Spontaneous signals in neuroimaging data may provide information on cortical health in disease and aging, but the relative sensitivity of different approaches is unknown. In the present study, we compared different but complementary indicators of neural dynamics in resting-state MEG and BOLD fMRI, and their relationship with blood flow. Participants included patients with post-stroke aphasia, age-matched controls, and young adults. The complexity of brain activity at rest was quantified in MEG using spectral analysis and multiscale entropy (MSE) measures, whereas BOLD variability was quantified as the standard deviation (SDBOLD), mean squared successive difference (MSSD), and sample entropy of the BOLD time series. We sought to assess the utility of signal variability and complexity measures as markers of age-related changes in healthy adults and perilesional dysfunction in chronic stroke. The results indicate that reduced BOLD variability is a robust finding in aging, whereas MEG measures are more sensitive to the cortical abnormalities associated with stroke. Furthermore, reduced complexity of MEG signals in perilesional tissue were correlated with hypoperfusion as assessed with arterial spin labeling (ASL), while no such relationship was apparent with BOLD variability. These findings suggest that MEG signal complexity offers a sensitive index of neural dysfunction in perilesional tissue in chronic stroke, and that these effects are clearly distinguishable from those associated with healthy aging.

Using magnetoencephalography, we investigated the potential of perilesional and contralesional activity to support language recovery in patients with poststroke aphasia. In healthy young controls, left-lateralized ventral frontotemporal regions responded to semantic anomalies during sentence comprehension and bilateral dorsal frontoparietal regions responded to syntactic anomalies. Older adults showed more extensive bilateral responses to the syntactic anomalies and less lateralized responses to the semantic anomalies, with decreased activation in the left occipital and parietal regions for both semantic and syntactic anomalies. In aphasic participants, we observed compensatory recruitment in the right hemisphere (RH), which varied depending on the type of linguistic information that was processed. For semantic anomalies, aphasic patients activated some preserved left hemisphere regions adjacent to the lesion, as well as homologous parietal and temporal RH areas. Patients also recruited right inferior and dorsolateral frontal cortex that was not activated in the healthy participants. Responses for syntactic anomalies did not reach significance in patients. Correlation analyses indicated that recruitment of homologous temporoparietal RH areas is associated with better semantic performance, whereas higher accuracy on the syntactic task was related to bilateral superior temporoparietal and right frontal activity. The results suggest that better recovery of semantic processing is associated with a shift to ventral brain regions in the RH. In contrast, preservation of syntactic processing is mediated by dorsal areas, bilaterally, although recovery of syntactic processing tends to be poorer than semantic. Hum Brain Mapp 37:2869-2893, 2016. © 2016 Wiley Periodicals, Inc.

Patients with Primary Progressive Aphasia (PPA) may react to linguistic stimuli differently than healthy controls, reflecting degeneration of language networks and engagement of compensatory mechanisms. We used magnetoencephalography (MEG) to evaluate oscillatory neural responses in sentence comprehension, in patients with PPA and age-matched controls. Participants viewed sentences containing semantically and syntactically anomalous words that evoke distinct oscillatory responses. For age-matched controls, semantic anomalies elicited left-lateralized 8–30 Hz power decreases distributed along ventral brain regions, whereas syntactic anomalies elicited bilateral power decreases in both ventral and dorsal regions. In comparison to controls, patients with PPA showed altered patterns of induced oscillations, characterized by delayed latencies and attenuated amplitude, which were correlated with linguistic impairment measured offline. The recruitment of right hemisphere temporo-parietal areas (also found in controls) was correlated with preserved semantic processing abilities, indicating that preserved neural activity in these regions was able to support successful semantic processing. In contrast, syntactic processing was more consistently impaired in PPA, regardless of neural activity patterns, suggesting that this domain of language is particularly vulnerable to the neuronal loss. In addition, we found that delayed peak latencies of oscillatory responses 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.

