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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. \u2018Splitting\u2019 views propose separate clinical entities: \u2018primary progressive apraxia of speech\u2019 when AoS occurs in the absence of expressive agrammatism, \u2018progressive agrammatic aphasia\u2019 (PAA) in the opposite case, and \u2018AOS + PAA\u2019 when mixed motor speech and language symptoms are clearly present. While therapeutic interventions typically vary depending on the predominant symptom (e.g. AoS versus expressive agrammatism), the existence of behavioural, 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 behaviour 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.<\/jats:p>\n               <jats:p>Our cross-sectional examination of brain-behaviour 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 behavioural dissociation\/association in previous reports. Second, we identified a \u2018left-right\u2019 and \u2018ventral-dorsal\u2019 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.<\/jats:p>\n               <jats:p>Our findings thus contribute to define the function and location of the epicentres 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.<\/jats:p>","DOI":"10.1093\/brain\/awad327","type":"journal-article","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T20:06:04Z","timestamp":1695758764000},"page":"607-626","source":"Crossref","is-referenced-by-count":28,"title":["Neural basis of speech and grammar symptoms in non-fluent variant primary progressive aphasia spectrum"],"prefix":"10.1093","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4534-1834","authenticated-orcid":false,"given":"Diego L","family":"Lorca-Puls","sequence":"first","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, UCSF Weill Institute for Neurosciences, University of California , SanFrancisco, CA 94158 , USA"},{"name":"Secci\u00f3n de Neurolog\u00eda, Departamento de Especialidades, Facultad de Medicina, Universidad de Concepci\u00f3n , Concepci\u00f3n, 4070105 , Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Gajardo-Vidal","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, UCSF Weill Institute for Neurosciences, University of California , SanFrancisco, CA 94158 , USA"},{"name":"Centro de Investigaci\u00f3n en Complejidad Social (CICS), Facultad de Gobierno, Universidad del Desarrollo , Santiago, 7590943 , Chile"},{"name":"Direcci\u00f3n de Investigaci\u00f3n y Doctorados, Vicerrector\u00eda de Investigaci\u00f3n y Doctorados, Universidad del Desarrollo , Concepci\u00f3n, 4070001 , Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Luisa","family":"Mandelli","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, UCSF Weill Institute for Neurosciences, University of California , SanFrancisco, CA 94158 , 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