Focused ultrasound (FUS) neuromodulation has been previously proposed as a promising technique to drive neuronal activity. Here, we explored motor- and cognitive-related brain regions of mice by targeting specific brain structures using FUS neuromodulation in the mega-Hz range under a specific type of anesthesia. Contralateral motor responses were observed showing successful target specificity of the FUS neuromodulation achieved with 1.9 MHz. Higher acoustic pressures increased the success rate from 20% (at the threshold, 1.45 MPa) to 70% (1.79 MPa). The estimated latency measured by electromyography was 266 ± 37 ms. Pupil dilation was observed when neuromodulating regions in the brain covering the superior colliculus and other anxiety-related structures such as hippocampus and locus coeruleus. This study demonstrated the capability of FUS to modulate target specific regions in the brain including pupil dilation induced by FUS for the first time. Furthermore, evoked responses by cognitive regions demonstrated the capability of FUS to modulate deeper structures in the brain.