUSI technology to study the brain in infancy during motor control performance. Aim 1 will assess the functional organization of the motor system in infants performing a reaching task. Typically developing infants will reach to targets, while brain activity will be recorded using fUSI and biomechanical and behavioral data will be collected. Our hypothesis is that fUSI will successfully detect increased motor-related brain activity during reaching. Aim 2 will develop tools to decode motor activity in the infant brain using fUSI. We will attempt to decode the direction of reaching movements from the fUSI activity – an essential component for building non-invasive brain-machine interface (BMI) systems for very young populations with motor impairments in the future. If successful, this project will provide neuroscience with high resolution imaging technology for monitoring brain activity in awake and behaving infants, while setting the foundation for the development of non-invasive ultrasonic BMI systems for infant motor rehabilitation.