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. © 2005 Elsevier Inc. All rights reserved.

A brief review of magnetic fields from the human visual system

Both the eye and brain generate magnetic fields when stimulated with a variety of visual cues. These magnetic fields can be measured with a magnetometer; a device which uses superconducting technology. The application of this technique to measuring the magnetooculogram, magnetoretinogram and visually evoked fields from the brain is described. So far the main use of this technique has been in pure research. Its potential for diagnosing ocular and neurological diseases is discussed.

The effects of vigabatrin of the visual system

This thesis considers the visual electrophysiological effects of vigabatrin (an anti-epileptic drug, which acts by increasing the levels of the inhibitory neurotransmitter GABA on the retina of the eye compared to the concentric visual field defects which have been found associated with the drug. Flash and pattern ERG's, EOG's multifocal ERG's (VERIS), flash and pattern VEP's and visual fields were tested. Although VEP's have been shown not to be affected by vigabatrin, these were recorded to complete the testing. Initially, of the eight vigabatrin patients with known visual field defects, 7 showed abnormally delayed 30Hz flicker a-wave latencies, 5 abnormally delayed 30Hz b-wave latencies and 6 abnormally low 30Hz amplitudes. Also 7 showed an abnormally prolonged latency of oscillatory potential 1 (OP1). The two patients taking vigabatrin at the time of testing showed low EOG Arden index values. The VERIS results correlated well with the severity of the visual field defects. Following this finding, eleven healthy subjects received vigabatrin over a 10-day period. No changes were seen in the visual fields, however, the photopic ERG b-wave latency significantly increased (although not to abnormal values). A matched pairs study with eleven vigabatrin, patients and eleven epileptic patients, who had never taken vigabatrin supported the findings of abnormal 30Hz flicker b-wave and OP latencies associated with vigabatrin, again with the VERIS results correlating to the severity of the visual field defect. The abnormal 30Hz flicker and VERIS responses indicate involvement of the cone photoreceptors and the OP's show an effect on the amacrine cells. The ERG increase in the photopic b-wave latency also suggests involvement of the bipolar cells, however, this effect and the reversible effect on the Arden index after cessation of the drug may be unrelated to the visual field defect. To conclude this thesis, a field specific VEP stimulus was developed to assess the retinal function in the peripheral field of paediatric patients. It comprises of a dartboard stimulus with a central 0-5 degree black and white chequered stimulus, a blank 5-30 degree annulus and a 30-60 degree peripheral chequered stimulus. When optimised on four vigabatrin patients it was found that no peripheral response can be evoked with a field loss exceeding 30-35 degrees. Co-operation was found to be successful in children as young as four years old.

The development of calibration and adaptive filtering procedures for neuromagnetic studies of human visual function

This thesis first considers the calibration and signal processing requirements of a neuromagnetometer for the measurement of human visual function. Gradiometer calibration using straight wire grids is examined and optimal grid configurations determined, given realistic constructional tolerances. Simulations show that for gradiometer balance of 1:104 and wire spacing error of 0.25mm the achievable calibration accuracy of gain is 0.3%, of position is 0.3mm and of orientation is 0.6°. Practical results with a 19-channel 2nd-order gradiometer based system exceed this performance. The real-time application of adaptive reference noise cancellation filtering to running-average evoked response data is examined. In the steady state, the filter can be assumed to be driven by a non-stationary step input arising at epoch boundaries. Based on empirical measures of this driving step an optimal progression for the filter time constant is proposed which improves upon fixed time constant filter performance. The incorporation of the time-derivatives of the reference channels was found to improve the performance of the adaptive filtering algorithm by 15-20% for unaveraged data, falling to 5% with averaging. The thesis concludes with a neuromagnetic investigation of evoked cortical responses to chromatic and luminance grating stimuli. The global magnetic field power of evoked responses to the onset of sinusoidal gratings was shown to have distinct chromatic and luminance sensitive components. Analysis of the results, using a single equivalent current dipole model, shows that these components arise from activity within two distinct cortical locations. Co-registration of the resulting current source localisations with MRI shows a chromatically responsive area lying along the midline within the calcarine fissure, possibly extending onto the lingual and cuneal gyri. It is postulated that this area is the human homologue of the primate cortical area V4.

