Antidepressant-Like Effect of Low-Intensity Transcranial Ultrasound Stimulation

Zhang, Daqu; Li, Hangdao; Sun, Junfeng; Hu, Weiwei; Jin, Wen; Li, Shengtian; Tong, Shanbao

doi:10.1109/tbme.2018.2845689

Cited by 70 publications

(47 citation statements)

References 58 publications

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“…LIPUS provides a promising new approach for the noninvasive modulation of brain activity and has numerous potential applications in the treatment of neurologic and psychiatric disease, such as epilepsy [ 26 ], stroke [ 27 ], depression [ 28 ] and disorders of consciousness [ 29 ]. In our study, we found that the anesthetic dose can affect the neuromodulation effect of ultrasound on the motor cortex when we used the ultrasound to stimulate different rodent disease models under anesthesia.…”

Section: Discussionmentioning

confidence: 99%

The effect of anesthetic dose on the motor response induced by low-intensity pulsed ultrasound stimulation

et al. 2018

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BackgroundLow-intensity pulsed ultrasound stimulation (LIPUS) has been proven to be a noninvasive method with high spatial resolution and deep penetration. Previous studies have qualitatively demonstrated that the electromyographic response caused by LIPUS in the mouse motor cortex is affected by the anesthetic state of the mice. However, the quantitative relationship between motor response and anesthetic dose remains unclear.ResultsExperimental results show that the success rate decreases stepwise as the isoflurane concentration/mouse weight ratio increases (ratios: [0.004%/g, 0.01%/g], success rate: ~ 90%; [0.012%/g, 0.014%/g], ~ 40%; [0.016%/g, 0.018%/g], ~ 7%; 0.024%/g, 0). The latency and duration of EMG increase significantly when the ratio is more than 0.016%/g. Compared with that at ratios from 0.004 to 0.016%/g, normalized EMG amplitude decreases significantly at ratios of 0.018%/g and 0.020%/g.ConclusionsQuantitative calculations indicate that the anesthetic dose has a significant regulatory effect on the motor response of mice during LIPUS. Our results have guiding significance for the selection of the anesthetic dose for LIPUS in mouse motor cortex experiments.

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Section: Discussionmentioning

confidence: 99%

The effect of anesthetic dose on the motor response induced by low-intensity pulsed ultrasound stimulation

et al. 2018

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“…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.…”

Section: Resultsmentioning

confidence: 99%

“…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.…”

Section: Resultsmentioning

confidence: 99%

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

Wang

Zhang

et al. 2019

Front. Neurosci.

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Background and objective: Low Intensity Transcranial Ultrasound Stimulation (TUS) is a new form of non-invasive brain modulation with promising data; however, systematic reviews on the brain modulatory effects of TUS on both animals and humans have not been well-conducted. We aimed to conduct a systematic review on the studies using the TUS to modulate the brain functions and associated behavioral changes in both animals and humans. Methods: A literature search for published studies in the past 10 years was conducted. Two authors independently reviewed the relevant articles. Data were extracted and qualitatively summarized. Quality of studies was assessed by the SYRCLE's risk of bias tool for preclinical studies or the PEDro scale for clinical studies. Results: A total of 24 animal studies (506 animals) and 11 human studies (213 subjects) were included. Findings based on most animal studies demonstrated the excitatory or suppressive modulatory effects of ultrasonic stimulations on motor cortex, somatosensory cortex, thalamus, prefrontal cortex, auditory, and visual areas. Brain modulatory effects also were found among healthy human subjects in seven studies and two clinical studies suggested TUS may result in potential benefits on patients with disorder of consciousness or chronic pain. The safety concerns of TUS seem to be minor based on the human studies. Conclusions: TUS appears to be a viable technique in modulating the brain functions; however, research on TUS is still in its early stages, especially in human studies. Parameters need to be optimized before launching systematic investigations in humans.

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“…LIPUS stimulation of olive-cerebellar pathways decreases tremor frequency in a rat model of essential tremor [27]. Seizure activity in the animal model of epilepsy is also suppressed by the LIPUS treatment [28–30] and depressive symptoms are reversed by LIPUS stimulation of the prelimbic cortex [31]. Furthermore, LIPUS stimulation of the ischemic cortex mitigates focal cerebral ischemia in a rat model of stroke induced by distal middle cerebral artery occlusion [24, 32].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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Modulating basal ganglia circuitry is of great significance in the improvement of motor function in Parkinson’s disease (PD). Here, for the first time, we demonstrate that noninvasive ultrasound deep brain stimulation (UDBS) of the subthalamic nucleus (STN) or the globus pallidus (GP) improves motor behavior in a subacute mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Immunohistochemical c-Fos protein expression confirms that there is a relatively high level of c-Fos expression in the STN-UDBS and GP-UDBS group compared with sham group (both p < 0.05). Furthermore, STN-UDBS or GP-UDBS significantly increases the latency to fall in the rotarod test on day 9 (p < 0.05) and decreases the time spent climbing down a vertical rod in the pole test on day 12 (p < 0.05). Moreover, our results reveal that STN-UDBS or GP-UDBS protects the dopamine (DA) neurons from MPTP neurotoxicity by downregulating Bax (p < 0.001), upregulating Bcl-2 (p < 0.01), blocking cytochrome c (Cyt C) release from mitochondria (p < 0.05), and reducing cleaved-caspase 3 activity (p < 0.01) in the ipsilateral substantia nigra (SN). Additionally, the safety of ultrasound stimulation is characterized by hematoxylin and eosin (HE) and Nissl staining; no hemorrhage or tissue damage is detected. These data demonstrate that UDBS enables modulation of STN or GP neural activity and leads to neuroprotection in PD mice, potentially serving as a noninvasive strategy for the clinical treatment of PD.

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Antidepressant-Like Effect of Low-Intensity Transcranial Ultrasound Stimulation

Abstract: TUS has been speculated to have therapeutic effect in depression. This study provide evidence for the antidepressant-like effects of TUS in rats for the first time.

Cited by 70 publications

References 58 publications

The effect of anesthetic dose on the motor response induced by low-intensity pulsed ultrasound stimulation

The effect of anesthetic dose on the motor response induced by low-intensity pulsed ultrasound stimulation

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

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

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