Crossed aphasia confirmed by fMRI in a case with nonfluent variant of primary progressive aphasia carrying a GRN mutation

Elisa Canu, Valentina Bessi, Michela Leocadi, Sonia Padiglioni, Benedetta Nacmias, Sandro Sorbi, Massimo Filippi, Federica Agosta

Research output: Contribution to journalArticlepeer-review


Objectives: To characterize patterns of language lateralization in a right-handed woman with nonfluent/agrammatic primary progressive aphasia (nfvPPA) clinical picture despite showing a prevalent right-sided brain damage. Methods: We report a case of a 58-year-old woman with nfvPPA diagnosis (age at onset = 55) previously described as a crossed aphasia case with progranulin mutation. At 2 years from the first visit, patient underwent 3DT1-weighted and a task-based functional MRI (fMRI). During the fMRI task, she was asked to perform a letter fluency test as the task of interest and to count forward as the control condition. Image processing and data analysis were performed using SPM12 and the effect of each task was tested at p < 0.05 FWE corrected. Results: The structural MRI confirmed a widespread right fronto-temporal atrophy mainly involving the right inferior frontal gyrus. During the letter fluency task, we observed an increased activation centered at the right inferior orbitofrontal gyrus and right middle frontal gyrus. By reducing the threshold, the pattern of functional activation was still dramatically prevalent at the right side. Conclusions: We provided evidence of the right language lateralization in a previously suspected crossed nfvPPA. Despite the long disease duration and the large amount of atrophy at the right side, there was no fMRI evidence of a left-hemisphere contribution to language function. We might speculate that compensatory effects do not appear when the premorbid language lateralization is purely right. The investigation of the underlying functional brain substrates in crossed nfvPPA cases may help understanding disease vulnerability in these neurodegenerative conditions.

Original languageEnglish
JournalJournal of Neurology
Publication statusPublished - Mar 21 2019


  • Crossed aphasia
  • Functional MRI (fMRI)
  • Nonfluent/agrammatic primary progressive aphasia
  • Progranulin (GRN) mutation

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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