Cognitive deficits are highly prevalent in multiple sclerosis (MS) and have a negative impact on daily life. Impairments in information processing speed are among the most commonly reported deficits in MS and are generally assessed by evaluating mean-level performance on time-limited tests. However, this approach to assessing performance ignores potential within-subject differences that may be useful for characterizing cognitive difficulties in MS. An alternative method of measuring performance on timed cognitive tasks is to examine the degree of within-subject variability, termed intraindividual variability (IIV). IIV provides information about the characteristics of an individual’s performance and may provide novel information about cognitive functioning in MS and other neurodegenerative disorders. The research presented in this dissertation examined IIV in performance as an indicator of cognitive functioning in persons with MS and explored the relations of performance variability to measures of neuronal connectivity derived from resting state functional magnetic resonance imaging (rsfMRI). Individuals with MS were found to be both slower and more variable on tests of information processing speed and attention. This variability was observed even when controlling for sensorimotor confounds and other systematic variables that may influence variability, such as practice and learning effects. IIV in performance was found to better distinguish MS patients from matched groups of healthy control subjects when compared to common clinical measures of cognitive performance or average response speed. These differences in IIV were also found consistently across six monthly assessments in a group with MS who remained clinically stable over this period. This stability in IIV suggests its feasibility as a measure of changes in longitudinal cognitive or clinical status. Using rsfMRI, greater stability in performance (i.e., lower IIV) was associated with greater functional connectivity between frontal lobe regions (i.e., ventral medial prefrontal cortex and frontal pole) in persons with MS. This increased connectivity appears to represent potential compensatory processes within mildly affected MS individuals. Together the findings demonstrate that IIV is an important characteristic of cognitive performance that may provide new insights into the cognitive deficits present in MS.

To characterize the relationship between dispersion-based intra-individual variability (IIVd) in neuropsychological test performance and brain volume among HIV seropositive and seronegative men and to determine the effects of cardiovascular risk and HIV infection on this relationship. Magnetic Resonance Imaging (MRI) was used to acquire high-resolution neuroanatomic data from 147 men age 50 and over, including 80 HIV seropositive (HIV+) and 67 seronegative controls (HIV-) in this cross-sectional cohort study. Voxel Based Morphometry was used to derive volumetric measurements at the level of the individual voxel. These brain structure maps were analyzed using Statistical Parametric Mapping (SPM2). IIVd was measured by computing intra-individual standard deviations (ISD’s) from the standardized performance scores of five neuropsychological tests: Wechsler Memory Scale-III Visual Reproduction I and II, Logical Memory I and II, Wechsler Adult Intelligence Scale-III Letter Number Sequencing. Total gray matter (GM) volume was inversely associated with IIVd. Among all subjects, IIVd -related GM atrophy was observed primarily in: 1) the inferior frontal gyrus bilaterally, the left inferior temporal gyrus extending to the supramarginal gyrus, spanning the lateral sulcus; 2) the right superior parietal lobule and intraparietal sulcus; and, 3) dorsal/ventral regions of the posterior section of the transverse temporal gyrus. HIV status, biological, and cardiovascular disease (CVD) variables were not linked to IIVd -related GM atrophy. IIVd in neuropsychological test performance may be a sensitive marker of cortical integrity in older adults, regardless of HIV infection status or CVD risk factors, and degree of intra-individual variability links with volume loss in specific cortical regions; independent of mean-level performance on neuropsychological tests.

Insufficient sleep duration is associated with poor physical and mental health outcomes, and many Americans report that they are not meeting sleep duration recommendations. Many individuals choose to restrict their own sleep, yet little is known about the source of this sleep deficit. Recent research efforts have used the Theory of Planned Behavior (TPB) to predict sleep health behavior. However, this research is limited in that it fails to measure volitional sleep behavior and focuses exclusively on between-person differences. This study addressed these limitations by using an intensive longitudinal design to test how constructs of the TPB relate to nightly sleep opportunity. Healthy college students (N=79) completed a week long study in which they completed 4 ecological momentary assessment signals per day that measured their attitudes, perceived norms, perceived behavioral control (PBC), and intentions relating to their nocturnal sleep opportunity. Participants wore an actiwatch each night of the study to measure their sleep opportunity. Analyses revealed between- and within-day variability of attitudes, perceived norms, PBC, and intentions. Further, there were significant between- and within-day trajectories of these constructs. Mixed linear models demonstrated that both intentions and PBC were significant predictors of subsequent sleep opportunity, and that PBC was the strongest predictor of future intentions. The between-and within-day patterns of these constructs highlight important considerations for their measurement, and provide insight into the potential refinement of sleep promotion efforts. Results also demonstrate that within-person changes in PBC and intentions predict subsequent sleep opportunity, demonstrating the need for a daily framework when using the TPB to predict sleep health behavior.

