Investigation of multisensory processing and structural brain differences in Autism Spectrum Disorder

This thesis is an investigation of structural brain abnormalities, as well as multisensory and unisensory processing deficits in autistic traits and Autism Spectrum Disorder (ASD). To achieve this, structural and functional magnetic resonance imaging (fMRI) and psychophysical techniques were employed. ASD is a neurodevelopmental condition which is characterised by the social communication and interaction deficits, as well as repetitive patterns of behaviour, interests and activities. These traits are thought to be present in a typical population. The Autism Spectrum Quotient questionnaire (AQ) was developed to assess the prevalence of autistic traits in the general population. Von dem Hagen et al. (2011) revealed a link between AQ with white matter (WM) and grey matter (GM) volume (using voxel-based-morphometry). However, their findings revealed no difference in GM in areas associated with social cognition. Cortical thickness (CT) measurements are known to be a more direct measure of cortical morphology than GM volume. Therefore, Chapter 2 investigated the relationship between AQ scores and CT in the same sample of participants. This study showed that AQ scores correlated with CT in the left temporo-occipital junction, left posterior cingulate, right precentral gyrus and bilateral precentral sulcus, in a typical population. These areas were previously associated with structural and functional differences in ASD. Thus the findings suggest, to some extent, autistic traits are reflected in brain structure - in the general population. The ability to integrate auditory and visual information is crucial to everyday life, and results are mixed regarding how ASD influences audiovisual integration. To investigate this question, Chapter 3 examined the Temporal Integration Window (TIW), which indicates how precisely sight and sound need to be temporally aligned so that a unitary audiovisual event can be perceived. 26 adult males with ASD and 26 age and IQ-matched typically developed males were presented with flash-beep (BF), point-light drummer, and face-voice (FV) displays with varying degrees of asynchrony and asked to make Synchrony Judgements (SJ) and Temporal Order Judgements (TOJ). Analysis of the data included fitting Gaussian functions as well as using an Independent Channels Model (ICM) to fit the data (Garcia-Perez & Alcala-Quintana, 2012). Gaussian curve fitting for SJs showed that the ASD group had a wider TIW, but for TOJ no group effect was found. The ICM supported these results and model parameters indicated that the wider TIW for SJs in the ASD group was not due to sensory processing at the unisensory level, but rather due to decreased temporal resolution at a decisional level of combining sensory information. Furthermore, when performing TOJ, the ICM revealed a smaller Point of Subjective Simultaneity (PSS; closer to physical synchrony) in the ASD group than in the TD group. Finding that audiovisual temporal processing is different in ASD encouraged us to investigate the neural correlates of multisensory as well as unisensory processing using functional magnetic resonance imaging fMRI. Therefore, Chapter 4 investigated audiovisual, auditory and visual processing in ASD of simple BF displays and complex, social FV displays. During a block design experiment, we measured the BOLD signal when 13 adults with ASD and 13 typically developed (TD) age-sex- and IQ- matched adults were presented with audiovisual, audio and visual information of BF and FV displays. Our analyses revealed that processing of audiovisual as well as unisensory auditory and visual stimulus conditions in both the BF and FV displays was associated with reduced activation in ASD. Audiovisual, auditory and visual conditions of FV stimuli revealed reduced activation in ASD in regions of the frontal cortex, while BF stimuli revealed reduced activation the lingual gyri. The inferior parietal gyrus revealed an interaction between stimulus sensory condition of BF stimuli and group. Conjunction analyses revealed smaller regions of the superior temporal cortex (STC) in ASD to be audiovisual sensitive. Against our predictions, the STC did not reveal any activation differences, per se, between the two groups. However, a superior frontal area was shown to be sensitive to audiovisual face-voice stimuli in the TD group, but not in the ASD group. Overall this study indicated differences in brain activity for audiovisual, auditory and visual processing of social and non-social stimuli in individuals with ASD compared to TD individuals. These results contrast previous behavioural findings, suggesting different audiovisual integration, yet intact auditory and visual processing in ASD. Our behavioural findings revealed audiovisual temporal processing deficits in ASD during SJ tasks, therefore we investigated the neural correlates of SJ in ASD and TD controls. Similar to Chapter 4, we used fMRI in Chapter 5 to investigate audiovisual temporal processing in ASD in the same participants as recruited in Chapter 4. BOLD signals were measured while the ASD and TD participants were asked to make SJ on audiovisual displays of different levels of asynchrony: the participants’ PSS, audio leading visual information (audio first), visual leading audio information (visual first). Whereas no effect of group was found with BF displays, increased putamen activation was observed in ASD participants compared to TD participants when making SJs on FV displays. Investigating SJ on audiovisual displays in the bilateral superior temporal gyrus (STG), an area involved in audiovisual integration (see Chapter 4), we found no group differences or interaction between group and levels of audiovisual asynchrony. The investigation of different levels of asynchrony revealed a complex pattern of results indicating a network of areas more involved in processing PSS than audio first and visual first, as well as areas responding differently to audio first compared to video first. These activation differences between audio first and video first in different brain areas are constant with the view that audio leading and visual leading stimuli are processed differently.

