Differential patterns of age-related cortical and subcortical functional connectivity in 6-to-10 year old children: A connectome-wide association study

Introduction: Typical brain development is characterized by specific patterns of maturation of functional networks. Cortico-cortical connectivity generally increases, whereas subcortico-cortical connections often decrease. Little is known about connectivity changes amongst different subcortical regions in typical development. Methods: This study examined age- and gender-related differences in functional connectivity between and within cortical and subcortical regions using two different approaches. The participants included 411 six- to ten-year-old typically developing children sampled from the population-based Generation R study. Functional connectomes were defined in native space using regions of interest from subject-specific FreeSurfer segmentations. Connections were defined as: (a) the correlation between regional mean time-series; and (b) the focal maximum of voxel-wise correlations within FreeSurfer regions. The association of age and gender with each functional connection was determined using linear regression. The preprocessing included the exclusion of children with excessive head motion and scrubbing to reduce the influence of minor head motion during scanning. Results: Cortico-cortical associations echoed previous findings that connectivity shifts from short to long-range with age. Subcortico-cortical associations with age were primarily negative in the focal network approach but were both positive and negative in the mean time-series network approach. Between subcortical regions, age-related associations were negative in both network approaches. Few connections had significant associations with gender. Conclusions: The present study replicates previously reported age-related patterns of connectivity in a relatively narrow age-range of children. In addition, we extended these findings by demonstrating decreased connectivity within the subcortex with increasing age. Lastly, we show the utility of a more focal approach that challenges the spatial assumptions made by the traditional mean time series approach

Sexual dimorphism in the parietal substrate associated with visuospatial cognition independent of general intelligence

Gender differences in visuospatial cognition (VSC) with male advantage are frequently reported in the literature. There is evidence for sexual dimorphisms in the human brain, one of which postulates more gray matter (GM) in females and more white matter (WM) in males relative to total intracranial volume. We investigated the neuroanatomy of VSC independent of general intelligence (g) in gender-separated populations, homogenous in age, education, memory performance, a memory- and brain morphology-related gene, and g. VSC and g were assessed with the Wechsler adult intelligence scale. The influence of g on VSC was removed using a hierarchical factor analysis and the Schmid-Leiman solution. Structural high-resolution magnetic resonance images were acquired and analyzed with voxel-based morphometry. As hypothesized, the clusters of positive correlations between local volumes and VSC performance independent of g were found mainly in parietal areas, but also in pre- and postcentral regions, predominantly in the WM in males, whereas in females these correlations were located in parietal and superior temporal areas, predominantly in the GM. Our results suggest that VSC depends more strongly on parietal WM structures in males and on parietal GM structures in females. This sex difference might have to do with the increased axonal and decreased somatodendritic tissue in males relative to females. Whether such gender-specific implementations of the VSC network can be explained genetically as suggested in investigations into the Turner syndrome or as a result of structural neural plasticity upon different experience and usage remains to be shown

Estrogen-Sensitive Learning is not Affected by Combination Ethinyl Estradiol and Levonorgestrel Oral Contraceptive Use

Two studies were conducted to explore the cognitive effects of combination ethinyl estradiol and levonorgestrel contraceptive use during late adolescence and young adulthood. Three groups of females, naturally cycling, active pill phase, and hormone-free interval phase, were tested on a battery of estrogen-sensitive, i.e., place learning and word generation, and estrogen-insensitive, i.e., map drawing, mental rotation, digit span, story recall, and object recall, tasks. Study 2 was conducted as a means to replicate the findings observed in Study 1 and to manipulate task difficulty and sensitivity. Two measures of mood were administered, and salivary estradiol levels at time of testing were assayed. Findings from both studies do not suggest mood or endogenous estrogen effects on cognition. Additionally, findings from both studies suggest no cognitive effects of combination ethinyl estradiol and levonorgestrel conceptive use. The large sample size of Study 2, n = 65, indicates sufficient power to detect statistical differences. These studies do not provide evidence of either cognitive detrimental or beneficial effects of combined oral contraceptive use during either late adolescence or young adulthood. Post-hoc analyses with a nondepressed subsample, however, suggest potential sparing of estrogen-sensitive place learning by active pill phase females relative to hormone-free interval and naturally cycling females during periods of low endogenous estrogens

Identifikation geschlechtsspezifischer Unterschiede und Zusammenhänge zu visuo-kognitiven Faktoren und einzelnen Testverfahren bei gesunden älteren Erwachsenen

Einleitung: Visuo-Kognition (VC) umfasst eine Vielzahl kognitiver Fähigkeiten, die sich bei neurodegenerativen Erkrankungen schon früh verändern können. Bis heute existiert kein einheitliches Modell der VC, was studienübergreifend Anwendung findet. Die Verwendung uneinheitlicher Begriffe und die unterschiedliche Zuteilung neuropsychologischer Testverfahren zu Subdomänen erschwert es, zu differenzieren, welche Veränderungen im Alter normal sind und welche auf ein pathologisches Geschehen hindeuten. Unklar ist zusätzlich, wie das Geschlecht die Visuo-Kognition beeinflusst. Diese Studie hat das Ziel, visuo-kognitive Subdomänen zu identifizieren und darzustellen, wie sich das Geschlecht auf die Subdomänen und einzelnen Testverfahren bei gesunden älteren Erwachsenen auswirkt. Methodik: Für die Beantwortung der Fragestellung wurden 100 (50 weiblich, 50 männlich) gesunde ältere Erwachsene (Alter 51 – 84 Jahre) neuropsychologisch untersucht. Dabei fanden verschiedene visuo-kognitive Testverfahren (VOSP, LPS 50+, BJLO, ROCF, CERAD+, CLOX) und global-kognitive Testverfahren Anwendung. Zur Identifizierung der Subdomänen wurden die Daten mittels Hauptkomponentenanalyse klassifiziert und mittels multivariater Kovarianzanalyse unter Kontrolle des Alters auf den Geschlechtszusammenhang analysiert. Die Berechnungen wurden durch Kovarianzanalysen und Diskriminanzanalysen komplettiert. Ergebnisse: Die Analysen ergeben ein Modell aus drei visuo-kognitiven Faktoren: komplexe visuo-kognitive Fähigkeiten, visuo-perzeptive Fähigkeiten und CLOX1+2. Dem ersten Faktor werden die Testverfahren BJLO, CERAD+ und ROCF zugeordnet, dem zweiten die Subtests 2-4 der VOSP, auf den dritten entfallen beide CLOX Tests. Ein Geschlechtsunterschied zeigt sich übergeordnet für alle Faktoren, sowie für die komplexen visuo-kognitiven Fähigkeiten. Dieser Effekt beruht hauptsächlich im moderaten Geschlechtsunterschied des BJLO, bei dem Männer signifikant bessere Ergebnisse erzielen. Alle anderen eingesetzten Testverfahren zeigen keinen signifikanten Leistungsunterschied zwischen Männern und Frauen. Conclusion: Die Studie kann zeigen, dass die VC eine heterogene kognitive Fähigkeit ist und sich in mehrere Subdomänen gliedern lässt. Das errechnete VC-Modell deckt sich mit Studien von Trojano et. al und de Renzi. Bei der Stichprobe gesunder älterer Erwachsener schneiden Männer im BJLO signifikant besser ab als Frauen, ansonsten lässt sich kein geschlechtsspezifischer Leistungsunterschied nachweisen