Ultrasound Neuromodulation as a New Brain Therapy

Beisteiner, Roland; Hallett, Mark; Lozano, Andrés M.

doi:10.1002/advs.202205634

Cited by 24 publications

(8 citation statements)

References 56 publications

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“…From previous TPS investigations which included sham controls and independent neurophysiological data (EEG and fMRI), there is clear evidence for TPS modulation of somatosensory evoked potentials, long-term neuroplastic changes, and long-term improvement of cognitive functions in AD and depression [ 2 , 6 , 9 , 48 ]. These findings, together with other clinical data [ 5 ], highlight the potential of ultrasound to develop towards a novel add-on neuromodulation therapy.…”

Section: Discussionmentioning

confidence: 53%

“…Brain stimulation was performed using the NEUROLITH TPS system (Storz Medical AG, Tägerwilen, Switzerland) and the methodology developed by our research group over the past decade [ 2 , 5 ]. The treatment protocol for PD encompassed ten TPS sessions conducted daily over a 2-week period, from Monday to Friday.…”

Section: Methodsmentioning

confidence: 99%

“…TPS bears the advantage that the small ultrasound foci are independent from pathological conductivity changes and specific brain areas can therefore be precisely targeted, even in the depth of the brain [ 3 , 4 ]. Although the field is still young, navigated ultrasound stimulation has shown promise in other neurological conditions [ 5 ], such as Alzheimer’s disease (AD) [ 5 , 6 ], disorders of consciousness [ 7 , 8 ], and depression [ 6 , 9 ], and might be a valuable adjunct treatment for Parkinson’s disease.…”

Section: Introductionmentioning

confidence: 99%

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Novel ultrasound neuromodulation therapy with transcranial pulse stimulation (TPS) in Parkinson’s disease: a first retrospective analysis

Osou,

Radjenovic,

Bender

et al. 2023

J Neurol

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Background Transcranial Pulse Stimulation (TPS) has been recently introduced as a novel ultrasound neuromodulation therapy with the potential to stimulate the human brain in a focal and targeted manner. Here, we present a first retrospective analysis of TPS as an add-on therapy for Parkinson’s disease (PD), focusing on feasibility, safety, and clinical effects. We also discuss the placebo response in non-invasive brain stimulation studies as an important context. Methods This retrospective clinical data analysis included 20 PD patients who received ten sessions of TPS intervention focused on the individual motor network. Safety evaluations were conducted throughout the intervention period. We analyzed changes in motor symptoms before and after TPS treatment using Unified Parkinson’s Disease Rating Scale part III (UPDRS-III). Results We found significant improvement in UPDRS-III scores after treatment compared to baseline (pre-TPS: 16.70 ± 8.85, post-TPS: 12.95 ± 8.55; p < 0.001; Cohen’s d = 1.38). Adverse events monitoring revealed no major side effects. Conclusion These preliminary findings suggest that TPS can further improve motor symptoms in PD patients already on optimized standard therapy. Findings have to be evaluated in context with the current literature on placebo effects.

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Section: Discussionmentioning

confidence: 53%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Novel ultrasound neuromodulation therapy with transcranial pulse stimulation (TPS) in Parkinson’s disease: a first retrospective analysis

Osou,

Radjenovic,

Bender

et al. 2023

J Neurol

Self Cite

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“…Furthermore, this technology may be applicable to other neuronal disorders originating from a dysfunction in the control of neurotransmitters, such as depression and drug addiction. [ 39–42 ] As introduced in a previous review, [ 43 ] ultrasound neuromodulations with tFUS are highlighted to be effective in brain therapeutics while the efficacies in some results were mild. The use of different ultrasound pulse sequences modulates different outcomes in treating Alzheimer's disease.…”

Section: Discussionmentioning

confidence: 99%

Bidirectional Neuronal Control of Epileptiform Activity by Repetitive Transcranial Focused Ultrasound Stimulations

Choi,

Koo,

Joo

et al. 2023

Advanced Science

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Repetitive stimulation procedures are used in neuromodulation techniques to induce persistent excitatory or inhibitory brain activity. The directivity of modulation is empirically regulated by modifying the stimulation length, interval, and strength. However, bidirectional neuronal modulations using ultrasound stimulations are rarely reported. This study presents bidirectional control of epileptiform activities with repetitive transcranial‐focused ultrasound stimulations in a rat model of drug‐induced acute epilepsy. It is found that repeated transmission of elongated (40 s), ultra‐low pressure (0.25 MPa) ultrasound can fully suppress epileptic activities in electro‐encephalography and cerebral blood volume measurements, while the change in bursting intervals from 40 to 20 s worsens epileptic activities even with the same burst length. Furthermore, the suppression induced by 40 s long bursts is transformed to excitatory states by a subsequent transmission. Bidirectional modulation of epileptic seizures with repeated ultrasound stimulation is achieved by regulating the changes in glutamate and γ‐Aminobutyric acid levels, as confirmed by measurements of expressed c‐Fos and GAD65 and multitemporal analysis of neurotransmitters in the interstitial fluid obtained via microdialysis.

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“…Transcranial low-intensity ultrasound (US) neuromodulation represents a promising therapeutic strategy for neurological and psychiatric disorders 1,2 . Noninvasive US neuromodulation typically uses lower fundamental frequencies of hundreds of kilohertz to a couple megahertz due to superior skull penetration 3–8 .…”

Section: Introductionmentioning

confidence: 99%

Ultrasound pulse repetition frequency preferentially activates different neuron populations independent of cell type

Sherman,

Bortz,

Antonio

et al. 2024

Preprint

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Transcranial ultrasound activates mechanosensitive cellular signaling and modulates neural dynamics. Given that intrinsic neuronal activity is limited to a couple hundred hertz and often exhibits frequency preference, we examined whether pulsing ultrasound at physiologic pulse repetition frequencies (PRFs) could selectively influence neuronal activity in the mammalian brain. We performed calcium imaging of individual motor cortex neurons, while delivering 0.35 MHz ultrasound at PRFs of 10, 40, and 140 Hz in awake mice. We found that most neurons were preferentially activated by only one of the three PRFs, highlighting unique cellular effects of physiologic PRFs. Further, ultrasound evoked responses were similar between excitatory neurons and parvalbumin positive interneurons regardless of PRFs, indicating that individual cell sensitivity dominates ultrasound-evoked effects, consistent with the heterogeneous mechanosensitive channel expression we found across single neurons in mice and humans. These results highlight the feasibility of tuning ultrasound neuromodulation effects through varying PRFs.

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Ultrasound Neuromodulation as a New Brain Therapy

Cited by 24 publications

References 56 publications

Novel ultrasound neuromodulation therapy with transcranial pulse stimulation (TPS) in Parkinson’s disease: a first retrospective analysis

Novel ultrasound neuromodulation therapy with transcranial pulse stimulation (TPS) in Parkinson’s disease: a first retrospective analysis

Bidirectional Neuronal Control of Epileptiform Activity by Repetitive Transcranial Focused Ultrasound Stimulations

Ultrasound pulse repetition frequency preferentially activates different neuron populations independent of cell type

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