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Arjan Hillebrand

Publications and source records attributed to Arjan Hillebrand.

18 recordsLinked to original sources
PubMed2005

The missing link: analogous human and primate cortical gamma oscillations.

Recent animal studies highlighting the relationship between functional imaging signals and the underlying neuronal activity have revealed the potential capabilities of non-invasive methods. However, the valuable exchange of information between animal and human studies remains restricted by the limited evidence of direct physiological links between species. In this study we used magnetoencephalography (MEG) to investigate the occurrence of 30-70 Hz (gamma) oscillations in human visual cortex, induced by the presentation of visual stimuli of varying contrast. These oscillations, well described in the animal literature, were observed in retinotopically concordant locations of visual cortex and show striking similarity to those found in primate visual cortex using surgically implanted electrodes. The amplitude of the gamma oscillations increases linearly with stimulus contrast in strong correlation with the gamma oscillations found in the local field potential (LFP) of the macaque. We demonstrate that non-invasive magnetic field measurements of gamma oscillations in human visual cortex concur with invasive measures of activation in primate visual cortex, suggesting both a direct representation of underlying neuronal activity and a concurrence between human and primate cortical activity.

Algorithms↗
PubMed2005

GLM-beamformer method demonstrates stationary field, alpha ERD and gamma ERS co-localisation with fMRI BOLD response in visual cortex.

Recently, we introduced a new 'GLM-beamformer' technique for MEG analysis that enables accurate localisation of both phase-locked and non-phase-locked neuromagnetic effects, and their representation as statistical parametric maps (SPMs). This provides a useful framework for comparison of the full range of MEG responses with fMRI BOLD results. This paper reports a 'proof of principle' study using a simple visual paradigm (static checkerboard). The five subjects each underwent both MEG and fMRI paradigms. We demonstrate, for the first time, the presence of a sustained (DC) field in the visual cortex, and its co-localisation with the visual BOLD response. The GLM-beamformer analysis method is also used to investigate the main non-phase-locked oscillatory effects: an event-related desynchronisation (ERD) in the alpha band (8-13 Hz) and an event-related synchronisation (ERS) in the gamma band (55-70 Hz). We show, using SPMs and virtual electrode traces, the spatio-temporal covariance of these effects with the visual BOLD response. Comparisons between MEG and fMRI data sets generally focus on the relationship between the BOLD response and the transient evoked response. Here, we show that the stationary field and changes in oscillatory power are also important contributors to the BOLD response, and should be included in future studies on the relationship between neuronal activation and the haemodynamic response.

Adult↗
PubMed2005

Assessing interactions of linear and nonlinear neuronal sources using MEG beamformers: a proof of concept.

OBJECTIVE: This study aimed to explore methods of assessing interactions between neuronal sources using MEG beamformers. However, beamformer methodology is based on the assumption of no linear long-term source interdependencies [VanVeen BD, vanDrongelen W, Yuchtman M, Suzuki A. Localization of brain electrical activity via linearly constrained minimum variance spatial filtering. IEEE Trans Biomed Eng 1997;44:867-80; Robinson SE, Vrba J. Functional neuroimaging by synthetic aperture magnetometry (SAM). In: Recent advances in Biomagnetism. Sendai: Tohoku University Press; 1999. p. 302-5]. Although such long-term correlations are not efficient and should not be anticipated in a healthy brain [Friston KJ. The labile brain. I. Neuronal transients and nonlinear coupling. Philos Trans R Soc Lond B Biol Sci 2000;355:215-36], transient correlations seem to underlie functional cortical coordination [Singer W. Neuronal synchrony: a versatile code for the definition of relations? Neuron 1999;49-65; Rodriguez E, George N, Lachaux J, Martinerie J, Renault B, Varela F. Perception's shadow: long-distance synchronization of human brain activity. Nature 1999;397:430-3; Bressler SL, Kelso J. Cortical coordination dynamics and cognition. Trends Cogn Sci 2001;5:26-36]. METHODS: Two periodic sources were simulated and the effects of transient source correlation on the spatial and temporal performance of the MEG beamformer were examined. Subsequently, the interdependencies of the reconstructed sources were investigated using coherence and phase synchronization analysis based on Mutual Information. Finally, two interacting nonlinear systems served as neuronal sources and their phase interdependencies were studied under realistic measurement conditions. RESULTS: Both the spatial and the temporal beamformer source reconstructions were accurate as long as the transient source correlation did not exceed 30-40 percent of the duration of beamformer analysis. In addition, the interdependencies of periodic sources were preserved by the beamformer and phase synchronization of interacting nonlinear sources could be detected. CONCLUSIONS: MEG beamformer methods in conjunction with analysis of source interdependencies could provide accurate spatial and temporal descriptions of interactions between linear and nonlinear neuronal sources. SIGNIFICANCE: The proposed methods can be used for the study of interactions between neuronal sources.

