Why Size Matters: Differences in Brain Volume Account for Apparent Sex Differences in Callosal Anatomy

PubMed Central

Luders, Eileen; Toga, Arthur W.; Thompson, Paul M.

2013-01-01

Numerous studies have demonstrated a sexual dimorphism of the human corpus callosum. However, the question remains if sex differences in brain size, which typically is larger in men than in women, or biological sex per se account for the apparent sex differences in callosal morphology. Comparing callosal dimensions between men and women matched for overall brain size may clarify the true contribution of biological sex, as any observed group difference should indicate pure sex effects. We thus examined callosal morphology in 24 male and 24 female brains carefully matched for overall size. In addition, we selected 24 extremely large male brains and 24 extremely small female brains to explore if observed sex effects might vary depending on the degree to which male and female groups differed in brain size. Using the individual T1-weighted brain images (n=96), we delineated the corpus callosum at midline and applied a well-validated surface-based mesh-modeling approach to compare callosal thickness at 100 equidistant points between groups determined by brain size and sex. The corpus callosum was always thicker in men than in women. However, this callosal sex difference was strongly determined by the cerebral sex difference overall. That is, the larger the discrepancy in brain size between men and women, the more pronounced the sex difference in callosal thickness, with hardly any callosal differences remaining between brain-size matched men and women. Altogether, these findings suggest that individual differences in brain size account for apparent sex differences in the anatomy of the corpus callosum. PMID:24064068

Being fat and smart: A comparative analysis of the fat-brain trade-off in mammals.

PubMed

Heldstab, Sandra A; van Schaik, Carel P; Isler, Karin

2016-11-01

Humans stand out among non-aquatic mammals by having both an extremely large brain and a relatively large amount of body fat. To understand the evolution of this human peculiarity we report a phylogenetic comparative study of 120 mammalian species, including 30 primates, using seasonal variation in adult body mass as a proxy of the tendency to store fat. Species that rely on storing fat to survive lean periods are expected to be less active because of higher costs of locomotion and have increased predation risk due to reduced agility. Because a fat-storage strategy reduces the net cognitive benefit of a large brain without reducing its cost, such species should be less likely to evolve a larger brain than non-fat-storing species. We therefore predict that the two strategies to buffer food shortages (storing body fat and cognitive flexibility) are compensatory, and therefore predict negative co-evolution between relative brain size and seasonal variation in body mass. This trade-off is expected to be stronger in predominantly arboreal species than in more terrestrial ones, as the cost of transporting additional adipose depots is higher for climbing than for horizontal locomotion. We did, indeed, find a significant negative correlation between brain size and coefficient of variation (CV) in body mass in both sexes for the subsample of arboreal species, both in all mammals and within primates. In predominantly terrestrial species, in contrast, this correlation was not significant. We therefore suggest that the adoption of habitually terrestrial locomotor habits, accompanied by a reduced reliance on climbing, has allowed for a primate of our body size the unique human combination of unusually large brains and unusually large adipose depots. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evolutionary Divergence in Brain Size between Migratory and Resident Birds

PubMed Central

Sol, Daniel; Garcia, Núria; Iwaniuk, Andrew; Davis, Katie; Meade, Andrew; Boyle, W. Alice; Székely, Tamás

2010-01-01

Despite important recent progress in our understanding of brain evolution, controversy remains regarding the evolutionary forces that have driven its enormous diversification in size. Here, we report that in passerine birds, migratory species tend to have brains that are substantially smaller (relative to body size) than those of resident species, confirming and generalizing previous studies. Phylogenetic reconstructions based on Bayesian Markov chain methods suggest an evolutionary scenario in which some large brained tropical passerines that invaded more seasonal regions evolved migratory behavior and migration itself selected for smaller brain size. Selection for smaller brains in migratory birds may arise from the energetic and developmental costs associated with a highly mobile life cycle, a possibility that is supported by a path analysis. Nevertheless, an important fraction (over 68%) of the correlation between brain mass and migratory distance comes from a direct effect of migration on brain size, perhaps reflecting costs associated with cognitive functions that have become less necessary in migratory species. Overall, our results highlight the importance of retrospective analyses in identifying selective pressures that have shaped brain evolution, and indicate that when it comes to the brain, larger is not always better. PMID:20224776

Comparative support for the expensive tissue hypothesis: Big brains are correlated with smaller gut and greater parental investment in Lake Tanganyika cichlids.

PubMed

Tsuboi, Masahito; Husby, Arild; Kotrschal, Alexander; Hayward, Alexander; Buechel, Séverine D; Zidar, Josefina; Løvlie, Hanne; Kolm, Niclas

2015-01-01

The brain is one of the most energetically expensive organs in the vertebrate body. Consequently, the energetic requirements of encephalization are suggested to impose considerable constraints on brain size evolution. Three main hypotheses concerning how energetic constraints might affect brain evolution predict covariation between brain investment and (1) investment into other costly tissues, (2) overall metabolic rate, and (3) reproductive investment. To date, these hypotheses have mainly been tested in homeothermic animals and the existing data are inconclusive. However, there are good reasons to believe that energetic limitations might play a role in large-scale patterns of brain size evolution also in ectothermic vertebrates. Here, we test these hypotheses in a group of ectothermic vertebrates, the Lake Tanganyika cichlid fishes. After controlling for the effect of shared ancestry and confounding ecological variables, we find a negative association between brain size and gut size. Furthermore, we find that the evolution of a larger brain is accompanied by increased reproductive investment into egg size and parental care. Our results indicate that the energetic costs of encephalization may be an important general factor involved in the evolution of brain size also in ectothermic vertebrates. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Dogs Have the Most Neurons, Though Not the Largest Brain: Trade-Off between Body Mass and Number of Neurons in the Cerebral Cortex of Large Carnivoran Species

PubMed Central

Jardim-Messeder, Débora; Lambert, Kelly; Noctor, Stephen; Pestana, Fernanda M.; de Castro Leal, Maria E.; Bertelsen, Mads F.; Alagaili, Abdulaziz N.; Mohammad, Osama B.; Manger, Paul R.; Herculano-Houzel, Suzana

2017-01-01

Carnivorans are a diverse group of mammals that includes carnivorous, omnivorous and herbivorous, domesticated and wild species, with a large range of brain sizes. Carnivory is one of several factors expected to be cognitively demanding for carnivorans due to a requirement to outsmart larger prey. On the other hand, large carnivoran species have high hunting costs and unreliable feeding patterns, which, given the high metabolic cost of brain neurons, might put them at risk of metabolic constraints regarding how many brain neurons they can afford, especially in the cerebral cortex. For a given cortical size, do carnivoran species have more cortical neurons than the herbivorous species they prey upon? We find they do not; carnivorans (cat, mongoose, dog, hyena, lion) share with non-primates, including artiodactyls (the typical prey of large carnivorans), roughly the same relationship between cortical mass and number of neurons, which suggests that carnivorans are subject to the same evolutionary scaling rules as other non-primate clades. However, there are a few important exceptions. Carnivorans stand out in that the usual relationship between larger body, larger cortical mass and larger number of cortical neurons only applies to small and medium-sized species, and not beyond dogs: we find that the golden retriever dog has more cortical neurons than the striped hyena, African lion and even brown bear, even though the latter species have up to three times larger cortices than dogs. Remarkably, the brown bear cerebral cortex, the largest examined, only has as many neurons as the ten times smaller cat cerebral cortex, although it does have the expected ten times as many non-neuronal cells in the cerebral cortex compared to the cat. We also find that raccoons have dog-like numbers of neurons in their cat-sized brain, which makes them comparable to primates in neuronal density. Comparison of domestic and wild species suggests that the neuronal composition of carnivoran brains is not affected by domestication. Instead, large carnivorans appear to be particularly vulnerable to metabolic constraints that impose a trade-off between body size and number of cortical neurons. PMID:29311850

Dogs Have the Most Neurons, Though Not the Largest Brain: Trade-Off between Body Mass and Number of Neurons in the Cerebral Cortex of Large Carnivoran Species.

PubMed

Jardim-Messeder, Débora; Lambert, Kelly; Noctor, Stephen; Pestana, Fernanda M; de Castro Leal, Maria E; Bertelsen, Mads F; Alagaili, Abdulaziz N; Mohammad, Osama B; Manger, Paul R; Herculano-Houzel, Suzana

2017-01-01

Carnivorans are a diverse group of mammals that includes carnivorous, omnivorous and herbivorous, domesticated and wild species, with a large range of brain sizes. Carnivory is one of several factors expected to be cognitively demanding for carnivorans due to a requirement to outsmart larger prey. On the other hand, large carnivoran species have high hunting costs and unreliable feeding patterns, which, given the high metabolic cost of brain neurons, might put them at risk of metabolic constraints regarding how many brain neurons they can afford, especially in the cerebral cortex. For a given cortical size, do carnivoran species have more cortical neurons than the herbivorous species they prey upon? We find they do not; carnivorans (cat, mongoose, dog, hyena, lion) share with non-primates, including artiodactyls (the typical prey of large carnivorans), roughly the same relationship between cortical mass and number of neurons, which suggests that carnivorans are subject to the same evolutionary scaling rules as other non-primate clades. However, there are a few important exceptions. Carnivorans stand out in that the usual relationship between larger body, larger cortical mass and larger number of cortical neurons only applies to small and medium-sized species, and not beyond dogs: we find that the golden retriever dog has more cortical neurons than the striped hyena, African lion and even brown bear, even though the latter species have up to three times larger cortices than dogs. Remarkably, the brown bear cerebral cortex, the largest examined, only has as many neurons as the ten times smaller cat cerebral cortex, although it does have the expected ten times as many non-neuronal cells in the cerebral cortex compared to the cat. We also find that raccoons have dog-like numbers of neurons in their cat-sized brain, which makes them comparable to primates in neuronal density. Comparison of domestic and wild species suggests that the neuronal composition of carnivoran brains is not affected by domestication. Instead, large carnivorans appear to be particularly vulnerable to metabolic constraints that impose a trade-off between body size and number of cortical neurons.

The coevolution of innovation and technical intelligence in primates

PubMed Central

Street, Sally E.; Whalen, Andrew; Laland, Kevin N.

2016-01-01

In birds and primates, the frequency of behavioural innovation has been shown to covary with absolute and relative brain size, leading to the suggestion that large brains allow animals to innovate, and/or that selection for innovativeness, together with social learning, may have driven brain enlargement. We examined the relationship between primate brain size and both technical (i.e. tool using) and non-technical innovation, deploying a combination of phylogenetically informed regression and exploratory causal graph analyses. Regression analyses revealed that absolute and relative brain size correlated positively with technical innovation, and exhibited consistently weaker, but still positive, relationships with non-technical innovation. These findings mirror similar results in birds. Our exploratory causal graph analyses suggested that technical innovation shares strong direct relationships with brain size, body size, social learning rate and social group size, whereas non-technical innovation did not exhibit a direct relationship with brain size. Nonetheless, non-technical innovation was linked to brain size indirectly via diet and life-history variables. Our findings support ‘technical intelligence’ hypotheses in linking technical innovation to encephalization in the restricted set of primate lineages where technical innovation has been reported. Our findings also provide support for a broad co-evolving complex of brain, behaviour, life-history, social and dietary variables, providing secondary support for social and ecological intelligence hypotheses. The ability to gain access to difficult-to-extract, but potentially nutrient-rich, resources through tool use may have conferred on some primates adaptive advantages, leading to selection for brain circuitry that underlies technical proficiency. PMID:26926276

The coevolution of innovation and technical intelligence in primates.

PubMed

Navarrete, Ana F; Reader, Simon M; Street, Sally E; Whalen, Andrew; Laland, Kevin N

2016-03-19

In birds and primates, the frequency of behavioural innovation has been shown to covary with absolute and relative brain size, leading to the suggestion that large brains allow animals to innovate, and/or that selection for innovativeness, together with social learning, may have driven brain enlargement. We examined the relationship between primate brain size and both technical (i.e. tool using) and non-technical innovation, deploying a combination of phylogenetically informed regression and exploratory causal graph analyses. Regression analyses revealed that absolute and relative brain size correlated positively with technical innovation, and exhibited consistently weaker, but still positive, relationships with non-technical innovation. These findings mirror similar results in birds. Our exploratory causal graph analyses suggested that technical innovation shares strong direct relationships with brain size, body size, social learning rate and social group size, whereas non-technical innovation did not exhibit a direct relationship with brain size. Nonetheless, non-technical innovation was linked to brain size indirectly via diet and life-history variables. Our findings support 'technical intelligence' hypotheses in linking technical innovation to encephalization in the restricted set of primate lineages where technical innovation has been reported. Our findings also provide support for a broad co-evolving complex of brain, behaviour, life-history, social and dietary variables, providing secondary support for social and ecological intelligence hypotheses. The ability to gain access to difficult-to-extract, but potentially nutrient-rich, resources through tool use may have conferred on some primates adaptive advantages, leading to selection for brain circuitry that underlies technical proficiency. © 2016 The Author(s).

Microfiberoptic fluorescence photobleaching reveals size-dependent macromolecule diffusion in extracellular space deep in brain.

PubMed

Zador, Zsolt; Magzoub, Mazin; Jin, Songwan; Manley, Geoffrey T; Papadopoulos, Marios C; Verkman, A S

2008-03-01

Diffusion in brain extracellular space (ECS) is important for nonsynaptic intercellular communication, extracellular ionic buffering, and delivery of drugs and metabolites. We measured macromolecular diffusion in normally light-inaccessible regions of mouse brain by microfiberoptic epifluorescence photobleaching, in which a fiberoptic with a micron-size tip is introduced deep in brain tissue. In brain cortex, the diffusion of a noninteracting molecule [fluorescein isothiocyanate (FITC)-dextran, 70 kDa] was slowed 4.5 +/- 0.5-fold compared with its diffusion in water (D(o)/D), and was depth-independent down to 800 microm from the brain surface. Diffusion was significantly accelerated (D(o)/D of 2.9+/-0.3) in mice lacking the glial water channel aquaporin-4. FITC-dextran diffusion varied greatly in different regions of brain, with D(o)/D of 3.5 +/- 0.3 in hippocampus and 7.4 +/- 0.3 in thalamus. Remarkably, D(o)/D in deep brain was strongly dependent on solute size, whereas diffusion in cortex changed little with solute size. Mathematical modeling of ECS diffusion required nonuniform ECS dimensions in deep brain, which we call "heterometricity," to account for the size-dependent diffusion. Our results provide the first data on molecular diffusion in ECS deep in brain in vivo and demonstrate previously unrecognized hindrance and heterometricity for diffusion of large macromolecules in deep brain.

In Pursuit of Neurophenotypes: The Consequences of Having Autism and a Big Brain

PubMed Central

Amaral, David G.; Li, Deana; Libero, Lauren; Solomon, Marjorie; Van de Water, Judy; Mastergeorge, Ann; Naigles, Letitia; Rogers, Sally; Nordahl, Christine Wu

2017-01-01

A consensus has emerged that despite common core features, autism spectrum disorder (ASD) has multiple etiologies and various genetic and biological characteristics. The fact that there are likely to be subtypes of ASD has complicated attempts to develop effective therapies. The UC Davis MIND Institute Autism Phenome Project is a longitudinal, multidisciplinary analysis of children with autism and age-matched typically developing controls; nearly 400 families are participating in this study. The overarching goal is to gather sufficient biological, medical, and behavioral data to allow definition of clinically meaningful subtypes of ASD. One reasonable hypothesis is that different subtypes of autism will demonstrate different patterns of altered brain organization or development i.e., different neurophenotypes. In this Commentary, we discuss one neurophenotype that is defined by megalencephaly, or having brain size that is large and disproportionate to body size. We have found that 15% of the boys with autism demonstrate this neurophenotype, though it is far less common in girls. We review behavioral and medical characteristics of the large-brained group of boys with autism in comparison to those with typically sized brains. While brain size in typically developing individuals is positively correlated with cognitive function, the children with autism and larger brains have more severe disabilities and poorer prognosis. This research indicates that phenotyping in autism, like genotyping, requires a very substantial cohort of subjects. Moreover, since brain and behavior relationships may emerge at different times during development, this effort highlights the need for longitudinal analyses to carry out meaningful phenotyping. PMID:28239961

Neocortex expansion is linked to size variations in gene families with chemotaxis, cell-cell signalling and immune response functions in mammals.

PubMed

Castillo-Morales, Atahualpa; Monzón-Sandoval, Jimena; de Sousa, Alexandra A; Urrutia, Araxi O; Gutierrez, Humberto

2016-10-01

Increased brain size is thought to have played an important role in the evolution of mammals and is a highly variable trait across lineages. Variations in brain size are closely linked to corresponding variations in the size of the neocortex, a distinct mammalian evolutionary innovation. The genomic features that explain and/or accompany variations in the relative size of the neocortex remain unknown. By comparing the genomes of 28 mammalian species, we show that neocortical expansion relative to the rest of the brain is associated with variations in gene family size (GFS) of gene families that are significantly enriched in biological functions associated with chemotaxis, cell-cell signalling and immune response. Importantly, we find that previously reported GFS variations associated with increased brain size are largely accounted for by the stronger link between neocortex expansion and variations in the size of gene families. Moreover, genes within these families are more prominently expressed in the human neocortex during early compared with adult development. These results suggest that changes in GFS underlie morphological adaptations during brain evolution in mammalian lineages. © 2016 The Authors.

Neocortex expansion is linked to size variations in gene families with chemotaxis, cell–cell signalling and immune response functions in mammals

PubMed Central

Castillo-Morales, Atahualpa; Monzón-Sandoval, Jimena; de Sousa, Alexandra A.

2016-01-01

Increased brain size is thought to have played an important role in the evolution of mammals and is a highly variable trait across lineages. Variations in brain size are closely linked to corresponding variations in the size of the neocortex, a distinct mammalian evolutionary innovation. The genomic features that explain and/or accompany variations in the relative size of the neocortex remain unknown. By comparing the genomes of 28 mammalian species, we show that neocortical expansion relative to the rest of the brain is associated with variations in gene family size (GFS) of gene families that are significantly enriched in biological functions associated with chemotaxis, cell–cell signalling and immune response. Importantly, we find that previously reported GFS variations associated with increased brain size are largely accounted for by the stronger link between neocortex expansion and variations in the size of gene families. Moreover, genes within these families are more prominently expressed in the human neocortex during early compared with adult development. These results suggest that changes in GFS underlie morphological adaptations during brain evolution in mammalian lineages. PMID:27707894

Female brain size affects the assessment of male attractiveness during mate choice.

PubMed

Corral-López, Alberto; Bloch, Natasha I; Kotrschal, Alexander; van der Bijl, Wouter; Buechel, Severine D; Mank, Judith E; Kolm, Niclas

2017-03-01

Mate choice decisions are central in sexual selection theory aimed to understand how sexual traits evolve and their role in evolutionary diversification. We test the hypothesis that brain size and cognitive ability are important for accurate assessment of partner quality and that variation in brain size and cognitive ability underlies variation in mate choice. We compared sexual preference in guppy female lines selected for divergence in relative brain size, which we have previously shown to have substantial differences in cognitive ability. In a dichotomous choice test, large-brained and wild-type females showed strong preference for males with color traits that predict attractiveness in this species. In contrast, small-brained females showed no preference for males with these traits. In-depth analysis of optomotor response to color cues and gene expression of key opsins in the eye revealed that the observed differences were not due to differences in visual perception of color, indicating that differences in the ability to process indicators of attractiveness are responsible. We thus provide the first experimental support that individual variation in brain size affects mate choice decisions and conclude that differences in cognitive ability may be an important underlying mechanism behind variation in female mate choice.

The mating brain: early maturing sneaker males maintain investment into the brain also under fast body growth in Atlantic salmon (Salmo salar).

PubMed

Kotrschal, Alexander; Trombley, Susanne; Rogell, Björn; Brannström, Ioana; Foconi, Eric; Schmitz, Monika; Kolm, Niclas

It has been suggested that mating behaviours require high levels of cognitive ability. However, since investment into mating and the brain both are costly features, their relationship is likely characterized by energetic trade-offs. Empirical data on the subject remains equivocal. We investigated if early sexual maturation was associated with brain development in Atlantic salmon ( Salmo salar ), in which males can either stay in the river and sexually mature at a small size (sneaker males) or migrate to the sea and delay sexual maturation until they have grown much larger (anadromous males). Specifically, we tested how sexual maturation may induce plastic changes in brain development by rearing juveniles on either natural or ad libitum feeding levels. After their first season we compared brain size and brain region volumes across both types of male mating tactics and females. Body growth increased greatly across both male mating tactics and females during ad libitum feeding as compared to natural feeding levels. However, despite similar relative increases in body size, early maturing sneaker males maintained larger relative brain size during ad libitum feeding levels as compared to anadromous males and females. We also detected several differences in the relative size of separate brain regions across feeding treatments, sexes and mating strategies. For instance, the relative size of the cognitive centre of the brain, the telencephalon, was largest in sneaker males. Our data support that a large relative brain size is maintained in individuals that start reproduction early also during fast body growth. We propose that the cognitive demands during complex mating behaviours maintain a high level of investment into brain development in reproducing individuals.

A Dense Poly(ethylene glycol) Coating Improves Penetration of Large Polymeric Nanoparticles within Brain Tissue

PubMed Central

Nance, Elizabeth A.; Woodworth, Graeme F.; Sailor, Kurt A.; Shih, Ting-Yu; Xu, Qingguo; Swaminathan, Ganesh; Xiang, Dennis; Eberhart, Charles; Hanes, Justin

2013-01-01

Prevailing opinion suggests that only substances up to 64 nm in diameter can move at appreciable rates through the brain extracellular space (ECS). This size range is large enough to allow diffusion of signaling molecules, nutrients, and metabolic waste products, but too small to allow efficient penetration of most particulate drug delivery systems and viruses carrying therapeutic genes, thereby limiting effectiveness of many potential therapies. We analyzed the movements of nanoparticles of various diameters and surface coatings within fresh human and rat brain tissue ex vivo and mouse brain in vivo. Nanoparticles as large as 114-nm in diameter diffused within the human and rat brain, but only if they were densely coated with poly(ethylene glycol) (PEG). Using these minimally adhesive PEG-coated particles, we estimated that human brain tissue ECS has some pores larger than 200 nm, and that more than one-quarter of all pores are ≥100 nm. These findings were confirmed in vivo in mice, where 40- and 100-nm, but not 200-nm, nanoparticles, spread rapidly within brain tissue, only if densely coated with PEG. Similar results were observed in rat brain tissue with paclitaxel-loaded biodegradable nanoparticles of similar size (85 nm) and surface properties. The ability to achieve brain penetration with larger nanoparticles is expected to allow more uniform, longer-lasting, and effective delivery of drugs within the brain, and may find use in the treatment of brain tumors, stroke, neuroinflammation, and other brain diseases where the blood-brain barrier is compromised or where local delivery strategies are feasible. PMID:22932224

High correlations between MRI brain volume measurements based on NeuroQuant® and FreeSurfer.

PubMed

Ross, David E; Ochs, Alfred L; Tate, David F; Tokac, Umit; Seabaugh, John; Abildskov, Tracy J; Bigler, Erin D

2018-05-30

NeuroQuant ® (NQ) and FreeSurfer (FS) are commonly used computer-automated programs for measuring MRI brain volume. Previously they were reported to have high intermethod reliabilities but often large intermethod effect size differences. We hypothesized that linear transformations could be used to reduce the large effect sizes. This study was an extension of our previously reported study. We performed NQ and FS brain volume measurements on 60 subjects (including normal controls, patients with traumatic brain injury, and patients with Alzheimer's disease). We used two statistical approaches in parallel to develop methods for transforming FS volumes into NQ volumes: traditional linear regression, and Bayesian linear regression. For both methods, we used regression analyses to develop linear transformations of the FS volumes to make them more similar to the NQ volumes. The FS-to-NQ transformations based on traditional linear regression resulted in effect sizes which were small to moderate. The transformations based on Bayesian linear regression resulted in all effect sizes being trivially small. To our knowledge, this is the first report describing a method for transforming FS to NQ data so as to achieve high reliability and low effect size differences. Machine learning methods like Bayesian regression may be more useful than traditional methods. Copyright © 2018 Elsevier B.V. All rights reserved.

Orbital Dynamics, Environmental Heterogeneity, and the Evolution of the Human Brain

ERIC Educational Resources Information Center

Grove, Matt

2012-01-01

Many explanations have been proposed for the evolution of our anomalously large brains, including social, ecological, and epiphenomenal hypotheses. Recently, an additional hypothesis has emerged, suggesting that advanced cognition and, by inference, increases in brain size, have been driven over evolutionary time by the need to deal with…

Evidence of a Conserved Molecular Response to Selection for Increased Brain Size in Primates

PubMed Central

Harrison, Peter W.; Caravas, Jason A.; Raghanti, Mary Ann; Phillips, Kimberley A.; Mundy, Nicholas I.

2017-01-01

The adaptive significance of human brain evolution has been frequently studied through comparisons with other primates. However, the evolution of increased brain size is not restricted to the human lineage but is a general characteristic of primate evolution. Whether or not these independent episodes of increased brain size share a common genetic basis is unclear. We sequenced and de novo assembled the transcriptome from the neocortical tissue of the most highly encephalized nonhuman primate, the tufted capuchin monkey (Cebus apella). Using this novel data set, we conducted a genome-wide analysis of orthologous brain-expressed protein coding genes to identify evidence of conserved gene–phenotype associations and species-specific adaptations during three independent episodes of brain size increase. We identify a greater number of genes associated with either total brain mass or relative brain size across these six species than show species-specific accelerated rates of evolution in individual large-brained lineages. We test the robustness of these associations in an expanded data set of 13 species, through permutation tests and by analyzing how genome-wide patterns of substitution co-vary with brain size. Many of the genes targeted by selection during brain expansion have glutamatergic functions or roles in cell cycle dynamics. We also identify accelerated evolution in a number of individual capuchin genes whose human orthologs are associated with human neuropsychiatric disorders. These findings demonstrate the value of phenotypically informed genome analyses, and suggest at least some aspects of human brain evolution have occurred through conserved gene–phenotype associations. Understanding these commonalities is essential for distinguishing human-specific selection events from general trends in brain evolution. PMID:28391320

"Life history space": a multivariate analysis of life history variation in extant and extinct Malagasy lemurs.

PubMed

Catlett, Kierstin K; Schwartz, Gary T; Godfrey, Laurie R; Jungers, William L

2010-07-01

Studies of primate life history variation are constrained by the fact that all large-bodied extant primates are haplorhines. However, large-bodied strepsirrhines recently existed. If we can extract life history information from their skeletons, these species can contribute to our understanding of primate life history variation. This is particularly important in light of new critiques of the classic "fast-slow continuum" as a descriptor of variation in life history profiles across mammals in general. We use established dental histological methods to estimate gestation length and age at weaning for five extinct lemur species. On the basis of these estimates, we reconstruct minimum interbirth intervals and maximum reproductive rates. We utilize principal components analysis to create a multivariate "life history space" that captures the relationships among reproductive parameters and brain and body size in extinct and extant lemurs. Our data show that, whereas large-bodied extinct lemurs can be described as "slow" in some fashion, they also varied greatly in their life history profiles. Those with relatively large brains also weaned their offspring late and had long interbirth intervals. These were not the largest of extinct lemurs. Thus, we distinguish size-related life history variation from variation that linked more strongly to ecological factors. Because all lemur species larger than 10 kg, regardless of life history profile, succumbed to extinction after humans arrived in Madagascar, we argue that large body size increased the probability of extinction independently of reproductive rate. We also provide some evidence that, among lemurs, brain size predicts reproductive rate better than body size. (c) 2010 Wiley-Liss, Inc.

What kind of noise is brain noise: anomalous scaling behavior of the resting brain activity fluctuations

PubMed Central

Fraiman, Daniel; Chialvo, Dante R.

2012-01-01

The study of spontaneous fluctuations of brain activity, often referred as brain noise, is getting increasing attention in functional magnetic resonance imaging (fMRI) studies. Despite important efforts, much of the statistical properties of such fluctuations remain largely unknown. This work scrutinizes these fluctuations looking at specific statistical properties which are relevant to clarify its dynamical origins. Here, three statistical features which clearly differentiate brain data from naive expectations for random processes are uncovered: First, the variance of the fMRI mean signal as a function of the number of averaged voxels remains constant across a wide range of observed clusters sizes. Second, the anomalous behavior of the variance is originated by bursts of synchronized activity across regions, regardless of their widely different sizes. Finally, the correlation length (i.e., the length at which the correlation strength between two regions vanishes) as well as mutual information diverges with the cluster's size considered, such that arbitrarily large clusters exhibit the same collective dynamics than smaller ones. These three properties are known to be exclusive of complex systems exhibiting critical dynamics, where the spatio-temporal dynamics show these peculiar type of fluctuations. Thus, these findings are fully consistent with previous reports of brain critical dynamics, and are relevant for the interpretation of the role of fluctuations and variability in brain function in health and disease. PMID:22934058

The social network-network: size is predicted by brain structure and function in the amygdala and paralimbic regions

PubMed Central

Von Der Heide, Rebecca; Vyas, Govinda

2014-01-01

The social brain hypothesis proposes that the large size of the primate neocortex evolved to support complex and demanding social interactions. Accordingly, recent studies have reported correlations between the size of an individual’s social network and the density of gray matter (GM) in regions of the brain implicated in social cognition. However, the reported relationships between GM density and social group size are somewhat inconsistent with studies reporting correlations in different brain regions. One factor that might account for these discrepancies is the use of different measures of social network size (SNS). This study used several measures of SNS to assess the relationships SNS and GM density. The second goal of this study was to test the relationship between social network measures and functional brain activity. Participants performed a social closeness task using photos of their friends and unknown people. Across the VBM and functional magnetic resonance imaging analyses, individual differences in SNS were consistently related to structural and functional differences in three regions: the left amygdala, right amygdala and the right entorhinal/ventral anterior temporal cortex. PMID:24493846

Regional selection of the brain size regulating gene CASC5 provides new insight into human brain evolution.

PubMed

Shi, Lei; Hu, Enzhi; Wang, Zhenbo; Liu, Jiewei; Li, Jin; Li, Ming; Chen, Hua; Yu, Chunshui; Jiang, Tianzi; Su, Bing

2017-02-01

Human evolution is marked by a continued enlargement of the brain. Previous studies on human brain evolution focused on identifying sequence divergences of brain size regulating genes between humans and nonhuman primates. However, the evolutionary pattern of the brain size regulating genes during recent human evolution is largely unknown. We conducted a comprehensive analysis of the brain size regulating gene CASC5 and found that in recent human evolution, CASC5 has accumulated many modern human specific amino acid changes, including two fixed changes and six polymorphic changes. Among human populations, 4 of the 6 amino acid polymorphic sites have high frequencies of derived alleles in East Asians, but are rare in Europeans and Africans. We proved that this between-population allelic divergence was caused by regional Darwinian positive selection in East Asians. Further analysis of brain image data of Han Chinese showed significant associations of the amino acid polymorphic sites with gray matter volume. Hence, CASC5 may contribute to the morphological and structural changes of the human brain during recent evolution. The observed between-population divergence of CASC5 variants was driven by natural selection that tends to favor a larger gray matter volume in East Asians.

Accurately Assessing the Risk of Schizophrenia Conferred by Rare Copy-Number Variation Affecting Genes with Brain Function

PubMed Central

Raychaudhuri, Soumya; Korn, Joshua M.; McCarroll, Steven A.; Altshuler, David; Sklar, Pamela; Purcell, Shaun; Daly, Mark J.

2010-01-01

Investigators have linked rare copy number variation (CNVs) to neuropsychiatric diseases, such as schizophrenia. One hypothesis is that CNV events cause disease by affecting genes with specific brain functions. Under these circumstances, we expect that CNV events in cases should impact brain-function genes more frequently than those events in controls. Previous publications have applied “pathway” analyses to genes within neuropsychiatric case CNVs to show enrichment for brain-functions. While such analyses have been suggestive, they often have not rigorously compared the rates of CNVs impacting genes with brain function in cases to controls, and therefore do not address important confounders such as the large size of brain genes and overall differences in rates and sizes of CNVs. To demonstrate the potential impact of confounders, we genotyped rare CNV events in 2,415 unaffected controls with Affymetrix 6.0; we then applied standard pathway analyses using four sets of brain-function genes and observed an apparently highly significant enrichment for each set. The enrichment is simply driven by the large size of brain-function genes. Instead, we propose a case-control statistical test, cnv-enrichment-test, to compare the rate of CNVs impacting specific gene sets in cases versus controls. With simulations, we demonstrate that cnv-enrichment-test is robust to case-control differences in CNV size, CNV rate, and systematic differences in gene size. Finally, we apply cnv-enrichment-test to rare CNV events published by the International Schizophrenia Consortium (ISC). This approach reveals nominal evidence of case-association in neuronal-activity and the learning gene sets, but not the other two examined gene sets. The neuronal-activity genes have been associated in a separate set of schizophrenia cases and controls; however, testing in independent samples is necessary to definitively confirm this association. Our method is implemented in the PLINK software package. PMID:20838587

Regional Variations in Brain Gyrification Are Associated with General Cognitive Ability in Humans

PubMed Central

Gregory, Michael D.; Kippenhan, J. Shane; Dickinson, Dwight; Carrasco, Jessica; Mattay, Venkata S.; Weinberger, Daniel R.; Berman, Karen F.

2016-01-01

Summary Searching for a neurobiological understanding of human intellectual capabilities has long occupied those very capabilities. Brain gyrification, or folding of the cortex, is as highly-evolved and variable a characteristic in humans as is intelligence. Indeed, gyrification scales with brain size, and relationships between brain size and intelligence have been demonstrated in humans [1-3]. However, gyrification shows a large degree of variability that is independent from brain size [4-6], suggesting that the former may independently contribute to cognitive abilities, and thus supporting a direct investigation of this parameter in the context of intelligence. Moreover, uncovering the regional pattern of such an association could offer insights into evolutionary and neural mechanisms. We tested for this brain-behavior relationship in two separate, independently-collected, large cohorts: 440 healthy adults and 662 healthy children, using high-resolution structural neuroimaging and comprehensive neuropsychometric batteries. In both samples, general cognitive ability was significantly associated (pfdr<0.01) with increasing gyrification in a network of neocortical regions, including large portions of the prefrontal cortex, inferior parietal lobule, and temporoparietal junction, as well as the insula, cingulate cortex, and fusiform gyrus, a regional distribution that was nearly identical in both samples (Dice similarity coefficient=0.80). This neuroanatomical pattern is consistent with an existing, well-known proposal, the Parieto-Frontal Integration Theory of Intelligence [7], and is also consistent with research in comparative evolutionary biology showing rapid neocortical expansion of these regions in humans relative to other species. These data provide a framework for understanding the neurobiology of human cognitive abilities, and suggest a potential neurocellular association. PMID:27133866

Brain enlargement and dental reduction were not linked in hominin evolution

PubMed Central

Smaers, Jeroen B.; Holloway, Ralph L.

2017-01-01

The large brain and small postcanine teeth of modern humans are among our most distinctive features, and trends in their evolution are well studied within the hominin clade. Classic accounts hypothesize that larger brains and smaller teeth coevolved because behavioral changes associated with increased brain size allowed a subsequent dental reduction. However, recent studies have found mismatches between trends in brain enlargement and posterior tooth size reduction in some hominin species. We use a multiple-variance Brownian motion approach in association with evolutionary simulations to measure the tempo and mode of the evolution of endocranial and dental size and shape within the hominin clade. We show that hominin postcanine teeth have evolved at a relatively consistent neutral rate, whereas brain size evolved at comparatively more heterogeneous rates that cannot be explained by a neutral model, with rapid pulses in the branches leading to later Homo species. Brain reorganization shows evidence of elevated rates only much later in hominin evolution, suggesting that fast-evolving traits such as the acquisition of a globular shape may be the result of direct or indirect selection for functional or structural traits typical of modern humans. PMID:28049819

Social brain volume is associated with in-degree social network size among older adults

PubMed Central

2018-01-01

The social brain hypothesis proposes that large neocortex size evolved to support cognitively demanding social interactions. Accordingly, previous studies have observed that larger orbitofrontal and amygdala structures predict the size of an individual's social network. However, it remains uncertain how an individual's social connectedness reported by other people is associated with the social brain volume. In this study, we found that a greater in-degree network size, a measure of social ties identified by a subject's social connections rather than by the subject, significantly correlated with a larger regional volume of the orbitofrontal cortex, dorsomedial prefrontal cortex and lingual gyrus. By contrast, out-degree size, which is based on an individual's self-perceived connectedness, showed no associations. Meta-analytic reverse inference further revealed that regional volume pattern of in-degree size was specifically involved in social inference ability. These findings were possible because our dataset contained the social networks of an entire village, i.e. a global network. The results suggest that the in-degree aspect of social network size not only confirms the previously reported brain correlates of the social network but also shows an association in brain regions involved in the ability to infer other people's minds. This study provides insight into understanding how the social brain is uniquely associated with sociocentric measures derived from a global network. PMID:29367402

Big Cat Coalitions: A Comparative Analysis of Regional Brain Volumes in Felidae.

