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

Sustained Magnetic Responses in Temporal Cortex Reflect Instantaneous Significance of Approaching and Receding Sounds

Rising sound intensity often signals an approaching sound source and can serve as a powerful warning cue, eliciting phasic attention, perception biases and emotional responses. How the evaluation of approaching sounds unfolds over time remains elusive. Here, we capitalised on the temporal resolution of magnetoencephalograpy (MEG) to investigate in humans a dynamic encoding of perceiving approaching and receding sounds. We compared magnetic responses to intensity envelopes of complex sounds to those of white noise sounds, in which intensity change is not perceived as approaching. Sustained magnetic fields over temporal sensors tracked intensity change in complex sounds in an approximately linear fashion, an effect not seen for intensity change in white noise sounds, or for overall intensity. Hence, these fields are likely to track approach/recession, but not the apparent (instantaneous) distance of the sound source, or its intensity as such. As a likely source of this activity, the bilateral inferior temporal gyrus and right temporo-parietal junction emerged. Our results indicate that discrete temporal cortical areas parametrically encode behavioural significance in moving sound sources where the signal unfolded in a manner reminiscent of evidence accumulation. This may help an understanding of how acoustic percepts are evaluated as behaviourally relevant, where our results highlight a crucial role of cortical areas

Cardiovascular actions of apelin-receptor agonism during Renin-Angiotensin system activation, exercise and in patients with chronic stable heart failure

The apelin-apelin receptor (APLNR) system is an important regulator of cardiovascular homeostasis both in health and disease. Principal actions of the apelin-APLNR system are positive inotropism, vasodilatation, diuresis and a potential anti-inflammatory role in vascular tissue. The significance of this system is highlighted in heart failure and pulmonary hypertension. Preclinical models of these diseases report downregulation of apelin- APLNR, whilst knockout strains develop more severe phenotypes, more rapidly. Moreover treatment with exogenous apelin retards or prevents disease progression. In man plasma apelin concentrations are reduced in heart failure and vary with disease severity. Initial increases are reported in mild heart failure suggesting a compensatory role, but are depressed in severe heart failure. Limited data profile myocardial APLNR expression in heart failure and in keeping with plasma apelin concentrations, expression is reduced in severe heart failure. Of interest, the APLNR most closely resembles the angiotensin II type 1 receptor (AT1R), sharing similar tissue expression and sequence homology, but mediates opposing physiological actions. Furthermore, emerging preclinical data support receptor interactions between the APLNR and AT1R that modify their native signalling pathways. It is likely that the apelin-APLNR system serves to antagonise the renin-angiotensin system. Given the established role of angiotensin II, arguably the most important peptide in cardiovascular pathophysiology, any system influencing its actions merits further investigation. Current clinical studies are limited to 20 minutes infusions and understanding its cardiovascular effects requires more prolonged administration. There are concerns of tachyphylaxis and interaction with the renin-angiotensin-aldosterone system (RAAS), possibly reducing efficacy of APLNR agonism in clinical settings. In a series of randomised, blinded crossover clinical trials 60 healthy volunteers and 20 patients with chronic stable heart failure were enrolled to assess the effects of (Pyr1)apelin-13 infusion at rest, during acute and subacute infusion, exercise and upregulation of the renin-angiotensin system. I have identified that APLNR agonism is unaffected by prevailing levels of angiotensin II activity in local vascular beds and systemic haemodynamic infusions. Furthermore, the efficacy of (Pyr1)apelin-13 is retained in healthy volunteers and patients with chronic stable heart failure during acute and subacute infusions. Finally, systemic (Pyr1)apelin-13 does not alter exercise performance in healthy individuals. My findings support a role in targeting the APLNR in chronic heart failure and predict that efficacy will be retained in chronic dosing. Future research directed at other patient groups with ventricular dysfunction is merited, in order to further characterise the utility of this system. These studies are encouraging; however, longer term studies may reveal effects beyond haemodynamic alterations and examine the effects on cardiac fibrosis and endothelial function. A long acting agonist is required to fully evaluate the role of APLNR signalling in cardiovascular disease

Hippocampal Theta-Phase Modulation of Replay Correlates with Configural-Relational Short-Term Memory Performance

Thereis now growing evidencethatthe hippocampus generatestheta rhythmsthat can phase biasfast neural oscillationsinthe neocortex, allowing coordination of widespread fast oscillatory populations outside limbic areas. A recent magnetoencephalographic study showed that maintenance of configural-relational scene information in a delayed match-to-sample (DMS) task was associated with replay of that information during the delay period. The periodicity of the replay was coordinated by the phase of the ongoing theta rhythm, and the degree of theta coordination during the delay period was positively correlated with DMS performance. Here, we reanalyzed these data to investigate which brain regions were involved in generating the theta oscillations that coordinated the periodic replay of configural- relational information. We used a beamformer algorithm to produce estimates of regional theta rhythms and constructed volumetric images of the phase-locking between the local theta cycle and the instances of replay (in the 13- 80 Hz band). We found that individual differences in DMS performancefor configural-relational associations were relatedtothe degree of phase coupling of instances of cortical reactivations to theta oscillations generated in the right posterior hippocampus and the right inferior frontal gyrus. This demonstrates that the timing of memory reactivations in humans is biased toward hippocampal theta phas