Brain↗
PubMed2005

A new approach to neuroimaging with magnetoencephalography.

We discuss the application of beamforming techniques to the field of magnetoencephalography (MEG). We argue that beamformers have given us an insight into the dynamics of oscillatory changes across the cortex not explored previously with traditional analysis techniques that rely on averaged evoked responses. We review several experiments that have used beamformers, with special emphasis on those in which the results have been compared to those observed in functional magnetic resonance imaging (fMRI) and on those studying induced phenomena. We suggest that the success of the beamformer technique, despite the assumption that there are no linear interactions between the mesoscopic local field potentials across distinct cortical areas, may tell us something of the balance between functional integration and segregation in the human brain. What is more, MEG beamformer analysis facilitates the study of these complex interactions within cortical networks that are involved in both sensory-motor and cognitive processes.

Algorithms↗
PubMed2005

Distinct contrast response functions in striate and extra-striate regions of visual cortex revealed with magnetoencephalography (MEG).

OBJECTIVE: To spatially and temporally characterise the cortical contrast response function to pattern onset stimuli in humans. METHODS: Magnetoencephalography (MEG) was used to investigate the human cortical contrast response function to pattern onset stimuli with high temporal and spatial resolution. A beamformer source reconstruction approach was used to spatially localise and identify the time courses of activity at various visual cortical loci. RESULTS: Consistent with the findings of previous studies, MEG beamformer analysis revealed two simultaneous generators of the pattern onset evoked response. These generators arose from anatomically discrete locations in striate and extra-striate visual cortex. Furthermore, these loci demonstrated notably distinct contrast response functions, with striate cortex increasing approximately linearly with contrast, whilst extra-striate visual cortex followed a saturating function. CONCLUSIONS: The generators that underlie the pattern onset visual evoked response arise from two distinct regions in striate and extra-striate visual cortex. SIGNIFICANCE: The spatially, temporally and functionally distinct mechanisms of contrast processing within the visual cortex may account for the disparate results observed across earlier studies and assist in elucidating causal mechanisms of aberrant contrast processing in neurological disorders.

Adult↗
PubMed2005

Real-time imaging of human cortical activity evoked by painful esophageal stimulation.

BACKGROUND & AIMS: Current models of visceral pain processing derived from metabolic brain imaging techniques fail to differentiate between exogenous (stimulus-dependent) and endogenous (non-stimulus-specific) neural activity. The aim of this study was to determine the spatiotemporal correlates of exogenous neural activity evoked by painful esophageal stimulation. METHODS: In 16 healthy subjects (8 men; mean age, 30.2 +/- 2.2 years), we recorded magnetoencephalographic responses to 2 runs of 50 painful esophageal electrical stimuli originating from 8 brain subregions. Subsequently, 11 subjects (6 men; mean age, 31.2 +/- 1.8 years) had esophageal cortical evoked potentials recorded on a separate occasion by using similar experimental parameters. RESULTS: Earliest cortical activity (P1) was recorded in parallel in the primary/secondary somatosensory cortex and posterior insula (approximately 85 ms). Significantly later activity was seen in the anterior insula (approximately 103 ms) and cingulate cortex (approximately 106 ms; P=.0001). There was no difference between the P1 latency for magnetoencephalography and cortical evoked potential (P=.16); however, neural activity recorded with cortical evoked potential was longer than with magnetoencephalography (P=.001). No sex differences were seen for psychophysical or neurophysiological measures. CONCLUSIONS: This study shows that exogenous cortical neural activity evoked by experimental esophageal pain is processed simultaneously in somatosensory and posterior insula regions. Activity in the anterior insula and cingulate-brain regions that process the affective aspects of esophageal pain-occurs significantly later than in the somatosensory regions, and no sex differences were observed with this experimental paradigm. Cortical evoked potential reflects the summation of cortical activity from these brain regions and has sufficient temporal resolution to separate exogenous and endogenous neural activity.

Adult↗
PubMed2004

Realistic spatial sampling for MEG beamformer images.

