Taking the sublexical route: brain dynamics of reading in the semantic variant of primary progressive aphasia

• Published in: Brain (London, England : 1878) England : 1878), 2020-08, Vol.143 (8), p.2545-2560
• Main Authors: Borghesani, Valentina, Hinkley, Leighton B N, Ranasinghe, Kamalini G, Thompson, Megan M C, Shwe, Wendy, Mizuiri, Danielle, Lauricella, Michael, Europa, Eduardo, Honma, Susanna, Miller, Zachary, Miller, Bruce, Vossel, Keith, Henry, Maya M L, Houde, John F, Gorno-Tempini, Maria L, Nagarajan, Srikantan S
• Format: Article
• Language: English
• Subjects: Aged; Aphasia, Primary Progressive - diagnostic imaging; Aphasia, Primary Progressive - physiopathology; Brain - diagnostic imaging; Brain - physiopathology; Brain Mapping - methods; Female; Humans; Image Interpretation, Computer-Assisted - methods; Magnetic Resonance Imaging - methods; Magnetoencephalography - methods; Male; Middle Aged; Original; Reading
• ISSN: 0006-8950; 1460-2156
• DOI: 10.1093/brain/awaa212

Reading aloud requires mapping an orthographic form to a phonological one. The mapping process relies on sublexical statistical regularities (e.g. 'oo' to |uː|) or on learned lexical associations between a specific visual form and a series of sounds (e.g. yacht to/jɑt/). Computational, neuroimaging, and neuropsychological evidence suggest that sublexical, phonological and lexico-semantic processes rely on partially distinct neural substrates: a dorsal (occipito-parietal) and a ventral (occipito-temporal) route, respectively. Here, we investigated the spatiotemporal features of orthography-to-phonology mapping, capitalizing on the time resolution of magnetoencephalography and the unique clinical model offered by patients with semantic variant of primary progressive aphasia (svPPA). Behaviourally, patients with svPPA manifest marked lexico-semantic impairments including difficulties in reading words with exceptional orthographic to phonological correspondence (irregular words). Moreover, they present with focal neurodegeneration in the anterior temporal lobe, affecting primarily the ventral, occipito-temporal, lexical route. Therefore, this clinical population allows for testing of specific hypotheses on the neural implementation of the dual-route model for reading, such as whether damage to one route can be compensated by over-reliance on the other. To this end, we reconstructed and analysed time-resolved whole-brain activity in 12 svPPA patients and 12 healthy age-matched control subjects while reading irregular words (e.g. yacht) and pseudowords (e.g. pook). Consistent with previous findings that the dorsal route is involved in sublexical, phonological processes, in control participants we observed enhanced neural activity over dorsal occipito-parietal cortices for pseudowords, when compared to irregular words. This activation was manifested in the beta-band (12-30 Hz), ramping up slowly over 500 ms after stimulus onset and peaking at ∼800 ms, around response selection and production. Consistent with our prediction, svPPA patients did not exhibit this temporal pattern of neural activity observed in controls this contrast. Furthermore, a direct comparison of neural activity between patients and controls revealed a dorsal spatiotemporal cluster during irregular word reading. These findings suggest that the sublexical/phonological route is involved in processing both irregular and pseudowords in svPPA. Together these results provide further evidence supporti