The utilisation of navigation systems in cars has given rise to road safety concerns, and the design and functionality of such systems must therefore be adjusted to the users’ needs, since they have to divide their attention between driving and the operation of the navigation system. The study was aimed at finding the optimum system response time (SRT) which would enable a driver to focus as much as possible on the road while attaining an efficient task completion time using an electronic navigational system. The research project consists of two separate experiments and was completed by 10 subjects. Experiment 1 included a temporal reproduction task and a secondary memory task. The subjects had to memorise two symbols and then reproduce six time spans ranging from 1 to 30 s to provide a baseline measurement of their time estimation abilities. Experiment 2 consisted of a simulated automobile driving task. While driving in the simulator the subjects completed a memorising task displayed on a touch screen. The task was presented with seven different system response times (SRTs) ranging from 0 to 30 s. The effects of different SRTs on the eye movement from road to monitor, regarding the duration of fixation and the frequency of change were evaluated. The distribution of gazes to the secondary task was analysed to provide information about the time estimation performance in the driving simulator. Other dependent variables tested were the accuracy of selected items, memory game performance, drive performance and the subjective state of the test person. The results of this study can be employed to find the optimum duration of inter-task delays for in-vehicle technical devices. / Psychology / M.A. (Psychology)

Adolescent depression is a major public health problem, which is associated with educational problems, long-term psychiatric illness and suicide. One major source of stress during adolescence is peer rejection. In this thesis, I investigate the nature of the relationship between peer rejection and adolescent depression. In a review of longitudinal and experimental studies, I describe a bi-directional relationship between peer rejection and depressive symptoms. I then outline how genetic, cognitive and neural vulnerability may modify the effects of peer rejection on adolescent depression. Finally, I introduce five empirical chapters which test these hypotheses using different methodological approaches. The first study is a molecular genetic analysis of a sample of adolescents with and without a diagnosis of mood disorder. I report an interaction between diagnostic group, environmental stress (though not peer rejection specifically) and 5HTTLPR genotype on symptoms of anxiety, which supports the role of genetic factors in modifying the relationship between environmental stress and adolescent mood disorder. The second study is a behavioural study of negative attention biases in a typically developing sample of adolescents. I report a negative attention bias in adolescents with low (versus high) self-esteem. Although the data do not support a causal role for attention biases in adolescent depression, such biased cognitions could also moderate responses to peer rejection, maintaining affective symptoms. A final set of three fMRI datasets investigates how neural circuitry may influence depressed adolescents’ responses to peer rejection at three distinct stages: i) expectation of peer feedback, ii) the receipt of peer rejection, iii) emotion regulation of peer rejection. Data show distinct behavioural and neural differences between depressed patients and healthy controls during expectation and reappraisal of peer rejection, although heightened emotional reactivity immediately following the receipt of peer rejection did not differentiate behavioural or neural responses in adolescents with and without depression.

Overexpression of the NR2B subunit of the NMDA receptor in the forebrain has been shown to improve learning and memory in mice (Tang et al 1999), which provides exciting implications for the enhancement of human cognition. However, it was first essential to establish replicability, and since the Tang et al (1999) study used only male mice we wished to investigate possible sex differences. On the hidden platform watermaze, we found a trend for male NR2BOE mice to learn the task more quickly than male wildtype mice (as observed by Tang et al. 1999), but the opposite trend in female mice; female NR2BOE mice were slower to reach the hidden platform than female wildtype mice. This pattern of results was also observed on the spatial reference Y memory task and open field task (for anxiety), although not on the spatial working memory T maze task (despite a sex difference). However, wildtype and NR2BOE mice performed at similar levels on the novel object recognition task, the spatial novelty preference task, visible platform watermaze and visual discrimination task. A battery of tests considering some species typical behaviours of mice demonstrated that wildtype and NR2BOE mice were comparable on tests of motor ability, strength, co-ordination, anxiety, burrowing and nesting. This suggests that our behavioural results are not due to a general impairment or enhancement of species typical behaviours. We considered the possibility that the difference between the results of Tang et al (1999) and those we observed may be caused by age differences; hence we attempted to replicate our results on the hidden platform watermaze, spatial reference Y maze and open field test in age matched mice. However, the second cohort of NR2BOE mice performed at similar levels to wildtype mice, and at significantly improved levels compared to the mice of the first cohort. We also considered the effects of knocking out the NR2B subunit on learning and memory, and NR1 subunit deletion within the hippocampus. On the spatial working memory T maze, these mouse strains performed similarly to their respective wildtype strains. Similarly, on a two beacon watermaze (with one indicating the platform position), mice lacking the NR2B subunit were able to locate the platform in a similar length of time. To ensure that the null results we had observed in the second cohort were not due to loss of the NR2B protein overexpression in the forebrain, we performed polymerase chain reactions (PCR), quantitative real-time PCR, and Western blots. We ascertained that the transgene was indeed present and that NR2B mRNA and protein levels were elevated in the hippocampi of the NR2BOE mice. In conclusion, it is unclear why the behaviours we observed in the NR2BOE mice are different to those published in the literature. It is possible that they may be due to differences in environmental enrichment, but the cause of the genotype by sex differences observed in the mice of cohort 1 is unclear. Nonetheless, we have advanced our knowledge of the effects of modifications in the levels of the NR2B subunit of the NMDA receptor on learning and behaviour.

