Henry Luckhoo

Investigating the electrophysiological basis of resting state networks using magnetoencephalography

In recent years the study of resting state brain networks (RSNs) has become an important area of neuroimaging. The majority of studies have used functional magnetic resonance imaging (fMRI) to measure temporal correlation between blood-oxygenation-level–dependent (BOLD) signals from different brain areas. However, BOLD is an indirect measure related to hemodynamics, and the electrophysiological basis of connectivity between spatially separate network nodes cannot be comprehensively assessed using this technique. In this paper we describe a means to characterize resting state brain networks independently using magnetoencephalography (MEG), a neuroimaging modality that bypasses the hemodynamic response and measures the magnetic fields associated with electrophysiological brain activity. The MEG data are analyzed using a unique combination of beamformer spatial filtering and independent component analysis (ICA) and require no prior assumptions about the spatial locations or patterns of the networks. This method results in RSNs with significant similarity in their spatial structure compared with RSNs derived independently using fMRI. This outcome confirms the neural basis of hemodynamic networks and demonstrates the potential of MEG as a tool for understanding the mechanisms that underlie RSNs and the nature of connectivity that binds network nodes.

Exploring mechanisms of spontaneous functional connectivity in MEG: How delayed network interactions lead to structured amplitude envelopes of band-pass filtered oscillations

Spontaneous (or resting-state) brain activity has attracted a growing body of neuroimaging research over the last decades. Whole-brain network models have proved helpful to investigate the source of slow (<0.1 Hz) correlated hemodynamic fluctuations revealed in fMRI during rest. However, the mechanisms mediating resting-state long-distance correlations and the relationship with the faster neural activity remain unclear. Novel insights coming from MEG studies have shown that the amplitude envelopes of alpha- and beta-frequency oscillations (~8-30 Hz) display similar correlation patterns as the fMRI signals. In this work, we combine experimental and theoretical work to investigate the mechanisms of spontaneous MEG functional connectivity. Using a simple model of coupled oscillators adapted to incorporate realistic whole-brain connectivity and conduction delays, we explore how slow and structured amplitude envelopes of band-pass filtered signals - fairly reproducing MEG data collected from 10 healthy subjects at rest - are generated spontaneously in the space-time structure of the brain network. Our simulation results show that the large-scale neuroanatomical connectivity provides an optimal network structure to support a regime with metastable synchronization. In this regime, different subsystems may temporarily synchronize at reduced collective frequencies (falling in the 8-30 Hz range due to the delays) while the global system never fully synchronizes. This mechanism modulates the frequency of the oscillators on a slow time-scale (<0.1 Hz) leading to structured amplitude fluctuations of band-pass filtered signals. Taken overall, our results reveal that the structured amplitude envelope fluctuations observed in resting-state MEG data may originate from spontaneous synchronization mechanisms naturally occurring in the space-time structure of the brain.

Inferring task-related networks using independent component analysis in magnetoencephalography.

A novel framework for analysing task-positive data in magnetoencephalography (MEG) is presented that can identify task-related networks. Techniques that combine beamforming, the Hilbert transform and temporal independent component analysis (ICA) have recently been applied to resting-state MEG data and have been shown to extract resting-state networks similar to those found in fMRI. Here we extend this approach in two ways. First, we systematically investigate optimisation of time-frequency windows for connectivity measurement. This is achieved by estimating the distribution of functional connectivity scores between nodes of known resting-state networks and contrasting it with a distribution of artefactual scores that are entirely due to spatial leakage caused by the inverse problem. We find that functional connectivity, both in the resting-state and during a cognitive task, is best estimated via correlations in the oscillatory envelope in the 8–20 Hz frequency range, temporally down-sampled with windows of 1–4 s. Second, we combine ICA with the general linear model (GLM) to incorporate knowledge of task structure into our connectivity analysis. The combination of ICA with the GLM helps overcome problems of these techniques when used independently: namely, the interpretation and separation of interesting independent components from those that represent noise in ICA and the correction for multiple comparisons when applying the GLM. We demonstrate the approach on a 2-back working memory task and show that this novel analysis framework is able to elucidate the functional networks involved in the task beyond that which is achieved using the GLM alone. We find evidence of localised task-related activity in the area of the hippocampus, which is difficult to detect reliably using standard methods. Task-positive ICA, coupled with the GLM, has the potential to be a powerful tool in the analysis of MEG data.

