Ultrasound functional neuroimaging reveals propagation of task-related brain activity in behaving primates

In recent decades, neuroimaging has played an invaluable role in improving the fundamental understanding of the brain. At the macro scale, neuroimaging modalities such as MRI, EEG, and MEG, exploit a wide field of view to explore the brain as a global network of interacting regions. However, this comes at the price of either limited spatiotemporal resolution or limited sensitivity. At the micro scale, electrophysiology is used to explore the dynamic aspects of neuronal activity with a very high temporal resolution. However, this modality requires a statistical averaging of several tens of single task responses. A large-scale neuroimaging modality of sufficient spatial and temporal resolution and sensitivity to study brain region activation dynamically would open new territories of possibility in neuroscience. We show that neurofunctional ultrasound imaging (fUS) is both able to assess brain activation during single cognitive tasks within superficial and deeper areas of the frontal cortex areas, and image the directional propagation of information within and between these regions. Equipped with an fUS device, two macaque rhesus monkeys were instructed before a stimulus appeared to rest (fixation) or to look towards (saccade) or away (antisaccade) from a stimulus. Our results identified an abrupt transient change in activity for all acquisitions in the supplementary eye field (SEF) when the animals were required to change a rule regarding the task cued by a stimulus. Simultaneous imaging in the anterior cingulate cortex and SEF revealed a time delay in the directional functional connectivity of 0.27 ± 0.07 s and 0.9 ± 0.2 s for animals S and Y, respectively. These results provide initial evidence that recording cerebral hemodynamics over large brain areas at a high spatiotemporal resolution and sensitivity with neurofunctional ultrasound can reveal instantaneous monitoring of endogenous brain signals and behavior.