<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article
  PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.1 20151215//EN" "JATS-journalpublishing1.dtd">
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" article-type="research-article" dtd-version="1.1" xml:lang="en"><front><journal-meta><journal-id journal-id-type="nlm-ta">J Neurol Neurosurg Psychiatry</journal-id><journal-id journal-id-type="hwp">jnnp</journal-id><journal-id journal-id-type="publisher-id">jnnp</journal-id><journal-title-group><journal-title>Journal of Neurology, Neurosurgery, and Psychiatry</journal-title><abbrev-journal-title>J Neurol Neurosurg Psychiatry</abbrev-journal-title></journal-title-group><issn pub-type="ppub">0022-3050</issn><issn pub-type="epub">1468-330X</issn><publisher><publisher-name>BMJ Publishing Group</publisher-name><publisher-loc>BMA House, Tavistock Square, London, WC1H 9JR</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">jnnp-2020-324256</article-id><article-id pub-id-type="doi">10.1136/jnnp-2020-324256</article-id><article-categories><subj-group subj-group-type="heading"><subject>Cognitive neurology</subject></subj-group><series-title>Original research</series-title></article-categories><title-group><article-title>Efficacy of spoken word comprehension therapy in patients with chronic aphasia: a cross-over randomised controlled trial with structural imaging</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes" equal-contrib="yes" id="author-79367445"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0003-2582-4914</contrib-id><name><surname>Fleming</surname><given-names>Victoria</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author" equal-contrib="yes" id="author-79714504"><name><surname>Brownsett</surname><given-names>Sonia</given-names></name><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author" id="author-79714517"><name><surname>Krason</surname><given-names>Anna</given-names></name><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author" id="author-79714560"><name><surname>Maegli</surname><given-names>Maria A</given-names></name><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author" id="author-79714570"><name><surname>Coley-Fisher</surname><given-names>Henry</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author" id="author-25974882"><name><surname>Ong</surname><given-names>Yean-Hoon</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author" id="author-79714598"><name><surname>Nardo</surname><given-names>Davide</given-names></name><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author" id="author-79714604"><name><surname>Leach</surname><given-names>Rupert</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author" id="author-79714618"><name><surname>Howard</surname><given-names>David</given-names></name><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author" id="author-50937578"><name><surname>Robson</surname><given-names>Holly</given-names></name><xref ref-type="aff" rid="aff8">8</xref></contrib><contrib contrib-type="author" id="author-79714636"><name><surname>Warburton</surname><given-names>Elizabeth</given-names></name><xref ref-type="aff" rid="aff9">9</xref></contrib><contrib contrib-type="author" id="author-51582017"><name><surname>Ashburner</surname><given-names>John</given-names></name><xref ref-type="aff" rid="aff10">10</xref></contrib><contrib contrib-type="author" id="author-50701023"><name><surname>Price</surname><given-names>Cathy J</given-names></name><xref ref-type="aff" rid="aff10">10</xref></contrib><contrib contrib-type="author" id="author-32957606"><name><surname>Crinion</surname><given-names>Jenny T</given-names></name><xref ref-type="aff" rid="aff11">11</xref></contrib><contrib contrib-type="author" id="author-21742095"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-0831-3541</contrib-id><name><surname>Leff</surname><given-names>Alexander P</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff11">11</xref></contrib></contrib-group><aff id="aff1"><label>1</label><institution content-type="department">UCL Queen Square Institute of Neurology</institution>, <institution>University College London</institution>, <addr-line content-type="city">London</addr-line>, <country>UK</country></aff><aff id="aff2"><label>2</label><institution content-type="department">School of Health and Rehabilitation Sciences</institution>, <institution>The University of Queensland</institution>, <addr-line content-type="city">Saint Lucia</addr-line>, <addr-line content-type="state">Queensland</addr-line>, <country>Australia</country></aff><aff id="aff3"><label>3</label><institution content-type="department">Centre of Research Excellence in Aphasia Recovery and Rehabilitation</institution>, <institution>La Trobe University</institution>, <addr-line content-type="city">Melbourne</addr-line>, <addr-line content-type="state">Victoria</addr-line>, <country>Australia</country></aff><aff id="aff4"><label>4</label><institution content-type="department">Department of Psychology and Language Sciences</institution>, <institution>University College London</institution>, <addr-line content-type="city">London</addr-line>, <country>UK</country></aff><aff id="aff5"><label>5</label><institution content-type="department">Department of Psychology</institution>, <institution>Universidad del Valle de Guatemala</institution>, <addr-line content-type="city">Guatemala</addr-line>, <country>Guatemala</country></aff><aff