{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T20:40:18Z","timestamp":1790023218964,"version":"4.0.1"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005788","name":"Medizinische Universit\u00e4t Wien","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005788","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&amp;amp;D Transl Res &amp;amp; Clin Interv"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Ultrasound neuromodulation has emerged as a promising adjunctive therapy in Alzheimer's disease (AD), yet a controversial issue remains: whether its reported long\u2010term therapeutic effects could be attributed to potential confounds rather than genuine neuromodulatory mechanisms. Although auditory confounds via air\u2010 or bone\u2010conducted sound have been discussed for immediate effects, their relevance for enduring therapeutic outcomes\u2014essential for clinical application\u2014remains unknown. This exploratory study is the first to examine whether long\u2010term cognitive and neural effects of transcranial pulse stimulation (TPS) in AD are linked to persistent auditory network activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>A comprehensive re\u2010analysis of task\u2010based and resting\u2010state functional magnetic resonance imaging (fMRI) data was conducted using data from the currently largest sham\u2010controlled clinical ultrasound neuromodulation study (Matt et\u00a0al., 2025). To isolate possible auditory contributions, we applied a contrast\u2010based framework targeting (1) air\u2010conducted sound, (2) combined air\u2010 and possibly bone\u2010conducted sound, and (3) bone\u2010conduction\u2013specific effects. Analyses included: (a) task\u2010based auditory cortex co\u2010activation, (b) functional connectivity between auditory and dorsal attention networks (the latter was modulated in the original study), (c) global efficiency within the auditory network, and (d) correlations with neuropsychological test battery scores.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>No significant long\u2010term activation of auditory cortices was observed in task\u2010based fMRI. Resting\u2010state analyses showed no altered connectivity between auditory and attention networks, no changes in auditory network global efficiency, and no associations between auditory metrics and cognitive performance. Effect\u2010size estimates were small, and 95% confidence intervals placed conservative upper bounds that argue against sizeable, sustained auditory confounds. These findings were consistent across all contrast conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Using data from a rigorously controlled cognitive trial, we found no evidence of long\u2010term auditory network effects following TPS. This makes it unlikely that auditory confounds are a key factor underlying the cognitive network effects observed with long\u2010term ultrasound neuromodulation in typical verum\u2010sham settings as investigated here.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Long\u2010term transcranial pulse stimulation effects were evaluated for potential auditory confounds using functional magnetic resonance imaging (fMRI).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Analyses included task\u2010fMRI, resting\u2010state functional connectivity, and auditory network efficiency.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>No auditory long\u2010term effects were detected.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Auditory confounds are unlikely to be the key factor for cognitive network effects.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/trc2.70198","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T05:50:04Z","timestamp":1767678604000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Ultrasound neuromodulation as a novel dementia therapy\u2014Investigation of possible long\u2010term confounds"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6643-6445","authenticated-orcid":false,"given":"Michael","family":"Mitterwallner","sequence":"first","affiliation":[{"name":"Functional Brain Diagnostics and Therapy Department of Neurology Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Matt","sequence":"additional","affiliation":[{"name":"Functional Brain Diagnostics and Therapy Department of Neurology Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Neurology Department of Medicine University of Toronto  Toronto Canada"},{"name":"Krembil Research Institute, University Health Network  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Beisteiner","sequence":"additional","affiliation":[{"name":"Functional Brain Diagnostics and Therapy Department of Neurology Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2024.1420255"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brs.2024.06.005"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202205634"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.201902583"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.12121"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40120\u2010022\u201000362\u20108"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.948204"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brs.2024.03.007"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357\u2010024\u201001305\u2010x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291725000406"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2024.59170"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trci.2019.06.007"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1620\/tjem.2022.J078"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/13872877251333614"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics15030359"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.88762.3"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brs.2020.08.014"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1063\/5.0011837"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.04.036"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.05.009"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brs.2019.03.005"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brs.2021.08.015"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brs.2022.05.004"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2023.1120410"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000167607.63000.38"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010230026"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2014.00225"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2008.09.005"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.40541"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep34026"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2020.00052"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201040998\u20100"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1037\/1082\u2010989X.8.4.434"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2013.00863"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhm013"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460\u20109568.2004.03277.x"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2025.01.004"}],"container-title":["Alzheimer's &amp; Dementia: Translational Research &amp; Clinical Interventions"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/trc2.70198","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/trc2.70198","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/trc2.70198","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T23:52:57Z","timestamp":1775865177000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/trc2.70198"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/trc2.70198"],"URL":"https:\/\/doi.org\/10.1002\/trc2.70198","archive":["Portico"],"relation":{},"ISSN":["2352-8737","2352-8737"],"issn-type":[{"value":"2352-8737","type":"print"},{"value":"2352-8737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-08-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70198"}}