Task induced modulation of neural oscillations in electrophysiological brain networks.

In recent years, one of the most important findings in systems neuroscience has been the identification of large scale distributed brain networks. These networks support healthy brain function and are perturbed in a number of neurological disorders (e.g. schizophrenia). Their study is therefore an important and evolving focus for neuroscience research. The majority of network studies are conducted using functional magnetic resonance imaging (fMRI) which relies on changes in blood oxygenation induced by neural activity. However recently, a small number of studies have begun to elucidate the electrical origin of fMRI networks by searching for correlations between neural oscillatory signals from spatially separate brain areas in magnetoencephalography (MEG) data. Here we advance this research area. We introduce two methodological extensions to previous independent component analysis (ICA) approaches to MEG network characterisation: 1) we show how to derive pan-spectral networks that combine independent components computed within individual frequency bands. 2) We show how to measure the temporal evolution of each network with millisecond temporal resolution. We apply our approach to ~10h of MEG data recorded in 28 experimental sessions during 3 separate cognitive tasks showing that a number of networks could be identified and were robust across time, task, subject and recording session. Further, we show that neural oscillations in those networks are modulated by memory load, and task relevance. This study furthers recent findings on electrodynamic brain networks and paves the way for future clinical studies in patients in which abnormal connectivity is thought to underlie core symptoms.

Dynamic state allocation for MEG source reconstruction

Our understanding of the dynamics of neuronal activity in the human brain remains limited, due in part to a lack of adequate methods for reconstructing neuronal activity from noninvasive electrophysiological data. Here, we present a novel adaptive time-varying approach to source reconstruction that can be applied to magnetoencephalography (MEG) and electroencephalography (EEG) data. The method is underpinned by a Hidden Markov Model (HMM), which infers the points in time when particular states re-occur in the sensor space data. HMM inference finds short-lived states on the scale of 100 ms. Intriguingly, this is on the same timescale as EEG microstates. The resulting state time courses can be used to intelligently pool data over these distinct and short-lived periods in time. This is used to compute time-varying data covariance matrices for use in beamforming, resulting in a source reconstruction approach that can tune its spatial filtering properties to those required at different points in time. Proof of principle is demonstrated with simulated data, and we demonstrate improvements when the method is applied to MEG.

Role of white-matter pathways in coordinating alpha oscillations in resting visual cortex.

In the absence of cognitive tasks and external stimuli, strong rhythmic fluctuations with a frequency ≈ 10 Hz emerge from posterior regions of human neocortex. These posterior α-oscillations can be recorded throughout the visual cortex and are particularly strong in the calcarine sulcus, where the primary visual cortex is located. The mechanisms and anatomical pathways through which local \alpha-oscillations are coordinated however, are not fully understood. In this study, we used a combination of magnetoencephalography (MEG), diffusion tensor imaging (DTI), and biophysical modeling to assess the role of white-matter pathways in coordinating cortical α-oscillations. Our findings suggest that primary visual cortex plays a special role in coordinating α-oscillations in higher-order visual regions. Specifically, the amplitudes of α-sources throughout visual cortex could be explained by propagation of α-oscillations from primary visual cortex through white-matter pathways. In particular, α-amplitudes within visual cortex correlated with both the anatomical and functional connection strengths to primary visual cortex. These findings reinforce the notion of posterior α-oscillations as intrinsic oscillations of the visual system. We speculate that they might reflect a default-mode of the visual system during which higher-order visual regions are rhythmically primed for expected visual stimuli by α-oscillations in primary visual cortex.

