Sexually size dimorphic brains and song complexity in passerine birds

Neural correlates of bird song involve the volume of particular song nuclei in the brain that govern song development, production, and perception. Intra- and interspecific variation in the volume of these song nuclei are associated with overall brain size, suggesting that the integration of complex songs into the brain requires general neural augmentation. In a comparative study of passerine birds based on generalized least square models, we tested this hypothesis by exploring the interspecific relationship between overall brain size and repertoire size. We found no significant association between song complexity of males and brain size adjusted for body size. However, species in which males produced complex songs tended to have sex differences in overall brain size. This pattern became stronger when we controlled statistically for female song complexity by using sex differences in song complexity. In species with large differences in song complexity, females evolved smaller brains than did males. Our results suggest no role for the evolution of extended neural space, as reflected by total brain size, owing to song complexity. However, factors associated with sexual selection mirrored by sex differences in song complexity were related to sexual dimorphism in overall brain size

Phylogeny and adaptive evolution of the brain-development gene microcephalin (MCPH1) in cetaceans.

BACKGROUND: Representatives of Cetacea have the greatest absolute brain size among animals, and the largest relative brain size aside from humans. Despite this, genes implicated in the evolution of large brain size in primates have yet to be surveyed in cetaceans. RESULTS: We sequenced ~1240 basepairs of the brain development gene microcephalin (MCPH1) in 38 cetacean species. Alignments of these data and a published complete sequence from Tursiops truncatus with primate MCPH1 were utilized in phylogenetic analyses and to estimate ω (rate of nonsynonymous substitution/rate of synonymous substitution) using site and branch models of molecular evolution. We also tested the hypothesis that selection on MCPH1 was correlated with brain size in cetaceans using a continuous regression analysis that accounted for phylogenetic history. Our analyses revealed widespread signals of adaptive evolution in the MCPH1 of Cetacea and in other subclades of Mammalia, however, there was not a significant positive association between ω and brain size within Cetacea. CONCLUSION: In conjunction with a recent study of Primates, we find no evidence to support an association between MCPH1 evolution and the evolution of brain size in highly encephalized mammalian species. Our finding of significant positive selection in MCPH1 may be linked to other functions of the gene

The Effects of Amygdalar Size Normalization on Group Analysis in Late-Life Depression

Structural MRI has been utilized in numerous ways to measure morphologic characteristics of subcortical brain regions. Volumetric analysis is frequently used to quantify the size of brain structures to ultimately compare size differences between individuals. In order to make such comparisons, inter-subject variability in brain and/or head size must be taken into consideration. A heterogeneous set of methods are commonly used to normalize regional volume by brain and/or head size yielding inconsistent findings making it diffcult to interpret and compare results from published volumetric studies. This study investigated the effect that various volume normalization methodologies might have on group analysis. Specifically, the amygdalae were the regions of interest in elderly, healthy and depressed individuals. Normalization methods investigated included spatial transformations, brain and head volume, and tissue volume techniques. Group analyses were conducted with independent t-tests by dividing amygdalar volumes by various volume measures, as well as with univariate analysis of covariance (ANCOVA) analyses by using amygdalar volumes as dependent variables and various volume measures as covariates. Repeated measures ANOVA was performed to assess the effect of each normalization procedure. Results indicate that volumetric differences between groups varied based on the normalization method utilized, which may explain, in part, the discrepancy found in amygdalar volumetric studies. We believe the findings of this study are extensible to other brain regions and demographics, and thus, investigators should carefully consider the normalization methods utilized in volumetric studies to properly interpret the results and conclusions

Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling

Large brain size is one of the defining characteristics of modern humans. Seckel syndrome (MIM 210600), a disorder of markedly reduced brain and body size, is associated with defective ATR-dependent DNA damage signaling. Only a single hypomorphic mutation of ATR has been identified in this genetically heterogeneous condition. We now report that mutations in the gene encoding pericentrin (PCNT)--resulting in the loss of pericentrin from the centrosome, where it has key functions anchoring both structural and regulatory proteins--also cause Seckel syndrome. Furthermore, we find that cells of individuals with Seckel syndrome due to mutations in PCNT (PCNT-Seckel) have defects in ATR-dependent checkpoint signaling, providing the first evidence linking a structural centrosomal protein with DNA damage signaling. These findings also suggest that other known microcephaly genes implicated in either DNA repair responses or centrosomal function may act in common developmental pathways determining human brain and body size

Brain Weight and Life-Span in Primate Species

In haplorhine primates (tarsiers, monkeys, apes, and humans), there is a significant correlation between brain weight and maximum life-span when the effect of body size is removed. There is also a significant correlation in haplorhine primates between brain weight and female age at first reproduction. For strepsirhine primates (lorises and lemurs), there are no significant correlations between brain weight and either life-span or female reproductive age when the effect of body size is removed. This lack of correlation in strepsirhine primates may be related to the fact that these primates are nocturnal and/or natives of the island of Madagascar, both of which conditions may reduce competition for resources and predation pressure. These findings suggest that in haplorhine primates the genetic systems controlling brain growth are linked to the systems governing the life cycle so that species with longer cycles have larger brains. When the effect of body weight is removed, leaf-eating haplorhines have significantly smaller brains and shorter lives than haplorhines with other diets. Harem-living haplorhines also have significantly smaller brains and shorter life-spans than troop-living haplorhines when the effect of body weight is removed. We also sought to test the rate-of-living hypothesis by determining whether primates with basal metabolic rates that are higher than would be expected for their body size have shorter maximum life-spans than would be expected for their body size. Metabolic rate is not correlated with life-span or female age at first reproduction when the effect of body size is removed

Characteristics and treatments of large cystic brain metastasis: radiosurgery and stereotactic aspiration.

