{"doi":"10.1016/j.brs.2020.03.016","title":"Transcranial focused ultrasound, pulsed at 40 Hz, activates microglia acutely and reduces Aβ load chronically, as demonstrated in vivo","abstract":"OBJECTIVE: Iaccarino 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. METHODS: ). Acute studies targeted tFUS into one hemisphere of brain centered on its hippocampus for 1 h. Chronic studies targeted comparable brain in each hemisphere for 1 h/day for five days. RESULTS: Acute 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). CONCLUSION: Our 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.","journal":"Brain stimulation","year":2020,"id":54641,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":101,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9559,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":281282,"name":"Lei Chen","orcid":"0000-0001-6935-8340","position":1,"is_corresponding":false},{"id":283412,"name":"C.K. Ezeokeke","orcid":null,"position":2,"is_corresponding":false},{"id":281283,"name":"Theresa Olmstead","orcid":"0000-0003-2472-2342","position":3,"is_corresponding":false},{"id":281284,"name":"Christine T. O. Nguyen","orcid":"0000-0002-3298-3086","position":4,"is_corresponding":false},{"id":283413,"name":"A. Sahota","orcid":null,"position":5,"is_corresponding":false},{"id":281285,"name":"Robert George Williams","orcid":"0000-0002-6842-6302","position":6,"is_corresponding":false},{"id":281286,"name":"Pierre D. Mourad","orcid":"0000-0003-2645-4177","position":7,"is_corresponding":false},{"id":283411,"name":"M S Bobola","orcid":null,"position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-18T21:04:14.743014Z","pmid":"32388044","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}