Heat transfer performance investigation of nanofluids flow in pipe

Different types of base fluids, such as water, engine oil, kerosene, ethanol, methanol, ethylene glycol etc. are usually used to increase the heat transfer performance in many engineering applications. But these conventional heat transfer fluids have often several limitations. One of those major limitations is that the thermal conductivity of each of these base fluids is very low and this results a lower heat transfer rate in thermal engineering systems. Such limitation also affects the performance of different equipments used in different heat transfer process industries. To overcome such an important drawback, researchers over the years have considered a new generation heat transfer fluid, simply known as nanofluid with higher thermal conductivity. This new generation heat transfer fluid is a mixture of nanometre-size particles and different base fluids. Different researchers suggest that adding spherical or cylindrical shape of uniform/non-uniform nanoparticles into a base fluid can remarkably increase the thermal conductivity of nanofluid. Such augmentation of thermal conductivity could play a more significant role in enhancing the heat transfer rate than that of the base fluid. Nanoparticles diameters used in nanofluid are usually considered to be less than or equal to 100 nm and the nanoparticles concentration usually varies from 5% to 10%. Different researchers mentioned that the smaller nanoparticles concentration with size diameter of 100 nm could enhance the heat transfer rate more significantly compared to that of base fluids. But it is not obvious what effect it will have on the heat transfer performance when nanofluids contain small size nanoparticles of less than 100 nm with different concentrations. Besides, the effect of static and moving nanoparticles on the heat transfer of nanofluid is not known too. The idea of moving nanoparticles brings the effect of Brownian motion of nanoparticles on the heat transfer. The aim of this work is, therefore, to investigate the heat transfer performance of nanofluid using a combination of smaller size of nanoparticles with different concentrations considering the Brownian motion of nanoparticles. A horizontal pipe has been considered as a physical system within which the above mentioned nanofluid performances are investigated under transition to turbulent flow conditions. Three different types of numerical models, such as single phase model, Eulerian-Eulerian multi-phase mixture model and Eulerian-Lagrangian discrete phase model have been used while investigating the performance of nanofluids. The most commonly used model is single phase model which is based on the assumption that nanofluids behave like a conventional fluid. The other two models are used when the interaction between solid and fluid particles is considered. However, two different phases, such as fluid and solid phases is also considered in the Eulerian-Eulerian multi-phase mixture model. Thus, these phases create a fluid-solid mixture. But, two phases in the Eulerian-Lagrangian discrete phase model are independent. One of them is a solid phase and the other one is a fluid phase. In addition, RANS (Reynolds Average Navier Stokes) based Standard κ-ω and SST κ-ω transitional models have been used for the simulation of transitional flow. While the RANS based Standard κ-ϵ, Realizable κ-ϵ and RNG κ-ϵ turbulent models are used for the simulation of turbulent flow. Hydrodynamic as well as temperature behaviour of transition to turbulent flows of nanofluids through the horizontal pipe is studied under a uniform heat flux boundary condition applied to the wall with temperature dependent thermo-physical properties for both water and nanofluids. Numerical results characterising the performances of velocity and temperature fields are presented in terms of velocity and temperature contours, turbulent kinetic energy contours, surface temperature, local and average Nusselt numbers, Darcy friction factor, thermal performance factor and total entropy generation. New correlations are also proposed for the calculation of average Nusselt number for both the single and multi-phase models. Result reveals that the combination of small size of nanoparticles and higher nanoparticles concentrations with the Brownian motion of nanoparticles shows higher heat transfer enhancement and thermal performance factor than those of water. Literature suggests that the use of nanofluids flow in an inclined pipe at transition to turbulent regimes has been ignored despite its significance in real-life applications. Therefore, a particular investigation has been carried out in this thesis with a view to understand the heat transfer behaviour and performance of an inclined pipe under transition flow condition. It is found that the heat transfer rate decreases with the increase of a pipe inclination angle. Also, a higher heat transfer rate is found for a horizontal pipe under forced convection than that of an inclined pipe under mixed convection.

