Auditory training changes temporal lobe connectivity in ‘Wernicke’s aphasia’: a randomised trial
Open accessAbstract
Introduction Aphasia is one of the most disabling sequelae after stroke, occurring in 25%–40% of stroke survivors. However, there remains a lack of good evidence for the efficacy or mechanisms of speech comprehension rehabilitation. Trial Design This within-subjects trial tested two concurrent interventions in 20 patients with chronic aphasia with speech comprehension impairment following left hemisphere stroke: (1) phonological training using ‘Earobics’ software and (2) a pharmacological intervention using donepezil, an acetylcholinesterase inhibitor. Donepezil was tested in a double-blind, placebo-controlled, cross-over design using block randomisation with bias minimisation. Methods The primary outcome measure was speech comprehension score on the comprehensive aphasia test. Magnetoencephalography (MEG) with an established index of auditory perception, the mismatch negativity response, tested whether the therapies altered effective connectivity at the lower (primary) or higher (secondary) level of the auditory network. Results Phonological training improved speech comprehension abilities and was particularly effective for patients with severe deficits. No major adverse effects of donepezil were observed, but it had an unpredicted negative effect on speech comprehension. The MEG analysis demonstrated that phonological training increased synaptic gain in the left superior temporal gyrus (STG). Patients with more severe speech comprehension impairments also showed strengthening of bidirectional connections between the left and right STG. Conclusions Phonological training resulted in a small but significant improvement in speech comprehension, whereas donepezil had a negative effect. The connectivity results indicated that training reshaped higher order phonological representations in the left STG and (in more severe patients) induced stronger interhemispheric transfer of information between higher levels of auditory cortex. Clinical trial registration This trial was registered with EudraCT (2005-004215-30, https://eudract.ema.europa.eu/) and ISRCTN (68939136, http://www.isrctn.com/).
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In that trial, donepezil appeared to block the therapeutic effects of the phonological therapy.
“The donepezil appeared to block the therapeutic effects of the phonological therapy.”
From Aphasia Recovery: When, How and Who to Treat? (2018) · cites this paper as [31]
In that trial, MEG scanning demonstrated that phonological training increased synaptic gain in residual parts of the left superior temporal gyrus.
“MEG scanning demonstrated that the phonological training increased synaptic gain in residual parts of the left superior temporal gyrus.”
From Aphasia Recovery: When, How and Who to Treat? (2018) · cites this paper as [31]
In a double-blind, placebo-controlled, cross-over RCT in chronic patients with a clinically significant auditory perceptual deficit (n=20), an off-the-shelf phonological e-therapy paired with donepezil produced a small but significant generalised improvement in speech perception, with more severely affected patients benefitting more.
“There was a small but significant generalised improvement in speech perception, with more severely affected patients benefitting more.”
From Aphasia Recovery: When, How and Who to Treat? (2018) · cites this paper as [31]
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Alves, P. N., Martins, I. P., Rorden, C., Berthier, M. L., Dávila, G., Leff, A. P., de Schotten, M. T., & Forkel, S. J. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.14.725241
Self-citationLazzari, F., Scalinci, F., Morelli, F., & Verrienti, G. (2026) · Neurological Sciences · doi:10.1007/s10072-026-09335-3
- Authors
- Woodhead, Z. V., Crinion, J., Teki, S., Penny, W., Price, C. J., & Leff, A. P.
- Affiliations
- Wellcome Centre for Human Neuroimaging (GB)
- University of Oxford (GB)
- Corresponding author
- Woodhead, Zoe VJ
- Venue
- Journal of Neurology, Neurosurgery & Psychiatry
- Publisher
- BMJ
- Published
- 2017-03-04
- Volume
- 88
- Issue
- 7
- Pages
- 586-594
- ISSN
- 0022-3050 (ISSN-L)
- 1468-330X
- PMC
- PMC5659142
- OpenAlex
- W2591767650
- Cited by
- 56
- References
- 43
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 3 · 2023: 5 · 2022: 9 · 2021: 8 · 2020: 7 · 2019: 6 · 2018: 6 · 2017: 4
- FWCI
- 3.61
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Journal of Neurology Neurosurgery & Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion, cc-by)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Wellcome Trust
- James S. McDonnell Foundation
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neurobiology of Language and Bilingualism
- Life Sciences › Neuroscience › Cognitive Neuroscience › Hearing Loss and Rehabilitation
- Health Sciences › Medicine › Rehabilitation › Stroke Rehabilitation and Recovery
- Keywords
- Wernicke's aphasia, speech understanding, chronic aphasia, left hemisphere stroke, phonological training, donepezil, acetylcholinesterase inhibitors, superior temporal gyrus, mismatch negativity, interhemispheric connectivity, aphasia rehabilitation
- MeSH terms
- Donepezil, Aphasia, Wernicke, Auditory Perception, Cholinesterase Inhibitors, Double-Blind Method, Female, Humans, Indans, Male, Middle Aged, Neuropsychological Tests, Piperidines, Speech Perception, Temporal Lobe, Magnetoencephalography, Comprehension
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