Verbal memory (VM) has been shown to be impacted in brain tumor (BT) survivors, but the nature of VM problems and underlying neuropathology are poorly understood and a long-term outlook is lacking. Our study examined hippocampus volume (HV) and VM in adult survivors of pediatric BT (n=32) and controls (n=48). Results indicate that disruption to a maturing brain in childhood is detectable 17 years (mean) after diagnosis, as HV is significantly lower in survivors compared to controls. Analysis of the VM scores shows that survivors have significantly lower overall immediate recall compared to controls, but learning slope, retention, and recognition are not different across the groups. Survivors’ memory profile indicates that auditory attention and retrieval difficulties could be contributing to their lower immediate recall. For survivors, HV is significantly correlated with delayed free recall but not with other VM indices. Implications of these findings are discussed.

<p>Understanding the structure of the brain has been a major goal of neuroscience research over the past century, driven in part by the understanding that brain structure closely follows function. Normative brain maps, or atlases, can be used to understand normal brain structure, and to identify structural differences resulting from disease. Recently, diffusion tensor magnetic resonance imaging has emerged as a powerful tool for brain atlasing; however, its utility is hindered by image resolution and signal limitations. These limitations can be overcome by imaging fixed ex-vivo specimens stained with MRI contrast agents, a technique known as diffusion tensor magnetic resonance histology (DT-MRH). DT-MRH represents a unique, quantitative tool for mapping the brain with unprecedented structural detail. This technique has engendered a new generation of 3D, digital brain atlases, capable of representing complex dynamic processes such as neurodevelopment. This dissertation explores the use of DT-MRH for quantitative brain atlasing in an animal model and initial work in the human brain. </p><p>Chapter 1 describes the advantages of the DT-MRH technique, and the motivations for generating a quantitative atlas of rat postnatal neurodevelopment. The second chapter covers optimization of the DT-MRH hardware and pulse sequence design for imaging the developing rat brain. Chapter 3 details the acquisition and curation of rat neurodevelopmental atlas data. Chapter 4 describes the creation and implementation of an ontology-based segmentation scheme for tracking changes in the developing brain. Chapters 5 and 6 pertain to analyses of volumetric changes and diffusion tensor parameter changes throughout rat postnatal neurodevelopment, respectively. Together, the first six chapters demonstrate many of the unique and scientifically valuable features of DT-MRH brain atlases in a popular animal model.</p><p>The final two chapters are concerned with translating the DT-MRH technique for use in human and non-human primate brain atlasing. Chapter 7 explores the validity of assumptions imposed by DT-MRH in the primate brain. Specifically, it analyzes computer models and experimental data to determine the extent to which intravoxel diffusion complexity exists in the rhesus macaque brain, a close model for the human brain. Finally, Chapter 8 presents conclusions and future directions for DT-MRH brain atlasing, and includes initial work in creating DT-MRH atlases of the human brain. In conclusion, this work demonstrates the utility of a DT-MRH brain atlasing with an atlas of rat postnatal neurodevelopment, and lays the foundation for creating a DT-MRH atlas of the human brain.</p> / Dissertation

Attention biases to trauma-related information contribute to symptom maintenance in Posttraumatic Stress Disorder (PTSD); this phenomenon has been observed through various behavioral studies, although findings from studies using a precise, direct bias task, the dot probe, have been mixed. PTSD neuroimaging studies have indicated atypical function in specific brain regions involved with attention bias; when viewing emotionally-salient cues or engaging in tasks that require attention, individuals with PTSD have demonstrated altered activity in brain regions implicated in cognitive control and attention allocation, including the medial prefrontal cortex (mPFC), dorsolateral prefrontal cortex (dlPFC) and amygdala. However, remarkably few PTSD neuroimaging studies have employed tasks that both measure attentional strategies being engaged and include emotionally-salient information. In the current study of attention biases in highly traumatized African-American adults, a version of the dot probe task that includes stimuli that are both salient (threatening facial expressions) and relevant (photographs of African-American faces) was administered to 19 participants with and without PTSD during functional magnetic resonance imaging (fMRI). I hypothesized that: 1) individuals with PTSD would show a significantly greater attention bias to threatening faces than traumatized controls; 2) PTSD symptoms would be associated with a significantly greater attentional bias toward threat expressed in African-American, but not Caucasian, faces; 3) PTSD symptoms would be significantly associated with abnormal activity in the mPFC, dlPFC, and amygdala during presentation of threatening faces. Behavioral data did not provide evidence of attentional biases associated with PTSD. However, increased activation in the dlPFC and regions of the mPFC in response to threat cues was found in individuals with PTSD, relative to traumatized controls without PTSD; this may reflect hyper-engaged cognitive control, attention, and conflict monitoring resources in these individuals. Additionally, viewing threat in same-race, both not other-race, faces was associated with increased activation in the mPFC. These findings have important theoretical and treatment implications, suggesting that PTSD, particularly in those individuals who have experienced chronic or multiple types of trauma, may be characterized less by top-down “deficits” or failures, but by imbalanced neurobiological and cognitive systems that become over-engaged in order to “control” the emotional disruption caused by trauma-related triggers.