Population level inference for multivariate MEG analysis

Multivariate analysis is a very general and powerful technique for analysing Magnetoencephalography (MEG) data. An outstanding problem however is how to make inferences that are consistent over a group of subjects as to whether there are condition-specific differences in data features, and what are those features that maximise these differences. Here we propose a solution based on Canonical Variates Analysis (CVA) model scoring at the subject level and random effects Bayesian model selection at the group level. We apply this approach to beamformer reconstructed MEG data in source space. CVA estimates those multivariate patterns of activation that correlate most highly with the experimental design; the order of a CVA model is then determined by the number of significant canonical vectors. Random effects Bayesian model comparison then provides machinery for inferring the optimal order over the group of subjects. Absence of a multivariate dependence is indicated by the null model being the most likely. This approach can also be applied to CVA models with a fixed number of canonical vectors but supplied with different feature sets. We illustrate the method by identifying feature sets based on variable-dimension MEG power spectra in the primary visual cortex and fusiform gyrus that are maximally discriminative of data epochs before versus after visual stimulation

Long-Term Preservation and Reusability of Open Access Scholar-Led Press Monographs

This brief report outlines some initial findings and challenges identified by the Community-Led Open Publication Infrastructures for Monographs (COPIM) project when looking to archive and preserve open access books produced by small, scholar-led presses. This paper is based on the research conducted by Work Package 7 in COPIM, which has a focus on the preservation and archiving of open access monographs in all their complexity, along with any accompanying materials.&nbsp

A 3‐D Model of Gas Generation, Migration, and Gas Hydrate Formation at a Young Convergent Margin (Hikurangi Margin, New Zealand)

We present a three-dimensional gas hydrate systems model of the southern Hikurangi subduction margin in eastern New Zealand. The model integrates thermal and microbial gas generation, migration, and hydrate formation. Modeling these processes has improved the understanding of factors controlling hydrate distribution. Three spatial trends of concentrated hydrate occurrence are predicted. The first trend (I) is aligned with the principal deformation front in the overriding Australian plate. Concentrated hydrate deposits are predicted at or near the apexes of anticlines and to be mainly sourced from focused migration and recycling of microbial gas generated beneath the hydrate stability zone. A second predicted trend (II) is related to deformation in the subducting Pacific plate associated with former Mesozoic subduction beneath Gondwana and the modern Pacific-Australian plate boundary. This trend is enhanced by increased advection of thermogenic gas through permeable layers in the subducting plate and focused migration into the Neogene basin fill above Cretaceous-Paleogene structures. The third trend (III) follows the northern margin of the Hikurangi Channel and is related to the presence of buried strata of the Hikurangi Channel system. The predicted trends are consistent with pronounced seismic reflection anomalies related to free gas in the pore space and strength of the bottom-simulating reflection. However, only trend I is also associated with clear and widespread seismic indications of concentrated gas hydrate. Total predicted hydrate masses at the southern Hikurangi Margin are between 52,800 and 69,800 Mt. This equates to 3.4–4.5 Mt hydrate/km2, containing 6.33 × 108–8.38 × 108 m3/km2 of methane

Working memory replay prioritizes weakly attended events

One view of working memory posits that maintaining a series of events requires their sequential and equal mnemonic replay. Another view is that the content of working memory maintenance is prioritized by attention. We decoded the dynamics for retaining a sequence of items using magnetoencephalography, wherein participants encoded sequences of three stimuli depicting a face, a manufactured object, or a natural item and maintained them in working memory for 5000 ms. Memory for sequence position and stimulus details were probed at the end of the maintenance period. Decoding of brain activity revealed that one of the three stimuli dominated maintenance independent of its sequence position or category; and memory was enhanced for the selectively replayed stimulus. Analysis of event-related responses during the encoding of the sequence showed that the selectively replayed stimuli were determined by the degree of attention at encoding. The selectively replayed stimuli had the weakest initial encoding indexed by weaker visual attention signals at encoding. These findings do not rule out sequential mnemonic replay but reveal that attention influences the content of working memory maintenance by prioritizing replay of weakly encoded events. We propose that the prioritization of weakly encoded stimuli protects them from interference during the maintenance period, whereas the more strongly encoded stimuli can be retrieved from long-term memory at the end of the delay period