Linear tuning of gamma amplitude and frequency to luminance contrast: evidence from a continuous mapping paradigm

Individual differences in the visual gamma (30–100Hz) response and their potential as trait markers of underlying physiology (particularly related to GABAergic inhibition) have become a matter of increasing interest in recent years. There is growing evidence, however, that properties of the gamma response (e.g., its amplitude and frequency) are highly stimulus dependent, and that individual differences in the gamma response may reflect individual differences in the stimulus tuning functions of gamma oscillations. Here, we measured the tuning functions of gamma amplitude and frequency to luminance contrast in eighteen participants using MEG. We used a grating stimulus in which stimulus contrast was modulated continuously over time. We found that both gamma amplitude and frequency were linearly modulated by stimulus contrast, but that the gain of this modulation (as reflected in the linear gradient) varied across individuals. We additionally observed a stimulus-induced response in the beta frequency range (10–25Hz), but neither the amplitude nor the frequency of this response was consistently modulated by the stimulus over time. Importantly, we did not find a correlation between the gain of the gamma-band amplitude and frequency tuning functions across individuals, suggesting that these may be independent traits driven by distinct neurophysiological processes

Assessment and elimination of the effects of head movement on MEG resting-state measures of oscillatory brain activity

Magnetoencephalography (MEG) is increasingly being used to study brain function because of its excellent temporal resolution and its direct association with brain activity at the neuronal level. One possible cause of error in the analysis of MEG data comes from the fact that participants, even MEG-experienced ones, move their head in the MEG system. Head movement can cause source localization errors during the analysis of MEG data, which can result in the appearance of source variability that does not reflect brain activity. The MEG community places great importance in eliminating this source of possible errors as is evident, for example, by recent efforts to develop head casts that limit head movement in the MEG system. In this work we use software tools to identify, assess and eliminate from the analysis of MEG data any possible correlations between head movement in the MEG system and widely-used measures of brain activity derived from MEG resting-state recordings. The measures of brain activity we study are a) the Hilbert-transform derived amplitude envelope of the beamformer time series and b) functional networks; both measures derived by MEG resting-state recordings. Ten-minute MEG resting-state recordings were performed on healthy participants, with head position continuously recorded. The sources of the measured magnetic signals were localized via beamformer spatial filtering. Temporal independent component analysis was subsequently used to derive resting-state networks. Significant correlations were observed between the beamformer envelope time series and head movement. The correlations were substantially reduced, and in some cases eliminated, after a participant-specific temporal highpass filter was applied to those time series. Regressing the head movement metrics out of the beamformer envelope time series had an even stronger effect in reducing these correlations. Correlation trends were also observed between head movement and the activation time series of the default-mode and frontal networks. Regressing the head movement metrics out of the beamformer envelope time series completely eliminated these correlations. Additionally, applying the head movement correction resulted in changes in the network spatial maps for the visual and sensorimotor networks. Our results a) show that the results of MEG resting-state studies that use the above-mentioned analysis methods are confounded by head movement effects, b) suggest that regressing the head movement metrics out of the beamformer envelope time series is a necessary step to be added to these analyses, in order to eliminate the effect that head movement has on the amplitude envelope of beamformer time series and the network time series and c) highlight changes in the connectivity spatial maps when head movement correction is applie

Oscillatory hyperactivity and hyperconnectivity in young APOE-ɛ4 carriers and hypoconnectivity in Alzheimer's disease

We studied resting-state oscillatory connectivity using magnetoencephalography in healthy young humans (N = 183) genotyped for APOE-ɛ4, the greatest genetic risk for Alzheimer’s disease (AD). Connectivity across frequencies, but most prevalent in alpha/beta, was increased in APOE-ɛ4 in a set of mostly right-hemisphere connections, including lateral parietal and precuneus regions of the Default Mode Network. Similar regions also demonstrated hyperactivity, but only in gamma (40–160 Hz). In a separate study of AD patients, hypoconnectivity was seen in an extended bilateral network that partially overlapped with the hyperconnected regions seen in young APOE-ɛ4 carriers. Using machine-learning, AD patients could be distinguished from elderly controls with reasonable sensitivity and specificity, while young APOE-e4 carriers could also be distinguished from their controls with above chance performance. These results support theories of initial hyperconnectivity driving eventual profound disconnection in AD and suggest that this is present decades before the onset of AD symptomology

Alzheimer's disease disrupts alpha and beta-band resting-state oscillatory network connectivity