Neuro-electromagnetic imaging of the human visual cortex

Methods of solving the neuro-electromagnetic inverse problem are examined and developed, with specific reference to the human visual cortex. The anatomy, physiology and function of the human visual system are first reviewed. Mechanisms by which the visual cortex gives rise to external electric and magnetic fields are then discussed, and the forward problem is described mathematically for the case of an isotropic, piecewise homogeneous volume conductor, and then for an anisotropic, concentric, spherical volume conductor. Methods of solving the inverse problem are reviewed, before a new technique is presented. This technique combines prior anatomical information gained from stereotaxic studies, with a probabilistic distributed-source algorithm to yield accurate, realistic inverse solutions. The solution accuracy is enhanced by using both visual evoked electric and magnetic responses simultaneously. The numerical algorithm is then modified to perform equivalent current dipole fitting and minimum norm estimation, and these three techniques are implemented on a transputer array for fast computation. Due to the linear nature of the techniques, they can be executed on up to 22 transputers with close to linear speedup. The latter part of the thesis describes the application of the inverse methods to the analysis of visual evoked electric and magnetic responses. The CIIm peak of the pattern onset evoked magnetic response is deduced to be a product of current flowing away from the surface areas 17, 18 and 19, while the pattern reversal P100m response originates in the same areas, but from oppositely directed current. Cortical retinotopy is examined using sectorial stimuli, the CI and CIm ;peaks of the pattern onset electric and magnetic responses are found to originate from areas V1 and V2 simultaneously, and they therefore do not conform to a simple cruciform model of primary visual cortex.

The visually evoked magnetic response (VEMR) to a pattern onset/offset stimulus

This study characterizes the visually evoked magnetic response (VEMR) to pattern onset/offset stimuli, using a single channel BTi magnetometer. The influence of stimulus parameters and recording protocols on the VEMR is studied with inferences drawn about the nature of cortical processing, its origins and optimal recording strategies. Fundamental characteristics are examined, such as the behaviour of successive averaged and unaveraged responses; the effects of environmental shielding; averaging; inter- and intrasubject variability and equipment specificity. The effects of varying check size, field size, contrast and refractive error on latency, amplitude and topographic distribution are also presented. Latency and amplitude trends are consistent with previous VEP findings and known anatomical properties of the visual system. Topographic results are consistent with the activity of sources organised according to the cruciform model of striate cortex. A striate origin for the VEMR is also suggested by the results to quarter, octant and annulus field stimuli. Similarities in the behaviour and origins of the sources contributing to the CIIm and CIIIm onset peaks are presented for a number of stimulus conditions. This would be consistent with differing processing event in the same, or similar neuronal populations. Focal field stimuli produce less predictable responses than full or half fields, attributable to a reduced signal to noise ratio and an increased sensitivity to variations in cortical morphology. Problems with waveform peak identification are encountered for full field stimuli that can only be resolved by the careful choice of stimulus parameters, comparisons with half field responses or with reference to the topographic distribution of each waveform peak. An anatomical study of occipital lobe morphology revealed large inter- and intrasubject variation in calcarine fissure shape and striate cortex distribution. An appreciation of such variability is important for VEMR interpretation, due to the technique's sensitivity to source depth and orientation, and it is used to explain the experimental results obtained.

Neuromagnetic investigations of functional organisation within human visual cortex

This thesis describes a series of experimental investigations into the functional organisation of human visual cortex using neuromagnetometry.This technique combines good spatial and temporal resolution enabling identification of the location and temporal response characteristics of cortical neurones within alert humans. To activate different neuronal populations and cortical areas a range of stimuli were used, the parameters of which were selected to match the known physiological properties of primate cortical neurones. In one series of experiments the evoked magnetic response was recorded to isoluminant red/green gratings. Co-registration of signal and magnetic resonance image data indicated a contribution to the response from visual areas V1, V2 and V4. To investigate the spatio-temporal characteristics of neurones within area V1 the evoked response was recorded for a range of stimulus spatial and temporal frequencies. The response to isoluminant red/green gratings was dominated by a major component which was found to have bandpass spatial frequency tuning with a peak at 1-2 cycles/degree, falling to the level of the noise at 6-8 cycles/degree. The temporal frequency tuning characteristics of the response showed bimodal sensitivity with peaks at 0-1Hz and 4Hz. In a further series of experiments the luminance evoked response was recorded to red/black, yellow/black and achromatic gratings and in all cases was found to be more complex than the isoluminant chromatic response, comprising up to three distinct components. The major response peak showed bandpass spatial frequency tuning characteristics, peaking at 6-8 cycles/degree, falling to the level of the noise at 12-16 cycles/degree. The results provide evidence to suggest that within area V1 the same neuronal population encodes both chromatic and luminance information and has spatial frequency tuning properties consistent with single-opponent cells. Furthermore, the results indicate that cells within area V1 encode chromatic motion information over a wide range of temporal frequencies with temporal response characteristics suggestive of the existence of a sub-population of cells sensitive to high temporal frequencies.

