Event Abstract Back to Event Modulation of Task-Related and Resting-State Oscillatory Responses in Primary Progressive Aphasia Aneta Kielar1*, Regina Jokel2 and Jed A. Meltzer2 1 University of Arizona, Speech, Language and Hearing Sciences, United States 2 Baycrest Hospital, Rotman Research Institute, Canada Introduction: Patients with PPA respond to linguistic stimuli differently than healthy controls, reflecting degeneration of language networks and engagement of compensatory mechanisms1,2,3,4,5. Although the location of neurodegeneration is thus far the best predictor of individual variation in linguistic performance across patients, alterations in network function beyond the regions of major atrophy may provide valuable information on how the brain copes with ongoing neurodegeneration. Aims: We used magnetoencephalography (MEG) to evaluate patterns of oscillatory responses during sentence comprehension and spontaneous brain electrical activity related to impairment and preservation of linguistic function in PPA. We asked whether impaired language processing in PPA is associated with altered patterns of induced and spontaneous oscillatory responses, and whether spared language functions can be associated with recruitment of preserved brain regions in the left and right hemispheres. Methods Participants: MEG data were acquired from 13 patients with PPA (Age: M = 69.62 years, SE = 2.08; Education = M = 14 years, SE = .85; 7 females) and 15 age-matched healthy controls (Age: M = 69 years, SE = 1.77; Education: M = 17 years, SE = .69, 4 females). Materials and Procedure: Participants performed a visual sentence comprehension task while their neural responses were examined using (MEG). The sentences included semantic anomalies (e.g., She went to the bakery for the loaf of books*/bread) and syntactically anomalous words (She going*/went to the bakery for the loaf of books) that evoked distinct electrophysiological responses. Results: Patients with PPA showed altered patterns of induced oscillations, characterized by delayed latencies and attenuated amplitude (Figure 1 A and B). In the left parietal region, PPA patients exhibited reversed sensitivity to semantic anomalies, with greater event-related desynchronization for control words instead (Figure 1 D). The recruitment of right hemisphere temporo-parietal areas (also found in controls) was correlated with preserved semantic processing abilities (Figure 1 E). In addition, delayed peak latencies of oscillatory responses to language stimuli were associated with lower accuracy for detecting semantic anomalies, suggesting that language deficits observed in PPA may be linked to delayed or slowed information processing. Patients with PPA exhibited altered spontaneous electrical activity, with a general shift to slower oscillations and decreased power at higher frequencies. These resting-state oscillatory abnormalities were correlated with slowed neural responses to language stimuli (Figure 1G), suggesting that degenerative pathology is linked with slower brain dynamics in both task-related and spontaneous activity. Discussion and Conclusions: The present results indicate that neuropathological changes in the brains of PPA patients result in slowed information processing, which, in turn, is linked with progressive cognitive decline. Preserved semantic processing is supported by the functionality of preserved right hemisphere regions. In contrast, syntactic processing seems to be more sensitive to the degeneration in left hemisphere language regions. The combination of spontaneous and language related oscillatory responses can reveal the extent of the neural tissue that is not directly atrophied, but is functionally compromised. Abnormalities in both resting-state and task-evoked oscillations can serve as sensitive indicators of neuronal damage associated with neurodegenerative conditions such as PPA. Figure 1 Acknowledgements This work was supported by a Basic Science Grant from the Ontario Brain Institute Ontario Neurodegenerative Disease Research Initiative (ONDRI) to JAM and RJ, an Alzheimer’s Association New Investigator Research Grant to JAM, and a postdoctoral research award from the Ontario Research Coalition to AK. We thank the participating volunteers and their families.