Whole-Brain Functional Ultrasound Imaging Reveals Brain Modules for Visuomotor Integration

Abstract

SummaryLarge numbers of brain regions are active during behaviors. A high-resolution, brain-wide activity map could identify brain regions involved in specific behaviors. We have developed functional ultrasound imaging to record whole-brain activity in behaving mice at a resolution of ∼100 μm. We detected 87 active brain regions during visual stimulation that evoked the optokinetic reflex, a visuomotor behavior that stabilizes the gaze both horizontally and vertically. Using a genetic mouse model of congenital nystagmus incapable of generating the horizontal reflex, we identified a subset of regions whose activity was reflex dependent. By blocking eye motion in control animals, we further separated regions whose activity depended on the reflex’s motor output. Remarkably, all reflex-dependent but eye motion-independent regions were located in the thalamus. Our work identifies functional modules of brain regions involved in sensorimotor integration and provides an experimental approach to monitor whole-brain activity of mice in normal and disease states.

Localized semi-nonnegative matrix factorization (LocaNMF) of widefield calcium imaging data

“…Furthermore, recent studies have shown that the spatial and temporal activity recorded from WFCI and fMRI during spontaneous activity show considerable similarities 3,36 . Given these conceptual similarities, we believe there are opportunities to adapt the methods we introduced here to fMRI or other three-dimensional (3D) functional imaging modalities 37,38 , while using a 3D atlas of brain regions to aid in localization of the extracted demixed components. We hope to pursue these directions in future work.…”

Functional ultrasound speckle decorrelation-based velocimetry of the brain

“…For the phantom validation experiment, a plastic micro tube (inner diameter 580 , Intramedic Inc.) was buried in a homemade agar phantom with an angle of ~ 30° (angled flow), and another plastic micro tube was aligned close to ~ 0° (transvers flow) in another homemade agar phantom. A blood solution was pumped through the tubes with a syringe pump (Harvard Apparatus) at speeds of 1,3,5,7,9,11,13,15,20,25, and 30 mm/s. SVD was performed to filter the background signal clutter by removing the first two highest singular value components.…”

“…Since the introduction of Power Doppler-based functional ultrasound imaging (fUS) 3 , an increasing number of studies are exploiting the truly impressive capabilities of fUS for functional brain imaging studies [4][5][6][7][8] . However, the exact relationship between the fUS signal and the underlying physiological parameters is not quantitatively established.…”

The first steps in vision: cell types, circuits, and repair

“…Finally, we developed functional ultrasound imaging to record whole-brain activity in behaving mice at a resolution of~100 lm and compared activity in healthy and FRMD7 mutant mice (Macé et al, 2018). In healthy mice, we detected 87 active brain regions during visual stimulation that evoked the optokinetic reflex.…”