Les Anelloviridae sont de petits virus à ADN simple brin de découverte récente, très largement répandus chez les vertébrés. Chez l'homme, 3 genres distincts ont été caractérisés : Alphatorquevirus (TTV), Betatorquevirus (TTMV), Gammatorquevirus (TTMDV), engendrant une infection chronique mais dont le pouvoir pathogène potentiel demeure encore méconnu. Leur épidémiologie est en constante réévaluation du fait de leur extrême variabilité et diversité génétique. Au cours de cette recherche à l'interface entre virologie et paléomicrobiologie, nous avons exploré l'histoire naturelle de ces virus via 2 axes interconnectés. D'une part la diversité génétique a été analysée lors d'une étude transversale au sein de populations contemporaines (française et afghane) et de populations anciennes datant du néolithique à l'époque moderne. D'autre part, leur évolution a été étudiée à l'échelle individuelle par une étude longitudinale au sein de 2 corpus (suivis de patient transplanté et de patient hémodialysé). Dans le but de compléter les données concernant cette famille virale unique, un travail méthodologique a été mis en oeuvre afin d'apporter des améliorations et de standardiser les protocoles d'analyse existants. La comparaison de distribution des Anelloviridae parmi plusieurs populations contemporaines, nous a permis d'observer des différences significatives de profils, notamment dans la population afghane. Notre méthodologie d'analyse d'échantillons anciens a mis en évidence la présence de souches Anelloviridae, attestant ainsi leur ancestralité et révélant également l'existence de variabilités inter- et intra-individuelles, similaires à l'infection des populations modernes. / Anelloviridae are small single-stranded DNA viruses, recently discovered, and widely spread among vertebrates. In humans, three distinct genera were characterised: Alphatorquevirus (TTV), Betatorquevirus (TTMV), Gammatorquevirus (TTMDV), leading to a chronic infection whose pathogenicity remains unknown. Their epidemiology is constantly evolving due to their extreme variability and genetic diversity. In this multidisciplinary research, combining virology, bioanthropology and palaeomicrobiology, we have used genetic analysis to explore the natural history of those viruses via two linked issues. On the one hand, the genetic diversity was analysed by way of a cross-sectional study within contemporary populations (French and Afghan) and ancient populations from the Neolithic period to Modern times. On the other hand, their evolution was studied at the individual level through a longitudinal study in two corpora (follow-ups of a transplanted patient and haemodialysis patients). In order to complement data regarding this unique viral family, a methodological process was established to improve and standardize existing analysis protocols. Comparison of Anelloviridae's distributions among several healthy contemporary populations allowed us to notice significant differences of partitions, especially an almost complete absence of TTMDV in the Afghan sample. Our methodology dedicated to ancient remains displayed the presence of Anelloviridae strains, testifying their ancestral origin and highlighting inter- and intra-individual variations, similar to infections in modern populations.