Objective: Neuroimaging studies in Alzheimer’s disease (AD) yield conflicting results due to selective investigation. We conducted a comprehensive magnetoencephalography study of connectivity changes in AD and healthy ageing in the resting-state. Methods: We performed a whole-brain, source-space assessment of oscillatory neural signalling in multiple frequencies comparing AD patients, elderly and young controls. We compared eyes-open and closed group oscillatory envelope activity in networks obtained through temporal independent component analysis, and calculated whole-brain node-based amplitude and phase connectivity. Results: In bilateral parietotemporal areas, oscillatory envelope amplitude increased with healthy ageing, whereas both local amplitude and node-to-global connectivity decreased with AD. AD-related decreases were spatially specific and restricted to the alpha and beta bands. A significant proportion of the variance in areas of peak group difference was explained by cognitive integrity, in addition to group. None of the groups differed in phase connectivity. Results were highly similar for eyes-open and closed resting-state. Conclusions: These results support the disconnection syndrome hypothesis and suggest that AD shows distinct and unique patterns of disrupted neural functioning, rather than accelerated healthy ageing. Significance: Whole-brain assessments show that disrupted regional oscillatory envelope amplitude and connectivity in the alpha and beta bands play a key role in AD

Balancing stimulus and goal-driven attentional demands: investigating the role of gamma oscillations in human early visual cortex using magnetoencephalography

"This thesis is presented for the degree of Doctor of Philosophy (PhD), August 2012"Thesis by publication.Includes bibliographical references.1. General introduction -- 2. Manipulating behavioural relevance of a salient item: an MEG -- 3. Induced and evoked neural correlates of orientation selectivity in human visual cortex -- 4. Sustained visuo-spatial attention increases high-frequency gamma synchronisation in human medial visual cortex -- 5. Investigating effects of stimulus salience and behavioural relevance on gamma synchronisation in early visual cortex -- 6. General discussion -- Appendix."Salient events tend to capture our attention. When such events are irrelevant to something we are looking for they need to be inhibited not to distract us. Efficient allocation of attention involves balancing of attentional demands driven by both salient events and current goals. To deal with the constantly changing visual input in light of attentional goals, it is crucial that visual brain areas participate in this balancing. The aim of this thesis is to investigate the role of early visual areas in the balancing of stimulus and goal-driven attentional demands. I primarily focus on the synchronisation of oscillatory activity in the gamma band, because its role in both neural communication and visual processing makes it a prime candidate for mediating the dynamic balancing of attentional demands. In Chapter 1 I review the literature on behavioural effects and neural processing of attentional demands. In Chapter 2, I focus on how evoked responses in early visual cortex are modulated when stimulus salience and behavioural relevance compete for attentional allocation. I then address how these factors interact to modulate gamma activity in three steps. In Chapter 3, I use a strong gamma-inducing stimulus to investigate how orientation, a stimulus property strongly represented in early visual cortex, affects the gamma response. In Chapter 4, I investigate how directing voluntary attention towards or away from that optimal stimulus affects the gamma response it induces. Finally, I address how stimulus and goal-driven factors combine to influence the gamma response when they compete for attentional allocation in Chapter 5. The main findings in this thesis are that stimulus and goal-driven factors influence gamma synchronisation in early visual cortex at different frequencies, and interact to modulate the gamma response when attentional demands are actively balanced. These findings contribute to our understanding of the role of early visual cortex in both low-level and attentional visual processing. I address the implications of these findings in Chapter 6." -- Abstract.Mode of access: World Wide Web.1 online resource (xii, 233 pages) illustrations (some coloured

Non-invasive brain mapping in epilepsy: applications from magnetoencephalography

Background Non-invasive in vivo neurophysiological recordings with EEG/MEG are key to the diagnosis, classification, and further understanding of epilepsy. Historically the emphasis of these recordings has been the localisation of the putative sources of epileptic discharges. More recent developments see new techniques studying oscillatory dynamics, connectivity and network properties. New method New analysis strategies for whole head MEG include the development of spatial filters or beamformers for source localisation, time–frequency analysis for cortical dynamics and graph theory applications for connectivity. Results The idea of epilepsy as a network disorder is not new, and new applications of structural and functional brain imaging show differences in cortical and subcortical networks in patients with epilepsy compared to controls. Concepts of ‘focal’ and ‘generalised’ are challenged by evidence of focal onsets in generalised epileptic discharges, and widespread network changes in focal epilepsy. Spectral analyses can show differences in induced cortical response profiles, particularly in photosensitive epilepsy. Comparison with existing method This review focuses on the application of MEG in the study of epilepsy, starting with a brief historical perspective, followed by novel applications of source localisation, time–frequency and connectivity analyses. Conclusion Novel MEG analyses approaches show altered cortical dynamics and widespread network alterations in focal and generalised epilepsies, and identification of regional network abnormalities may have a role in epilepsy surgery evaluation