The development of the visual system in pre-term infants as assessed by electrophysiological techniques

In an endeavour to provide further insight into the maturation of the human visual system, the contiguous development of the pattern reversal VEP, flash VEP and flash ERG was studied in a group of neurologically normal pre-term infants, born between 28 and 35 weeks gestation. Maturational changes were observed in all the evoked electrophysiological responses recorded, these were mainly characterised by an increase in the complexity of the waveform and a shortening in the latency of the response. Initially the ERG was seen to consist of a broad b-wave only, with the a-wave emerging at an average age of 40 weeks PMA. The a-wave showed only a slight reduction in latency and a modest increase in amplitude as the infant grows older, whereas the changes seen in the ERG b-wave were much more dramatic. Pattern reversal VEPs were successfully recorded for the first time during the pre-term period. Flash VEPs were also recorded for comparison. The neonatal pattern reversal VEP consistently showed a major positive component (P1) of long latency. As the infant grew older, the latency of the P1 component decreased and was found to be negatively correlated with PMA at recording. The appearance of the N1 and N2 components became more frequent as the infant matured. The majority of infants were found to be myopic at birth and refractive error was correlated with PMA, with emmetropisation occurring at about 45 weeks PMA. The pattern reversal VEP in response to 2o checks was apparently unaffected by refractive error.

The investigation of oscillatory changes in the visual cortex using synthetic aperture magnetometry

This thesis is an exploration of the oscillatory changes occurring in the visual cortex as measured by a functional imaging technique known as Synthetic Aperture Magnetometry (SAM), and how these compare to the BOLD response, across a number of different experimental paradigms. In chapter one the anatomy and physiology of the visual pathways and cortex are outlined, introducing the reader to structures and terms used throughout the thesis whilst chapter two introduces both the technology and analysis techniques required to record MEG and fMRI and also outlines the theory behind SAM. In chapter three the temporal frequency tuning of both striate and extrastriate cortex is investigated, showing fundamental differences in both tuning characteristics and oscillatory power changes between the two areas. Chapter four introduces the concept of implied-motion and investigates the role of area V5 / MT in the perception of such stimuli and shows, for the first time, the temporal evolution of the response in this area. Similarly a close link is shown between the early evoked potential, produced by the stimulus, and previous BOLD responses. Chapter five investigates the modulation of cortical oscillations to both shifts in attention and varying stimulus contrast. It shows that there are both induced and evoked modulation changes with attention, consistent with areas previously known to show BOLD responses. Chapter six involves a direct comparison of cortical oscillatory changes with those of the BOLD response in relation to the parametric variation of a motion coherence stimulus. It is shown that various cortical areas show a linear BOLD response to motion coherence and, for the first time, that both induced oscillatory and evoked activity also vary linearly in areas coincidental with the BOLD response. The final chapter is a summary of the main conclusions and suggests further work.

Studies on the luminance-related characteristics of the transient pattern reversal electroretinogram

The electroretinogram evoked by reversal pattern stimulation (rPERG) is known to contain both pattern contrast and luminance related components. The retinal mechanisms of the transient rPERGs subserving these functional characteristics are the main concern in the present studies. Considerable attention has been paid to the luminance-related characteristics of the response. The transient PERGs were found to consist of two subsequent processes using low frequency attenuation analysis. The processes overlapped and the individual difference in each process timings formed the major cause for the variations of the negative potential waveform of the transient rPERGs. Attention has been paid to those having ‘notch’ type of variation. Under different contrast levels, the amplitudes of the positive and negative potentials were linearly increased with higher contrast level and the negative potential showed a higher sensitivity to contrast changes and higher contrast gain. Under lower contrast levels, the decreased amplitudes made the difference in the timing course of the positive and negative processes evident, interpreting the appearance of the notch in some cases. Visual adaptation conditions for recording the transient rPERG were discussed. Another effort was to study the large variation of the transient rPERGs (especially the positive potential, P50) in the elderly who’s distant and near visual acuity were normal. It was found that reduction of retinal illumination contributed mostly to the P50 amplitude loss and contrast loss mostly to the negative potential (N95) amplitude loss. Senile miosis was thought to have little effect on the reduction of the retinal illumination, while the changes in the optics of the eye was probably the major cause for it, which interpreted the larger individual variation of the P50 amplitude of the elderly PERGs. Convex defocus affected the transient rPERGs more effectively than concave lenses, especially the N95 amplitude in the elderly. The disability of accommodation and the type and the degree of subjects’ ametropia should be taken into consideration when the elderly rPERGs were analysed.