There remains a high degree of scepticism about acupuncture since its theoretical basis has no clear reference in Western medical and scientific terms, making any associations between neurophysiology and specific acupuncture concepts difficult to determine. Using neuroimaging and engineering approaches to understand its physiological basis may engender greater acceptance of and improvement in the clinical application of acupuncture. Research into the efficacy of acupuncture has raised a number of difficult methodological issues, particularly in relation to the selection of appropriate controls. Separating specific effects from non-specific effects is complex because acupuncture is a physical, invasive, manual procedure involving time and ritual. Sham acupuncture results show only the difference between sham and real acupuncture not the real affect of acupuncture, and other controls may produce distinct subjective and objective effects. Point injection (the injection of a small amount of a substance at an acupoint), a recent innovation of traditional acupuncture, aims to enhance and prolong the stimulation effect in a standardised, reproducible manner. By providing precise, measurable acupoint stimulation applied incrementally in a specifically designed paradigm, an acupoint could act as its own control. This firstly requires injection to be validated against traditional needling. Aims 1. To develop an instrument for reproducible saline delivery at an acupoint. 2. To cross-validate saline acupoint injection (PI) with traditional needle acupuncture (TA). 3. To demonstrate central nervous system (CNS) effects of acupuncture both in health and chronic pain. Hypothesis The primary hypothesis is that stimulation of specific acupoints with linearly incremental saline injection produces differential effects within the CNS observable with functional magnetic resonance imaging (fMRI) allowing investigation of acupuncture in health and chronic pain. Novelty As neuroimaging has not yet clearly defined the brain structures that may be modulated by acupuncture, this project is exploratory in nature. It is expected that acupuncture effects can be robustly imaged with fMRI in healthy subjects and those suffering chronic pain. The demonstrated effects will result from the acupuncture process of progressive point stimulation by tissue distension rather than needle insertion or biological noise. It is proposed to examine the putative modulation of pain by acupuncture within the extensively mapped neuromatrix of cortical and subcortical regions, including the somatic, insula, and limbic cortices, and thalamus. Detailed information regarding differences in brain response between acupuncture in normal and diseased states will expand understanding of acupuncture as a clinical tool. The dilemma of sham stimulation or arbitrary controls will be addressed by confirming PI as a valid, reproducible stimulation method. Methods and Results A series of empirical experiments was designed and conducted to determine the effects of stimulation of different acupoints. 1. Chapters 1 and 3 outline the current understanding of acupuncture in the Western milieu and a review of the neuroimaging literature respectively. 2. In Chapter 2, the report of PI tested against TA in healthy volunteers to determine equivalence of physiological effect demonstrates no statistically significant differences between the methodologies. 3. Chapter 4 reports the design and validation of a task specific microprocessor controlled syringe driver. 4. Four differing acupoints were tested during an fMRI experiment described in Chapter 5; different activation areas were demonstrated across the acupoints providing early support for the hypothesis that different acupoints may have different effects. A subset of brain areas recognised within the pain neuromatrix was delineated, congruent spatially and directionally with those reported in pharmacological analgesia studies. 5. As outlined in Chapter 6, heart rate variability can be measured rapidly in a stressful environment to provide meaningful data on the response of the autonomic nervous system to acupuncture stimulation. 6. The hypothesis of different acupoints having different effects was tested in subjects suffering chronic pain by contrasting an accepted and a neutral acupoint, the results being reported in Chapter 7. Conclusion Despite a long history of clinical usage, appropriate scientific studies have not yet addressed the basic effectiveness and efficacy of acupuncture. This thesis presents a series of empirical studies designed to address a number of the questions arising in the literature and provides converging evidence of the manner in which different acupoints modulate the CNS, specifically within the pain neuromatrix.