PubMed

Sakai, Sharleen T; Arsznov, Bradley M; Hristova, Ani E; Yoon, Elise J; Lundrigan, Barbara L

2016-01-01

Broad-based species comparisons across mammalian orders suggest a number of factors that might influence the evolution of large brains. However, the relationship between these factors and total and regional brain size remains unclear. This study investigated the relationship between relative brain size and regional brain volumes and sociality in 13 felid species in hopes of revealing relationships that are not detected in more inclusive comparative studies. In addition, a more detailed analysis was conducted of four focal species: lions ( Panthera leo ), leopards ( Panthera pardus ), cougars ( Puma concolor ), and cheetahs ( Acinonyx jubatus ). These species differ markedly in sociality and behavioral flexibility, factors hypothesized to contribute to increased relative brain size and/or frontal cortex size. Lions are the only truly social species, living in prides. Although cheetahs are largely solitary, males often form small groups. Both leopards and cougars are solitary. Of the four species, leopards exhibit the most behavioral flexibility, readily adapting to changing circumstances. Regional brain volumes were analyzed using computed tomography. Skulls ( n = 75) were scanned to create three-dimensional virtual endocasts, and regional brain volumes were measured using either sulcal or bony landmarks obtained from the endocasts or skulls. Phylogenetic least squares regression analyses found that sociality does not correspond with larger relative brain size in these species. However, the sociality/solitary variable significantly predicted anterior cerebrum (AC) volume, a region that includes frontal cortex. This latter finding is despite the fact that the two social species in our sample, lions and cheetahs, possess the largest and smallest relative AC volumes, respectively. Additionally, an ANOVA comparing regional brain volumes in four focal species revealed that lions and leopards, while not significantly different from one another, have relatively larger AC volumes than are found in cheetahs or cougars. Further, female lions possess a significantly larger AC volume than conspecific males; female lion values were also larger than those of the other three species (regardless of sex). These results may reflect greater complexity in a female lion's social world, but additional studies are necessary. These data suggest that within family comparisons may reveal variations not easily detected by broad comparative analyses.

Big Cat Coalitions: A Comparative Analysis of Regional Brain Volumes in Felidae

PubMed Central

Sakai, Sharleen T.; Arsznov, Bradley M.; Hristova, Ani E.; Yoon, Elise J.; Lundrigan, Barbara L.

2016-01-01

Broad-based species comparisons across mammalian orders suggest a number of factors that might influence the evolution of large brains. However, the relationship between these factors and total and regional brain size remains unclear. This study investigated the relationship between relative brain size and regional brain volumes and sociality in 13 felid species in hopes of revealing relationships that are not detected in more inclusive comparative studies. In addition, a more detailed analysis was conducted of four focal species: lions (Panthera leo), leopards (Panthera pardus), cougars (Puma concolor), and cheetahs (Acinonyx jubatus). These species differ markedly in sociality and behavioral flexibility, factors hypothesized to contribute to increased relative brain size and/or frontal cortex size. Lions are the only truly social species, living in prides. Although cheetahs are largely solitary, males often form small groups. Both leopards and cougars are solitary. Of the four species, leopards exhibit the most behavioral flexibility, readily adapting to changing circumstances. Regional brain volumes were analyzed using computed tomography. Skulls (n = 75) were scanned to create three-dimensional virtual endocasts, and regional brain volumes were measured using either sulcal or bony landmarks obtained from the endocasts or skulls. Phylogenetic least squares regression analyses found that sociality does not correspond with larger relative brain size in these species. However, the sociality/solitary variable significantly predicted anterior cerebrum (AC) volume, a region that includes frontal cortex. This latter finding is despite the fact that the two social species in our sample, lions and cheetahs, possess the largest and smallest relative AC volumes, respectively. Additionally, an ANOVA comparing regional brain volumes in four focal species revealed that lions and leopards, while not significantly different from one another, have relatively larger AC volumes than are found in cheetahs or cougars. Further, female lions possess a significantly larger AC volume than conspecific males; female lion values were also larger than those of the other three species (regardless of sex). These results may reflect greater complexity in a female lion’s social world, but additional studies are necessary. These data suggest that within family comparisons may reveal variations not easily detected by broad comparative analyses. PMID:27812324

A mathematical model for human brain cooling during cold-water near-drowning.

PubMed

Xu, X; Tikuisis, P; Giesbrecht, G

1999-01-01

A two-dimensional mathematical model was developed to estimate the contributions of different mechanisms of brain cooling during cold-water near-drowning. Mechanisms include 1) conductive heat loss through tissue to the water at the head surface and in the upper airway and 2) circulatory cooling to aspirated water via the lung and via venous return from the scalp. The model accounts for changes in boundary conditions, blood circulation, respiratory ventilation of water, and head size. Results indicate that conductive heat loss through the skull surface or the upper airways is minimal, although a small child-sized head will conductively cool faster than a large adult-sized head. However, ventilation of cold water may provide substantial brain cooling through circulatory cooling. Although it seems that water breathing is required for rapid "whole" brain cooling, it is possible that conductive cooling may provide some advantage by cooling the brain cortex peripherally and the brain stem centrally via the upper airway.

Allometric Analysis Detects Brain Size-Independent Effects of Sex and Sex Chromosome Complement on Human Cerebellar Organization

PubMed Central

Mankiw, Catherine; Park, Min Tae M.; Reardon, P.K.; Fish, Ari M.; Clasen, Liv S.; Greenstein, Deanna; Blumenthal, Jonathan D.; Lerch, Jason P.; Chakravarty, M. Mallar

2017-01-01

The cerebellum is a large hindbrain structure that is increasingly recognized for its contribution to diverse domains of cognitive and affective processing in human health and disease. Although several of these domains are sex biased, our fundamental understanding of cerebellar sex differences—including their spatial distribution, potential biological determinants, and independence from brain volume variation—lags far behind that for the cerebrum. Here, we harness automated neuroimaging methods for cerebellar morphometrics in 417 individuals to (1) localize normative male–female differences in raw cerebellar volume, (2) compare these to sex chromosome effects estimated across five rare sex (X/Y) chromosome aneuploidy (SCA) syndromes, and (3) clarify brain size-independent effects of sex and SCA on cerebellar anatomy using a generalizable allometric approach that considers scaling relationships between regional cerebellar volume and brain volume in health. The integration of these approaches shows that (1) sex and SCA effects on raw cerebellar volume are large and distributed, but regionally heterogeneous, (2) human cerebellar volume scales with brain volume in a highly nonlinear and regionally heterogeneous fashion that departs from documented patterns of cerebellar scaling in phylogeny, and (3) cerebellar organization is modified in a brain size-independent manner by sex (relative expansion of total cerebellum, flocculus, and Crus II-lobule VIIIB volumes in males) and SCA (contraction of total cerebellar, lobule IV, and Crus I volumes with additional X- or Y-chromosomes; X-specific contraction of Crus II-lobule VIIIB). Our methods and results clarify the shifts in human cerebellar organization that accompany interwoven variations in sex, sex chromosome complement, and brain size. SIGNIFICANCE STATEMENT Cerebellar systems are implicated in diverse domains of sex-biased behavior and pathology, but we lack a basic understanding of how sex differences in the human cerebellum are distributed and determined. We leverage a rare neuroimaging dataset to deconvolve the interwoven effects of sex, sex chromosome complement, and brain size on human cerebellar organization. We reveal topographically variegated scaling relationships between regional cerebellar volume and brain size in humans, which (1) are distinct from those observed in phylogeny, (2) invalidate a traditional neuroimaging method for brain volume correction, and (3) allow more valid and accurate resolution of which cerebellar subcomponents are sensitive to sex and sex chromosome complement. These findings advance understanding of cerebellar organization in health and sex chromosome aneuploidy. PMID:28314818

Coevolution of cultural intelligence, extended life history, sociality, and brain size in primates

PubMed Central

Street, Sally E.; Navarrete, Ana F.; Laland, Kevin N.

2017-01-01

Explanations for primate brain expansion and the evolution of human cognition and culture remain contentious despite extensive research. While multiple comparative analyses have investigated variation in brain size across primate species, very few have addressed why primates vary in how much they use social learning. Here, we evaluate the hypothesis that the enhanced reliance on socially transmitted behavior observed in some primates has coevolved with enlarged brains, complex sociality, and extended lifespans. Using recently developed phylogenetic comparative methods we show that, across primate species, a measure of social learning proclivity increases with absolute and relative brain volume, longevity (specifically reproductive lifespan), and social group size, correcting for research effort. We also confirm relationships of absolute and relative brain volume with longevity (both juvenile period and reproductive lifespan) and social group size, although longevity is generally the stronger predictor. Relationships between social learning, brain volume, and longevity remain when controlling for maternal investment and are therefore not simply explained as a by-product of the generally slower life history expected for larger brained species. Our findings suggest that both brain expansion and high reliance on culturally transmitted behavior coevolved with sociality and extended lifespan in primates. This coevolution is consistent with the hypothesis that the evolution of large brains, sociality, and long lifespans has promoted reliance on culture, with reliance on culture in turn driving further increases in brain volume, cognitive abilities, and lifespans in some primate lineages. PMID:28739950

Brain regions implicated in inhibitory control and appetite regulation are activated in response to food portion size and energy density in children.

PubMed

English, L K; Fearnbach, S N; Lasschuijt, M; Schlegel, A; Anderson, K; Harris, S; Wilson, S J; Fisher, J O; Savage, J S; Rolls, B J; Keller, K L

2016-10-01

Large portions of energy-dense foods drive energy intake but the brain mechanisms underlying this effect are not clear. Our main objective was to investigate brain function in response to food images varied by portion size (PS) and energy density (ED) in children using functional magnetic resonance imaging (fMRI). Blood-oxygen-level-dependent (BOLD) fMRI was completed in 36 children (ages 7-10 years) after a 2-h fast while viewing food images at two levels of PS (Large PS, Small PS) and two levels of ED (High ED, Low ED). Children rated perceived fullness pre- and post-fMRI, as well as liking of images on visual analog scales post-fMRI. Anthropometrics were completed 4 weeks before the fMRI. Large PS vs Small PS and High ED vs Low ED were compared with region-of-interest analyses using Brain Voyager v 2.8. Region-of-interest analyses revealed that activation in the right inferior frontal gyrus (P=0.03) was greater for Large PS vs Small PS. Activation was reduced for High ED vs Low ED in the left hypothalamus (P=0.03). Main effects were no longer significant after adjustment for pre-fMRI fullness and liking ratings (PS, P=0.92; ED, P=0.58). This is the first fMRI study to report increased activation to large portions in a brain region that is involved in inhibitory control. These findings may contribute to understanding why some children overeat when presented with large portions of palatable food.

Brain size is correlated with endangerment status in mammals.

PubMed

Abelson, Eric S

2016-02-24

Increases in relative encephalization (RE), brain size after controlling for body size, comes at a great metabolic cost and is correlated with a host of cognitive traits, from the ability to count objects to higher rates of innovation. Despite many studies examining the implications and trade-offs accompanying increased RE, the relationship between mammalian extinction risk and RE is unknown. I examine whether mammals with larger levels of RE are more or less likely to be at risk of endangerment than less-encephalized species. I find that extant species with large levels of encephalization are at greater risk of endangerment, with this effect being strongest in species with small body sizes. These results suggest that RE could be a valuable asset in estimating extinction vulnerability. Additionally, these findings suggest that the cost-benefit trade-off of RE is different in large-bodied species when compared with small-bodied species. © 2016 The Author(s).

Cerebral complexity preceded enlarged brain size and reduced olfactory bulbs in Old World monkeys

PubMed Central

Gonzales, Lauren A.; Benefit, Brenda R.; McCrossin, Monte L.; Spoor, Fred

2015-01-01

Analysis of the only complete early cercopithecoid (Old World monkey) endocast currently known, that of 15-million-year (Myr)-old Victoriapithecus, reveals an unexpectedly small endocranial volume (ECV) relative to body size and a large olfactory bulb volume relative to ECV, similar to extant lemurs and Oligocene anthropoids. However, the Victoriapithecus brain has principal and arcuate sulci of the frontal lobe not seen in the stem catarrhine Aegyptopithecus, as well as a distinctive cercopithecoid pattern of gyrification, indicating that cerebral complexity preceded encephalization in cercopithecoids. Since larger ECVs, expanded frontal lobes, and reduced olfactory bulbs are already present in the 17- to 18-Myr-old ape Proconsul these features evolved independently in hominoids (apes) and cercopithecoids and much earlier in the former. Moreover, the order of encephalization and brain reorganization was apparently different in hominoids and cercopithecoids, showing that brain size and cerebral organization evolve independently. PMID:26138795

Sperm whales and killer whales with the largest brains of all toothed whales show extreme differences in cerebellum.

PubMed

Ridgway, Sam H; Hanson, Alicia C

2014-01-01

Among cetaceans, killer whales and sperm whales have the widest distribution in the world's oceans. Both species use echolocation, are long-lived, and have the longest periods of gestation among whales. Sperm whales dive much deeper and much longer than killer whales. It has long been thought that sperm whales have the largest brains of all living things, but our brain mass evidence, from published sources and our own specimens, shows that big males of these two species share this distinction. Despite this, we also find that cerebellum size is very different between killer whales and sperm whales. The sperm whale cerebellum is only about 7% of the total brain mass, while the killer whale cerebellum is almost 14%. These results are significant because they contradict claims that the cerebellum scales proportionally with the rest of the brain in all mammals. They also correct the generalization that all cetaceans have enlarged cerebella. We suggest possible reasons for the existence of such a large cerebellar size difference between these two species. Cerebellar function is not fully understood, and comparing the abilities of animals with differently sized cerebella can help uncover functional roles of the cerebellum in humans and animals. Here we show that the large cerebellar difference likely relates to evolutionary history, diving, sensory capability, and ecology. © 2014 S. Karger AG, Basel.

Nootropic nanocomplex with enhanced blood-brain barrier permeability for treatment of traumatic brain injury-associated neurodegeneration.

PubMed

Park, Jeongmin; Choi, Eunshil; Shin, Seulgi; Lim, Sungsu; Kim, Dohee; Baek, Suji; Lee, Kang Pa; Lee, Jae Jun; Lee, Byeong Han; Kim, Bokyung; Jeong, Keunsoo; Baik, Ja-Hyun; Kim, Yun Kyung; Kim, Sehoon

2018-06-15

Traumatic brain injury (TBI) is an intracranial injury which can induce immediate neuroinflammation and long-term neurological deficits. Methylene blue (MB) as a nootropic has a great potential to treat neurodegeneration after TBI because of its anti-inflmmatory and neuroprotective functions. However, its limited accumulation to the brain across the blood-brain barrier (BBB) remains a major hurdle to be overcome. In this paper, we present a polymer surfactant-encapsulated nanocomplex of MB as a delivery system with high BBB permeability for efficacious treatment of TBI-induced neurodegeneration. MB was formulated via electrostatically/hydrophobically directed assembly with fatty acid and Pluronic surfactant (F-127 or F-68) to construct nanocomplexes of two different colloidal sizes (<10 nm and ~108 nm in hydrodynamic diameter for NanoMB-127 and NanoMB-68, respectively). Compared to uncomplexed free MB, formulation into the ultrasmall nanocomplex (NanoMB-127) significantly enhanced the uptake of MB by blood-brain vascular endothelial bEnd3 cells in vitro, and indeed improved its BBB penetration upon systemic administration to normal mice in vivo. However, large-size NanoMB-68 showed negligible BBB crossing despite the efficient bEnd3 cell internalization in vitro, probably due to the unfavorable pharmacokinetic profile associated with its large particle size. By virtue of the efficient BBB penetration and cellular uptake, ultrasmall NanoMB-127 was shown to distinctively reduce the expression level of an inflammatory cytokine with no notable toxicity in vitro and also considerably prevent the neurodegeneration after TBI in mice at much lower doses than free MB. Overall, the Pluronic-supported nanocomplexation method allows efficient brain delivery of MB, offering a novel way of enhancing the efficacy of neurotherapeutics to treat brain diseases. Copyright © 2018. Published by Elsevier B.V.

Allometric Analysis Detects Brain Size-Independent Effects of Sex and Sex Chromosome Complement on Human Cerebellar Organization.

PubMed

Mankiw, Catherine; Park, Min Tae M; Reardon, P K; Fish, Ari M; Clasen, Liv S; Greenstein, Deanna; Giedd, Jay N; Blumenthal, Jonathan D; Lerch, Jason P; Chakravarty, M Mallar; Raznahan, Armin

2017-05-24

The cerebellum is a large hindbrain structure that is increasingly recognized for its contribution to diverse domains of cognitive and affective processing in human health and disease. Although several of these domains are sex biased, our fundamental understanding of cerebellar sex differences-including their spatial distribution, potential biological determinants, and independence from brain volume variation-lags far behind that for the cerebrum. Here, we harness automated neuroimaging methods for cerebellar morphometrics in 417 individuals to (1) localize normative male-female differences in raw cerebellar volume, (2) compare these to sex chromosome effects estimated across five rare sex (X/Y) chromosome aneuploidy (SCA) syndromes, and (3) clarify brain size-independent effects of sex and SCA on cerebellar anatomy using a generalizable allometric approach that considers scaling relationships between regional cerebellar volume and brain volume in health. The integration of these approaches shows that (1) sex and SCA effects on raw cerebellar volume are large and distributed, but regionally heterogeneous, (2) human cerebellar volume scales with brain volume in a highly nonlinear and regionally heterogeneous fashion that departs from documented patterns of cerebellar scaling in phylogeny, and (3) cerebellar organization is modified in a brain size-independent manner by sex (relative expansion of total cerebellum, flocculus, and Crus II-lobule VIIIB volumes in males) and SCA (contraction of total cerebellar, lobule IV, and Crus I volumes with additional X- or Y-chromosomes; X-specific contraction of Crus II-lobule VIIIB). Our methods and results clarify the shifts in human cerebellar organization that accompany interwoven variations in sex, sex chromosome complement, and brain size. SIGNIFICANCE STATEMENT Cerebellar systems are implicated in diverse domains of sex-biased behavior and pathology, but we lack a basic understanding of how sex differences in the human cerebellum are distributed and determined. We leverage a rare neuroimaging dataset to deconvolve the interwoven effects of sex, sex chromosome complement, and brain size on human cerebellar organization. We reveal topographically variegated scaling relationships between regional cerebellar volume and brain size in humans, which (1) are distinct from those observed in phylogeny, (2) invalidate a traditional neuroimaging method for brain volume correction, and (3) allow more valid and accurate resolution of which cerebellar subcomponents are sensitive to sex and sex chromosome complement. These findings advance understanding of cerebellar organization in health and sex chromosome aneuploidy. Copyright © 2017 the authors 0270-6474/17/375222-11$15.00/0.

Life history of roach, Rutilus rutilus (Cyprinidae, Teleostei). A qualitative and quantitative study on the development of sensory brain areas.

PubMed

Brandstätter, R; Kotrschal, K

1989-01-01

The present study deals with aspects of the brain development in the roach, Rutilus rutilus, a common mid-European cyprinid fish. The morphogenesis of selected brain areas from hatching to early juveniles was examined on serial paraffin cross-sections. From early juveniles to large adults, brain growth was quantitatively analyzed by computer-aided planimetry. The hatchlings of roach show a cytologically distinct optic tectum, but a poorly differentiated brainstem, reflecting the predominance of the optic sense during the larval planktivorous period. The differentiation and outgrowth of chemosensory brainstem centers is related to the onset and development of benthivorous feeding in juveniles. The optic tectum decreases in size relative to the total brain volume from juveniles through adults. The corpus cerebelli increases in relative size, whereas chemosensory and acousticolateral centers grow isometrically with the brain as a whole.

Brain architecture and social complexity in modern and ancient birds.

PubMed

Burish, Mark J; Kueh, Hao Yuan; Wang, Samuel S-H

2004-01-01

Vertebrate brains vary tremendously in size, but differences in form are more subtle. To bring out functional contrasts that are independent of absolute size, we have normalized brain component sizes to whole brain volume. The set of such volume fractions is the cerebrotype of a species. Using this approach in mammals we previously identified specific associations between cerebrotype and behavioral specializations. Among primates, cerebrotypes are linked principally to enlargement of the cerebral cortex and are associated with increases in the complexity of social structure. Here we extend this analysis to include a second major vertebrate group, the birds. In birds the telencephalic volume fraction is strongly correlated with social complexity. This correlation accounts for almost half of the observed variation in telencephalic size, more than any other behavioral specialization examined, including the ability to learn song. A prominent exception to this pattern is owls, which are not social but still have very large forebrains. Interpolating the overall correlation for Archaeopteryx, an ancient bird, suggests that its social complexity was likely to have been on a par with modern domesticated chickens. Telencephalic volume fraction outperforms residuals-based measures of brain size at separating birds by social structure. Telencephalic volume fraction may be an anatomical substrate for social complexity, and perhaps cognitive ability, that can be generalized across a range of vertebrate brains, including dinosaurs. Copyright 2004 S. Karger AG, Basel

Birds have primate-like numbers of neurons in the forebrain

PubMed Central

Olkowicz, Seweryn; Kocourek, Martin; Lučan, Radek K.; Porteš, Michal; Fitch, W. Tecumseh; Herculano-Houzel, Suzana; Němec, Pavel

2016-01-01

Some birds achieve primate-like levels of cognition, even though their brains tend to be much smaller in absolute size. This poses a fundamental problem in comparative and computational neuroscience, because small brains are expected to have a lower information-processing capacity. Using the isotropic fractionator to determine numbers of neurons in specific brain regions, here we show that the brains of parrots and songbirds contain on average twice as many neurons as primate brains of the same mass, indicating that avian brains have higher neuron packing densities than mammalian brains. Additionally, corvids and parrots have much higher proportions of brain neurons located in the pallial telencephalon compared with primates or other mammals and birds. Thus, large-brained parrots and corvids have forebrain neuron counts equal to or greater than primates with much larger brains. We suggest that the large numbers of neurons concentrated in high densities in the telencephalon substantially contribute to the neural basis of avian intelligence. PMID:27298365

Manipulation complexity in primates coevolved with brain size and terrestriality

PubMed Central

Heldstab, Sandra A.; Kosonen, Zaida K.; Koski, Sonja E.; Burkart, Judith M.; van Schaik, Carel P.; Isler, Karin

2016-01-01

Humans occupy by far the most complex foraging niche of all mammals, built around sophisticated technology, and at the same time exhibit unusually large brains. To examine the evolutionary processes underlying these features, we investigated how manipulation complexity is related to brain size, cognitive test performance, terrestriality, and diet quality in a sample of 36 non-human primate species. We categorized manipulation bouts in food-related contexts into unimanual and bimanual actions, and asynchronous or synchronous hand and finger use, and established levels of manipulative complexity using Guttman scaling. Manipulation categories followed a cumulative ranking. They were particularly high in species that use cognitively challenging food acquisition techniques, such as extractive foraging and tool use. Manipulation complexity was also consistently positively correlated with brain size and cognitive test performance. Terrestriality had a positive effect on this relationship, but diet quality did not affect it. Unlike a previous study on carnivores, we found that, among primates, brain size and complex manipulations to acquire food underwent correlated evolution, which may have been influenced by terrestriality. Accordingly, our results support the idea of an evolutionary feedback loop between manipulation complexity and cognition in the human lineage, which may have been enhanced by increasingly terrestrial habits. PMID:27075921

Influences of Brain Size, Sex, and Sex Chromosome Complement on the Architecture of Human Cortical Folding.

PubMed

Fish, Ari M; Cachia, Arnaud; Fischer, Clara; Mankiw, Catherine; Reardon, P K; Clasen, Liv S; Blumenthal, Jonathan D; Greenstein, Deanna; Giedd, Jay N; Mangin, Jean-François; Raznahan, Armin

2017-12-01

Gyrification is a fundamental property of the human cortex that is increasingly studied by basic and clinical neuroscience. However, it remains unclear if and how the global architecture of cortical folding varies with 3 interwoven sources of anatomical variation: brain size, sex, and sex chromosome dosage (SCD). Here, for 375 individuals spanning 7 karyotype groups (XX, XY, XXX, XYY, XXY, XXYY, XXXXY), we use structural neuroimaging to measure a global sulcation index (SI, total sulcal/cortical hull area) and both determinants of sulcal area: total sulcal length and mean sulcal depth. We detail large and patterned effects of sex and SCD across all folding metrics, but show that these effects are in fact largely consistent with the normative scaling of cortical folding in health: larger human brains have disproportionately high SI due to a relative expansion of sulcal area versus hull area, which arises because disproportionate sulcal lengthening overcomes a lack of proportionate sulcal deepening. Accounting for these normative allometries reveals 1) brain size-independent sulcal lengthening in males versus females, and 2) insensitivity of overall folding architecture to SCD. Our methodology and findings provide a novel context for future studies of human cortical folding in health and disease. Published by Oxford University Press 2016.

A combined MR and CT study for precise quantitative analysis of the avian brain

NASA Astrophysics Data System (ADS)

Jirak, Daniel; Janacek, Jiri; Kear, Benjamin P.

2015-10-01

Brain size is widely used as a measure of behavioural complexity and sensory-locomotive capacity in avians but has largely relied upon laborious dissections, endoneurocranial tissue displacement, and physical measurement to derive comparative volumes. As an alternative, we present a new precise calculation method based upon coupled magnetic resonance (MR) imaging and computed tomography (CT). Our approach utilizes a novel interactive Fakir probe cross-referenced with an automated CT protocol to efficiently generate total volumes and surface areas of the brain tissue and endoneurocranial space, as well as the discrete cephalic compartments. We also complemented our procedures by using sodium polytungstate (SPT) as a contrast agent. This greatly enhanced CT applications but did not degrade MR quality and is therefore practical for virtual brain tissue reconstructions employing multiple imaging modalities. To demonstrate our technique, we visualized sex-based brain size differentiation in a sample set of Ring-necked pheasants (Phasianus colchicus). This revealed no significant variance in relative volume or surface areas of the primary brain regions. Rather, a trend towards isometric enlargement of the total brain and endoneurocranial space was evidenced in males versus females, thus advocating a non-differential sexually dimorphic pattern of brain size increase amongst these facultatively flying birds.

Brain architecture of the Pacific White Shrimp Penaeus vannamei Boone, 1931 (Malacostraca, Dendrobranchiata): correspondence of brain structure and sensory input?

PubMed

Meth, Rebecca; Wittfoth, Christin; Harzsch, Steffen

2017-08-01

Penaeus vannamei (Dendrobranchiata, Decapoda) is best known as the "Pacific White Shrimp" and is currently the most important crustacean in commercial aquaculture worldwide. Although the neuroanatomy of crustaceans has been well examined in representatives of reptant decapods ("ground-dwelling decapods"), there are only a few studies focusing on shrimps and prawns. In order to obtain insights into the architecture of the brain of P. vannamei, we use neuroanatomical methods including X-ray micro-computed tomography, 3D reconstruction and immunohistochemical staining combined with confocal laser-scanning microscopy and serial sectioning. The brain of P. vannamei exhibits all the prominent neuropils and tracts that characterize the ground pattern of decapod crustaceans. However, the size proportion of some neuropils is salient. The large lateral protocerebrum that comprises the visual neuropils as well as the hemiellipsoid body and medulla terminalis is remarkable. This observation corresponds with the large size of the compound eyes of these animals. In contrast, the remaining median part of the brain is relatively small. It is dominated by the paired antenna 2 neuropils, while the deutocerebral chemosensory lobes play a minor role. Our findings suggest that visual input from the compound eyes and mechanosensory input from the second pair of antennae are major sensory modalities, which this brain processes.

Statistical Misconceptions and Rushton's Writings on Race.

ERIC Educational Resources Information Center

Cernovsky, Zack Z.

The term "statistical significance" is often misunderstood or abused to imply a large effect size. A recent example is in the work of J. P. Rushton (1988, 1990) on differences between Negroids and Caucasoids. Rushton used brain size and cranial size as indicators of intelligence, using Pearson "r"s ranging from 0.03 to 0.35.…

The von Economo neurons in fronto-insular and anterior cingulate cortex

PubMed Central

Allman, John M.; Tetreault, Nicole A.; Hakeem, Atiya Y.; Manaye, Kebreten F.; Semendeferi, Katerina; Erwin, Joseph M.; Park, Soyoung; Goubert, Virginie; Hof, Patrick R.

2011-01-01

The von Economo neurons (VENs) are large bipolar neurons located in fronto-insular cortex (FI) and anterior limbic area (LA) in great apes and humans but not in other primates. Our stereological counts of VENs in FI and LA show them to be more numerous in humans than in apes. In humans, small numbers of VENs appear the 36th week post conception, with numbers increasing during the first eight months after birth. There are significantly more VENs in the right hemisphere in postnatal brains; this may be related to asymmetries in the autonomic nervous system. VENs are also present in elephants and whales and may be a specialization related to very large brain size. The large size and simple dendritic structure of these projection neurons suggest that they rapidly send basic information from FI and LA to other parts of the brain, while slower neighboring pyramids send more detailed information. Selective destruction of VENs in early stages of fronto-temporal dementia implies that they are involved in empathy, social awareness, and self-control, consistent with evidence from functional imaging. PMID:21534993

Microhabitat use, trophic patterns, and the evolution of brain structure in African cichlids.

PubMed

Huber, R; van Staaden, M J; Kaufman, L S; Liem, K F

1997-01-01

The species assemblages of cichlids in the three largest African Great Lakes are among the richest concentrations of vertebrate species on earth. The faunas are broadly similar in terms of trophic diversity, species richness, rates of endemism, and taxonomic composition, yet they are historically independent of each other. Hence, they offer a true and unique evolutionary experiment to test hypotheses concerning the mutual dependencies of ecology and brain morphology. We examined the brains of 189 species of cichlids from the three large lakes: Victoria, Tanganyika, and Malawi. A first paper demonstrated that patterns of evolutionary change in cichlid brain morphology are similar across taxonomic boundaries as well as across the three lakes [van Staaden et al., 1995 ZACS 98: 165-178]. Here we report a close relationship between the relative sizes of various brain structures and variables related to the utilization of habitat and prey. Causality is difficult to assign in this context, nonetheless, prey size and agility, turbidity levels, depth, and substrate complexity are all highly predictive of variation in brain structure. Areas associated with primary sensory functions such as vision and taste relate significantly to differences in feeding habits. Turbidity and depth are closely associated with differences in eye size, and large eyes are associated with species that pick plankton from the water column. Piscivorous taxa and others that utilize motile prey are characterized by a well developed optic tectum and a large cerebellum compared to species that prey on molluscs or plants. Structures relating to taste are well developed in species feeding on benthos over muddy or sandy substrates. The data militated against the existence of compensatory changes in brain structure. Thus enhanced development of a particular function is generally not accompanied by a parallel reduction of structures related to other modalities. Although genetic and environmental influences during ontogeny of the brain cannot be isolated, this study provides a rich source of hypotheses concerning the way the nervous system functions under various environmental conditions and how it has responded to natural selection.

Relaxed genetic control of cortical organization in human brains compared with chimpanzees

PubMed Central

Gómez-Robles, Aida; Hopkins, William D.; Schapiro, Steven J.; Sherwood, Chet C.

2015-01-01

The study of hominin brain evolution has focused largely on the neocortical expansion and reorganization undergone by humans as inferred from the endocranial fossil record. Comparisons of modern human brains with those of chimpanzees provide an additional line of evidence to define key neural traits that have emerged in human evolution and that underlie our unique behavioral specializations. In an attempt to identify fundamental developmental differences, we have estimated the genetic bases of brain size and cortical organization in chimpanzees and humans by studying phenotypic similarities between individuals with known kinship relationships. We show that, although heritability for brain size and cortical organization is high in chimpanzees, cerebral cortical anatomy is substantially less genetically heritable than brain size in humans, indicating greater plasticity and increased environmental influence on neurodevelopment in our species. This relaxed genetic control on cortical organization is especially marked in association areas and likely is related to underlying microstructural changes in neural circuitry. A major result of increased plasticity is that the development of neural circuits that underlie behavior is shaped by the environmental, social, and cultural context more intensively in humans than in other primate species, thus providing an anatomical basis for behavioral and cognitive evolution. PMID:26627234

Mammalian brain development and our grandmothering life history.

PubMed

Hawkes, Kristen; Finlay, Barbara L

2018-05-02

Among mammals, including humans, adult brain size and the relative size of brain components depend precisely on the duration of a highly regular process of neural development. Much wider variation is seen in rates of body growth and the state of neural maturation at life history events like birth and weaning. Large brains result from slow maturation, which in humans is accompanied by weaning early with respect to both neural maturation and longevity. The grandmother hypothesis proposes this distinctive combination of life history features evolved as ancestral populations began to depend on foods that just weaned juveniles couldn't handle. Here we trace possible reciprocal connections between brain development and life history, highlighting the resulting extended neural plasticity in a wider cognitive ecology of allomaternal care that distinguishes human ontogeny with consequences for other peculiarities of our lineage. Copyright © 2018 Elsevier Inc. All rights reserved.

Microcephaly genes evolved adaptively throughout the evolution of eutherian mammals

PubMed Central

2014-01-01

Background Genes associated with the neurodevelopmental disorder microcephaly display a strong signature of adaptive evolution in primates. Comparative data suggest a link between selection on some of these loci and the evolution of primate brain size. Whether or not either positive selection or this phenotypic association are unique to primates is unclear, but recent studies in cetaceans suggest at least two microcephaly genes evolved adaptively in other large brained mammalian clades. Results Here we analyse the evolution of seven microcephaly loci, including three recently identified loci, across 33 eutherian mammals. We find extensive evidence for positive selection having acted on the majority of these loci not just in primates but also across non-primate mammals. Furthermore, the patterns of selection in major mammalian clades are not significantly different. Using phylogenetically corrected comparative analyses, we find that the evolution of two microcephaly loci, ASPM and CDK5RAP2, are correlated with neonatal brain size in Glires and Euungulata, the two most densely sampled non-primate clades. Conclusions Together with previous results, this suggests that ASPM and CDK5RAP2 may have had a consistent role in the evolution of brain size in mammals. Nevertheless, several limitations of currently available data and gene-phenotype tests are discussed, including sparse sampling across large evolutionary distances, averaging gene-wide rates of evolution, potential phenotypic variation and evolutionary reversals. We discuss the implications of our results for studies of the genetic basis of brain evolution, and explicit tests of gene-phenotype hypotheses. PMID:24898820

Characteristics and Treatments of Large Cystic Brain Metastasis: Radiosurgery and Stereotactic Aspiration

PubMed Central

Kim, Moinay; Cheok, Stephanie; Chung, Lawrance K.; Ung, Nolan; Thill, Kimberly; Voth, Brittany; Kwon, Do Hoon; Kim, Jeong Hoon; Kim, Chang Jin; Tenn, Stephen; Lee, Percy

2015-01-01

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. PMID:25977901

Development of neural basis for chinese orthographic neighborhood size effect.

PubMed

Zhao, Jing; Li, Qing-Lin; Ding, Guo-Sheng; Bi, Hong-Yan

2016-02-01

The brain activity of orthographic neighborhood size (N size) effect in Chinese character naming has been studied in adults, meanwhile behavioral studies have revealed a developmental trend of Chinese N-size effect in developing readers. However, it is unclear whether and how the neural mechanism of N-size effect changes in Chinese children along with development. Here we address this issue using functional magnetic resonance imaging. Forty-four students from the 3(rd) , 5(th) , and 7(th) grades were scanned during silent naming of Chinese characters. After scanning, all participants took part in an overt naming test outside the scanner, and results of the naming task showed that the 3(rd) graders named characters from large neighborhoods faster than those from small neighborhoods, revealing a facilitatory N-size effect; the 5(th) graders showed null N-size effect while the 7(th) graders showed an inhibitory N-size effect. Neuroimaging results revealed that only the 3(rd) graders exhibited a significant N-size effect in the left middle occipital activity, with greater activation for large N-size characters. Results of 5(th) and 7(th) graders showed significant N-size effects in the left middle frontal gyrus, in which 5(th) graders induced greater activation in large N-size condition than in small N-size condition, while 7(th) graders exhibited an opposite effect which was similar to the adult pattern reported in a previous study. The current findings suggested the transition from broadly tuned to finely tuned orthographic representation with reading development, and the inhibition from neighbors' phonology for higher graders. Hum Brain Mapp 37:632-647, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Similar Brain Activation during False Belief Tasks in a Large Sample of Adults with and without Autism

PubMed Central

Dufour, Nicholas; Redcay, Elizabeth; Young, Liane; Mavros, Penelope L.; Moran, Joseph M.; Triantafyllou, Christina; Gabrieli, John D. E.; Saxe, Rebecca

2013-01-01

Reading about another person’s beliefs engages ‘Theory of Mind’ processes and elicits highly reliable brain activation across individuals and experimental paradigms. Using functional magnetic resonance imaging, we examined activation during a story task designed to elicit Theory of Mind processing in a very large sample of neurotypical (N = 462) individuals, and a group of high-functioning individuals with autism spectrum disorders (N = 31), using both region-of-interest and whole-brain analyses. This large sample allowed us to investigate group differences in brain activation to Theory of Mind tasks with unusually high sensitivity. There were no differences between neurotypical participants and those diagnosed with autism spectrum disorder. These results imply that the social cognitive impairments typical of autism spectrum disorder can occur without measurable changes in the size, location or response magnitude of activity during explicit Theory of Mind tasks administered to adults. PMID:24073267

Similar brain activation during false belief tasks in a large sample of adults with and without autism.