The Neural Dynamics of Fronto-Parietal Networks in Childhood Revealed using Magnetoencephalography

Our ability to hold information in mind is limited, requires a high degree of cognitive control, and is necessary for many subsequent cognitive processes. Children, in particular, are highly variable in how, trial-by-trial, they manage to recruit cognitive control in service of memory. Fronto-parietal networks, typically recruited under conditions where this cognitive control is needed, undergo protracted development. We explored, for the first time, whether dynamic changes in fronto-parietal activity could account for childrens variability in tests of visual short-term memory (VSTM). We recorded oscillatory brain activity using magnetoencephalography (MEG) as 9- to 12-year-old children and adults performed a VSTM task. We combined temporal independent component analysis (ICA) with general linear modeling to test whether the strength of fronto-parietal activity correlated with VSTM performance on a trial-by-trial basis. In children, but not adults, slow frequency theta (4–7 Hz) activity within a right lateralized fronto-parietal network in anticipation of the memoranda predicted the accuracy with which those memory items were subsequently retrieved. These findings suggest that inconsistent use of anticipatory control mechanism contributes significantly to trial-to-trial variability in VSTM maintenance performance.

Multi-session statistics on beamformed MEG data

Beamforming has been widely adopted as a source reconstruction technique in the analysis of magnetoencephalography data. Most beamforming implementations incorporate a spatially-varying rescaling (which we term weights normalisation) to correct for the inherent depth bias in raw beamformer estimates. Here, we demonstrate that such rescaling can cause critical problems whenever analyses are performed over multiple sessions of separately beamformed data, for example when comparing effect sizes between different populations. Importantly, we show that the weights-normalised beamformer estimates of neural activity can even lead to a reversal in the inferred sign of the effect being measured. We instead recommend that no weights normalisation be carried out; any depth bias is instead accounted for in the calculation of multi-session (e.g. group) statistics. We demonstrate the severity of the weights normalisation confound with a 2-D simulation, and in real MEG data by performing a group statistical analysis to detect differences in alpha power in eyes-closed rest compared with continuous visual stimulation.

Fusion of Magnetometer and Gradiometer Sensors of MEG in the Presence of Multiplicative Error

Novel neuroimaging techniques have provided unprecedented information on the structure and function of the living human brain. Multimodal fusion of data from different sensors promises to radically improve this understanding, yet optimal methods have not been developed. Here, we demonstrate a novel method for combining multichannel signals. We show how this method can be used to fuse signals from the magnetometer and gradiometer sensors used in magnetoencephalography (MEG), and through extensive experiments using simulation, head phantom and real MEG data, show that it is both robust and accurate. This new approach works by assuming that the lead fields have multiplicative error. The criterion to estimate the error is given within a spatial filter framework such that the estimated power is minimized in the worst case scenario. The method is compared to, and found better than, existing approaches. The closed-form solution and the conditions under which the multiplicative error can be optimally estimated are provided. This novel approach can also be employed for multimodal fusion of other multichannel signals such as MEG and EEG. Although the multiplicative error is estimated based on beamforming, other methods for source analysis can equally be used after the lead-field modification.

Modeling Alpha-Band Functional Connectivity for MEG Resting State Data: Oscillations and Delays in a Spiking Neuron Model

The study of structural and functional connectivity (SC,FC) and dynamics in spontaneous brain activity is a rapidly growing field of research [1]. The existence of Resting State Networks (RSN) has been well established in fMRI over the past decade, [1] and computational models [2] have successfully captured their connectivity patterns and slow oscillations, but have not been applied to recent MEG findings of coherent RSN [3] yet. Here, we extended a recent neurophysiologically realistic spiking-neuron model of spontaneous fMRI activity [4] to exhibit noisy oscillatory activity in the alpha band (Figure ​(Figure1A,1A, bottom) and studied how connectivity and delays influenced the model fit with the oscillatory MEG FC. The global network was described by a graph of nodes (local populations of excitatory and inhibitory spiking neurons), connected to each other according to a DTI-derived anatomical connectivity matrix, which fixed the relative connectivity and delay/distance structure, but left global scaling factors W (coupling weight) and ps (propagation speed in m/s) as free parameters in the model. FC was measured by correlating the low-pass filtered Power Envelopes of the bandlimited signal. Simulations showed the largest margin of good concordance with empirical FC over W when neurophysiologically realistic delays (5-10 m/s) were included (Figure ​(Figure1C1C). Figure 1 A: Sketch of the global model graph, each node consisting of local populations of spiking neurons. The model is capable of producing alpha oscillations (bottom). B: Empirical and simulated FC are fitted and C: the model best captures the empirical pattern ...