Continuum neural field models mimic the large scale spatio-temporal dynamics of interacting neurons on a cortical surface. For smooth Mexican hat kernels, with short-range excitation and long-range inhibition, they support various localised structures as well as travelling waves similar to those seen in real cortex. These non-local models have been extensively studied, both analytically and numerically, yet there remain open challenges in their study. Here we provide new numerical and analytical treatments for the study of spatio-temporal pattern formation in neural field models. In this context, the description of spreading patterns with a well identified interface is of particular interest, as is their dependence on boundary conditions. This Thesis is dedicated to the analyses of one- and two-dimensional localised states as well as travelling waves in neural fields. Firstly we analyse the effects of Dirichlet boundary conditions on shaping and creating localised bumps in one- dimensional spatial models, and then on the development of labyrinthine structures in two spatial dimensions. Linear stability analysis is used to understand how spatially extended patterns may develop in the absence and presence of boundary conditions. For the case without boundary conditions we recover the results of Amari, namely the widest bump among two branches of solutions is stable. However, new stable solutions can arise with an imposed Dirichlet boundary condition. For a Heaviside non-linearity, the Amari model allows a description of solutions using an equivalent interface dynamics. We generalise this reduced, yet exact, description by deriving a normal velocity rule that can account for boundary conditions. We extend this approach to further treat neural field models with spike frequency adaptation. These can exhibit breathers and travelling waves. The latter can take the form of spiral waves, to which we devote particular attention. We further study neural fields on feature spaces in the primary visual cortex (V$1$), where cells respond preferentially to edges of a particular orientation. Considering a general form of the synaptic kernel which includes an orientation preference at each spatial point, we present the construction and stability of orientation bumps, as well as stripes. To date there has been surprisingly little analysis of spatio-temporal pattern formation in neural field equations described on curved surfaces. Finally, we study travelling fronts and pulses on non-flat geometries, where we consider the effects of inhomogeneities on the propagation velocity of these waves. In all sections, theoretical results for pattern formation are shown to be in excellent agreement with simulations of the full neural field models.

Manipulating somatic representations has been found to alter somatic experiences; however, the precise mechanisms underlying these altered somatic experiences are as yet unclear. This thesis primarily investigated the mechanisms underlying altered somatic experiences following illusions that manipulated perception of the body representation. The current thesis also addressed individual differences in somatic perception across individuals with propensities towards various clinical conditions, including amplified somatosensory sensitivity and medically unexplained symptoms (MUS). The pilot investigation in Chapter 3 provided evidence for susceptibility and ownership towards somatic illusions generated using the MIRAGE mediated-reality system, thus validating manipulations induced using this system. In Chapter 4, longer and shorter body representations were judged as veridical (or normal) following stretched and shrunken illusions respectively, while in contrast to early studies ownership was not lost as a result of the illusory manipulations. An association between self-reported somatic sensitivity and illusion strength was also observed for females, with females reporting increased somatic sensitivity being more susceptible to the illusion. Chapter 5 demonstrated that illusory alterations of body shape and size improved perception of near threshold tactile stimuli. However, changes in tactile perception were driven by differing mechanisms when body size at the site of stimulation was altered, whilst similar mechanisms drove this change when body size away from the site of stimulation was altered. Interestingly, a detached condition (in which the finger-tip and stump were disconnected) resulted in a significant reduction in overall positive reports of feeling tactile stimuli. Finally, overall false-touch reports and reduced sensitivity (i.e., the inability to discern between touch present and absent trials) were found to be characteristic of those with propensities towards MUS. Chapter 6 demonstrated that a purely visual illusion, in the absence of any real somatic input, did not interfere with external tactile perception or lead to different response patterns between individuals with increased or decreased tendencies towards MUS. The thesis provides evidence for the dynamic and bidirectional flexibility of the body representation by providing direct evidence for the immediate updating of the body representation following size-altering illusory manipulations. These illusions also altered external somatic sensations via different underlying mechanisms and reflected individual differences in response patterns between healthy and sub-clinical populations, thus suggesting that susceptibility to such illusions may be clinically relevant, and useful in identifying the nature various psychological pathologies.

