Safety of focused ultrasound neuromodulation in humans with temporal lobe epilepsy

Stern, John M.; Spivak, Norman M.; Becerra, Sergio; Kuhn, Taylor; Korb, Alexander; Kronemyer, David; Khanlou, Négar; Reyes, Samuel D.; Monti, Martin M.; Schnakers, Caroline; Walshaw, Patricia D.; Keselman, Inna; Cohen, Mark S.; Yong, William H.; Fried, Itzhak; Jordan, Sheldon E.; Schafer, Mark E.; Engel, Jerome; Bystritsky, Alexander

doi:10.1016/j.brs.2021.06.003

Cited by 54 publications

(44 citation statements)

References 38 publications

(48 reference statements)

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“…US only , i.e., US used as a purely neuromodulatory tool, has also been explored in conditions other than AD, including depression, disorders of consciousness, and epilepsy, as well as in healthy individuals, with primary outcome measures including safety and feasibility and, in many instances, constituting proof-of-concept studies and including, for example, EEG recordings and fMR imaging [ 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ]. Importantly, most of the studies either reported no adverse events, or sensory responses.…”

Section: Discussionmentioning

confidence: 99%

Ultrasound-Mediated Bioeffects in Senescent Mice and Alzheimer’s Mouse Models

et al. 2022

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Ultrasound is routinely used for a wide range of diagnostic imaging applications. However, given that ultrasound can operate over a wide range of parameters that can all be modulated, its applicability extends far beyond the bioimaging field. In fact, the modality has emerged as a hybrid technology that effectively assists drug delivery by transiently opening the blood–brain barrier (BBB) when combined with intravenously injected microbubbles, and facilitates neuromodulation. Studies in aged mice contributed to an insight into how low-intensity ultrasound brings about its neuromodulatory effects, including increased synaptic plasticity and improved cognitive functions, with a potential role for neurogenesis and the modulation of NMDA receptor-mediated neuronal signalling. This work is complemented by studies in mouse models of Alzheimer’s disease (AD), a form of pathological aging. Here, ultrasound was mainly employed as a BBB-opening tool that clears protein aggregates via microglial activation and neuronal autophagy, thereby restoring cognition. We discuss the currently available ultrasound approaches and how studies in senescent mice are relevant for AD and can accelerate the application of low-intensity ultrasound in the clinic.

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Section: Discussionmentioning

confidence: 99%

Ultrasound-Mediated Bioeffects in Senescent Mice and Alzheimer’s Mouse Models

et al. 2022

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“…Secondary outcomes include changes in seizure frequency, neurological status, neuropsychological profile, and psychological profile. An initial publication from this group reported that among 8 patients who underwent LIFU sonication of the temporal lobe followed by resection of the affected side, no abnormal histological or neuropsychological changes were observed ( 76 ).…”

Section: Fus-mediated Thermal Ablationmentioning

confidence: 99%

Clinical Intervention Using Focused Ultrasound (FUS) Stimulation of the Brain in Diverse Neurological Disorders

et al. 2022

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Various surgical techniques and pharmaceutical treatments have been developed to improve the current technologies of treating brain diseases. Focused ultrasound (FUS) is a new brain stimulation modality that can exert a therapeutic effect on diseased brain cells, with this effect ranging from permanent ablation of the pathological neural circuit to transient excitatory/inhibitory modulation of the neural activity depending on the acoustic energy of choice. With the development of intraoperative imaging technology, FUS has become a clinically available noninvasive neurosurgical option with visual feedback. Over the past 10 years, FUS has shown enormous potential. It can deliver acoustic energy through the physical barrier of the brain and eliminate abnormal brain cells to treat patients with Parkinson's disease and essential tremor. In addition, FUS can help introduce potentially beneficial therapeutics at the exact brain region where they need to be, bypassing the brain's function barrier, which can be applied for a wide range of central nervous system disorders. In this review, we introduce the current FDA-approved clinical applications of FUS, ranging from thermal ablation to blood barrier opening, as well as the emerging applications of FUS in the context of pain control, epilepsy, and neuromodulation. We also discuss the expansion of future applications and challenges. Broadening FUS technologies requires a deep understanding of the effect of ultrasound when targeting various brain structures in diverse disease conditions in the context of skull interface, anatomical structure inside the brain, and pathology.

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“…Most of these human studies provide safety data in the form of neurological examinations and/or structural MRI before and after sonication. Comprehensive reviews also suggest a favorable human safety profile ( 19 , 26 , 41 , 42 ). A recent report ( 41 ) described qualitative safety and side effect assessments in 65 participants who previously completed one or more LIFU experiments.…”

Section: Challenges and Limitationsmentioning

confidence: 99%

Low Intensity Focused Ultrasound for Non-invasive and Reversible Deep Brain Neuromodulation—A Paradigm Shift in Psychiatric Research

et al. 2022

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This article describes an emerging non-invasive neuromodulatory technology, called low intensity focused ultrasound (LIFU). This technology is potentially paradigm shifting as it can deliver non-invasive and reversible deep brain neuromodulation through acoustic sonication, at millimeter precision. Low intensity focused ultrasound's spatial precision, yet non-invasive nature sets it apart from current technologies, such as transcranial magnetic or electrical stimulation and deep brain stimulation. Additionally, its reversible effects allow for the causal study of deep brain regions implicated in psychiatric illness. Studies to date have demonstrated that LIFU can safely modulate human brain activity at cortical and subcortical levels. Due to its novelty, most researchers and clinicians are not aware of the potential applications and promise of this technique, underscoring the need for foundational papers to introduce the community to LIFU. This mini-review and synthesis of recent advances examines several key papers on LIFU administered to humans, describes the population under study, parameters used, and relevant findings that may guide future research. We conclude with a concise overview of some of the more pressing questions to date, considerations when interpreting new data from an emerging field, and highlight the opportunities and challenges in this exciting new area of study.

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Safety of focused ultrasound neuromodulation in humans with temporal lobe epilepsy

Cited by 54 publications

References 38 publications

Ultrasound-Mediated Bioeffects in Senescent Mice and Alzheimer’s Mouse Models

Ultrasound-Mediated Bioeffects in Senescent Mice and Alzheimer’s Mouse Models

Clinical Intervention Using Focused Ultrasound (FUS) Stimulation of the Brain in Diverse Neurological Disorders

Low Intensity Focused Ultrasound for Non-invasive and Reversible Deep Brain Neuromodulation—A Paradigm Shift in Psychiatric Research

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