Verbal memory deficits are among the most prominent cognitive sequelae in individuals with left temporal lobe epilepsy (LTLE). However, relationships between verbal memory function and white matter integrity (WMI) in the left temporal lobe remain unclear. Current study aims included determining fractional anisotropy (FA) and mean diffusivity (MD) differences as an index of WMI between participants with left temporal lobe epilepsy (LTLE), participants with right TLE (RTLE), and controls, establishing group differences based on verbal memory function between TLE groups, and describing relationships between WMI and verbal memory function within TLE groups. Probabilistic tractography defined the left fornix (FRX), left uncinate fasciculus (UF), left parahippocampal cingulum (PHC), and a control region, the left corticospinal tract (CST), in 26 LTLE, 29 RTLE, and 20 control participants. The LTLE group demonstrated significantly lower fractional anisotropy (FA) along the PHC compared with controls. LTLE and RTLE groups did not differ significantly on measures of verbal memory until analyses were restricted to participants with left-lateralized language functioning. PHC FA was negatively correlated with semantic memory function in LTLE, but positively associated with episodic memory functioning in RTLE. Overall, findings highlight the PHC as vulnerable in LTLE, and differentially related to verbal memory functioning based on TLE group. Both findings are likely secondary to left-lateralized white matter disruption in LTLE. The current study also highlighted the importance of identifying homogenous groups to more clearly identify brain-behavior relationships. Current findings further define left-lateralized white matter alternations and related verbal memory deficits in TLE. Implications for these findings are presented in context with previous TLE literature, and future directions for further study are discussed.

Diffusion Tensor Magnetic Resonance Imaging was used to examine the age-related changes in white matter structural integrity in the common chimpanzee. Fractional Anisotropy(FA), a measure derived from the diffusion tensor data is sensitive to developmental and pathological changes in axonal density, myelination, size and coherence of organization of fibers within a voxel and thus reflects the white matter structural integrity. There is substantial evidence that white matter structural integrity decreases with age in humans. The long-term goal of this study is to compare the age-related changes in the white matter structural integrity among humans and chimpanzess to provide potential insights into the unique features of human aging. Different methods, including Region Of Interest (ROI) analysis, Tract Based Spatial Statistics (TBSS) are used to describe age-related changes in FA in a group of 21 chimpanzees. Strengths and limitations of these methods were discussed.

Older age is a primary risk factor for the development of cardiovascular disease in part through the stiffening of the large cardiothoracic elastic arteries (e.g., aorta, carotid arteries). Aging is also associated with reduced cognitive function, cerebrovascular reactivity and brain white matter integrity, but whether these changes in brain structure and function are associated with age-related large artery stiffness remains unclear. In contrast, older adults who have high aerobic fitness demonstrate attenuated large artery stiffness and better cognitive performance compared to their sedentary counterparts, but the effects of aerobic fitness on white matter integrity and cerebrovascular reactivity with aging are conflicting and limited. Moreover, whether high aerobic fitness-associated lower large artery stiffness in older adults is associated with, and perhaps mediates, the beneficial changes in cognitive function and white matter structure remains unknown. The purpose of this study was to investigate the extent to which high aerobic fitness is associated with preserved white matter structure, cerebrovascular reactivity, and cognitive performance in aged individuals, and if these changes in brain structure and function are associated with attenuated large artery stiffness. In young (n=19, 23.6 ± 2.5 years) and old (n=22, 64.4 ± 4.2 years) healthy adults, large elastic artery stiffness was measured by carotid-femoral pulse wave velocity (cfPWV, aortic stiffness) via non-invasive applanation tonometry of carotid and femoral pulse waveforms and carotid artery beta-stiffness index (β-stiffness index) and compliance using high-resolution ultrasound and carotid blood pressure via applanation tonometry. Aerobic fitness was measured as maximal exercise oxygen uptake (VO2max) using respiratory gas analysis on an upright cycle ergometer. Older subjects were stratified as high or low fit based on gender and age VO2max classification. Letter, pattern and N-Back cognitive tests were used to assess processing speed and working memory respectively. Fractional anisotropy (FA) from diffusion tensor images and Blood Oxygenation Level Dependent (BOLD) imaging was used to assess cerebrovascular reactivity (CVR) response to a breath hold and brain activation during a working memory task. The association between large artery stiffness and FA was then assessed using a voxel-wise general linear model approach and a region-of-interest analysis. Our results confirmed age-related increases in cfPWV, carotid β-stiffness index and central (carotid) but not brachial systolic blood pressure, and expected reductions in carotid compliance, VO2max, working memory and processing speed, and in white matter integrity in select brain regions (bilateral cingulate, frontal, occipital, temporal). In contrast, we found no age-associated differences in CVR to breath hold stimulus or change in BOLD response to the N-Back. In our cohort of health adults, we found that the age-related changes in large artery stiffness were not attenuated by high compared with low VO2max. Among older adults, large elastic artery stiffness was not associated with regional white matter integrity or cerebrovascular reactivity in any regions-of-interest. Greater carotid artery compliance and lower β-stiffness index was associated with higher processing speed, while compliance was related to higher d'Prime scores and lower reaction time on the 2-Back task among the older adults. CVR to a breath hold stimulus was not related to any measure of cognitive performance. VO2max was not associated with any measures of vascular function, brain structure, function or cognition, indicating relations between large artery stiffness and cognition were independent of aerobic fitness capacity. Taken together, these data suggest that select measures of cognitive performance, but not white matter structure or CVR, may be susceptible to age-related changes in carotid stiffness/compliance and that are unaffected by aerobic fitness. More work is needed to understand the mechanisms by which age-related declines in carotid artery compliance and increased carotid stiffness are associated with reductions in cognitive function in older adults.

