Adaptation is a reduction in a neural response to a sensory stimulus resulting from repeated presentation of the stimulus and is an important aspect of sensory neural coding. This phenomenon is sensitive to changes in parameters of the repeating stimuli and the adaptation will be greatest when the stimuli are identical and diminish with changes in stimulus parameters between repetitions. In the auditory system it has been shown the specificity of cortical adaptation relates primarily to the frequency of a stimulus, with wider frequency separations between sequentially presented stimuli resulting in a reduced level of adaptation. This frequency specific adaptation has been measured at multiple scales, in EEG recordings in humans and at the single unit level in animals but the results from each implicate different underlying neural mechanisms. This thesis attempts to elucidate some of those differences by investigating the effects of the differences in methodology between the studies, the inter-species differences in adaptation characteristics and the effects of anaesthesia on sensory neural processing. This touches upon the forward and inverse modelling problems in computational neuroscience and also the issues with relating results from EEG in awake humans with single neuron recordings in anaesthetised animals. The thesis starts by building on previous work looking at whether the frequency selectivity of adaptation can be changed by the temporal properties of the adapting stimuli. It was found that a sharpening of frequency selectivity of adaptation could be induced by using multiple repeated adapters but not with single onset, prolonged duration adapters. This repetition induced sharpening was also shown to act independently of attention despite there being an attentionally induced sharpening effect on adaptation. This EEG adaptation tuning was explained by an extension of a computational model previously proposed to explain stimulus specific adaptation and oddball responses in single neurons. The model was a two-layer network with independently adapting synapses and is able to quantitatively reproduce the observed non-monotonic adaptation and sharpening of tuning observed in our EEG responses, and the effects of repeated and prolonged adapters. To further investigate this then this study was replicated in an anaesthetised animal model with recordings directly from auditory cortex. This study showed none of the repetition induced sharpening effects and dramatically quantitatively different adaptation results compared to the human studies. To help explain these results then recordings were made in awake guinea pigs with chronically implanted intracranial EEG electrodes and invasive depth electrodes to discover whether these differences were a result of species or anaesthesia. These experiments start to explain some of the discrepancies seen before, with adaptation time constants orders of magnitude different to those in humans and differences in their innate frequency selectivity. Alongside this then the effects of anaesthesia on the results were investigated under a range of anaesthetic regimes including opiates, NMDA antagonists and GABA potentiators. It was shown that anaesthetic choice has substantial effects on sensory signalling, temporal processing and cross-modal interactions which result in multifaceted effects on the characteristics of adaptation. This thesis builds on previous work on the plasticity of frequency selectivity of adaptation in auditory cortex and helps to characterise this phenomenon and explain its mechanisms. This work also highlights the difficulties of directly relating studies and findings between humans and animal studies of the auditory system, demonstrating the magnitude of difference in temporal and frequency processing between species and also shows the substantial changes in sensory processing induced by anaesthesia and modulated by anaesthetic choice.

