A - 90 Verbal Fluency Changes with Age and Theta-Gamma Phase-Amplitude Coupling

Abstract Objective Semantic judgement involves the capacity to understand and conceptualize words and relate them to meaning. We examined the neural mechanisms involved in semantic judgement during aging and how this affects performance on a neuropsychological assessment of verbal fluency. Methods One-hundred and sixty participants (Mage = 49.76, SDage = 15.21, age range = 21–87, Nfemale = 81) completed a semantic judgement task with related and unrelated conditions during magnetoencephalography (MEG). Participants also completed phonemic (Controlled Oral Word Association Test [COWAT], letters F-A-S) and semantic (Animals) tasks. Both tasks were z-scored and averaged as a measure of verbal fluency. MEG data were transformed into the time-frequency domain and significant task-related oscillatory responses were imaged to identify the underlying anatomical areas. Whole-brain paired-t tests were performed to assess conditional differences; voxel timeseries data were extracted from the resulting peaks to calculate theta-gamma phase-amplitude coupling (PAC). PAC difference scores (unrelated-related) were calculated for subsequent analyses. Results Whole-brain contrasts revealed significant conditional differences in the theta and gamma ranges in the left hippocampus (p < 0.001), with stronger responses in unrelated compared to related trials. A linear regression revealed that age and the PAC difference scores predicted verbal fluency (R = 0.322, F(2,150) = 8.698, p < 0.001). Specifically, stronger theta-gamma PAC in the unrelated compared to related condition and increased age were associated with lower verbal fluency scores (PAC difference score: β = −0.538, p = 0.032, 95% CI [−1.029, −0.047]; Age: β = −0.016, p < 0.001, 95% CI [−0.026, −0.007]). Conclusions These preliminary findings suggest differences in theta-gamma PAC in the hippocampus are associated with verbal fluency with implications for understanding the neural underpinnings of performance on verbal fluency assessments.