There remains a high degree of scepticism about acupuncture since its theoretical basis has no clear reference in Western medical and scientific terms, making any associations between neurophysiology and specific acupuncture concepts difficult to determine. Using neuroimaging and engineering approaches to understand its physiological basis may engender greater acceptance of and improvement in the clinical application of acupuncture. Research into the efficacy of acupuncture has raised a number of difficult methodological issues, particularly in relation to the selection of appropriate controls. Separating specific effects from non-specific effects is complex because acupuncture is a physical, invasive, manual procedure involving time and ritual. Sham acupuncture results show only the difference between sham and real acupuncture not the real affect of acupuncture, and other controls may produce distinct subjective and objective effects. Point injection (the injection of a small amount of a substance at an acupoint), a recent innovation of traditional acupuncture, aims to enhance and prolong the stimulation effect in a standardised, reproducible manner. By providing precise, measurable acupoint stimulation applied incrementally in a specifically designed paradigm, an acupoint could act as its own control. This firstly requires injection to be validated against traditional needling. Aims 1. To develop an instrument for reproducible saline delivery at an acupoint. 2. To cross-validate saline acupoint injection (PI) with traditional needle acupuncture (TA). 3. To demonstrate central nervous system (CNS) effects of acupuncture both in health and chronic pain. Hypothesis The primary hypothesis is that stimulation of specific acupoints with linearly incremental saline injection produces differential effects within the CNS observable with functional magnetic resonance imaging (fMRI) allowing investigation of acupuncture in health and chronic pain. Novelty As neuroimaging has not yet clearly defined the brain structures that may be modulated by acupuncture, this project is exploratory in nature. It is expected that acupuncture effects can be robustly imaged with fMRI in healthy subjects and those suffering chronic pain. The demonstrated effects will result from the acupuncture process of progressive point stimulation by tissue distension rather than needle insertion or biological noise. It is proposed to examine the putative modulation of pain by acupuncture within the extensively mapped neuromatrix of cortical and subcortical regions, including the somatic, insula, and limbic cortices, and thalamus. Detailed information regarding differences in brain response between acupuncture in normal and diseased states will expand understanding of acupuncture as a clinical tool. The dilemma of sham stimulation or arbitrary controls will be addressed by confirming PI as a valid, reproducible stimulation method. Methods and Results A series of empirical experiments was designed and conducted to determine the effects of stimulation of different acupoints. 1. Chapters 1 and 3 outline the current understanding of acupuncture in the Western milieu and a review of the neuroimaging literature respectively. 2. In Chapter 2, the report of PI tested against TA in healthy volunteers to determine equivalence of physiological effect demonstrates no statistically significant differences between the methodologies. 3. Chapter 4 reports the design and validation of a task specific microprocessor controlled syringe driver. 4. Four differing acupoints were tested during an fMRI experiment described in Chapter 5; different activation areas were demonstrated across the acupoints providing early support for the hypothesis that different acupoints may have different effects. A subset of brain areas recognised within the pain neuromatrix was delineated, congruent spatially and directionally with those reported in pharmacological analgesia studies. 5. As outlined in Chapter 6, heart rate variability can be measured rapidly in a stressful environment to provide meaningful data on the response of the autonomic nervous system to acupuncture stimulation. 6. The hypothesis of different acupoints having different effects was tested in subjects suffering chronic pain by contrasting an accepted and a neutral acupoint, the results being reported in Chapter 7. Conclusion Despite a long history of clinical usage, appropriate scientific studies have not yet addressed the basic effectiveness and efficacy of acupuncture. This thesis presents a series of empirical studies designed to address a number of the questions arising in the literature and provides converging evidence of the manner in which different acupoints modulate the CNS, specifically within the pain neuromatrix.

