Evidence map›Paper›PMID 32388044›Full record

ArticleBrain stimulation

Transcranial focused ultrasound, pulsed at 40 Hz, activates microglia acutely and reduces Aβ load chronically, as demonstrated in vivo.

M S Bobola, L Chen, C K Ezeokeke, T A Olmstead, C Nguyen, A Sahota, R G Williams, P D Mourad

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain stimulation. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 2 pooled it
4.2field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

57 citing papers in PubMed, 2 syntheses or guidelines pooled it, 97 citations in OpenAlex.

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  13. Perivascular brain clearance as a therapeutic target in cerebral amyloid angiopathy and Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
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  19. TRPC6 is a mechanosensitive channel essential for ultrasound neuromodulation in the mammalian brain.Proceedings of the National Academy of Sciences of the United States of America · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

M S BobolaDepartment of Neurological Surgery, University of Washington, Seattle, WA, USA.
L ChenDepartment of Neurological Surgery, University of Washington, Seattle, WA, USA.
C K EzeokekeDepartment of Neurological Surgery, University of Washington, Seattle, WA, USA.
T A OlmsteadDepartment of Neurological Surgery, University of Washington, Seattle, WA, USA.
C NguyenDepartment of Neurological Surgery, University of Washington, Seattle, WA, USA.
A SahotaDepartment of Neurological Surgery, University of Washington, Seattle, WA, USA.
R G WilliamsDepartment of Neurological Surgery, University of Washington, Seattle, WA, USA.
P D MouradDepartment of Neurological Surgery, University of Washington, Seattle, WA, USA; Division of Engineering and Mathematics, University of Washington, Bothell, WA, USA. Electronic address: doumitt@uw.edu.
University of Washington · USNeurological Surgery · US

Funding

Towards deep brain monitoring with superficial EEG sensors plus neuromodulatory focused ultrasoundR21EY027557 · NEI · UNIVERSITY OF WASHINGTON · PI MOURAD, PIERRE D · 2016 to 2017
$464k
NEI NIH HHS R21 EY027557
6 · The paper itself

Abstract

objectiveIaccarino et al. (2016) [1] exposed 1 h of light flickering at 40 Hz to awake 5XFAD Alzheimer's Disease (AD) mouse models, generating action potentials at 40 Hz, activating ∼54% of microglia to colocalize with Aβ plaque, acutely, and clearing ∼ 50% of Aβ plaque after seven days, but only in the visual cortex. HYPOTHESIS: Transcranially delivered, focused ultrasound (tFUS) can replicate the results of Iaccarino et al. (2016) [1] but throughout its area of application.

methodsWe exposed sedated 5XFAD mice to tFUS (2.0 MHz carrier frequency, 40 Hz pulse repetition frequency, 400 μs-long pulses, spatial peak pulse average value of 190 W/cm

resultsAcute application of tFUS activated more microglia that colocalized with Aβ plaque relative to sham ultrasound (36.0 ± 4.6% versus 14.2 ± 2.6% [mean ± standard error], z = 2.45, p < 0.014) and relative to the contralateral hemisphere of treated brain (36.0 ± 4.6% versus 14.3 ± 4.0%, z = 2.61, p < 0.009). Chronic application over five days reduced their Aβ plaque burden by nearly half relative to paired sham animals (47.4 ± 5.8%, z = - 2.79, p < 0.005).

conclusionOur results compare to those of Iaccarino et al. (2016) [1] but throughout the area of ultrasound-exposed brain. Our results also compare to those achieved by medications that target Aβ, but over a substantially shorter period of time. The proximity of our ultrasound protocol to those shown safe for non-human primates and humans may motivate its rapid translation to human studies.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsBrainMiceMicrogliaUltrasonic TherapyAmyloid beta-Peptidesactivated microgliaAlzheimer’s diseasecleared amyloid beta plaquenear diagnostic ultrasound

Identifiers

PMID32388044
PMCPMC7308193
OpenAlexW3014859431

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.