title: Frontal white matter tracts sustaining speech production in primary progressive aphasia.
abstract: In primary progressive aphasia (PPA), speech and language difficulties are caused by neurodegeneration of specific brain networks. In the nonfluent/agrammatic variant (nfvPPA), motor speech and grammatical deficits are associated with atrophy in a left fronto-insular-striatal network previously implicated in speech production. In vivo dissection of the crossing white matter (WM) tracts within this "speech production network" is complex and has rarely been performed in health or in PPA. We hypothesized that damage to these tracts would be specific to nfvPPA and would correlate with differential aspects of the patients' fluency abilities. We prospectively studied 25 PPA and 21 healthy individuals who underwent extensive cognitive testing and 3 T MRI. Using residual bootstrap Q-ball probabilistic tractography on high angular resolution diffusion-weighted imaging (HARDI), we reconstructed pathways connecting posterior inferior frontal, inferior premotor, insula, supplementary motor area (SMA) complex, striatum, and standard ventral and dorsal language pathways. We extracted tract-specific diffusion tensor imaging (DTI) metrics to assess changes across PPA variants and perform brain-behavioral correlations. Significant WM changes in the left intrafrontal and frontostriatal pathways were found in nfvPPA, but not in the semantic or logopenic variants. Correlations between tract-specific DTI metrics with cognitive scores confirmed the specific involvement of this anterior-dorsal network in fluency and suggested a preferential role of a posterior premotor-SMA pathway in motor speech. This study shows that left WM pathways connecting the speech production network are selectively damaged in nfvPPA and suggests that different tracts within this system are involved in subcomponents of fluency. These findings emphasize the emerging role of diffusion imaging in the differential diagnosis of neurodegenerative diseases.
authors.affiliation: Memory and Aging Center, Department of Neurology, and MariaLuisa.Mandelli@ucsf.edu.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Mandelli
authors.affiliation: Memory and Aging Center, Department of Neurology, and Department of Neurology, San Francisco, California 94143.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Caverzasi
authors.affiliation: Memory and Aging Center, Department of Neurology, and.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Binney
authors.affiliation: Memory and Aging Center, Department of Neurology, and.
authors.forename: Maya L
authors.initials: ML
authors.lastname: Henry
authors.affiliation: Memory and Aging Center, Department of Neurology, and.
authors.forename: Iryna
authors.initials: I
authors.lastname: Lobach
authors.affiliation: Memory and Aging Center, Department of Neurology, and.
authors.forename: Nikolas
authors.identifier: http://orcid.org/0000-0001-6244-078X
authors.initials: N
authors.lastname: Block
authors.affiliation: Department of Neurology, San Francisco, California 94143, Graduate Group in Bioengineering, University of California, Berkeley, California 94720-1762.
authors.forename: Bagrat
authors.initials: B
authors.lastname: Amirbekian
authors.affiliation: Center for Aphasia and Related Disorders, Veterans Administration Northern California Health Care System, Martinez, California 94553, and.
authors.forename: Nina
authors.initials: N
authors.lastname: Dronkers
authors.affiliation: Memory and Aging Center, Department of Neurology, and.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
authors.affiliation: Department of Neurology, San Francisco, California 94143, Graduate Group in Bioengineering, University of California, Berkeley, California 94720-1762, Department of Radiology and Biomedical Imaging, University of California, San Francisco, California 94107.
authors.forename: Roland G
authors.initials: RG
authors.lastname: Henry
authors.affiliation: Memory and Aging Center, Department of Neurology, and.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Gorno-Tempini
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D018888:Aphasia, Primary Progressive / Q000473:pathology*; D001284:Atrophy; D001931:Brain Mapping; D056324:Diffusion Tensor Imaging; D005260:Female; D005625:Frontal Lobe / Q000473:pathology*; D006801:Humans; D021621:Imaging, Three-Dimensional; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D009415:Nerve Net / Q000473:pathology*; D013068:Speech Production Measurement
keywords: diffusion tensor imaging; frontal tracts; primary progressive aphasia; speech production; tractography; white matter