Sleepiness contributes to between 20 and 30% of all heavy vehicle accidents throughout the world each year. Professional drivers are particularly susceptible to the effects of sleepiness, due to chronic or acute sleep deprivation, time-on-task effects, driving at circadian low points, and increased daytime sleepiness resulting from sleep disorders. Population surveys of heavy vehicle drivers indicates that a small proportion of drivers use pharmaceutical means in order to help maintain alertness during long-haul trips. Despite the known benefits of amphetamine-type stimulants on reducing fatigue and sleepiness, epidemiological evidence suggests that a large percentage of fatally injured professional drivers test positive to amphetamines. The primary objective of the current thesis was to determine the underlying causes of these sleep- and drug-related accidents. Experimentally, driving performance can be broken down into specific components that can be examined independently. Measures of behavioural disposition provide an indication of the drivers’ mood, ability to determine a change in performance and sleepiness, and whether the driver can make appropriate decisions regarding their ability to drive safely when sleep-deprived. Simulated driving tasks are commonly used to detect driving-related performance in a controlled and safe environment. The task of driving involves a number of components, including attention and vigilance, processing speed and reaction time, visual processes, and executive functioning, which can be measured using neurocognitive tasks. Smaller, pre-conscious neural processes that are undetected by behavioural tasks may also be affected by sleep deprivation, and in turn, affect driving performance. Electrophysiological (eventrelated potentials; ERPs) and neuroimaging (functional magnetic resonance imaging; fMRI) measures can be used to determine the neural underpinnings of visual and auditory processes after sleep deprivation. The aim of this thesis was to determine the effects of one night of sleep deprivation on these driving-related processes in professional drivers. In Experiment 1, nineteen professional drivers underwent two randomised sessions; one session following a normal night of sleep and one session following 24-hours of sleep deprivation. Behavioural disposition, simulated driving performance, neurocognitive measures related to driving, and visual and auditory ERPs were examined in both sessions. Subjective ratings of sleepiness and sleepiness symptoms increased significantly following sleep deprivation. Simulated driving performance and neurocognitive measures of vigilance and reaction time were impaired after sleep deprivation, whereas tasks examining processing speed and executive functioning were less susceptible to sleep deprivation. Event-related potentials of visual and auditory processing indicated that early visual processes were unaffected by sleep deprivation, whereas the amplitude of later cognitive processing was attenuated after sleep deprivation. Driving also involves the ability of the driver to divide his or her attention between different sensory modalities in the driving environment. Experiment 2 presents a functional neuroimaging experiment examining the effect of sleep deprivation on neural activations that occur in response to a cross-modal divided attention task. There was no significant effect of sleep deprivation on behavioural performance. Following sleep deprivation, increased activation was observed in the temporal gyrus, cerebellum and precuneus, compared to activations observed after normal sleep. As no behavioural changes were observed, the results suggest that additional activation may act as a compensatory mechanism. The restorative effect of d-amphetamine on sleep deprivation related impairment was examined in Experiment 3. This pilot study examined eight professional drivers who were past or current users of amphetamine across four, randomised sessions; after normal sleep with oral placebo, after sleep deprivation with oral placebo, after normal sleep with 0.42mg/kg oral d-amphetamine, and after sleep deprivation and 0.42mg/kg oral d-amphetamine. Measures of behavioural disposition appeared to be more affected by d-amphetamine administration after sleep deprivation compared to simulated driving and neurocognitive performance, however these findings need further clarification in a larger sample. The results of the present thesis highlight the detrimental influence of sleep deprivation on a range of driving-related processes. The experienced, professional drivers in this study were able to recognise signs and symptoms of sleepiness, and acted upon these indicators appropriately. Measures of driving-related performance on both simulated driving, and simple neurocognitive tasks were negatively affected by sleep loss, although there is likely to be a discrepancy between on-road and laboratory behaviour. ERP and neuroimaging findings in the present thesis suggest that these sleep-related behavioural effects are caused by small changes in neural processing and neural recruitment. Sleep deprivation can have large implications for safe driving, and this study highlights the importance of promoting and educating the driving public about the dangers of driving when sleepy.

No description available.

Early experience critically shapes cognitive, affective, and behavioral development, and experiences of early life stress (ELS) have been documented to negatively impact developmental trajectories. An increasing need exists for innovative intervention development to ameliorate negative impacts of ELS. Translational neuroscience approaches hold promise for addressing the needs of individuals who have experienced ELS through the development and testing of targeted intervention strategies grounded in neuroscientific knowledge. The current dissertation work employed a translational neuroscience approach to improve inhibitory control (IC) in a group of adolescents (N=20) exposed to a range of ELS via a brief, computerized training paradigm. Baseline analyses of the association between ELS and IC revealed a positive relationship (i.e., increased ELS, increased IC performance), counter to hypotheses. The IC training did not significantly improve IC in the training group compared to the control group over time, contrary to hypotheses and previous work demonstrating the effectiveness of this IC training in young adults. Transfer of training effects to a non-trained IC task and to real-world risk-taking behavior were limited. ELS demonstrated some moderation of neural effects of IC training. The use of neuroimaging in this dissertation work allowed for further investigation of neural mechanisms even in the absence of significant behavioral training, transfer, and moderation effects. Results are discussed in the context of the utility of such IC training approaches for adolescents with ELS exposure and of translational neuroscience approaches more broadly. Future directions for IC training, translational neuroscience intervention approaches, and the incorporation of neuroimaging in this work are explored. This dissertation includes unpublished co-authored material. / 10000-01-01