PubMed

Dufour, Nicholas; Redcay, Elizabeth; Young, Liane; Mavros, Penelope L; Moran, Joseph M; Triantafyllou, Christina; Gabrieli, John D E; Saxe, Rebecca

2013-01-01

Reading about another person's beliefs engages 'Theory of Mind' processes and elicits highly reliable brain activation across individuals and experimental paradigms. Using functional magnetic resonance imaging, we examined activation during a story task designed to elicit Theory of Mind processing in a very large sample of neurotypical (N = 462) individuals, and a group of high-functioning individuals with autism spectrum disorders (N = 31), using both region-of-interest and whole-brain analyses. This large sample allowed us to investigate group differences in brain activation to Theory of Mind tasks with unusually high sensitivity. There were no differences between neurotypical participants and those diagnosed with autism spectrum disorder. These results imply that the social cognitive impairments typical of autism spectrum disorder can occur without measurable changes in the size, location or response magnitude of activity during explicit Theory of Mind tasks administered to adults.

Mammalian Collection on Noah's Ark: The Effects of Beauty, Brain and Body Size

PubMed Central

Frynta, Daniel; Šimková, Olga; Lišková, Silvie; Landová, Eva

2013-01-01

The importance of today's zoological gardens as the so-called “Noah's Ark” grows as the natural habitat of many species quickly diminishes. Their potential to shelter a large amount of individuals from many species gives us the opportunity to reintroduce a species that disappeared in nature. However, the selection of animals to be kept in zoos worldwide is highly selective and depends on human decisions driven by both ecological criteria such as population size or vulnerability and audience-driven criteria such as aesthetic preferences. Thus we focused our study on the most commonly kept and bred animal class, the mammals, and we asked which factors affect various aspects of the mammalian collection of zoos. We analyzed the presence/absence, population size, and frequency per species of each of the 123 mammalian families kept in the worldwide zoo collection. Our aim was to explain these data using the human-perceived attractiveness of mammalian families, their body weight, relative brain size and species richness of the family. In agreement with various previous studies, we found that the body size and the attractiveness of mammals significantly affect all studied components of the mammalian collection of zoos. There is a higher probability of the large and attractive families to be kept. Once kept, these animals are presented in larger numbers in more zoos. On the contrary, the relative mean brain size only affects the primary selection whether to keep the family or not. It does not affect the zoo population size or the number of zoos that keep the family. PMID:23690985

Mammalian collection on Noah's Ark: the effects of beauty, brain and body size.

PubMed

Frynta, Daniel; Šimková, Olga; Lišková, Silvie; Landová, Eva

2013-01-01

The importance of today's zoological gardens as the so-called "Noah's Ark" grows as the natural habitat of many species quickly diminishes. Their potential to shelter a large amount of individuals from many species gives us the opportunity to reintroduce a species that disappeared in nature. However, the selection of animals to be kept in zoos worldwide is highly selective and depends on human decisions driven by both ecological criteria such as population size or vulnerability and audience-driven criteria such as aesthetic preferences. Thus we focused our study on the most commonly kept and bred animal class, the mammals, and we asked which factors affect various aspects of the mammalian collection of zoos. We analyzed the presence/absence, population size, and frequency per species of each of the 123 mammalian families kept in the worldwide zoo collection. Our aim was to explain these data using the human-perceived attractiveness of mammalian families, their body weight, relative brain size and species richness of the family. In agreement with various previous studies, we found that the body size and the attractiveness of mammals significantly affect all studied components of the mammalian collection of zoos. There is a higher probability of the large and attractive families to be kept. Once kept, these animals are presented in larger numbers in more zoos. On the contrary, the relative mean brain size only affects the primary selection whether to keep the family or not. It does not affect the zoo population size or the number of zoos that keep the family.

Multivariate Meta-Analysis of Brain-Mass Correlations in Eutherian Mammals

PubMed Central

Steinhausen, Charlene; Zehl, Lyuba; Haas-Rioth, Michaela; Morcinek, Kerstin; Walkowiak, Wolfgang; Huggenberger, Stefan

2016-01-01

The general assumption that brain size differences are an adequate proxy for subtler differences in brain organization turned neurobiologists toward the question why some groups of mammals such as primates, elephants, and whales have such remarkably large brains. In this meta-analysis, an extensive sample of eutherian mammals (115 species distributed in 14 orders) provided data about several different biological traits and measures of brain size such as absolute brain mass (AB), relative brain mass (RB; quotient from AB and body mass), and encephalization quotient (EQ). These data were analyzed by established multivariate statistics without taking specific phylogenetic information into account. Species with high AB tend to (1) feed on protein-rich nutrition, (2) have a long lifespan, (3) delayed sexual maturity, and (4) long and rare pregnancies with small litter sizes. Animals with high RB usually have (1) a short life span, (2) reach sexual maturity early, and (3) have short and frequent gestations. Moreover, males of species with high RB also have few potential sexual partners. In contrast, animals with high EQs have (1) a high number of potential sexual partners, (2) delayed sexual maturity, and (3) rare gestations with small litter sizes. Based on these correlations, we conclude that Eutheria with either high AB or high EQ occupy positions at the top of the network of food chains (high trophic levels). Eutheria of low trophic levels can develop a high RB only if they have small body masses. PMID:27746724

Brain size regulations by cbp haploinsufficiency evaluated by in-vivo MRI based volumetry

NASA Astrophysics Data System (ADS)

Ateca-Cabarga, Juan C.; Cosa, Alejandro; Pallarés, Vicente; López-Atalaya, José P.; Barco, Ángel; Canals, Santiago; Moratal, David

2015-11-01

The Rubinstein-Taybi Syndrome (RSTS) is a congenital disease that affects brain development causing severe cognitive deficits. In most cases the disease is associated with dominant mutations in the gene encoding the CREB binding protein (CBP). In this work, we present the first quantitative analysis of brain abnormalities in a mouse model of RSTS using magnetic resonance imaging (MRI) and two novel self-developed automated algorithms for image volumetric analysis. Our results quantitatively confirm key syndromic features observed in RSTS patients, such as reductions in brain size (-16.31%, p < 0.05), white matter volume (-16.00%, p < 0.05), and corpus callosum (-12.40%, p < 0.05). Furthermore, they provide new insight into the developmental origin of the disease. By comparing brain tissues in a region by region basis between cbp+/- and cbp+/+ littermates, we found that cbp haploinsufficiency is specifically associated with significant reductions in prosencephalic tissue, such us in the olfactory bulb and neocortex, whereas regions evolved from the embryonic rhombencephalon were spared. Despite the large volume reductions, the proportion between gray-, white-matter and cerebrospinal fluid were conserved, suggesting a role of CBP in brain size regulation. The commonalities with holoprosencephaly and arhinencephaly conditions suggest the inclusion of RSTS in the family of neuronal migration disorders.

Endocranial Casts of Pre-Mammalian Therapsids Reveal an Unexpected Neurological Diversity at the Deep Evolutionary Root of Mammals.

PubMed

Benoit, Julien; Fernandez, Vincent; Manger, Paul R; Rubidge, Bruce S

2017-01-01

The origin and evolution of the mammalian brain has long been the focus of scientific enquiry. Conversely, little research has focused on the palaeoneurology of the stem group of Mammaliaformes, the Permian and Triassic non-mammaliaform Therapsida (NMT). This is because the majority of the NMT have a non-ossified braincase, making the study of their endocranial cast (sometimes called the "fossil brain") problematic. Thus, descriptions of the morphology and size of NMT endocranial casts have been based largely on approximations rather than reliable determination. Accordingly, here we use micro-CT scans of the skulls of 1 Dinocephalia and 3 Biarmosuchia, which are NMT with a fully ossified braincase and thus a complete endocast. For the first time, our work enables the accurate determination of endocranial shape and size in NMT. This study suggests that NMT brain size falls in the upper range of the reptilian and amphibian variation. Brain size in the dicynodont Kawingasaurus is equivalent to that of early Mammaliaformes, whereas the Dinocephalia show evidence of a secondary reduction of brain size. In addition, unlike other NMT in which the endocast has a tubular shape and its parts are arranged in a linear manner, the biarmosuchian endocast is strongly flexed at the level of the midbrain, creating a near right angle between the fore- and hindbrain. These data highlight an unexpected diversity of endocranial size and morphology in NMT, features that are usually considered conservative in this group. © 2017 S. Karger AG, Basel.

Superresolution Imaging of Aquaporin-4 Cluster Size in Antibody-Stained Paraffin Brain Sections

PubMed Central

Smith, Alex J.; Verkman, Alan S.

2015-01-01

The water channel aquaporin-4 (AQP4) forms supramolecular clusters whose size is determined by the ratio of M1- and M23-AQP4 isoforms. In cultured astrocytes, differences in the subcellular localization and macromolecular interactions of small and large AQP4 clusters results in distinct physiological roles for M1- and M23-AQP4. Here, we developed quantitative superresolution optical imaging methodology to measure AQP4 cluster size in antibody-stained paraffin sections of mouse cerebral cortex and spinal cord, human postmortem brain, and glioma biopsy specimens. This methodology was used to demonstrate that large AQP4 clusters are formed in AQP4−/− astrocytes transfected with only M23-AQP4, but not in those expressing only M1-AQP4, both in vitro and in vivo. Native AQP4 in mouse cortex, where both isoforms are expressed, was enriched in astrocyte foot-processes adjacent to microcapillaries; clusters in perivascular regions of the cortex were larger than in parenchymal regions, demonstrating size-dependent subcellular segregation of AQP4 clusters. Two-color superresolution imaging demonstrated colocalization of Kir4.1 with AQP4 clusters in perivascular areas but not in parenchyma. Surprisingly, the subcellular distribution of AQP4 clusters was different between gray and white matter astrocytes in spinal cord, demonstrating regional specificity in cluster polarization. Changes in AQP4 subcellular distribution are associated with several neurological diseases and we demonstrate that AQP4 clustering was preserved in a postmortem human cortical brain tissue specimen, but that AQP4 was not substantially clustered in a human glioblastoma specimen despite high-level expression. Our results demonstrate the utility of superresolution optical imaging for measuring the size of AQP4 supramolecular clusters in paraffin sections of brain tissue and support AQP4 cluster size as a primary determinant of its subcellular distribution. PMID:26682810

Transcallosal transfer of information and functional asymmetry of the human brain.

PubMed

Nowicka, Anna; Tacikowski, Pawel

2011-01-01

The corpus callosum is the largest commissure in the brain and acts as a "bridge" of nerve fibres connecting the two cerebral hemispheres. It plays a crucial role in interhemispheric integration and is responsible for normal communication and cooperation between the two hemispheres. Evolutionary pressures guiding brain size are accompanied by reduced interhemispheric and enhanced intrahemispheric connectivity. Some lines of evidence suggest that the speed of transcallosal conduction is limited in large brains (e.g., in humans), thus favouring intrahemispheric processing and brain lateralisation. Patterns of directional symmetry/asymmetry of transcallosal transfer time may be related to the degree of brain lateralisation. Neural network modelling and electrophysiological studies on interhemispheric transmission provide data supporting this supposition.

Brain size and limits to adult neurogenesis.

PubMed

Paredes, Mercedes F; Sorrells, Shawn F; Garcia-Verdugo, Jose M; Alvarez-Buylla, Arturo

2016-02-15

The walls of the cerebral ventricles in the developing embryo harbor the primary neural stem cells from which most neurons and glia derive. In many vertebrates, neurogenesis continues postnatally and into adulthood in this region. Adult neurogenesis at the ventricle has been most extensively studied in organisms with small brains, such as reptiles, birds, and rodents. In reptiles and birds, these progenitor cells give rise to young neurons that migrate into many regions of the forebrain. Neurogenesis in adult rodents is also relatively widespread along the lateral ventricles, but migration is largely restricted to the rostral migratory stream into the olfactory bulb. Recent work indicates that the wall of the lateral ventricle is highly regionalized, with progenitor cells giving rise to different types of neurons depending on their location. In species with larger brains, young neurons born in these spatially specified domains become dramatically separated from potential final destinations. Here we hypothesize that the increase in size and topographical complexity (e.g., intervening white matter tracts) in larger brains may severely limit the long-term contribution of new neurons born close to, or in, the ventricular wall. We compare the process of adult neuronal birth, migration, and integration across species with different brain sizes, and discuss how early regional specification of progenitor cells may interact with brain size and affect where and when new neurons are added. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

Combining the boundary shift integral and tensor-based morphometry for brain atrophy estimation

NASA Astrophysics Data System (ADS)

Michalkiewicz, Mateusz; Pai, Akshay; Leung, Kelvin K.; Sommer, Stefan; Darkner, Sune; Sørensen, Lauge; Sporring, Jon; Nielsen, Mads

2016-03-01

Brain atrophy from structural magnetic resonance images (MRIs) is widely used as an imaging surrogate marker for Alzheimers disease. Their utility has been limited due to the large degree of variance and subsequently high sample size estimates. The only consistent and reasonably powerful atrophy estimation methods has been the boundary shift integral (BSI). In this paper, we first propose a tensor-based morphometry (TBM) method to measure voxel-wise atrophy that we combine with BSI. The combined model decreases the sample size estimates significantly when compared to BSI and TBM alone.

The evolution of modern human brain shape

PubMed Central

Neubauer, Simon; Hublin, Jean-Jacques; Gunz, Philipp

2018-01-01

Modern humans have large and globular brains that distinguish them from their extinct Homo relatives. The characteristic globularity develops during a prenatal and early postnatal period of rapid brain growth critical for neural wiring and cognitive development. However, it remains unknown when and how brain globularity evolved and how it relates to evolutionary brain size increase. On the basis of computed tomographic scans and geometric morphometric analyses, we analyzed endocranial casts of Homo sapiens fossils (N = 20) from different time periods. Our data show that, 300,000 years ago, brain size in early H. sapiens already fell within the range of present-day humans. Brain shape, however, evolved gradually within the H. sapiens lineage, reaching present-day human variation between about 100,000 and 35,000 years ago. This process started only after other key features of craniofacial morphology appeared modern and paralleled the emergence of behavioral modernity as seen from the archeological record. Our findings are consistent with important genetic changes affecting early brain development within the H. sapiens lineage since the origin of the species and before the transition to the Later Stone Age and the Upper Paleolithic that mark full behavioral modernity. PMID:29376123

The evolution of modern human brain shape.

PubMed

Neubauer, Simon; Hublin, Jean-Jacques; Gunz, Philipp

2018-01-01

Modern humans have large and globular brains that distinguish them from their extinct Homo relatives. The characteristic globularity develops during a prenatal and early postnatal period of rapid brain growth critical for neural wiring and cognitive development. However, it remains unknown when and how brain globularity evolved and how it relates to evolutionary brain size increase. On the basis of computed tomographic scans and geometric morphometric analyses, we analyzed endocranial casts of Homo sapiens fossils ( N = 20) from different time periods. Our data show that, 300,000 years ago, brain size in early H. sapiens already fell within the range of present-day humans. Brain shape, however, evolved gradually within the H. sapiens lineage, reaching present-day human variation between about 100,000 and 35,000 years ago. This process started only after other key features of craniofacial morphology appeared modern and paralleled the emergence of behavioral modernity as seen from the archeological record. Our findings are consistent with important genetic changes affecting early brain development within the H. sapiens lineage since the origin of the species and before the transition to the Later Stone Age and the Upper Paleolithic that mark full behavioral modernity.

Gold nanoparticle imaging and radiotherapy of brain tumors in mice

PubMed Central

Hainfeld, James F; Smilowitz, Henry M; O'Connor, Michael J; Dilmanian, Farrokh Avraham; Slatkin, Daniel N

2013-01-01

Aim To test intravenously injected gold nanoparticles for x-ray imaging and radiotherapy enhancement of large, imminently lethal, intracerebral malignant gliomas. Materials & methods Gold nanoparticles approximately 11 nm in size were injected intravenously and brains imaged using microcomputed tomography. A total of 15 h after an intravenous dose of 4 g Au/kg was administered, brains were irradiated with 30 Gy 100 kVp x-rays. Results Gold uptake gave a 19:1 tumor-to-normal brain ratio with 1.5% w/w gold in tumor, calculated to increase local radiation dose by approximately 300%. Mice receiving gold and radiation (30 Gy) demonstrated 50% long term (>1 year) tumor-free survival, whereas all mice receiving radiation only died. Conclusion Intravenously injected gold nanoparticles cross the blood–tumor barrier, but are largely blocked by the normal blood–brain barrier, enabling high-resolution computed tomography tumor imaging. Gold radiation enhancement significantly improved long-term survival compared with radiotherapy alone. This approach holds promise to improve therapy of human brain tumors and other cancers. PMID:23265347

Stereotactic radiosurgery for small brain metastases and implications regarding management with systemic therapy alone.

PubMed

Trifiletti, Daniel M; Hill, Colin; Cohen-Inbar, Or; Xu, Zhiyuan; Sheehan, Jason P

2017-09-01

While stereotactic radiosurgery (SRS) has been shown effective in the management of brain metastases, small brain metastases (≤10 mm) can pose unique challenges. Our aim was to investigate the efficacy of SRS in the treatment of small brain metastases, as well as elucidate clinically relevant factors impacting local failure (LF). We utilized a large, single-institution cohort to perform a retrospective analysis of patients with brain metastases up to 1 cm in maximal dimension. Clinical and radiosurgical parameters were investigated for an association with LF and compared using a competing risk model to calculate cumulative incidence functions, with death and whole brain radiotherapy serving as competing risks. 1596 small brain metastases treated with SRS among 424 patients were included. Among these tumors, 33 developed LF during the follow-up period (2.4% at 12 months following SRS). Competing risk analysis demonstrated that LF was dependent on tumor size (0.7% if ≤2 mm and 3.0% if 2-10 mm at 12 months, p = 0.016). Other factors associated with increasing risk of LF were the decreasing margin dose, increasing maximal tumor diameter, volume, and radioresistant tumors (each p < 0.01). 22 tumors (0.78%) developed radiographic radiation necrosis following SRS, and this incidence did not differ by tumor size (≤2 mm and 2-10 mm, p = 0.200). This large analysis confirms that SRS remains an effective modality in treatment of small brain metastases. In light of the excellent local control and relatively low risk of toxicity, patients with small brain metastases who otherwise have a reasonable expected survival should be considered for radiosurgical management.

A new Homo erectus (Zhoukoudian V) brain endocast from China.

PubMed

Wu, Xiujie; Schepartz, Lynne A; Liu, Wu

2010-01-22

A new Homo erectus endocast, Zhoukoudian (ZKD) V, is assessed by comparing it with ZKD II, ZKD III, ZKD X, ZKD XI, ZKD XII, Hexian, Trinil II, Sambungmacan (Sm) 3, Sangiran 2, Sangiran 17, KNM-ER 3733, KNM-WT 15 000, Kabwe, Liujiang and 31 modern Chinese. The endocast of ZKD V has an estimated endocranial volume of 1140 ml. As the geological age of ZKD V is younger than the other ZKD H. erectus, evolutionary changes in brain morphology are evaluated. The brain size of the ZKD specimens increases slightly over time. Compared with the other ZKD endocasts, ZKD V shows important differences, including broader frontal and occipital lobes, some indication of fuller parietal lobes, and relatively large brain size that reflect significant trends documented in later hominin brain evolution. Bivariate and principal component analyses indicate that geographical variation does not characterize the ZKD, African and other Asian specimens. The ZKD endocasts share some common morphological and morphometric features with other H. erectus endocasts that distinguish them from Homo sapiens.

Brain enlargement is associated with regression in preschool-age boys with autism spectrum disorders

PubMed Central

Nordahl, Christine Wu; Lange, Nicholas; Li, Deana D.; Barnett, Lou Ann; Lee, Aaron; Buonocore, Michael H.; Simon, Tony J.; Rogers, Sally; Ozonoff, Sally; Amaral, David G.

2011-01-01

Autism is a heterogeneous disorder with multiple behavioral and biological phenotypes. Accelerated brain growth during early childhood is a well-established biological feature of autism. Onset pattern, i.e., early onset or regressive, is an intensely studied behavioral phenotype of autism. There is currently little known, however, about whether, or how, onset status maps onto the abnormal brain growth. We examined the relationship between total brain volume and onset status in a large sample of 2- to 4-y-old boys and girls with autism spectrum disorder (ASD) [n = 53, no regression (nREG); n = 61, regression (REG)] and a comparison group of age-matched typically developing controls (n = 66). We also examined retrospective head circumference measurements from birth through 18 mo of age. We found that abnormal brain enlargement was most commonly found in boys with regressive autism. Brain size in boys without regression did not differ from controls. Retrospective head circumference measurements indicate that head circumference in boys with regressive autism is normal at birth but diverges from the other groups around 4–6 mo of age. There were no differences in brain size in girls with autism (n = 22, ASD; n = 24, controls). These results suggest that there may be distinct neural phenotypes associated with different onsets of autism. For boys with regressive autism, divergence in brain size occurs well before loss of skills is commonly reported. Thus, rapid head growth may be a risk factor for regressive autism. PMID:22123952

Defining Face Perception Areas in the Human Brain: A Large-Scale Factorial fMRI Face Localizer Analysis

ERIC Educational Resources Information Center

Rossion, Bruno; Hanseeuw, Bernard; Dricot, Laurence

2012-01-01

A number of human brain areas showing a larger response to faces than to objects from different categories, or to scrambled faces, have been identified in neuroimaging studies. Depending on the statistical criteria used, the set of areas can be overextended or minimized, both at the local (size of areas) and global (number of areas) levels. Here…

The Expensive-Tissue Hypothesis in Vertebrates: Gut Microbiota Effect, a Review.

PubMed

Huang, Chun Hua; Yu, Xin; Liao, Wen Bo

2018-06-17

The gut microbiota is integral to an organism’s digestive structure and has been shown to play an important role in producing substrates for gluconeogenesis and energy production, vasodilator, and gut motility. Numerous studies have demonstrated that variation in diet types is associated with the abundance and diversity of the gut microbiota, a relationship that plays a significant role in nutrient absorption and affects gut size. The Expensive-Tissue Hypothesis states (ETH) that the metabolic requirement of relatively large brains is offset by a corresponding reduction of the other tissues, such as gut size. However, how the trade-off between gut size and brain size in vertebrates is associated with the gut microbiota through metabolic requirements still remains unexplored. Here, we review research relating to and discuss the potential influence of gut microbiota on the ETH.

Ravens, New Caledonian crows and jackdaws parallel great apes in motor self-regulation despite smaller brains.

PubMed

Kabadayi, Can; Taylor, Lucy A; von Bayern, Auguste M P; Osvath, Mathias

2016-04-01

Overriding motor impulses instigated by salient perceptual stimuli represent a fundamental inhibitory skill. Such motor self-regulation facilitates more rational behaviour, as it brings economy into the bodily interaction with the physical and social world. It also underlies certain complex cognitive processes including decision making. Recently, MacLean et al. (MacLean et al. 2014 Proc. Natl Acad. Sci. USA 111, 2140-2148. (doi:10.1073/pnas.1323533111)) conducted a large-scale study involving 36 species, comparing motor self-regulation across taxa. They concluded that absolute brain size predicts level of performance. The great apes were most successful. Only a few of the species tested were birds. Given birds' small brain size-in absolute terms-yet flexible behaviour, their motor self-regulation calls for closer study. Corvids exhibit some of the largest relative avian brain sizes-although small in absolute measure-as well as the most flexible cognition in the animal kingdom. We therefore tested ravens, New Caledonian crows and jackdaws in the so-called cylinder task. We found performance indistinguishable from that of great apes despite the much smaller brains. We found both absolute and relative brain volume to be a reliable predictor of performance within Aves. The complex cognition of corvids is often likened to that of great apes; our results show further that they share similar fundamental cognitive mechanisms.

Sample Size Estimation for Alzheimer's Disease Trials from Japanese ADNI Serial Magnetic Resonance Imaging.

PubMed

Fujishima, Motonobu; Kawaguchi, Atsushi; Maikusa, Norihide; Kuwano, Ryozo; Iwatsubo, Takeshi; Matsuda, Hiroshi

2017-01-01

Little is known about the sample sizes required for clinical trials of Alzheimer's disease (AD)-modifying treatments using atrophy measures from serial brain magnetic resonance imaging (MRI) in the Japanese population. The primary objective of the present study was to estimate how large a sample size would be needed for future clinical trials for AD-modifying treatments in Japan using atrophy measures of the brain as a surrogate biomarker. Sample sizes were estimated from the rates of change of the whole brain and hippocampus by the k-means normalized boundary shift integral (KN-BSI) and cognitive measures using the data of 537 Japanese Alzheimer's Neuroimaging Initiative (J-ADNI) participants with a linear mixed-effects model. We also examined the potential use of ApoE status as a trial enrichment strategy. The hippocampal atrophy rate required smaller sample sizes than cognitive measures of AD and mild cognitive impairment (MCI). Inclusion of ApoE status reduced sample sizes for AD and MCI patients in the atrophy measures. These results show the potential use of longitudinal hippocampal atrophy measurement using automated image analysis as a progression biomarker and ApoE status as a trial enrichment strategy in a clinical trial of AD-modifying treatment in Japanese people.

Brain activity during a lower limb functional task in a real and virtual environment: A comparative study.

PubMed

Pacheco, Thaiana Barbosa Ferreira; Oliveira Rego, Isabelle Ananda; Campos, Tania Fernandes; Cavalcanti, Fabrícia Azevedo da Costa

2017-01-01

Virtual Reality (VR) has been contributing to Neurological Rehabilitation because of its interactive and multisensory nature, providing the potential of brain reorganization. Given the use of mobile EEG devices, there is the possibility of investigating how the virtual therapeutic environment can influence brain activity. To compare theta, alpha, beta and gamma power in healthy young adults during a lower limb motor task in a virtual and real environment. Ten healthy adults were submitted to an EEG assessment while performing a one-minute task consisted of going up and down a step in a virtual environment - Nintendo Wii virtual game "Basic step" - and in a real environment. Real environment caused an increase in theta and alpha power, with small to large size effects mainly in the frontal region. VR caused a greater increase in beta and gamma power, however, with small or negligible effects on a variety of regions regarding beta frequency, and medium to very large effects on the frontal and the occipital regions considering gamma frequency. Theta, alpha, beta and gamma activity during the execution of a motor task differs according to the environment that the individual is exposed - real or virtual - and may have varying size effects if brain area activation and frequency spectrum in each environment are taken into consideration.

The impact of sample size on the reproducibility of voxel-based lesion-deficit mappings.

PubMed

Lorca-Puls, Diego L; Gajardo-Vidal, Andrea; White, Jitrachote; Seghier, Mohamed L; Leff, Alexander P; Green, David W; Crinion, Jenny T; Ludersdorfer, Philipp; Hope, Thomas M H; Bowman, Howard; Price, Cathy J

2018-07-01

This study investigated how sample size affects the reproducibility of findings from univariate voxel-based lesion-deficit analyses (e.g., voxel-based lesion-symptom mapping and voxel-based morphometry). Our effect of interest was the strength of the mapping between brain damage and speech articulation difficulties, as measured in terms of the proportion of variance explained. First, we identified a region of interest by searching on a voxel-by-voxel basis for brain areas where greater lesion load was associated with poorer speech articulation using a large sample of 360 right-handed English-speaking stroke survivors. We then randomly drew thousands of bootstrap samples from this data set that included either 30, 60, 90, 120, 180, or 360 patients. For each resample, we recorded effect size estimates and p values after conducting exactly the same lesion-deficit analysis within the previously identified region of interest and holding all procedures constant. The results show (1) how often small effect sizes in a heterogeneous population fail to be detected; (2) how effect size and its statistical significance varies with sample size; (3) how low-powered studies (due to small sample sizes) can greatly over-estimate as well as under-estimate effect sizes; and (4) how large sample sizes (N ≥ 90) can yield highly significant p values even when effect sizes are so small that they become trivial in practical terms. The implications of these findings for interpreting the results from univariate voxel-based lesion-deficit analyses are discussed. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Joint genetic analysis of hippocampal size in mouse and human identifies a novel gene linked to neurodegenerative disease.

PubMed

Ashbrook, David G; Williams, Robert W; Lu, Lu; Stein, Jason L; Hibar, Derrek P; Nichols, Thomas E; Medland, Sarah E; Thompson, Paul M; Hager, Reinmar

2014-10-03

Variation in hippocampal volume has been linked to significant differences in memory, behavior, and cognition among individuals. To identify genetic variants underlying such differences and associated disease phenotypes, multinational consortia such as ENIGMA have used large magnetic resonance imaging (MRI) data sets in human GWAS studies. In addition, mapping studies in mouse model systems have identified genetic variants for brain structure variation with great power. A key challenge is to understand how genetically based differences in brain structure lead to the propensity to develop specific neurological disorders. We combine the largest human GWAS of brain structure with the largest mammalian model system, the BXD recombinant inbred mouse population, to identify novel genetic targets influencing brain structure variation that are linked to increased risk for neurological disorders. We first use a novel cross-species, comparative analysis using mouse and human genetic data to identify a candidate gene, MGST3, associated with adult hippocampus size in both systems. We then establish the coregulation and function of this gene in a comprehensive systems-analysis. We find that MGST3 is associated with hippocampus size and is linked to a group of neurodegenerative disorders, such as Alzheimer's.

Surface shape analysis with an application to brain surface asymmetry in schizophrenia.

PubMed

Brignell, Christopher J; Dryden, Ian L; Gattone, S Antonio; Park, Bert; Leask, Stuart; Browne, William J; Flynn, Sean

2010-10-01

Some methods for the statistical analysis of surface shapes and asymmetry are introduced. We focus on a case study where magnetic resonance images of the brain are available from groups of 30 schizophrenia patients and 38 controls, and we investigate large-scale brain surface shape differences. Key aspects of shape analysis are to remove nuisance transformations by registration and to identify which parts of one object correspond with the parts of another object. We introduce maximum likelihood and Bayesian methods for registering brain images and providing large-scale correspondences of the brain surfaces. Brain surface size-and-shape analysis is considered using random field theory, and also dimension reduction is carried out using principal and independent components analysis. Some small but significant differences are observed between the the patient and control groups. We then investigate a particular type of asymmetry called torque. Differences in asymmetry are observed between the control and patient groups, which add strength to other observations in the literature. Further investigations of the midline plane location in the 2 groups and the fitting of nonplanar curved midlines are also considered.

The evolution of self-control

PubMed Central

MacLean, Evan L.; Hare, Brian; Nunn, Charles L.; Addessi, Elsa; Amici, Federica; Anderson, Rindy C.; Aureli, Filippo; Baker, Joseph M.; Bania, Amanda E.; Barnard, Allison M.; Boogert, Neeltje J.; Brannon, Elizabeth M.; Bray, Emily E.; Bray, Joel; Brent, Lauren J. N.; Burkart, Judith M.; Call, Josep; Cantlon, Jessica F.; Cheke, Lucy G.; Clayton, Nicola S.; Delgado, Mikel M.; DiVincenti, Louis J.; Fujita, Kazuo; Herrmann, Esther; Hiramatsu, Chihiro; Jacobs, Lucia F.; Jordan, Kerry E.; Laude, Jennifer R.; Leimgruber, Kristin L.; Messer, Emily J. E.; de A. Moura, Antonio C.; Ostojić, Ljerka; Picard, Alejandra; Platt, Michael L.; Plotnik, Joshua M.; Range, Friederike; Reader, Simon M.; Reddy, Rachna B.; Sandel, Aaron A.; Santos, Laurie R.; Schumann, Katrin; Seed, Amanda M.; Sewall, Kendra B.; Shaw, Rachael C.; Slocombe, Katie E.; Su, Yanjie; Takimoto, Ayaka; Tan, Jingzhi; Tao, Ruoting; van Schaik, Carel P.; Virányi, Zsófia; Visalberghi, Elisabetta; Wade, Jordan C.; Watanabe, Arii; Widness, Jane; Young, Julie K.; Zentall, Thomas R.; Zhao, Yini

2014-01-01

Cognition presents evolutionary research with one of its greatest challenges. Cognitive evolution has been explained at the proximate level by shifts in absolute and relative brain volume and at the ultimate level by differences in social and dietary complexity. However, no study has integrated the experimental and phylogenetic approach at the scale required to rigorously test these explanations. Instead, previous research has largely relied on various measures of brain size as proxies for cognitive abilities. We experimentally evaluated these major evolutionary explanations by quantitatively comparing the cognitive performance of 567 individuals representing 36 species on two problem-solving tasks measuring self-control. Phylogenetic analysis revealed that absolute brain volume best predicted performance across species and accounted for considerably more variance than brain volume controlling for body mass. This result corroborates recent advances in evolutionary neurobiology and illustrates the cognitive consequences of cortical reorganization through increases in brain volume. Within primates, dietary breadth but not social group size was a strong predictor of species differences in self-control. Our results implicate robust evolutionary relationships between dietary breadth, absolute brain volume, and self-control. These findings provide a significant first step toward quantifying the primate cognitive phenome and explaining the process of cognitive evolution. PMID:24753565

Linking brains and brawn: exercise and the evolution of human neurobiology.

PubMed

Raichlen, David A; Polk, John D

2013-01-07

The hunting and gathering lifestyle adopted by human ancestors around 2 Ma required a large increase in aerobic activity. High levels of physical activity altered the shape of the human body, enabling access to new food resources (e.g. animal protein) in a changing environment. Recent experimental work provides strong evidence that both acute bouts of exercise and long-term exercise training increase the size of brain components and improve cognitive performance in humans and other taxa. However, to date, researchers have not explored the possibility that the increases in aerobic capacity and physical activity that occurred during human evolution directly influenced the human brain. Here, we hypothesize that proximate mechanisms linking physical activity and neurobiology in living species may help to explain changes in brain size and cognitive function during human evolution. We review evidence that selection acting on endurance increased baseline neurotrophin and growth factor signalling (compounds responsible for both brain growth and for metabolic regulation during exercise) in some mammals, which in turn led to increased overall brain growth and development. This hypothesis suggests that a significant portion of human neurobiology evolved due to selection acting on features unrelated to cognitive performance.

Brain shape convergence in the adaptive radiation of New World monkeys

PubMed Central

Aristide, Leandro; dos Reis, Sergio Furtado; Machado, Alessandra C.; Lima, Inaya; Lopes, Ricardo T.; Perez, S. Ivan

2016-01-01

Primates constitute one of the most diverse mammalian clades, and a notable feature of their diversification is the evolution of brain morphology. However, the evolutionary processes and ecological factors behind these changes are largely unknown. In this work, we investigate brain shape diversification of New World monkeys during their adaptive radiation in relation to different ecological dimensions. Our results reveal that brain diversification in this clade can be explained by invoking a model of adaptive peak shifts to unique and shared optima, defined by a multidimensional ecological niche hypothesis. Particularly, we show that the evolution of convergent brain phenotypes may be related to ecological factors associated with group size (e.g., social complexity). Together, our results highlight the complexity of brain evolution and the ecological significance of brain shape changes during the evolutionary diversification of a primate clade. PMID:26858427

Planum Temporale Asymmetries Correlate with Corpus Callosum Axon Fiber Density in Chimpanzees (Pan troglodytes)

PubMed Central

Hopkins, William D.; Pilger, John F.; Storz, Rachel; Ambrose, Alex; Hof, Patrick R.; Sherwood, Chet C.

