Evaluation of the lexico-semantic process in patients with primary progressive aphasia by eye-tracking and neuroimaging methods

Primary progressive aphasia (PPA) is a neurodegenerative disease, in which language functions are primarily affected, while other cognitive skills are relatively preserved. Patients may present semantic variant PPA (PPA-S) with predominant comprehension deficit, or non-semantic PPA (PPA-NS) with preserved understanding but non-fluent and/or agrammatic speech. With disease progression, as a result of the spread of atrophy to the inferior frontal gyrus (IFG), the temporoparietal junction (TPJ), and the left anterior temporal lobe (ATL), word-object associations and comprehension may be impaired, leading to mixed-type PPA. The aim of this study is to detect early impairments in word-object association in PPA and to identify the atrophy pattern of the disease. Eleven non-semantic PPA patients and 10 healthy controls had to perform a word-object matching task, which consisted of 24 trials. The participants were asked to touch the corresponding target among 16 objects on an elliptical plane on the touch-sensitive computer screen after the target word was displayed. In each trial, 7 distractors from the same semantic category (related distractor), and 8 from another semantic category (unrelated distractor) were included. Eye movements were recorded using the EyeLink 1000 eye-tracking device. In addition, cortical thickness maps were computed by analyzing structural brain MRI images of the participants with the FreeSurfer software. IFG and TPJ atrophy was observed in the PPA patient group in addition to the ATL atrophy specific to semantic PPA. In the word-object matching task, 99.5% of the control group and 90.6% of the PPA group gave correct answers. However, analysis of the eye movements showed that PPA patients looked longer at the distractors than at the target objects and could find the target object by eliminating specifically each of the related distractors. These findings show that atrophy spreading to the ATL in PPA cases, who did not yet develop clinical comprehension impairments, maybe the anatomical finding of the progression to mixed-type PPA, and word-object association impairment detected by eye-tracking analysis may be a preclinical symptom of the comprehension impairment.