Neural processing of visual attention : modulation of the orientation-induced gamma response

Stimulus-induced gamma oscillations are a general neuronal feature, and are thought to play a functional role in visual processing. If gamma oscillations indeed reflect cortical processing, their degree of synchronisation should be modulated by attention. Using magnetoencephalography, we investigated how oscillatory responses to a stimulus optimal for inducing gamma in visual cortex changes with spatial attention. In separate blocks, subjects traced the orientation of either a parafoveal grating patch or a small line at fixation that each unpredictably and independently rotated up to 40 degrees around one of four angles, but were both always present. We observed a sustained attention-related increase in gamma power (30-70 Hz) in early visual cortex contralateral to the grating, supporting a role for gamma in visual processing, even as early as V1/V2. In addition to gamma, we also investigated modulations in other frequency bands, and found the classic decrease in alpha power (5-15 Hz) with attention, strongly supporting our attentional manipulation. We subsequently investigated how actively inhibiting a stimulus affects the gamma response, by manipulating the behavioural relevance to grating stimuli, providing further insights in the functional significance of gamma oscillations in visual processing.1 page(s

Spatial attention increases high-frequency gamma synchronisation in human medial visual cortex

Visual information processing involves the integration of stimulus and goal-driven information, requiring neuronal communication. Gamma synchronisation is linked to neuronal communication, and is known to be modulated in visual cortex both by stimulus properties and voluntarily-directed attention. Stimulus-driven modulations of gamma activity are particularly associated with early visual areas such as V1, whereas attentional effects are generally localised to higher visual areas such as V4. The absence of a gamma increase in early visual cortex is at odds with robust attentional enhancements found with other measures of neuronal activity in this area. Here we used magnetoencephalography (MEG) to explore the effect of spatial attention on gamma activity in human early visual cortex using a highly effective gamma-inducing stimulus and strong attentional manipulation. In separate blocks, subjects tracked either a parafoveal grating patch that induced gamma activity in contralateral medial visual cortex, or a small line at fixation, effectively attending away from the gamma-inducing grating. Both items were always present, but rotated unpredictably and independently of each other. The rotating grating induced gamma synchronisation in medial visual cortex at 30-70. Hz, and in lateral visual cortex at 60-90. Hz, regardless of whether it was attended. Directing spatial attention to the grating increased gamma synchronisation in medial visual cortex, but only at 60-90. Hz. These results suggest that the generally found increase in gamma activity by spatial attention can be localised to early visual cortex in humans, and that stimulus and goal-driven modulations may be mediated at different frequencies within the gamma range.9 page(s

Induced and evoked neural correlates of orientation selectivity in human visual cortex

Orientation discrimination is much better for patterns oriented along the horizontal or vertical (cardinal) axes than for patterns oriented obliquely, but the neural basis for this is not known. Previous animal neurophysiology and human neuroimaging studies have demonstrated only a moderate bias for cardinal versus oblique orientations, with fMRI showing a larger response to cardinals in primary visual cortex (V1) and EEG demonstrating both increased magnitudes and reduced latencies of transient evoked responses. Here, using MEG, we localised and characterised induced gamma and transient evoked responses to stationary circular grating patches of three orientations (0, 45, and 90° from vertical). Surprisingly, we found that the sustained gamma response was larger for oblique, compared to cardinal, stimuli. This "inverse oblique effect" was also observed in the earliest (80. ms) evoked response, whereas later responses (120. ms) showed a trend towards the reve rse, "classic, oblique response. Source localisation demonstrated that the sustained gamma and early evoked responses were localised to medial visual cortex, whilst the later evoked responses came from both this early visual area and a source in a more inferolateral extrastriate region. These results suggest that (1) the early evoked and sustained gamma responses manifest the initial tuning of V1 neurons, with the stronger response to oblique stimuli possibly reflecting increased tuning widths for these orientations, and (2) the classic behavioural oblique effect is mediated by an extrastriate cortical area and may also implicate feedback from extrastriate to primary visual cortex.11 page(s