Brain metastasis represents one of the most common causes of intracranial tumors in adults, and the incidence of brain metastasis continues to rise due to the increasing survival of cancer patients. Yet, the development of cystic brain metastasis remains a relatively rare occurrence. In this review, we describe the characteristics of cystic brain metastasis and evaluate the combined use of stereotactic aspiration and radiosurgery in treating large cystic brain metastasis. The results of several studies show that stereotactic radiosurgery produces comparable local tumor control and survival rates as other surgery protocols. When the size of the tumor interferes with radiosurgery, stereotactic aspiration of the metastasis should be considered to reduce the target volume as well as decreasing the chance of radiation induced necrosis and providing symptomatic relief from mass effect. The combined use of stereotactic aspiration and radiosurgery has strong implications in improving patient outcomes

Accelerated Evolution of the ASPM Gene Controlling Brain Size Begins Prior to Human Brain Expansion

Primary microcephaly (MCPH) is a neurodevelopmental disorder characterized by global reduction in cerebral cortical volume. The microcephalic brain has a volume comparable to that of early hominids, raising the possibility that some MCPH genes may have been evolutionary targets in the expansion of the cerebral cortex in mammals and especially primates. Mutations in ASPM, which encodes the human homologue of a fly protein essential for spindle function, are the most common known cause of MCPH. Here we have isolated large genomic clones containing the complete ASPM gene, including promoter regions and introns, from chimpanzee, gorilla, orangutan, and rhesus macaque by transformation-associated recombination cloning in yeast. We have sequenced these clones and show that whereas much of the sequence of ASPM is substantially conserved among primates, specific segments are subject to high Ka/Ks ratios (nonsynonymous/synonymous DNA changes) consistent with strong positive selection for evolutionary change. The ASPM gene sequence shows accelerated evolution in the African hominoid clade, and this precedes hominid brain expansion by several million years. Gorilla and human lineages show particularly accelerated evolution in the IQ domain of ASPM. Moreover, ASPM regions under positive selection in primates are also the most highly diverged regions between primates and nonprimate mammals. We report the first direct application of TAR cloning technology to the study of human evolution. Our data suggest that evolutionary selection of specific segments of the ASPM sequence strongly relates to differences in cerebral cortical size

Microglia-derived microvesicles affect microglia phenotype in glioma

Extracellular-released vesicles (EVs), such as microvesicles (MV) and exosomes (Exo) provide a new type of inter-cellular communication, directly transferring a ready to use box of information, consisting of proteins, lipids and nucleic acids. In the nervous system, EVs participate to neuron-glial cross-talk, a bidirectional communication important to preserve brain homeostasis and, when dysfunctional, involved in several CNS diseases. We investigated whether microglia-derived EVs could be used to transfer a protective phenotype to dysfunctional microglia in the context of a brain tumor. When MV, isolated from microglia stimulated with LPS/IFNg were brain injected in glioma-bearing mice, we observed a phenotype switch of tumor associated myeloid cells (TAMs) and a reduction of tumor size. Our findings indicate that the MV cargo, which contains upregulated transcripts for several inflammation-related genes, can transfer information in the brain of glioma bearing mice modifying microglial gene expression, reducing neuronal death and glioma invasion, thus promoting the recovery of brain homeostasis

Brain processing of contagious itch in patients with atopic dermatitis

Several studies show that itch and scratching cannot only be induced by pruritogens like histamine or cowhage, but also by the presentation of certain (audio-) visual stimuli like pictures on crawling insects or videos showing other people scratching. This phenomenon is coined Contagious itch (CI). Due to the fact that CI is more profound in patients with the chronic itchy skin disease atopic dermatitis (AD), we believe that it is highly relevant to study brain processing of CI in this group. Knowledge on brain areas involved in CI in AD-patients can provide us with useful hints regarding non-invasive treatments that AD-patients could profit from when they are confronted with itch-inducing situations in daily life. Therefore, this study investigated the brain processing of CI in AD-patients. 11 AD-patients underwent fMRI scans during the presentation of an itch inducing experimental video (EV) and a non-itch inducing control video (CV). Perfusion based brain activity was measured using arterial spin labeling functional MRI. As expected, the EV compared to the CV led to an increase in itch and scratching (p \u3c 0.05). CI led to a significant increase in brain activity in the supplementary motor area, left ventral striatum and right orbitofrontal cortex (threshold: p \u3c 0.001; cluster size k \u3e 50). Moreover, itch induced by watching the EV was by trend correlated with activity in memory-related regions including the temporal cortex and the (pre-) cuneus as well as the posterior operculum, a brain region involved in itch processing (threshold: p \u3c 0.005; cluster size k \u3e 50). These findings suggest that the fronto-striatal circuit, which is associated with the desire to scratch, might be a target region for non-invasive treatments in AD patients. © 2017 Schut, Mochizuki, Grossman, Lin, Conklin, Mohamed, Gieler, Kupfer and Yosipovitch