Recent studies have found associations between prolonged stress response and white matter (WM) microstructure in individuals with schizophrenia, as well as correlations between early life trauma and WM integrity in individuals with schizophrenia and non-psychiatric controls; however, psychosocial correlates of WM dysfunction have not yet been adequately explored in individuals experiencing attenuated psychotic symptoms (APS, subthreshold versions of positive psychotic symptoms). This study examines WM microstructure using traditional and free-water corrected diffusion metrics within a community sample of 66 16 to 30-year-olds experiencing a range of APS to examine the contribution of perceived stress and childhood trauma to the relationship between APS and WM abnormalities, as well as examine the moderating influence of sex assigned at birth (herein referred to as sex) to these relationships. We found that overall symptom severity on the Structured Interview for Psychosis-risk Syndromes (SIPS) was associated with higher extracellular free-water (FW) across the whole brain, lower free-water corrected fractional anisotropy values (FAT), and higher free-water corrected radial diffusivity (RDT). Further, childhood trauma significantly moderated the relationship between SIPS scores and both FAT and RDT, controlling for biological sex at birth, such that in the presence of APS, childhood trauma was associated with higher FAT and lower RDT, and in lower APS the opposite pattern was seen, with childhood trauma associated with lower FAT and lower RDT. After stratifying for sex, childhood trauma moderated the SIPS – FAT and RDT relationships in males similar to findings in the whole sample, though this relationship was not present in females. Perceived stress was not a significant moderator in the total sample, though was a significant moderator of the APS – FA relationship in males only. This study represents an important step toward identifying mechanisms for WM dysfunction within individuals with psychosis spectrum disorders, as well as identifying important targets for interventions. / Psychology

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Nach einem ausführlichem Überblick über den Kenntnisstand der Genetik und Neurowissenschaft von allgemeiner Intelligenz und einer methodischen Anmerkung zur Notwendigkeit der Berücksichtigung latenter Variablen in den kognitiven Neurowissenschaften am Beispiel einer Reanalyse publizierter Ergebnisse wir das am besten etablierte Gehirnkorrelat der Intelligenz, die Gehirngröße, aus evolutionsgenetischer Perspektive neu betrachtet. Schätzungen des Koeffizienten additiv-genetischer deuten an, dass es keine rezente direktionale Selektion auf Gehirngröße gegeben hat, was ihre Validität als Proxy für Intelligenz in evolutionären Studien in Frage stellt. Stattdessen deuten Korrelationen der Gesichtssymmetrie älterer Männer mit Intelligenz und Informationsverarbeitungsgeschwindigkeit an, dass organismusweite Entwicklungsstabilität eine wichtige Grundlage von unterschieden in kognitiven Fähigkeiten sein könnte. Im zweiten Teil dieser Arbeit geht es vornehmlich um die Alterung kognitiver Fähigkeiten, beginnend mit einem allgemeinen Überblick. Daten einer Stichprobe von über 130 Individuen zeigen dann, dass die Integrität verschiedener Nervenbahnen im Gehirn hoch korreliert, was die Extraktion eines Generalfaktors der Traktintegrität erlaubt, der mit Informationsverarbeitungsgeschwindigkeit korreliert. Der einzige Trakt mit schwacher Ladung auf diesem Generalfaktor ist das Splenium des Corpus Callosum, welches mit Veränderungen der Intelligenz über 6 Jahrzehnte korreliert und den Effekt des Bet2 adrenergischem Rezeptorgens (ADRB2) auf diese Veränderung mediiert, möglicherweise durch Effekte auf neuronale Komopensationsprozesse. Schließlich wird auf Basis neuer Analyseverfahren für Magnetresonanzdaten gezeigt, dass vermehrte Eiseneinlagerungen im Gehirn, vermutlich Marker für zerebrale Mikroblutungen, sowohl mit lebenslang stabilen Intelligenzunterschieden als auch mit der altersbedingten Veränderung kognitiver Fähigkeiten assoziiert sind. / After an extensive review of what is known about the genetics and neuroscience of general intelligence and a methodological note emphasising the necessity to consider latent variables in cognitive neuroscience studies, exemplified by a re-analysis of published results, the most well-established brain correlate of intelligence, brain size, is revisited from an evolutionary genetic perspective. Estimates of the coefficient of additive genetic variation in brain size suggest that there was no recent directional selection on brain size, questioning its validity as a proxy for intelligence in evolutionary analyses. Instead, correlations of facial fluctuating asymmetry with intelligence and information processing speed in old men suggest that organism-wide developmental stability might be an important cause of individual differences in cognitive ability. The second half of the thesis focuses on cognitive ageing, beginning with a general review. In a sample of over 130 subjects it has then been found that the integrity of different white matter tracts in the brain is highly correlated, allowing for the extraction of a general factor of white matter tract integrity, which is correlated with information processing speed. The only tract not loading highly on this general factor is the splenium of the corpus callosum, which is correlated with changes in intelligence over 6 decades and mediates the effect of the beta2 adrenergic receptor gene (ADRB2) on cognitive ageing, possibly due to its involvement in neuronal compensation processes. Finally, using a novel analytic method for magnetic resonance data, it is shown that more iron depositions in the brain, presumably markers of a history of cerebral microbleeds, are associated with both lifelong-stable intelligence differences and age-related decline in cognitive functioning.