This thesis has examined nonlinear signal summation using a combination of EEG and computational modelling. Nonlinearities are essential to many perceptual phenomena, but remain poorly understood beyond the earliest levels of the sensory pathways. Many nonlinear physiological phenomena, such as cross-orientation suppression (XOS), can be readily described by models of normalisation for neuronal gain control in primary visual cortex (V1). However, there are several nonlinearities that normalisation cannot fully explain. For example, super saturation – which can occur in around 17% of V1 and 25% of V2 neurons in macaque (Peirce, 2007b) – would be considered metabolically wasteful within a framework of normalisation: an over- exertion of the normalisation pool upon the excitatory response of a neuron. It seems unlikely that this non-monotonic nonlinearity does not serve a purpose. Considering this, gain control may not be the only function served by nonlinearities in the visual system (and beyond). Peirce (2007b, 2011, 2013) proposed that nonlinearities in V1 could also be used by neurons in mid-level vision to detect signal conjunctions for combinations of stimuli. This kind of signal summation would make possible neurons with more complex receptive field preferences than are commonly observed in V1. For example, neurons that are sensitive to multiple orientations and a narrow bandwidth of spatial frequencies would be useful for detecting patterns coherent plaids. However, at any one point in time, several different nonlinearities can occur in response to a stimulus. Being able to distinguish one from the other is more difficult than it might at first seem. The experiments described throughout this thesis aimed to disentangle nonlinearities, identify those that were selective for specific stimulus combinations and characterise them. In Chapter 3 we used transient electroencephalography (EEG) to measure the earliest component – C1 – of visual evoked potentials (VEPs) to brief presentations of gratings and their combinations into coherent and non-coherent plaids. By comparing the C1 response to gratings and plaids, we aimed to measure the degree of nonlinear summation taking place for coherent and non-coherent grating combinations. The outcome was inconclusive; there was limited evidence to suggest the involvement of extra nonlinearities in the processing of coherent plaids that were not involved in processing non-coherent plaids. This might be an inherent problem with the transient EEG approach. Although it produces a rich time course of data following the presentation of a stimulus, the response is the sum of many nonlinearities. To overcome this, we took an alternative approach in Chapter 4 and used the two-frequency method of steady-state EEG. This allows you to tag each of the grating components forming a plaid, as well as directly measure nonlinearities at intermodulation frequencies. We found a plaid-selective intermodulation response, which was larger for coherent plaids than it was for non-coherent plaids. In support of this representing an additional nonlinearity beyond normalisation, the degree of component suppression did not differ between coherent and non-coherent plaids for any of the grating components used. We generated a simple two-layered computational model of signal summation to try and explain the complexity of responses generated in to combinations of gratings. The model took the form of a logical AND gate, allowing it to respond selectively to conjunctions of signals. It appears that this kind of mechanism can represent well the responses we observed using EEG. It is not clear how a mechanism that makes use of saturating nonlinearities to perform selective signal summation would behave across contrast. At lower contrast levels, before many neurons reach the rising slope of their dynamic range, it might be that the mechanism fails altogether. Using a similar paradigm to Chapter 4, we measured intermodulation responses across a wide range of contrast levels in Chapter 5. We again found a selective intermodulation response that was larger for coherent plaids. However, this difference only occurred at the highest component contrast level that we used – 32%. Having found a nonlinearity in the visual system that appeared to selective for particular combinations of grating stimuli, we wanted to investigate whether similar nonlinearities are put to use in other brain regions. In Chapter 6 we generated auditory stimuli – three pure tones – that were combined to form a consonant and a dissonant chord. Substantial component suppression was observed for one of the components. However, no intermodulation responses or component-based harmonic responses were observed. Bringing these findings together, the transient approach to measuring nonlinear responses is somewhat limited, and provided only hints at what might be the presence of ‘conjunction’ detectors in mid-level vision. On the other hand, it appears that the two-frequency approach is extremely useful for measuring and disentangling multiple nonlinear responses. Here – in the visual system, at least – this was useful for distinguishing responses relating to lateral inhibition caused by the presence of multiple stimulus components from responses relating to the combination of responses relating to those stimulus components in the brain. Conjunction detectors that operate at moderate to high contrast levels appear to be present in mid-level vision. In the one auditory study that we conducted, no clear pattern of results were observed, making it difficult to assess the usefulness of the two-frequency approach in that domain.

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.

This thesis addressed the question of whether global, 'executive' control processes are involved in switching between discrete cognitive tasks. The involvement of executive working memory processes in the control of switching was examined, using a combination of cognitive and cognitive neuropsychological methods. In all studies, participants switched unpredictably between two simple tasks, and in some cases they also performed concurrent tasks. The focus throughout was on two putative areas of executive control that may influence task switching, goal-directed advance processing, and the suppression of interference between tasks. The first series of experiments explored whether the central executive of working memory is required to prepare for a task switch, but found no evidence that this is the case, whether an endogenous or an exogenous method of task cueing is used. The possibility was then raised that cognitive control does not just operate when the task switches, and a further study showed that this is, indeed, the case. However, two experiments using different task cueing methods did not reveal any evidence that executive processes in working memory carry out this control. It did, however, appear that the central executive is required for overall task performance, as opposed to task switching, when the method of cueing requires that participants keep track of and update information about which task is to be performed. The final study examined task switching and executive function in a group of patients with damage to the frontal lobes, and to posterior areas of the brain. Although a number of participants showed evidence of executive deficits, they had no difficulty in switching in a speeded response task. In conclusion, it is argued that local, rather than global, control processes are involved in switching tasks in the present paradigm, and implications are discussed for theories and investigation of executive control. 2

No description available.

