Investigating the functional properties of the somatosensory cortex during experimental visceral pain using magnetoencephalography

Background The somatosensory cortex has been inconsistently activated in pain studies and the functional properties of subregions within this cortical area are poorly understood. To address this we used magnetoencephalography (MEG), a brain imaging technique capable of recording changes in cortical neural activity in real-time, to investigate the functional properties of the somatosensory cortex during different phases of the visceral pain experience. Methods In eight participants (4 male), 151-channel whole cortex MEG was used to detect cortical neural activity during 25 trials lasting 20 seconds each. Each trial comprised four separate periods of 5 seconds in duration. During each of the periods, different visual cues were presented, indicating that period 1=rest, period 2=anticipation, period 3=pain and period 4=post pain. During period 3, participants received painful oesophageal balloon distensions (four at 1 Hz). Regions of cortical activity were identified using Synthetic Aperture Magnetometry (SAM) and by the placement of virtual electrodes in regions of interest within the somatosensory cortex, time-frequency wavelet plots were generated. Results SAM analysis revealed significant activation with the primary (S1) and secondary (S2) somatosensory cortices. The time-frequency wavelet spectrograms showed that activation in S1 increased during the anticipation phase and continued during the presentation of the stimulus. In S2, activation was tightly time and phase-locked to the stimulus within the pain period. Activations in both regions predominantly occurred within the 10–15 Hz and 20–30 Hz frequency bandwidths. Discussion These data are consistent with the role of S1 and S2 in the sensory discriminatory aspects of pain processing. Activation of S1 during anticipation and then pain may be linked to its proposed role in attentional as well as sensory processing. The stimulus-related phasic activity seen in S2 demonstrates that this region predominantly encodes information pertaining to the nature and intensity of the stimulus.

Dissociating the spatio-temporal characteristics of cortical neuronal activity associated with human volitional swallowing in the healthy adult brain

Human swallowing represents a complex highly coordinated sensorimotor function whose functional neuroanatomy remains incompletely understood. Specifically, previous studies have failed to delineate the temporo-spatial sequence of those cerebral loci active during the differing phases of swallowing. We therefore sought to define the temporal characteristics of cortical activity associated with human swallowing behaviour using a novel application of magnetoencephalography (MEG). In healthy volunteers (n = 8, aged 28-45), 151-channel whole cortex MEG was recorded during the conditions of oral water infusion, volitional wet swallowing (5 ml bolus), tongue thrust or rest. Each condition lasted for 5 s and was repeated 20 times. Synthetic aperture magnetometry (SAM) analysis was performed on each active epoch and compared to rest. Temporal sequencing of brain activations utilised time-frequency wavelet plots of regions selected using virtual electrodes. Following SAM analysis, water infusion preferentially activated the caudolateral sensorimotor cortex, whereas during volitional swallowing and tongue movement, the superior sensorimotor cortex was more strongly active. Time-frequency wavelet analysis indicated that sensory input from the tongue simultaneously activated caudolateral sensorimotor and primary gustatory cortex, which appeared to prime the superior sensory and motor cortical areas, involved in the volitional phase of swallowing. Our data support the existence of a temporal synchrony across the whole cortical swallowing network, with sensory input from the tongue being critical. Thus, the ability to non-invasively image this network, with intra-individual and high temporal resolution, provides new insights into the brain processing of human swallowing. © 2004 Elsevier Inc. All rights reserved.

Spatio-temporal imaging of corticaldesynchronization 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.

Neuroimaging in human amblyopia

Functional magnetic resonance imaging (fMRI), positron emission tomography (PET) and magnetoencephalography (MEG) have been the principal neuroimaging tools used to assess the site and nature of cortical deficits in human amblyopia. A review of this growing body of work is presented here with particular reference to various controversial issues, including whether or not the primary visual cortex is dysfunctional, the involvement of higher-order visual areas, neural differences between strabismic and anisometropic amblyopes, and the effects of modern-day drug treatments. We also present our own recent MEG work in which we used the analysis technique of synthetic aperture magnetometry (SAM) to examine the effects of strabismic amblyopia on cortical function. Our results provide evidence that the neuronal assembly associated with form perception in the extrastriate cortex may be dysfunctional in amblyopia, and that the nature of this dysfunction may relate to a change in the normal temporal pattern of neuronal discharges. Based on these results and existing literature, we conclude that a number of cortical areas show reduced levels of activation in amblyopia, including primary and secondary visual areas and regions within the parieto-occipital cortex and ventral temporal cortex. Copyright © 2006 Taylor & Francis Group, LLC.