2012-01-01

The corpus callosum (CC) is the major white matter tract that connects the two cerebral hemispheres. Some have theorized that individual differences in behavioral and brain asymmetries are linked to variation in the density of axon fibers that traverse different sections of the CC. In this study, we examined whether variation in axon fiber density in the CC was associated with variation in asymmetries in the planum temporale (PT) in a sample of 20 post-mortem chimpanzee brains. We further tested for sex differences in small and large CC fiber proportions and density in the chimpanzees. We found that the distribution of small and large fibers within the CC of chimpanzees follows a similar pattern to those reported in humans. We also found that chimpanzees with larger asymmetries in the PT had fewer large fibers in the posterior portion of the CC, particularly among females. As has been reported in human brains, the findings reported here indicate that individual differences in brain asymmetries are associated with variation in interhemispheric connectivity as manifest in axon fiber density and size. PMID:22766214

DBMap: a TreeMap-based framework for data navigation and visualization of brain research registry

NASA Astrophysics Data System (ADS)

Zhang, Ming; Zhang, Hong; Tjandra, Donny; Wong, Stephen T. C.

2003-05-01

The purpose of this study is to investigate and apply a new, intuitive and space-conscious visualization framework to facilitate efficient data presentation and exploration of large-scale data warehouses. We have implemented the DBMap framework for the UCSF Brain Research Registry. Such a novel utility would facilitate medical specialists and clinical researchers in better exploring and evaluating a number of attributes organized in the brain research registry. The current UCSF Brain Research Registry consists of a federation of disease-oriented database modules, including Epilepsy, Brain Tumor, Intracerebral Hemorrphage, and CJD (Creuzfeld-Jacob disease). These database modules organize large volumes of imaging and non-imaging data to support Web-based clinical research. While the data warehouse supports general information retrieval and analysis, there lacks an effective way to visualize and present the voluminous and complex data stored. This study investigates whether the TreeMap algorithm can be adapted to display and navigate categorical biomedical data warehouse or registry. TreeMap is a space constrained graphical representation of large hierarchical data sets, mapped to a matrix of rectangles, whose size and color represent interested database fields. It allows the display of a large amount of numerical and categorical information in limited real estate of computer screen with an intuitive user interface. The paper will describe, DBMap, the proposed new data visualization framework for large biomedical databases. Built upon XML, Java and JDBC technologies, the prototype system includes a set of software modules that reside in the application server tier and provide interface to backend database tier and front-end Web tier of the brain registry.

Neoadjuvant chemotherapy for atypical teratoid rhabdoid tumors: case report.

PubMed

Thatikunta, Meena; Mutchnick, Ian; Elster, Jennifer; Thompson, Matthew P; Huang, Michael A; Spalding, Aaron C; Moriarty, Thomas

2017-05-01

Atypical teratoid rhabdoid tumors (ATRTs) are a rare pediatric brain tumor with high mortality rate. Several large series have reported achieving gross-total resection (GTR) in less than 50% of patients due to the lesions' large size, vascularity, and limited blood volume in young patients. While neoadjuvant chemotherapy for choroid plexus carcinomas in pediatric patients has become widely accepted, it has not been used as widely for other pediatric brain tumors. To the best of the authors' knowledge, there are only 3 published cases of neoadjuvant chemotherapy for ATRTs. In the present report, the authors present a fourth case of neoadjuvant chemotherapy for ATRT and review the available literature on this strategy. A 17-month-old child presented with a left ventricular ATRT for which imaging raised concern for a highly vascularized tumor. The authors undertook neoadjuvant chemotherapy with 2 cycles of Head Start II therapy, which reduced the size of the ventricular tumor by 35% and decreased the vascularity of the lesion on imaging. The estimated blood loss during resection was 425 ml and GTR was achieved. The patient continued with postoperative chemotherapy but suffered an on-therapy recurrence. While higher-quality data are necessary, available evidence suggests that neoadjuvant chemotherapy can reduce the size and vascularity of ATRTs and facilitate a surgical avenue for large or "inoperable" tumors.

Diversity in olfactory bulb size in birds reflects allometry, ecology, and phylogeny

PubMed Central

Corfield, Jeremy R.; Price, Kasandra; Iwaniuk, Andrew N.; Gutierrez-Ibañez, Cristian; Birkhead, Tim; Wylie, Douglas R.

2015-01-01

The relative size of olfactory bulbs (OBs) is correlated with olfactory capabilities across vertebrates and is widely used to assess the relative importance of olfaction to a species’ ecology. In birds, variations in the relative size of OBs are correlated with some behaviors; however, the factors that have led to the high level of diversity seen in OB sizes across birds are still not well understood. In this study, we use the relative size of OBs as a neuroanatomical proxy for olfactory capabilities in 135 species of birds, representing 21 orders. We examine the scaling of OBs with brain size across avian orders, determine likely ancestral states and test for correlations between OB sizes and habitat, ecology, and behavior. The size of avian OBs varied with the size of the brain and this allometric relationship was for the most part isometric, although species did deviate from this trend. Large OBs were characteristic of more basal species and in more recently derived species the OBs were small. Living and foraging in a semi-aquatic environment was the strongest variable driving the evolution of large OBs in birds; olfaction may provide cues for navigation and foraging in this otherwise featureless environment. Some of the diversity in OB sizes was also undoubtedly due to differences in migratory behavior, foraging strategies and social structure. In summary, relative OB size in birds reflect allometry, phylogeny and behavior in ways that parallel that of other vertebrate classes. This provides comparative evidence that supports recent experimental studies into avian olfaction and suggests that olfaction is an important sensory modality for all avian species. PMID:26283931

Robust Machine Learning-Based Correction on Automatic Segmentation of the Cerebellum and Brainstem.

PubMed

Wang, Jun Yi; Ngo, Michael M; Hessl, David; Hagerman, Randi J; Rivera, Susan M

2016-01-01

Automated segmentation is a useful method for studying large brain structures such as the cerebellum and brainstem. However, automated segmentation may lead to inaccuracy and/or undesirable boundary. The goal of the present study was to investigate whether SegAdapter, a machine learning-based method, is useful for automatically correcting large segmentation errors and disagreement in anatomical definition. We further assessed the robustness of the method in handling size of training set, differences in head coil usage, and amount of brain atrophy. High resolution T1-weighted images were acquired from 30 healthy controls scanned with either an 8-channel or 32-channel head coil. Ten patients, who suffered from brain atrophy because of fragile X-associated tremor/ataxia syndrome, were scanned using the 32-channel head coil. The initial segmentations of the cerebellum and brainstem were generated automatically using Freesurfer. Subsequently, Freesurfer's segmentations were both manually corrected to serve as the gold standard and automatically corrected by SegAdapter. Using only 5 scans in the training set, spatial overlap with manual segmentation in Dice coefficient improved significantly from 0.956 (for Freesurfer segmentation) to 0.978 (for SegAdapter-corrected segmentation) for the cerebellum and from 0.821 to 0.954 for the brainstem. Reducing the training set size to 2 scans only decreased the Dice coefficient ≤0.002 for the cerebellum and ≤ 0.005 for the brainstem compared to the use of training set size of 5 scans in corrective learning. The method was also robust in handling differences between the training set and the test set in head coil usage and the amount of brain atrophy, which reduced spatial overlap only by <0.01. These results suggest that the combination of automated segmentation and corrective learning provides a valuable method for accurate and efficient segmentation of the cerebellum and brainstem, particularly in large-scale neuroimaging studies, and potentially for segmenting other neural regions as well.

Robust Machine Learning-Based Correction on Automatic Segmentation of the Cerebellum and Brainstem

PubMed Central

Wang, Jun Yi; Ngo, Michael M.; Hessl, David; Hagerman, Randi J.; Rivera, Susan M.

2016-01-01

Automated segmentation is a useful method for studying large brain structures such as the cerebellum and brainstem. However, automated segmentation may lead to inaccuracy and/or undesirable boundary. The goal of the present study was to investigate whether SegAdapter, a machine learning-based method, is useful for automatically correcting large segmentation errors and disagreement in anatomical definition. We further assessed the robustness of the method in handling size of training set, differences in head coil usage, and amount of brain atrophy. High resolution T1-weighted images were acquired from 30 healthy controls scanned with either an 8-channel or 32-channel head coil. Ten patients, who suffered from brain atrophy because of fragile X-associated tremor/ataxia syndrome, were scanned using the 32-channel head coil. The initial segmentations of the cerebellum and brainstem were generated automatically using Freesurfer. Subsequently, Freesurfer’s segmentations were both manually corrected to serve as the gold standard and automatically corrected by SegAdapter. Using only 5 scans in the training set, spatial overlap with manual segmentation in Dice coefficient improved significantly from 0.956 (for Freesurfer segmentation) to 0.978 (for SegAdapter-corrected segmentation) for the cerebellum and from 0.821 to 0.954 for the brainstem. Reducing the training set size to 2 scans only decreased the Dice coefficient ≤0.002 for the cerebellum and ≤ 0.005 for the brainstem compared to the use of training set size of 5 scans in corrective learning. The method was also robust in handling differences between the training set and the test set in head coil usage and the amount of brain atrophy, which reduced spatial overlap only by <0.01. These results suggest that the combination of automated segmentation and corrective learning provides a valuable method for accurate and efficient segmentation of the cerebellum and brainstem, particularly in large-scale neuroimaging studies, and potentially for segmenting other neural regions as well. PMID:27213683

Dietary quality and encephalization in platyrrhine primates.

PubMed

Allen, Kari L; Kay, Richard F

2012-02-22

The high energetic costs of building and maintaining large brains are thought to constrain encephalization. The 'expensive-tissue hypothesis' (ETH) proposes that primates (especially humans) overcame this constraint through reduction of another metabolically expensive tissue, the gastrointestinal tract. Small guts characterize animals specializing on easily digestible diets. Thus, the hypothesis may be tested via the relationship between brain size and diet quality. Platyrrhine primates present an interesting test case, as they are more variably encephalized than other extant primate clades (excluding Hominoidea). We find a high degree of phylogenetic signal in the data for diet quality, endocranial volume and body size. Controlling for phylogenetic effects, we find no significant correlation between relative diet quality and relative endocranial volume. Thus, diet quality fails to account for differences in platyrrhine encephalization. One taxon, in particular, Brachyteles, violates predictions made by ETH in having a large brain and low-quality diet. Dietary reconstructions of stem platyrrhines further indicate that a relatively high-quality diet was probably in place prior to increases in encephalization. Therefore, it is unlikely that a shift in diet quality was a primary constraint release for encephalization in platyrrhines and, by extrapolation, humans.

TDat: An Efficient Platform for Processing Petabyte-Scale Whole-Brain Volumetric Images.

PubMed

Li, Yuxin; Gong, Hui; Yang, Xiaoquan; Yuan, Jing; Jiang, Tao; Li, Xiangning; Sun, Qingtao; Zhu, Dan; Wang, Zhenyu; Luo, Qingming; Li, Anan

2017-01-01

Three-dimensional imaging of whole mammalian brains at single-neuron resolution has generated terabyte (TB)- and even petabyte (PB)-sized datasets. Due to their size, processing these massive image datasets can be hindered by the computer hardware and software typically found in biological laboratories. To fill this gap, we have developed an efficient platform named TDat, which adopts a novel data reformatting strategy by reading cuboid data and employing parallel computing. In data reformatting, TDat is more efficient than any other software. In data accessing, we adopted parallelization to fully explore the capability for data transmission in computers. We applied TDat in large-volume data rigid registration and neuron tracing in whole-brain data with single-neuron resolution, which has never been demonstrated in other studies. We also showed its compatibility with various computing platforms, image processing software and imaging systems.

Sex differences in the adolescent brain and body: Findings from the saguenay youth study.

PubMed

Paus, Tomáš; Wong, Angelita Pui-Yee; Syme, Catriona; Pausova, Zdenka

2017-01-02

This Mini-Review describes sex differences in 66 quantitative characteristics of the brain and body measured in a community-based sample of 1,024 adolescents 12-18 years of age, members of the Saguenay Youth Study. Using an extensive phenotyping protocol, we have obtained measures in a number of domains, including brain structure, cognition, mental health, substance use, body composition, metabolism, cardiovascular reactivity, and life style. For each measure, we provide estimates of effect size (Cohen's d) and sex-specific correlations with age (Pearson R). In total 59 of the 66 characteristics showed sex differences (at a nominal P < 0.05), with small (32), medium-sized (13), and large (11) effects. Some, but not all, of these sex differences increase during adolescence; this appears to be the case mostly for anatomical and physiological measures. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

On the possibility of using multi-element phased arrays for shock-wave action on deep brain structures

NASA Astrophysics Data System (ADS)

Rosnitskiy, P. B.; Gavrilov, L. R.; Yuldashev, P. V.; Sapozhnikov, O. A.; Khokhlova, V. A.

2017-09-01

A noninvasive ultrasound surgery method that relies on using multi-element focused phased arrays is being successfully used to destroy tumors and perform neurosurgical operations in deep structures of the human brain. However, several drawbacks that limit the possibilities of the existing systems in their clinical use have been revealed: a large size of the hemispherical array, impossibility of its mechanical movement relative to the patient's head, limited volume of dynamic focusing around the center of curvature of the array, and side effect of overheating skull. Here we evaluate the possibility of using arrays of smaller size and aperture angles to achieve shock-wave formation at the focus for thermal and mechanical ablation (histotripsy) of brain tissue taking into account current intensity limitations at the array elements. The proposed approach has potential advantages to mitigate the existing limitations and expand the possibilities of transcranial ultrasound surgery.

Noninvasive, localized, and transient brain drug delivery using focused ultrasound and microbubbles

NASA Astrophysics Data System (ADS)

Choi, James J.

In the United States, Alzheimer's disease (AD), Parkinson's disease (PD), and brain cancer caused 72,432, 19,566 and 12,886 deaths in 2006, respectively. Whereas the number of deaths due to major disorders such as heart disease, stroke, and prostate cancer have decreased since 2006, deaths attributed to AD, PD, and brain cancer have not. Treatment options for patients with CNS disorders remain limited despite significant advances in knowledge of CNS disease pathways and development of neurologically potent agents. One of the major obstacles is that the cerebral microvasculature is lined by a specialized and highly regulated blood-brain barrier (BBB) that prevents large agents from entering the brain extracellular space. The purpose of this dissertation is to design a noninvasive, localized, and transient BBB opening system using focused ultrasound (FUS) and determine ultrasound and microbubble conditions that can effectively and safely deliver large pharmacologically-relevant-sized agents to the brain. To meet this end, an in vivo mouse brain drug delivery system using a stereotactic-based targeting method was developed. FUS was applied noninvasively through the intact skin and skull, which allowed for long-term and high-throughput studies. With this system, more than 150 mice were exposed to one of 31 distinct acoustic and microbubble conditions. The feasibility of delivering a large MRI contrast agent was first demonstrated in vivo in both wild-type and transgenic Alzheimer's disease model (APP/PS1) mice. A wide range of acoustic and microbubble conditions were then evaluated for their ability to deliver agents to a target region. Interestingly, the possible design space of parameters was found to be vast and different conditions resulted in distinct spatial distributions and doses delivered. In particular, BBB opening was shown to be dependent on the microbubble diameter, acoustic pressure, pulse repetition frequency (PRF), and pulse length (PL). Each set of conditions determined both the size of agents that can traverse the BBB, and also the level of safety of the technique. In one set of conditions (peak-rarefactional pressure: 0.61 MPa, PRF: 10 Hz, PL: 20 ms), large 70-kDa dextran was delivered to a target region, but were associated with detectable damaged sites as indicated by dark neurons, microvacuolations, and erythrocyte extravasations. Another set of conditions (peak-rarefactional pressure: 0.46 MPa, PRF: 5 Hz, PL: 0.2 ms) delivered 3-kDa dextran homogeneously and diffusely to a target region in the brain without any detectable dark neurons, microvacuolations, or erythrocyte extravasations. Each distinct set of conditions may thus be used for different clinical application, i.e., treatment of brain cancer and AD. In conclusion, an effective method to noninvasively, locally, and transiently deliver large therapeutic agents through the BBB was developed.

Neuroradiologic Characteristics of Primary Angiitis of the Central Nervous System According to the Affected Vessel Size.

PubMed

Thaler, Christian; Kaufmann-Bühler, Ann-Katrin; Gansukh, Tserenchunt; Gansukh, Amarjargal; Schuster, Simon; Bachmann, Henrike; Thomalla, Götz; Magnus, Tim; Matschke, Jakob; Fiehler, Jens; Siemonsen, Susanne

2017-09-05

Magnetic resonance imaging (MRI) has an important impact in diagnosing primary angiitis of the central nervous system (PACNS). However, neuroradiologic findings may vary immensely, making an easy and definite diagnosis challenging. In this retrospective, single center study, we analyzed neuroradiologic findings of patients with PACNS diagnosed at our hospital between 2009 and 2014. Furthermore, we classified patients according to the affected vessel size and compared imaging characteristics between the subgroups. Thirty-three patients were included (mean age 43 [±15.3] years, 17 females) in this study. Patients with positive angiographic findings were classified as either medium or large vessel PACNS and presented more ischemic lesions (p < 0.001) and vessel wall enhancement (p = 0.017) compared to patients with small vessel PACNS. No significant differences were detected for the distribution of contrast-enhancing lesions (parenchymal or leptomeningeal), hemorrhages, or lesions with mass effect. Twenty-five patients underwent brain biopsy. Patients with medium or large vessel PACNS were less likely to have positive biopsy results. It is essential to differentiate between small and medium/large vessel PACNS since results in MRI, digital subtraction angiography and brain biopsy may differ immensely. Since image quality of MR scanners improves gradually and brain biopsy may often be nonspecific or negative, our results emphasize the importance of MRI/MRA in the diagnosis process of PACNS.

Multimodal neuroimaging of male and female brain structure in health and disease across the life span.

PubMed

Jahanshad, Neda; Thompson, Paul M

2017-01-02

Sex differences in brain development and aging are important to identify, as they may help to understand risk factors and outcomes in brain disorders that are more prevalent in one sex compared with the other. Brain imaging techniques have advanced rapidly in recent years, yielding detailed structural and functional maps of the living brain. Even so, studies are often limited in sample size, and inconsistent findings emerge, one example being varying findings regarding sex differences in the size of the corpus callosum. More recently, large-scale neuroimaging consortia such as the Enhancing Neuro Imaging Genetics through Meta Analysis Consortium have formed, pooling together expertise, data, and resources from hundreds of institutions around the world to ensure adequate power and reproducibility. These initiatives are helping us to better understand how brain structure is affected by development, disease, and potential modulators of these effects, including sex. This review highlights some established and disputed sex differences in brain structure across the life span, as well as pitfalls related to interpreting sex differences in health and disease. We also describe sex-related findings from the ENIGMA consortium, and ongoing efforts to better understand sex differences in brain circuitry. © 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc. © 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.

Brain size evolution in pipefishes and seahorses: the role of feeding ecology, life history and sexual selection.

PubMed

Tsuboi, M; Lim, A C O; Ooi, B L; Yip, M Y; Chong, V C; Ahnesjö, I; Kolm, N

2017-01-01

Brain size varies greatly at all taxonomic levels. Feeding ecology, life history and sexual selection have been proposed as key components in generating contemporary diversity in brain size across vertebrates. Analyses of brain size evolution have, however, been limited to lineages where males predominantly compete for mating and females choose mates. Here, we present the first original data set of brain sizes in pipefishes and seahorses (Syngnathidae) a group in which intense female mating competition occurs in many species. After controlling for the effect of shared ancestry and overall body size, brain size was positively correlated with relative snout length. Moreover, we found that females, on average, had 4.3% heavier brains than males and that polyandrous species demonstrated more pronounced (11.7%) female-biased brain size dimorphism. Our results suggest that adaptations for feeding on mobile prey items and sexual selection in females are important factors in brain size evolution of pipefishes and seahorses. Most importantly, our study supports the idea that sexual selection plays a major role in brain size evolution, regardless of on which sex sexual selection acts stronger. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

All brains are made of this: a fundamental building block of brain matter with matching neuronal and glial masses.

PubMed

Mota, Bruno; Herculano-Houzel, Suzana

2014-01-01

How does the size of the glial and neuronal cells that compose brain tissue vary across brain structures and species? Our previous studies indicate that average neuronal size is highly variable, while average glial cell size is more constant. Measuring whole cell sizes in vivo, however, is a daunting task. Here we use chi-square minimization of the relationship between measured neuronal and glial cell densities in the cerebral cortex, cerebellum, and rest of brain in 27 mammalian species to model neuronal and glial cell mass, as well as the neuronal mass fraction of the tissue (the fraction of tissue mass composed by neurons). Our model shows that while average neuronal cell mass varies by over 500-fold across brain structures and species, average glial cell mass varies only 1.4-fold. Neuronal mass fraction varies typically between 0.6 and 0.8 in all structures. Remarkably, we show that two fundamental, universal relationships apply across all brain structures and species: (1) the glia/neuron ratio varies with the total neuronal mass in the tissue (which in turn depends on variations in average neuronal cell mass), and (2) the neuronal mass per glial cell, and with it the neuronal mass fraction and neuron/glia mass ratio, varies with average glial cell mass in the tissue. We propose that there is a fundamental building block of brain tissue: the glial mass that accompanies a unit of neuronal mass. We argue that the scaling of this glial mass is a consequence of a universal mechanism whereby numbers of glial cells are added to the neuronal parenchyma during development, irrespective of whether the neurons composing it are large or small, but depending on the average mass of the glial cells being added. We also show how evolutionary variations in neuronal cell mass, glial cell mass and number of neurons suffice to determine the most basic characteristics of brain structures, such as mass, glia/neuron ratio, neuron/glia mass ratio, and cell densities.

Can Cooler Heads Prevail?

NASA Astrophysics Data System (ADS)

Rice, A. R.

2015-12-01

The significant correlation between dropping temperatures throughout the Pliocene and the concomitant explosive expansion of the Hominid brain has led a number of workers to postulate climate change drove human evolution. Our brain (that of Homo sapiens), comprises 1-2 percent of our body weight but consumes 20 -25 percent of the body's caloric intake. We are "hotheads". Brains are extremely sensitive to overheating but we are endowed with unparalleled thermal regulation, much of it given over to protecting the Central Nervous System (CNS). Will there be reversed trends with global warming? The human brain has been shrinking since the end of the Ice Ages, losing about 150cc over the past 10,000 years. Polar bear skulls have been downsizing as well. Almost all mass extinctions or evolutionary upheavals are attributed to global warming: e.g. the Permian/Triassic (P/T) event, i.e., "The Great Dying", 250 million years ago (~90% of all life forms wiped out); the Paleocene/ Eocene Thermal Maximum (PETM) 55 million years ago. They may be analogs for what might await us. Large creatures, whose body size inhibits cooling, melted away during the PETM. Horses, initially the size of dogs then, reduced to the size of cats. An unanticipated hazard for humans that may attend extreme global warming is dumbing down or needing to retreat to the Poles as did those creatures that survived the P/T event (some references: http://johnhawks.net/research/hawks-2011-brain-size-selection-holocene; Kandel, E. et al Principles of Neural Science 4th ed. New York (US): McGraw-Hill, 2000; Selective Brain Cooling in Early Hominids:phylogenetic and evolutionary implications, Reeser, H., reeser@flmnh.ufl.edu; How the body controls brain temperature; the temperature shielding effect of cerebral blood flow, Mingming Z. et al. J Appl Physiol. 2006 November; 101(5): 1481-1488; news.nationalgeographic.com/ news/2014/03/140327-climate-change-shrinks-salamanders-global-warming-science/; Heat illness and heat stroke, www.ozemedicine.com/wiki/doku.php?id=heat illness 7/3/2010)

Variations and asymmetries in regional brain surface in the genus Homo.

PubMed

Balzeau, Antoine; Holloway, Ralph L; Grimaud-Hervé, Dominique

2012-06-01

Paleoneurology is an important field of research within human evolution studies. Variations in size and shape of an endocast help to differentiate among fossil hominin species whereas endocranial asymmetries are related to behavior and cognitive function. Here we analyse variations of the surface of the frontal, parieto-temporal and occipital lobes among different species of Homo, including 39 fossil hominins, ten fossil anatomically modern Homo sapiens and 100 endocasts of extant modern humans. We also test for the possible asymmetries of these features in a large sample of modern humans and observe individual particularities in the fossil specimens. This study contributes important new information about the brain evolution in the genus Homo. Our results show that the general pattern of surface asymmetry for the different regional brain surfaces in fossil species of Homo does not seem to be different from the pattern described in a large sample of anatomically modern H. sapiens, i.e., the right hemisphere has a larger surface than the left, as do the right frontal, the right parieto-temporal and the left occipital lobes compared with the contra-lateral side. It also appears that Asian Homo erectus specimens are discriminated from all other samples of Homo, including African and Georgian specimens that are also sometimes included in that taxon. The Asian fossils show a significantly smaller relative size of the parietal and temporal lobes. Neandertals and anatomically modern H. sapiens, who share the largest endocranial volume of all hominins, show differences when considering the relative contribution of the frontal, parieto-temporal and occipital lobes. These results illustrate an original variation in the pattern of brain organization in hominins independent of variations in total size. The globularization of the brain and the enlargement of the parietal lobes could be considered derived features observed uniquely in anatomically modern H. sapiens. Copyright © 2012 Elsevier Ltd. All rights reserved.

A Geographic Cline of Skull and Brain Morphology among Individuals of European Ancestry

PubMed Central

Bakken, Trygve E.; Dale, Anders M.; Schork, Nicholas J.

2011-01-01

Background Human skull and brain morphology are strongly influenced by genetic factors, and skull size and shape vary worldwide. However, the relationship between specific brain morphology and genetically-determined ancestry is largely unknown. Methods We used two independent data sets to characterize variation in skull and brain morphology among individuals of European ancestry. The first data set is a historical sample of 1,170 male skulls with 37 shape measurements drawn from 27 European populations. The second data set includes 626 North American individuals of European ancestry participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI) with magnetic resonance imaging, height and weight, neurological diagnosis, and genome-wide single nucleotide polymorphism (SNP) data. Results We found that both skull and brain morphological variation exhibit a population-genetic fingerprint among individuals of European ancestry. This fingerprint shows a Northwest to Southeast gradient, is independent of body size, and involves frontotemporal cortical regions. Conclusion Our findings are consistent with prior evidence for gene flow in Europe due to historical population movements and indicate that genetic background should be considered in studies seeking to identify genes involved in human cortical development and neuropsychiatric disease. PMID:21849792

Insular dwarfism in hippos and a model for brain size reduction in Homo floresiensis.

PubMed

Weston, Eleanor M; Lister, Adrian M

2009-05-07

Body size reduction in mammals is usually associated with only moderate brain size reduction, because the brain and sensory organs complete their growth before the rest of the body during ontogeny. On this basis, 'phyletic dwarfs' are predicted to have a greater relative brain size than 'phyletic giants'. However, this trend has been questioned in the special case of dwarfism of mammals on islands. Here we show that the endocranial capacities of extinct dwarf species of hippopotamus from Madagascar are up to 30% smaller than those of a mainland African ancestor scaled to equivalent body mass. These results show that brain size reduction is much greater than predicted from an intraspecific 'late ontogenetic' model of dwarfism in which brain size scales to body size with an exponent of 0.35. The nature of the proportional change or grade shift observed here indicates that selective pressures on brain size are potentially independent of those on body size. This study demonstrates empirically that it is mechanistically possible for dwarf mammals on islands to evolve significantly smaller brains than would be predicted from a model of dwarfing based on the intraspecific scaling of the mainland ancestor. Our findings challenge current understanding of brain-body allometric relationships in mammals and suggest that the process of dwarfism could in principle explain small brain size, a factor relevant to the interpretation of the small-brained hominin found on the Island of Flores, Indonesia.

Insular dwarfism in hippos and a model for brain size reduction in Homo floresiensis

PubMed Central

Weston, Eleanor M.; Lister, Adrian M.

2009-01-01

Body size reduction in mammals is usually associated with only moderate brain size reduction as the brain and sensory organs complete their growth before the rest of the body during ontogeny1,2. On this basis “phyletic dwarfs” are predicted to have a higher relative brain size than “phyletic giants”1,3. This trend has been questioned, however, in the special case of dwarfism of mammals on islands4. Here we show that the endocranial capacities of extinct dwarf species of hippopotamus from Madagascar are up to 30% smaller than those of a mainland African ancestor scaled to equivalent body mass. These results show brain size reduction is much greater than predicted from an intraspecific ‘late ontogenetic’ model of dwarfism where brain size scales to body size with an exponent of 0.35. The nature of the proportional change or grade shift2,5 observed here indicates that selective pressures upon brain size are potentially independent from those on body size. This study demonstrates empirically that it is mechanistically possible for dwarf mammals on islands to evolve significantly smaller brains than would be predicted from a model of dwarfing based on the intraspecific scaling of the mainland ancestor. Our findings challenge our understanding of brain-body allometric relationships in mammals and suggest that the process of dwarfism could in principle explain small brain size, a factor relevant to the interpretation of the small-brained hominin found on the Island of Flores, Indonesia6. PMID:19424156

[Electron microscopic study of the An-750 strain of Powassan virus isolated in the Soviet Union].

PubMed

Sobolev, S G; Shestopalova, N M; Linev, M B; Rubin, S G

1978-01-01

Electron microscopic examinations of brains of white mice inoculated with the An 750 strain isolated for the first time from adult mosquitoes and with the prototype LB strain of Powassan virus were carried out. The method of combination of light and electron microscopy used in the study permitted to compare ultrastructural changes in one cell with the results of light microscopy. Sizes of virions and their localizations in the brain cells were determined. Virus particles were found in large and small neurons as well as in glial elements. Subcellular changes in neurons associated with virus multiplication are described. The causes of differences in sizes of virions measured in ultrathin sections are discussed.

Regulation of behaviorally associated gene networks in worker honey bee ovaries

PubMed Central

Wang, Ying; Kocher, Sarah D.; Linksvayer, Timothy A.; Grozinger, Christina M.; Page, Robert E.; Amdam, Gro V.

2012-01-01

SUMMARY Several lines of evidence support genetic links between ovary size and division of labor in worker honey bees. However, it is largely unknown how ovaries influence behavior. To address this question, we first performed transcriptional profiling on worker ovaries from two genotypes that differ in social behavior and ovary size. Then, we contrasted the differentially expressed ovarian genes with six sets of available brain transcriptomes. Finally, we probed behavior-related candidate gene networks in wild-type ovaries of different sizes. We found differential expression in 2151 ovarian transcripts in these artificially selected honey bee strains, corresponding to approximately 20.3% of the predicted gene set of honey bees. Differences in gene expression overlapped significantly with changes in the brain transcriptomes. Differentially expressed genes were associated with neural signal transmission (tyramine receptor, TYR) and ecdysteroid signaling; two independently tested nuclear hormone receptors (HR46 and ftz-f1) were also significantly correlated with ovary size in wild-type bees. We suggest that the correspondence between ovary and brain transcriptomes identified here indicates systemic regulatory networks among hormones (juvenile hormone and ecdysteroids), pheromones (queen mandibular pheromone), reproductive organs and nervous tissues in worker honey bees. Furthermore, robust correlations between ovary size and neuraland endocrine response genes are consistent with the hypothesized roles of the ovaries in honey bee behavioral regulation. PMID:22162860

Brain scaling in mammalian evolution as a consequence of concerted and mosaic changes in numbers of neurons and average neuronal cell size

PubMed Central

Herculano-Houzel, Suzana; Manger, Paul R.; Kaas, Jon H.

2014-01-01

Enough species have now been subject to systematic quantitative analysis of the relationship between the morphology and cellular composition of their brain that patterns begin to emerge and shed light on the evolutionary path that led to mammalian brain diversity. Based on an analysis of the shared and clade-specific characteristics of 41 modern mammalian species in 6 clades, and in light of the phylogenetic relationships among them, here we propose that ancestral mammal brains were composed and scaled in their cellular composition like modern afrotherian and glire brains: with an addition of neurons that is accompanied by a decrease in neuronal density and very little modification in glial cell density, implying a significant increase in average neuronal cell size in larger brains, and the allocation of approximately 2 neurons in the cerebral cortex and 8 neurons in the cerebellum for every neuron allocated to the rest of brain. We also propose that in some clades the scaling of different brain structures has diverged away from the common ancestral layout through clade-specific (or clade-defining) changes in how average neuronal cell mass relates to numbers of neurons in each structure, and how numbers of neurons are differentially allocated to each structure relative to the number of neurons in the rest of brain. Thus, the evolutionary expansion of mammalian brains has involved both concerted and mosaic patterns of scaling across structures. This is, to our knowledge, the first mechanistic model that explains the generation of brains large and small in mammalian evolution, and it opens up new horizons for seeking the cellular pathways and genes involved in brain evolution. PMID:25157220

Brain interstitial fluid TNF-α after subarachnoid hemorrhage

PubMed Central

Hanafy, Khalid A.; Grobelny, Bartosz; Fernandez, Luis; Kurtz, Pedro; Connolly, ES; Mayer, Stephan A.; Schindler, Christian; Badjatia, Neeraj

2010-01-01

Objective: TNF-α is an inflammatory cytokine that plays a central role in promoting the cascade of events leading to an inflammatory response. Recent studies have suggested that TNF-α may play a key role in the formation and rupture of cerebral aneurysms, and that the underlying cerebral inflammatory response is a major determinate of outcome following subrarachnoid hemorrhage (SAH). Methods: We studied 14 comatose SAH patients who underwent multimodality neuromonitoring with intracranial pressure (ICP) and cerebral microdialysis as part of their clinical care. Continuous physiological variables were time-locked every 8 hours and recorded at the same point that brain interstitial fluid TNF-α was measured in brain microdialysis samples. Significant associations were determined using generalized estimation equations. Results: Each patient had a mean of 9 brain tissue TNF-α measurements obtained over an average of 72 hours of monitoring. TNF-α levels rose progressively over time. Predictors of elevated brain interstitial TNF-α included higher brain interstitial fluid glucose levels (β=0.066, P<0.02), intraventricular hemorrhage (β=0.085, P<0.021), and aneurysm size >6 mm (β=0.14, p<0.001). There was no relationship between TNF-α levels and the burden of cisternal SAH; concurrent measurements of serum glucose, or lactate-pyruvate ratio. Interpretation: Brain interstitial TNF-α levels are elevated after SAH, and are associated with large aneurysm size, the burden of intraventricular blood, and elevation brain interstitial glucose levels. PMID:20110094

Cohort Study of Multiple Brain Lesions in Sport Divers: Role of a Patent Foramen Ovale

NASA Technical Reports Server (NTRS)

Knauth, Michael; Ries, Stefan; Pohimann, Stefan; Kerby, Tina; Forstring, Michael; Daffertshofer, Michael; Hennerici,Michael; Sartor, Klaus

1997-01-01

To investigate the role of a patent foramen ovale in the pathogenesis of multiple brain lesions acquired by sport divers in the absence of reported decompression symptoms. Design: Prospective double blind cohort study. . Setting Diving clubs around Heidelberg and departments of neuroradiology and neurology. Subjects: 87 sport divers with a minimum of 160 scuba dives (dives with self contained underwater breathing apparatus). Main outcome measures: Presence of multiple brain lesions visualised by cranial magnetic resonance imaging and presence and size of patent foramen ovale as documented by echocontrast transcranial Doppler ultrasonograhy. Results: 25 subjects were found to have a right-to-left shunt, 13 with a patent foramen ovale of high haemodynamic relevance. A total of 41 brain lesions were detected in 11 divers. There were seven brain lesions in seven divers without a right-to-left shunt and 34 lesions in four divers with a right-to-left shunt Multiple brain lesions occurred exclusively in three divers with a large patent foramen ovale (P=0.004). Conclusions: Multiple brain lesions in sport divers were associated with presence of a large patent foramen ovale. This association suggests paradoxical gas embolism as the pathological mechanism. A patent foramen ovale of high haemodynamic relevance seems to be an important risk factor for developing multiple brain lesions in sport divers.

Predator-driven brain size evolution in natural populations of Trinidadian killifish (Rivulus hartii)

PubMed Central

Walsh, Matthew R.; Broyles, Whitnee; Beston, Shannon M.; Munch, Stephan B.

2016-01-01

Vertebrates exhibit extensive variation in relative brain size. It has long been assumed that this variation is the product of ecologically driven natural selection. Yet, despite more than 100 years of research, the ecological conditions that select for changes in brain size are unclear. Recent laboratory selection experiments showed that selection for larger brains is associated with increased survival in risky environments. Such results lead to the prediction that increased predation should favour increased brain size. Work on natural populations, however, foreshadows the opposite trajectory of evolution; increased predation favours increased boldness, slower learning, and may thereby select for a smaller brain. We tested the influence of predator-induced mortality on brain size evolution by quantifying brain size variation in a Trinidadian killifish, Rivulus hartii, from communities that differ in predation intensity. We observed strong genetic differences in male (but not female) brain size between fish communities; second generation laboratory-reared males from sites with predators exhibited smaller brains than Rivulus from sites in which they are the only fish present. Such trends oppose the results of recent laboratory selection experiments and are not explained by trade-offs with other components of fitness. Our results suggest that increased male brain size is favoured in less risky environments because of the fitness benefits associated with faster rates of learning and problem-solving behaviour. PMID:27412278

Bigger Brains or Bigger Nuclei? Regulating the Size of Auditory Structures in Birds

PubMed Central

Kubke, M. Fabiana; Massoglia, Dino P.; Carr, Catherine E.

