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.

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.

Early gamma-band activity as a function of threat processing in the extrastriate visual cortex

Various neuroimaging investigations have revealed that perception of emotional pictures is associated with greater visual cortex activity than their neutral counterparts. It has further been proposed that threat-related information is rapidly processed, suggesting that the modulation of visual cortex activity should occur at an early stage. Additional studies have demonstrated that oscillatory activity in the gamma band range (40-100 Hz) is associated with threat processing. Magnetoencephalography (MEG) was used to investigate such activity during perception of task-irrelevant, threat-related versus neutral facial expressions. Our results demonstrated a bilateral reduction in gamma band activity for expressions of threat, specifically anger, compared with neutral faces in extrastriate visual cortex (BA 18) within 50-250 ms of stimulus onset. These results suggest that gamma activity in visual cortex may play a role in affective modulation of visual processing, in particular with the perception of threat cues.

Induced gamma activity in primary visual cortex is related to luminance and not color contrast: an MEG study

Gamma activity in the visual cortex has been reported in numerous EEG studies of coherent and illusory figures. A dominant theme of many such findings has been that temporal synchronization in the gamma band in response to these identifiable percepts is related to perceptual binding of the common features of the stimulus. In two recent studies using magnetoencephalography (MEG) and the beamformer analysis technique, we have shown that the magnitude of induced gamma activity in visual cortex is dependent upon independent stimulus features such as spatial frequency and contrast. In particular, we showed that induced gamma activity is maximal in response to gratings of 3 cycles per degree (3 cpd) of high luminance contrast. In this work, we set out to examine stimulus contrast further by using isoluminant red/green gratings that possess color but not luminance contrast using the same cohort of subjects. We found no induced gamma activity in V1 or visual cortex in response to the isoluminant gratings in these subjects who had previously shown strong induced gamma activity in V1 for luminance contrast gratings.

The role of oscillatory brain activity in object processing and figure-ground segmentation in human vision

The perception of an object as a single entity within a visual scene requires that its features are bound together and segregated from the background and/or other objects. Here, we used magnetoencephalography (MEG) to assess the hypothesis that coherent percepts may arise from the synchronized high frequency (gamma) activity between neurons that code features of the same object. We also assessed the role of low frequency (alpha, beta) activity in object processing. The target stimulus (i.e. object) was a small patch of a concentric grating of 3c/°, viewed eccentrically. The background stimulus was either a blank field or a concentric grating of 3c/° periodicity, viewed centrally. With patterned backgrounds, the target stimulus emerged--through rotation about its own centre--as a circular subsection of the background. Data were acquired using a 275-channel whole-head MEG system and analyzed using Synthetic Aperture Magnetometry (SAM), which allows one to generate images of task-related cortical oscillatory power changes within specific frequency bands. Significant oscillatory activity across a broad range of frequencies was evident at the V1/V2 border, and subsequent analyses were based on a virtual electrode at this location. When the target was presented in isolation, we observed that: (i) contralateral stimulation yielded a sustained power increase in gamma activity; and (ii) both contra- and ipsilateral stimulation yielded near identical transient power changes in alpha (and beta) activity. When the target was presented against a patterned background, we observed that: (i) contralateral stimulation yielded an increase in high-gamma (>55 Hz) power together with a decrease in low-gamma (40-55 Hz) power; and (ii) both contra- and ipsilateral stimulation yielded a transient decrease in alpha (and beta) activity, though the reduction tended to be greatest for contralateral stimulation. The opposing power changes across different regions of the gamma spectrum with 'figure/ground' stimulation suggest a possible dual role for gamma rhythms in visual object coding, and provide general support of the binding-by-synchronization hypothesis. As the power changes in alpha and beta activity were largely independent of the spatial location of the target, however, we conclude that their role in object processing may relate principally to changes in visual attention.

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.

