Mapping and modulating whole-brain motor circuits using ultrasound

<span style="font-weight: 400;">The primary motor cortex (M1) plays a critical role in motor control in mice. However, our previous work has shown that mice are still able to perform a reach-grab-eat motor task even when M1 is optogenetically inhibited. We hypothesize that, during M1 inhibition, mice engage compensatory neural circuits to successfully complete the task. To investigate this, we used functional ultrasound (fUS) to map whole-brain activity during the motor task and used transcranial focused ultrasound (tFUS) to noninvasively suppress M1 activity, providing a more translationally relevant approach for neural modulation.</span> <span style="font-weight: 400;">In this study, we present the first protocol for mapping and modulating whole-brain motor circuits in awake, head-fixed mice using fUS and tFUS. We compare two headpost materials - Clear Resin V4 and TPX polymethylpentene - to optimize whole-brain imaging quality. Using fUS, we measured cerebral blood volume (CBV) during resting-state scans (when the mouse was awake but not engaged in the task) and during the reach-grab-eat task, providing insights into whole-brain activity patterns associated with motor execution. Additionally, we applied tFUS to reduce CBV and modulate M1 activity during the task, aiming to impair motor performance by reducing dexterity, accuracy, and the overall ability to successfully complete the reach task.</span> <span style="font-weight: 400;">We found that TPX polymethylpentene provided the best imaging quality, making fUS suitable for whole-brain imaging in awake, head-fixed mice. We observed a correlation between CBV and reach-related activity, and while neuromodulation effects on motor performance were noted, further studies are needed to assess their significance. These findings have clinical implications for understanding compensatory neural mechanisms and functional recovery in patients recovering from stroke or other neurological disorders affecting limb movement.</span>