Visit-to-visit variability in blood pressure (BP) increases stroke risk, independent of mean BP. However, its physiological validity, the ideal method of measurement and the mechanisms increasing cardiovascular risk are unclear. In meta-analyses of individual patient data, I pooled associations between BP variability and risk of stroke, all cardiovascular events and death. I then determined antihypertensive drug-class differences in cardiovascular risk, intra-individual (I-VR) and inter-individual BP variability (M-VR). In 500 Oxford Vascular Study (OXVASC) patients undergoing thrice-daily home (HBPM) and awake ambulatory monitoring (ABPM), associations between mean, maximum or variability in BP (CV-BP) were determined with premorbid BP, hypertensive arteriopathy (creatinine, aortic stiffness, cognitive impairment, stroke versus TIA and leukoaraiosis) and cardiovascular events. In 200 patients, I determined associations with pulsatility or stiffness (pulse wave velocity) in cerebral and aortic vessels. There was a 21% and 27% increased risk of stroke and myocardial infarction per standard deviation of CV-SBP in 318700 patients, independent of mean SBP. In 244,479 patients, SBP variability was reduced by CCBs and diuretics within (I-VR=0.89, 95% CI=0.82-0.96, p=0.0001) and between individuals (M-VR 0.83, 0.77-0.89, p<0.0001), especially in the first year of treatment, explaining drug class differences in stroke risk (OR=0.76, 0.68-0.87, p<0.0001). In OXVASC, drug class differences on day-to-day SBP variability were greatest immediately after waking. Residual hypertension after treatment on HBPM but not ABPM (BP>135/85) predicted recurrent cardiovascular events (HR 2.82, 1.44-5.51, p=0.002 vs. 1.48, 0.68-3.23, p=0.33), reflecting stronger associations with premorbid BP and hypertensive arteriopathy, due largely to inaccuracy of ABPM in patients aged >65 years. Furthermore, day-to-day maximum and CV-SBP were associated with premorbid BP, hypertensive arteriopathy and cardiovascular events, with no additional predictive value of mean SBP when analysed with maximum SBP. Maximum SBP was greater in men and CV-SBP in women, whilst age and creatinine determined both. Increased stroke risk may partly be due to the association between BP variability and cerebral pulsatility, which was correlated with leukoaraiosis (p=0.01) and determined by aortic stiffness (p=0.016) and pulsatility (p<0.001). BP variability is clinically significant and physiologically valid, and is treatable with CCBs and diuretics. After TIA or minor stroke, HBPM best identifies residual hypertension and demonstrates the predictive value of BP variability and maximum BP, but associated arterial changes might explain some of the increased stroke risk.

In our everyday lives, we must often weigh the different attributes of items in order to select the item that best fits our current goals, allowing us to make optimal decisions. Construal Level Theory proposes a psychological mechanism for re-weighting attributes, utilizing selective attention as the process by which we implement self-control. It has been hypothesized that switching attention between attributes is facilitated by the suppression of cortical oscillations over posterior brain regions within the alpha (8-12 Hz) frequency range. To test this idea, we re-examined previously collected whole-brain electroencephalography (EEG) data from a dietary choice experiment in which participants made decisions naturally or with a weight loss incentive. Prior analysis found that although hungry subjects primarily relied on taste properties while responding naturally, they increased their behavioral and neural weighting of health when motivated to lose weight. Reanalyzing this data using time-frequency analyses, we compared alpha oscillations related to healthy versus unhealthy foods under natural and self-control conditions. We predicted that when participants exercised self-control we would see suppression of alpha oscillations over occipital sensors starting around 400 ms post-stimulus onset, for trials presenting healthy relative to unhealthy foods; no such suppression should appear during natural responding when ignoring health information. Consistent with our hypothesis, we found a significant decrease in alpha oscillations over occipital sensors between 440 and 800 ms post-stimulus onset for healthy compared to unhealthy items in the self-control condition. No such effect was seen for health information in natural choice, or for taste. Our findings extend previous research by linking alpha band suppression to the neural re-weighting of multiple attributes, suggesting a neuro-cognitive mechanism for self-control that uses selective attention to choose between multiple attributes.