Functional source separation applied to induced visual gamma activity

Objective of this work was to explore the performance of a recently introduced source extraction method, FSS (Functional Source Separation), in recovering induced oscillatory change responses from extra-cephalic magnetoencephalographic (MEG) signals. Unlike algorithms used to solve the inverse problem, FSS does not make any assumption about the underlying biophysical source model; instead, it makes use of task-related features (functional constraints) to estimate source/s of interest. FSS was compared with blind source separation (BSS) approaches such as Principal and Independent Component Analysis, PCA and ICA, which are not subject to any explicit forward solution or functional constraint, but require source uncorrelatedness (PCA), or independence (ICA). A visual MEG experiment with signals recorded from six subjects viewing a set of static horizontal black/white square-wave grating patterns at different spatial frequencies was analyzed. The beamforming technique Synthetic Aperture Magnetometry (SAM) was applied to localize task-related sources; obtained spatial filters were used to automatically select BSS and FSS components in the spatial area of interest. Source spectral properties were investigated by using Morlet-wavelet time-frequency representations and significant task-induced changes were evaluated by means of a resampling technique; the resulting spectral behaviours in the gamma frequency band of interest (20-70 Hz), as well as the spatial frequency-dependent gamma reactivity, were quantified and compared among methods. Among the tested approaches, only FSS was able to estimate the expected sustained gamma activity enhancement in primary visual cortex, throughout the whole duration of the stimulus presentation for all subjects, and to obtain sources comparable to invasively recorded data.

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. © 2005 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

The spatial distribution and temporal dynamics of brain regions activated during the perception of object and non-object patterns

Both animal and human studies suggest that the efficiency with which we are able to grasp objects is attributable to a repertoire of motor signals derived directly from vision. This is in general agreement with the long-held belief that the automatic generation of motor signals by the perception of objects is based on the actions they afford. In this study, we used magnetoencephalography (MEG) to determine the spatial distribution and temporal dynamics of brain regions activated during passive viewing of object and non-object targets that varied in the extent to which they afforded a grasping action. Synthetic Aperture Magnetometry (SAM) was used to localize task-related oscillatory power changes within specific frequency bands, and the time course of activity within given regions-of-interest was determined by calculating time-frequency plots using a Morlet wavelet transform. Both single subject and group-averaged data on the spatial distribution of brain activity are presented. We show that: (i) significant reductions in 10-25 Hz activity within extrastriate cortex, occipito-temporal cortex, sensori-motor cortex and cerebellum were evident with passive viewing of both objects and non-objects; and (ii) reductions in oscillatory activity within the posterior part of the superior parietal cortex (area Ba7) were only evident with the perception of objects. Assuming that focal reductions in low-frequency oscillations (< 30 Hz) reflect areas of heightened neural activity, we conclude that: (i) activity within a network of brain areas, including the sensori-motor cortex, is not critically dependent on stimulus type and may reflect general changes in visual attention; and (ii) the posterior part of the superior parietal cortex, area Ba7, is activated preferentially by objects and may play a role in computations related to grasping. © 2006 Elsevier Inc. All rights reserved.

