title: Auditory training changes temporal lobe connectivity in 'Wernicke's aphasia': a randomised trial.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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 registrationThis trial was registered with EudraCT (2005-004215-30, https://eudract.ema.europa.eu/) and ISRCTN (68939136, http://www.isrctn.com/).
authors.affiliation: Department of Brain Repair and Rehabilitation, University College London, London, UK.|Wellcome Trust Centre for Neuroimaging, University College London, London, UK.|Department of Experimental Psychology, University of Oxford, Oxford, UK.
authors.forename: Zoe Vj
authors.initials: ZV
authors.lastname: Woodhead
authors.affiliation: Institute of Cognitive Neuroscience, University College London, London, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Crinion
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
authors.forename: Sundeep
authors.initials: S
authors.lastname: Teki
authors.affiliation: Wellcome Trust Centre for Neuroimaging, University College London, London, UK.
authors.forename: Will
authors.initials: W
authors.lastname: Penny
authors.affiliation: Wellcome Trust Centre for Neuroimaging, University College London, London, UK.
authors.forename: Cathy J
authors.initials: CJ
authors.lastname: Price
authors.affiliation: Wellcome Trust Centre for Neuroimaging, University College London, London, UK.|Institute of Cognitive Neuroscience, University College London, London, UK.
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Leff
mesh_terms: D001041:Aphasia, Wernicke / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001307:Auditory Perception / Q000502:physiology*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D032882:Comprehension / Q000502:physiology; D000077265:Donepezil; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007189:Indans / Q000627:therapeutic use; D015225:Magnetoencephalography / Q000379:methods; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010880:Piperidines / Q000627:therapeutic use; D013067:Speech Perception / Q000502:physiology; D013702:Temporal Lobe / Q000473:pathology*
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil
keywords: Wernicke’s aphasia; magnetoencephalography; pharmacological trial; phonological training; speech comprehension