The spatial resolution achievable using magnetoencephalography (MEG) beamformer techniques is inhomogeneous across the brain and is related directly to the amplitude of the underlying electrical sources [Barnes and Hillebrand, Hum Brain Mapp 2003;18:1-12; Gross et al., Proc Natl Acad Sci USA 2001;98:694-699; Van Veen et al., IEEE Trans Biomed Eng 1997;44:867-860; Vrba and Robinson, Proc 12th Int Conf Biomagn 2001]. We set out to examine what an adequate level of spatial sampling of the brain volume is in a realistic situation, and what implications these inhomogeneities have for region-of-interest analysis. As a basis for these calculations, we used a simple retinotopic mapping experiment where stimuli were 17-Hz reversing gratings presented in either left or right visual hemifield. Beamformer weights were calculated based on the covariance of the MEG data in a 0-80 Hz bandwidth. We then estimated volumetric full-width half-maximum (FWHM) maps at a range of sampling levels. We show that approximately 10% of the 1 mm cubic voxels in the occipital volume have a FWHM smoothness of <5 mm, and 80% <10 mm in three subjects. This was despite relatively low mean signal-to-noise ratios (SNR) values of 1.5. We demonstrate how visualization of these FWHM maps can be used to avoid some of the pitfalls implicit in beamformer region-of-interest analysis.

Brain↗
PubMed2004

The temporal frequency tuning of human visual cortex investigated using synthetic aperture magnetometry.

Using synthetic aperture magnetometry (SAM) analyses of magnetoencephalographic (MEG) data, we investigated the variation in cortical response magnitude and frequency as a function of stimulus temporal frequency. In two separate experiments, a reversing checkerboard stimulus was used in the right or left lower visual field at frequencies from 0 to 21 Hz. Average temporal frequency tuning curves were constructed for regions-of-interest located within medial visual cortex and V5/MT. In medial visual cortex, it was found that both the frequency and magnitude of the steady-state response varied as a function of the stimulus frequency, with multiple harmonics of the stimulus frequency being found in the response. The maximum fundamental response was found at a stimulus frequency of 8 Hz, whilst the maximum broadband response occurred at 4 Hz. In contrast, the magnitude and frequency content of the evoked onset response showed no dependency on stimulus frequency. Whilst medial visual cortex showed a power increase during stimulation, extra-striate areas such as V5/MT exhibited a bilateral event-related desynchronisation (ERD). The frequency content of this ERD did not depend on the stimulus frequency but was a broadband power reduction across the 5-20 Hz frequency range. The magnitude of this ERD within V5/MT was strongly low-pass tuned for stimulus frequency, and showed only a moderate preference for stimuli in the contralateral visual field.

Adult↗
PubMed2004

Visual word recognition: the first half second.

We used magnetoencephalography (MEG) to map the spatiotemporal evolution of cortical activity for visual word recognition. We show that for five-letter words, activity in the left hemisphere (LH) fusiform gyrus expands systematically in both the posterior-anterior and medial-lateral directions over the course of the first 500 ms after stimulus presentation. Contrary to what would be expected from cognitive models and hemodynamic studies, the component of this activity that spatially coincides with the visual word form area (VWFA) is not active until around 200 ms post-stimulus, and critically, this activity is preceded by and co-active with activity in parts of the inferior frontal gyrus (IFG, BA44/6). The spread of activity in the VWFA for words does not appear in isolation but is co-active in parallel with spread of activity in anterior middle temporal gyrus (aMTG, BA 21 and 38), posterior middle temporal gyrus (pMTG, BA37/39), and IFG.

Adult↗
PubMed2004

A general linear model for MEG beamformer imaging.

A new general linear model (GLM) beamformer method is described for processing magnetoencephalography (MEG) data. A standard nonlinear beamformer is used to determine the time course of neuronal activation for each point in a predefined source space. A Hilbert transform gives the envelope of oscillatory activity at each location in any chosen frequency band (not necessary in the case of sustained (DC) fields), enabling the general linear model to be applied and a volumetric T statistic image to be determined. The new method is illustrated by a two-source simulation (sustained field and 20 Hz) and is shown to provide accurate localization. The method is also shown to locate accurately the increasing and decreasing gamma activities to the temporal and frontal lobes, respectively, in the case of a scintillating scotoma. The new method brings the advantages of the general linear model to the analysis of MEG data and should prove useful for the localization of changing patterns of activity across all frequency ranges including DC (sustained fields).

