Claire M. Stevenson

Measuring functional connectivity using MEG: Methodology and comparison with fcMRI

Functional connectivity (FC) between brain regions is thought to be central to the way in which the brain processes information. Abnormal connectivity is thought to be implicated in a number of diseases. The ability to study FC is therefore a key goal for neuroimaging. Functional connectivity (fc) MRI has become a popular tool to make connectivity measurements but the technique is limited by its indirect nature. A multimodal approach is therefore an attractive means to investigate the electrodynamic mechanisms underlying hemodynamic connectivity. In this paper, we investigate resting state FC using fcMRI and magnetoencephalography (MEG). In fcMRI, we exploit the advantages afforded by ultra high magnetic field. In MEG we apply envelope correlation and coherence techniques to source space projected MEG signals. We show that beamforming provides an excellent means to measure FC in source space using MEG data. However, care must be taken when interpreting these measurements since cross talk between voxels in source space can potentially lead to spurious connectivity and this must be taken into account in all studies of this type. We show good spatial agreement between FC measured independently using MEG and fcMRI; FC between sensorimotor cortices was observed using both modalities, with the best spatial agreement when MEG data are filtered into the β band. This finding helps to reduce the potential confounds associated with each modality alone: while it helps reduce the uncertainties in spatial patterns generated by MEG (brought about by the ill posed inverse problem), addition of electrodynamic metric confirms the neural basis of fcMRI measurements. Finally, we show that multiple MEG based FC metrics allow the potential to move beyond what is possible using fcMRI, and investigate the nature of electrodynamic connectivity. Our results extend those from previous studies and add weight to the argument that neural oscillations are intimately related to functional connectivity and the BOLD response.

Optimising experimental design for MEG beamformer imaging

In recent years, the use of beamformers for source localisation has significantly improved the spatial accuracy of magnetoencephalography. In this paper, we examine techniques by which to optimise experimental design, and ensure that the application of beamformers yields accurate results. We show that variation in the experimental duration, or variation in the bandwidth of a signal of interest, can significantly affect the accuracy of a beamformer reconstruction of source power. Specifically, power will usually be underestimated if covariance windows are made too short, or bandwidths too narrow. The accuracy of spatial localisation may also be reduced. We conclude that for optimum accuracy, experimenters should aim to collect as much data as possible, and use a bandwidth spanning the entire frequency distribution of the signal of interest. This minimises distortion to reconstructed source images, time courses and power estimation. In the case where experimental duration is short, and small covariance windows are therefore used, we show that accurate power estimation can be achieved by matrix regularisation. However, large amounts of regularisation cause a loss in the spatial resolution of the MEG beamformer, hence regularisation should be used carefully, particularly if multiple sources in close proximity are expected.

Changes in brain network activity during working memory tasks: A magnetoencephalography study

In this study, we elucidate the changes in neural oscillatory processes that are induced by simple working memory tasks. A group of eight subjects took part in modified versions of the N-back and Sternberg working memory paradigms. Magnetoencephalography (MEG) data were recorded, and subsequently processed using beamformer based source imaging methodology. Our study shows statistically significant increases in θ oscillations during both N-back and Sternberg tasks. These oscillations were shown to originate in the medial frontal cortex, and further to scale with memory load. We have also shown that increases in θ oscillations are accompanied by decreases in β and γ band oscillations at the same spatial coordinate. These decreases were most prominent in the 20-40 Hz frequency range, although spectral analysis showed that γ band power decrease extends up to at least 80 Hz. β/γ Power decrease also scales with memory load. Whilst θ increases were predominately observed in the medial frontal cortex, β/γ decreases were associated with other brain areas, including nodes of the default mode network (for the N-back task) and areas associated with language processing (for the Sternberg task). These observations are in agreement with intracranial EEG and fMRI studies. Finally, we have shown an intimate relationship between changes in β/γ band oscillatory power at spatially separate network nodes, implying that activity in these nodes is not reflective of uni-modal task driven changes in spatially separate brain regions, but rather represents correlated network activity. The utility of MEG as a non-invasive means to measure neural oscillatory modulation has been demonstrated and future studies employing this technology have the potential to gain a better understanding of neural oscillatory processes, their relationship to functional and effective connectivity, and their correspondence to BOLD fMRI.

