Focused ultrasound brain stimulation to anesthetized rats induces long‐term changes in somatosensory evoked potentials

Yoo, Seung‐Schik; Yoon, Kyungho; Croce, Phillip; Cammalleri, Amanda; Margolin, Ryan W.; Lee, Wonhye

doi:10.1002/ima.22262

Cited by 42 publications

(39 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A small (16 mm in diameter, 12 mm in height) and light (~ 6 g in weight) FUS transducer was built in-house (Fig. 1 a) [ 44 ]. A disc-shape zirconate titanate (PbZr x Ti (1−x) O 3 ; PZT) ceramic (American Piezo Ceramics, Mackeyville, PA) was used and fitted (air-backed) inside of a custom-built plastic housing.…”

Section: Methodsmentioning

confidence: 99%

“…To enable the experimentation in freely-moving small animals, one critical technical element is to make the transducer wearable. Accordingly, we developed a miniaturized, light-weight FUS transducer that can be worn (and detachable) by Sprague–Dawley rats (anesthetized) and demonstrated that FUS can be delivered to their primary somatosensory areas, with possibility for inducing long-term neuromodulatory effects [ 44 ]. A 3D-printed applicator that is designed to adjust the position of the transducer was attached to a pedestal, which was implanted onto the rat skull.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Transcranial focused ultrasound stimulation of motor cortical areas in freely-moving awake rats

et al. 2018

Self Cite

View full text Add to dashboard Cite

BackgroundLow-intensity transcranial focused ultrasound (tFUS) has emerged as a new non-invasive modality of brain stimulation with the potential for high spatial selectivity and penetration depth. Anesthesia is typically applied in animal-based tFUS brain stimulation models; however, the type and depth of anesthesia are known to introduce variability in responsiveness to the stimulation. Therefore, the ability to conduct sonication experiments on awake small animals, such as rats, is warranted to avoid confounding effects of anesthesia.ResultsWe developed a miniature tFUS headgear, operating at 600 kHz, which can be attached to the skull of Sprague–Dawley rats through an implanted pedestal, allowing the ultrasound to be transcranially delivered to motor cortical areas of unanesthetized freely-moving rats. Video recordings were obtained to monitor physical responses from the rat during acoustic brain stimulation. The stimulation elicited body movements from various areas, such as the tail, limbs, and whiskers. Movement of the head, including chewing behavior, was also observed. When compared to the light ketamine/xylazine and isoflurane anesthetic conditions, the response rate increased while the latency to stimulation decreased in the awake condition. The individual variability in response rates was smaller during the awake condition compared to the anesthetic conditions. Our analysis of latency distribution of responses also suggested possible presence of acoustic startle responses mixed with stimulation-related physical movement. Post-tFUS monitoring of animal behaviors and histological analysis performed on the brain did not reveal any abnormalities after the repeated tFUS sessions.ConclusionsThe wearable miniature tFUS configuration allowed for the stimulation of motor cortical areas in rats and elicited sonication-related movements under both awake and anesthetized conditions. The awake condition yielded diverse physical responses compared to those reported in existing literatures. The ability to conduct an experiment in freely-moving awake animals can be gainfully used to investigate the effects of acoustic neuromodulation free from the confounding effects of anesthesia, thus, may serve as a translational platform to large animals and humans.Electronic supplementary materialThe online version of this article (10.1186/s12868-018-0459-3) contains supplementary material, which is available to authorized users.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Transcranial focused ultrasound stimulation of motor cortical areas in freely-moving awake rats

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…One step further than studying ultrasound effects on single cortical neuronal activities, we investigate potential sustained therapeutic effects of acoustic energy on inter-neuronal synaptic connectivity at deep brain. tFUS targeting the deep brain were demonstrated recently (Dallapiazza et al, 2018;, and non-transient neuromodulatory effects were also observed in anesthetized rat Yoo et al, 2017) and monkey models. These are early evidences of ultrasound-induced neuroplasticity, a concept which we further explored in the well characterized system of hippocampal long-term potentiation (LTP) and depression (LTD) in rats.…”

Section: Introductionmentioning

confidence: 92%

Intrinsic Cell-type Selectivity and Inter-neuronal Connectivity Alteration by Transcranial Focused Ultrasound

Kang

Niu²,

Krook-Magnuson

et al. 2019

Preprint

View full text Add to dashboard Cite

Transcranial focused ultrasound (tFUS) is a promising neuromodulation technique, but its mechanisms remain unclear. We investigate the effect of tFUS stimulation on different neuron types and synaptic connectivity in in vivo anesthetized rodent brains.Single units were separated into regular-spiking and fast-spiking units based on their extracellular spike shapes, further validated in transgenic optogenetic mice models of light-excitable excitatory and inhibitory neurons. For the first time, we show that excitatory neurons are significantly less responsive to low ultrasound pulse repetition frequencies (UPRFs), whereas the spike rates of inhibitory neurons do not change significantly across all UPRF levels. Our results suggest that we can preferentially target specific neuron types noninvasively by altering the tFUS UPRF. We also report in vivo observation of long-term synaptic connectivity changes induced by noninvasive tFUS in rats. This finding suggests tFUS can be used to encode temporally dependent stimulation paradigms into neural circuits and non-invasively elicit long-term changes in synaptic connectivity.

show abstract

“…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%

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.

View full text Add to dashboard Cite

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.

show abstract

Focused ultrasound brain stimulation to anesthetized rats induces long‐term changes in somatosensory evoked potentials

Cited by 42 publications

References 32 publications

Transcranial focused ultrasound stimulation of motor cortical areas in freely-moving awake rats

Transcranial focused ultrasound stimulation of motor cortical areas in freely-moving awake rats

Intrinsic Cell-type Selectivity and Inter-neuronal Connectivity Alteration by Transcranial Focused Ultrasound

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

Contact Info

Product

Resources

About