Neural basis of speech and grammar symptoms in non-fluent variant primary progressive aphasia spectrum
Por:
Lorca-Puls DL, Gajardo-Vidal A, Mandelli ML, Illán-Gala I, Ezzes Z, Wauters LD, Battistella G, Bogley R, Ratnasiri B, Licata AE, Battista P, García AM, Tee BL, Lukic S, Boxer AL, Rosen HJ, Seeley WW, Grinberg LT, Spina S, Miller BL, Miller ZA, Henry ML, Dronkers NF, Gorno-Tempini ML
Publicada:
1 feb 2024
Ahead of Print:
1 ene 2024
Resumen:
The non-fluent/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' 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 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.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 '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 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.
Lorca-Puls et al. dissect the neuroanatomy of the most characteristic clinical features of nfvPPA: impaired motor speech and agrammatism. They propose that nfvPPA be reinterpreted as a spectrum disorder subsuming multiple speech-language phenotypes that are closely linked by the underlying neuroanatomy and neuropathology.
Filiaciones:
Lorca-Puls DL:
Memory and Aging Center, Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA
Sección de Neurología, Departamento de Especialidades, Facultad de Medicina, Universidad de Concepción, Concepción, 4070105, Chile
Gajardo-Vidal A:
Memory and Aging Center, Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA
Centro de Investigación en Complejidad Social (CICS), Facultad de Gobierno, Universidad del Desarrollo, Santiago, 7590943, Chile
Dirección de Investigación y Doctorados, Vicerrectoría de Investigación y Doctorados, Universidad del Desarrollo, Concepción, 4070001, Chile
Mandelli ML:
Memory and Aging Center, Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA
Illán-Gala I:
Sant Pau Memory Unit, Department of Neurology, Biomedical Research Institute Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, 08025, Spain
Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, 28029, Spain
Global Brain Health Institute, University of California, San Francisco, CA 94143, USA
Ezzes Z:
Memory and Aging Center, Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA
Wauters LD:
Memory and Aging Center, Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA
Department of Speech, Language, and Hearing Sciences, University of Texas, Austin, TX 78712-0114, USA
Battistella G:
Memory and Aging Center, Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA
Department of Otolaryngology, Head and Neck Surgery, Massachusetts Eye and Ear and Harvard Medical School, Boston, MA 02114, USA
Bogley R:
Memory and Aging Center, Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA
Ratnasiri B:
Memory and Aging Center, Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA
Licata AE:
Memory and Aging Center, Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA
Battista P:
Memory and Aging Center, Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA
Global Brain Health Institute, University of California, San Francisco, CA 94143, USA
Laboratory of Neuropsychology, Istituti Clinici Scientifici Maugeri IRCCS, Bari, 70124, Italy
García AM:
Global Brain Health Institute, University of California, San Francisco, CA 94143, USA
Centro de Neurociencias Cognitivas, Universidad de San Andrés, Buenos Aires, B1644BID, Argentina
Departamento de Lingüística y Literatura, Facultad de Humanidades, Universidad de Santiago de Chile, Santiago, 9160000, Chile
Tee BL:
Memory and Aging Center, Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA
Global Brain Health Institute, University of California, San Francisco, CA 94143, USA
Lukic S:
Memory and Aging Center, Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA
Department of Communication Sciences and Disorders, Ruth S. Ammon College of Education and Health Sciences, Adelphi University, Garden City, NY 11530-0701, USA
Boxer AL:
Memory and Aging Center, Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA
Rosen HJ:
Memory and Aging Center, Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA
Seeley WW:
Memory and Aging Center, Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA
Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA
Grinberg LT:
Memory and Aging Center, Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA
Global Brain Health Institute, University of California, San Francisco, CA 94143, USA
Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA
Spina S:
Memory and Aging Center, Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA
Miller BL:
Memory and Aging Center, Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA
Global Brain Health Institute, University of California, San Francisco, CA 94143, USA
Miller ZA:
Memory and Aging Center, Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA
Henry ML:
Department of Speech, Language, and Hearing Sciences, University of Texas, Austin, TX 78712-0114, USA
Department of Neurology, Dell Medical School, University of Texas, Austin, TX 78712, USA
Dronkers NF:
Department of Psychology, University of California, Berkeley, CA 94720, USA
Department of Neurology, University of California, Davis, CA 95817, USA
Gorno-Tempini ML:
Memory and Aging Center, Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA
Green Published
|