Skin texture and colour play an important role in the judgment of apparent health (Fink, Grammer, & Thornhill, 2001; Jones, Little, Burt, & Perrett, 2004; Matts, Fink, Grammer, & Burquest, 2007; Samson, Fink, & Matts, 2010; Stephen, Coetzee, Law Smith, & Perrett, 2009a; Stephen, Coetzee, & Perrett, 2011), and have been linked to aspects of physiological health, including fitness, immunity and fertility (Armstrong & Welsman, 2001; Jones et al., 2015; Stephen et al., 2011). The current thesis examines the contribution of skin condition to health perception in Malaysian Chinese. The thesis comprises six chapters. Chapter one offers a general introduction to the topic. It outlines key literature on health perception, and explains the research problem, the objectives and relevance of the studies conducted. Chapter 2 consists of three studies which examine Malaysian Chinese participants’ perception of apparent health. The three studies revealed the significance of both skin texture, and skin colour in forming health perceptions. Examining the sensitivity threshold of human vision to colour changes, Chapter 3 discovered that individuals tend to be more sensitive to changes in redness and yellowness than luminance; and this extra-sensitivity in chrominance is specific to the perception of human faces, and not non-face objects or colour patches. Following the finding of preference for slightly yellower skin, Chapter 4 reported a supplementation study, whereby an increment in skin yellowness and redness was observed for participants who were prescribed the fruit and vegetable smoothie (and not for the control group). Using the face images obtained in the intervention study, the three perceptual studies in Chapter 5 were designed to examine the amount of carotenoid colouration that is needed to optimize healthy appearance of Malaysian Chinese faces. Too much colour change was not preferred and, in the last study, it seems that the appropriate amount of carotenoid colouration preferred is only one third of the amount observed in the intervention study. Collectively, these nine studies deepen our knowledge of health perception, especially the importance of skin colour in determining perceived human facial health. Implications and suggestions for future research are presented in Chapter 6.

The physiology and function of nociceptive and opioid signalling pathways undergo substantial postnatal maturation, and supraspinal µ-opioid receptor (MOR)-mediated control of nociceptive signalling is significantly different in juveniles and adults. Here the, mechanisms responsible for these changes were investigated. [35S]GTPγS assays utilising the MOR-selective agonist DAMGO demonstrated concentration-dependent G protein activation within rostral ventromedial medulla (RVM) tissue which was significantly different between rats aged postnatal day (P) 21 and adults (>P40) (adult: EC50 = 351.1 nM; Emax = 179% basal response; P21: EC50 = 129.3 nM; Emax = 150.9% basal response; Extra sum-of-squares F-test comparing concentration-response curves; P < 0.001). However in adult tissue, co-application of DAMGO with the ganglioside GM1 (1 µM), which has previously been shown to alter MOR G protein coupling from Gi to Gs, revealed that modulation of MOR by GM1 was not responsible for this difference (P > 0.05). Aside from expression on neurones, MOR are expressed by microglia, though the extent and functional consequences are subject to some controversy. Intracellular imaging of changes in calcium concentration using the fluorescent indicator dye Fura-2 showed that ATP-induced concentration-dependent increases in intracellular calcium were significantly increased in primary microglial cultures isolated from adult (EC50 = 2.91 µM; Emax = 0.37 Fmax - F0, the increase in 340/380 nm fluorescence ratio from baseline) versus neonatal (P1) (EC50 = 3.03 µM; Emax = 0.20 Fmax - F0; Extra sum-of-squares F-test comparing concentration-response curves; P < 0.01) brain tissue, and that co-application of DAMGO (1 µM) potentiated responses in adult microglia (EC50 = 1.56 µM; Emax = 0.57 Fmax - F0) but inhibited responses in neonatal microglia (EC50 = 2.65 µM; Emax = 0.14 Fmax - F0), suggesting postnatal alterations in microglial modulation of nociceptive signalling. Additionally, the expression of opioid receptors and their endogenous ligands human mid-brain were investigated using TaqMan RT-PCR. This did not reveal any age-related alterations in mRNA transcript levels of these genes (P > 0.05 for all), confirming previous findings in rats. Previously it has been demonstrated that painful experience during the neonatal period can have a lasting influence on pain processing and adult sensory thresholds. Investigations into opioidergic signalling as one of the mechanisms responsible were conducted with hindpaw injection of complete Freund’s adjuvant (CFA; 10 µl), which induced oedema and erythema in rats aged P1, P10 and P21. As expected this failed to induce decreases in mechanical paw withdrawal threshold (PWT) in P1 rats, in contrast to all other ages. Examining infiltrating macrophages during the acute inflammatory process revealed significant alterations between adults and neonates in cells expressing ED1 and mannose receptor, suggesting altered peripheral inflammatory processes in the neonate. Despite the aforementioned postnatal alterations in MOR-mediated control of nociception, administration of the opioid receptor antagonist naltrexone (3 mg/kg) unmasked resolved inflammatory hyperalgesia in rats injured as early as P10, showing that constitutive MOR activity is able to suppress latent pain sensitisation from an early age but not from birth, highlighting the functional immaturity of this system in early postnatal life. The impact of neonatal inflammation on hyperalgesic priming, a model of the transition from acute to chronic pain, was also investigated. CFA at P1 failed to alter adult responses to hindpaw injection of carrageenan (5 µl; 1%)-induced inflammation, did not alter the development of hyperalgesic priming (increased duration of response to hindpaw injection of PGE2; 1 µg/5 µl) and did not itself induce priming. These results suggest that previously observed life-long effects of neonatal injury are dependent on nociceptive signalling to the spinal cord rather than the presence of inflammation itself.