Balancing the demands of two tasks: an investigation of cognitive-motor dual-tasking in relapsing remitting multiple sclerosis

Background: People with relapsing remitting MS (PwRRMS) suffer disproportionate decrements in gait under dual-task conditions, when walking and a cognitive task are combined. There has been much less investigation of the impact of cognitive demands on balance. This study investigated whether: (1) PwRRMS show disproportionate decrements in postural stability under dual-task conditions compared to healthy controls; (2) dual-task decrements are associated with everyday dual-tasking difficulties. In addition, the impact of mood, fatigue and disease severity on dual-tasking were also examined. Methods: 34 PwRRMS and 34 matched controls completed cognitive (digit span) and balance (movement of centre of pressure on a Biosway, on stable and unstable surfaces) tasks under single and dual-task conditions. Everyday dual-tasking was measured using the DTQ. Mood was measured by the HADS. Fatigue was measured via the MFIS. Results: No differences in age, gender, years of education, estimated pre-morbid IQ or baseline digit span between the groups. Compared to healthy controls, PwRRMS showed a significantly greater decrement in postural stability under dual-task conditions on an unstable surface (p=0.007), but not a stable surface (p=0.679). PwRRMS reported higher levels of everyday dual-tasking difficulties (p<0.001). Balance decrement scores were not correlated with everyday dual-tasking difficulties, or with fatigue. Stable surface balance decrement scores were significantly associated with levels of anxiety (rho=0.527, p=0.001) and depression (rho=0.451, p=0.007). Conclusion: RRMS causes difficulties with dual-tasking, impacting balance, particularly under challenging conditions, which may contribute to an increased risk of gait difficulties and falls. The striking relationship between anxiety/depression and dual-task decrement suggests that worry may be contributing to dual-task difficulties.

Simulation tools for the analysis of single electronic systems

Developments in theory and experiment have raised the prospect of an electronic technology based on the discrete nature of electron tunnelling through a potential barrier. This thesis deals with novel design and analysis tools developed to study such systems. Possible devices include those constructed from ultrasmall normal tunnelling junctions. These exhibit charging effects including the Coulomb blockade and correlated electron tunnelling. They allow transistor-like control of the transfer of single carriers, and present the prospect of digital systems operating at the information theoretic limit. As such, they are often referred to as single electronic devices. Single electronic devices exhibit self quantising logic and good structural tolerance. Their speed, immunity to thermal noise, and operating voltage all scale beneficially with junction capacitance. For ultrasmall junctions the possibility of room temperature operation at sub picosecond timescales seems feasible. However, they are sensitive to external charge; whether from trapping-detrapping events, externally gated potentials, or system cross-talk. Quantum effects such as charge macroscopic quantum tunnelling may degrade performance. Finally, any practical system will be complex and spatially extended (amplifying the above problems), and prone to fabrication imperfection. This summarises why new design and analysis tools are required. Simulation tools are developed, concentrating on the basic building blocks of single electronic systems; the tunnelling junction array and gated turnstile device. Three main points are considered: the best method of estimating capacitance values from physical system geometry; the mathematical model which should represent electron tunnelling based on this data; application of this model to the investigation of single electronic systems. (DXN004909)

Surface acoustic wave streaming in a PDMS microfluidic system: effect of frequency and fluid geometry & A remote ultrasonic glucose sensor