2012-01-01

Increases in the size of the neuronal structures that mediate specific behaviors are believed to be related to enhanced computational performance. It is not clear, however, what developmental and evolutionary mechanisms mediate these changes, nor whether an increase in the size of a given neuronal population is a general mechanism to achieve enhanced computational ability. We addressed the issue of size by analyzing the variation in the relative number of cells of auditory structures in auditory specialists and generalists. We show that bird species with different auditory specializations exhibit variation in the relative size of their hindbrain auditory nuclei. In the barn owl, an auditory specialist, the hind-brain auditory nuclei involved in the computation of sound location show hyperplasia. This hyperplasia was also found in songbirds, but not in non-auditory specialists. The hyperplasia of auditory nuclei was also not seen in birds with large body weight suggesting that the total number of cells is selected for in auditory specialists. In barn owls, differences observed in the relative size of the auditory nuclei might be attributed to modifications in neurogenesis and cell death. Thus, hyperplasia of circuits used for auditory computation accompanies auditory specialization in different orders of birds. PMID:14726625

When larger brains do not have more neurons: increased numbers of cells are compensated by decreased average cell size across mouse individuals

PubMed Central

Herculano-Houzel, Suzana; Messeder, Débora J.; Fonseca-Azevedo, Karina; Pantoja, Nilma A.

2015-01-01

There is a strong trend toward increased brain size in mammalian evolution, with larger brains composed of more and larger neurons than smaller brains across species within each mammalian order. Does the evolution of increased numbers of brain neurons, and thus larger brain size, occur simply through the selection of individuals with more and larger neurons, and thus larger brains, within a population? That is, do individuals with larger brains also have more, and larger, neurons than individuals with smaller brains, such that allometric relationships across species are simply an extension of intraspecific scaling? Here we show that this is not the case across adult male mice of a similar age. Rather, increased numbers of neurons across individuals are accompanied by increased numbers of other cells and smaller average cell size of both types, in a trade-off that explains how increased brain mass does not necessarily ensue. Fundamental regulatory mechanisms thus must exist that tie numbers of neurons to numbers of other cells and to average cell size within individual brains. Finally, our results indicate that changes in brain size in evolution are not an extension of individual variation in numbers of neurons, but rather occur through step changes that must simultaneously increase numbers of neurons and cause cell size to increase, rather than decrease. PMID:26082686

When larger brains do not have more neurons: increased numbers of cells are compensated by decreased average cell size across mouse individuals.

PubMed

Herculano-Houzel, Suzana; Messeder, Débora J; Fonseca-Azevedo, Karina; Pantoja, Nilma A

2015-01-01

There is a strong trend toward increased brain size in mammalian evolution, with larger brains composed of more and larger neurons than smaller brains across species within each mammalian order. Does the evolution of increased numbers of brain neurons, and thus larger brain size, occur simply through the selection of individuals with more and larger neurons, and thus larger brains, within a population? That is, do individuals with larger brains also have more, and larger, neurons than individuals with smaller brains, such that allometric relationships across species are simply an extension of intraspecific scaling? Here we show that this is not the case across adult male mice of a similar age. Rather, increased numbers of neurons across individuals are accompanied by increased numbers of other cells and smaller average cell size of both types, in a trade-off that explains how increased brain mass does not necessarily ensue. Fundamental regulatory mechanisms thus must exist that tie numbers of neurons to numbers of other cells and to average cell size within individual brains. Finally, our results indicate that changes in brain size in evolution are not an extension of individual variation in numbers of neurons, but rather occur through step changes that must simultaneously increase numbers of neurons and cause cell size to increase, rather than decrease.

Custom fit 3D-printed brain holders for comparison of histology with MRI in marmosets.

PubMed

Guy, Joseph R; Sati, Pascal; Leibovitch, Emily; Jacobson, Steven; Silva, Afonso C; Reich, Daniel S

2016-01-15

MRI has the advantage of sampling large areas of tissue and locating areas of interest in 3D space in both living and ex vivo systems, whereas histology has the ability to examine thin slices of ex vivo tissue with high detail and specificity. Although both are valuable tools, it is currently difficult to make high-precision comparisons between MRI and histology due to large differences inherent to the techniques. A method combining the advantages would be an asset to understanding the pathological correlates of MRI. 3D-printed brain holders were used to maintain marmoset brains in the same orientation during acquisition of ex vivo MRI and pathologic cutting of the tissue. The results of maintaining this same orientation show that sub-millimeter, discrete neuropathological features in marmoset brain consistently share size, shape, and location between histology and ex vivo MRI, which facilitates comparison with serial imaging acquired in vivo. Existing methods use computational approaches sensitive to data input in order to warp histologic images to match large-scale features on MRI, but the new method requires no warping of images, due to a preregistration accomplished in the technique, and is insensitive to data formatting and artifacts in both MRI and histology. The simple method of using 3D-printed brain holders to match brain orientation during pathologic sectioning and MRI acquisition enables rapid and precise comparison of small features seen on MRI to their underlying histology. Published by Elsevier B.V.

Food portion size and energy density evoke different patterns of brain activation in children12

PubMed Central

Fearnbach, S Nicole; Wilson, Stephen J; Fisher, Jennifer O; Savage, Jennifer S; Rolls, Barbara J; Keller, Kathleen L

2017-01-01

Background: Large portions of food promote intake, but the mechanisms that drive this effect are unclear. Previous neuroimaging studies have identified the brain-reward and decision-making systems that are involved in the response to the energy density (ED) (kilocalories per gram) of foods, but few studies have examined the brain response to the food portion size (PS). Objective: We used functional MRI (fMRI) to determine the brain response to food images that differed in PSs (large and small) and ED (high and low). Design: Block-design fMRI was used to assess the blood oxygen level–dependent (BOLD) response to images in 36 children (7–10 y old; girls: 50%), which was tested after a 2-h fast. Pre-fMRI fullness and liking were rated on visual analog scales. A whole-brain cluster-corrected analysis was used to compare BOLD activation for main effects of the PS, ED, and their interaction. Secondary analyses were used to associate BOLD contrast values with appetitive traits and laboratory intake from meals for which the portions of all foods were increased. Results: Compared with small-PS cues, large-PS cues were associated with decreased activation in the inferior frontal gyrus (P < 0.01). Compared with low-ED cues, high-ED cues were associated with increased activation in multiple regions (e.g., in the caudate, cingulate, and precentral gyrus) and decreased activation in the insula and superior temporal gyrus (P < 0.01 for all). A PS × ED interaction was shown in the superior temporal gyrus (P < 0.01). BOLD contrast values for high-ED cues compared with low-ED cues in the insula, declive, and precentral gyrus were negatively related to appetitive traits (P < 0.05). There were no associations between the brain response to the PS and either appetitive traits or intake. Conclusions: Cues regarding food PS may be processed in the lateral prefrontal cortex, which is a region that is implicated in cognitive control, whereas ED activates multiple areas involved in sensory and reward processing. Possible implications include the development of interventions that target decision-making and reward systems differently to moderate overeating. PMID:27881393

Single-voxel and multi-voxel spectroscopy yield comparable results in the normal juvenile canine brain when using 3 Tesla magnetic resonance imaging.

PubMed

Lee, Alison M; Beasley, Michaela J; Barrett, Emerald D; James, Judy R; Gambino, Jennifer M

2018-06-10

Conventional magnetic resonance imaging (MRI) characteristics of canine brain diseases are often nonspecific. Single- and multi-voxel spectroscopy techniques allow quantification of chemical biomarkers for tissues of interest and may help to improve diagnostic specificity. However, published information is currently lacking for the in vivo performance of these two techniques in dogs. The aim of this prospective, methods comparison study was to compare the performance of single- and multi-voxel spectroscopy in the brains of eight healthy, juvenile dogs using 3 Tesla MRI. Ipsilateral regions of single- and multi-voxel spectroscopy were performed in symmetric regions of interest of each brain in the parietal (n = 3), thalamic (n = 2), and piriform lobes (n = 3). In vivo single-voxel spectroscopy and multi-voxel spectroscopy metabolite ratios from the same size and multi-voxel spectroscopy ratios from different sized regions of interest were compared. No significant difference was seen between single-voxel spectroscopy and multi-voxel spectroscopy metabolite ratios for any lobe when regions of interest were similar in size and shape. Significant lobar single-voxel spectroscopy and multi-voxel spectroscopy differences were seen between the parietal lobe and thalamus (P = 0.047) for the choline to N-acetyl aspartase ratios when large multi-voxel spectroscopy regions of interest were compared to very small multi-voxel spectroscopy regions of interest within the same lobe; and for the N-acetyl aspartase to creatine ratios in all lobes when single-voxel spectroscopy was compared to combined (pooled) multi-voxel spectroscopy datasets. Findings from this preliminary study indicated that single- and multi-voxel spectroscopy techniques using 3T MRI yield comparable results for similar sized regions of interest in the normal canine brain. Findings also supported using the contralateral side as an internal control for dogs with brain lesions. © 2018 American College of Veterinary Radiology.

The effects of laboratory housing and spatial enrichment on brain size and metabolic rate in the eastern mosquitofish, Gambusia holbrooki

PubMed Central

Turschwell, Mischa P.; White, Craig R.

2016-01-01

ABSTRACT It has long been hypothesised that there is a functional correlation between brain size and metabolic rate in vertebrates. The present study tested this hypothesis in wild-caught adult mosquitofish Gambusia holbrooki by testing for an intra-specific association between resting metabolic rate (RMR) and brain size while controlling for variation in body size, and through the examination of the effects of spatial enrichment and laboratory housing on body mass-independent measures of brain size and RMR. Controlling for body mass, there was no relationship between brain size and RMR in wild-caught fish. Contrary to predictions, spatial enrichment caused a decrease in mass-independent brain size, highlighting phenotypic plasticity in the adult brain. As expected, after controlling for differences in body size, wild-caught fish had relatively larger brains than fish that had been maintained in the laboratory for a minimum of six weeks, but wild-caught fish also had significantly lower mass-independent RMR. This study demonstrates that an organisms' housing environment can cause significant plastic changes to fitness related traits including brain size and RMR. We therefore conclude that current standard laboratory housing conditions may cause captive animals to be non-representative of their wild counterparts, potentially undermining the transferability of previous laboratory-based studies of aquatic ectothermic vertebrates to wild populations. PMID:26794608

Head circumference and brain size in autism spectrum disorder: A systematic review and meta-analysis.

PubMed

Sacco, Roberto; Gabriele, Stefano; Persico, Antonio M

2015-11-30

Macrocephaly and brain overgrowth have been associated with autism spectrum disorder. We performed a systematic review and meta-analysis to provide an overall estimate of effect size and statistical significance for both head circumference and total brain volume in autism. Our literature search strategy identified 261 and 391 records, respectively; 27 studies defining percentages of macrocephalic patients and 44 structural brain imaging studies providing total brain volumes for patients and controls were included in our meta-analyses. Head circumference was significantly larger in autistic compared to control individuals, with 822/5225 (15.7%) autistic individuals displaying macrocephaly. Structural brain imaging studies measuring brain volume estimated effect size. The effect size is higher in low functioning autistics compared to high functioning and ASD individuals. Brain overgrowth was recorded in 142/1558 (9.1%) autistic patients. Finally, we found a significant interaction between age and total brain volume, resulting in larger head circumference and brain size during early childhood. Our results provide conclusive effect sizes and prevalence rates for macrocephaly and brain overgrowth in autism, confirm the variation of abnormal brain growth with age, and support the inclusion of this endophenotype in multi-biomarker diagnostic panels for clinical use. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Whole Brain Size and General Mental Ability: A Review

PubMed Central

Rushton, J. Philippe; Ankney, C. Davison

2009-01-01

We review the literature on the relation between whole brain size and general mental ability (GMA) both within and between species. Among humans, in 28 samples using brain imaging techniques, the mean brain size/GMA correlation is 0.40 (N = 1,389; p < 10−10); in 59 samples using external head size measures it is 0.20 (N = 63,405; p < 10−10). In 6 samples using the method of correlated vectors to distill g, the general factor of mental ability, the mean r is 0.63. We also describe the brain size/GMA correlations with age, socioeconomic position, sex, and ancestral population groups, which also provide information about brain–behavior relationships. Finally, we examine brain size and mental ability from an evolutionary and behavior genetic perspective. PMID:19283594

Large-scale Scanning Transmission Electron Microscopy (Nanotomy) of Healthy and Injured Zebrafish Brain.

PubMed

Kuipers, Jeroen; Kalicharan, Ruby D; Wolters, Anouk H G; van Ham, Tjakko J; Giepmans, Ben N G

2016-05-25

Large-scale 2D electron microscopy (EM), or nanotomy, is the tissue-wide application of nanoscale resolution electron microscopy. Others and we previously applied large scale EM to human skin pancreatic islets, tissue culture and whole zebrafish larvae(1-7). Here we describe a universally applicable method for tissue-scale scanning EM for unbiased detection of sub-cellular and molecular features. Nanotomy was applied to investigate the healthy and a neurodegenerative zebrafish brain. Our method is based on standardized EM sample preparation protocols: Fixation with glutaraldehyde and osmium, followed by epoxy-resin embedding, ultrathin sectioning and mounting of ultrathin-sections on one-hole grids, followed by post staining with uranyl and lead. Large-scale 2D EM mosaic images are acquired using a scanning EM connected to an external large area scan generator using scanning transmission EM (STEM). Large scale EM images are typically ~ 5 - 50 G pixels in size, and best viewed using zoomable HTML files, which can be opened in any web browser, similar to online geographical HTML maps. This method can be applied to (human) tissue, cross sections of whole animals as well as tissue culture(1-5). Here, zebrafish brains were analyzed in a non-invasive neuronal ablation model. We visualize within a single dataset tissue, cellular and subcellular changes which can be quantified in various cell types including neurons and microglia, the brain's macrophages. In addition, nanotomy facilitates the correlation of EM with light microscopy (CLEM)(8) on the same tissue, as large surface areas previously imaged using fluorescent microscopy, can subsequently be subjected to large area EM, resulting in the nano-anatomy (nanotomy) of tissues. In all, nanotomy allows unbiased detection of features at EM level in a tissue-wide quantifiable manner.

Large-scale Scanning Transmission Electron Microscopy (Nanotomy) of Healthy and Injured Zebrafish Brain

PubMed Central

Kuipers, Jeroen; Kalicharan, Ruby D.; Wolters, Anouk H. G.

2016-01-01

Large-scale 2D electron microscopy (EM), or nanotomy, is the tissue-wide application of nanoscale resolution electron microscopy. Others and we previously applied large scale EM to human skin pancreatic islets, tissue culture and whole zebrafish larvae1-7. Here we describe a universally applicable method for tissue-scale scanning EM for unbiased detection of sub-cellular and molecular features. Nanotomy was applied to investigate the healthy and a neurodegenerative zebrafish brain. Our method is based on standardized EM sample preparation protocols: Fixation with glutaraldehyde and osmium, followed by epoxy-resin embedding, ultrathin sectioning and mounting of ultrathin-sections on one-hole grids, followed by post staining with uranyl and lead. Large-scale 2D EM mosaic images are acquired using a scanning EM connected to an external large area scan generator using scanning transmission EM (STEM). Large scale EM images are typically ~ 5 - 50 G pixels in size, and best viewed using zoomable HTML files, which can be opened in any web browser, similar to online geographical HTML maps. This method can be applied to (human) tissue, cross sections of whole animals as well as tissue culture1-5. Here, zebrafish brains were analyzed in a non-invasive neuronal ablation model. We visualize within a single dataset tissue, cellular and subcellular changes which can be quantified in various cell types including neurons and microglia, the brain's macrophages. In addition, nanotomy facilitates the correlation of EM with light microscopy (CLEM)8 on the same tissue, as large surface areas previously imaged using fluorescent microscopy, can subsequently be subjected to large area EM, resulting in the nano-anatomy (nanotomy) of tissues. In all, nanotomy allows unbiased detection of features at EM level in a tissue-wide quantifiable manner. PMID:27285162

Evolution of brain-body allometry in Lake Tanganyika cichlids.

PubMed

Tsuboi, Masahito; Kotrschal, Alexander; Hayward, Alexander; Buechel, Severine Denise; Zidar, Josefina; Løvlie, Hanne; Kolm, Niclas

2016-07-01

Brain size is strongly associated with body size in all vertebrates. This relationship has been hypothesized to be an important constraint on adaptive brain size evolution. The essential assumption behind this idea is that static (i.e., within species) brain-body allometry has low ability to evolve. However, recent studies have reported mixed support for this view. Here, we examine brain-body static allometry in Lake Tanganyika cichlids using a phylogenetic comparative framework. We found considerable variation in the static allometric intercept, which explained the majority of variation in absolute and relative brain size. In contrast, the slope of the brain-body static allometry had relatively low variation, which explained less variation in absolute and relative brain size compared to the intercept and body size. Further examination of the tempo and mode of evolution of static allometric parameters confirmed these observations. Moreover, the estimated evolutionary parameters indicate that the limited observed variation in the static allometric slope could be a result of strong stabilizing selection. Overall, our findings suggest that the brain-body static allometric slope may represent an evolutionary constraint in Lake Tanganyika cichlids. © 2016 The Author(s).

Pediatric Brain Extraction Using Learning-based Meta-algorithm

PubMed Central

Shi, Feng; Wang, Li; Dai, Yakang; Gilmore, John H.; Lin, Weili; Shen, Dinggang

2012-01-01

Magnetic resonance imaging of pediatric brain provides valuable information for early brain development studies. Automated brain extraction is challenging due to the small brain size and dynamic change of tissue contrast in the developing brains. In this paper, we propose a novel Learning Algorithm for Brain Extraction and Labeling (LABEL) specially for the pediatric MR brain images. The idea is to perform multiple complementary brain extractions on a given testing image by using a meta-algorithm, including BET and BSE, where the parameters of each run of the meta-algorithm are effectively learned from the training data. Also, the representative subjects are selected as exemplars and used to guide brain extraction of new subjects in different age groups. We further develop a level-set based fusion method to combine multiple brain extractions together with a closed smooth surface for obtaining the final extraction. The proposed method has been extensively evaluated in subjects of three representative age groups, such as neonate (less than 2 months), infant (1–2 years), and child (5–18 years). Experimental results show that, with 45 subjects for training (15 neonates, 15 infant, and 15 children), the proposed method can produce more accurate brain extraction results on 246 testing subjects (75 neonates, 126 infants, and 45 children), i.e., at average Jaccard Index of 0.953, compared to those by BET (0.918), BSE (0.902), ROBEX (0.901), GCUT (0.856), and other fusion methods such as Majority Voting (0.919) and STAPLE (0.941). Along with the largely-improved computational efficiency, the proposed method demonstrates its ability of automated brain extraction for pediatric MR images in a large age range. PMID:22634859

How Do the Size, Charge and Shape of Nanoparticles Affect Amyloid β Aggregation on Brain Lipid Bilayer?

NASA Astrophysics Data System (ADS)

Kim, Yuna; Park, Ji-Hyun; Lee, Hyojin; Nam, Jwa-Min

2016-01-01

Here, we studied the effect of the size, shape, and surface charge of Au nanoparticles (AuNPs) on amyloid beta (Aβ) aggregation on a total brain lipid-based supported lipid bilayer (brain SLB), a fluid platform that facilitates Aβ-AuNP aggregation process. We found that larger AuNPs induce large and amorphous aggregates on the brain SLB, whereas smaller AuNPs induce protofibrillar Aβ structures. Positively charged AuNPs were more strongly attracted to Aβ than negatively charged AuNPs, and the stronger interactions between AuNPs and Aβ resulted in fewer β-sheets and more random coil structures. We also compared spherical AuNPs, gold nanorods (AuNRs), and gold nanocubes (AuNCs) to study the effect of nanoparticle shape on Aβ aggregation on the brain SLB. Aβ was preferentially bound to the long axis of AuNRs and fewer fibrils were formed whereas all the facets of AuNCs interacted with Aβ to produce the fibril networks. Finally, it was revealed that different nanostructures induce different cytotoxicity on neuroblastoma cells, and, overall, smaller Aβ aggregates induce higher cytotoxicity. The results offer insight into the roles of NPs and brain SLB in Aβ aggregation on the cell membrane and can facilitate the understanding of Aβ-nanostructure co-aggregation mechanism and tuning Aβ aggregate structures.

The neural representation of social networks.

PubMed

Weaverdyck, Miriam E; Parkinson, Carolyn

2018-05-24

The computational demands associated with navigating large, complexly bonded social groups are thought to have significantly shaped human brain evolution. Yet, research on social network representation and cognitive neuroscience have progressed largely independently. Thus, little is known about how the human brain encodes the structure of the social networks in which it is embedded. This review highlights recent work seeking to bridge this gap in understanding. While the majority of research linking social network analysis and neuroimaging has focused on relating neuroanatomy to social network size, researchers have begun to define the neural architecture that encodes social network structure, cognitive and behavioral consequences of encoding this information, and individual differences in how people represent the structure of their social world. Copyright © 2018 Elsevier Ltd. All rights reserved.

Neuronal factors determining high intelligence.

PubMed

Dicke, Ursula; Roth, Gerhard

2016-01-05

Many attempts have been made to correlate degrees of both animal and human intelligence with brain properties. With respect to mammals, a much-discussed trait concerns absolute and relative brain size, either uncorrected or corrected for body size. However, the correlation of both with degrees of intelligence yields large inconsistencies, because although they are regarded as the most intelligent mammals, monkeys and apes, including humans, have neither the absolutely nor the relatively largest brains. The best fit between brain traits and degrees of intelligence among mammals is reached by a combination of the number of cortical neurons, neuron packing density, interneuronal distance and axonal conduction velocity--factors that determine general information processing capacity (IPC), as reflected by general intelligence. The highest IPC is found in humans, followed by the great apes, Old World and New World monkeys. The IPC of cetaceans and elephants is much lower because of a thin cortex, low neuron packing density and low axonal conduction velocity. By contrast, corvid and psittacid birds have very small and densely packed pallial neurons and relatively many neurons, which, despite very small brain volumes, might explain their high intelligence. The evolution of a syntactical and grammatical language in humans most probably has served as an additional intelligence amplifier, which may have happened in songbirds and psittacids in a convergent manner. © 2015 The Author(s).

Genetic and neurodevelopmental influences in autistic disorder.

PubMed

Nicolson, Rob; Szatmari, Peter

2003-09-01

In the past, autism was considered to be largely psychogenic. However, research in the last 2 decades indicates that autism is largely caused by genetic factors that lead to abnormal brain development. This article reviews research into the genetic and neurodevelopmental factors underlying autism. We review the findings from genetic and brain-imaging studies of autism over the past 15 years and synthesize these findings as a guide for future research. Genome scans and association studies have suggested potential genomic regions and genes, respectively, that may be involved in the etiology of autism, and there have been some replications of these results. Similarly, the findings that brain volume is exaggerated in autism and corpus callosum size is reduced have also been independently replicated. Unfortunately, studies of other subcortical structures remain inconclusive or contradictory. Overwhelming evidence now supports a neurobiological basis for autism. However, further refinements will be needed to guide future studies, particularly to identify the most informative phenotypes to investigate. Additionally, studies examining the role of genetic factors in the brain abnormalities underlying autism will likely lead to further findings that will enhance our understanding of autism's causes.

Electrophysiological property and chemical sensitivity of primary afferent neurons that innervate rat whisker hair follicles.

PubMed

Ikeda, Ryo; Gu, Jianguo

2016-01-01

Whisker hair follicles are sensory organs that sense touch and perform tactile discrimination in animals, and they are sites where sensory impulses are initiated when whisker hairs touch an object. The sensory signals are then conveyed by whisker afferent fibers to the brain for sensory perception. Electrophysiological property and chemical sensitivity of whisker afferent fibers, important factors affecting whisker sensory processing, are largely not known. In the present study, we performed patch-clamp recordings from pre-identified whisker afferent neurons in whole-mount trigeminal ganglion preparations and characterized their electrophysiological property and sensitivity to ATP, serotonin and glutamate. Of 97 whisker afferent neurons examined, 67% of them are found to be large-sized (diameter ≥45 µm) cells and 33% of them are medium- to small-sized (diameter <45 µm) cells. Almost every large-sized whisker afferent neuron fires a single action potential but many (40%) small/medium-sized whisker afferent neurons fire multiple action potentials in response to prolonged stepwise depolarization. Other electrophysiological properties including resting membrane potential, action potential threshold, and membrane input resistance are also significantly different between large-sized and small/medium-sized whisker afferent neurons. Most large-sized and many small/medium-sized whisker afferent neurons are sensitive to ATP and/or serotonin, and ATP and/or serotonin could evoke strong inward currents in these cells. In contrast, few whisker afferent neurons are sensitive to glutamate. Our results raise a possibility that ATP and/or serotonin may be chemical messengers involving sensory signaling for different types of rat whisker afferent fibers.

Estrogen regulation of microcephaly genes and evolution of brain sexual dimorphism in primates.

PubMed

Shi, Lei; Lin, Qiang; Su, Bing

2015-06-30

Sexual dimorphism in brain size is common among primates, including humans, apes and some Old World monkeys. In these species, the brain size of males is generally larger than that of females. Curiously, this dimorphism has persisted over the course of primate evolution and human origin, but there is no explanation for the underlying genetic controls that have maintained this disparity in brain size. In the present study, we tested the effect of the female hormone (estradiol) on seven genes known to be related to brain size in both humans and nonhuman primates, and we identified half estrogen responsive elements (half EREs) in the promoter regions of four genes (MCPH1, ASPM, CDK5RAP2 and WDR62). Likewise, at sequence level, it appears that these half EREs are generally conserved across primates. Later testing via a reporter gene assay and cell-based endogenous expression measurement revealed that estradiol could significantly suppress the expression of the four affected genes involved in brain size. More intriguingly, when the half EREs were deleted from the promoters, the suppression effect disappeared, suggesting that the half EREs mediate the regulation of estradiol on the brain size genes. We next replicated these experiments using promoter sequences from chimpanzees and rhesus macaques, and observed a similar suppressive effect of estradiol on gene expression, suggesting that this mechanism is conserved among primate species that exhibit brain size dimorphism. Brain size dimorphism among certain primates, including humans, is likely regulated by estrogen through its sex-dependent suppression of brain size genes during development.

Diurnal fluctuations in brain volume: Statistical analyses of MRI from large populations.

PubMed

Nakamura, Kunio; Brown, Robert A; Narayanan, Sridar; Collins, D Louis; Arnold, Douglas L

2015-09-01

We investigated fluctuations in brain volume throughout the day using statistical modeling of magnetic resonance imaging (MRI) from large populations. We applied fully automated image analysis software to measure the brain parenchymal fraction (BPF), defined as the ratio of the brain parenchymal volume and intracranial volume, thus accounting for variations in head size. The MRI data came from serial scans of multiple sclerosis (MS) patients in clinical trials (n=755, 3269 scans) and from subjects participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI, n=834, 6114 scans). The percent change in BPF was modeled with a linear mixed effect (LME) model, and the model was applied separately to the MS and ADNI datasets. The LME model for the MS datasets included random subject effects (intercept and slope over time) and fixed effects for the time-of-day, time from the baseline scan, and trial, which accounted for trial-related effects (for example, different inclusion criteria and imaging protocol). The model for ADNI additionally included the demographics (baseline age, sex, subject type [normal, mild cognitive impairment, or Alzheimer's disease], and interaction between subject type and time from baseline). There was a statistically significant effect of time-of-day on the BPF change in MS clinical trial datasets (-0.180 per day, that is, 0.180% of intracranial volume, p=0.019) as well as the ADNI dataset (-0.438 per day, that is, 0.438% of intracranial volume, p<0.0001), showing that the brain volume is greater in the morning. Linearly correcting the BPF values with the time-of-day reduced the required sample size to detect a 25% treatment effect (80% power and 0.05 significance level) on change in brain volume from 2 time-points over a period of 1year by 2.6%. Our results have significant implications for future brain volumetric studies, suggesting that there is a potential acquisition time bias that should be randomized or statistically controlled to account for the day-to-day brain volume fluctuations. Copyright © 2015 Elsevier Inc. All rights reserved.

Signal Sampling for Efficient Sparse Representation of Resting State FMRI Data

PubMed Central

Ge, Bao; Makkie, Milad; Wang, Jin; Zhao, Shijie; Jiang, Xi; Li, Xiang; Lv, Jinglei; Zhang, Shu; Zhang, Wei; Han, Junwei; Guo, Lei; Liu, Tianming

2015-01-01

As the size of brain imaging data such as fMRI grows explosively, it provides us with unprecedented and abundant information about the brain. How to reduce the size of fMRI data but not lose much information becomes a more and more pressing issue. Recent literature studies tried to deal with it by dictionary learning and sparse representation methods, however, their computation complexities are still high, which hampers the wider application of sparse representation method to large scale fMRI datasets. To effectively address this problem, this work proposes to represent resting state fMRI (rs-fMRI) signals of a whole brain via a statistical sampling based sparse representation. First we sampled the whole brain’s signals via different sampling methods, then the sampled signals were aggregate into an input data matrix to learn a dictionary, finally this dictionary was used to sparsely represent the whole brain’s signals and identify the resting state networks. Comparative experiments demonstrate that the proposed signal sampling framework can speed-up by ten times in reconstructing concurrent brain networks without losing much information. The experiments on the 1000 Functional Connectomes Project further demonstrate its effectiveness and superiority. PMID:26646924

A Dictionary Learning Approach for Signal Sampling in Task-Based fMRI for Reduction of Big Data

PubMed Central

Ge, Bao; Li, Xiang; Jiang, Xi; Sun, Yifei; Liu, Tianming

2018-01-01

The exponential growth of fMRI big data offers researchers an unprecedented opportunity to explore functional brain networks. However, this opportunity has not been fully explored yet due to the lack of effective and efficient tools for handling such fMRI big data. One major challenge is that computing capabilities still lag behind the growth of large-scale fMRI databases, e.g., it takes many days to perform dictionary learning and sparse coding of whole-brain fMRI data for an fMRI database of average size. Therefore, how to reduce the data size but without losing important information becomes a more and more pressing issue. To address this problem, we propose a signal sampling approach for significant fMRI data reduction before performing structurally-guided dictionary learning and sparse coding of whole brain's fMRI data. We compared the proposed structurally guided sampling method with no sampling, random sampling and uniform sampling schemes, and experiments on the Human Connectome Project (HCP) task fMRI data demonstrated that the proposed method can achieve more than 15 times speed-up without sacrificing the accuracy in identifying task-evoked functional brain networks. PMID:29706880

A Dictionary Learning Approach for Signal Sampling in Task-Based fMRI for Reduction of Big Data.

PubMed

Ge, Bao; Li, Xiang; Jiang, Xi; Sun, Yifei; Liu, Tianming

2018-01-01

The exponential growth of fMRI big data offers researchers an unprecedented opportunity to explore functional brain networks. However, this opportunity has not been fully explored yet due to the lack of effective and efficient tools for handling such fMRI big data. One major challenge is that computing capabilities still lag behind the growth of large-scale fMRI databases, e.g., it takes many days to perform dictionary learning and sparse coding of whole-brain fMRI data for an fMRI database of average size. Therefore, how to reduce the data size but without losing important information becomes a more and more pressing issue. To address this problem, we propose a signal sampling approach for significant fMRI data reduction before performing structurally-guided dictionary learning and sparse coding of whole brain's fMRI data. We compared the proposed structurally guided sampling method with no sampling, random sampling and uniform sampling schemes, and experiments on the Human Connectome Project (HCP) task fMRI data demonstrated that the proposed method can achieve more than 15 times speed-up without sacrificing the accuracy in identifying task-evoked functional brain networks.

Smart Moves: Effects of Relative Brain Size on Establishment Success of Invasive Amphibians and Reptiles

PubMed Central

Amiel, Joshua J.; Tingley, Reid; Shine, Richard

2011-01-01

Brain size relative to body size varies considerably among animals, but the ecological consequences of that variation remain poorly understood. Plausibly, larger brains confer increased behavioural flexibility, and an ability to respond to novel challenges. In keeping with that hypothesis, successful invasive species of birds and mammals that flourish after translocation to a new area tend to have larger brains than do unsuccessful invaders. We found the same pattern in ectothermic terrestrial vertebrates. Brain size relative to body size was larger in species of amphibians and reptiles reported to be successful invaders, compared to species that failed to thrive after translocation to new sites. This pattern was found in six of seven global biogeographic realms; the exception (where relatively larger brains did not facilitate invasion success) was Australasia. Establishment success was also higher in amphibian and reptile families with larger relative brain sizes. Future work could usefully explore whether invasion success is differentially associated with enlargement of specific parts of the brain (as predicted by the functional role of the forebrain in promoting behavioural flexibility), or with a general size increase (suggesting that invasion success is facilitated by enhanced perceptual and motor skills, as well as cognitive ability). PMID:21494328

Smart moves: effects of relative brain size on establishment success of invasive amphibians and reptiles.

PubMed

Amiel, Joshua J; Tingley, Reid; Shine, Richard

2011-04-06

Brain size relative to body size varies considerably among animals, but the ecological consequences of that variation remain poorly understood. Plausibly, larger brains confer increased behavioural flexibility, and an ability to respond to novel challenges. In keeping with that hypothesis, successful invasive species of birds and mammals that flourish after translocation to a new area tend to have larger brains than do unsuccessful invaders. We found the same pattern in ectothermic terrestrial vertebrates. Brain size relative to body size was larger in species of amphibians and reptiles reported to be successful invaders, compared to species that failed to thrive after translocation to new sites. This pattern was found in six of seven global biogeographic realms; the exception (where relatively larger brains did not facilitate invasion success) was Australasia. Establishment success was also higher in amphibian and reptile families with larger relative brain sizes. Future work could usefully explore whether invasion success is differentially associated with enlargement of specific parts of the brain (as predicted by the functional role of the forebrain in promoting behavioural flexibility), or with a general size increase (suggesting that invasion success is facilitated by enhanced perceptual and motor skills, as well as cognitive ability).

Non-invasive brain stimulation in Parkinson's disease: Exploiting crossroads of cognition and mood.

PubMed

Dinkelbach, Lars; Brambilla, Michela; Manenti, Rosa; Brem, Anna-Katharine

2017-04-01

Cognitive impairments and depression are common non-motor manifestations in Parkinson's disease (PD). Recent evidence suggests that both partially arise via the same frontostriatal network, opening the opportunity for concomitant treatment with non-invasive brain stimulation (NIBS) techniques such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). In this systematic review, we evaluate the effects of NIBS on cognition and/or mood in 19 placebo-controlled studies involving 561 PD patients. Outcomes depended on the area stimulated and the technique used. rTMS over the dorsolateral-prefrontal cortex (DLPFC) resulted in significant reductions in scores of depressive symptoms with moderate to large effect sizes along with increased performance in several tests of cognitive functions. tDCS over the DLPFC improved performance in several cognitive measures, including executive functions with large effect sizes. Additional effects of tDCS on mood were not detectable; however, only non-depressed patients were assessed. Further confirmatory research is needed to clarify the contribution that NIBS could make in the care of PD patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Humans use compression heuristics to improve the recall of social networks.

PubMed

Brashears, Matthew E

2013-01-01

The ability of primates, including humans, to maintain large social networks appears to depend on the ratio of the neocortex to the rest of the brain. However, observed human network size frequently exceeds predictions based on this ratio (e.g., "Dunbar's Number"), implying that human networks are too large to be cognitively managed. Here I show that humans adaptively use compression heuristics to allow larger amounts of social information to be stored in the same brain volume. I find that human adults can remember larger numbers of relationships in greater detail when a network exhibits triadic closure and kin labels than when it does not. These findings help to explain how humans manage large and complex social networks with finite cognitive resources and suggest that many of the unusual properties of human social networks are rooted in the strategies necessary to cope with cognitive limitations.