Magnetoencephalography:technical improvements in image co-registration and studies of visual cortical oscillations

The work presented in this thesis is divided into two distinct sections. In the first, the functional neuroimaging technique of Magnetoencephalography (MEG) is described and a new technique is introduced for accurate combination of MEG and MRI co-ordinate systems. In the second part of this thesis, MEG and the analysis technique of SAM are used to investigate responses of the visual system in the context of functional specialisation within the visual cortex. In chapter one, the sources of MEG signals are described, followed by a brief description of the necessary instrumentation for accurate MEG recordings. This chapter is concluded by introducing the forward and inverse problems of MEG, techniques to solve the inverse problem, and a comparison of MEG with other neuroimaging techniques. Chapter two provides an important contribution to the field of research with MEG. Firstly, it is described how MEG and MRI co-ordinate systems are combined for localisation and visualisation of activated brain regions. A previously used co-registration methods is then described, and a new technique is introduced. In a series of experiments, it is demonstrated that using fixed fiducial points provides a considerable improvement in the accuracy and reliability of co-registration. Chapter three introduces the visual system starting from the retina and ending with the higher visual rates. The functions of the magnocellular and the parvocellular pathways are described and it is shown how the parallel visual pathways remain segregated throughout the visual system. The structural and functional organisation of the visual cortex is then described. Chapter four presents strong evidence in favour of the link between conscious experience and synchronised brain activity. The spatiotemporal responses of the visual cortex are measured in response to specific gratings. It is shown that stimuli that induce visual discomfort and visual illusions share their physical properties with those that induce highly synchronised gamma frequency oscillations in the primary visual cortex. Finally chapter five is concerned with localization of colour in the visual cortex. In this first ever use of Synthetic Aperture Magnetometry to investigate colour processing in the visual cortex, it is shown that in response to isoluminant chromatic gratings, the highest magnitude of cortical activity arise from area V2.

Development and application of magnetoencephalographic methods in the investigation of the human visual system

This thesis is an exploration of the organisation and functioning of the human visual system using the non-invasive functional imaging modality magnetoencephalography (MEG). Chapters one and two provide an introduction to the ‘human visual system and magnetoencephalographic methodologies. These chapters subsequently describe the methods by which MEG can be used to measure neuronal activity from the visual cortex. Chapter three describes the development and implementation of novel analytical tools; including beamforming based analyses, spectrographic movies and an optimisation of group imaging methods. Chapter four focuses on the use of established and contemporary analytical tools in the investigation of visual function. This is initiated with an investigation of visually evoked and induced responses; covering visual evoked potentials (VEPs) and event related synchronisation/desynchronisation (ERS/ERD). Chapter five describes the employment of novel methods in the investigation of cortical contrast response and demonstrates distinct contrast response functions in striate and extra-striate regions of visual cortex. Chapter six use synthetic aperture magnetometry (SAM) to investigate the phenomena of visual cortical gamma oscillations in response to various visual stimuli; concluding that pattern is central to its generation and that it increases in amplitude linearly as a function of stimulus contrast, consistent with results from invasive electrode studies in the macaque monkey. Chapter seven describes the use of driven visual stimuli and tuned SAM methods in a pilot study of retinotopic mapping using MEG; finding that activity in the primary visual cortex can be distinguished in four quadrants and two eccentricities of the visual field. Chapter eight is a novel implementation of the SAM beamforming method in the investigation of a subject with migraine visual aura; the method reveals desynchronisation of the alpha and gamma frequency bands in occipital and temporal regions contralateral to observed visual abnormalities. The final chapter is a summary of main conclusions and suggested further work.

Investigation of the neural correlates of recognition memory using magnetoencephalography

Neuroimaging literature has identified several regions involved in encoding and recognition processes. A review of the literature illustrated considerable variations in the precise location and mechanisms of these processes, and it was these variations that were investigated in the studies in this thesis. Magnetoencephalography (MEG) was used as the neuroimaging tool and a preliminary study identified Synthetic Aperture Magnetometry (SAM) and not a traditional dipole fitting technique, as an appropriate tool for identifying the multiple cortical regions involved in recognition memory. It has been suggested that there is hemispheric asymmetry in encoding and recognition processes. There are two main hypotheses: the first suggesting that there is task-specificity, the second that this specificity is determined by stimulus modality. A series of experiments was completed with two main aims: first to produce consistent and complementary recognition memory data with MEG, and second to determine whether there exists any hemispheric asymmetry in recognition memory. The results obtained from five experiments demonstrated activation of prefrontal and middle temporal structures, which were consistent with those reported in previous neuroimaging studies. It was suggested that this diverse activation may be explained by the involvement of a semantic network during recognition memory processes. In support of this, a subsequent study involving a semantic encoding task demonstrated that category-specific differences in cortical activation also existed in the recognition memory phase. Controlling for the involvement of such semantic processes produced predominantly bilateral activation. It was suggested that the apparent hemispheric asymmetry findings reported in the literature may be due to the 'coarse' temporal analysis available with earlier imaging techniques, which over-simplified the networks reported by being unable to recognise the early complex processes associated with semantic processing which these MEG studies were able to identify. The importance of frequency-specific activations, specifically theta synchronisation and alpha desynchronisation, in memory processes was also investigated.

