Moving Beyond Processing and Analysis-Related Variation in Neuroscience

When fields lack consensus standards and ground truths for their analytic methods, reproducibility tends to be more of an ideal than a reality. Such has been the case for functional neuroimaging, where there exists a sprawling space of tools from which scientists can construct processing pipelines and draw interpretations. We provide a critical evaluation of the impact of differences observed in results across five independently developed functional MRI minimal preprocessing pipelines. We show that even when handling the same exact data, inter-pipeline agreement was only moderate, with the specific steps that contribute to the lack of agreement varying across pipeline comparisons. Using a densely sampled test-retest dataset, we show that the limitations imposed by inter-pipeline agreement mainly become appreciable when the reliability of the underlying data is high. We highlight the importance of comparison among analytic tools and parameters, as both widely debated (e.g., global signal regression) and commonly overlooked (e.g., MNI template version) decisions were each found to lead to marked variation. We provide recommendations for incorporating tool-based variability in functional neuroimaging analyses and a supporting infrastructure.

Age-Related Variation in Sympathetic Nerve Distribution in the Human Spleen

Introduction: The cholinergic anti-inflammatory pathway (CAIP) has been proposed as an efferent neural pathway dampening the systemic inflammatory response via the spleen. The CAIP activates the splenic neural plexus and a subsequent series of intrasplenic events, which at least require a close association between sympathetic nerves and T cells. Knowledge on this pathway has mostly been derived from rodent studies and only scarce information is available on the innervation of the human spleen. This study aimed to investigate the sympathetic innervation of different structures of the human spleen, the topographical association of nerves with T cells and age-related variations in nerve distribution.Materials and Methods: Spleen samples were retrieved from a diagnostic archive and were allocated to three age groups; neonates, 10–25 and 25–70 years of age. Sympathetic nerves and T cells were identified by immunohistochemistry for tyrosine hydroxylase (TH) and the membrane marker CD3, respectively. The overall presence of sympathetic nerves and T cells was semi-automatically quantified and expressed as total area percentage. A predefined scoring system was used to analyze the distribution of nerves within different splenic structures.Results: Sympathetic nerves were observed in all spleens and their number appeared to slightly increase from birth to adulthood and to decrease afterward. Irrespective to age, more than halve of the periarteriolar lymphatic sheaths (PALSs) contained sympathetic nerves in close association with T cells. Furthermore, discrete sympathetic nerves were observed in the capsule, trabeculae and red pulp and comparable to the total amount of sympathetic nerves, showed a tendency to decrease with age. No correlation was found between the number of T cells and sympathetic nerves.Conclusion: The presence of discrete sympathetic nerves in the splenic parenchyma, capsule and trabecular of human spleens could suggest a role in functions other than vasoregulation. In the PALS, sympathetic nerves were observed to be in proximity to T cells and is suggestive for the existence of the CAIP in humans. Since sympathetic nerve distribution shows interspecies and age-related variation, and our general understanding of the relative and spatial contribution of splenic innervation in immune regulation is incomplete, it remains difficult to estimate the anti-inflammatory potential of targeting splenic nerves in patients.

Growth and development of trabecular structure in the calcaneus of Japanese macaques (Macaca fuscata) reflects locomotor behavior, life-history, and neuromuscular development.

We aim to broaden the analysis of bone structure by suggesting a new way to incorporate the interactions between behavior, neuromuscular development, and life-history. We examine the associations between these variables and age-related variation in trabecular structure in the calcaneus of Japanese macaques (Macaca fuscata). If skeletal markers linking these variables can be established, our inferences of the biology and behavior of fossil species would be significantly improved. We μCT scanned the calcaneus in a cross-sectional sample of 36 juveniles aged between 0 and 7 years old and 5 adults at the Primate Research Institute, Japan. We calculated whole bone averages of standard trabecular properties and generated whole-bone morphometric maps of bone volume fraction and Youngs modulus. Trabecular structure is increasingly heterogeneous in older individuals. BV/TV decreases during the first month of life and increases afterwards, coinciding with the onset of independent locomotion. At birth, primary Youngs modulus is oriented orthogonal to the ossification center, but after locomotor onset bone structure becomes stiffest in the direction of joint surfaces and muscle attachments. Age-related variation in bone volume fraction is best predicted by an interaction between neuromaturation, body mass, and locomotor independence. Results support the common assumption that trabecular structure dynamically adapts to novel joint loading conditions during ontogeny. The timing of independent locomotion, body size, and neuromuscular development, are all correlated to age-related variation in the trabecular structure of the macaque calcaneus. The causal mechanisms behind the observed patterns cannot be directly inferred from our cross-sectional study. If the model presented in this paper holds up under longitudinal experimental conditions, trabecular structure can be used both to infer behavior from fossil morphology and to serve as a valuable proxy for neuromuscular maturation and life history events like locomotor onset and the achievement of an adult-like gait.

Aging-related variation of cuticular hydrocarbons in wild type and variant Drosophila melanogaster

The cuticle of all insects is covered with hydrocarbons which have multiple functions. Cuticular hydrocarbons (CHCs) basically serve to protect insects against environmental harm and to reduce dehydration. In many species, some CHCs also act as pheromones. CHCs have been intensively studied in Drosophila species and more specially in D. melanogaster. In this species, flies produce about 40 CHCs forming a complex sex- and species-specific bouquet. The quantitative and qualitative pattern of the CHC bouquet was characterized during the first days of adult life but remains unexplored in aging flies. Here, we characterized CHCs during the whole—or a large period of—adult life in males and females of several wild type and transgenic lines. Both types of lines included standard and variant CHC profiles. Some of the genotypes tested here showed very dramatic and unexpected aging-related variation based on their early days profile. This study provides a concrete dataset to better understand the mechanisms underlying the establishment and maintenance of CHCs on the fly cuticle. It could be useful to determine physiological parameters, including age and response to climate variation, in insects collected in the wild.