The effect of brain size evolution on feeding propensity, digestive efficiency, and juvenile growth

PubMed Central

Kotrschal, Alexander; Corral‐Lopez, Alberto; Szidat, Sönke; Kolm, Niclas

2015-01-01

One key hypothesis in the study of brain size evolution is the expensive tissue hypothesis; the idea that increased investment into the brain should be compensated by decreased investment into other costly organs, for instance the gut. Although the hypothesis is supported by both comparative and experimental evidence, little is known about the potential changes in energetic requirements or digestive traits following such evolutionary shifts in brain and gut size. Organisms may meet the greater metabolic requirements of larger brains despite smaller guts via increased food intake or better digestion. But increased investment in the brain may also hamper somatic growth. To test these hypotheses we here used guppy (Poecilia reticulata) brain size selection lines with a pronounced negative association between brain and gut size and investigated feeding propensity, digestive efficiency (DE), and juvenile growth rate. We did not find any difference in feeding propensity or DE between large‐ and small‐brained individuals. Instead, we found that large‐brained females had slower growth during the first 10 weeks after birth. Our study provides experimental support that investment into larger brains at the expense of gut tissue carries costs that are not necessarily compensated by a more efficient digestive system. PMID:26420573

Gut Microbes and the Brain: Paradigm Shift in Neuroscience

PubMed Central

Knight, Rob; Mazmanian, Sarkis K.; Cryan, John F.; Tillisch, Kirsten

2014-01-01

The discovery of the size and complexity of the human microbiome has resulted in an ongoing reevaluation of many concepts of health and disease, including diseases affecting the CNS. A growing body of preclinical literature has demonstrated bidirectional signaling between the brain and the gut microbiome, involving multiple neurocrine and endocrine signaling mechanisms. While psychological and physical stressors can affect the composition and metabolic activity of the gut microbiota, experimental changes to the gut microbiome can affect emotional behavior and related brain systems. These findings have resulted in speculation that alterations in the gut microbiome may play a pathophysiological role in human brain diseases, including autism spectrum disorder, anxiety, depression, and chronic pain. Ongoing large-scale population-based studies of the gut microbiome and brain imaging studies looking at the effect of gut microbiome modulation on brain responses to emotion-related stimuli are seeking to validate these speculations. This article is a summary of emerging topics covered in a symposium and is not meant to be a comprehensive review of the subject. PMID:25392516

Development of induced glioblastoma by implantation of a human xenograft in Yucatan minipig as a large animal model.

PubMed

Khoshnevis, Mehrdad; Carozzo, Claude; Bonnefont-Rebeix, Catherine; Belluco, Sara; Leveneur, Olivia; Chuzel, Thomas; Pillet-Michelland, Elodie; Dreyfus, Matthieu; Roger, Thierry; Berger, François; Ponce, Frédérique

2017-04-15

Glioblastoma is the most common and deadliest primary brain tumor for humans. Despite many efforts toward the improvement of therapeutic methods, prognosis is poor and the disease remains incurable with a median survival of 12-14.5 months after an optimal treatment. To develop novel treatment modalities for this fatal disease, new devices must be tested on an ideal animal model before performing clinical trials in humans. A new model of induced glioblastoma in Yucatan minipigs was developed. Nine immunosuppressed minipigs were implanted with the U87 human glioblastoma cell line in both the left and right hemispheres. Computed tomography (CT) acquisitions were performed once a week to monitor tumor growth. Among the 9 implanted animals, 8 minipigs showed significant macroscopic tumors on CT acquisitions. Histological examination of the brain after euthanasia confirmed the CT imaging findings with the presence of an undifferentiated glioma. Yucatan minipig, given its brain size and anatomy (gyrencephalic structure) which are comparable to humans, provides a reliable brain tumor model for preclinical studies of different therapeutic METHODS: in realistic conditions. Moreover, the short development time, the lower cyclosporine and caring cost and the compatibility with the size of commercialized stereotactic frames make it an affordable and practical animal model, especially in comparison with large breed pigs. This reproducible glioma model could simulate human anatomical conditions in preclinical studies and facilitate the improvement of novel therapeutic devices, designed at the human scale from the outset. Copyright © 2017 Elsevier B.V. All rights reserved.

Engagement of large-scale networks is related to individual differences in inhibitory control

PubMed Central

Congdon, Eliza; Mumford, Jeanette A.; Cohen, Jessica R.; Galvan, Adriana; Aron, Adam R.; Xue, Gui; Miller, Eric; Poldrack, Russell A.

2010-01-01

Understanding which brain regions regulate the execution, and suppression, of goal-directed behavior has implications for a number of areas of research. In particular, understanding which brain regions engaged during tasks requiring the execution and inhibition of a motor response provides insight into the mechanisms underlying individual differences in response inhibition ability. However, neuroimaging studies examing the relation between activation and stopping have been inconsistent regarding the direction of the relationship, and also regarding the anatomical location of regions that correlate with behavior. These limitations likely arise from the relatively low power of vox-elwise correlations with small sample sizes. Here, we pooled data over five separate fMRI studies of the Stop-signal task in order to obtain a sufficiently large sample size to robustly detect brain/behavior correlations. In addition, rather than performing mass univariate correlation analysis across all voxels, we increased statistical power by reducing the dimensionality of the data set using independent components analysis and then examined correlations between behavior and the resulting component scores. We found that components reflecting activity in regions thought to be involved in stopping were associated with better stopping ability, while activity in a default-mode network was associated with poorer stopping ability across individuals. These results clearly show a relationship between individual differences in stopping ability in specific activated networks, including regions known to be critical for the behavior. The results also highlight the usefulness of using dimensionality reduction to increase the power to detect brain/behavior correlations in individual differences research. PMID:20600962

Classification of brain MRI with big data and deep 3D convolutional neural networks

NASA Astrophysics Data System (ADS)

Wegmayr, Viktor; Aitharaju, Sai; Buhmann, Joachim

2018-02-01

Our ever-aging society faces the growing problem of neurodegenerative diseases, in particular dementia. Magnetic Resonance Imaging provides a unique tool for non-invasive investigation of these brain diseases. However, it is extremely difficult for neurologists to identify complex disease patterns from large amounts of three-dimensional images. In contrast, machine learning excels at automatic pattern recognition from large amounts of data. In particular, deep learning has achieved impressive results in image classification. Unfortunately, its application to medical image classification remains difficult. We consider two reasons for this difficulty: First, volumetric medical image data is considerably scarcer than natural images. Second, the complexity of 3D medical images is much higher compared to common 2D images. To address the problem of small data set size, we assemble the largest dataset ever used for training a deep 3D convolutional neural network to classify brain images as healthy (HC), mild cognitive impairment (MCI) or Alzheimers disease (AD). We use more than 20.000 images from subjects of these three classes, which is almost 9x the size of the previously largest data set. The problem of high dimensionality is addressed by using a deep 3D convolutional neural network, which is state-of-the-art in large-scale image classification. We exploit its ability to process the images directly, only with standard preprocessing, but without the need for elaborate feature engineering. Compared to other work, our workflow is considerably simpler, which increases clinical applicability. Accuracy is measured on the ADNI+AIBL data sets, and the independent CADDementia benchmark.

Normative brain size variation and brain shape diversity in humans.

PubMed

Reardon, P K; Seidlitz, Jakob; Vandekar, Simon; Liu, Siyuan; Patel, Raihaan; Park, Min Tae M; Alexander-Bloch, Aaron; Clasen, Liv S; Blumenthal, Jonathan D; Lalonde, Francois M; Giedd, Jay N; Gur, Ruben C; Gur, Raquel E; Lerch, Jason P; Chakravarty, M Mallar; Satterthwaite, Theodore D; Shinohara, Russell T; Raznahan, Armin

2018-06-15

Brain size variation over primate evolution and human development is associated with shifts in the proportions of different brain regions. Individual brain size can vary almost twofold among typically developing humans, but the consequences of this for brain organization remain poorly understood. Using in vivo neuroimaging data from more than 3000 individuals, we find that larger human brains show greater areal expansion in distributed frontoparietal cortical networks and related subcortical regions than in limbic, sensory, and motor systems. This areal redistribution recapitulates cortical remodeling across evolution, manifests by early childhood in humans, and is linked to multiple markers of heightened metabolic cost and neuronal connectivity. Thus, human brain shape is systematically coupled to naturally occurring variations in brain size through a scaling map that integrates spatiotemporally diverse aspects of neurobiology. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

The ventricles of the brain in the N. American mink (Mustela vison (Brisson, 1756)).

PubMed

Gościcka, D; Stankiewicz, W; Szpinda, M

1993-01-01

Using anatomical as well as radiographic and tomographic methods, sixty brains of the N. American mink were examined. It was found that the brain consists of four ventricles. Also, it was noted that the posterior horn was missing and that there was the olfactory recess present in the lateral ventricle, a large-size interthalamic connection present in the third ventricle, and a flat, necklace-like bottom in the fourth ventricle. Only recently, the ins and outs of the mink's anatomical structure have begun to absorb anatomists. Apparently, it is related to the fact that furry animals, among them the mink, are being domesticated as if "before our eyes". For this reason and because of the easy access to material, examining of the brain ventricles in the mink was taken up.

Aging and unusual catecholamine-containing structures in the mouse brain.

PubMed

Masuoka, D T; Jonsson, G; Finch, C E

1979-06-22

Brains of C57BL/6J mice, aged 4, 8 and 20--29 months, were examined by the Falck-Hillarp histochemical fluorescence technique. Numerous large, intensely fluorescent green to yellow-green spots (LIFS) were observed in the brains of senescent mice. LIFS were generally round to ovoid in shape and ranged in size from about 10 micrometer to about 30 micrometer. Histochemical and pharmacological procedures and spectral analysis indicated that the formaldehyde-induced fluorescence of the LIFS was due to the presence of catecholamines (CA) rather than aging pigment. Their distribution in the brain suggests an association with nerve axons or terminals rather than cell bodies. The number of LIFS in the hypothalamus increased progressively during aging. It is proposed that LIFS may represent age-related, unusual CA accumulation in enlargements proximal to axonal or terminal portions undergoing spontaneous degeneration.

Large-for-size liver transplant: a single-center experience.

PubMed

Akdur, Aydincan; Kirnap, Mahir; Ozcay, Figen; Sezgin, Atilla; Ayvazoglu Soy, Hatice Ebru; Karakayali Yarbug, Feza; Yildirim, Sedat; Moray, Gokhan; Arslan, Gulnaz; Haberal, Mehmet

2015-04-01

The ideal ratio between liver transplant graft mass and recipient body weight is unknown, but the graft probably must weigh 0.8% to 2.0% recipient weight. When this ratio > 4%, there may be problems due to large-for-size transplant, especially in recipients < 10 kg. This condition is caused by discrepancy between the small abdominal cavity and large graft and is characterized by decreased blood supply to the liver graft and graft dysfunction. We evaluated our experience with large-for-size grafts. We retrospectively evaluated 377 orthotopic liver transplants that were performed from 2001-2014 in our center. We included 188 pediatric transplants in our study. There were 58 patients < 10 kg who had living-donor living transplant with graft-to-bodyweight ratio > 4%. In 2 patients, the abdomen was closed with a Bogota bag. In 5 patients, reoperation was performed due to vascular problems and abdominal hypertension, and the abdomen was closed with a Bogota bag. All Bogota bags were closed in 2 weeks. After closing the fascia, 10 patients had vascular problems that were diagnosed in the operating room by Doppler ultrasonography, and only the skin was closed without fascia closure. No graft loss occurred due to large-for-size transplant. There were 8 patients who died early after transplant (sepsis, 6 patients; brain death, 2 patients). There was no major donor morbidity or donor mortality. Large-for-size graft may cause abdominal compartment syndrome due to the small size of the recipient abdominal cavity, size discrepancies in vascular caliber, insufficient portal circulation, and disturbance of tissue oxygenation. Abdominal closure with a Bogota bag in these patients is safe and effective to avoid abdominal compartment syndrome. Early diagnosis by ultrasonography in the operating room after fascia closure and repeated ultrasonography at the clinic may help avoid graft loss.

The adaptive significance of adult neurogenesis: an integrative approach

PubMed Central

Konefal, Sarah; Elliot, Mick; Crespi, Bernard

2013-01-01

Adult neurogenesis in mammals is predominantly restricted to two brain regions, the dentate gyrus (DG) of the hippocampus and the olfactory bulb (OB), suggesting that these two brain regions uniquely share functions that mediate its adaptive significance. Benefits of adult neurogenesis across these two regions appear to converge on increased neuronal and structural plasticity that subserves coding of novel, complex, and fine-grained information, usually with contextual components that include spatial positioning. By contrast, costs of adult neurogenesis appear to center on potential for dysregulation resulting in higher risk of brain cancer or psychological dysfunctions, but such costs have yet to be quantified directly. The three main hypotheses for the proximate functions and adaptive significance of adult neurogenesis, pattern separation, memory consolidation, and olfactory spatial, are not mutually exclusive and can be reconciled into a simple general model amenable to targeted experimental and comparative tests. Comparative analysis of brain region sizes across two major social-ecological groups of primates, gregarious (mainly diurnal haplorhines, visually-oriented, and in large social groups) and solitary (mainly noctural, territorial, and highly reliant on olfaction, as in most rodents) suggest that solitary species, but not gregarious species, show positive associations of population densities and home range sizes with sizes of both the hippocampus and OB, implicating their functions in social-territorial systems mediated by olfactory cues. Integrated analyses of the adaptive significance of adult neurogenesis will benefit from experimental studies motivated and structured by ecologically and socially relevant selective contexts. PMID:23882188

The costs and benefits of flexibility as an expression of behavioural plasticity: a primate perspective.

PubMed

van Schaik, Carel P

2013-05-19

Traditional neo-Darwinism ascribes geographical variation in morphology or in behaviour to varying selection on local genotypes. However, mobile and long-lived organisms cannot achieve local adaptation this way, leading to a renewed interest in plasticity. I examined geographical variation in orang-utan subsistence and social behaviour, and found this to be largely owing to behavioural plasticity, here called flexibility, both in the form of flexible individual decisions and of socially transmitted (cultural) innovations. Although comparison with other species is difficult, the extent of such flexibility is almost certainly limited by brain size. It is shown that brains can only increase relative to body size where the cognitive benefits they produce are reliably translated into improved survival rate. This means that organisms that are very small, face many predators, live in highly seasonal environments, or lack opportunities for social learning cannot evolve greater flexibility, and must achieve local adaptation through selection on specific genotypes. On the other hand, as body and brain size increase, local adaptation is increasingly achieved through selection on plasticity. The species involved are also generally those that most need it, being more mobile and longer-lived. Although high plasticity buffers against environmental change, the most flexible organisms face a clear limit because they respond slowly to selection. Thus, paradoxically, the largest-brained animals may actually be vulnerable to the more drastic forms of environmental change, such as those induced by human actions.

Multisession stereotactic radiosurgery for large benign brain tumors of >3cm- early clinical outcomes

PubMed Central

Memon, Muhammad Ali; Ahmed, Usman; Saleem, Muhammad Abid; Bhatti, Amer Iqtidar; Ahmed, Naveed; Hashim, Abdul Sattar M.

2012-01-01

Objective To evaluate the clinical outcome of linear accelerator based multisession stereotactic radiosurgery (SRS) for large benign brain tumors of >3cm. Methods Between June 2009 and May 2011, 35 patients having large benign brain tumors of >3cm (≥15 cm3) were treated by multisession stereotactic radiosurgery. This retrospective study was carried out at Neurospinal & Medical Institute Karachi. There were 17 (48.6 %) males and 18(51.4 %) females. Median age was 36 years (range: 13-65 years). Median target volume was 49.4 cm3 (range: 15-184 cm3). The median marginal dose was 25 Gy (range: 20–27.5Gy) prescribed to a median 75% isodose line (range: 65-100 %). Median number of 5 fractions were used ranging 3-5 fractions. Results All the patients tolerated treatment very well. 21 (58.3%) patients had remarkable clinical improvement of neurological symptoms, 14 (38.9%) patients had stable symptoms, and only one patient had transient worsening of symptoms. No permanent neurological damage or radiation injury was seen. Radiologically, 9 (25.7%) patients achieved reduction in size of the tumor, 26(74.3 %) patients were having stable disease, and overall control rate was found to be 100 %. Median follow-up time from the end of SRS was 6.4 months (range: 1-22.5months). Conclusion Linear accelerator based multisession stereotactic radiosurgery for large benign brain tumors of >3cm is effective and well tolerated. PMID:29296340

The impact of brain size on pilot performance varies with aviation training and years of education

PubMed Central

Adamson, Maheen M.; Samarina, Viktoriya; Xiangyan, Xu; Huynh, Virginia; Kennedy, Quinn; Weiner, Michael; Yesavage, Jerome; Taylor, Joy L.

2010-01-01

Previous studies have consistently reported age-related changes in cognitive abilities and brain structure. Previous studies also suggest compensatory roles for specialized training, skill, and years of education in the age-related decline of cognitive function. The Stanford/VA Aviation Study examines the influence of specialized training and skill level (expertise) on age-related changes in cognition and brain structure. This preliminary report examines the effect of aviation expertise, years of education, age, and brain size on flight simulator performance in pilots aged 45–68 years. Fifty-one pilots were studied with structural magnetic resonance imaging, flight simulator, and processing speed tasks. There were significant main effects of age (p < .01) and expertise (p < .01), but not of whole brain size (p > .1) or education (p > .1), on flight simulator performance. However, even though age and brain size were correlated (r = −0.41), age differences in flight simulator performance were not explained by brain size. Both aviation expertise and education were involved in an interaction with brain size in predicting flight simulator performance (p < .05). These results point to the importance of examining measures of expertise and their interactions to assess age-related cognitive changes. PMID:20193103

Sociability and brain development in BALB/cJ and C57BL/6J mice.

PubMed

Fairless, Andrew H; Dow, Holly C; Kreibich, Arati Sadalge; Torre, Matthew; Kuruvilla, Mariyam; Gordon, Elliot; Morton, Elizabeth A; Tan, Junhao; Berrettini, Wade H; Li, Hongzhe; Abel, Ted; Brodkin, Edward S

2012-03-17

Sociability--the tendency to seek social interaction--propels the development of social cognition and social skills, but is disrupted in autism spectrum disorders (ASD). BALB/cJ and C57BL/6J inbred mouse strains are useful models of low and high levels of juvenile sociability, respectively, but the neurobiological and developmental factors that account for the strains' contrasting sociability levels are largely unknown. We hypothesized that BALB/cJ mice would show increasing sociability with age but that C57BL/6J mice would show high sociability throughout development. We also hypothesized that littermates would resemble one another in sociability more than non-littermates. Finally, we hypothesized that low sociability would be associated with low corpus callosum size and increased brain size in BALB/cJ mice. Separate cohorts of C57BL/6J and BALB/cJ mice were tested for sociability at 19-, 23-, 31-, 42-, or 70-days-of-age, and brain weights and mid-sagittal corpus callosum area were measured. BALB/cJ sociability increased with age, and a strain by age interaction in sociability between 31 and 42 days of age suggested strong effects of puberty on sociability development. Sociability scores clustered according to litter membership in both strains, and perinatal litter size and sex ratio were identified as factors that contributed to this clustering in C57BL/6J, but not BALB/cJ, litters. There was no association between corpus callosum size and sociability, but smaller brains were associated with lower sociability in BALB/cJ mice. The associations reported here will provide directions for future mechanistic studies of sociability development. Copyright © 2011 Elsevier B.V. All rights reserved.

Sociability and brain development in BALB/cJ and C57BL/6J mice

PubMed Central

Fairless, Andrew H.; Dow, Holly C.; Kreibich, Arati Sadalge; Torre, Matthew; Kuruvilla, Mariyam; Gordon, Elliot; Morton, Elizabeth A.; Tan, Junhao; Berrettini, Wade H.; Li, Hongzhe; Abel, Ted; Brodkin, Edward S.

2012-01-01

Sociability—the tendency to seek social interaction–propels the development of social cognition and social skills, but is disrupted in autism spectrum disorders (ASD). BALB/cJ and C57BL/6J inbred mouse strains are useful models of low and high levels of juvenile sociability, respectively, but the neurobiological and developmental factors that account for the strains’ contrasting sociability levels are largely unknown. We hypothesized that BALB/cJ mice would show increasing sociability with age but that C57BL/6J mice would show high sociability throughout development. We also hypothesized that littermates would resemble one another in sociability more than non-littermates. Finally, we hypothesized that low sociability would be associated with low corpus callosum size and increased brain size in BALB/cJ mice. Separate cohorts of C57BL/6J and BALB/cJ mice were tested for sociability at 19-, 23-, 31-, 42-, or 70-days-of-age, and brain weights and mid-sagittal corpus callosum area were measured. BALB/cJ sociability increased with age, and a strain by age interaction in sociability between 31 and 42 days of age suggested strong effects of puberty on sociability development. Sociability scores clustered according to litter membership in both strains, and perinatal litter size and sex ratio were identified as factors that contributed to this clustering in C57BL/6J, but not BALB/cJ, litters. There was no association between corpus callosum size and sociability, but smaller brains were associated with lower sociability in BALB/cJ mice. The associations reported here will provide directions for future mechanistic studies of sociability development. PMID:22178318

Brain size and visual environment predict species differences in paper wasp sensory processing brain regions (hymenoptera: vespidae, polistinae).

PubMed

O'Donnell, Sean; Clifford, Marie R; DeLeon, Sara; Papa, Christopher; Zahedi, Nazaneen; Bulova, Susan J

2013-01-01

The mosaic brain evolution hypothesis predicts that the relative volumes of functionally distinct brain regions will vary independently and correlate with species' ecology. Paper wasp species (Hymenoptera: Vespidae, Polistinae) differ in light exposure: they construct open versus enclosed nests and one genus (Apoica) is nocturnal. We asked whether light environments were related to species differences in the size of antennal and optic processing brain tissues. Paper wasp brains have anatomically distinct peripheral and central regions that process antennal and optic sensory inputs. We measured the volumes of 4 sensory processing brain regions in paper wasp species from 13 Neotropical genera including open and enclosed nesters, and diurnal and nocturnal species. Species differed in sensory region volumes, but there was no evidence for trade-offs among sensory modalities. All sensory region volumes correlated with brain size. However, peripheral optic processing investment increased with brain size at a higher rate than peripheral antennal processing investment. Our data suggest that mosaic and concerted (size-constrained) brain evolution are not exclusive alternatives. When brain regions increase with brain size at different rates, these distinct allometries can allow for differential investment among sensory modalities. As predicted by mosaic evolution, species ecology was associated with some aspects of brain region investment. Nest architecture variation was not associated with brain investment differences, but the nocturnal genus Apoica had the largest antennal:optic volume ratio in its peripheral sensory lobes. Investment in central processing tissues was not related to nocturnality, a pattern also noted in mammals. The plasticity of neural connections in central regions may accommodate evolutionary shifts in input from the periphery with relatively minor changes in volume. © 2013 S. Karger AG, Basel.

Evolution of brain and culture: the neurological and cognitive journey from Australopithecus to Albert Einstein.

PubMed

Falk, Dean

2016-06-20

Fossil and comparative primatological evidence suggest that alterations in the development of prehistoric hominin infants kindled three consecutive evolutionary-developmental (evo-devo) trends that, ultimately, paved the way for the evolution of the human brain and cognition. In the earliest trend, infants' development of posture and locomotion became delayed because of anatomical changes that accompanied the prolonged evolution of bipedalism. Because modern humans have inherited these changes, our babies are much slower than other primates to reach developmental milestones such as standing, crawling, and walking. The delay in ancestral babies' physical development eventually precipitated an evolutionary reversal in which they became increasing unable to cling independently to their mothers. For the first time in prehistory, babies were, thus, periodically deprived of direct physical contact with their mothers. This prompted the emergence of a second evo-devo trend in which infants sought contact comfort from caregivers using evolved signals, including new ways of crying that are conserved in modern babies. Such signaling stimulated intense reciprocal interactions between prehistoric mothers and infants that seeded the eventual emergence of motherese and, subsequently, protolanguage. The third trend was for an extreme acceleration in brain growth that began prior to the last trimester of gestation and continued through infants' first postnatal year (early "brain spurt"). Conservation of this trend in modern babies explains why human brains reach adult sizes that are over three times those of chimpanzees. The fossil record of hominin cranial capacities together with comparative neuroanatomical data suggest that, around 3 million years ago, early brain spurts began to facilitate an evolutionary trajectory for increasingly large adult brains in association with neurological reorganization. The prehistoric increase in brain size eventually caused parturition to become exceedingly difficult, and this difficulty, known as the "obstetrical dilemma", is likely to constrain the future evolution of brain size and, thus, privilege ongoing evolution in neurological reorganization. In modern babies, the brain spurt is accompanied by formation and tuning (pruning) of neurological connections, and development of dynamic higher-order networks that facilitate acquisition of grammatical language and, later in development, other advanced computational abilities such as musical or mathematical perception and performance. The cumulative evidence suggests that the emergence and refinement of grammatical language was a prime mover of hominin brain evolution.

Visual Systems for Interactive Exploration and Mining of Large-Scale Neuroimaging Data Archives

PubMed Central

Bowman, Ian; Joshi, Shantanu H.; Van Horn, John D.

2012-01-01

While technological advancements in neuroimaging scanner engineering have improved the efficiency of data acquisition, electronic data capture methods will likewise significantly expedite the populating of large-scale neuroimaging databases. As they do and these archives grow in size, a particular challenge lies in examining and interacting with the information that these resources contain through the development of compelling, user-driven approaches for data exploration and mining. In this article, we introduce the informatics visualization for neuroimaging (INVIZIAN) framework for the graphical rendering of, and dynamic interaction with the contents of large-scale neuroimaging data sets. We describe the rationale behind INVIZIAN, detail its development, and demonstrate its usage in examining a collection of over 900 T1-anatomical magnetic resonance imaging (MRI) image volumes from across a diverse set of clinical neuroimaging studies drawn from a leading neuroimaging database. Using a collection of cortical surface metrics and means for examining brain similarity, INVIZIAN graphically displays brain surfaces as points in a coordinate space and enables classification of clusters of neuroanatomically similar MRI images and data mining. As an initial step toward addressing the need for such user-friendly tools, INVIZIAN provides a highly unique means to interact with large quantities of electronic brain imaging archives in ways suitable for hypothesis generation and data mining. PMID:22536181

Specialization and group size: brain and behavioural correlates of colony size in ants lacking morphological castes

PubMed Central

Amador-Vargas, Sabrina; Gronenberg, Wulfila; Wcislo, William T.; Mueller, Ulrich

2015-01-01

Group size in both multicellular organisms and animal societies can correlate with the degree of division of labour. For ants, the task specialization hypothesis (TSH) proposes that increased behavioural specialization enabled by larger group size corresponds to anatomical specialization of worker brains. Alternatively, the social brain hypothesis proposes that increased levels of social stimuli in larger colonies lead to enlarged brain regions in all workers, regardless of their task specialization. We tested these hypotheses in acacia ants (Pseudomyrmex spinicola), which exhibit behavioural but not morphological task specialization. In wild colonies, we marked, followed and tested ant workers involved in foraging tasks on the leaves (leaf-ants) and in defensive tasks on the host tree trunk (trunk-ants). Task specialization increased with colony size, especially in defensive tasks. The relationship between colony size and brain region volume was task-dependent, supporting the TSH. Specifically, as colony size increased, the relative size of regions within the mushroom bodies of the brain decreased in trunk-ants but increased in leaf-ants; those regions play important roles in learning and memory. Our findings suggest that workers specialized in defence may have reduced learning abilities relative to leaf-ants; these inferences remain to be tested. In societies with monomorphic workers, brain polymorphism enhanced by group size could be a mechanism by which division of labour is achieved. PMID:25567649

Anatomical analysis of an aye-aye brain (Daubentonia madagascariensis, primates: Prosimii) combining histology, structural magnetic resonance imaging, and diffusion-tensor imaging.

PubMed

Kaufman, Jason A; Ahrens, Eric T; Laidlaw, David H; Zhang, Song; Allman, John M

2005-11-01

This report presents initial results of a multimodal analysis of tissue volume and microstructure in the brain of an aye-aye (Daubentonia madagascariensis). The left hemisphere of an aye-aye brain was scanned using T2-weighted structural magnetic resonance imaging (MRI) and diffusion-tensor imaging (DTI) prior to histological processing and staining for Nissl substance and myelinated fibers. The objectives of the experiment were to estimate the volume of gross brain regions for comparison with published data on other prosimians and to validate DTI data on fiber anisotropy with histological measurements of fiber spread. Measurements of brain structure volumes in the specimen are consistent with those reported in the literature: the aye-aye has a very large brain for its body size, a reduced volume of visual structures (V1 and LGN), and an increased volume of the olfactory lobe. This trade-off between visual and olfactory reliance is likely a reflection of the nocturnal extractive foraging behavior practiced by Daubentonia. Additionally, frontal cortex volume is large in the aye-aye, a feature that may also be related to its complex foraging behavior and sensorimotor demands. Analysis of DTI data in the anterior cingulum bundle demonstrates a strong correlation between fiber spread as measured from histological sections and fiber spread as measured from DTI. These results represent the first quantitative comparison of DTI data and fiber-stained histology in the brain. (c) 2005 Wiley-Liss, Inc.

Brain size predicts problem-solving ability in mammalian carnivores

PubMed Central

Benson-Amram, Sarah; Dantzer, Ben; Stricker, Gregory; Swanson, Eli M.; Holekamp, Kay E.

2016-01-01

Despite considerable interest in the forces shaping the relationship between brain size and cognitive abilities, it remains controversial whether larger-brained animals are, indeed, better problem-solvers. Recently, several comparative studies have revealed correlations between brain size and traits thought to require advanced cognitive abilities, such as innovation, behavioral flexibility, invasion success, and self-control. However, the general assumption that animals with larger brains have superior cognitive abilities has been heavily criticized, primarily because of the lack of experimental support for it. Here, we designed an experiment to inquire whether specific neuroanatomical or socioecological measures predict success at solving a novel technical problem among species in the mammalian order Carnivora. We presented puzzle boxes, baited with food and scaled to accommodate body size, to members of 39 carnivore species from nine families housed in multiple North American zoos. We found that species with larger brains relative to their body mass were more successful at opening the boxes. In a subset of species, we also used virtual brain endocasts to measure volumes of four gross brain regions and show that some of these regions improve model prediction of success at opening the boxes when included with total brain size and body mass. Socioecological variables, including measures of social complexity and manual dexterity, failed to predict success at opening the boxes. Our results, thus, fail to support the social brain hypothesis but provide important empirical support for the relationship between relative brain size and the ability to solve this novel technical problem. PMID:26811470

Brain size predicts problem-solving ability in mammalian carnivores.

PubMed

Benson-Amram, Sarah; Dantzer, Ben; Stricker, Gregory; Swanson, Eli M; Holekamp, Kay E

2016-03-01

Despite considerable interest in the forces shaping the relationship between brain size and cognitive abilities, it remains controversial whether larger-brained animals are, indeed, better problem-solvers. Recently, several comparative studies have revealed correlations between brain size and traits thought to require advanced cognitive abilities, such as innovation, behavioral flexibility, invasion success, and self-control. However, the general assumption that animals with larger brains have superior cognitive abilities has been heavily criticized, primarily because of the lack of experimental support for it. Here, we designed an experiment to inquire whether specific neuroanatomical or socioecological measures predict success at solving a novel technical problem among species in the mammalian order Carnivora. We presented puzzle boxes, baited with food and scaled to accommodate body size, to members of 39 carnivore species from nine families housed in multiple North American zoos. We found that species with larger brains relative to their body mass were more successful at opening the boxes. In a subset of species, we also used virtual brain endocasts to measure volumes of four gross brain regions and show that some of these regions improve model prediction of success at opening the boxes when included with total brain size and body mass. Socioecological variables, including measures of social complexity and manual dexterity, failed to predict success at opening the boxes. Our results, thus, fail to support the social brain hypothesis but provide important empirical support for the relationship between relative brain size and the ability to solve this novel technical problem.

Resuscitation with Lyophilized Plasma Is Safe and Improves Neurological Recovery in a Long-Term Survival Model of Swine Subjected to Traumatic Brain Injury, Hemorrhagic Shock, and Polytrauma.

PubMed

Georgoff, Patrick E; Nikolian, Vahagn C; Halaweish, Ihab; Chtraklin, Kiril; Bruhn, Peter J; Eidy, Hassan; Rasmussen, Monica; Li, Yongqing; Srinivasan, Ashok; Alam, Hasan B

2017-07-01

We have shown previously that fresh frozen plasma (FFP) and lyophilized plasma (LP) decrease brain lesion size and improve neurological recovery in a swine model of traumatic brain injury (TBI) and hemorrhagic shock (HS). In this study, we examine whether these findings can be validated in a clinically relevant model of severe TBI, HS, and polytrauma. Female Yorkshire swine were subjected to TBI (controlled cortical impact), hemorrhage (40% volume), grade III liver and splenic injuries, rib fracture, and rectus abdominis crush. The animals were maintained in a state of shock (mean arterial pressure 30-35 mm Hg) for 2 h, and then randomized to resuscitation with normal saline (NS), FFP, or LP (n = 5 swine/group). Animals were recovered and monitored for 30 d, during which time neurological recovery was assessed. Brain lesion sizes were measured via magnetic resonance imaging (MRI) on post-injury days (PID) three and 10. Animals were euthanized on PID 30. The severity of shock and response to resuscitation was similar in all groups. When compared with NS-treated animals, plasma-treated animals (FFP and LP) had significantly lower neurologic severity scores (PID 1-7) and a faster return to baseline neurological function. There was no significant difference in brain lesion sizes between groups. LP treatment was well tolerated and similar to FFP. In this clinically relevant large animal model of severe TBI, HS, and polytrauma, we have shown that plasma-based resuscitation strategies are safe and result in neurocognitive recovery that is faster than recovery after NS-based resuscitation.

How to Train an Injured Brain? A Pilot Feasibility Study of Home-Based Computerized Cognitive Training.

PubMed

Verhelst, Helena; Vander Linden, Catharine; Vingerhoets, Guy; Caeyenberghs, Karen

2017-02-01

Computerized cognitive training programs have previously shown to be effective in improving cognitive abilities in patients suffering from traumatic brain injury (TBI). These studies often focused on a single cognitive function or required expensive hardware, making it difficult to be used in a home-based environment. This pilot feasibility study aimed to evaluate the feasibility of a newly developed, home-based, computerized cognitive training program for adolescents who suffered from TBI. Additionally, feasibility of study design, procedures, and measurements were examined. Case series, longitudinal, pilot, feasibility intervention study with one baseline and two follow-up assessments. Nine feasibility outcome measures and criteria for success were defined, including accessibility, training motivation/user experience, technical smoothness, training compliance, participation willingness, participation rates, loss to follow-up, assessment timescale, and assessment procedures. Five adolescent patients (four boys, mean age = 16 years 7 months, standard deviation = 9 months) with moderate to severe TBI in the chronic stage were recruited and received 8 weeks of cognitive training with BrainGames. Effect sizes (Cohen's d) were calculated to determine possible training-related effects. The new cognitive training intervention, BrainGames, and study design and procedures proved to be feasible; all nine feasibility outcome criteria were met during this pilot feasibility study. Estimates of effect sizes showed small to very large effects on cognitive measures and questionnaires, which were retained after 6 months. Our pilot study shows that a longitudinal intervention study comprising our novel, computerized cognitive training program and two follow-up assessments is feasible in adolescents suffering from TBI in the chronic stage. Future studies with larger sample sizes will evaluate training-related effects on cognitive functions and underlying brain structures.

Altered resting state neuromotor connectivity in men with chronic prostatitis/chronic pelvic pain syndrome: A MAPP

PubMed Central

Kutch, Jason J.; Yani, Moheb S.; Asavasopon, Skulpan; Kirages, Daniel J.; Rana, Manku; Cosand, Louise; Labus, Jennifer S.; Kilpatrick, Lisa A.; Ashe-McNalley, Cody; Farmer, Melissa A.; Johnson, Kevin A.; Ness, Timothy J.; Deutsch, Georg; Harris, Richard E.; Apkarian, A. Vania; Clauw, Daniel J.; Mackey, Sean C.; Mullins, Chris; Mayer, Emeran A.

2015-01-01

Brain network activity associated with altered motor control in individuals with chronic pain is not well understood. Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a debilitating condition in which previous studies have revealed altered resting pelvic floor muscle activity in men with CP/CPPS compared to healthy controls. We hypothesized that the brain networks controlling pelvic floor muscles would also show altered resting state function in men with CP/CPPS. Here we describe the results of the first test of this hypothesis focusing on the motor cortical regions, termed pelvic-motor, that can directly activate pelvic floor muscles. A group of men with CP/CPPS (N = 28), as well as group of age-matched healthy male controls (N = 27), had resting state functional magnetic resonance imaging scans as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network study. Brain maps of the functional connectivity of pelvic-motor were compared between groups. A significant group difference was observed in the functional connectivity between pelvic-motor and the right posterior insula. The effect size of this group difference was among the largest effect sizes in functional connectivity between all pairs of 165 anatomically-defined subregions of the brain. Interestingly, many of the atlas region pairs with large effect sizes also involved other subregions of the insular cortices. We conclude that functional connectivity between motor cortex and the posterior insula may be among the most important markers of altered brain function in men with CP/CPPS, and may represent changes in the integration of viscerosensory and motor processing. PMID:26106574

Random-Walk Model of Diffusion in Three Dimensions in Brain Extracellular Space: Comparison with Microfiberoptic Photobleaching Measurements

PubMed Central

Jin, Songwan; Zador, Zsolt; Verkman, A. S.