Synchronization processes in nonlinear systems and their relation to cortical oscillatory dynamics

This thesis was focused on theoretical models of synchronization to cortical dynamics as measured by magnetoencephalography (MEG). Dynamical systems theory was used in both identifying relevant variables for brain coordination and also in devising methods for their quantification. We presented a method for studying interactions of linear and chaotic neuronal sources using MEG beamforming techniques. We showed that such sources can be accurately reconstructed in terms of their location, temporal dynamics and possible interactions. Synchronization in low-dimensional nonlinear systems was studied to explore specific correlates of functional integration and segregation. In the case of interacting dissimilar systems, relevant coordination phenomena involved generalized and phase synchronization, which were often intermittent. Spatially-extended systems were then studied. For locally-coupled dissimilar systems, as in the case of cortical columns, clustering behaviour occurred. Synchronized clusters emerged at different frequencies and their boundaries were marked through oscillation death. The macroscopic mean field revealed sharp spectral peaks at the frequencies of the clusters and broader spectral drops at their boundaries. These results question existing models of Event Related Synchronization and Desynchronization. We re-examined the concept of the steady-state evoked response following an AM stimulus. We showed that very little variability in the AM following response could be accounted by system noise. We presented a methodology for detecting local and global nonlinear interactions from MEG data in order to account for residual variability. We found crosshemispheric nonlinear interactions of ongoing cortical rhythms concurrent with the stimulus and interactions of these rhythms with the following AM responses. Finally, we hypothesized that holistic spatial stimuli would be accompanied by the emergence of clusters in primary visual cortex resulting in frequency-specific MEG oscillations. Indeed, we found different frequency distributions in induced gamma oscillations for different spatial stimuli, which was suggestive of temporal coding of these spatial stimuli. Further, we addressed the bursting character of these oscillations, which was suggestive of intermittent nonlinear dynamics. However, we did not observe the characteristic-3/2 power-law scaling in the distribution of interburst intervals. Further, this distribution was only seldom significantly different to the one obtained in surrogate data, where nonlinear structure was destroyed. In conclusion, the work presented in this thesis suggests that advances in dynamical systems theory in conjunction with developments in magnetoencephalography may facilitate a mapping between levels of description int he brain. this may potentially represent a major advancement in neuroscience.

Modulation of network oscillatory activity and GABAergic synaptic transmission by CB1 cannabinoid receptors in the rat medial entorhinal cortex

Cannabinoids modulate inhibitory GABAergic neurotransmission in many brain regions. Within the temporal lobe, cannabinoid receptors are highly expressed, and are located presynaptically at inhibitory terminals. Here, we have explored the role of type-1 cannabinoid receptors (CB1Rs) at the level of inhibitory synaptic currents and field-recorded network oscillations. We report that arachidonylcyclopropylamide, an agonist at CB1R, inhibits GABAergic synaptic transmission onto both superficial and deep medial entorhinal (mEC) neurones, but this has little effect on network oscillations in beta/gamma frequency bands. By contrast, the CB1R antagonist/inverse agonist LY320135 (500?nM), increased GABAergic synaptic activity and beta/gamma oscillatory activity in superficial mEC, was suppressed, whilst that in deep mEC was enhanced. These data indicate that cannabinoid-mediated effects on inhibitory synaptic activity may be constitutively active in vitro, and that modulation of CB1R activation using inverse agonists unmasks complex effects of CBR function on network activity.

Functional connectivity of gamma EEG activity is modulated at low frequency during conscious recollection

We examined two subjectively distinct memory states that are elicited during recognition memory in humans and compared them in terms of the gamma oscillations (20–60 Hz) in the electroencepahalogram (EEG) that they induced. These subjective states, ‘recollection’ and ‘familiarity’ both entail correct recognition but one involves a clear and conscious recollection of the event including memory for contextual detail whilst the other involves a sense of familiarity without clear recollection. Here we show that during a verbal recognition memory test, the subjective experience of ‘recollection’ induced higher amplitude gamma oscillations than the subjective experience of ‘familiarity’ in the time period 300–500 ms after stimulus presentation. Recollection, but not familiarity, was also associated with greater functional connectivity in the gamma frequency range between frontal and parietal sites. Furthermore, the magnitude of the gamma functional connectivity varied over time and was modulated at 3 Hz. Previous studies in animals have shown local theta frequency modulation (3–7 Hz) of gamma-oscillations but this is the first time that a similar effect has been reported in the human EEG.

Induced gamma activity is associated with conscious awareness of pattern masked nouns

The aim of this study was to explore the relationship between electroencephalographic (EEG) activity in the gamma frequency range and conscious awareness of a visual stimulus. EEG was recorded from subjects while they were shown backward-masked words only some of which they were able to discriminate correctly. The results showed that activity in the gamma frequency range increase with reported awareness of a word independently of whether it was correctly discriminated or not. It is concluded that gamma power is associated with awareness-dependent visual processing but not with processing that occurs in the absence of awareness.

