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Efficacy of spoken word comprehension therapy in patients with chronic aphasia: a cross-over randomised controlled trial with structural imaging
  1. Victoria Fleming1,
  2. Sonia Brownsett2,3,
  3. Anna Krason4,
  4. Maria A Maegli5,
  5. Henry Coley-Fisher1,
  6. Yean-Hoon Ong1,
  7. Davide Nardo6,
  8. Rupert Leach1,
  9. David Howard7,
  10. Holly Robson8,
  11. Elizabeth Warburton9,
  12. John Ashburner10,
  13. Cathy J Price10,
  14. Jenny T Crinion11,
  15. Alexander P Leff1,11
  1. 1 UCL Queen Square Institute of Neurology, University College London, London, UK
  2. 2 School of Health and Rehabilitation Sciences, The University of Queensland, Saint Lucia, Queensland, Australia
  3. 3 Centre of Research Excellence in Aphasia Recovery and Rehabilitation, La Trobe University, Melbourne, Victoria, Australia
  4. 4 Department of Psychology and Language Sciences, University College London, London, UK
  5. 5 Department of Psychology, Universidad del Valle de Guatemala, Guatemala, Guatemala
  6. 6 MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, Cambridgeshire, UK
  7. 7 School of Education, Communication and Language Sciences, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK
  8. 8 Psychology and Clinical Language Sciences, University of Reading, Reading, Berkshire, UK
  9. 9 Department of Medicine, University of Cambridge, Cambridge, Cambridgeshire, UK
  10. 10 Wellcome Centre for Human Neuroimaging, University College London, London, UK
  11. 11 Institute of Cognitive Neuroscience, University College London, London, UK
  1. Correspondence to Dr Victoria Fleming, Institute of Cognitive Neuroscience, University College London, London, UK; victoria.fleming{at}


Objective The efficacy of spoken language comprehension therapies for persons with aphasia remains equivocal. We investigated the efficacy of a self-led therapy app, ‘Listen-In’, and examined the relation between brain structure and therapy response.

Methods A cross-over randomised repeated measures trial with five testing time points (12-week intervals), conducted at the university or participants' homes, captured baseline (T1), therapy (T2-T4) and maintenance (T5) effects. Participants with chronic poststroke aphasia and spoken language comprehension impairments completed consecutive Listen-In and standard care blocks (both 12 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 (T2-T4) for each participant (subgroup, n=25) were analysed using cross-sectional and longitudinal voxel-based morphometry.

Results Thirty-five participants completed, on average, 85 hours (IQR=70–100) 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%, Cohen’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.

Conclusions 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.

Trial registration number NCT02540889.

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  • VF and SB contributed equally.

  • Contributors APL led on the funding application (NIHR-i4i) with input from SB, DH, HR, EW, JC, RL and CP. VF, SB, DH, HR, EW and JC provided overall direction. VF, SB, APL, MM, DH and HR designed the bespoke outcomes; DN, Y-HO and HC-F created computerised versions. VF, SB, Y-HO and APL devised the therapy programme. VF, SB, AK and HC-F conducted patient testing. VF conducted data analyses with direction from SB and APL; JA devised and verified the imaging analyses and interpretation. RL contributed ideas as a patient expert. CP assisted with recruitment and scanning. VF, SB and APL wrote the manuscript; VF and SB contributed equally. All authors provided critical feedback that helped shape the research study and manuscript.

  • Funding This study is funded by the National Institute for Health Research (NIHR) Invention for Innovation (i4i) Programme (Award Reference Number II-LB-0813–20004). Brain imaging was supported at the Wellcome Centre for Human Neuroimaging (203147/Z/16/Z) with additional funding to CJP (205103/Z/16/Z).

  • Disclaimer The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval Ethical approval was obtained from the National Research Ethics Service, Hampstead Committee (15/LO/0569).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available by email request to the Principal Investigator (

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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