2008-01-01

Diffusion through the extracellular space (ECS) in brain is important in drug delivery, intercellular communication, and extracellular ionic buffering. The ECS comprises ∼20% of brain parenchymal volume and contains cell-cell gaps ∼50 nm. We developed a random-walk model to simulate macromolecule diffusion in brain ECS in three dimensions using realistic ECS dimensions. Model inputs included ECS volume fraction (α), cell size, cell-cell gap geometry, intercellular lake (expanded regions of brain ECS) dimensions, and molecular size of the diffusing solute. Model output was relative solute diffusion in water versus brain ECS (Do/D). Experimental Do/D for comparison with model predictions was measured using a microfiberoptic fluorescence photobleaching method involving stereotaxic insertion of a micron-size optical fiber into mouse brain. Do/D for the small solute calcein in different regions of brain was in the range 3.0–4.1, and increased with brain cell swelling after water intoxication. Do/D also increased with increasing size of the diffusing solute, particularly in deep brain nuclei. Simulations of measured Do/D using realistic α, cell size and cell-cell gap required the presence of intercellular lakes at multicell contact points, and the contact length of cell-cell gaps to be least 50-fold smaller than cell size. The model accurately predicted Do/D for different solute sizes. Also, the modeling showed unanticipated effects on Do/D of changing ECS and cell dimensions that implicated solute trapping by lakes. Our model establishes the geometric constraints to account quantitatively for the relatively modest slowing of solute and macromolecule diffusion in brain ECS. PMID:18469079

Random-walk model of diffusion in three dimensions in brain extracellular space: comparison with microfiberoptic photobleaching measurements.

PubMed

Jin, Songwan; Zador, Zsolt; Verkman, A S

2008-08-01

Diffusion through the extracellular space (ECS) in brain is important in drug delivery, intercellular communication, and extracellular ionic buffering. The ECS comprises approximately 20% of brain parenchymal volume and contains cell-cell gaps approximately 50 nm. We developed a random-walk model to simulate macromolecule diffusion in brain ECS in three dimensions using realistic ECS dimensions. Model inputs included ECS volume fraction (alpha), cell size, cell-cell gap geometry, intercellular lake (expanded regions of brain ECS) dimensions, and molecular size of the diffusing solute. Model output was relative solute diffusion in water versus brain ECS (D(o)/D). Experimental D(o)/D for comparison with model predictions was measured using a microfiberoptic fluorescence photobleaching method involving stereotaxic insertion of a micron-size optical fiber into mouse brain. D(o)/D for the small solute calcein in different regions of brain was in the range 3.0-4.1, and increased with brain cell swelling after water intoxication. D(o)/D also increased with increasing size of the diffusing solute, particularly in deep brain nuclei. Simulations of measured D(o)/D using realistic alpha, cell size and cell-cell gap required the presence of intercellular lakes at multicell contact points, and the contact length of cell-cell gaps to be least 50-fold smaller than cell size. The model accurately predicted D(o)/D for different solute sizes. Also, the modeling showed unanticipated effects on D(o)/D of changing ECS and cell dimensions that implicated solute trapping by lakes. Our model establishes the geometric constraints to account quantitatively for the relatively modest slowing of solute and macromolecule diffusion in brain ECS.

Brain size growth in wild and captive chimpanzees (Pan troglodytes).

PubMed

Cofran, Zachary

2018-05-24

Despite many studies of chimpanzee brain size growth, intraspecific variation is under-explored. Brain size data from chimpanzees of the Taï Forest and the Yerkes Primate Research Center enable a unique glimpse into brain growth variation as age at death is known for individuals, allowing cross-sectional growth curves to be estimated. Because Taï chimpanzees are from the wild but Yerkes apes are captive, potential environmental effects on neural development can also be explored. Previous research has revealed differences in growth and health between wild and captive primates, but such habitat effects have yet to be investigated for brain growth. Here, I use an iterative curve fitting procedure to estimate brain growth and regression parameters for each population, statistically comparing growth models using bootstrapped confidence intervals. Yerkes and Taï brain sizes overlap at all ages, although the sole Taï newborn is at the low end of captive neonatal variation. Growth rate and duration are statistically indistinguishable between the two populations. Resampling the Yerkes sample to match the Taï sample size and age group composition shows that ontogenetic variation in the two groups are remarkably similar despite the latter's limited size. Best fit growth curves for each sample indicate cessation of brain size growth at around 2 years, earlier than has previously been reported. The overall similarity between wild and captive chimpanzees points to the canalization of brain growth in this species. © 2018 Wiley Periodicals, Inc.

‘My Virtual Dream’: Collective Neurofeedback in an Immersive Art Environment

PubMed Central

Kovacevic, Natasha; Ritter, Petra; Tays, William; Moreno, Sylvain; McIntosh, Anthony Randal

2015-01-01

While human brains are specialized for complex and variable real world tasks, most neuroscience studies reduce environmental complexity, which limits the range of behaviours that can be explored. Motivated to overcome this limitation, we conducted a large-scale experiment with electroencephalography (EEG) based brain-computer interface (BCI) technology as part of an immersive multi-media science-art installation. Data from 523 participants were collected in a single night. The exploratory experiment was designed as a collective computer game where players manipulated mental states of relaxation and concentration with neurofeedback targeting modulation of relative spectral power in alpha and beta frequency ranges. Besides validating robust time-of-night effects, gender differences and distinct spectral power patterns for the two mental states, our results also show differences in neurofeedback learning outcome. The unusually large sample size allowed us to detect unprecedented speed of learning changes in the power spectrum (~ 1 min). Moreover, we found that participants' baseline brain activity predicted subsequent neurofeedback beta training, indicating state-dependent learning. Besides revealing these training effects, which are relevant for BCI applications, our results validate a novel platform engaging art and science and fostering the understanding of brains under natural conditions. PMID:26154513

Reliable individual-level neural markers of high-level language processing: A necessary precursor for relating neural variability to behavioral and genetic variability.

PubMed

Mahowald, Kyle; Fedorenko, Evelina

2016-10-01

The majority of functional neuroimaging investigations aim to characterize an average human brain. However, another important goal of cognitive neuroscience is to understand the ways in which individuals differ from one another and the significance of these differences. This latter goal is given special weight by the recent reconceptualization of neurological disorders where sharp boundaries are no longer drawn either between health and neuropsychiatric and neurodevelopmental disorders, or among different disorders (e.g., Insel et al., 2010). Consequently, even the variability in the healthy population can inform our understanding of brain disorders. However, because the use of functional neural markers is still in its infancy, no consensus presently exists about which measures (e.g., effect size?, extent of activation?, degree of lateralization?) are the best ones to use. We here attempt to address this question with respect to one large-scale neural system: the set of brain regions in the frontal and temporal cortices that jointly support high-level linguistic processing (e.g., Binder et al., 1997; Fedorenko, Hsieh, Nieto-Castanon, Whitfield-Gabrieli, & Kanwisher, 2010). In particular, using data from 150 individuals all of whom had performed a language "localizer" task contrasting sentences and nonword sequences (Fedorenko et al., 2010), we: a) characterize the distributions of the values for four key neural measures of language activity (region effect sizes, region volumes, lateralization based on effect sizes, and lateralization based on volumes); b) test the reliability of these measures in a subset of 32 individuals who were scanned across two sessions; c) evaluate the relationship among the different regions of the language system; and d) evaluate the relationship among the different neural measures. Based on our results, we provide some recommendations for future studies of brain-behavior and brain-genes relationships. Although some of our conclusions are specific to the language system, others (e.g., the fact that effect-size-based measures tend to be more reliable than volume-based measures) are likely to generalize to the rest of the brain. Copyright © 2016 Elsevier Inc. All rights reserved.

Pupillometry in brain death: differences in pupillary diameter between paediatric and adult subjects.

PubMed

Olgun, Gokhan; Newey, Christopher R; Ardelt, Agnieszka

2015-11-01

The determination of brain death in neonates, infants, children and adults relies on a clinical diagnosis based on the absence of neurological function with a known irreversible cause of brain injury. Evaluation of pupil size and non-reactivity is a requisite for determination of brain death. There are no studies in the literature that quantitatively assess pupil size in brain dead children and adults. Infants, children and adults diagnosed with brain death were included in the study. Pupils were measured with a quantitative pupillometer (Forsite; Neuroptics, Irvine, CA, USA). Median, minimum and maximum pupil sizes were documented and the results were adjudicated for age, vasopressor use and temperature. Median right and left pupil sizes were 5.01 ± 0.85 mm and 5.12 ± 0.87 mm, respectively, with a range between 3.69 and 7.34 mm. Paediatric pupils were larger than adult pupils (right pupil 5.53 vs 4.73 mm p: 0.018; left pupil 5.87 vs 4.77 mm P: 0.03), and there was no correlation of pupil size with temperature or increasing number of vasopressors. This is the first study in the literature objectively evaluating pupil sizes in infants, children and adults diagnosed with brain death. We observed variation between observed pupil size and that expected based on brain death determination guidelines.

Brain damage and behavioural disorders in fish induced by plastic nanoparticles delivered through the food chain.

PubMed

Mattsson, Karin; Johnson, Elyse V; Malmendal, Anders; Linse, Sara; Hansson, Lars-Anders; Cedervall, Tommy

2017-09-13

The tremendous increases in production of plastic materials has led to an accumulation of plastic pollution worldwide. Many studies have addressed the physical effects of large-sized plastics on organisms, whereas few have focused on plastic nanoparticles, despite their distinct chemical, physical and mechanical properties. Hence our understanding of their effects on ecosystem function, behaviour and metabolism of organisms remains elusive. Here we demonstrate that plastic nanoparticles reduce survival of aquatic zooplankton and penetrate the blood-to-brain barrier in fish and cause behavioural disorders. Hence, for the first time, we uncover direct interactions between plastic nanoparticles and brain tissue, which is the likely mechanism behind the observed behavioural disorders in the top consumer. In a broader perspective, our findings demonstrate that plastic nanoparticles are transferred up through a food chain, enter the brain of the top consumer and affect its behaviour, thereby severely disrupting the function of natural ecosystems.

Brain Mass and Encephalization Quotients in the Domestic Industrial Pig (Sus scrofa)

PubMed Central

Minervini, Serena; Accogli, Gianluca; Pirone, Andrea; Graïc, Jean-Marie; Cozzi, Bruno; Desantis, Salvatore

2016-01-01

In the present study we examined the brain of fetal, newborn, and adult pigs raised for meat production. The fresh and formalin-fixed weights of the brain have been recorded and used, together with body weight, to calculate the Encephalization Quotient (EQ). The weight of the cerebellum has been used to calculate the Cerebellar Quotient (CQ). The results have been discussed together with analogue data obtained in other terrestrial Cetartiodactyla (including the domestic bovine, sheep, goat, and camel), domesticated Carnivora, Proboscidata, and Primates. Our study, based on a relatively large experimental series, corrects former observations present in the literature based on smaller samples, and emphasizes that the domestic pig has a small brain relative to its body size (EQ = 0.38 for adults), possibly due to factors linked to the necessity of meat production and improved body weight. Comparison with other terrestrial Cetartiodactyla indicates a similar trend for all domesticated species. PMID:27351807

Wnt/Notum spatial feedback inhibition controls neoblast differentiation to regulate reversible growth of the planarian brain

PubMed Central

Hill, Eric M.; Petersen, Christian P.

2015-01-01

Mechanisms determining final organ size are poorly understood. Animals undergoing regeneration or ongoing adult growth are likely to require sustained and robust mechanisms to achieve and maintain appropriate sizes. Planarians, well known for their ability to undergo whole-body regeneration using pluripotent adult stem cells of the neoblast population, can reversibly scale body size over an order of magnitude by controlling cell number. Using quantitative analysis, we showed that after injury planarians perfectly restored brain:body proportion by increasing brain cell number through epimorphosis or decreasing brain cell number through tissue remodeling (morphallaxis), as appropriate. We identified a pathway controlling a brain size set-point that involves feedback inhibition between wnt11-6/wntA/wnt4a and notum, encoding conserved antagonistic signaling factors expressed at opposite brain poles. wnt11-6/wntA/wnt4a undergoes feedback inhibition through canonical Wnt signaling but is likely to regulate brain size in a non-canonical pathway independently of beta-catenin-1 and APC. Wnt/Notum signaling tunes numbers of differentiated brain cells in regenerative growth and tissue remodeling by influencing the abundance of brain progenitors descended from pluripotent stem cells, as opposed to regulating cell death. These results suggest that the attainment of final organ size might be accomplished by achieving a balance of positional signaling inputs that regulate the rates of tissue production. PMID:26525673

Sex Differences in Intelligence and Brain Size: A Developmental Theory.

ERIC Educational Resources Information Center

Lynn, Richard

1999-01-01

Proposes a developmental theory of sex differences in intelligence that states that the faster maturation and brain size growth in girls up to age 15 compensates for their smaller brain size so that sex differences in intelligence are very small. Discusses evidence that supports this theory. (SLD)

Müller-Lyer figures influence the online reorganization of visually guided grasping movements.

PubMed

Heath, Matthew; Rival, Christina; Neely, Kristina; Krigolson, Olav

2006-03-01

In advance of grasping a visual object embedded within fins-in and fins-out Müller-Lyer (ML) configurations, participants formulated a premovement grip aperture (GA) based on the size of a neutral preview object. Preview objects were smaller, veridical, or larger than the size of the to-be-grasped target object. As a result, premovement GA associated with the small and large preview objects required significant online reorganization to appropriately grasp the target object. We reasoned that such a manipulation would provide an opportunity to examine the extent to which the visuomotor system engages egocentric and/or allocentric visual cues for the online, feedback-based control of action. It was found that the online reorganization of GA was reliably influenced by the ML figures (i.e., from 20 to 80% of movement time), regardless of the size of the preview object, albeit the small and large preview objects elicited more robust illusory effects than the veridical preview object. These results counter the view that online grasping control is mediated by absolute visual information computed with respect to the observer (e.g., Glover in Behav Brain Sci 27:3-78, 2004; Milner and Goodale in The visual brain in action 1995). Instead, the impact of the ML figures suggests a level of interaction between egocentric and allocentric visual cues in online action control.

Nonlocal Intracranial Cavity Extraction

PubMed Central

Manjón, José V.; Eskildsen, Simon F.; Coupé, Pierrick; Romero, José E.; Collins, D. Louis; Robles, Montserrat

2014-01-01

Automatic and accurate methods to estimate normalized regional brain volumes from MRI data are valuable tools which may help to obtain an objective diagnosis and followup of many neurological diseases. To estimate such regional brain volumes, the intracranial cavity volume (ICV) is often used for normalization. However, the high variability of brain shape and size due to normal intersubject variability, normal changes occurring over the lifespan, and abnormal changes due to disease makes the ICV estimation problem challenging. In this paper, we present a new approach to perform ICV extraction based on the use of a library of prelabeled brain images to capture the large variability of brain shapes. To this end, an improved nonlocal label fusion scheme based on BEaST technique is proposed to increase the accuracy of the ICV estimation. The proposed method is compared with recent state-of-the-art methods and the results demonstrate an improved performance both in terms of accuracy and reproducibility while maintaining a reduced computational burden. PMID:25328511

A study of the comparative anatomy of the brain of domestic ruminants using magnetic resonance imaging.

PubMed

Schmidt, M J; Langen, N; Klumpp, S; Nasirimanesh, F; Shirvanchi, P; Ondreka, N; Kramer, M

2012-01-01

Although magnetic resonance imaging has been used to examine the brain of domestic ruminants, detailed information relating the precise anatomical features in these species is lacking. In this study the brain structures of calves (Bos taurus domesticus), sheep (Ovis aries), goats (Capra hircus) and a mesaticephalic dog (Canis lupis familiaris) were examined using T2-weighed Turbo Spin Echo sequences; three-dimensional models based on high-resolution gradient echo scans were used to identify brain sulci and gyri in two-dimensional images. The ruminant brains examined were similar in structure and organisation to those of other mammals but particular features included the deep depression of the insula and the pronounced gyri of the cortices, the dominant position of the visual (optic nerve, optic chiasm and rostral colliculus) and olfactory (olfactory bulb, olfactory tracts and piriform lobe) systems, and the relatively large size of the diencephalon. Copyright © 2010 Elsevier Ltd. All rights reserved.

Specialization and group size: brain and behavioural correlates of colony size in ants lacking morphological castes.

PubMed

Amador-Vargas, Sabrina; Gronenberg, Wulfila; Wcislo, William T; Mueller, Ulrich

2015-02-22

Group size in both multicellular organisms and animal societies can correlate with the degree of division of labour. For ants, the task specialization hypothesis (TSH) proposes that increased behavioural specialization enabled by larger group size corresponds to anatomical specialization of worker brains. Alternatively, the social brain hypothesis proposes that increased levels of social stimuli in larger colonies lead to enlarged brain regions in all workers, regardless of their task specialization. We tested these hypotheses in acacia ants (Pseudomyrmex spinicola), which exhibit behavioural but not morphological task specialization. In wild colonies, we marked, followed and tested ant workers involved in foraging tasks on the leaves (leaf-ants) and in defensive tasks on the host tree trunk (trunk-ants). Task specialization increased with colony size, especially in defensive tasks. The relationship between colony size and brain region volume was task-dependent, supporting the TSH. Specifically, as colony size increased, the relative size of regions within the mushroom bodies of the brain decreased in trunk-ants but increased in leaf-ants; those regions play important roles in learning and memory. Our findings suggest that workers specialized in defence may have reduced learning abilities relative to leaf-ants; these inferences remain to be tested. In societies with monomorphic workers, brain polymorphism enhanced by group size could be a mechanism by which division of labour is achieved. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Effects of intensive neuropsychological rehabilitation for acquired brain injury.

PubMed

Holleman, Meike; Vink, Martie; Nijland, Rinske; Schmand, Ben

2018-06-01

The objective of the study was to examine the effects of a comprehensive neuropsychological rehabilitation programme (Intensive NeuroRehabilitation, INR) on the emotional and behavioural consequences of acquired brain injury (ABI). The participants were 75 adult patients suffering from ABI (33 traumatic brain injury, 14 stroke, 10 tumour, 6 hypoxia, 12 other), all of whom were admitted to the INR treatment programme. The main outcome measures were: general psychological well-being (Symptom-Checklist-90), depression and anxiety (Beck Depression Inventory-II, Hospital Anxiety and Depression Scale, State Trait Anxiety Inventory), and quality of life (Quality of Life in Brain Injury). The study was a non-blinded, waiting-list controlled trial. During the waiting-list period no or minimal care was provided. Multivariate analysis of the main outcome measures showed large effect sizes for psychological well-being (partial η 2  = .191, p < .001), depression (partial η 2  = .168, p < .001), and anxiety (partial η 2  = .182, p < .001), and a moderate effect size for quality of life (partial η 2  = .130, p = .001). Changes on neuropsychological tests did not differ between the groups. It was concluded that the INR programme improved general psychological well-being, depressive symptoms, anxiety, and quality of life. The programme does not affect cognitive functioning.

Encephalization in tropical teleost fishes and comparison with their mode of life.

PubMed

Bauchot, R; Randall, J E; Ridet, J M; Bauchot, M L

1989-01-01

The brains were dissected from a total of 1225 fishes representing 737 species, 310 genera and 113 families of tropical and subtropical teleosts. Each fish was weighed before brain dissection, and each brain weighed after its removal. The encephalization coefficient k was determined for each fish from a quadratic formula; to conveniently compare brain size of one species with that of another, we used an encephalization index so that an encephalization index of 100 is the average for all the species investigated. The encephalization indices for the families of fishes studied varied from 7 for the Moringuidae to 233 for the Coryphaenidae. There is no strong correlation in relative brain size with phylogenetic position. Although there is a general trend for the more highly evolved fishes to have larger brains, this is partially obscured by some high values in certain primitive groups and low ones in the more advanced. Elongate fishes have lower encephalization indices in general. This may in part be related to low phylogenetic position of most elongate species (anguilliform fishes, for example), in part to the greater relative body weight due to the longer vertebral column (and usually more numerous fin rays as as well), and to their usual mode of swimming by lateral undulations of the body (the most primitive type of aquatic locomotion--one in which the spinal cord plays a major role). No difference could be noted in the encephalization indices of herbivorous families of fishes compared to carnivorous ones. Within a genus, among medium to large-size fishes, those species of larger size tend to have lower encephalization indices. This may be related to larger fishes having less to fear of predators. Fishes which in some passive way avoid predation have low indices in general. This is particularly true of benthic species which conceal themselves by flattened form, fleshy protuberances or protective coloration, or which bury in the sediment or take refuge in burrows. Also correlated with low indices is some form of predator deterence such as production of skin toxins, presence of venomous spines or ability to enlarge the body by inflation. Fishes which have more than a single sense highly developed exhibit a larger relative brain size than those with only one well developed sense. Fishes which live in a complex community of high species diversity, such as a coral reef, have higher indices, in general, than those which dwell on mud and sand flat. Pelagic fishes, such as scombrids and carangids, are among those with the highest indices.(ABSTRACT TRUNCATED AT 400 WORDS)

Single-Fraction Versus Multifraction (3 × 9 Gy) Stereotactic Radiosurgery for Large (>2 cm) Brain Metastases: A Comparative Analysis of Local Control and Risk of Radiation-Induced Brain Necrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Minniti, Giuseppe, E-mail: gminniti@ospedalesantandrea.it; IRCCS Neuromed, Pozzilli; Scaringi, Claudia

Purpose: To investigate the local control and radiation-induced brain necrosis in patients with brain metastases >2 cm in size who received single-fraction or multifraction stereotactic radiosurgery (SRS); factors associated with clinical outcomes and the development of brain radionecrosis were assessed. Methods and Materials: Two hundred eighty-nine consecutive patients with brain metastases >2.0 cm who received SRS as primary treatment at Sant'Andrea Hospital, University of Rome Sapienza, Rome, Italy, were analyzed. Cumulative incidence analysis was used to compare local control and radiation-induced brain necrosis between groups from the time of SRS. To achieve a balanced distribution of baseline covariates between treatment groups, amore » propensity score analysis was used. Results: The 1-year cumulative local control rates were 77% in the single-fraction SRS (SF-SRS) group and 91% in the multifraction SRS (MF-SRS) group (P=.01). Recurrences occurred in 25 and 11 patients who received SF-SRS or MF-SRS (P=.03), respectively. Thirty-one patients (20%) undergoing SF-SRS and 11 (8%) subjected to MF-SRS experienced brain radionecrosis (P=.004); the 1-year cumulative incidence rate of radionecrosis was 18% and 9% (P=.01), respectively. Significant differences between the 2 groups in terms of local control and risk of radionecrosis were maintained after propensity score adjustment. Conclusions: Multifraction SRS at a dose of 27 Gy in 3 daily fractions seems to be an effective treatment modality for large brain metastases, associated with better local control and a reduced risk of radiation-induced radionecrosis as compared with SF-SRS.« less

Congenital heart disease affects cerebral size but not brain growth.

PubMed

Ortinau, Cynthia; Inder, Terrie; Lambeth, Jennifer; Wallendorf, Michael; Finucane, Kirsten; Beca, John

2012-10-01

Infants with congenital heart disease (CHD) have delayed brain maturation and alterations in brain volume. Brain metrics is a simple measurement technique that can be used to evaluate brain growth. This study used brain metrics to test the hypothesis that alterations in brain size persist at 3 months of age and that infants with CHD have slower rates of brain growth than control infants. Fifty-seven infants with CHD underwent serial brain magnetic resonance imaging (MRI). To evaluate brain growth across the first 3 months of life, brain metrics were undertaken using 19 tissue and fluid spaces shown on MRIs performed before surgery and again at 3 months of age. Before surgery, infants with CHD have smaller frontal, parietal, cerebellar, and brain stem measures (p < 0.001). At 3 months of age, alterations persisted in all measures except the cerebellum. There was no difference between control and CHD infants in brain growth. However, the cerebellum trended toward greater growth in infants with CHD. Somatic growth was the primary factor that related to brain growth. Presence of focal white matter lesions before and after surgery did not relate to alterations in brain size or growth. Although infants with CHD have persistent alterations in brain size at 3 months of age, rates of brain growth are similar to that of healthy term infants. Somatic growth was the primary predictor of brain growth, emphasizing the importance of optimal weight gain in this population.

Individual differences in the dominance of interhemispheric connections predict cognitive ability beyond sex and brain size.

PubMed

Martínez, Kenia; Janssen, Joost; Pineda-Pardo, José Ángel; Carmona, Susanna; Román, Francisco Javier; Alemán-Gómez, Yasser; Garcia-Garcia, David; Escorial, Sergio; Quiroga, María Ángeles; Santarnecchi, Emiliano; Navas-Sánchez, Francisco Javier; Desco, Manuel; Arango, Celso; Colom, Roberto

2017-07-15

Global structural brain connectivity has been reported to be sex-dependent with women having increased interhemispheric connectivity (InterHc) and men having greater intrahemispheric connectivity (IntraHc). However, (a) smaller brains show greater InterHc, (b) larger brains show greater IntraHc, and (c) women have, on average, smaller brains than men. Therefore, sex differences in brain size may modulate sex differences in global brain connectivity. At the behavioural level, sex-dependent differences in connectivity are thought to contribute to men-women differences in spatial and verbal abilities. But this has never been tested at the individual level. The current study assessed whether individual differences in global structural connectome measures (InterHc, IntraHc and the ratio of InterHc relative to IntraHc) predict spatial and verbal ability while accounting for the effect of sex and brain size. The sample included forty men and forty women, who did neither differ in age nor in verbal and spatial latent components defined by a broad battery of tests and tasks. High-resolution T 1 -weighted and diffusion-weighted images were obtained for computing brain size and reconstructing the structural connectome. Results showed that men had higher IntraHc than women, while women had an increased ratio InterHc/IntraHc. However, these sex differences were modulated by brain size. Increased InterHc relative to IntraHc predicted higher spatial and verbal ability irrespective of sex and brain size. The positive correlations between the ratio InterHc/IntraHc and the spatial and verbal abilities were confirmed in 1000 random samples generated by bootstrapping. Therefore, sex differences in global structural connectome connectivity were modulated by brain size and did not underlie sex differences in verbal and spatial abilities. Rather, the level of dominance of InterHc over IntraHc may be associated with individual differences in verbal and spatial abilities in both men and women. Copyright © 2017 Elsevier Inc. All rights reserved.

Differences between brain mass and body weight scaling to height: potential mechanism of reduced mass-specific resting energy expenditure of taller adults.

PubMed

Heymsfield, Steven B; Chirachariyavej, Thamrong; Rhyu, Im Joo; Roongpisuthipong, Chulaporn; Heo, Moonseong; Pietrobelli, Angelo

2009-01-01

Adult resting energy expenditure (REE) scales as height( approximately 1.5), whereas body weight (BW) scales as height( approximately 2). Mass-specific REE (i.e., REE/BW) is thus lower in tall subjects compared with their shorter counterparts, the mechanism of which is unknown. We evaluated the hypothesis that high-metabolic-rate brain mass scales to height with a power significantly less than that of BW, a theory that if valid would provide a potential mechanism for height-related REE effects. The hypothesis was tested by measuring brain mass on a large (n = 372) postmortem sample of Thai men. Since brain mass-body size relations may be influenced by age, the hypothesis was secondarily explored in Thai men age < or =45 yr (n = 299) and with brain magnetic resonance imaging (MRI) studies in Korean men (n = 30) age > or =20<30 yr. The scaling of large body compartments was examined in a third group of Asian men living in New York (NY, n = 28) with MRI and dual-energy X-ray absorptiometry. Brain mass scaled to height with a power (mean +/- SEE; 0.46 +/- 0.13) significantly smaller (P < 0.001) than that of BW scaled to height (2.36 +/- 0.19) in the whole group of Thai men; brain mass/BW scaled negatively to height (-1.94 +/- 0.20, P < 0.001). Similar results were observed in younger Thai men, and results for brain mass/BW vs. height were directionally the same (P = 0.09) in Korean men. Skeletal muscle and bone scaled to height with powers similar to that of BW (i.e., approximately 2-3) in the NY Asian men. Models developed using REE estimates in Thai men suggest that brain accounts for most of the REE/BW height dependency. Tall and short men thus differ in relative brain mass, but the proportions of BW as large compartments appear independent of height, observations that provide a potential mechanistic basis for related differences in REE and that have implications for the study of adult energy requirements.

Evidence for Decreased Brain Parenchymal Volume After Large Intracerebral Hemorrhages: a Potential Mechanism Limiting Intracranial Pressure Rises.

PubMed

Williamson, Michael R; Colbourne, Frederick

2017-08-01

Potentially fatal intracranial pressure (ICP) rises commonly occur after large intracerebral hemorrhages (ICH). We monitored ICP after infusing 100-160 μL of autologous blood (vs. 0 μL control) into the striatum of rats in order to test the validity of this common model with regard to ICP elevations. Other endpoints included body temperature, behavioral impairment, lesion volume, and edema. Also, we evaluated hippocampal CA1 sector and somatosensory cortical neuron morphology to assess whether global ischemic injury occurred. Despite massive blood infusions, ICP only modestly increased (160 μL 10.8 ± 2.1 mmHg for <36 h vs. control 3.4 ± 0.5 mmHg), with little peri-hematoma edema at 3 days. Body temperature was not affected. Behavioral deficits and tissue loss were infusion volume-dependent. There was no histological evidence of hippocampal or cortical injury, indicating that cell death was confined to the hematoma and closely surrounding tissue. Surprisingly, the most severe hemorrhages significantly increased cell density (~15-20%) and reduced cell body size (~30%) in regions outside the injury site. Additionally, decreased cell size and increased density were observed after collagenase-induced ICH. Parenchymal volume is seemingly reduced after large ICH. Thus, in addition to well-known compliance mechanisms (e.g., displacement of cerebrospinal fluid and cerebral blood), reduced brain parenchymal volume appears to limit ICP rises in rodents with very large mass lesions.

Internal pilots for a class of linear mixed models with Gaussian and compound symmetric data

PubMed Central

Gurka, Matthew J.; Coffey, Christopher S.; Muller, Keith E.

2015-01-01

SUMMARY An internal pilot design uses interim sample size analysis, without interim data analysis, to adjust the final number of observations. The approach helps to choose a sample size sufficiently large (to achieve the statistical power desired), but not too large (which would waste money and time). We report on recent research in cerebral vascular tortuosity (curvature in three dimensions) which would benefit greatly from internal pilots due to uncertainty in the parameters of the covariance matrix used for study planning. Unfortunately, observations correlated across the four regions of the brain and small sample sizes preclude using existing methods. However, as in a wide range of medical imaging studies, tortuosity data have no missing or mistimed data, a factorial within-subject design, the same between-subject design for all responses, and a Gaussian distribution with compound symmetry. For such restricted models, we extend exact, small sample univariate methods for internal pilots to linear mixed models with any between-subject design (not just two groups). Planning a new tortuosity study illustrates how the new methods help to avoid sample sizes that are too small or too large while still controlling the type I error rate. PMID:17318914

INTERDISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY: Influence of Blurred Ways on Pattern Recognition of a Scale-Free Hopfield Neural Network

NASA Astrophysics Data System (ADS)

Chang, Wen-Li

2010-01-01

We investigate the influence of blurred ways on pattern recognition of a Barabási-Albert scale-free Hopfield neural network (SFHN) with a small amount of errors. Pattern recognition is an important function of information processing in brain. Due to heterogeneous degree of scale-free network, different blurred ways have different influences on pattern recognition with same errors. Simulation shows that among partial recognition, the larger loading ratio (the number of patterns to average degree P/langlekrangle) is, the smaller the overlap of SFHN is. The influence of directed (large) way is largest and the directed (small) way is smallest while random way is intermediate between them. Under the ratio of the numbers of stored patterns to the size of the network P/N is less than 0. 1 conditions, there are three families curves of the overlap corresponding to directed (small), random and directed (large) blurred ways of patterns and these curves are not associated with the size of network and the number of patterns. This phenomenon only occurs in the SFHN. These conclusions are benefit for understanding the relation between neural network structure and brain function.

Gut microbes and the brain: paradigm shift in neuroscience.

PubMed

Mayer, Emeran A; Knight, Rob; Mazmanian, Sarkis K; Cryan, John F; Tillisch, Kirsten

2014-11-12

The discovery of the size and complexity of the human microbiome has resulted in an ongoing reevaluation of many concepts of health and disease, including diseases affecting the CNS. A growing body of preclinical literature has demonstrated bidirectional signaling between the brain and the gut microbiome, involving multiple neurocrine and endocrine signaling mechanisms. While psychological and physical stressors can affect the composition and metabolic activity of the gut microbiota, experimental changes to the gut microbiome can affect emotional behavior and related brain systems. These findings have resulted in speculation that alterations in the gut microbiome may play a pathophysiological role in human brain diseases, including autism spectrum disorder, anxiety, depression, and chronic pain. Ongoing large-scale population-based studies of the gut microbiome and brain imaging studies looking at the effect of gut microbiome modulation on brain responses to emotion-related stimuli are seeking to validate these speculations. This article is a summary of emerging topics covered in a symposium and is not meant to be a comprehensive review of the subject. Copyright © 2014 the authors 0270-6474/14/3415490-07$15.00/0.

Comments on "Brain Size and Cerebral Glucose Metabolic Rate in Nonspecific Mental Retardation and Down Syndrome."

ERIC Educational Resources Information Center

Willerman, Lee; Schultz, Robert T.

1995-01-01

The relationship between mental retardation and brain size is discussed. Research suggests that a common path for many otherwise idiopathic mild retardation cases (genetic or environmental) could be small brain size, indicating reduced information processing capacity. Suggestions are made for further research on neuron number. (SLD)

Understanding the role of conscientiousness in healthy aging: where does the brain come in?

PubMed

Patrick, Christopher J

2014-05-01

In reviewing this impressive series of articles, I was struck by 2 points in particular: (a) the fact that the empirically oriented articles focused on analyses of data from very large samples, with the articles by Friedman, Kern, Hampson, and Duckworth (2014) and Kern, Hampson, Goldbert, and Friedman (2014) highlighting an approach to merging existing data sets through use of "metric bridges" to address key questions not addressable through 1 data set alone, and (b) the fact that the articles as a whole included limited mention of neuroscientific (i.e., brain research) concepts, methods, and findings. One likely reason for the lack of reference to brain-oriented work is the persisting gap between smaller sample size lab-experimental and larger sample size multivariate-correlational approaches to psychological research. As a strategy for addressing this gap and bringing a distinct neuroscientific component to the National Institute on Aging's conscientiousness and health initiative, I suggest that the metric bridging approach highlighted by Friedman and colleagues could be used to connect existing large-scale data sets containing both neurophysiological variables and measures of individual difference constructs to other data sets containing richer arrays of nonphysiological variables-including data from longitudinal or twin studies focusing on personality and health-related outcomes (e.g., Terman Life Cycle study and Hawaii longitudinal studies, as described in the article by Kern et al., 2014). (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Brain composition and olfactory learning in honey bees

PubMed Central

Gronenberg, Wulfila; Couvillon, Margaret J.

2015-01-01

Correlations between brain or brain component size and behavioral measures are frequently studied by comparing different animal species, which sometimes introduces variables that complicate interpretation in terms of brain function. Here, we have analyzed the brain composition of honey bees (Apis mellifera) that have been individually tested in an olfactory learning paradigm. We found that the total brain size correlated with the bees’ learning performance. Among different brain components, only the mushroom body, a structure known to be involved in learning and memory, showed a positive correlation with learning performance. In contrast, visual neuropils were relatively smaller in bees that performed better in the olfactory learning task, suggesting modality-specific behavioral specialization of individual bees. This idea is also supported by inter-individual differences in brain composition. Some slight yet statistically significant differences in the brain composition of European and Africanized honey bees are reported. Larger bees had larger brains, and by comparing brains of different sizes, we report isometric correlations for all brain components except for a small structure, the central body. PMID:20060918

Effects of compression injury on brain mitochondrial and tissue viability evaluated by a multiparametric monitoring system

NASA Astrophysics Data System (ADS)

Barbiro-Michaely, Efrat; Bachbut, Galit; Mayevsky, Avraham

2008-02-01

Neurosurgical procedures involve brain compression created by retractors. Although it is clear that retractors are causing damage to the brain tissue, the pathophysiology of the retraction was not investigated in details. In the present study we used the multiparametric monitoring approach for real time evaluation of mitochondrial function, hemodynamic, ionic and electrical activities monitored contralaterally to the retractor placement on the brain. The aims of the study were to test the effects of retractor size and severity of the compression on the degree of damage to the cerebral tissue. A special probe was lowered towards the cerebral cortex, (2mm and 4mm in depth) using a micromanipulator. Compression lasted for 30 minutes, than the retractor was elevated back to its initial position and monitoring continued for two hours. Additionally, two sizes of retractors were used 6mm and 3mm in diameter, the 3mm retractor included an intracranial pressure (ICP) probe. The results show that the combination of a large retractor with the depth of 4mm yielded high mortality rate (62%) of the rats while the use of a smaller retractor decreased significantly the percentage of mortality. Also, compression to the depth of 4mm increased tissue injury as compared to 2mm depth. In conclusion, the present study raises the importance and significance of multiparametric monitoring, and not only ICP and cerebral blood flow of the areas nearby the retractor position and not only the retraction site, as well as the effect of the retractor size on the damage induced to the cerebral tissue.