The basal ganglia (BG) are a group of highly interconnected nuclei that are located deep at the base of the cerebral cortex. They participate in multiple neural circuits or 'loops' with cognitive and motor areas of the cerebral cortex. The basal ganglia has primarily been thought to be involved in motor control and learning, but more recently a number of brain imaging studies have shown that the basal ganglia are involved also in cognitive function. The aim of this work is to investigate the role of the basal ganglia in cognitive control and motor learning by examining its involvement in GO/WAIT and GO/NO-GO tasks, and Motor Prediction task, respectively. Ultra-high field (7 Tesla) fMRI is used to provide higher BOLD contrast and thus higher achievable spatial resolution. A dual echo gradient echo EPI method is used to obtain high quality images from both cortical and sub-cortical regions. A common neural basis across different forms of response inhibition using GO/WAIT and GO/NO-GO cognitive paradigms is observed in the experiments of Chapter 4, as well as distinct brain regions involved in withholding and cancelling of motor responses. Using the GO/WAIT cognitive paradigm in Chapter 5 individuals with Tourette syndrome (TS) are compared to age and gender-matched control healthy subjects (CS), and it is shown that TS subjects are unable to recruit critical cortical and sub-cortical nodes that are typically involved in mediating behavioural inhibition. Furthermore, in Chapter 6, the role of the basal ganglia in motor learning is investigated using the Motor Prediction task. The findings show that the basal ganglia and midbrain regions (i.e., habenula) are involved in motor prediction and enhancing the reinforcement learning process. This thesis aims to investigate the basal ganglia function in cognitive and motor tasks, and concludes with suggested further studies to advance our understanding of the role of the basal ganglia nuclei in cognitive function.

Studies investigating human information processing have provided evidence that in some cases, movements can be prepared in advance. Although evidence for motor preparation has been shown at cortical and spinal levels, motor preparation at a subcortical level is not well described. One line of inquiry has involved the use of a startling acoustic stimulus (115-124 dB) that can act as an early trigger for pre-programmed actions in reaction time (RT) tasks. In light of this new research paradigm, the startle reflex may be used as a tool to investigate motor preparation. Here, six experiments were conducted that work towards the goals of understanding the mechanism of RT shortening due to startle, and motor preparation at a subcortical level. The first section (2 experiments) of this dissertation provides evidence that when a motor action can be prepared in advance, it is pre-programmed and stored subcortically awaiting the normal cortical “go” signal. A startle appears to activate structures directly that are involved with the voluntary response channel leading to early triggering of the pre-programmed response, and dramatically reduced RT. In the current dissertation we investigated alternative mechanisms to explain startle RT facilitation, including the stimulus intensity effect, and a fast transcortical route, with results supporting the original subcortical storage hypothesis. The second section (4 experiments) presents data which together provide insight into motor programming processes, and the circumstances under which a response is pre-programmed. For example, when the possibility of not having to make the response existed, a known response was not pre-programmed. Similarly, no pre-programming occurred when certainty existed regarding when to respond. However, while a previous experiment showed that having to make a choice between several response alternatives precluded pre-programming, this dissertation shows that if possible response alternatives are not in conflict with one another, multiple responses can be prepared in parallel. Finally, the complexity of a response such as one involving multiple sequenced sub-components may limit the ability to pre-program in a simple RT task. Taken together, these results suggest that pre-programming is dependent on the task characteristics and appears to involve implementation of strategies to increase programming efficiency. / Education, Faculty of / Kinesiology, School of / Graduate