Algorithms↗
PubMed2004

Induced visual illusions and gamma oscillations in human primary visual cortex.

Using magnetoencephalography, we studied the spatiotemporal properties of cortical responses in terms of event-related synchronization and event-related desynchronization to a range of stripe patterns in subjects with no neurological disorders. These stripes are known for their tendency to induce a range of abnormal sensations, such as illusions, nausea, dizziness, headache and attacks of pattern-sensitive epilepsy. The optimal stimulus must have specific physical properties, and maximum abnormalities occur at specific spatial frequency and contrast. Despite individual differences in the severity of discomfort experienced, psychophysical studies have shown that most observers experience some degree of visual anomaly on viewing such patterns. In a separate experiment, subjects reported the incidence of illusions and discomfort to each pattern. We found maximal cortical power in the gamma range (30-60 Hz) confined to the region of the primary visual cortex in response to patterns of 2-4 cycles per degree, peaking at 3 cycles per degree. This coincides with the peak of mean illusions and discomfort, also maximal for patterns of 2-4 cycles per degree. We show that gamma band activity in V1 is a narrow band function of spatial frequency. We hypothesize that the intrinsic properties of gamma oscillations may underlie visual discomfort and play a role in the onset of seizures.

Adult↗
PubMed2004

Spatio-temporal imaging of cortical desynchronization in migraine visual aura: a magnetoencephalography case study.

OBJECTIVE: To determine cortical oscillatory changes involved in migraine visual aura using magnetoencephalography (MEG). BACKGROUND: Visual aura in the form of scintillating scotoma precedes migraine in many cases. The involvement of cortical spreading depression within striate and extra-striate cortical areas is implicated in the generation of the disturbance, but the details of its progression, the effects on cortical oscillations, and the mechanisms of aura generation are unclear. METHODS: We used MEG to directly image changes in cortical oscillatory power during an episode of scintillating scotoma in a patient who experiences aura without subsequent migraine headache. Using the synthetic aperture magnetometry method of MEG source imaging, focal changes in cortical oscillatory power were observed over a 20-minute period and visualized in coregistration with the patient's magnetic resonance image. RESULTS: Alpha band desynchronization in both the left extra-striate and temporal cortex persisted for the duration of reported visual disturbance, terminating abruptly upon disappearance of scintillations. Gamma frequency desynchronization in the left temporal lobe continued for 8 to 10 minutes following the reported end of aura. CONCLUSIONS: Observations implicate the extra-striate and temporal cortex in migraine visual aura and suggest involvement of alpha desynchronization in generation of phosphenes and gamma desynchronization in sustained inhibition of visual function.

Cortical Synchronization↗
PubMed2003

Statistical flattening of MEG beamformer images.

We propose a method of correction for multiple comparisons in MEG beamformer based Statistical Parametric Maps (SPMs). We introduce a modification to the minimum-variance beamformer, in which beamformer weights and SPMs of source-power change are computed in distinct steps. This approach allows the calculation of image smoothness based on the computed weights alone. In the first instance we estimate image smoothness by looking at local spatial correlations in residual images generated using random data; we then go on to show how the smoothness of the SPM can be obtained analytically by measuring the correlations between the adjacent weight vectors. In simulations we show that the smoothness of the SPM is highly inhomogeneous and depends on the source strength. We show that, for the minimum variance beamformer, knowledge of image smoothness is sufficient to allow for correction of the multiple comparison problem. Per-voxel threshold estimates, based on the voxels extent (or cluster size) in flattened space, provide accurate corrected false positive error rates for these highly inhomogeneously smooth images.

Algorithms↗
PubMed2003

Accuracy and applications of group MEG studies using cortical source locations estimated from participants' scalp surfaces.

We contend that powerful group studies can be conducted using magnetoencephalography (MEG), which can provide useful insights into the approximate distribution of the neural activity detected with MEG without requiring magnetic resonance imaging (MRI) for each participant. Instead, a participant's MRI is approximated with one chosen as a best match on the basis of the scalp surface from a database of available MRIs. Because large inter-individual variability in sulcal and gyral patterns is an inherent source of blurring in studies using grouped functional activity, the additional error introduced by this approximation procedure has little effect on the group results, and offers a sufficiently close approximation to that of the participants to yield a good indication of the true distribution of the grouped neural activity. T1-weighted MRIs of 28 adults were acquired in a variety of MR systems. An artificial functional image was prepared for each person in which eight 5 x 5 x 5 mm regions of brain activation were simulated. Spatial normalisation was applied to each image using transformations calculated using SPM99 with (1) the participant's actual MRI, and (2) the best matched MRI substituted from those of the other 27 participants. The distribution of distances between the locations of points using real and substituted MRIs had a modal value of 6 mm with 90% of cases falling below 12.5 mm. The effects of this approach on real grouped SAM source imaging of MEG data in a verbal fluency task are also shown. The distribution of MEG activity in the estimated average response is very similar to that produced when using the real MRIs.