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Abnormal oscillatory brain activity in dementia may indicate incipient neuronal/synaptic dysfunction, rather than frank structural atrophy. Leveraging a potential link between the degree of abnormal oscillatory activity and cognitive symptom severity, one could localize brain regions in a diseased but pre-atrophic state, which may be more amenable to interventions. In the current study, we evaluated the relationships among cognitive deficits, regional volumetric changes, and resting-state magnetoencephalography abnormalities in patients with mild cognitive impairment (MCI; N = 10; age: 75.9 AE 7.3) or primary progressive aphasia (PPA; N = 12; 69.7 AE 8.0), and compared them to normal aging [young (N = 18; 24.6 AE 3.5), older controls (N = 24; 67.2 AE 9.7]. Whole-brain source-level resting-state estimates of relative oscillatory power in the delta (1-4 Hz), theta (4-7 Hz), alpha (8-12 Hz), and beta (15-30 Hz) bands were combined with gray matter volumes and cognitive scores to examine between-group differences and brain-behavior correlations. Language and executive function (EF) abilities were impaired in patients with PPA, while episodic memory was impaired in MCI. Widespread oscillatory speeding and volumetric shrinkage was associated with normal aging, whereas the trajectory in PPA indicated widespread oscillatory slowing with additional volumetric reductions. Increases in delta and decreases in alpha power uniquely predicted group membership to PPA. Beyond volumetric reductions, more delta predicted poorer memory. In patients with MCI, no consistent group difference among oscillatory measures was found. The contributions of delta/alpha power on memory abilities were larger than volumetric differences. Spontaneous oscillatory abnormalities in association with cognitive symptom severity can serve as a marker of neuronal dysfunction in dementia, providing targets for promising treatments. K E Y W O R D S dementia, magnetoencephalography, mild cognitive impairment, normal aging, primary progressive aphasia, resting-state

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Post-stroke aphasia is a consequence of localized stroke-related damage as well as global disturbances in a highly interactive and bilaterally-distributed language network. Aphasia is increasingly accepted as a network disorder and it should be treated as such when examining the reorganization and recovery mechanisms after stroke. In the current study, we sought to investigate reorganized patterns of electrophysiological connectivity, derived from resting-state magnetoencephalography (rsMEG), in post-stroke chronic (>6 months after onset) aphasia. We implemented amplitude envelope correlations (AEC), a metric of connectivity commonly used to describe slower aspects of interregional communication in resting-state electrophysiological data. The main focus was on identifying the oscillatory frequency bands and frequency-specific spatial topology of connections associated with preserved language abilities after stroke.RsMEG was recorded for 5 minutes in 21 chronic stroke survivors with aphasia and in 20 matched healthy controls. Source-level MEG activity was reconstructed and summarized within 72 atlas-defined brain regions (or nodes). A 72×72 leakage-corrected connectivity (of AEC) matrix was obtained for frequencies from theta to gamma (4–128 Hz). Connectivity was compared between groups, and, the correlations between connectivity and subscale scores from the Western Aphasia Battery (WAB) were evaluated in the stroke group, using partial least squares analyses. Posthoc multiple regression analyses were also conducted on a graph theory measure of node strengths, derived from significant connectivity results, to control for node-wise properties (local spectral power and lesion sizes) and demographic and stroke-related variables.Connectivity among the left hemisphere regions, i.e. those ipsilateral to the stroke lesion, was greatly reduced in stroke survivors with aphasia compared to matched healthy controls in the alpha (8-13 Hz; p=0.011) and beta (15-30 Hz; p=0.001) bands. The spatial topology of hypoconnectivity in the alpha vs. beta bands was distinct, revealing a greater involvement of ventral frontal, temporal and parietal areas in alpha, and dorsal frontal and parietal areas in beta. The node strengths from alpha and beta group differences remained significant after controlling for nodal spectral power. AEC correlations with WAB subscales of object naming and fluency were significant. Greater alpha connectivity was associated with better naming performance (p=0.045), and greater connectivity in both the alpha (p=0.033) and beta (p=0.007) bands was associated with better speech fluency performance. The spatial topology was distinct between these frequency bands. The node strengths remained significant after controlling for age, time post stroke onset, nodal spectral power and nodal lesion sizes.Our findings provide important insights into the electrophysiological connectivity profiles (frequency and spatial topology) potentially underpinning preserved language abilities in stroke survivors with aphasia.