This thesis investigates rest-activity and sleep profiles in neurodegeneration and brain cancer. Study 1 comprised longitudinal field assessments of rest-activity, sleep and memory in controls and memory-impairment individuals with: subjective memory complaint (SMC), amnestic mild cognitive impairment (aMCI), mild and moderate Alzheimer’s disease (AD). Four questions were addressed: (1) is SMC a prodromal stage of AD? (2) do characteristics of SMC predict future decline? (3) does cholinergic medication (ChEI) impact rest-activity and sleep of moderate AD patients? and (4) are there factors predicting response to ChEI? Study 2 assessed rest-activity and melatonin rhythms in a brain cancer patient (JJB), and post-mortem analysis of brain tissue assessed infiltration of cancer cells on the circadian clock (SCN). Both studies used questionnaires, cognitive tests, electroencephalography and actigraphy simultaneously at patients’ homes. In Study 1, the SMC group showed a reduced activity amplitude to be correlated with increasing memory impairment severity, lower sleep quality and efficiency. Increased sleep fragmentation was observed in all memory-impaired groups, although not correlated to impairment severity. Increased fragmentation of rest-activity rhythm correlated with increasing memory impairment severity in all groups except SMC. Following ChEI medication with donepezil, moderate AD patients showed increased sleep fragmentation, probably due to potentiation of available acetylcholine known to maintain arousal. Higher daytime-activity and lower activity in the rest-phase, when drug-naïve, predicted improved cognition following ChEIs. In Study 2, cancer cell infiltration of the patient’s SCN was confirmed. However, a robust circadian rest-activity period with a misaligned melatonin phase, was recorded, indicating that the effects of partial SCN lesions in humans are complex and this result was possibly in part are due to the masking effect of social behaviour.

At present, there are few clinically effective pain therapies available to treat chronic pain. One reason is due to a lack of understanding about how pain emerges in the brain. Excitingly, an emerging body of work suggests that the perfusion imaging technique, arterial spin labelling (ASL), is particularly well-suited to investigate this issue. The primary aim of this thesis is to develop and optimise a quantitative perfusion imaging approach to investigate the neural correlates of both experimental and pathological tonic pain. In Chapter 2, we explore different methods of inducing ongoing pain in healthy subjects. Results from this study show that mechanically induced pain is well suited for use in ASL FMRI experiments. In Chapter 3, we compare currently available ASL FMRI approaches for investigating tonic states, using a range of sensory paradigms. Results from these experiments support the use of an optimised version of Continuous ASL (CASL) FMRI to obtain whole-brain perfusion. Additionally, we discuss our decision to proceed with the newly acquired pseudo-continuous ASL (pCASL); a novel ASL technique that benefits from maximal signal-to-noise (SNR) across a whole-brain volume. In Chapter 4 we implement the pCASL FMRI approach to image the neural correlates of ongoing experimental pain. Results from the investigation of parametrically modulated ongoing mechanical pain show robust pain-related activation of key pain related regions that are monotonically active with an increase in stimulus intensity. Additionally, data from this experiment shows the presence of complex perfusion dynamics relative to pain worthy of further study. In Chapter 5, we optimised the pCASL sequence to obtain absolute perfusion changes across the whole-brain volume, using multi-inversion times, so that we could investigate the perfusion dynamics observed in Chapter 4. Results show that absolute perfusion changes during tonic pain are considerably less than for regions recruited during a non- pain task. Additionally, dynamic perfusion changes show complex stimulus responses across all active regions regardless of stimulus type. We conclude that while the technique is well suited to quantify absolute perfusion, the mechanisms underlying the dynamic changes in CBF (neuronal signal, neurovascular coupling) need further study. Finally, in Chapter 6, we implement the absolute perfusion approach developed in Chaper 5 to interrogate the neural correlates of the genetic pain disease, Erythromelalgia, and pleasurable relief. The results of this study show pain-related activation (and relief-induced reduction) of key pain-related regions. We conclude from these results that the ASL technique developed over the course of this thesis can be used to study a range of pain pathologies. Taken together, the results of this thesis document the development of a powerful perfusion imaging technique capable of quantifying absolute perfusion changes across a whole-brain volume. The data presented here from investigations of both experimental and pathological pain states supports the use of this technique in future tonic pain studies, as well as other neuroscience applications. We are confident that implementation of this imaging approach will provide integral insight into the mechanisms of ongoing pain states; and further the development of novel efficacious pain treatment options.