Functional neuroimaging and behavioural studies on global form processing in the human visual system

Magnetoencephalography (MEG), functional magnetic resonance imaging (fMRI) and behavioural experiments were used to investigate the neural processes underlying global form perception in human vision. Behavioural studies using Glass patterns examined sensitivity for detecting radial, rotational and horizontal structure. Neuroimaging experiments using either Glass patterns or arrays of Gabor patches determined the spatio-temporal neural responseto global form. MEG data were analysed using synthetic aperture magnetometry (SAM) to spatially map event-related cortical oscillatory power changes: the temporal sequencing of activity within a discrete cortical area was determined using a Morlet wavelet transform. A case study was conducted to determine the effects of strbismic amblyopia on global form processing: all other observers were normally-sighted. The main findings from normally-sighted observers were: 1) sensitivity to horizontal structure was less than for radial or rotational structure; 2) the neural response to global structure was a reduction in cortical oscillatory power (10-30 Hz) within a network of extrastriate areas, including V4 and V3a; 3) the extend of reduced cortical power was least for horizontal patters; 4) V1 was not identified as a region of peak activity with either MEG or fMRI. The main findings with the strabismic amblyope were: 1) sensitivity for detection of radial, rotational, and horizontal structure was reduced when viewed with the amblyopic- relative to the fellow- eye; 2) cortical power changes within V4 to the presentation of rotational Glass patterns were less when viewed with the amblyopic- compared with the fellow- eye. The main conclusions are: 1) a network of extrastriate cortical areas are involved in the analysis of global form, with the most prominent change in neural activity being a reduction in oscillatory power within the 10-30 Hz band; 2) in strabismic amblyopia, the neuronal assembly associated with form perception in extrastriate cortex may be dysfunctional, the nature of this dysfunction may be a change in the normal temporal pattern of neuronal discharges; 3) MEG, fMRI and behavioural measures support the notion that different neural processes underlie the perception of horizontal as opposed to radial or rotational structure.

Effective electromagnetic noise cancellation with beamformers and synthetic gradiometry in shielded and partly shielded environments

The major challenge of MEG, the inverse problem, is to estimate the very weak primary neuronal currents from the measurements of extracranial magnetic fields. The non-uniqueness of this inverse solution is compounded by the fact that MEG signals contain large environmental and physiological noise that further complicates the problem. In this paper, we evaluate the effectiveness of magnetic noise cancellation by synthetic gradiometers and the beamformer analysis method of synthetic aperture magnetometry (SAM) for source localisation in the presence of large stimulus-generated noise. We demonstrate that activation of primary somatosensory cortex can be accurately identified using SAM despite the presence of significant stimulus-related magnetic interference. This interference was generated by a contact heat evoked potential stimulator (CHEPS), recently developed for thermal pain research, but which to date has not been used in a MEG environment. We also show that in a reduced shielding environment the use of higher order synthetic gradiometry is sufficient to obtain signal-to-noise ratios (SNRs) that allow for accurate localisation of cortical sensory function.