Adaptation is a fundamental property of the nervous system that underlies the maintenance of successful actions through flexible reconfiguration of sensorimotor processing. The primary aims of this thesis are 1) to investigate the computational and neural underpinnings of sensorimotor memory formation during prism adaptation (PA) in humans, and 2) how they interact with anodal transcranial direct current stimulation (a-tDCS) of the primary motor cortex (M1), in order to 3) improve efficacy of prism therapy for post-stroke spatial neglect. In chapter 4, we modify an influential state-space model of adaptation in order to characterize the contribution of short and long memory timescales to motor behaviour as sensorimotor after-effects (AEs) develop during PA. This enables us, in the multimodal 7 Tesla MRI experiment reported in chapter 5, to demonstrate that the level of M1 excitation:inhibition causally sets the relative contribution of long versus short memory timescales during PA, thus determining behavioural persistence of the AE at retention in young healthy adults. This finding offers a bridge between different levels of investigation by providing a biologically plausible neuro-computational model of how sensorimotor memories are formed and enhanced by a-tDCS. In chapter 6, we use the ageing motor system as a model of reduced GABAergic inhibition and show that the age-related decrease in M1 GABA explains why older adults demonstrate more persistent prism AEs. Taken together, these data indicate that the reduction in M1 GABAergic inhibition via excitatory a-tDCS during PA has the potential to enhance persistence of adaptation memory in both young and older adults. Informed by these results, we subsequently ask whether standard (multi-session) PA therapy combined with left M1 a-tDCS translates to greater and/or longer-lasting clinical improvements in post-stroke spatial neglect patients. In chapter 7, we compare the multimodal neuroimaging data of six neglect patients to normative data of age-matched controls. We show that in all patients, the lesion interrupted long-range frontoparietal connections, and we provide direct evidence for a pathological left dominance of activity within the lateral occipital cortex during deployment of bilateral visuospatial attention. In chapter 8, we present the behavioural performance of these patients throughout the two phases of the clinical study (i.e. before and after either PA + real M1 a-tDCS or PA + sham M1 atDCS). There was no clear effect of a-tDCS on the therapeutic effect of PA in these patients. The results of the studies presented in this thesis provide a novel insight into the neurocomputational mechanisms of sensorimotor memory formation and its modulation by a-tDCS in the healthy brain. Further investigation of how these mechanisms relate to therapeutic improvements following PA in certain neglect patients is needed.

xv, 169 p. ; ill. (some col.) A print copy of this thesis is available through the UO Libraries. Search the library catalog for the location and call number. / Improvements in neuroimaging techniques have made it possible to answer questions regarding the neural organization for the processing of syntax in normal participants. In this series of experiments we examined the effects of linguistic proficiency and age of second language acquisition on neural organization for syntactic processing. We examined these factors using two complementary methodologies: event-related potentials (ERPs), which affords a temporal resolution on the order of milliseconds, and functional magnetic resonance imaging (fMRI), with spatial resolution on the order of millimeters. In order to compare results across methodologies, we used an auditory syntactic violation paradigm with similar experimental parameters in each methodology. In Chapter II we examined neural organization for syntactic processing using ERPs in monolingual native speakers of higher and lower proficiency and found that violations elicited an early onset (100 ms) anterior negativity (EOAN) followed by a later positivity (P600) in all participants. Compared to lower proficiency participants, higher proficiency participants showed an EOAN that was more focal spatially and temporally, and showed a larger P600. These results were supported by a correlational analysis of a larger group of monolingual native speakers with a wide range of proficiency scores. This analysis also found a relationship between childhood socioeconomic status and the recruitment of the EOAN over left hemisphere sites, raising the hypothesis that effects of childhood experience may endure into adulthood. In Chapter III we examined the effects of age of acquisition on syntactic processing by recruiting a group of late learners of English who were matched for proficiency with a group of monolingual native speakers from Chapter II. While in native speakers violations elicited a robust EOAN, this effect was absent in the late learner group, suggesting that early language exposure is important for the recruitment of resources reflected in this effect and independently of proficiency. In Chapter IV we gathered ERP and fMRI data from monolingual native speakers and found proficiency differences in the recruitment for syntactic processing of left inferior frontal and posterior regions. We linked proficiency-related modulations in the different ERP syntactic effects to specific fMRI activations indexing syntactic processing. / Adviser: Helen J. Neville