Selective attention is a mechanism used to allocate resources to information processing. Both mood states and emotionally salient stimuli can influence which information is selectively attended. This information is subsequently processed in a more elaborative manner and affects task performance. The experiments presented in this thesis explore the influence of mood and emotional stimuli on selective attention and consequently task performance. Mood induction procedures were used to induce transient neutral, sad, and happy mood states in healthy volunteers. A systematic review and meta-analysis of 41 studies using sad mood induction procedures showed cognitive impairments in performance in the context of task neutral stimuli. In contrast biases in attention towards mood-congruent negative stimuli led to improved task performance. A series of three behavioural experiments with 197 participants demonstrated that participants made decisions on the basis of less information when that information was preceded by emotional but not neutral stimuli. Induced mood state did not affect performance. The behavioural and neural correlates of visual attentional processing to emotional stimuli were explored using magnetoencephalography in 24 healthy participants following sad, happy, and neutral mood induction procedures. The M300, a component associated with selective attention, had greater amplitude following presentation of negative compared with positive stimuli, which was associated with improved task performance. Reduced M300 amplitude and impairments in performance occurred following sad mood induction procedures. The experiments presented in this thesis demonstrate prioritized processing of emotional information and provide some evidence for impaired performance following sad mood induction procedures.

The notion that we are voluntary agents who exercise power to choose and, in doing so, determine some of what happens in the world has been an important notion in certain theological accounts concerning our relationship with God (e.g. 'the freewill defence' for God's goodness and omnipotence in light of moral evil and accounts of human moral responsibility in relation to God). However, it has been claimed that the physicalism supported by contemporary neuroscience research calls into question human voluntary agency and, with it, human power to choose. Emergentist (or non-reductive physicalist) accounts of psychological phenomena have been presented as a way of reconciling the physicalism supported by contemporary neuroscience and the theologically important notion of human power to choose. But there are several issues that remain for the plausibility of the required kind of emergentist account; namely - Does recent neuroscience research show that voluntary agency is an illusion? and Is there evidence for neurophysiological causes which, along with neurophysiological conditions, determine all we do? In this dissertation I set out to address these issues and, in doing so, present an account of voluntary agency as power to choose in the state of being aware of alternatives. I argue that this account allows for the notion that human beings determine some of what happens in a way that is consistent with what contemporary neuroscience shows. Thus, contemporary neuroscience does not undermine this notion of human voluntary agency; or, then, the predominant theological view that we are morally responsible in our relationship with God.