id="aff6"><label>6</label><institution content-type="department">MRC Cognition and Brain Sciences Unit</institution>, <institution>University of Cambridge</institution>, <addr-line content-type="city">Cambridge</addr-line>, <addr-line content-type="state">Cambridgeshire</addr-line>, <country>UK</country></aff><aff id="aff7"><label>7</label><institution content-type="department">School of Education, Communication and Language Sciences</institution>, <institution>Newcastle University</institution>, <addr-line content-type="city">Newcastle upon Tyne</addr-line>, <addr-line content-type="state">Tyne and Wear</addr-line>, <country>UK</country></aff><aff id="aff8"><label>8</label><institution content-type="department">Psychology and Clinical Language Sciences</institution>, <institution>University of Reading</institution>, <addr-line content-type="city">Reading</addr-line>, <addr-line content-type="state">Berkshire</addr-line>, <country>UK</country></aff><aff id="aff9"><label>9</label><institution content-type="department">Department of Medicine</institution>, <institution>University of Cambridge</institution>, <addr-line content-type="city">Cambridge</addr-line>, <addr-line content-type="state">Cambridgeshire</addr-line>, <country>UK</country></aff><aff id="aff10"><label>10</label><institution content-type="department">Wellcome Centre for Human Neuroimaging</institution>, <institution>University College London</institution>, <addr-line content-type="city">London</addr-line>, <country>UK</country></aff><aff id="aff11"><label>11</label><institution content-type="department">Institute of Cognitive Neuroscience</institution>, <institution>University College London</institution>, <addr-line content-type="city">London</addr-line>, <country>UK</country></aff><author-notes><corresp><label>Correspondence to</label> Dr Victoria Fleming, Institute of Cognitive Neuroscience, University College London, London, UK; <email>victoria.fleming@ucl.ac.uk</email></corresp></author-notes><pub-date pub-type="ppub"><month>11</month><year>2020</year></pub-date><pub-date pub-type="epub"><day>5</day><month>11</month><year>2020</year></pub-date><elocation-id>jnnp-2020-324256</elocation-id><history><date date-type="received"><day>15</day><month>06</month><year>2020</year></date><date date-type="rev-recd"><day>17</day><month>09</month><year>2020</year></date><date date-type="accepted"><day>07</day><month>10</month><year>2020</year></date></history><permissions><copyright-statement>&#x00A9; Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.</copyright-statement><copyright-year>2020</copyright-year></permissions><self-uri xlink:title="pdf" xlink:href="jnnp-2020-324256.pdf"/><abstract><sec><title>Objective</title><p>The efficacy of spoken language comprehension therapies for persons with aphasia remains equivocal. We investigated the efficacy of a self-led therapy app, &#x2018;Listen-In&#x2019;, and examined the relation between brain structure and therapy response.</p></sec><sec><title>Methods</title><p>A cross-over randomised repeated measures trial with five testing time points (12-week intervals), conducted at the university or participants&#x0027; homes, captured baseline (T<sub>1</sub>), therapy (T<sub>2</sub>-T<sub>4</sub>) and maintenance (T<sub>5</sub>) effects. Participants with chronic poststroke aphasia and spoken language comprehension impairments completed consecutive Listen-In and standard care blocks (both 12&#x2009;weeks with order randomised). Repeated measures analyses of variance compared change in spoken language comprehension on two co-primary outcomes over therapy versus standard care. Three structural MRI scans (T<sub>2</sub>-T<sub>4</sub>) for each participant (subgroup, n=25) were analysed using cross-sectional and longitudinal voxel-based morphometry.</p></sec><sec><title>Results</title><p>Thirty-five participants completed, on average, 85 hours (IQR=70&#x2013;100) of Listen-In (therapy first, n=18). The first study-specific co-primary outcome (Auditory Comprehension Test (ACT)) showed large and significant improvements for trained spoken words over therapy versus standard care (11&#x0025;, Cohen&#x2019;s d=1.12). Gains were largely maintained at 12 and 24 weeks. There were no therapy effects on the second standardised co-primary outcome (Comprehensive Aphasia Test: Spoken Words and Sentences). Change on ACT trained words was associated with volume of pretherapy right hemisphere white matter and post-therapy grey matter tissue density changes in bilateral temporal lobes.</p></sec><sec><title>Conclusions</title><p>Individuals with chronic aphasia can improve their spoken word comprehension many years after stroke. Results contribute to hemispheric debates implicating the right hemisphere in therapy-driven language recovery. Listen-In will soon be available on GooglePlay.</p></sec><sec><title>Trial registration number</title><p><ext-link ext-link-type="clintrialgov" xlink:href="NCT02540889">NCT02540889</ext-link>.</p></sec></abstract><funding-group specific-use="FundRef"><award-group id="funding-1"><funding-source><institution-wrap><institution-id institution-id-type="FundRef">http://dx.doi.org/10.13039/501100000272</institution-id><institution>National Institute for Health Research</institution></institution-wrap></funding-source><award-id>II-LB-0813-20004</award-id></award-group></funding-group></article-meta></front></article>