Distinct spatiotemporal patterns of neuronal functional connectivity in primary progressive aphasia variants

Abstract

Primary progressive aphasia is a syndrome characterized by progressive loss of language abilities with three main phenotypic clinical presentations, including logopenic, non-fluent/agrammatic, and semantic variants. Previous imaging studies have shown unique anatomic impacts within language networks in each variant. However, direct measures of spontaneous neuronal activity and functional integrity of these impacted neural networks in primary progressive aphasia are lacking. The aim of this study was to characterize the spatial and temporal patterns of resting state neuronal synchronizations in primary progressive aphasia syndromes. We hypothesized that resting state brain oscillations will show unique deficits within language network in each variant of primary progressive aphasia. We examined 39 patients with primary progressive aphasia including logopenic variant (n = 14, age = 61 ± 9 years), non-fluent/agrammatic variant (n = 12, age = 71 ± 8 years) and semantic variant (n = 13, age = 65 ± 7 years) using magnetoencephalographic imaging, compared to a control group that was matched in age and gender to each primary progressive aphasia subgroup (n = 20, age = 65 ± 5 years). Each patient underwent a complete clinical evaluation including a comprehensive battery of language tests. We examined the whole-brain resting state functional connectivity as measured by imaginary coherence in each patient group compared to the control cohort, in three frequency oscillation bands-delta-theta (2-8 Hz); alpha (8-12 Hz); beta (12-30 Hz). Each variant showed a distinct spatiotemporal pattern of altered functional connectivity compared to age-matched controls. Specifically, we found significant hyposynchrony of alpha and beta frequency within the left posterior temporal and occipital cortices in patients with the logopenic variant, within the left inferior frontal cortex in patients with the non-fluent/agrammatic variant, and within the left temporo-parietal junction in patients with the semantic variant. Patients with logopenic variant primary progressive aphasia also showed significant hypersynchrony of delta-theta frequency within bilateral medial frontal and posterior parietal cortices. Furthermore, region of interest-based analyses comparing the spatiotemporal patterns of variant-specific regions of interest identified in comparison to age-matched controls showed significant differences between primary progressive aphasia variants themselves. We also found distinct patterns of regional spectral power changes in each primary progressive aphasia variant, compared to age-matched controls. Our results demonstrate neurophysiological signatures of network-specific neuronal dysfunction in primary progressive aphasia variants. The unique spatiotemporal patterns of neuronal synchrony signify diverse neurophysiological disruptions and pathological underpinnings of the language network in each variant.

Abnormal language-related oscillatory responses in primary progressive aphasia

“…Thus, areas that are functionally connected to regions of atrophy are likely also to show abnormal responses in the early stages of degeneration as the proteinopathy begins to affect them. Recent studies of neural activity in PPA using resting-state recordings have also shown that functional abnormalities exist in widespread networks beyond the zones of atrophy ( Bonakdarpour et al, 2017 ; Ranasinghe et al, 2017 ), and that functional connectivity in the healthy brain predicts the spread of atrophy in PPA ( Mandelli et al, 2016 ).…”

Functional anomaly mapping reveals local and distant dysfunction caused by brain lesions

“…This may help to clarify the nature of the signal, and may also provide critical evidence regarding the brain basis of stroke recovery, the basis of day-to-day fluctuations in behavioral performance, and also the basis of behavioral response to neurorehabilitation, medications, and neuromodulation. Finally, efforts have been made to use resting BOLD data to identify functional changes in several clinical populations, often examining changes in resting state connectivity (He et al, 2007;Liu et al, 2018;Nair et al, 2015;Park et al, 2018;Ranasinghe et al, 2017); likewise, the technique described here may be applied to other populations without gross anatomical damage to identify functional anomalies in individuals with neurodegenerative disorders, psychiatric disorders, developmental disorders, or other clinical populations. Beyond clinical applications, this technique could also potentially be used to measure development or skill acquisition (e.g., literacy) or examine any source of individual difference in brain function, such as sensory experience (e.g., blind or deaf populations), multilingualism, or socioeconomic status.…”

Taking the sub-lexical route: brain dynamics of reading in the semantic variant of Primary Progressive Aphasia

“…MEG has only been deployed recently to investigate PPA (e.g., Kielar et al, 2018), but has already shown its potential as a tool to study the neurophysiological signatures of network-level alterations due to neurodegenerative disorders. It can be instrumental in identifying syndromespecific changes in the spectral properties of oscillatory responses (Ranasinghe et al, 2017;Sami et al, 2018). As suggested by task-free fMRI evidence, these functional alterations might precede structural ones and may be key for early diagnosis (Bonakdarpour et al, 2017).…”