• Zoe Vj Woodhead, Jennifer Crinion, Sundeep Teki, Will Penny, Cathy J Price, and Alexander P Leff.
• Department of Brain Repair and Rehabilitation, University College London, London, UK.
• J. Neurol. Neurosurg. Psychiatr. 2017 Jul 1; 88 (7): 586594586-594.

IntroductionAphasia 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 DesignThis 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.MethodsThe 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.ResultsPhonological 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.ConclusionsPhonological 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 registrationThis trial was registered with EudraCT (2005-004215-30, https://eudract.ema.europa.eu/) and ISRCTN (68939136, http://www.isrctn.com/).© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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