Le polymorphisme génétique du virus de l’hépatite B (VHB) a déjà été étudié pourtenter de comprendre les facteurs viraux influençant l'évolution de la maladie, mais les étudessont discordantes. Ceci peut être lié au fait que les précédents travaux n’ont été menés quedans des populations avec une faible variété de génotypes et présentant des charges viralesplasmatiques (CVP) élevées.Nous avons donc étudié la variabilité du génome complet du VHB chez 422 individusinfectés chroniquement, naïfs de traitements anti-viraux et dont 38% présentaient une CVPinférieure à 103 UI/mL. L’optimisation de l’amplification par PCR du génome complet duVHB nous a permis de séquencer en technique Sanger plus de 90% du génome pour 320échantillons. Le séquençage direct a mis en évidence des co-infections. Ceci a été confirmé enséquençage clonal par pyroséquençage de 27 échantillons qui a montré des proportions departicules défectives variables mais toujours en co-infections avec des sous-populationssauvages. Le génotypage des séquences obtenues par technique Sanger a montré une grandereprésentativité des génotypes les plus fréquents (A à E) ainsi que 60 potentiels recombinantsinter-génotypiques. Cependant le séquençage clonal par pyroséquençage et clonage vectorielclassique de ces derniers montre la présence de co-infections de plusieurs génotypes ou laprésence de génotypes intermédiaires entre génotypes proches. Ceci est en défaveur derecombinaison par échange de matériel génétique comme ce qui a été suggéré dans lalittérature.Cette étude sera complétée par l’analyse de corrélation entre les polymorphismes et lesmarqueurs de mauvaise évolution de la pathologie. / The genetic polymorphism of hepatitis B virus (HBV) has been investigated tounderstand its impact on disease evolution, with discordant results. This could be due to thenarrow range of genotype and plasmatic viral load in these studies.We analysed complete genome variability of circulating HBV, in 422 chronicallyinfected patients. All were naive of anti-viral treatement and 38% had a plasmatic viral loadbelow 103 UI/mL. After optimisation of full length genome PCR amplification, we obtainedSanger sequences for more than 90% of HBV genome in 320 samples. We detected by directsequencing multiples co-infections that were confirmed by clonal pyrosequencing in 27samples. Defective viruses were always observed in co-infection with wild type virus. Directsequences showed a large representation of the most frequent genotypes (A to E), but also 60potential inter-genotypic recombinants. Clonal pyrosequencing and vectorial sequencingshowed that these potential recombinants were co-infections with different genotypes orintermediate genotypes located between close genotypes. These observations are incontradiction with the hypothesis described in the literature on recombination by geneticmaterial exchange.This study will be completed by a correlation analysis between the polymorphisms andmarkers of bad prognosis during HBV-induced disease.

Traditionally, reaction time (RT) was conceived of as an average speed of a number of responses made by an individual, or mean RT. Increasingly, however, intraindividual variability in reaction time (RT IIV) – the consistency of responses by a single person across trials – is used as an additional or even alternative measure. RT IIV is often found to be elevated in a number of conditions that affect the central nervous system functioning, such as traumatic brain injury or neurodegenerative diseases. It can predict change in cognitive performance in ageing, progression from normal ageing to mild cognitive impairment, and even death. Therefore, RT IIV may be of great practical importance. However, RT IIV and mean RT are correlated; therefore it is often problematic to draw conclusions about unique associations between these and other variables. One objective of the work presented in this thesis was to investigate determinants and correlates of simple and choice RT IIV and to test which associations may be accounted for by the individual differences in mean RT. The first investigation was concerned with age differences in RT IIV. Following a systematic review of literature, a series of meta-analyses demonstrated that older individuals (aged 60 years and above) have greater RT IIV than young or middle-aged adults in simple and choice RT tasks. The effects were reduced but still significant when RT IIV was adjusted for mean RT. The next study was a cross-sectional investigation of the associations between age and RT IIV, as well as of sex differences in RT IIV, across the lifespan in participants ranging in age from 4 to 75. Non-linear effects of age were found for RT IIV measures, such that variability decreased with age in children and increased with age in older adults. A novel finding from this study was that sex differences in RT IIV were present among adults but not children, suggesting that there might be an age threshold at which sexes diverge in their RT IIV trajectories. The results also indicated that findings regarding RT IIV may differ depending on the variability measure used (that is, whether and how mean RT is controlled). The second study on the same sample investigated variability on a trial-by-trial basis. Specifically, it tested the hypothesis that sex differences in variability are due to females being disproportionately slower at the first trial which inflates their overall RT IIV. This hypothesis was not supported. Another investigation used longitudinal data from the West of Scotland Twenty-07 study. Three cohorts of individuals aged approximately 15, 35 and 55, were followed up for 20 years and had RT data collected at four occasions. Analyses confirmed non-linear effects of age on RT IIV found in the earlier cross-sectional investigation. The final study investigated the effect of high altitude on RT IIV. It found that altitude-related increase in RT IIV is fully accounted for by general slowing of RT at high altitude. The overall pattern of results obtained from the investigations suggests that RT IIV increases with age in adults and that not all of the increase is due to general slowing. Moreover, the results show that sex differences in RT IIV are not uniform across the lifespan. Finally, whereas associations of RT IIV with some variables, for example age, are relatively robust to controlling for mean RT, others are fully attenuated by such practice.