Adult↗
PubMed2003

The use of anatomical constraints with MEG beamformers.

Synthetic Aperture Magnetometry (SAM) is a beamformer approach for the localisation of neuronal activity from EEG/MEG data. SAM estimates the optimum orientation of each source in a predefined source space by a nonlinear search for the orientation that maximises the beamformer output. However, MEG is most sensitive to cortical sources and these sources are generally oriented perpendicular to the surface. The reconstructed neuronal activity can therefore reasonably be constrained to the cortical surface, orientated perpendicular to it, therefore removing the search for the optimum orientation for the computation of the beamformer weights. This paper sets out to compare the performance of a constrained and unconstrained beamformer (SAM), with respect to the localisation accuracy of the source reconstructions and the spatial resolution. Fifty sources were randomly placed on a cortical surface estimated from an MRI, and we simulated data over a range of different signal-to-noise ratios (SNRs) for each source. These datasets were analysed using both an unconstrained beamformer (SAM) and a constrained beamformer (with the sources orientated perpendicular to the cortical surface). The influence of errors in the estimation of the surface location and surface normals on the performance of the constrained beamformer, representing MEG/MRI coregistration and segmentation errors, were also examined. The spatial resolution of the beamformer improves, typically by a factor of four by applying anatomical constraints, and the localisation accuracy improves marginally. However, the advantage in spatial resolution disappears when errors are introduced into the orientation and location constraints, and, moreover, the localisation accuracy of the inaccurately constrained beamformer degrades rapidly. We conclude that the use of anatomical constraints is only advantageous if the MEG/MRI coregistration error is smaller than 2 mm and the error in the estimation of the cortical surface orientation is smaller than 10 degrees.

Algorithms↗
PubMed2003

Group imaging of task-related changes in cortical synchronisation using nonparametric permutation testing.

Synthetic aperture magnetometry (SAM) is a nonlinear beamformer technique for producing 3D images of cortical activity from magnetoencephalography data. We have previously shown how SAM images can be spatially normalised and averaged to form a group image. In this paper we show how nonparametric permutation methods can be used to make robust statistical inference about group SAM data. Data from a biological motion direction discrimination experiment were analysed using both a nonparametric analysis toolbox (SnPM) and a conventional parametric approach utilising Gaussian field theory. In data from a group of six subjects, we were able to show robust group activation at the P < 0.05 (corrected) level using the nonparametric methods, while no significant clusters were found using the conventional parametric approach. Activation was found using SnPM in several regions of right occipital-temporal cortex, including the superior temporal sulcus, V5/MT, the fusiform gyrus, and the lateral occipital complex.

Adult↗
PubMed2002

Task-related changes in cortical synchronization are spatially coincident with the hemodynamic response.

Using group functional Magnetic Resonance Imaging (fMRI) and group Magnetoencephalography (MEG) we studied two cognitive paradigms: A language task involving covert letter fluency and a visual task involving biological motion direction discrimination. The MEG data were analyzed using an adaptive beam-former technique known as Synthetic Aperture Magnetometry (SAM), which provides continuous 3-D images of cortical power changes. These images were spatially normalized and averaged across subjects to provide a group SAM image in the same template space as the group fMRI data. The results show that frequency-specific, task-related changes in cortical synchronization, detected using MEG, match those areas of the brain showing an evoked cortical hemodynamic response with fMRI. The majority of these changes were event-related desynchronizations (ERDs) in the 5-10 Hz and 15-25 Hz frequency ranges. Our study demonstrates how SAM, spatial normalization, and intersubject averaging enable group MEG studies to be performed. SAM analysis also allows the MEG experiment to have exactly the same task design as the corresponding fMRI experiment. This new analysis framework represents an important advance in the use of MEG as a cognitive neuroimaging technique and also allows mutual cross-validation with fMRI.

Adult↗