<p>DOI: <a href="https://doi.org/10.1093/brain/awad327">10.1093/brain/awad327</a></p>

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Neural basis of speech and grammar symptoms

Neural basis of speech and grammar symptoms - https://academic.oup.com/brain/advance-article-abstract/doi/10.1093/brain/awad327/7285775?redirectedFrom=fulltext&login=false

The nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA) is a neurodegenerative syndrome primarily defined by the presence of apraxia of speech (AoS) and/or expressive agrammatism. In addition, many patients exhibit dysarthria and/or receptive agrammatism. This leads to substantial phenotypic variation within the speech-language domain across individuals and time, in terms of both the specific combination of symptoms as well as their severity. How to resolve such phenotypic heterogeneity in nfvPPA is a matter of debate. “Splitting” views propose separate clinical entities: “primary progressive apraxia of speech” (PPAOS) when AoS occurs in the absence of expressive agrammatism, “progressive agrammatic aphasia” (PAA) in the opposite case, and “AOS + PAA” when mixed motor speech and language symptoms are clearly present. While therapeutic interventions typically vary depending on the predominant symptom (e.g., AoS vs expressive agrammatism), the existence of behavioral, anatomical, and pathological overlap across these phenotypes argues against drawing such clear-cut boundaries. In the current study, we contribute to this debate by mapping behavior to brain in a large, prospective cohort of well- characterized patients with nfvPPA (n = 104). We sought to advance scientific understanding of nfvPPA and the neural basis of speech-language by uncovering where in the brain the degree of MRI-based atrophy is associated with inter-patient variability in the presence and severity of AoS, dysarthria, expressive agrammatism, or receptive agrammatism. Our cross-sectional examination of brain-behavior relationships revealed three main observations. First, we found that the neural correlates of AoS and expressive agrammatism in nfvPPA lie side by side in the left posterior inferior frontal lobe, explaining their behavioral dissociation/association in previous reports. Second, we identified a “left-right” and “ventral-dorsal” neuroanatomical distinction between AoS versus dysarthria, highlighting (i) that dysarthria, but not AoS, is significantly influenced by tissue loss in right-hemisphere motor-speech regions and (ii) that, within the left hemisphere, dysarthria and AoS map onto dorsally versus ventrally located motor-speech regions, respectively. Third, we confirmed that, within the large-scale grammar network, left frontal tissue loss is preferentially involved in expressive agrammatism and left temporal tissue loss in receptive agrammatism. Our findings thus contribute to define the function and location of the epicenters within the large-scale neural networks vulnerable to neurodegenerative changes in nfvPPA. We propose that nfvPPA be redefined as an umbrella term subsuming a spectrum of speech and/or language phenotypes that are closely linked by the underlying neuroanatomy and neuropathology. 

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Neural basis of speech and grammar symptoms in nonfluent variant primary progressive aphasia spectrum

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