For decades, neuroscience has greatly contributed to our foundational understanding of human behavior. More recently, the findings and methods of neuroscience have been applied to study the process of decision-making in order to offer advanced insights into the neural mechanisms that influence economic and consumer choices. In this thesis, I will address how customized marketing strategies can be enriched through the integration of consumer neuroscience, an integrative field anchored in the biological, cognitive and affective mechanisms of consumer behavior. By recognizing and utilizing these multidisciplinary interdependencies, marketers can enhance their advertising and promotional mix to elicit desired neural and affective consumer responses and measure these reactions in order to enhance purchasing decisions. The principal objective of this thesis is to present a comprehensive review of consumer neuroscience and to elucidate why it is an increasingly important area of study within the framework of human behavior. I will also describe how the insights gained from this emerging field can be leveraged to optimize marketing activities. Finally, I propose an experiment that illuminates key research questions, which may have considerable impact on the discipline of consumer neuroscience as well as the marketing industry.

<p>The research studies presented as this dissertation constitute a methodologically diverse and conceptually integrative approach to understanding impulsiveness in the context of cognitive control and decision making. Broadly, these findings address the validity of current conceptions of trait impulsiveness, relationships between those traits and brain or laboratory measures of cognitive control, and links between impulsive traits and economic decisions under conditions of delay or uncertainty. The findings presented in this thesis affirm the multidimensional nature of impulsiveness as a construct, and link individual differences in specific impulsive types to behavioral and neurobiological measures of control function. The nature of motor, attentional, and nonplanning impulsive types are contextualized by reference to evidence supporting a broad theory of behavioral control based on hierarchical organization of action, ranging from concrete acts to abstract plans and strategies. We provide evidence linking concrete forms of urgent/motor impulsiveness to behavior and brain activation during response-related control, and more abstract and future-oriented premedititative/nonplanning impulsiveness to strategic control signals in more rostral PFC. Finally, these findings are complemented by causal evidence from a neurostimulation study linking a contextual control network to risky decision making and attentional impulsiveness.</p> / Dissertation

The DSM-IV characterizes dissociation as “disruption in the usually integrated functions of consciousness, memory, identity, or perception of the environment” (American Psychiatric Association, 1994, p. 477) and it has been tenuously linked with trauma, but “lacks a single, coherent referent … that all investigators in the field embrace” (Cardena, 1994). It is known that dissociation is a spectrum (Bernstein and Putnam, 1986; Shor, Orne, and O’Connell, 1962; Spiegel, 1963; Tellegen and Atkinson, 1974), and low levels of dissociation can be a part of normal functioning, allowing us to do two things at once (Butler, Duran and Jasiukitis, 1996), but higher levels can interfere with daily functioning. The present study used survey techniques to investigate the link between dissociation and trauma. Survey results showed a significant correlation between trauma and dissociation. The current investigation also used the high temporal and spatial resolution of electroencephalographic techniques to identify the neurophysiological correlates of dissociation. Specifically, the current investigation recorded early and late event-related potentials in participants who rated high and low in dissociation while they viewed affective pictures in order to determine if there were electrophysiological differences in responses to emotional stimuli. Electroencephalographic results were nonsignificant, but trends indicated that high dissociators showed a heightened response to affective photos at P1 and the late positive potential compared with low dissociators. If the results are thought to be reliable, the trends may indicate that high dissociators were not actively dissociating during the task, and because high dissociators have usually experienced trauma, they are more sensitive to emotional stimuli. Further research is needed to support these theories.

