Safety of Clinical Ultrasound Neuromodulation

Radjenovic, S.; Dörl, Gregor; Gaal, Martin; Beisteiner, Roland

doi:10.3390/brainsci12101277

Cited by 8 publications

(7 citation statements)

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“…The technique has recently attracted significant attention for transcranial modulation of the central nervous system, particularly since it was recognized that nerve activity could be excited or suppressed, depending on the combination of ultrasound parameters, experimental models and conditions ( Naor et al, 2016 ; Fomenko et al, 2018 ; Blackmore et al, 2019 ; Rabut et al, 2020 ; Wang et al, 2020 ; Zhang T. T. et al, 2021 ; Badadhe et al, 2022 ). High intensity focused ultrasound is understood to ablate tissue due to heat generated by the mechanical wave interacting with the tissue, whereas low intensity ultrasound has demonstrated a favorable safety profile ( Pasquinelli et al, 2019 ; Radjenovic et al, 2022 ). However, despite a growing literature on the parameter dependence of the excitatory and suppressive effects of low intensity ultrasound, the underlying mechanisms of action are not yet fully understood ( Kamimura et al, 2020 ; Dell'Italia et al, 2022 ).…”

Section: Less Invasive Neuromodulation Strategiesmentioning

confidence: 99%

Nanoparticle-based optical interfaces for retinal neuromodulation: a review

Stoddart,

Begeng,

Tong

et al. 2024

Front. Cell. Neurosci.

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Degeneration of photoreceptors in the retina is a leading cause of blindness, but commonly leaves the retinal ganglion cells (RGCs) and/or bipolar cells extant. Consequently, these cells are an attractive target for the invasive electrical implants colloquially known as “bionic eyes.” However, after more than two decades of concerted effort, interfaces based on conventional electrical stimulation approaches have delivered limited efficacy, primarily due to the current spread in retinal tissue, which precludes high-acuity vision. The ideal prosthetic solution would be less invasive, provide single-cell resolution and an ability to differentiate between different cell types. Nanoparticle-mediated approaches can address some of these requirements, with particular attention being directed at light-sensitive nanoparticles that can be accessed via the intrinsic optics of the eye. Here we survey the available known nanoparticle-based optical transduction mechanisms that can be exploited for neuromodulation. We review the rapid progress in the field, together with outstanding challenges that must be addressed to translate these techniques to clinical practice. In particular, successful translation will likely require efficient delivery of nanoparticles to stable and precisely defined locations in the retinal tissues. Therefore, we also emphasize the current literature relating to the pharmacokinetics of nanoparticles in the eye. While considerable challenges remain to be overcome, progress to date shows great potential for nanoparticle-based interfaces to revolutionize the field of visual prostheses.

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Section: Less Invasive Neuromodulation Strategiesmentioning

confidence: 99%

Nanoparticle-based optical interfaces for retinal neuromodulation: a review

Stoddart,

Begeng,

Tong

et al. 2024

Front. Cell. Neurosci.

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“…In most studies peak pressures lie below 10 MPa with FUS peaks clearly lower than TPS peaks. [ 44 ] ISPTA.3 values typically reach 1000 mW cm −2 with FUS and are clearly lower with TPS (100 mW cm −2 ). A special feature of the ultrashort TPS pulses (about 3 µs) is that they cannot produce thermal bioeffects and secondary maxima via standing waves.…”

Section: Safety Of Clinical Ultrasound Neuromodulationmentioning

confidence: 99%

“…In the largest patient observation currently published ( n = 101, TPS technique, Radjenovic et al. [ 44 ] ), intra‐treatment adverse events were reported by about 3% of the patients, post‐treatment events were noted by about 13%. Over all human ultrasound neuromodulation studies ever published, the following mild to moderate adverse events have been reported: localized pain at head or neck, general headache, painless pressure sensations at the stimulation site, muscle twitches, heating sensations, itchiness, anxiety, uncomfortable feelings, mood deterioration, difficulty paying attention, confusion, tenseness, disorientation, noise sensitivity, tingling, nausea, sleepiness, tiredness, dizziness, unsteady gait, tremor worsening, and sweating.…”