A multimodal investigation of dynamic face perception using functional magnetic resonance imaging and magnetoencephalography

Motion is an important aspect of face perception that has been largely neglected to date. Many of the established findings are based on studies that use static facial images, which do not reflect the unique temporal dynamics available from seeing a moving face. In the present thesis a set of naturalistic dynamic facial emotional expressions was purposely created and used to investigate the neural structures involved in the perception of dynamic facial expressions of emotion, with both functional Magnetic Resonance Imaging (fMRI) and Magnetoencephalography (MEG). Through fMRI and connectivity analysis, a dynamic face perception network was identified, which is demonstrated to extend the distributed neural system for face perception (Haxby et al.,2000). Measures of effective connectivity between these regions revealed that dynamic facial stimuli were associated with specific increases in connectivity between early visual regions, such as inferior occipital gyri and superior temporal sulci, along with coupling between superior temporal sulci and amygdalae, as well as with inferior frontal gyri. MEG and Synthetic Aperture Magnetometry (SAM) were used to examine the spatiotemporal profile of neurophysiological activity within this dynamic face perception network. SAM analysis revealed a number of regions showing differential activation to dynamic versus static faces in the distributed face network, characterised by decreases in cortical oscillatory power in the beta band, which were spatially coincident with those regions that were previously identified with fMRI. These findings support the presence of a distributed network of cortical regions that mediate the perception of dynamic facial expressions, with the fMRI data providing information on the spatial co-ordinates paralleled by the MEG data, which indicate the temporal dynamics within this network. This integrated multimodal approach offers both excellent spatial and temporal resolution, thereby providing an opportunity to explore dynamic brain activity and connectivity during face processing.

Oscillatory beta activity mediates neuroplastic effects of motor cortex stimulation in humans

Continuous theta burst stimulation (cTBS) is a repetitive transcranial magnetic stimulation protocol that can inhibithumanmotor cortex (M1) excitability and impair movement for ≤1 h. While offering valuable insights into brain function and potential therapeutic benefits, these neuroplastic effects are highly variable between individuals. The source of this variability, and the electrophysiological mechanisms underlying the inhibitory after-effects, are largely unknown. In this regard, oscillatory activity at beta frequency (15-35 Hz) is of particular interest as it is elevated in motor disorders such as Parkinson's disease and modulated during the generation of movements. Here, we used a source-level magnetoencephalography approach to investigate the hypothesis that the presence of neuroplastic effects following cTBS is associated with concurrent changes in oscillatory M1 beta activity. M1 cortices were localized with a synthetic aperture magnetometry beamforming analysis of visually cued index finger movements. Virtual electrode analysis was used to reconstruct the spontaneous and movement-related oscillatory activity in bilateral M1 cortices, before and from 10 to 45 min after cTBS. We demonstrate that 40 s of cTBS applied over left M1 reduced corticospinal excitability in the right index finger of 8/16 participants. In these responder participants only, cTBS increased the power of the spontaneous beta oscillations in stimulated M1 and delayed reaction times in the contralateral index finger. No further changes were observed in the latency or power of movement-related beta oscillations. These data provide insights into the electrophysiological mechanisms underlying cTBS-mediated impairment of motor function and demonstrate the association between spontaneous oscillatory beta activity in M1 and the inhibition of motor function. © 2013 the authors.

Hybrid Fe3O4 /GaAs (100) structure for spintronics

Fe3O4 GaAs hybrid structures have been studied using reflection high-energy electron diffraction (RHEED), x-ray photoelectron spectroscopy (XPS), x-ray magnetic circular dichroism (XMCD), and low-temperature vibrating-sample magnetometry (VSM). The samples were prepared by oxidizing epitaxial Fe thin films in a partial pressure of 5× 10-5 mbar of oxygen at 500 K for 180 s. Clear RHEED patterns were observed, suggesting the epitaxial growth of Fe oxides with a cubic structure. The XPS spectra show that the oxides were Fe3O4 rather than γ- Fe2O3, as there were no shake-up satellites between the two Fe 2p peaks. This was further confirmed by the XMCD measurements, which show ferromagnetic coupling between the Fe cations, with no evidence of intermixing at the interface. The VSM measurements show that the films have a magnetic uniaxial anisotropy and a "quick" saturation property, with the easy axes along the [011] direction. This detailed study offers further insight into the structure, interface, and magnetic properties of this hybrid Fe3O4 GaAs (100) structure as a promising system for spintronic application. © 2005 American Institute of Physics.