Neuronal network dynamics during epileptogenesis in the medial temporal lobe

Epilepsy is one of the most common neurological disorders, a large fraction of which is resistant to pharmacotherapy. In this light, understanding the mechanisms of epilepsy and its intractable forms in particular could create new targets for pharmacotherapeutic intervention. The current project explores the dynamic changes in neuronal network function in the chronic temporal lobe epilepsy (TLE) in rat and human brain in vitro. I focused on the process of establishment of epilepsy (epileptogenesis) in the temporal lobe. Rhythmic behaviour of the hippocampal neuronal networks in healthy animals was explored using spontaneous oscillations in the gamma frequency band (SγO). The use of an improved brain slice preparation technique resulted in the natural occurence (in the absence of pharmacological stimulation) of rhythmic activity, which was then pharmacologically characterised and compared to other models of gamma oscillations (KA- and CCh-induced oscillations) using local field potential recording technique. The results showed that SγO differed from pharmacologically driven models, suggesting higher physiological relevance of SγO. Network activity was also explored in the medial entorhinal cortex (mEC), where spontaneous slow wave oscillations (SWO) were detected. To investigate the course of chronic TLE establishment, a refined Li-pilocarpine-based model of epilepsy (RISE) was developed. The model significantly reduced animal mortality and demonstrated reduced intensity, yet high morbidy with almost 70% mean success rate of developing spontaneous recurrent seizures. We used SγO to characterize changes in the hippocampal neuronal networks throughout the epileptogenesis. The results showed that the network remained largely intact, demonstrating the subtle nature of the RISE model. Despite this, a reduction in network activity was detected during the so-called latent (no seizure) period, which was hypothesized to occur due to network fragmentation and an abnormal function of kainate receptors (KAr). We therefore explored the function of KAr by challenging SγO with kainic acid (KA). The results demonstrated a remarkable decrease in KAr response during the latent period, suggesting KAr dysfunction or altered expression, which will be further investigated using a variety of electrophysiological and immunocytochemical methods. The entorhinal cortex, together with the hippocampus, is known to play an important role in the TLE. Considering this, we investigated neuronal network function of the mEC during epileptogenesis using SWO. The results demonstrated a striking difference in AMPAr function, with possible receptor upregulation or abnormal composition in the early development of epilepsy. Alterations in receptor function inevitably lead to changes in the network function, which may play an important role in the development of epilepsy. Preliminary investigations were made using slices of human brain tissue taken following surgery for intratctable epilepsy. Initial results showed that oscillogenesis could be induced in human brain slices and that such network activity was pharmacologically similar to that observed in rodent brain. Overall, our findings suggest that excitatory glutamatergic transmission is heavily involved in the process of epileptogenesis. Together with other types of receptors, KAr and AMPAr contribute to epilepsy establishment and may be the key to uncovering its mechanism.

Atypical connectivity in autistic spectrum disorders

Autism is a developmental disorder that is currently defined in terms of a triad of impairments in social interaction, communication, and behavioural flexibility. Psychological models have focussed on deficits in high level social and cognitive processes, such as ‘weak central coherence’ and deficits in ‘theory of mind’. Converging evidence from different fields of neuroscience research indicates that the underlying neural dysfunction is associated with atypical patterns of cortical connectivity (Rippon et al., 2007). This arises very early in development and results in sensory, perceptual and cognitive deficits at a much earlier and more fundamental level than previously suggested, but with cascading effects on higher level psychological and social processes. Earlier research in this sphere has focussed mainly on patterns of underconnectivity in distributed cortical networks underpinning process such as language and executive function. (Just et al., 2007). Such research mainly utilises imaging techniques with high spatial resolution. This paper focuses on evidence associated with local over-connectivity, evident in more low level and transitory processes and hence more easily measurable with techniques with high temporal resolution, such as MEG and EEG. Results are described which provide evidence of such local over-connectivity, characterised by atypical results in the gamma frequency range (Brown et al., 2005) together with discussions about the future directions of such research and its implications for remediation.

