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This exploratory re-analysis tests whether transcranial pulse stimulation (TPS) leads to persistent auditory network activation. Task-based and resting-state fMRI were analyzed using the largest sham-controlled dataset, applying auditory-specific sound contrasts and auditory network metrics. Results found no sustained auditory cortical activation, connectivity changes, efficiency alterations, or cognitive correlations; effect sizes were small with conservative confidence limits.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/ultrasound-neuromodulation-as-a-novel-dementia-therapyinvestigation-of-possible-long-term-confounds/442111/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/ultrasound-neuromodulation-as-a-novel-dementia-therapyinvestigation-of-possible-long-term-confounds/442111.png","ImageObject",300,407,{"name":92,"@type":93},"supergirl","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-30","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What long-term confound does the study investigate after TPS in AD?","Question",{"text":112,"@type":113},"It investigates whether long-term cognitive and neural effects could be explained by persistent activation of auditory networks rather than genuine neuromodulation mechanisms.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How did the researchers test for auditory contributions?",{"text":117,"@type":113},"They re-analyzed task-based and resting-state fMRI using auditory-specific contrasts (air-conducted, combined air-and bone-conducted, and bone-conduction–specific) and examined task co-activation, auditory–dorsal attention connectivity, global efficiency, and links to cognitive test scores.",{"name":119,"@type":110,"acceptedAnswer":120},"What were the main findings regarding long-term auditory effects?",{"text":121,"@type":113},"No significant long-term auditory cortex activation was observed, auditory–attention connectivity was unchanged at rest, auditory network global efficiency did not differ, and auditory metrics did not correlate with cognitive performance.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},442111,1790741605,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":44,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},962088121634,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","DOI: 10.1002/trc2.70198  \nRESEARCH ARTICLE  \nUltrasound neuromodulation as a novel dementia  \ntherapy—Investigation of possible long-term confounds  \nMichael Mitterwallner1   Eva Matt1  Robert Chen2, 3  Roland Beisteiner1  \n1 Functional Brain Diagnostics and Therapy, Department of Neurology, Medical University of Vienna, Vienna, Austria  \n2 Division of Neurology, Department of Medicine, University of Toronto, Toronto, Canada  \n3 Krembil Research Institute, University Health Network, Toronto, Canada  \nCorrespondence  \nRoland Beisteiner, MD, MA, Functional Brain Diagnostics and Therapy, Department of Neurology, Medical University of Vienna, Spitalgasse 23, Vienna, Austria.  \nEmail: [roland.beisteiner@meduniwien.ac.at](roland.beisteiner@meduniwien.ac.at)  \nFunding information  \nMedical University of Vienna; Herzfelder Foundation  \nAbstract  \nINTRODUCTION: Ultrasound neuromodulation has emerged as a promising adjunctive therapy in Alzheimer’s disease (AD), yet a controversial issue remains: whether its reported long-term therapeutic effects could be attributed to potential confounds rather than genuine neuromodulatory mechanisms. Although auditory confounds via air-or bone-conducted sound have been discussed for immediate effects, their relevance for enduring therapeutic outcomes—essential for clinical application—remains unknown. This exploratory study is the first to examine whether long-term cognitive and neural effects of transcranial pulse stimulation (TPS) inAD are linked to persistent auditory network activation.  \nMETHODS: A comprehensive re-analysis of task-based and resting-state functional magnetic resonance imaging (fMRI) data was conducted using data from the currently largest sham-controlled clinical ultrasound neuromodulation study (Matt et al., 2025). To isolate possible auditory contributions, we applied a contrast-based framework targeting (1) air-conducted sound,(2) combined air-and possibly bone-conducted sound, and (3) bone-conduction–specific effects. Analyses included: (a) task-based auditory cortex co-activation,(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. RESULTS: No significant long-term activation of auditory cortices was observed in task-based fMRI. Resting-state 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. Effectsize 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.  \nCONCLUSION: Using data from a rigorously controlled cognitive trial, we found no evidence of long-term auditory network effects following TPS. This makes it unlikely that auditory confounds are a key factor underlying the cognitive network effects  \nThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.  \n© 2026 The Author(s). Alzheimer’s & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer’s Association.  \nAlzheimer’s Dement. 2026;12:e70198.  \n[https://doi.org/10.1002/trc2.70198](https://doi.org/10.1002/trc2.70198)  \nwi[leyonlinelibrary.com/journal/trc2](leyonlinelibrary.com/journal/trc2)  \n1of9  \nMITTERWALLNER ET AL.  \nobserved with long-term ultrasound neuromodulation in typical verum-sham settings as investigated here.  \nKEYWORDS  \nAlzheimer’s disease, auditory confounds, functional MRI (fMRI), transcranial pulse stimulation (TPS), ultrasound neuromo","cbCaitgXgEVqnWiY","https://ap.wps.com/l/cbCaitgXgEVqnWiY","pdf",2040674,"English","# Introduction\n## Ultrasound neuromodulation and dementia relevance\n## Study rationale: long-term confounds\n# Methods\n## Re-analysis of sham-controlled TPS fMRI data\n## Auditory-specific contrast framework\n## Task-fMRI and resting-state connectivity/efficiency analyses\n# Results\n## Task-based auditory activation\n## Resting-state network connectivity\n## Auditory network efficiency and cognitive associations\n# Conclusion\n## Implications for long-term TPS effects","[{\"question\":\"What long-term confound does the study investigate after TPS in AD?\",\"answer\":\"It investigates whether long-term cognitive and neural effects could be explained by persistent activation of auditory networks rather than genuine neuromodulation mechanisms.\"},{\"question\":\"How did the researchers test for auditory contributions?\",\"answer\":\"They re-analyzed task-based and resting-state fMRI using auditory-specific contrasts (air-conducted, combined air-and bone-conducted, and bone-conduction–specific) and examined task co-activation, auditory–dorsal attention connectivity, global efficiency, and links to cognitive test scores.\"},{\"question\":\"What were the main findings regarding long-term auditory effects?\",\"answer\":\"No significant long-term auditory cortex activation was observed, auditory–attention connectivity was unchanged at rest, auditory network global efficiency did not differ, and auditory metrics did not correlate with cognitive performance.\"}]","Ultrasound neuromodulation as a novel dementia therapy—Investigation of possible long-term confounds | PDF",1790699061,23]