Aphasia is among the most debilitating of symptoms affecting stroke survivors. Speech and language therapy (SLT) is effective, but many hours of practice are required to make clinically meaningful ...gains. One solution to this ‘dosage’ problem is to automate therapeutic approaches via self-supporting apps so people with aphasia (PWA) can amass practice as it suits them. However, response to therapy is variable and no clinical trial has yet identified the key brain regions required to engage with word-retrieval therapy.
Between Sep 7, 2020 and Mar 1, 2022 at University College London in the UK, we carried out a phase II, item-randomised clinical trial in 27 PWA using a novel, self-led app, ‘iTalkBetter’, which utilises confrontation naming therapy. Unlike previously reported apps, it has a real-time utterance verification system that drives its adaptive therapy algorithm. Therapy items were individually randomised to provide balanced lists of ‘trained’ and ‘untrained’ items matched on key psycholinguistic variables and baseline performance. PWA practised with iTalkBetter over a 6-week therapy block. Structural and functional MRI data were collected to identify therapy-related changes in brain states. A repeated-measures design was employed. The trial was registered at ClinicalTrials.gov (NCT04566081).
iTalkBetter significantly improved naming ability by 13% for trained items compared with no change for untrained items, an average increase of 29 words (SD = 26) per person; beneficial effects persisted at three months. PWA’s propositional speech also significantly improved. iTalkBetter use was associated with brain volume increases in right auditory and left anterior prefrontal cortices. Task-based fMRI identified dose-related activity in the right temporoparietal junction.
Our findings suggested that iTalkBetter significantly improves PWAs’ naming ability on trained items. The effect size is similar to a previous RCT of computerised therapy, but this is the first study to show transfer to a naturalistic speaking task. iTalkBetter usage and dose caused observable changes in brain structure and function to key parts of the surviving language perception, production and control networks. iTalkBetter is being rolled-out as an app for all PWA and anomia: https://www.ucl.ac.uk/icn/research/research-groups/neurotherapeutics/projects/digital-interventions-neuro-rehabilitation-0 so that they can increase their dosage of practice-based SLT.
National Institute for Health and Care Research, Wellcome Centre for Human Neuroimaging.
Genome-wide association studies have generated an increasing number of common genetic variants associated with neurological and psychiatric disease risk. An improved understanding of the genetic ...control of gene expression in human brain is vital considering this is the likely modus operandum for many causal variants. However, human brain sampling complexities limit the explanatory power of brain-related expression quantitative trait loci (eQTL) and allele-specific expression (ASE) signals. We address this, using paired genomic and transcriptomic data from putamen and substantia nigra from 117 human brains, interrogating regulation at different RNA processing stages and uncovering novel transcripts. We identify disease-relevant regulatory loci, find that splicing eQTLs are enriched for regulatory information of neuron-specific genes, that ASEs provide cell-specific regulatory information with evidence for cellular specificity, and that incomplete annotation of the brain transcriptome limits interpretation of risk loci for neuropsychiatric disease. This resource of regulatory data is accessible through our web server, http://braineacv2.inf.um.es/.
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