This thesis describes two separate projects. The first is a theoretical and experimental investigation of surface acoustic wave streaming in microfluidics. The second is the development of a novel acoustic glucose sensor. A separate abstract is given for each here. Optimization of acoustic streaming in microfluidic channels by SAWs Surface Acoustic Waves, (SAWs) actuated on flat piezoelectric substrates constitute a convenient and versatile tool for microfluidic manipulation due to the easy and versatile interfacing with microfluidic droplets and channels. The acoustic streaming effect can be exploited to drive fast streaming and pumping of fluids in microchannels and droplets (Shilton et al. 2014; Schmid et al. 2011), as well as size dependant sorting of particles in centrifugal flows and vortices (Franke et al. 2009; Rogers et al. 2010). Although the theory describing acoustic streaming by SAWs is well understood, very little attention has been paid to the optimisation of SAW streaming by the correct selection of frequency. In this thesis a finite element simulation of the fluid streaming in a microfluidic chamber due to a SAW beam was constructed and verified against micro-PIV measurements of the fluid flow in a fabricated device. It was found that there is an optimum frequency that generates the fastest streaming dependent on the height and width of the chamber. It is hoped this will serve as a design tool for those who want to optimally match SAW frequency with a particular microfluidic design. An acoustic glucose sensor Diabetes mellitus is a disease characterised by an inability to properly regulate blood glucose levels. In order to keep glucose levels under control some diabetics require regular injections of insulin. Continuous monitoring of glucose has been demonstrated to improve the management of diabetes (Zick et al. 2007; Heinemann & DeVries 2014), however there is a low patient uptake of continuous glucose monitoring systems due to the invasive nature of the current technology (Ramchandani et al. 2011). In this thesis a novel way of monitoring glucose levels is proposed which would use ultrasonic waves to ‘read’ a subcutaneous glucose sensitive-implant, which is only minimally invasive. The implant is an acoustic analogy of a Bragg stack with a ‘defect’ layer that acts as the sensing layer. A numerical study was performed on how the physical changes in the sensing layer can be deduced by monitoring the reflection amplitude spectrum of ultrasonic waves reflected from the implant. Coupled modes between the skin and the sensing layer were found to be a potential source of error and drift in the measurement. It was found that by increasing the number of layers in the stack that this could be minimized. A laboratory proof of concept system was developed using a glucose sensitive hydrogel as the sensing layer. It was possible to monitor the changing thickness and speed of sound of the hydrogel due to physiological relevant changes in glucose concentration.

LHC main dipole magnet circuits: sustaining near-nominal beam energies

Crossing the Franco-Swiss border, the Large Hadron Collider (LHC), designed to collide 7 TeV proton beams, is the world's largest and most powerful particle accelerator the operation of which was originally intended to commence in 2008. Unfortunately, due to an interconnect discontinuity in one of the main dipole circuit's 13 kA superconducting busbars, a catastrophic quench event occurred during initial magnet training, causing significant physical system damage. Furthermore, investigation into the cause found that such discontinuities were not only present in the circuit in question, but throughout the entire LHC. This prevented further magnet training and ultimately resulted in the maximum sustainable beam energy being limited to approximately half that of the design nominal, 3.5-4 TeV, for the first three years of operation (Run 1, 2009-2012) and a major consolidation campaign being scheduled for the first long shutdown (LS 1, 2012-2014). Throughout Run 1, a series of studies attempted to predict the amount of post-installation training quenches still required to qualify each circuit to nominal-energy current levels. With predictions in excess of 80 quenches (each having a recovery time of 8-12+ hours) just to achieve 6.5 TeV and close to 1000 quenches for 7 TeV, it was decided that for Run 2, all systems be at least qualified for 6.5 TeV operation. However, even with all interconnect discontinuities scheduled to be repaired during LS 1, numerous other concerns regarding circuit stability arose. In particular, observations of an erratic behaviour of magnet bypass diodes and the degradation of other potentially weak busbar sections, as well as observations of seemingly random millisecond spikes in beam losses, known as unidentified falling object (UFO) events, which, if persist at 6.5 TeV, may eventually deposit sufficient energy to quench adjacent magnets. In light of the above, the thesis hypothesis states that, even with the observed issues, the LHC main dipole circuits can safely support and sustain near-nominal proton beam energies of at least 6.5 TeV. Research into minimising the risk of magnet training led to the development and implementation of a new qualification method, capable of providing conclusive evidence that all aspects of all circuits, other than the magnets and their internal joints, can safely withstand a quench event at near-nominal current levels, allowing for magnet training to be carried out both systematically and without risk. This method has become known as the Copper Stabiliser Continuity Measurement (CSCM). Results were a success, with all circuits eventually being subject to a full current decay from 6.5 TeV equivalent current levels, with no measurable damage occurring. Research into UFO events led to the development of a numerical model capable of simulating typical UFO events, reproducing entire Run 1 measured event data sets and extrapolating to 6.5 TeV, predicting the likelihood of UFO-induced magnet quenches. Results provided interesting insights into the involved phenomena as well as confirming the possibility of UFO-induced magnet quenches. The model was also capable of predicting that such events, if left unaccounted for, are likely to be commonplace or not, resulting in significant long-term issues for 6.5+ TeV operation. Addressing the thesis hypothesis, the following written works detail the development and results of all CSCM qualification tests and subsequent magnet training as well as the development and simulation results of both 4 TeV and 6.5 TeV UFO event modelling. The thesis concludes, post-LS 1, with the LHC successfully sustaining 6.5 TeV proton beams, but with UFO events, as predicted, resulting in otherwise uninitiated magnet quenches and being at the forefront of system availability issues.