Which physiological components are more suitable for visual ERP based brain-computer interface?:A preliminary MEG/EEG study

We investigated which evoked response component occurring in the first 800 ms after stimulus presentation was most suitable to be used in a classical P300-based brain-computer interface speller protocol. Data was acquired from 275 Magnetoencephalographic sensors in two subjects and from 61 Electroencephalographic sensors in four. To better characterize the evoked physiological responses and minimize the effect of response overlap, a 1000 ms Inter Stimulus Interval was preferred to the short (

Abnormal visual habituation in pediatric photosensitive epilepsy

Objective - To investigate visual habituation – a measure of visual cortical excitability – in photosensitive patients in pediatric age and compare the findings with a matched sample with idiopathic generalized epilepsies without photosensitivity and with normally developing children. Methods - We presented a full-field black-and-white checkerboard pattern, at 3 reversal/s with 100% contrast binocularly for 600 consecutive trials and measured the N75–P100 and P100–N145 pattern-reversal visual evoked potential inter-peak amplitudes and N75, P100, N145 latencies for the six blocks of 100 responses. As a measure of habituation we used the slope of the linear regression line of the N75–P100 and P100–N145 peak-to-peak amplitudes. The slope of the linear regression line of the N75–P100 and P100–N145 latencies was also analyzed. Results - Statistical analysis revealed significant differences between the three groups in the slope index of N75–P100 PR-VEP amplitude, with increased or constant amplitude in the PS group compare to the IGE and ND across the six blocks. Conclusions - Our results support the notion that photosensitivity is associated with altered control of excitatory and inhibitory cortical processes. The causal relationship between habituation deficit and photo-paroxysmal response needs to be further investigated with longitudinal studies. Significance This study supports the hypothesis that suppression of PR-VEP is a sensitive intermediate phenotype, which discriminates patients with photosensitivity from those with generalized epilepsies in pediatric age.

Ingroup categorization affects the structural encoding of other-race faces:evidence from the N170 event-related potential

The current research examined the influence of ingroup/outgroup categorization on brain event-related potentials measured during perceptual processing of own- and other-race faces. White participants performed a sequential matching task with upright and inverted faces belonging either to their own race (White) or to another race (Black) and affiliated with either their own university or another university by a preceding visual prime. Results demonstrated that the right-lateralized N170 component evoked by test faces was modulated by race and by social category: the N170 to own-race faces showed a larger inversion effect (i.e., latency delay for inverted faces) when the faces were categorized as other-university rather than own-university members; the N170 to other-race faces showed no modulation of its inversion effect by university affiliation. These results suggest that neural correlates of structural face encoding (as evidenced by the N170 inversion effects) can be modulated by both visual (racial) and nonvisual (social) ingroup/outgroup status. © 2014 © 2014 Taylor & Francis.

Local Field Potentials in the Gustatory Cortex Carry Taste Information

It has been recently shownthat localfield potentials (LFPs)fromthe auditory and visual cortices carry information about sensory stimuli, but whether this is a universal property of sensory cortices remains to be determined. Moreover, little is known about the temporal dynamics of sensory information contained in LFPs following stimulus onset. Here we investigated the time course of the amount of stimulus information in LFPs and spikes from the gustatory cortex of awake rats subjected to tastants and water delivery on the tongue. We found that the phase and amplitude of multiple LFP frequencies carry information about stimuli, which have specific time courses after stimulus delivery. The information carried by LFP phase and amplitude was independent within frequency bands, since the joint information exhibited neither synergy nor redundancy. Tastant information in LFPs was also independent and had a different time course from the information carried by spikes. These findings support the hypothesis that the brain uses different frequency channels to dynamically code for multiple features of a stimulus.

Local Field Potentials in the Gustatory Cortex Carry Taste Information

It has been recently shownthat localfield potentials (LFPs)fromthe auditory and visual cortices carry information about sensory stimuli, but whether this is a universal property of sensory cortices remains to be determined. Moreover, little is known about the temporal dynamics of sensory information contained in LFPs following stimulus onset. Here we investigated the time course of the amount of stimulus information in LFPs and spikes from the gustatory cortex of awake rats subjected to tastants and water delivery on the tongue. We found that the phase and amplitude of multiple LFP frequencies carry information about stimuli, which have specific time courses after stimulus delivery. The information carried by LFP phase and amplitude was independent within frequency bands, since the joint information exhibited neither synergy nor redundancy. Tastant information in LFPs was also independent and had a different time course from the information carried by spikes. These findings support the hypothesis that the brain uses different frequency channels to dynamically code for multiple features of a stimulus.