4.7 Article

A novel frontal pathway underlies verbal fluency in primary progressive aphasia

Journal

BRAIN
Volume 136, Issue -, Pages 2619-2628

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/brain/awt163

Keywords

aphasia; white matter; language; tractography; dementia; freesurfer; frontal aslant tract; tractography

Funding

  1. National Institute on Deafness and Communication Disorders (NIDCD) [DC008552]
  2. National Institute on Aging (NIA) [AG13854]
  3. National Institute of Neurological Disorders and Stroke (NINDS) [NS075075]
  4. National Centre for Research Resources [5KL2RR025740]
  5. Guy's and St Thomas' Charity
  6. Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, King's College London

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The frontal aslant tract is a direct pathway connecting Broca's region with the anterior cingulate and pre-supplementary motor area. This tract is left lateralized in right-handed subjects, suggesting a possible role in language. However, there are no previous studies that have reported an involvement of this tract in language disorders. In this study we used diffusion tractography to define the anatomy of the frontal aslant tract in relation to verbal fluency and grammar impairment in primary progressive aphasia. Thirty-five patients with primary progressive aphasia and 29 control subjects were recruited. Tractography was used to obtain indirect indices of microstructural organization of the frontal aslant tract. In addition, tractography analysis of the uncinate fasciculus, a tract associated with semantic processing deficits, was performed. Damage to the frontal aslant tract correlated with performance in verbal fluency as assessed by the Cinderella story test. Conversely, damage to the uncinate fasciculus correlated with deficits in semantic processing as assessed by the Peabody Picture Vocabulary Test. Neither tract correlated with grammatical or repetition deficits. Significant group differences were found in the frontal aslant tract of patients with the non-fluent/agrammatic variant and in the uncinate fasciculus of patients with the semantic variant. These findings indicate that degeneration of the frontal aslant tract underlies verbal fluency deficits in primary progressive aphasia and further confirm the role of the uncinate fasciculus in semantic processing. The lack of correlation between damage to the frontal aslant tract and grammar deficits suggests that verbal fluency and grammar processing rely on distinct anatomical networks.

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