In everyday life we regularly update our expectations about the locations at which sensory events may occur, and about the motor responses that are appropriate in a given situation. The experiments in this thesis investigated the neural correlates of perceptual processes and motor preparation during human decision making, and the regions that causally contribute to decision making in the human brain. In Chapter 3, I used electroencephalography (EEG) to investigate whether alpha-band (~8-14 Hz) oscillations provide a graded index of participants’ preparatory attentional states. Time-frequency analysis revealed that manipulating spatial certainty regarding the location of an upcoming visual target led to parametric changes in the lateralization of preparatory occipito-parietal alpha oscillations, and to parametric modulation of parieto-central beta-band (~15-25 Hz) power typically associated with response preparation. In Chapter 4, I used EEG to investigate whether evolution of lateralization of sensorimotor alpha- and beta-band activity reflected participants’ evolving expectations about an upcoming motor response. Lateralization of activity in both frequency bands varied parametrically with the available evidence, suggesting such lateralized activity correlates with participants’ internal decision variables. Further analysis identified unique contributions to lateralized and non-lateralized oscillatory activity due to the prior evidence, evidence update, and surprise related to the observed information at each stage of the task. In Chapter 5, I extended the paradigm developed in Chapter 4 for use with online repetitive transcranial magnetic stimulation (TMS) and concurrent EEG recording. Delivery of TMS during decision making allowed investigation of the causal role played by a left hemisphere medial intraparietal region that is the putative human homologue of the macaque medial intraparietal cortex (MIP). MIP stimulation disrupted decision-making behaviour by biasing participants’ decisions against contralateral-to-stimulation (i.e., right-handed) responses. Comparison of the magnitude of TMS-induced changes in behaviour and beta-band activity demonstrated that the intraparietal cortex plays a causal role both in decision making and in the appearance of beta-band activity over the motor cortex. In Chapter 6, the broader consequences of the experimental work presented in this thesis are discussed, in addition to promising directions for future research.

Le phénomène de Clignement Attentionnel (Attentional Blink, AB), fait référence à une diminution transitoire du rapport exact d’une deuxième cible (C2) si celle-ci est présentée trop tôt après une première cible (C1) lors d’une présentation visuelle sérielle rapide (rapid serial visual presentation, RSVP), et ce, quand les deux cibles doivent être rapportées. Cette étude a examiné l’existence possible d’asymétries hémisphèriques dans le traitement attentionnel ainsi que l’éventualité que la présentation de cibles à deux hémisphères différents puisse diminuer le AB chez des participants neurologiquement sains et l’abolir dans le cas d’un patient callosotomisé. Pour ce faire, nous avons employé un paradigme modifié du AB dans lequel les cibles pouvaient apparaître dans n’importe quelle de quatre RSVP, une dans chaque quadrant du champ visuel, pour permettre des essais dans lesquels les deux cibles puissent être présentées au même hémisphère et d’autres où chaque cible était présentée à un hémisphère différent. Bien que nous n’ayons trouvé aucune diminution de l’effet AB lors de présentation inter-hémisphérique, dans les deux populations à l’étude, le taux de bonnes réponses globales à la deuxième cible était plus élevé quand les cibles étaient présentées à des hémisphères différents. Nous avons également trouvé un avantage de l’hémisphère gauche chez le patient callosotomisé. / The Attentional Blink (AB) refers to a transient impairment in the accurate report of a second target (T2) if it closely follows the presentation of a first target (T1) in a rapid serial visual presentation (RSVP), when both targets must be reported. This study investigated both the possibility of hemispheric asymmetries of attentional processes as well as the possibility that presenting targets to different hemispheres could diminish the AB in neurologically intact participants and abolish it in the case of a split-brain patient. To do so, a modified AB paradigm was used in which targets could appear in any of four simultaneous RSVP streams, one in each quadrant of the visual field, so as to have trials in which both targets were presented to the same hemispheres and trials in which targets were presented to different hemispheres. Although no evidence of a diminished AB was observed by presenting targets to separate hemispheres, in both neurologically intact individuals and the split-brain patient, overall accuracy was higher when targets were presented to separate hemispheres. A left hemisphere advantage was only observed in the split-brain patient.

Executive functions, like the capacity to control and organize thoughts and behavior, develop from childhood to young adulthood. Although task switching and working memory processes are known to undergo strong developmental changes from childhood to adulthood, it is currently unknown how task switching processes are modulated between childhood and adulthood given that working memory processes are central to task switching. The aim of the current study is therefore to examine this question using a combined cue- and memory-based task switching paradigm in children (N = 25) and young adults (N = 25) in combination with neurophysiological (EEG) methods. We obtained an unexpected paradoxical effect suggesting that memory-based task switching is better in late childhood than in young adulthood. No group differences were observed in cue-based task switching. The neurophysiological data suggest that this effect is not due to altered attentional selection (P1, N1) or processes related to the updating, organization, and implementation of the new task-set (P3). Instead, alterations were found in the resolution of task-set conflict and the selection of an appropriate response (N2) when a task has to be switched. Our observation contrasts findings showing that cognitive control mechanisms reach their optimal functioning in early adulthood.