## 1 Introduction  
Our nervous system consists of the central and peripheral nervous systems (CNS, PNS), which have similar ion channel/modulator compositions [1; 2]. In the CNS, functional neural circuits implicated in different neurological diseases overlap significantly with one another (e.g., overlapping circuits for dementia, aphasia, and Alzheimer's disease [3]), and certain neural circuits are not restricted to one region but spread throughout the brain (e.g., the pain matrix [4]). Collectively, this has led to the challenge of developing selective and effective drugs that target certain neurological diseases with limited off-target side effects. The recent advancement of optogenetic neuromodulation offers the much-needed selectivity at the expense of invasive and permanent gene modification of neural tissues. On the other hand, neuromodulation with focal delivery of physical energy to an affected area in patients has drawn growing attention as a non-drug alternative for managing neurological diseases and symptoms. The most widely used stimulus modality in neuromodulation is electrical stimulation, including electrical stimulation of the brain for treating movement disorders, stroke, tinnitus, depression, and addiction [5], as well as stimulation of the spinal cord and peripheral nerves for managing various types of chronic injuries and pain [6; 7; 8]. Besides electrical stimulation, other modalities of stimuli have been implemented that allow no-contact delivery of physical energy deep into the neuronal tissue, including focused ultrasound [9], transcranial electromagnetic stimulation (TMS) [10; 11], and infrared light pulses [12]. TMS uses a strong magnetic field of 2 to 3 T to evoke current pulses in the tissue, but it faces the challenge of precisely localizing the activated areas in the brain because of the electrical and magnetic anisotropy of the brain and skull tissues. Infrared light pulses affect neural activity by delivering a spatially precise thermal stimulus, but the local heating of the targeted region remains a concern of the method. On the other hand, ultrasound (US), as a mechanical wave operating at 250 KHz to 50 MHz, allows spatially and temporally precise delivery of energy deep into the tissue with controllable heating. Hence, US can be considered as an ideal means for non- or minimally invasive neuromodulation. The effects of US on the CNS have been shown to disrupt the blood brain barrier and evoke excitatory and/or inhibitory responses in both motor and sensory neurons [13; 14; 15; 16; 17; 18; 19; 20; 21; 22; 23]. In addition, transcranial ultrasonic stimulation (TUS) as a non-invasive brain stimulation technique has been investigated in primates. TUS of the frontal eye field evokes a transient increase of neural activities in the supplementary eye field in awake macaques as measured by multi-channel single-unit recordings [24]. In addition, a 40 s-long TUS of certain brain regions can lead to long-lasting neuromodulatory effects up to two hours post-stimulation, according to a functional MRI study in macaques [25]. Especially, TUS of the supplementary motor area and frontal polar cortex causes those brain regions to interact more selectively with the rest of the brain. Outcomes of those researches have led to the successful translation of US stimulation, after approval by the U.S. Food and Drug Administration (FDA), to treat medical-refractory patients with essential tremor [26]. Electrophysiological recording from the rat hippocampal dentate gyrus has been reported to simultaneously enhance (at the fiber volley) and suppress (in dendritic layers) the compound action potentials (CAP) in response to US stimulation [27]. In line with this, another ex vivo study based on calcium imaging, shows low-intensity focused pulsed US can evoke electrical activities in the mouse hippocampal slices [28]. However, two most recent studies suggest that US neuromodulation of the CNS does not directly activate brain regions in mice, but through an indirect auditory cochlear pathway [29; 30].