Relating BOLD fMRI and neural oscillations through convolution and optimal linear weighting

The exact relationship between neural activity and BOLD fMRI is unknown. However, several recent findings, recorded invasively in both humans and monkeys, show a positive correlation of BOLD to high-frequency (30-150 Hz) oscillatory power changes and a negative correlation to low-frequency (8-30 Hz) power changes arising from cortical areas. In this study, we computed the time series correlation between BOLD GE-EPI fMRI at 7 T and neural activity measures from noninvasive MEG, using a time-frequency beam former for source localisation. A sinusoidal drifting grating was presented visually for 4 s followed by a 20 s rest period in both recording modalities. The MEG time series were convolved with either a measured or canonical haemodynamic response function (HRF) for comparison with the measured BOLD data, and the BOLD data were deconvolved with either a measured or a canonical HRF for comparison with the measured MEG. In the visual cortex, the higher frequencies (mid-gamma=52-75 Hz and high-gamma=75-98 Hz) were positively correlated with BOLD whilst the lower frequencies (alpha=8-12 Hz and beta=12-25 Hz) were negatively correlated with BOLD. Furthermore, regression including all frequency bands predicted BOLD better than stimulus timing alone, although no individual frequency band predicted BOLD as well as stimulus timing. For this paradigm, there was, in general, no difference between using the SPM canonical HRF compared to the subject-specific measured HRF. In conclusion, MEG replicates findings from invasive recordings with regard to time series correlations with BOLD data. Conversely, deconvolution of BOLD data provides a neural estimate which correlates well with measured neural effects as a function of neural oscillation frequency.

Simultaneous EEG source localisation and artifact rejection during concurrent fMRI by means of spatial filtering

The simultaneous application of functional MRI and EEG represents an attractive, non-invasive technique for the combined measurement of electrical and haemodynamic activity in the human brain. Simultaneous EEG/fMRI provides a brain imaging modality with millimeter spatial accuracy, and millisecond temporal resolution. However, simultaneously acquired measurements are difficult due to the artifacts that are induced in the EEG by both the temporally varying field gradients used in MRI, and also blood flow effects. In this paper we apply an EEG beamformer spatial filter to EEG data recorded simultaneously with fMRI. We show, using this technique, that it is possible to localise accurately electrical effects in the brain, and that the localisation of driven oscillatory responses in the human visual cortex are spatially co-incident with the fMRI BOLD response. We also show how the beamformer can be used to extract timecourses of electrical activity from areas of interest in the brain. Such timecourses have millisecond time resolution. Finally, we show that in addition to source localisation, the beamformer spatial filter acts to reject interference in EEG signals, thus increasing the effective signal to noise ratio of electrical measurements. We show that the EEG-beamformer can eliminate effectively the ballistocardiogram artifact as well as residual gradient artifacts that remain in EEG data following correction using averaged artifact subtraction techniques.

β-Band Correlates of the fMRI BOLD Response

Oscillatory activity in the β‐band (15–30 Hz) has been studied in detail in the sensorimotor cortex. It has been postulated that β‐activity acts as a localized gating of cortical activity. Here, the induced oscillatory response in the β‐band is measured by magnetoencephalography, and the hemodynamic response is measured by fMRI. We assess the linearity of the responses to stimuli of varying duration in the primary motor cortex and to a sinusoidal drifting grating of varying contrast amplitude and drift frequency in the visual cortex. In this way, we explore the nature of β‐oscillations and their relationship with hemodynamic effects. Excellent spatial colocalization of BOLD and β‐activity in both central and lateral (MT) visual areas and sensorimotor areas suggests that the two are intimately related. In contrast to the BOLD response, the level of β‐desynchronization is not modulated by stimulus contrast or by stimulus duration, consistent with a gating role. The amplitude of β‐desynchronization in the central visual area is however modulated by drift frequency, and this seems to parallel the modulation in BOLD amplitude at the same location. Hum Brain Mapp, 2011.

Exploring the feasibility of simultaneous electroencephalography/functional magnetic resonance imaging at 7 T

The increased blood oxygenation level-dependent contrast available at high field makes the implementation of combined EEG/fMRI experiments at 7 T highly worthwhile from the point of view of fMRI data quality, but the higher field poses greater technical challenges for achieving good quality EEG data. A study of the feasibility of recording EEG signals from human subjects at 7 T using a commercially available, MR-compatible EEG system has therefore been carried out. This involved systematic measurement of the sources of noise in EEG recordings made in the 7 T scanner and measurement of RF heating effects on a gel phantom in the presence of a 32-electrode EEG cap. Having found no significant safety concerns and identified a set-up (involving switching off the magnets cryo-cooler pumps and mounting the EEG amplifier on a cantilever) that limited scanner-induced noise, combined EEG/fMRI experiments employing visual stimulation were then successfully carried out on two human subjects. With the use of beamformer-based analysis of the EEG data, driven responses and alpha-band, event-related desynchronisation were identified in both subjects.