The drug sensitivity of neurones of the Nucleus ventralis lateralis (VL) of the thalamus, and their synaptic activation by electrical stimulation of brachium conjunctivum (BC), precruciate cortex and entopenduncular nucleus, (EN) has been studied in anesthetized and in decerebrate cats. Cells evoked with short latency by BC stimulation were particularly sensitive to excitation by iontophoretically applied acetylcholine (ACh) and L-glutamate (LG) when compared with cells of more dorsal thalamic nuclei. The VL neurones did not exhibit such an enhanced sensitivity to DL-homocysteic acid and N-methyl aspartic acid. The α-methyl derivative of glutamic acid (α-MG) was found in many cases to depress or block the excitation of thalamic neurones by LG, but had no effect on ACh excitation. α-MG sometimes depressed the effects of other excitatory amino acids, but to a lesser degree than those produced by LG. Short latency single action potential and late burst responses evoked in VL by BC or cortical stimulation have been reported by other workers and were confirmed in this study. However, it was found that both cortical and BC stimulus evoked early burst responses which were observed only in anesthetized animals. EN stimulation evoked burst response in VL neurones with latencies of 4-22 msec. Both the early burst and the EN evoked responses could be converted to shorter latency single spikes by iontophoretically applied amino acids and ACh. ACh facilitated synaptic activation by cortical and BC stimuli but could either excite or depress the responses to EN stimulation. Iontophoretically applied atropine and dihydro-β-erythroidine blocked ACh excitation of VL cells but did not alter their synaptic activation, although atropine could reverse the ACh depression of EN evoked responses. Intravenous atropine in doses of 0.5-1.0 mgm/kgm also blocked these ACh effects, but in addition markedly reduced the BC evoked field response in VL without affecting the response to cortical stimulation. It was concluded that the pathways from EN and motor cortex to VL are unlikely to be cholinergically mediated, but that ACh may be the synaptic transmitter for at least part of the cerebello-thalamic pathway. Pentobarbital and α-chloralose were potent blockers of ACh excitation in VL neurones.. It was shown that neurones of EN give rise to collateral axon branches which project to VL and N. centrum-medianum. Stimulation of sensori-motor cortex evoked cell and field responses in the lateral, but not the medial parts of the centrum medianum-Parafascicular complex. / Medicine, Faculty of / Cellular and Physiological Sciences, Department of / Graduate

Rationale: Chronic cough (cough >8 weeks) is common, leads to an impaired quality of life, and is difficult to treat. Despite intensive investigation, ~40% of patients referred to a specialist cough clinic will remain resistant to treatment targeted at peripheral triggers such as reflux disease, rhino-sinusitis or airways inflammation. An improved understanding of underlying mechanisms in such patients would facilitate drug development. I propose that there are several important similarities between pain and cough that can be exploited better to understand underlying mechanisms. In chronic pain, a long-lasting up-regulation of afferent pain processing may be generated by changes within the central nervous system, mediated by the NMDA receptor and/or by impaired inhibitory mechanisms. A similar central neuronal up-regulation of cough may also be responsible for the pathogenesis of chronic cough (CC). Methods: A series of experimental studies were performed to address this hypothesis. Firstly, the anti-tussive and analgesic effect of ketamine, an NMDA receptor antagonist, was investigated in CC patients and healthy controls (HC). Pain thresholds were measured using electrical stimulation in the oesophagus, pharynx and chest wall. Cough sensitivity was measured using standard capsaicin cough challenges. Secondly, I designed and tested novel capsaicin cough challenges in CC patients, asthmatics (A) and HC. ED50 (dose inducing and least 50% maximal cough frequency) and Cmax (maximal cough frequency) was compared by group and gender. Finally, I investigated 2 independent mechanisms of cough inhibition. Results:(i) CC patients, but not HC, had cough induced by oesophageal electrical stimulation, whilst pain thresholds were similar. Ketamine had a significant analgesic effect but no antitussive effect in CC or HC.(ii) CC patients had both cough hypersensitivity (lower ED50) and cough hyper-responsiveness (higher Cmax) on full capsaicin dose-response curves. (iii) Both a painful cold stimulus applied to the hand and conscious cough suppression significantly inhibited capsaicin-induced cough responses in CC and HC.Conclusions:CC patients exhibited increased oesophageal sensitivity to cough, but not pain, providing evidence for a process of central sensitisation in the brainstem. Higher capsaicin-induced cough frequencies in CC may also be mediated by an increased gain within the CNS, possibly because of failed tonic inhibitory mechanisms. Furthermore, CC patients may have poorer conscious control of coughing. In conclusion, an improved understanding of mechanisms in cough will provide a strong scientific rationale for the development of novel therapeutics.

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No description available.