We studied resting-state oscillatory connectivity using magnetoencephalography in healthy young humans (N = 183) genotyped for APOE-ɛ4, the greatest genetic risk for Alzheimer’s disease (AD). Connectivity across frequencies, but most prevalent in alpha/beta, was increased in APOE-ɛ4 in a set of mostly right-hemisphere connections, including lateral parietal and precuneus regions of the Default Mode Network. Similar regions also demonstrated hyperactivity, but only in gamma (40–160 Hz). In a separate study of AD patients, hypoconnectivity was seen in an extended bilateral network that partially overlapped with the hyperconnected regions seen in young APOE-ɛ4 carriers. Using machine-learning, AD patients could be distinguished from elderly controls with reasonable sensitivity and specificity, while young APOE-e4 carriers could also be distinguished from their controls with above chance performance. These results support theories of initial hyperconnectivity driving eventual profound disconnection in AD and suggest that this is present decades before the onset of AD symptomology.
The resting activity of the brain can be described by so-called intrinsic connectivity networks (ICNs), which consist of spatially and temporally distributed, but functionally connected, nodes. The coordinated activity of the resting state can be explored via magnetoencephalography (MEG) by studying frequency-dependent functional brain networks at the source level. Although many algorithms for the analysis of brain connectivity have been proposed, the reliability of network metrics derived from both static and dynamic functional connectivity is still unknown. This is a particular problem for studies of associations between ICN metrics and personality variables or other traits, and for studies of differences between patient and control groups, which both depend critically on the reliability of the metrics used. A detailed investigation of the reliability of metrics derived from resting-state MEG repeat scans is therefore a prerequisite for the development of connectomic biomarkers. Here, we first estimated both static (SFC) and dynamic functional connectivity (DFC) after beamforming source reconstruction using the imaginary part of the phase locking index (iPLV) and the correlation of the amplitude envelope (CorEnv). Using our approach, functional network microstates (FCμstates) were derived from the DFC and chronnectomics were computed from the evolution of FCμstates across experimental time. In both temporal scales, the reliability of network metrics (SFC), the FCμstates and the related chronnectomics were evaluated for every frequency band. Chronnectomic statistics and FCμstates were generally more reliable than node-wise static network metrics. CorEnv-based network metrics were more reproducible at the static approach. The reliability of chronnectomics have been evaluated also in a second dataset. This study encourages the analysis of MEG resting-state via DFC.
Juvenile myoclonic epilepsy (JME) is a form of idiopathic generalized epilepsy. It is yet unclear to what extent JME leads to abnormal network activation patterns. Here, we characterized statistical regularities in magnetoencephalograph (MEG) resting-state networks and their differences between JME patients and controls by combining a pairwise maximum entropy model (pMEM) and novel energy landscape analyses for MEG. First, we fitted the pMEM to the MEG oscillatory power in the front-oparietal network (FPN) and other resting-state networks, which provided a good estimation of the occurrence probability of network states. Then, we used energy values derived from the pMEM to depict an energy landscape, with a higher energy state corresponding to a lower occurrence probability. JME patients showed fewer local energy minima than controls and had elevated energy values for the FPN within the theta, beta, and gamma bands. Furthermore, simulations of the fitted pMEM showed that the proportion of time the FPN was occupied within the basins of energy minima was shortened in JME patients. These network alterations were highlighted by significant classification of individual participants employing energy values as multivariate features. Our findings suggested that JME patients had altered multistability in selective functional networks and frequency bands in the fronto-parietal cortices.
Benign Epilepsy with Centro-Temporal Spikes (BECTS) is a common childhood epilepsy associated with deficits in several neurocognitive domains. Neurophysiological studies in BECTS often focus on centro-temporal spikes, but these correlate poorly with morphology and cognitive impairments. To better understand the neural profile of BECTS, we studied background brain oscillations, thought to be integrally involved in neural network communication, in sensorimotor areas. We used independent component analysis of temporally correlated sources on magnetoencephalography recordings to assess sensorimotor resting-state network activity in BECTS patients and typically developing controls. We also investigated the variability of oscillatory characteristics within focal primary motor cortex (M1), localized with a separate finger abduction task. We hypothesized that background oscillations would differ between patients and controls in the sensorimotor network but not elsewhere, especially in the beta band (13-30 Hz) because of its role in network communication and motor processing. The results support our hypothesis: in the sensorimotor network, patients had a greater variability in oscillatory amplitude compared to controls, whereas there was no difference in the visual network. Network measures did not correlate with age. The coefficient of variation of resting M1 peak frequency correlated negatively with age in the beta band only, and was greater than average for a number of patients. Our results point toward a "disorganized" functional sensorimotor network in BECTS, supporting a neurodevelopmental delay in sensorimotor cortex. Our findings further suggest that investigating the variability of oscillatory peak frequency may be a useful tool to investigate deficits of disorganization in neurodevelopmental disorders.
Understanding how human brain microstructure influences functional connectivity is an important endeavor. In this work, magnetic resonance imaging data from ninety healthy participants were used to calculate structural connectivity matrices using the streamline count, fractional anisotropy, radial diffusivity and a myelin measure (derived from multi-component relaxometry) to assign connection strength. Unweighted binarized structural connectivity matrices were also constructed. Magnetoencephalography resting-state data from those participants were used to calculate functional connectivity matrices, via correlations of the Hilbert envelopes of beamformer timeseries in the delta, theta, alpha and beta frequency bands. Non-negative matrix factorization was performed to identify the components of the functional connectivity. Shortest-path-length and search-information analyses of the structural connectomes were used to predict functional connectivity patterns for each participant. The microstructure-informed algorithms predicted the components of the functional connectivity more accurately than they predicted the total functional connectivity. This provides a methodology to understand functional mechanisms better. The shortest-path-length algorithm exhibited the highest prediction accuracy. Of the weights of the structural connectivity matrices, the streamline count and the myelin measure gave the most accurate predictions, while the fractional anisotropy performed poorly. Overall, different structural metrics paint very different pictures of the structural connectome and its relationship to functional connectivity.
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