This thesis considers the phenomenological experience of e-reading (reading on an electronic screen) as a way-in to discussing wider issues of technology and our encounter with objects in our environments. By considering the resistance shown toward reading on iPads and Kindles in popular and academic discourse as a source of valuable “folk phenomenological” report, this thesis hopes to shed light on both the particular engagement of portable e-reading and the general experience of embodied encounters with artefacts. The first chapter will consider the shortcomings of contemporary definitions of technology and aims to provide its own definition commensurate to the task of describing the intimate and very human encounter with equipment, an encounter which will be described as “technological.” In the second chapter an ontology (begun in the background of the first) will be developed which primarily considers our encounter with things that are as embodied as ourselves. This ontology sees evolution as an epistemological concern, with every evolutionary act occurring as a response to environmental pressures and producing a knowledge of that environment. This knowledge, it will be argued, in light of conclusions drawn from an engagement with Object Oriented Ontology, can be tested only via repeatable successful action with that which might be known. Such evolutionary concerns, it will be further argued, are equally applicable to our artefacts. The third chapter will focus on metaphor and critical theory to consider how e-reading in particular might function as a material metaphor, enabling productive thought. It will conclude with readings of three texts which put the language of all three chapters to work. This thesis draws on several fields, including Critical Theory, Cognitive Neuroscience, Evolutionary Epistemology, and Philosophy, the bringing together of which is intended to be of use to the still emerging Digital Humanities and the work's home discipline of English Studies as it gets used to the substantial alterations in the substrate of its object of study.

Individuals diagnosed with schizotypal personality disorder (SPD) exhibit patterns of cognitive deficits in (1) attention (Lees-Roitman, Cornblatt, Bergman, Obuchowski, Mitropoulou, Keefe, Silverman, & Siever, 1997), (2) memory (Bergman, Harvey, Lees-Roitman, Mohs, Margerm, Silverman, & Siever, 1998), (3) executive functioning (Cadenhead, Perry, Shafer, & Braff, 1999), and recently (4) neuromotor functioning (Neumann & Walker, 1999), similar to individuals with a diagnosis of schizophrenia. Furthermore, recent research suggests a link between neuromotor and cognitive functioning in schizophrenia spectrum disorders (SSDs) (Neumann & Walker, 2003). The current study is an extension of research on non-drug-induced neuromotor disturbances in individuals with SPD and examines how such disturbances covary with neurocognitive measures. Approximately thirty-three adults (18-65) were rated for SPD symptoms. Motor assessments included a computerized motor task and finger tapping test. Cognitive assessments included measures of attention, verbal and visual memory, and executive functioning. Consistent with previous research, the SPD group displayed significant right hand (left hemisphere) motor disturbances (i.e., increased force and force variability) compared to healthy controls after excluding all cases reporting a history of head injury. In addition, results indicate significant associations between motor, cognitive, and symptom variables. Consistent with previous research, neuromotor functioning and the relationships between motor and cognitive functioning varied as a function of Time of Day (TOD) of testing. Understanding the relationship between neuromotor and neurocognitive functioning may help elucidate the neural systems that contribute the symptoms characteristic of SSDs.

The main aim of the experiments reported in this thesis was to explore the neural mechanisms underlying the temporal orienting of attention. In Chapter 3, I explored the possible dissociation between exogenous and endogenous temporal orienting by comparing reaction times to targets appearing after rhythmic or symbolic cues. Behavioural results provided evidence for the existence of dissociable exogenous and endogenous types of temporal orienting of attention. The experiment in Chapter 4 combined spatiotemporal expectations using rhythmic moving cues to test the modulatory effect of exogenous temporal orienting in the brain. Specifically, I used EEG to test the effect of temporal orienting on perceptual and motor stages of target analysis, as well as on anticipatory oscillatory brain activity. The time-frequency analysis revealed that rhythmic cues can entrain slow brains oscillations, providing a putative mechanism for enhancing the perceptual processing of expected events. Spatiotemporal expectations also modulated the amplitude of visual responses and the timing and amount of preparatory motor activity. In Chapter 5, I used a novel task to explore the neural modulatory effects of spatial and temporal expectations acting in isolation or in coordination. For the first time, the analysis of early visual responses demonstrated that temporal expectations alone, independently of spatial orienting, can enhance early visual perceptual processes. The time-frequency analysis in this experiment showed a desynchronisation of alpha oscillations focused over central-parietal electrodes induced by rhythmic cues that were independent of spatial expectations. When rhythmic cues carried spatiotemporal information, the alpha desynchronisation also spread over contralateral occipital electrodes. In Chapter 6, fMRI was used to test the possible neural dissociation between motor and temporal orienting. The results confirmed the large overlap between these two processes, but also indicated independent behavioural and neural effects of temporal orienting. Temporal orienting activated the left IPS across motor conditions, further implicating the left IPS in temporal orienting. Based on the results of these experiments, directions for future studies are discussed.

