RESUMEN
Cortical ischaemic strokes result in cognitive deficits depending on the area of the affected brain. However, we have demonstrated that difficulties with attention and processing speed can occur even with small subcortical infarcts. Symptoms appear independent of lesion location, suggesting they arise from generalized disruption of cognitive networks. Longitudinal studies evaluating directional measures of functional connectivity in this population are lacking. We evaluated six patients with minor stroke exhibiting cognitive impairment 6-8 weeks post-infarct and four age-similar controls. Resting-state magnetoencephalography data were collected. Clinical and imaging evaluations of both groups were repeated 6- and 12 months later. Network Localized Granger Causality was used to determine differences in directional connectivity between groups and across visits, which were correlated with clinical performance. Directional connectivity patterns remained stable across visits for controls. After the stroke, inter-hemispheric connectivity between the frontoparietal cortex and the non-frontoparietal cortex significantly increased between visits 1 and 2, corresponding to uniform improvement in reaction times and cognitive scores. Initially, the majority of functional links originated from non-frontal areas contralateral to the lesion, connecting to ipsilesional brain regions. By visit 2, inter-hemispheric connections, directed from the ipsilesional to the contralesional cortex significantly increased. At visit 3, patients demonstrating continued favourable cognitive recovery showed less reliance on these inter-hemispheric connections. These changes were not observed in those without continued improvement. Our findings provide supporting evidence that the neural basis of early post-stroke cognitive dysfunction occurs at the network level, and continued recovery correlates with the evolution of inter-hemispheric connectivity.
RESUMEN
Identifying the directed connectivity that underlie networked activity between different cortical areas is critical for understanding the neural mechanisms behind sensory processing. Granger causality (GC) is widely used for this purpose in functional magnetic resonance imaging analysis, but there the temporal resolution is low, making it difficult to capture the millisecond-scale interactions underlying sensory processing. Magnetoencephalography (MEG) has millisecond resolution, but only provides low-dimensional sensor-level linear mixtures of neural sources, which makes GC inference challenging. Conventional methods proceed in two stages: First, cortical sources are estimated from MEG using a source localization technique, followed by GC inference among the estimated sources. However, the spatiotemporal biases in estimating sources propagate into the subsequent GC analysis stage, may result in both false alarms and missing true GC links. Here, we introduce the Network Localized Granger Causality (NLGC) inference paradigm, which models the source dynamics as latent sparse multivariate autoregressive processes and estimates their parameters directly from the MEG measurements, integrated with source localization, and employs the resulting parameter estimates to produce a precise statistical characterization of the detected GC links. We offer several theoretical and algorithmic innovations within NLGC and further examine its utility via comprehensive simulations and application to MEG data from an auditory task involving tone processing from both younger and older participants. Our simulation studies reveal that NLGC is markedly robust with respect to model mismatch, network size, and low signal-to-noise ratio, whereas the conventional two-stage methods result in high false alarms and mis-detections. We also demonstrate the advantages of NLGC in revealing the cortical network-level characterization of neural activity during tone processing and resting state by delineating task- and age-related connectivity changes.
