Slowing is slowing: Delayed neural responses to words are linked to abnormally slow resting state activity in primary...

Neurodegenerative disorders are often characterized by neuronal "slowing," which may be assessed in different ways. In the present study, we examined the latency of neural responses to linguistic stimuli in participants diagnosed with primary progressive aphasia (PPA), as well as changes in the power spectra of resting state activity, both measured with MEG. Compared to both age-matched and younger controls, patients with PPA showed a delayed latency of 8-30 Hz event-related desynchronization (ERD) in response to semantic anomalies. In addition, resting-state MEG revealed increased power in the lower frequency delta and theta bands, but decreased activity in the higher alpha and beta bands. The task-induced and spontaneous measures of neural dynamics were related, such that increased peak latencies in response to words were correlated with a shift of spontaneous oscillatory dynamics towards lower frequencies. In contrast, older controls showed similar task related ERD latencies as younger controls, but also "speeding" of spontaneous activity, i.e. a shift towards faster frequencies. In PPA patients both increased peak latencies on task and increased slow oscillations at rest were associated with less accurate performance on the language task and poorer performance on offline cognitive measures, beyond variance accounted for by structural atrophy. A mediation analysis indicated that increased theta power accounted for the relationship between delayed electrophysiological responses and reduced accuracy in PPA patients. These results indicate that the neuropathological changes in PPA result in slowing of both task-related and spontaneous neuronal activity, linked to functional decline, whereas the speeding of spontaneous activity in healthy aging seems to have a protective or compensatory effect.