Section: Safety Of Clinical Ultrasound Neuromodulationmentioning

confidence: 99%

“…Over all human ultrasound neuromodulation studies ever published, the following mild to moderate adverse events have been reported: localized pain at head or neck, general headache, painless pressure sensations at the stimulation site, muscle twitches, heating sensations, itchiness, anxiety, uncomfortable feelings, mood deterioration, difficulty paying attention, confusion, tenseness, disorientation, noise sensitivity, tingling, nausea, sleepiness, tiredness, dizziness, unsteady gait, tremor worsening, and sweating. [ 4 , 44 , 46 , 47 ] It is important to realize that adverse events are also reported when sham (placebo) stimulations are applied. [ 47 ]…”

Section: Safety Of Clinical Ultrasound Neuromodulationmentioning

confidence: 99%

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Ultrasound Neuromodulation as a New Brain Therapy

2023

Self Cite

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Within the last decade, ultrasound has been “rediscovered” as a technique for brain therapies. Modern technologies allow focusing ultrasound through the human skull for highly focal tissue ablation, clinical neuromodulatory brain stimulation, and targeted focal blood‐brain‐barrier opening. This article gives an overview on the state‐of‐the‐art of the most recent application: ultrasound neuromodulation as a new brain therapy. Although research centers have existed for decades, the first treatment centers were not established until 2020, and clinical applications are spreading rapidly.

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“… 15 In contrast, ultrasonic stimulation can be precisely targeted with a neuronavigation device in such cases, because ultrasound does not rely on electrical conductivity in the brain. 16 Transcranial pulse stimulation (TPS) is a novel noninvasive technique for navigated neuromodulation based on single ultrashort high‐intensity ultrasound pulses (~3 μs) repeated every 200–300 ms. 17 , 18 Due to the high‐spatial resolution of deep focal lengths, TPS can noninvasively modulate neural targets deep in the human cortex. 19 TPS uses lower focused ultrasound frequencies that can stimulate a depth of up to 8 cm, reaching deep brain structures such as the thalamus lying at a distance between 5 and 6.5 cm from the scalp.…”

Section: Introductionmentioning

confidence: 99%

Transcranial pulse stimulation in Alzheimer's disease

Chen

You

et al. 2023

CNS Neurosci Ther

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BackgroundTranscranial pulse stimulation (TPS) is a novel noninvasive ultrasonic brain stimulation that can increase cortical and corticospinal excitability, induce neuroplasticity, and increase functional connectivity within the brain. Several trials have confirmed its potential in treating Alzheimer's disease (AD).ObjectiveTo investigate the effect and safety of TPS on AD.DesignA systematic review.MethodsPubMed, Embase via Ovid, Web of Science, Cochrane Library, CNKI (China National Knowledge Infrastructure), VIP (China Science and Technology Journal Database), and WanFang were searched from inception to April 1, 2023. Study selection, data extraction, and quality evaluation of the studies were conducted by two reviewers independently, with any controversy resolved by consensus. The Methodological Index for Nonrandomized Studies was used to assess the risk of bias.ResultsFive studies were included in this review, with a total of 99 patients with AD. For cognitive performance, TPS significantly improved the scores of the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) test battery, Alzheimer's Disease Assessment Scale (cognitive), Montreal Cognitive Assessment, and Mini‐Mental Status Examination. For depressive symptoms, TPS significantly reduced the scores of the Alzheimer's Disease Assessment Scale (affective), Geriatric Depression Score, and Beck Depression Inventory. By functional magnetic resonance imaging, studies have shown that TPS improved cognitive performance in AD patients by increasing functional connectivity in the hippocampus, parahippocampal cortex, precuneus, and parietal cortex, and activating cortical activity in the bilateral hippocampus. TPS alleviated depressive symptoms in AD patients by decreasing functional connectivity between the ventromedial network (left frontal orbital cortex) and the salience network (right anterior insula). Adverse events in this review, including headache, worsening mood, jaw pain, nausea, and drowsiness, were reversible and lasted no longer than 1 day. No serious adverse events or complications were observed.ConclusionsTPS is promising in improving cognitive performance and reducing depressive symptoms in patients with AD. TPS may be a safe adjunct therapy in the treatment of AD. However, these findings lacked a sham control and were limited by the small sample size of the included studies. Further research may be needed to better explore the potential of TPS.Patient and Public InvolvementPatients and the public were not involved in this study.

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Safety of Clinical Ultrasound Neuromodulation

Cited by 8 publications

References 57 publications

Nanoparticle-based optical interfaces for retinal neuromodulation: a review

Nanoparticle-based optical interfaces for retinal neuromodulation: a review

Ultrasound Neuromodulation as a New Brain Therapy

Transcranial pulse stimulation in Alzheimer's disease

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