Neural basis for sentence comprehension deficits in frontotemporal dementia

Many patients with frontotemporal dementia (FTD) have impaired sentence comprehension. However, the pattern of comprehension difficulty appears to vary depending on the clinical subgroup. The purpose of this study was to elucidate the neural basis for these deficits in FTD. We studied patients with two different presentations: Three patients with Progressive Non-Fluent Ahasia (PNFA), and five non-aphasic patients with a dysexecutive and social impairment (EXEC). The FTD patient subgroups were compared to a cohort of 11 healthy seniors with intact sentence comprehension. We monitored regional cerebral activity with blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) while subjects read sentences featuring both a grammatically complex object-relative center-embedded clause and a long linkage between the head noun phrase (NP) and the gap where the NP is interpreted in the center-embedded clause. Subjects decided whether the agent of the action is a male or a female. Healthy seniors activated both ventral portions of inferior frontal cortex (vIFC) and dorsal portions of IFC (dIFC) in the left hemisphere, often associated with grammatical and working memory components of these sentences, respectively. PNFA patients differed from healthy controls since they have reduced activation of left vIFC, while EXEC patients have less recruitment of left dIFC. We conclude that FTD subgroups have distinct patterns of sentence comprehension difficulty in part because of selective interruptions of a large-scale neural network for sentence processing.