Why are patients with progressive nonfluent aphasia nonfluent?

Objective: To investigate the cognitive and neural basis for nonfluent speech in progressive nonfluent aphasia (PNFA). Background: Nonfluent speech is the hallmark feature of PNFA, and this has been attributed to impairments in syntactic processing, motor-speech planning, and executive functioning that also occur in these patients. Patients with PNFA have left inferior frontal atrophy. Methods: A large semi-structured speech sample and neuropsychological measures of language and executive functioning were examined in 16 patients with PNFA, 12 patients with behavioral-variant frontotemporal dementia (bvFTD), and 13 age-matched controls. Speech fluency was quantified as words per minute (WPM) in the semi-structured speech sample. Stepwise linear regression analyses were used to relate WPM to grammatic, motor-speech planning, and executive aspects of patient functioning. These measures were then related to cortical thickness in 8 patients with PNFA and 7 patients with bvFTD using structural MRI. Results: WPM was significantly reduced in patients with PNFA relative to controls and patients with bvFTD. Regression analyses revealed that only grammatic measures predicted WPM in PNFA, whereas executive measures were the only significant predictor of WPM in bvFTD. Cortical thinning was significant in PNFA relative to controls in left inferior frontal and anterior-superior temporal regions, and a regression analysis related this area to reduced WPM in PNFA. Significant cortical thinning associated with limited grammatic processing also was seen in the left inferior frontal-superior temporal region in PNFA, and this overlapped with the area of frontal-temporal thinning related to reduced WPM. Conclusion: Nonfluent speech in PNFA may be due in part to difficulty with grammatic processing associated with left inferior frontal and anterior-superior temporal disease.