Investigating spatial specificity and data averaging in MEG

This study shows that the spatial specificity of MEG beamformer estimates of electrical activity can be affected significantly by the way in which covariance estimates are calculated. We define spatial specificity as the ability to extract independent timecourse estimates of electrical brain activity from two separate brain locations in close proximity. Previous analytical and simulated results have shown that beamformer estimates are affected by narrowing the time frequency window in which covariance estimates are made. Here we build on this by both experimental validation of previous results, and investigating the effect of data averaging prior to covariance estimation. In appropriate circumstances, we show that averaging has a marked effect on spatial specificity. However the averaging process results in ill-conditioned covariance matrices, thus necessitating a suitable matrix regularisation strategy, an example of which is described. We apply our findings to an MEG retinotopic mapping paradigm. A moving visual stimulus is used to elicit brain activation at different retinotopic locations in the visual cortex. This gives the impression of a moving electrical dipolar source in the brain. We show that if appropriate beamformer optimisation is applied, the moving source can be tracked in the cortex. In addition to spatial reconstruction of the moving source, we show that timecourse estimates can be extracted from neighbouring locations of interest in the visual cortex. If appropriate methodology is employed, the sequential activation of separate retinotopic locations can be observed. The retinotopic paradigm represents an ideal platform to test the spatial specificity of source localisation strategies. We suggest that future comparisons of MEG source localisation techniques (e.g. beamformer, minimum norm, Bayesian) could be made using this retinotopic mapping paradigm.

Paired pulse depression in the somatosensory cortex: associations between MEG and BOLD fMRI.

Interpretation of the blood oxygen level dependent (BOLD) response measured using functional magnetic resonance imaging (fMRI) requires an understanding of the underlying neuronal activity. Here we report on a study using both magnetoencephalography (MEG) and BOLD fMRI, to measure the brains functional response to electrical stimulation of the median nerve in a paired pulse paradigm. Interstimulus Intervals (ISIs) of 0.25, 0.5, 0.75, 1.0, 1.5 and 2.0 s are used to investigate how the MEG detected neural response to a second pulse is affected by that from a preceding pulse and if these MEG modulations are reflected in the BOLD response. We focus on neural oscillatory activity in the β-band (13-30 Hz) and the P35m component of the signal averaged evoked response in the sensorimotor cortex. A spatial separation of β ERD and ERS following each pulse is demonstrated suggesting that these two effects arise from separate neural generators, with ERS exhibiting a closer spatial relationship with the BOLD response. The spatial distribution and extent of BOLD activity were unaffected by ISI, but modulations in peak amplitude and latency were observed. Non-linearities in both induced oscillatory activity ERS and in the signal averaged evoked response are found for ISIs of up to 2s when the signal averaged evoked response has returned to baseline, with the P35m component displaying paired pulse depression effects. The β-band ERS magnitude was modulated by ISI, however the ERD magnitude was not. These results support the assumption that BOLD non-linearity arises not only from a non-linear vascular response to neural activity but also a non-linear neural response to the stimulus with ISI up to 2 s.

Source localisation in concurrent EEG/fMRI: applications at 7T.

This paper investigates the application of source reconstruction methodologies to EEG data recorded in concurrent EEG/fMRI experiments at 7T. An EEG phantom containing a dipolar current source is described and used to investigate the accuracy of source localisation. Both dipole fitting and beamformer algorithms are shown to yield accurate locations for the dipole within the phantom. Source reconstruction methodologies are also shown to reduce significantly the level of interference in the recorded EEG, caused by the MR scanner. A comparison between beamformer and dipole fitting approaches is made and it is shown that, due to its adaptive weighting parameters, the beamformer provides better suppression of interference when compared to the dipole fit. In addition it is shown that, in the case of the beamformer, use of a high EEG channel density improves the level of interference reduction, and the ratio of measured signal to interference can be improved by a factor of approximately 1.6 if the number of EEG electrodes is increased from 32 to 64. The interference reduction properties of source localisation are shown theoretically, in simulation, and in phantom data. Finally, in-vivo experiments conducted at 7T show that effects in the gamma band can be recorded using simultaneous EEG/fMRI. These results are achieved by application of beamformer methodology to 64 channel EEG data.