Non-thermal focused ultrasound induced reversible reduction of essential tremor in a rat model

Brain Modulatory Effects by Low-Intensity Transcranial Ultrasound Stimulation (TUS): A Systematic Review on Both Animal and Human Studies

“…A total of 156 articles were subjected to full-text review, of which 121 articles were removed for the following reasons: review or commentary ( n = 52), study regarding the application of ultrasound in neurosurgery ( n = 7), technique papers regarding the design of ultrasound system, stimulation protocol, parameter optimization and properties improvement ( n = 39), computational modeling or simulation study ( n = 4), ultrasonic stimulation targeting peripheral or cranial nerves rather than cortical and subcortical structures ( n = 4), study with surrogate biomarkers as outcomes exclusively ( n = 14), study regarding seizure control ( n = 1) and study using mixed ultrasound magnetic stimulation ( n = 1). Ultimately 35 studies (Tufail et al, 2010; Yoo et al, 2011a,b, 2018; Deffieux et al, 2013; Hameroff et al, 2013; Kim et al, 2013, 2014a,b, 2015; Legon et al, 2014, 2018a,b; Chu et al, 2015; Guo et al, 2015, 2018; Lee et al, 2015, 2016a,b,c; Ai et al, 2016, 2018; Monti et al, 2016; Yu et al, 2016; Wattiez et al, 2017; Dallapiazza et al, 2018; Daniels et al, 2018; Gibson et al, 2018; Sato et al, 2018; Xie et al, 2018; Yang et al, 2018; Zhang et al, 2018; Li et al, 2019; Sharabi et al, 2019) were selected for inclusion in this review, including 24 animal and 11 human studies.…”

“…Brain targets varied from study to study, including motor cortex (Tufail et al, 2010; Yoo et al, 2011a; Kim et al, 2014a,b; Lee et al, 2014, 2016c), somatosensory cortex (Lee et al, 2014, 2016c; Guo et al, 2018; Xie et al, 2018; Li et al, 2019), thalamus (Yoo et al, 2011b; Dallapiazza et al, 2018), prefrontal (Deffieux et al, 2013; Wattiez et al, 2017), visual areas (Yoo et al, 2011a; Kim et al, 2015; Lee et al, 2016c; Sato et al, 2018), auditory areas (Daniels et al, 2018), and medulla oblongata region (Sharabi et al, 2019). Excitatory effects of TUS in normal animals were found in 14 studies, as represented in limb movements (Tufail et al, 2010; Kim et al, 2014a,b), electromyography (EMG) (Lee et al, 2014; Sato et al, 2018; Sharabi et al, 2019), fMRI (Yoo et al, 2011a; Yang et al, 2018), PET (Kim et al, 2013), EEG power spectrum (Yu et al, 2016), visual evoked potential (VEP) (Kim et al, 2015; Lee et al, 2016c), neuronal recordings (Wattiez et al, 2017; Guo et al, 2018; Li et al, 2019), and recovery time after anesthesia (Yoo et al, 2011b). Inhibitory effects in normal animals were also found in 6 studies, as represented by suppression of SEP, VEP, and auditory evoked potential (AEP) (Yoo et al, 2011a, 2018; Chu et al, 2015; Kim et al, 2015; Dallapiazza et al, 2018; Daniels et al, 2018).…”

“…One study showed that TUS altered the cortico-muscular coupling (i.e., coupling relationship between stimulated motor cortex and effector muscle), which was significantly enhanced with the increase of the number of tone bursts applied (Xie et al, 2018). Experimental rats with diseases conditions were used in three articles: the first reported that 360 trials (400 ms per trial) ultrasonic stimulation over the ischemic core at an intensity of = 2.155 W/cm 2 (spatial peak pulse average intensity, ISPPA) significantly reduced the volume of lesion and improved the neurological outcomes in stroke rats, as comparison to the sham stimulation (Guo et al, 2015), the second showed that prefrontal 2-week ultrasonic stimulation at an intensity of 7.59 W/cm 2 (ISPPA) improved the depression-like behaviors of depressed rats (Zhang et al, 2018) and the third reported that TUS at an intensity of 27.2 W/cm 2 (ISPPA) over the medulla oblongata region could suppress the essential tremors (Sharabi et al, 2019) in Harmaline-induced rats.…”

Noninvasive Ultrasound Deep Brain Stimulation for the Treatment of Parkinson’s Disease Model Mouse

“…Ultrasound is a mechanical wave [19], which can pass through an intact human skull and evoke neural activity [20–22]. Low intensity pulsed ultrasound (LIPUS) has shown great promise for the modulation of brain function and reversal of neurological and psychiatric dysfunction [23, 24]. LIPUS evokes motor response in mice when ultrasound was used to stimulate the motor cortex [25] and increases antisaccade latencies when ultrasound was delivered to the left frontal eye field in monkeys [26].…”

A thermal mechanism underlies tFUS neuromodulation

“…In Sharabi et al, despite claiming a nonthermal mechanism for sonication, there was no mention of measuring or validating any thermal change. Interestingly, while Yoo et al did report temperature changes from an I SPPA of 23 W/cm 2 , Sharabi et al [4] used an even higher intensity of 27.2 W/cm 2 with no measurement of thermal change to support the claim that it was not thermal.…”