Altered resting-state EEG source functional connectivity in schizophrenia:the effect of illness duration

Despite the increasing body of evidence supporting the hypothesis of schizophrenia as a disconnection syndrome, studies of resting-state EEG Source Functional Connectivity (EEG-SFC) in people affected by schizophrenia are sparse. The aim of the present study was to investigate resting-state EEG-SFC in 77 stable, medicated patients with schizophrenia (SCZ) compared to 78 healthy volunteers (HV). In order to study the effect of illness duration, SCZ were divided in those with a short duration of disease (SDD; n = 25) and those with a long duration of disease (LDD; n = 52). Resting-state EEG recordings in eyes closed condition were analyzed and lagged phase synchronization (LPS) indices were calculated for each ROI pair in the source-space EEG data. In delta and theta bands, SCZ had greater EEG-SFC than HV; a higher theta band connectivity in frontal regions was observed in LDD compared with SDD. In the alpha band, SCZ showed lower frontal EEG-SFC compared with HV whereas no differences were found between LDD and SDD. In the beta1 band, SCZ had greater EEG-SFC compared with HVs and in the beta2 band, LDD presented lower frontal and parieto-temporal EEG-SFC compared with HV. In the gamma band, SDD had greater connectivity values compared with LDD and HV. This study suggests that resting state brain network connectivity is abnormally organized in schizophrenia, with different patterns for the different EEG frequency components and that EEG can be a powerful tool to further elucidate the complexity of such disordered connectivity.

Generation of optical frequency combs in fibres:an optical pulse analysis

The innovation of optical frequency combs (OFCs) generated in passive mode-locked lasers has provided astronomy with unprecedented accuracy for wavelength calibration in high-resolution spectroscopy in research areas such as the discovery of exoplanets or the measurement of fundamental constants. The unique properties of OCFs, namely a highly dense spectrum of uniformly spaced emission lines of nearly equal intensity over the nominal wavelength range, is not only beneficial for high-resolution spectroscopy. Also in the low- to medium-resolution domain, the OFCs hold the promise to revolutionise the calibration techniques. Here, we present a novel method for generation of OFCs. As opposed to the mode-locked laser-based approach that can be complex, costly, and difficult to stabilise, we propose an all optical fibre-based system that is simple, compact, stable, and low-cost. Our system consists of three optical fibres where the first one is a conventional single-mode fibre, the second one is an erbium-doped fibre and the third one is a highly nonlinear low-dispersion fibre. The system is pumped by two equally intense continuous-wave (CW) lasers. To be able to control the quality and the bandwidth of the OFCs, it is crucial to understand how optical solitons arise out of the initial modulated CW field in the first fibre. Here, we numerically investigate the pulse evolution in the first fibre using the technique of the solitons radiation beat analysis. Having applied this technique, we realised that formation of higherorder solitons is supported in the low-energy region, whereas, in the high-energy region, Kuznetsov-Ma solitons appear.

Retinotopic mapping of the primary visual cortex - a challenge for MEG imaging of the human cortex

Magnetoencephalography (MEG) can be used to reconstruct neuronal activity with high spatial and temporal resolution. However, this reconstruction problem is ill-posed, and requires the use of prior constraints in order to produce a unique solution. At present there are a multitude of inversion algorithms, each employing different assumptions, but one major problem when comparing the accuracy of these different approaches is that often the true underlying electrical state of the brain is unknown. In this study, we explore one paradigm, retinotopic mapping in the primary visual cortex (V1), for which the ground truth is known to a reasonable degree of accuracy, enabling the comparison of MEG source reconstructions with the true electrical state of the brain. Specifically, we attempted to localize, using a beanforming method, the induced responses in the visual cortex generated by a high contrast, retinotopically varying stimulus. Although well described in primate studies, it has been an open question whether the induced gamma power in humans due to high contrast gratings derives from V1 rather than the prestriate cortex (V2). We show that the beanformer source estimate in the gamma and theta bands does vary in a manner consistent with the known retinotopy of V1. However, these peak locations, although retinotopically organized, did not accurately localize to the cortical surface. We considered possible causes for this discrepancy and suggest that improved MEG/magnetic resonance imaging co-registration and the use of more accurate source models that take into account the spatial extent and shape of the active cortex may, in future, improve the accuracy of the source reconstructions.