<p>Elevated levels of anxiety are a common response to stressful competitive sports situations, are known to moderate athletic performance and are referred to as an unpleasant emotional state associated with perceptions of situational threat. The empirical studies in this dissertation considered primarily psychometric, methodological and conceptual issues of relevance for the study of anxiety and sports performance. In Study I, athletes were followed across a full competitive season to explore patterns of inter- and intra-individual variability of anxiety and self-confidence in relation to performance. The findings imply intra-individual anxiety and self-confidence variability to affect performance differently than the specific intensity level and are discussed in relation to more stable personality dispositions such as private self-consciousness. Study II evaluated the psychometric properties of the 27-item Competitive State Anxiety Inventory-2 (CSAI-2) and alternative versions of this scale. General support for a 17-item version (CSAI-2R) was found, but there are also psychometric limitations future research needs to resolve. Study III investigated assessment of intensity and directional ratings on single anxiety items with reference to the conceptualisation of anxiety symptoms as interpreted on a debilitative-facilitative continuum. The findings question the importance and rationale of assessing anxiety direction and revealed serious concerns with assessment procedures and statistical techniques applied in previous research. These concerns were also supported in Study IV, which explored athletes’ idiosyncratic experiences of debilitative and facilitative anxiety symptoms in terms of intensity and emotional valence. The findings are discussed and summarised in a model in order to increase conceptual clarity and provide implications for future research regarding anxiety and related emotional performance states.</p>

Elevated levels of anxiety are a common response to stressful competitive sports situations, are known to moderate athletic performance and are referred to as an unpleasant emotional state associated with perceptions of situational threat. The empirical studies in this dissertation considered primarily psychometric, methodological and conceptual issues of relevance for the study of anxiety and sports performance. In Study I, athletes were followed across a full competitive season to explore patterns of inter- and intra-individual variability of anxiety and self-confidence in relation to performance. The findings imply intra-individual anxiety and self-confidence variability to affect performance differently than the specific intensity level and are discussed in relation to more stable personality dispositions such as private self-consciousness. Study II evaluated the psychometric properties of the 27-item Competitive State Anxiety Inventory-2 (CSAI-2) and alternative versions of this scale. General support for a 17-item version (CSAI-2R) was found, but there are also psychometric limitations future research needs to resolve. Study III investigated assessment of intensity and directional ratings on single anxiety items with reference to the conceptualisation of anxiety symptoms as interpreted on a debilitative-facilitative continuum. The findings question the importance and rationale of assessing anxiety direction and revealed serious concerns with assessment procedures and statistical techniques applied in previous research. These concerns were also supported in Study IV, which explored athletes’ idiosyncratic experiences of debilitative and facilitative anxiety symptoms in terms of intensity and emotional valence. The findings are discussed and summarised in a model in order to increase conceptual clarity and provide implications for future research regarding anxiety and related emotional performance states.