The electroencephalogram (EEG) reflects summated, slow post-synaptic potentials of cortical neurons. Sensory, motor or cognitive events (such as a fast-rising sensory stimulus, a brisk self-paced movement or a stimulus-triggered cognitive task) can elicit transient changes in the ongoing human EEG, called event-related potentials (ERPs). ERPs are widely used in clinical practice, and believed to reflect the activity of the sensory system activated by the stimulus (for example, laser-evoked potentials are used to substantiate the neuropathic nature of clinical pain conditions). When ERPs are elicited by pairs or trains of stimuli delivered at short inter-stimulus intervals (ISIs), the magnitude of the ERP elicited by the repeated stimuli is markedly reduced, a phenomenon known as response decrement. While the interval between two consecutive stimuli becomes longer, the reduced response is recovered. Thus, this phenomenon has been traditionally interpreted in terms of neural refractoriness of generators of ERPs ("neural refractoriness hypothesis"). This thesis, however, challenges this neural refractoriness hypothesis by describing the results of manipulating the preceding events of the eliciting stimulus. The first study examined the effect of variable and short ISIs on sensory ERPs, delivering trains of auditory and electrical stimuli with random ISIs ranging from 100 to 1000ms. In the second study, pairs of laser stimuli were presented in two comparable conditions. In the constant condition, the ISI was identical across trials in each block, while in the variable condition, the ISI was variable across trials. By directly comparing ERPs elicited by laser stimulation, this study aimed to explore whether lack of saliency in the eliciting stimulus could explain the response decrement during stimulus repetition. Finally, the third study tested the hypothesis that the reduced eliciting ERPs would recover if saliency were introduced by changing the modality of the preceding event. Thus, trains of three stimuli (S1-S2-S3) with 1s ISI were presented; S2 was either same or different in modality as S1 and S3 in each block. Results from these three experiments demonstrate that this "refractoriness hypothesis" does not hold, and suggest that the magnitude of ERPs is only partly related to the magnitude of the incoming sensory input, and instead largely reflects neural activities triggered by salient events in the sensory environment. These results are important for the correct interpretation of ERPs in both physiological and clinical studies.

Clinical and behavioural evidence has shown that the threat value of pain biases decisions about whether a stimulus is perceived as painful or not, and if yes, how intense is the sensation. This thesis aims to investigate the neural mechanisms underlying the effect of perceived threat on perceptual decisions about pain. The first study investigates the neural mechanisms underlying the effect of threat on the decision about the quality of the sensation, i.e., whether it is perceived as painful or not. The perception of pain (relative to no pain) was associated with activation in the anterior insula as well as an increased connectivity between this region and the mid-cingulate cortex (MCC). Activity in the MCC was correlated with the threat-related bias to perceived pain. In the second study, probabilistic tractography was performed with diffusion tensor imaging to investigate the structural connectivity between subdivisions of the insula and other pain-related regions. Additional analyses revealed that the structural connectivity between the anterior insula and the MCC, and between the posterior insula and somatosensory cortices, is positively correlated with the threat-related bias toward pain. In the third study, a multivariate pattern analysis (MVPA) was performed to investigate whether pain can be decoded from functional neuroimaging data acquired during the anticipation and during the receipt of pain. The results show that pain can be predicted by the pattern of neural activity in the right anterior insula during anticipation and stimulation. The fourth study investigated the effect of uncertainty about the stimulation intensity as a form of threat on the perceived intensity of pain. Uncertainty was found to be associated with an increased activation in the anterior insula. Overall, these findings suggest that a neural network consisting of the anterior insula and the MCC plays a key role in decisions about the quality and the quantity of nociceptive sensation. Results from the MVPA analysis support the notion that perceptual decisions are encoded by a distributed network of brain regions. The variability in anatomical connections between these regions may account for the individual differences in the susceptibility to a threat-mediated bias toward pain.