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.

The objective of these experiments was to explore long-term memory in Caenorhabditis elegans. This examination of memory in a simple organism with accessible genetics and a well understood biology may permit later work to define the cellular processes that underlie long-term memory. Habituation training with a vibrational stimulus was administered on Day 1, and the retention test of a block of stimuli was given 24 h after the end of training on Day 2. Long-term retention of habituation was evident as a lower level of responding on Day 2 relative to the level of responding on Day 2 of untrained controls or the initial level of responding of worms on Day 1. In Experiments 1 and 2, a habituation training protocol that produced long-term retention of habituation was established, and the effects of stimulus number, interstimulus interval (ISI), and distribution of training on both short-term and long-term habituation were examined. In Experiment 1 (10-s ISI), there appeared to be a floor effect which resulted in a low level of responding regardless of training on Day 1; thus no evidence for long-term habituation after training at a 10-s ISI could be found. In Experiment 2 (60-s ISI), worms that received distributed and massed habituation training with 60 stimuli showed a significantly lower level of responding relative to untrained controls. The distributed habituation training appeared to be more effective at inducing long-term habituation and was used in the subsequent experiments. To characterize the effects of heat shock treatments used in the behavioral experiments that follow, the effects of heat shock on two assays, the induction of a heat shock protein gene, hsp16, and the rate of egg-laying were measured in Experiment 3. All heat shock treatments used caused the induction of hsp16. In addition, the number of eggs laid during a fixed interval after heat shock was sensitive to the heat shock treatments given in Experiments 4 through 8. In Experiments 4 through 8, the effects of heat shock on short- and long-term habituation were examined. Heat shock, which acts as a general cellular stressor, was administered at different times before, during and after training. In Experiment 4, heat shock (45 min, 32°C) was administered, ending 2 h before training on Day 1. Heat shock before training did not affect the initial level of responding on Day 1, habituation during training, short-term retention of habituation between blocks of training or long-term retention of habituation. In Experiment 5, heat shock (45 min, 32°C) was administered during the rest periods of distributed training in the 1-h interval after each training block. While heat shock during training had no significant effect on responding on Day 1, long-term habituation was blocked. In Experiment 6, the possibility that heat shock before training would prevent the disruption of long-term habituation by heat shock during training by inducing thermal tolerance was examined. This was tested by administering heat shock (45 min, 32°C) that ended 2 h before training and heat shock during training. It was found that heat shock before training did not prevent the disruption of long-term habituation by heat shock during training. In Experiment 7, the effect of heat shock that ended 2 h before the retention test on Day 2 on the retention of long-term habituation was examined. It was found that heat shock on Day 2 did not disrupt the retention of habituation. Finally, in Experiment 8, the effect of brief heat shock (15 min, 32°C) at different intervals in the rest period following the training blocks was examined in an attempt to more narrowly define a critical period for consolidation of long-term habituation. Although there was no significant effect of brief heat shock on retention of habituation, the pattern of the data suggests that there may be a period of greater vulnerability worth further investigation. In summary, heat shock given before training or before the retention test did not affect long-term habituation, while heat shock during training disrupted consolidation of long-term habituation. Taken together, these behavioral results provide the foundation for an investigation of the cellular processes underlying long-term memory in C. elegans. By exploring the dynamics of the formation of long-term habituation, intervals of time critical to the formation of long-term habituation were defined. This in turn will help to focus attention on the cellular processes whose activity during those intervals of time may be important to the consolidation of long-term memory. / Arts, Faculty of / Psychology, Department of / Graduate