Current State of Potential Mechanisms Supporting Low Intensity Focused Ultrasound for Neuromodulation

Dell’Italia, John; Sanguinetti, Joseph L.; Monti, Martin M.; Bystritsky, Alexander; Reggente, Nicco

doi:10.3389/fnhum.2022.872639

Cited by 43 publications

(42 citation statements)

References 123 publications

(217 reference statements)

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“…The mechanisms of ultrasound neuromodulation have been extensively studied but not fully understood where ultrasound, as a mechanical pressure can act on mechanosensitive ion channels, has attracted much attention (31). Piezo is a mechanically sensitive ion channel that contains two isoforms, Piezo1 and Piezo2, of which Piezo1, is widely expressed in the central nervous system (32)(33)(34).…”

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Low-intensity pulsed ultrasound attenuates postoperative neurocognitive impairment and salvages hippocampal synaptogenesis in aged mice

Wang

Liu

Chang

et al. 2022

Preprint

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Background Postoperative neurocognitive impairment is an urgent problem with global aging accelerating. The prevention and treatment of postoperative neurocognitive impairment have been widely investigated but lack effective strategies. Low-intensity pulsed ultrasound (LIPUS), a non-invasive tool, has shown an effect on neuroprotection, but whether it could attenuate the postoperative neurocognitive impairment and the underlying mechanism remains unknow. Methods An experimental set-up for LIPUS stimulation of the hippocampus was well established. HE staining was used to determine the morphology of hippocampus after LIPUS application. A laparotomy model in aged mice was applied, and Morris water maze was used to assess cognitive function. RT-qPCR and western blotting were used to detect levels of inflammatory cytokines, synapse associated protein in the hippocampus, respectively. Immunofluorescent staining was also used to determine the neural activation and Piezo1 expression. Results After the anesthesia/surgery, the hippocampus of aged mice showed increased levels of inflammation and decreased synaptogenesis, while LIPUS intervention improved cognitive impairment, reduced hippocampal neuroinflammation, and improved synaptogenesis. We further found that LIPUS might improve synaptogenesis through the Piezo1-mediated calpain1/extracellular regulated protein kinases (Erk) pathway. Conclusion Our results suggested that LIPUS could be used as an effective physical intervention to improve postoperative cognitive dysfunction in the aged population.

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Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Low-intensity pulsed ultrasound attenuates postoperative neurocognitive impairment and salvages hippocampal synaptogenesis in aged mice

Wang

Liu

Chang

et al. 2022

Preprint

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“…tFUS has become an emerging and attractive NIBS technique due to its high spatial resolution and deeper target of brain stimulation [ 127 ]. Although many animal trials have reported the benefits of tFUS for stroke [ 128 , 129 , 130 , 131 ], its application in post-stroke patients is still rare.…”

Section: Overview Of Neuromodulation and Nibsmentioning

confidence: 99%

Noninvasive Brain Stimulation for Neurorehabilitation in Post-Stroke Patients

Zhou

et al. 2023

Brain Sciences

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Characterized by high morbidity, mortality, and disability, stroke usually causes symptoms of cerebral hypoxia due to a sudden blockage or rupture of brain vessels, and it seriously threatens human life and health. Rehabilitation is the essential treatment for post-stroke patients suffering from functional impairments, through which hemiparesis, aphasia, dysphagia, unilateral neglect, depression, and cognitive dysfunction can be restored to various degrees. Noninvasive brain stimulation (NIBS) is a popular neuromodulatory technology of rehabilitation focusing on the local cerebral cortex, which can improve clinical functions by regulating the excitability of corresponding neurons. Increasing evidence has been obtained from the clinical application of NIBS, especially repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). However, without a standardized protocol, existing studies on NIBS show a wide variation in terms of stimulation site, frequency, intensity, dosage, and other parameters. Its application for neurorehabilitation in post-stroke patients is still limited. With advances in neuronavigation technologies, functional near-infrared spectroscopy, and functional MRI, specific brain regions can be precisely located for stimulation. On the basis of our further understanding on neural circuits, neuromodulation in post-stroke rehabilitation has also evolved from single-target stimulation to co-stimulation of two or more targets, even circuits and the network. The present study aims to review the findings of current research, discuss future directions of NIBS application, and finally promote the use of NIBS in post-stroke rehabilitation.

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“…The idea of LITFUS-induced inhibition in areas relevant for executing heightened affect regulation and cognitive control as an underlying mechanism is supported by LITFUS modelling approaches. Given the applied parameters (Table S1), modelling would predict inhibition on a neuronal level (29,30).…”

Section: Litfus For Human Affect Neuromodulationmentioning

confidence: 99%

Inhibition of midfrontal theta with transcranial ultrasound predicts greater approach versus withdrawal behavior in humans

Ziebell¹,

Rodrigues²,

Forster³

et al. 2022

Preprint

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Low-intensity transcranial focused ultrasound (LITFUS) is an emerging non-invasive neuromodulation technique that holds potential for precision targeting of deep brain regions while avoiding side effects such as headaches or skin irritations. Our double-blind within-subjects study (N = 152) utilized LITFUS targeting the right prefrontal cortex, which was found to positively enhance self-reported global mood in earlier work. Building on prior studies, we utilized a virtual T-maze task that enabled us to operationalize conflicts in approach versus withdrawal behavior while recording electroencephalographic midfrontal theta (MFT). As MFT has repeatedly been shown to be a marker of cognitive load and cognitive conflict, MFT power was predicted to be related to reduced approach and heightened withdrawal in behavioral conflict situations. We hypothesized LITFUS would positively enhance self-reported mood and decrease MFT, with the LITFUS-induced downregulation of MFT resulting in an amplification of approach behavior and a reduction of withdrawal behavior. Results indicated that LITFUS led to significant MFT decreases, which significantly predicted increases in approach behavior and decreases in withdrawal behavior. This study expands LITFUS evidence on a physiological and behavioral level with a large sample size of human subjects, suggesting the promise of further research based on this distinct LITFUS-MFT-behavior link to influence conflict monitoring and its behavioral consequences. Eventually, this can serve as a foundation for future clinical work to establish LITFUS interventions for emotional and motivational mental health.

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Current State of Potential Mechanisms Supporting Low Intensity Focused Ultrasound for Neuromodulation

Cited by 43 publications

References 123 publications

WITHDRAWN: Low-intensity pulsed ultrasound attenuates postoperative neurocognitive impairment and salvages hippocampal synaptogenesis in aged mice

WITHDRAWN: Low-intensity pulsed ultrasound attenuates postoperative neurocognitive impairment and salvages hippocampal synaptogenesis in aged mice

Noninvasive Brain Stimulation for Neurorehabilitation in Post-Stroke Patients

Inhibition of midfrontal theta with transcranial ultrasound predicts greater approach versus withdrawal behavior in humans

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