Mild Traumatic Brain Injury (mTBI), often called concussion, has become a growing public health concern, prevalent in both athletic and military settings. In response, many researchers have explored cognitive outcomes post-mTBI, with a plethora of meta-analyses summarizing these findings; however, these meta-analyses examine solely mean performances on cognitive tasks, ignoring intra-individual variability (IIV) in cognitive performance that may elucidate neuropsychological impairment following mTBI. The current thesis involved two studies, responding to both the growing meta-analytic research and limited IIV findings. Study 1: Many meta-analyses have amalgamated individual study results on post-mTBI neuropsychological outcomes. With the abundance of meta-analyses, a systematic review of meta-analyses stands as the next logical step. Method: A systematic literature search yielded 11 meta-analyses meeting inclusion criteria (i.e., English-language systematic reviews/meta-analyses covering post-mTBI observational cognitive research on late adolescents/adults), with their findings qualitatively synthesized based on moderator variables (i.e., cognitive domain, time since injury, past head injury, participant characteristics, comparison group, assessment technique, and persistent symptoms). Results: The overall effect sizes ranged for both general (range: .07-.61) and sports-related mTBI (range: .40-.81) and differed both between and within cognitive domains, with executive functions appearing most sensitive to multiple mTBI. Cognitive domains varied in recovery rates, but overall recovery occurred by 90 days post-injury for most individuals and by seven days post-injury for athletes. Greater age/education and male gender produced smaller effects sizes, while high school athletes suffered the largest deficits post-mTBI. Control-group comparisons yielded larger effects than within-person designs, while assessment techniques had limited moderating effects. Conclusions: Overall, meta-analytic review quality remained low with few studies assessing publication or study quality bias. Meta-analyses consistently identified adverse acute mTBI-related effects and fairly rapid symptom resolution. Study 2: The long-term outcomes of executive functions and IIV following mTBI are unclear due to inconsistent and limited research, respectively. Further, the relationship between physical activity (PA) and cognitive performance at young adulthood remains almost fully unexplored. In turn, the current study aimed to (a) assess the diagnostic utility of both executive functions and IIV at predicting mTBI history and (b) evaluate the interaction between PA levels and mTBI on both of these cognitive metrics. Method: Altogether 138 self-identified athletes (Mage = 19.9 ± 1.91 years, 60.8% female, 19.6% 1 mTBI, 18.1% 2+ mTBIs) completed three executive-related cognitive tasks (i.e., N-Back, Go/No-go, Local-Global). Ordinal logistic regression analyses examined the joint effect of person-mean and IIV as predictors of mTBI status. Multi-level models examined mTBI and PA levels as predictors of trial-to-trial changes in performance. Results: Only mean response time (RT) for the Local-Global task predicted mTBI status, while no IIV variables reached unique significance. PA levels predicted subtle within-task decreases in RT across Local-Global trials. Conclusions: IIV research on mTBI remains limited; however, the preliminary results do not indicate any additional predictive value of IIV indices above mean performances. For executive functions, shifting appeared most affected, with past researchers identifying post-mTBI impairment in attentional processing. Higher PA levels minutely benefited within-task shifting and mean inhibitory performance, although these finding require cautious interpretation. / Graduate / 0622 / jkarr@uvic.ca

Decisions often require weighing the costs and benefits of available prospects. Value-based decision making depends on the coordination of multiple cognitive faculties, making it potentially susceptible to at least two forms of variability. First, there is heterogeneity in brain organization across individuals in areas of association cortex that exhibit decision-related activity. Second, a person’s preferences can fluctuate even for repetitive decision scenarios. Using functional magnetic resonance imaging (fMRI) and behavioral experiments in humans, this project explored how these distinct sources of variability impact choice evaluation, localization of valuation in the brain, and the links between valuation and other cognitive phenomena. Group-level findings suggest that valuation processes share a neural representation with the “default network” (DN) in medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC). Study 1 examined brain network variability in an open dataset of resting-state fMRI (n=100) by quantitatively testing the hypothesis that the spatial layout of the DN is unique to each person. Functional network topography was well-aligned across individuals in PCC, but highly idiosyncratic in mPFC. These results highlighted that the apparent overlap of cognitive functions in these areas should be evaluated within individuals. Study 2 examined variability in the integration of rewards with subjective costs of time and effort. Two computerized behavioral experiments (total n=132) tested how accept-or-reject foraging decisions were influenced by demands for physical effort, cognitive effort, and unfilled delay. The results showed that people’s willingness to incur the three types of costs differed when they experienced a single type of demand, but gradually converged when all three were interleaved. The results could be accounted for by a computational model in which contextual factors altered the perceived cost of temporal delay. Finally, Study 3 asked whether the apparent cortical overlap between valuation effects and the DN persisted after accounting for individual variability in brain topography and behavior. Using fMRI scans designed to evoke valuation and DN-like effects (n=18), we reproduced the idiosyncratic network topography from Study 1, and observed valuation-related effects in individually identified DN regions. Collectively, these findings advance our taxonomic understanding of higher-order cognitive processes, suggesting that seemingly dissimilar valuation and DN-related functions engage overlapping cortical mechanisms.