A Porcine Model of Traumatic Brain Injury via Head Rotational Acceleration

PubMed Central

Cullen, D. Kacy; Harris, James P.; Browne, Kevin D.; Wolf, John A; Duda, John E.; Meaney, David F.; Margulies, Susan S.; Smith, Douglas H.

2017-01-01

Unique from other brain disorders, traumatic brain injury (TBI) generally results from a discrete biomechanical event that induces rapid head movement. The large size and high organization of the human brain makes it particularly vulnerable to traumatic injury from rotational accelerations that can cause dynamic deformation of the brain tissue. Therefore, replicating the injury biomechanics of human TBI in animal models presents a substantial challenge, particularly with regard to addressing brain size and injury parameters. Here we present the historical development and use of a porcine model of head rotational acceleration. By scaling up the rotational forces to account for difference in brain mass between swine and humans, this model has been shown to produce the same tissue deformations and identical neuropathologies found in human TBI. The parameters of scaled rapid angular accelerations applied for the model reproduce inertial forces generated when the human head suddenly accelerates or decelerates in falls, collisions, or blunt impacts. The model uses custom-built linkage assemblies and a powerful linear actuator designed to produce purely impulsive nonimpact head rotation in different angular planes at controlled rotational acceleration levels. Through a range of head rotational kinematics, this model can produce functional and neuropathological changes across the spectrum from concussion to severe TBI. Notably, however, the model is very difficult to employ, requiring a highly skilled team for medical management, biomechanics, neurological recovery, and specialized outcome measures including neuromonitoring, neurophysiology, neuroimaging, and neuropathology. Nonetheless, while challenging, this clinically relevant model has proven valuable for identifying mechanisms of acute and progressive neuropathologies as well as for the evaluation of noninvasive diagnostic techniques and potential neuroprotective treatments following TBI. PMID:27604725

Brain reorganization, not relative brain size, primarily characterizes anthropoid brain evolution.

PubMed

Smaers, J B; Soligo, C

2013-05-22

Comparative analyses of primate brain evolution have highlighted changes in size and internal organization as key factors underlying species diversity. It remains, however, unclear (i) how much variation in mosaic brain reorganization versus variation in relative brain size contributes to explaining the structural neural diversity observed across species, (ii) which mosaic changes contribute most to explaining diversity, and (iii) what the temporal origin, rates and processes are that underlie evolutionary shifts in mosaic reorganization for individual branches of the primate tree of life. We address these questions by combining novel comparative methods that allow assessing the temporal origin, rate and process of evolutionary changes on individual branches of the tree of life, with newly available data on volumes of key brain structures (prefrontal cortex, frontal motor areas and cerebrocerebellum) for a sample of 17 species (including humans). We identify patterns of mosaic change in brain evolution that mirror brain systems previously identified by electrophysiological and anatomical tract-tracing studies in non-human primates and functional connectivity MRI studies in humans. Across more than 40 Myr of anthropoid primate evolution, mosaic changes contribute more to explaining neural diversity than changes in relative brain size, and different mosaic patterns are differentially selected for when brains increase or decrease in size. We identify lineage-specific evolutionary specializations for all branches of the tree of life covered by our sample and demonstrate deep evolutionary roots for mosaic patterns associated with motor control and learning.

Brain reorganization, not relative brain size, primarily characterizes anthropoid brain evolution

PubMed Central

Smaers, J. B.; Soligo, C.

2013-01-01

Comparative analyses of primate brain evolution have highlighted changes in size and internal organization as key factors underlying species diversity. It remains, however, unclear (i) how much variation in mosaic brain reorganization versus variation in relative brain size contributes to explaining the structural neural diversity observed across species, (ii) which mosaic changes contribute most to explaining diversity, and (iii) what the temporal origin, rates and processes are that underlie evolutionary shifts in mosaic reorganization for individual branches of the primate tree of life. We address these questions by combining novel comparative methods that allow assessing the temporal origin, rate and process of evolutionary changes on individual branches of the tree of life, with newly available data on volumes of key brain structures (prefrontal cortex, frontal motor areas and cerebrocerebellum) for a sample of 17 species (including humans). We identify patterns of mosaic change in brain evolution that mirror brain systems previously identified by electrophysiological and anatomical tract-tracing studies in non-human primates and functional connectivity MRI studies in humans. Across more than 40 Myr of anthropoid primate evolution, mosaic changes contribute more to explaining neural diversity than changes in relative brain size, and different mosaic patterns are differentially selected for when brains increase or decrease in size. We identify lineage-specific evolutionary specializations for all branches of the tree of life covered by our sample and demonstrate deep evolutionary roots for mosaic patterns associated with motor control and learning. PMID:23536600

Embolic Brain Infarcts: A Rare Fatal Complication of Preoperative Embolization of a Massive Solitary Fibrous Tumor of the Pleura

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patel, Shreyas R., E-mail: Shrey000@gmail.com; Vachhani, Prasann; Moeslein, Fred

Solitary fibrous tumor of the pleura (SFTP) is a rare intrathoracic neoplasm, often giant in size and highly vascular, which can make surgical resection very challenging. Preoperative percutaneous embolization before surgical removal can significantly reduce the risk of uncontrollable intraoperative hemorrhage. However, a rare potential life threatening complication could result from embolization of SFTP and must be taken into consideration. This report describes a 69-year-old female with a large right thoracic SFTP, who underwent preoperative angiography and embolization and developed diffuse embolic brain infarcts immediately after the administration of polyvinyl alcohol particles.

Mapping the Schizophrenia Genes by Neuroimaging: The Opportunities and the Challenges

PubMed Central

2018-01-01

Schizophrenia (SZ) is a heritable brain disease originating from a complex interaction of genetic and environmental factors. The genes underpinning the neurobiology of SZ are largely unknown but recent data suggest strong evidence for genetic variations, such as single nucleotide polymorphisms, making the brain vulnerable to the risk of SZ. Structural and functional brain mapping of these genetic variations are essential for the development of agents and tools for better diagnosis, treatment and prevention of SZ. Addressing this, neuroimaging methods in combination with genetic analysis have been increasingly used for almost 20 years. So-called imaging genetics, the opportunities of this approach along with its limitations for SZ research will be outlined in this invited paper. While the problems such as reproducibility, genetic effect size, specificity and sensitivity exist, opportunities such as multivariate analysis, development of multisite consortia for large-scale data collection, emergence of non-candidate gene (hypothesis-free) approach of neuroimaging genetics are likely to contribute to a rapid progress for gene discovery besides to gene validation studies that are related to SZ. PMID:29324666

The mimetic transition: a simulation study of the evolution of learning by imitation.

PubMed

Higgs, P G

2000-07-07

Culturally transmitted ideas or memes must have had a large effect on the survival and fecundity of early humans. Those with better techniques of obtaining food and making tools, clothing and shelters would have had a substantial advantage. It has been proposed that memes can explain why our species has an unusually large brain and high cognitive ability: the brain evolved because of selection for the ability to imitate. This article presents an evolutionary model of a population in which culturally transmitted memes can have both positive and negative effects on the fitness of individuals. It is found that genes for increased imitative ability are selectively favoured. The model predicts that imitative ability increases slowly until a mimetic transition occurs where memes become able to spread like an epidemic. At this point there is a dramatic increase in the imitative ability, the number of memes known per individual and the mean fitness of the population. Selection for increased imitative ability is able to overcome substantial selection against increased brain size in some cases.

The mimetic transition: a simulation study of the evolution of learning by imitation.

PubMed Central

Higgs, P G

2000-01-01

Culturally transmitted ideas or memes must have had a large effect on the survival and fecundity of early humans. Those with better techniques of obtaining food and making tools, clothing and shelters would have had a substantial advantage. It has been proposed that memes can explain why our species has an unusually large brain and high cognitive ability: the brain evolved because of selection for the ability to imitate. This article presents an evolutionary model of a population in which culturally transmitted memes can have both positive and negative effects on the fitness of individuals. It is found that genes for increased imitative ability are selectively favoured. The model predicts that imitative ability increases slowly until a mimetic transition occurs where memes become able to spread like an epidemic. At this point there is a dramatic increase in the imitative ability, the number of memes known per individual and the mean fitness of the population. Selection for increased imitative ability is able to overcome substantial selection against increased brain size in some cases. PMID:10972132

Food Web Structure Shapes the Morphology of Teleost Fish Brains.

PubMed

Edmunds, Nicholas B; McCann, Kevin S; Laberge, Frédéric

2016-01-01

Previous work showed that teleost fish brain size correlates with the flexible exploitation of habitats and predation abilities in an aquatic food web. Since it is unclear how regional brain changes contribute to these relationships, we quantitatively examined the effects of common food web attributes on the size of five brain regions in teleost fish at both within-species (plasticity or natural variation) and between-species (evolution) scales. Our results indicate that brain morphology is influenced by habitat use and trophic position, but not by the degree of littoral-pelagic habitat coupling, despite the fact that the total brain size was previously shown to increase with habitat coupling in Lake Huron. Intriguingly, the results revealed two potential evolutionary trade-offs: (i) relative olfactory bulb size increased, while relative optic tectum size decreased, across a trophic position gradient, and (ii) the telencephalon was relatively larger in fish using more littoral-based carbon, while the cerebellum was relatively larger in fish using more pelagic-based carbon. Additionally, evidence for a within-species effect on the telencephalon was found, where it increased in size with trophic position. Collectively, these results suggest that food web structure has fundamentally contributed to the shaping of teleost brain morphology. © 2016 S. Karger AG, Basel.

Is the social brain theory applicable to human individual differences? Relationship between sociability personality dimension and brain size.

PubMed

Horváth, Klára; Martos, János; Mihalik, Béla; Bódizs, Róbert

2011-06-17

Our study intends to examine whether the social brain theory is applicable to human individual differences. According to the social brain theory primates have larger brains as it could be expected from their body sizes due to the adaptation to a more complex social life. Regarding humans there were few studies about the relationship between theory of mind and frontal and temporal brain lobes. We hypothesized that these brain lobes, as well as the whole cerebrum and neocortex are in connection with the Sociability personality dimension that is associated with individuals' social lives. Our findings support this hypothesis as Sociability correlated positively with the examined brain structures if we control the effects of body size differences and age. These results suggest that the social brain theory can be extended to human interindividual differences and they have some implications to personality psychology too.

Polymer Nanoparticles as Smart Carriers for the Enhanced Release of Therapeutic Agents to the CNS.

PubMed

Gagliardi, Mariacristina; Borri, Claudia

2017-01-01

The brain is the most protected organ in the human body; its protective shield, relying on a complex system of cells, proteins and transporters, prevents potentially harmful substances from entering the brain from the bloodstream but, on the other hand, it also stops drugs administered via the systemic route. To improve the efficacy of pharmacological treatments, targeted drug delivery by means of polymer nanoparticles is a challenging but, at the same time, efficient strategy. Thanks to a highly multidisciplinary approach, several ways to overcome the brain protection have provided effective solutions to treat a large number of diseases. Important advances in polymer science, together with the development of novel techniques for nanocarrier preparation, and the discovery of novel targeting ligands and molecules, allow a fine-tuning of size, shape, chemicophysical properties and surface chemistry of functional particulate systems; it enables the improvement of the therapeutic performances for several drugs, also toward districts that are difficult to be treated, such as the brain. This review focuses on the great strides made from scientists and doctors in the development of polymer nano-sized drug delivery systems for brain diseases. Even though the optimal nanocarrier was not yet discovered, important advances were made to strive for safer, performant and successful systems, with the expectation to find soon better solutions to cure some still untreatable pathologies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Graph-theoretical analysis of resting-state fMRI in pediatric obsessive-compulsive disorder

PubMed Central

Armstrong, Casey C.; Moody, Teena D.; Feusner, Jamie D.; McCracken, James T.; Chang, Susanna; Levitt, Jennifer G.; Piacentini, John C.; O'Neill, Joseph

2018-01-01

Background fMRI graph theory reveals resting-state brain networks, but has never been used in pediatric OCD. Methods Whole-brain resting-state fMRI was acquired at 3 T from 21 children with OCD and 20 age-matched healthy controls. BOLD connectivity was analyzed yielding global and local graph-theory metrics across 100 child-based functional nodes. We also compared local metrics between groups in frontopolar, supplementary motor, and sensorimotor cortices, regions implicated in recent neuroimaging and/or brain stimulation treatment studies in OCD. Results As in adults, the global metric small-worldness was significantly (P<0.05) lower in patients than controls, by 13.5% (%mean difference = 100%×(OCD mean – control mean)/control mean). This suggests less efficient information transfer in patients. In addition, modularity was lower in OCD (15.1%, P<0.01), suggesting less granular-- or differently organized-- functional brain parcellation. Higher clustering coefficients (23.9-32.4%, P<0.05) were observed in patients in frontopolar, supplementary motor, sensorimotor, and cortices with lower betweenness centrality (-63.6%, P<0.01) at one frontopolar site. These findings are consistent with more locally intensive connectivity or less interaction with other brain regions at these sites. Limitations Relatively large node size; relatively small sample size, comorbidities in some patients. Conclusions Pediatric OCD patients demonstrate aberrant global and local resting-state network connectivity topologies compared to healthy children. Local results accord with recent views of OCD as a disorder with sensorimotor component. PMID:26773910

Differences between chronological and brain age are related to education and self-reported physical activity.

PubMed

Steffener, Jason; Habeck, Christian; O'Shea, Deirdre; Razlighi, Qolamreza; Bherer, Louis; Stern, Yaakov

2016-04-01

This study investigated the relationship between education and physical activity and the difference between a physiological prediction of age and chronological age (CA). Cortical and subcortical gray matter regional volumes were calculated from 331 healthy adults (range: 19-79 years). Multivariate analyses identified a covariance pattern of brain volumes best predicting CA (R(2) = 47%). Individual expression of this brain pattern served as a physiologic measure of brain age (BA). The difference between CA and BA was predicted by education and self-report measures of physical activity. Education and the daily number of flights of stairs climbed (FOSC) were the only 2 significant predictors of decreased BA. Effect sizes demonstrated that BA decreased by 0.95 years for each year of education and by 0.58 years for 1 additional FOSC daily. Effects of education and FOSC on regional brain volume were largely driven by temporal and subcortical volumes. These results demonstrate that higher levels of education and daily FOSC are related to larger brain volume than predicted by CA which supports the utility of regional gray matter volume as a biomarker of healthy brain aging. Copyright © 2016 Elsevier Inc. All rights reserved.

Longitudinal Regional Brain Development and Clinical Risk Factors in Extremely Preterm Infants.

PubMed

Kersbergen, Karina J; Makropoulos, Antonios; Aljabar, Paul; Groenendaal, Floris; de Vries, Linda S; Counsell, Serena J; Benders, Manon J N L

2016-11-01

To investigate third-trimester extrauterine brain growth and correlate this with clinical risk factors in the neonatal period, using serially acquired brain tissue volumes in a large, unselected cohort of extremely preterm born infants. Preterm infants (gestational age <28 weeks) underwent brain magnetic resonance imaging (MRI) at around 30 weeks postmenstrual age and again around term equivalent age. MRIs were segmented in 50 different regions covering the entire brain. Multivariable regression analysis was used to determine the influence of clinical variables on volumes at both scans, as well as on volumetric growth. MRIs at term equivalent age were available for 210 infants and serial data were available for 131 infants. Growth over these 10 weeks was greatest for the cerebellum, with an increase of 258%. Sex, birth weight z-score, and prolonged mechanical ventilation showed global effects on brain volumes on both scans. The effect of brain injury on ventricular size was already visible at 30 weeks, whereas growth data and volumes at term-equivalent age revealed the effect of brain injury on the cerebellum. This study provides data about third-trimester extrauterine volumetric brain growth in preterm infants. Both global and local effects of several common clinical risk factors were found to influence serial volumetric measurements, highlighting the vulnerability of the human brain, especially in the presence of brain injury, during this period. Copyright © 2016 Elsevier Inc. All rights reserved.

Explaining brain size variation: from social to cultural brain.

PubMed

van Schaik, Carel P; Isler, Karin; Burkart, Judith M

2012-05-01

Although the social brain hypothesis has found near-universal acceptance as the best explanation for the evolution of extensive variation in brain size among mammals, it faces two problems. First, it cannot account for grade shifts, where species or complete lineages have a very different brain size than expected based on their social organization. Second, it cannot account for the observation that species with high socio-cognitive abilities also excel in general cognition. These problems may be related. For birds and mammals, we propose to integrate the social brain hypothesis into a broader framework we call cultural intelligence, which stresses the importance of the high costs of brain tissue, general behavioral flexibility and the role of social learning in acquiring cognitive skills. Copyright © 2012 Elsevier Ltd. All rights reserved.

Complex pattern of variation in neurocranial ontogeny revealed by CT-scanning.

PubMed

Anzelmo, Marisol; Ventrice, Fernando; Kelmansky, Diana; Sardi, Marina

2018-05-01

The neurocranium of hominid species has been largely studied with reference to the midsagittal plane, with variations being attributed to brain evolution. By contrast, there is limited information on variation in non-midsagittal regions, which are the points of insertion of muscles and bony structures related to mastication. This work aims to analyze ontogenetic changes and sexual dimorphism (SD) in midsagittal and non-midsagittal neurocranial structures from a contemporary human sample comprising 138 computed tomography (CT) cranial images of individuals ranging from infants to adults. Morphology of the vault and the base was assessed by registering landmarks and semilandmarks, which were analyzed by geometric morphometrics, and the endocranial volume (EV). The results of regressions and Kruskal-Wallis test indicate that the major size and shape changes in both midsagittal and non-midsagittal regions occur during infancy and juvenility; shape changes are also associated with an increase in EV. The size of the midsagittal vault, the shape of the non-midsagittal vault and the size of the base show an extension of ontogenetic trajectories. Sexes show similar changes in shape but different changes in size. We conclude that brain growth appears to be an important factor influencing the morphology of the neurocranium, at least during infancy and childhood. Subsequent changes may be attributed to osteogenic activity and the differential growth of the brain lobes. Masticatory-related bony structures and muscles may not be strong enough factors to induce independent modifications in non-midsagittal structures. The small influence of the cranial muscles would explain why the human neurocranium is a quite integrated structure.

Miniaturized integration of a fluorescence microscope

PubMed Central

Ghosh, Kunal K.; Burns, Laurie D.; Cocker, Eric D.; Nimmerjahn, Axel; Ziv, Yaniv; Gamal, Abbas El; Schnitzer, Mark J.

2013-01-01

The light microscope is traditionally an instrument of substantial size and expense. Its miniaturized integration would enable many new applications based on mass-producible, tiny microscopes. Key prospective usages include brain imaging in behaving animals towards relating cellular dynamics to animal behavior. Here we introduce a miniature (1.9 g) integrated fluorescence microscope made from mass-producible parts, including semiconductor light source and sensor. This device enables high-speed cellular-level imaging across ∼0.5 mm2 areas in active mice. This capability allowed concurrent tracking of Ca2+ spiking in >200 Purkinje neurons across nine cerebellar microzones. During mouse locomotion, individual microzones exhibited large-scale, synchronized Ca2+ spiking. This is a mesoscopic neural dynamic missed by prior techniques for studying the brain at other length scales. Overall, the integrated microscope is a potentially transformative technology that permits distribution to many animals and enables diverse usages, such as portable diagnostics or microscope arrays for large-scale screens. PMID:21909102

Miniaturized integration of a fluorescence microscope.

PubMed

Ghosh, Kunal K; Burns, Laurie D; Cocker, Eric D; Nimmerjahn, Axel; Ziv, Yaniv; Gamal, Abbas El; Schnitzer, Mark J

2011-09-11

The light microscope is traditionally an instrument of substantial size and expense. Its miniaturized integration would enable many new applications based on mass-producible, tiny microscopes. Key prospective usages include brain imaging in behaving animals for relating cellular dynamics to animal behavior. Here we introduce a miniature (1.9 g) integrated fluorescence microscope made from mass-producible parts, including a semiconductor light source and sensor. This device enables high-speed cellular imaging across ∼0.5 mm2 areas in active mice. This capability allowed concurrent tracking of Ca2+ spiking in >200 Purkinje neurons across nine cerebellar microzones. During mouse locomotion, individual microzones exhibited large-scale, synchronized Ca2+ spiking. This is a mesoscopic neural dynamic missed by prior techniques for studying the brain at other length scales. Overall, the integrated microscope is a potentially transformative technology that permits distribution to many animals and enables diverse usages, such as portable diagnostics or microscope arrays for large-scale screens.

Framework for cognitive analysis of dynamic perfusion computed tomography with visualization of large volumetric data

NASA Astrophysics Data System (ADS)

Hachaj, Tomasz; Ogiela, Marek R.

2012-10-01

The proposed framework for cognitive analysis of perfusion computed tomography images is a fusion of image processing, pattern recognition, and image analysis procedures. The output data of the algorithm consists of: regions of perfusion abnormalities, anatomy atlas description of brain tissues, measures of perfusion parameters, and prognosis for infracted tissues. That information is superimposed onto volumetric computed tomography data and displayed to radiologists. Our rendering algorithm enables rendering large volumes on off-the-shelf hardware. This portability of rendering solution is very important because our framework can be run without using expensive dedicated hardware. The other important factors are theoretically unlimited size of rendered volume and possibility of trading of image quality for rendering speed. Such rendered, high quality visualizations may be further used for intelligent brain perfusion abnormality identification, and computer aided-diagnosis of selected types of pathologies.

General proactive interference and the N450 response.

PubMed

Tays, William J; Dywan, Jane; Segalowitz, Sidney J

2009-10-25

Strategic repetition of verbal stimuli can effectively produce proactive interference (PI) effects in the Sternberg working memory task. Unique fronto-cortical activation to PI-eliciting letter probes has been interpreted as reflecting brain responses to PI. However, the use of only a small set of stimuli (e.g., letters and digits) requires constant repetition of stimuli in both PI and baseline trials, potentially creating a general PI effect in all conditions. We used event-related potentials to examine general PI effects by contrasting the interference-related frontal N450 response in two Sternberg tasks using a small versus large set size. We found that the N450 response differed significantly from baseline during the small set-size task only for response-conflict PI trials but not when PI was created solely from stimulus repetition. During the large set-size task N450 responses in both the familiarity-based and response-conflict PI conditions differed from baseline but not from each other. We conclude that the general stimulus repetition inherent in small set-size conditions can mask effects of familiarity-based PI and complicate the interpretation of any associated neural response.

The relation between statistical power and inference in fMRI

PubMed Central

Wager, Tor D.; Yarkoni, Tal

2017-01-01

Statistically underpowered studies can result in experimental failure even when all other experimental considerations have been addressed impeccably. In fMRI the combination of a large number of dependent variables, a relatively small number of observations (subjects), and a need to correct for multiple comparisons can decrease statistical power dramatically. This problem has been clearly addressed yet remains controversial—especially in regards to the expected effect sizes in fMRI, and especially for between-subjects effects such as group comparisons and brain-behavior correlations. We aimed to clarify the power problem by considering and contrasting two simulated scenarios of such possible brain-behavior correlations: weak diffuse effects and strong localized effects. Sampling from these scenarios shows that, particularly in the weak diffuse scenario, common sample sizes (n = 20–30) display extremely low statistical power, poorly represent the actual effects in the full sample, and show large variation on subsequent replications. Empirical data from the Human Connectome Project resembles the weak diffuse scenario much more than the localized strong scenario, which underscores the extent of the power problem for many studies. Possible solutions to the power problem include increasing the sample size, using less stringent thresholds, or focusing on a region-of-interest. However, these approaches are not always feasible and some have major drawbacks. The most prominent solutions that may help address the power problem include model-based (multivariate) prediction methods and meta-analyses with related synthesis-oriented approaches. PMID:29155843

Dynamic analysis of the blood-brain barrier disruption in experimental stroke using time domain in vivo fluorescence imaging.

PubMed

Abulrob, Abedelnasser; Brunette, Eric; Slinn, Jacqueline; Baumann, Ewa; Stanimirovic, Danica

2008-01-01

The blood-brain barrier (BBB) disruption following cerebral ischemia can be exploited to deliver imaging agents and therapeutics into the brain. The aim of this study was (a) to establish novel in vivo optical imaging methods for longitudinal assessment of the BBB disruption and (b) to assess size selectivity and temporal patterns of the BBB disruption after a transient focal ischemia. The BBB permeability was assessed using in vivo time domain near-infrared optical imaging after contrast enhancement with either free Cy5.5 (1 kDa) or Cy5.5 conjugated with bovine serum albumin (BSA) (67 kDa) in mice subjected to either 60- or 20-minute transient middle cerebral artery occlusion (MCAO) and various times of reperfusion (up to 14 days). In vivo imaging observations were corroborated by ex vivo brain imaging and microscopic analyses of fluorescent tracer extravasation. The in vivo optical contrast enhancement with Cy5.5 was spatially larger than that observed with BSA-Cy5.5. Longitudinal studies after a transient 20-minute MCAO suggested a bilateral BBB disruption, more pronounced in the ipsilateral hemisphere, peaking at day 7 and resolving at day 14 after ischemia. The area differential between the BBB disruption for small and large molecules could potentially be useful as a surrogate imaging marker for assessing perinfarct tissues to which neuroprotective therapies of appropriate sizes could be delivered.

Body mass estimates of hominin fossils and the evolution of human body size.

PubMed

Grabowski, Mark; Hatala, Kevin G; Jungers, William L; Richmond, Brian G

2015-08-01

Body size directly influences an animal's place in the natural world, including its energy requirements, home range size, relative brain size, locomotion, diet, life history, and behavior. Thus, an understanding of the biology of extinct organisms, including species in our own lineage, requires accurate estimates of body size. Since the last major review of hominin body size based on postcranial morphology over 20 years ago, new fossils have been discovered, species attributions have been clarified, and methods improved. Here, we present the most comprehensive and thoroughly vetted set of individual fossil hominin body mass predictions to date, and estimation equations based on a large (n = 220) sample of modern humans of known body masses. We also present species averages based exclusively on fossils with reliable taxonomic attributions, estimates of species averages by sex, and a metric for levels of sexual dimorphism. Finally, we identify individual traits that appear to be the most reliable for mass estimation for each fossil species, for use when only one measurement is available for a fossil. Our results show that many early hominins were generally smaller-bodied than previously thought, an outcome likely due to larger estimates in previous studies resulting from the use of large-bodied modern human reference samples. Current evidence indicates that modern human-like large size first appeared by at least 3-3.5 Ma in some Australopithecus afarensis individuals. Our results challenge an evolutionary model arguing that body size increased from Australopithecus to early Homo. Instead, we show that there is no reliable evidence that the body size of non-erectus early Homo differed from that of australopiths, and confirm that Homo erectus evolved larger average body size than earlier hominins. Copyright © 2015 Elsevier Ltd. All rights reserved.

Light enough to travel or wise enough to stay? Brain size evolution and migratory behavior in birds.

PubMed

Vincze, Orsolya

2016-09-01

Brain size relative to body size is smaller in migratory than in nonmigratory birds. Two mutually nonexclusive hypotheses had been proposed to explain this association. On the one hand, the "energetic trade-off hypothesis" claims that migratory species were selected to have smaller brains because of the interplay between neural tissue volume and migratory flight. On the other hand, the "behavioral flexibility hypothesis" argues that resident species are selected to have higher cognitive capacities, and therefore larger brains, to enable survival in harsh winters, or to deal with environmental seasonality. Here, I test the validity and setting of these two hypotheses using 1466 globally distributed bird species. First, I show that the negative association between migration distance and relative brain size is very robust across species and phylogeny. Second, I provide strong support for the energetic trade-off hypothesis, by showing the validity of the trade-off among long-distance migratory species alone. Third, using resident and short-distance migratory species, I demonstrate that environmental harshness is associated with enlarged relative brain size, therefore arguably better cognition. My study provides the strongest comparative support to date for both the energetic trade-off and the behavioral flexibility hypotheses, and highlights that both mechanisms contribute to brain size evolution, but on different ends of the migratory spectrum. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Handedness- and brain size-related efficiency differences in small-world brain networks: a resting-state functional magnetic resonance imaging study.

PubMed

Li, Meiling; Wang, Junping; Liu, Feng; Chen, Heng; Lu, Fengmei; Wu, Guorong; Yu, Chunshui; Chen, Huafu

2015-05-01

The human brain has been described as a complex network, which integrates information with high efficiency. However, the relationships between the efficiency of human brain functional networks and handedness and brain size remain unclear. Twenty-one left-handed and 32 right-handed healthy subjects underwent a resting-state functional magnetic resonance imaging scan. The whole brain functional networks were constructed by thresholding Pearson correlation matrices of 90 cortical and subcortical regions. Graph theory-based methods were employed to further analyze their topological properties. As expected, all participants demonstrated small-world topology, suggesting a highly efficient topological structure. Furthermore, we found that smaller brains showed higher local efficiency, whereas larger brains showed higher global efficiency, reflecting a suitable efficiency balance between local specialization and global integration of brain functional activity. Compared with right-handers, significant alterations in nodal efficiency were revealed in left-handers, involving the anterior and median cingulate gyrus, middle temporal gyrus, angular gyrus, and amygdala. Our findings indicated that the functional network organization in the human brain was associated with handedness and brain size.

The association between birth order, sibship size and glioma development in adulthood.

PubMed

Amirian, E; Scheurer, Michael E; Bondy, Melissa L

2010-06-01

The etiology of brain tumors is still largely unknown. Previous research indicates that infectious agents and immunological characteristics may influence adult glioma risk. The purpose of our study was to evaluate the effects of birth order and sibship size (total number of siblings), as indicators of the timing and frequency of early life infections, on adult glioma risk using a population of 489 cases and 540 cancer-free controls from the Harris County Brain Tumor Study. Odds ratios for birth order and sibship size were calculated separately from multivariable logistic regression models, adjusting for sex, family history of cancer, education, and age. Each one-unit increase in birth order confers a 13% decreased risk of glioma development in adulthood (OR = 0.87, 95% CI = 0.79-0.97). However, sibship size was not significantly associated with adult glioma status (OR = 0.97, 95% CI = 0.91-1.04). Our study indicates that individuals who were more likely to develop common childhood infections at an earlier age (those with a higher birth order) may be more protected against developing glioma in adulthood. More biological and epidemiological research is warranted to clarify the exact mechanisms through which the timing of common childhood infections and the course of early life immune development affect gliomagenesis.

Inhibition of VEGF Signaling Reduces Diabetes-Exacerbated Brain Swelling, but Not Infarct Size, in Large Cerebral Infarction in Mice.

PubMed

Kim, Eunhee; Yang, Jiwon; Park, Keun Woo; Cho, Sunghee

2017-12-30

In light of repeated translational failures with preclinical neuroprotection-based strategies, this preclinical study reevaluates brain swelling as an important pathological event in diabetic stroke and investigates underlying mechanism of the comorbidity-enhanced brain edema formation. Type 2 (mild), type 1 (moderate), and mixed type 1/2 (severe) diabetic mice were subjected to transient focal ischemia. Infarct volume, brain swelling, and IgG extravasation were assessed at 3 days post-stroke. Expression of vascular endothelial growth factor (VEGF)-A, endothelial-specific molecule-1 (Esm1), and the VEGF receptor 2 (VEGFR2) was determined in the ischemic brain. Additionally, SU5416, a VEGFR2 inhibitor, was treated in the type 1/2 diabetic mice, and stroke outcomes were determined. All diabetic groups displayed bigger infarct volume and brain swelling compared to nondiabetic mice, and the increased swelling was disproportionately larger relative to infarct enlargement. Diabetic conditions significantly increased VEGF-A, Esm1, and VEGFR2 expressions in the ischemic brain compared to nondiabetic mice. Notably, in diabetic mice, VEGFR2 mRNA levels were positively correlated with brain swelling, but not with infarct volume. Treatment with SU5416 in diabetic mice significantly reduced brain swelling. The study shows that brain swelling is a predominant pathological event in diabetic stroke and that an underlying event for diabetes-enhanced brain swelling includes the activation of VEGF signaling. This study suggests consideration of stroke therapies aiming at primarily reducing brain swelling for subjects with diabetes.

Developmental nicotine exposure affects larval brain size and the adult dopaminergic system of Drosophila melanogaster.

PubMed

Morris, Melanie; Shaw, Ariel; Lambert, Madison; Perry, Haley Halperin; Lowenstein, Eve; Valenzuela, David; Velazquez-Ulloa, Norma Andrea

2018-06-14

Pregnant women may be exposed to nicotine if they smoke or use tobacco products, nicotine replacement therapy, or via e-cigarettes. Prenatal nicotine exposure has been shown to have deleterious effects on the nervous system in mammals including changes in brain size and in the dopaminergic system. The genetic and molecular mechanisms for these changes are not well understood. A Drosophila melanogaster model for these effects of nicotine exposure could contribute to faster identification of genes and molecular pathways underlying these effects. The purpose of this study was to determine if developmental nicotine exposure affects the nervous system of Drosophila melanogaster, focusing on changes to brain size and the dopaminergic system at two developmental stages. We reared flies on control or nicotine food from egg to 3rd instar larvae or from egg to adult and determined effectiveness of the nicotine treatment. We used immunohistochemistry to visualize the whole brain and dopaminergic neurons, using tyrosine hydroxylase as the marker. We measured brain area, tyrosine hydroxylase fluorescence, and counted the number of dopaminergic neurons in brain clusters. We detected an increase in larval brain hemisphere area, a decrease in tyrosine hydroxylase fluorescence in adult central brains, and a decrease in the number of neurons in the PPM3 adult dopaminergic cluster. We tested involvement of Dα7, one of the nicotinic acetylcholine receptor subunits, and found it was involved in eclosion, as previously described, but not involved in brain size. We conclude that developmental nicotine exposure in Drosophila melanogaster affects brain size and the dopaminergic system. Prenatal nicotine exposure in mammals has also been shown to have effects on brain size and in the dopaminergic system. This study further establishes Drosophila melanogaster as model organism to study the effects of developmental nicotine exposure. The genetic and molecular tools available for Drosophila research will allow elucidation of the mechanisms underlying the effects of nicotine exposure during development.

Personalising exercise recommendations for brain health: considerations and future directions.

PubMed

Barha, Cindy K; Galea, Liisa A; Nagamatsu, Lindsay S; Erickson, Kirk I; Liu-Ambrose, Teresa

2017-04-01

The societal value of strategies that delay the onset and progression of dementia cannot be overstated. Physical activity-unstructured and structured-is a promising, cost-effective strategy for the promotion of brain health. However, a large degree of variation exists in its efficacy. Therefore, to increase its utility as 'medication' for healthy cognitive ageing, it is imperative to identify key moderators and mediators of the positive effects of targeted exercise training on brain health. In this commentary, we focus on the type of targeted exercise training, the determinants of individual variation, including biological sex and genotypic factors, and the mechanisms by which exercise exerts its influence on the brain. We argue that a better understanding of these factors will allow for evidence-based, personalised, tailored exercise recommendations that go beyond the one-size-fits-all approach to successfully combat dementia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Graph Theoretical Analysis Reveals: Women's Brains Are Better Connected than Men's.

PubMed

Szalkai, Balázs; Varga, Bálint; Grolmusz, Vince

2015-01-01

Deep graph-theoretic ideas in the context with the graph of the World Wide Web led to the definition of Google's PageRank and the subsequent rise of the most popular search engine to date. Brain graphs, or connectomes, are being widely explored today. We believe that non-trivial graph theoretic concepts, similarly as it happened in the case of the World Wide Web, will lead to discoveries enlightening the structural and also the functional details of the animal and human brains. When scientists examine large networks of tens or hundreds of millions of vertices, only fast algorithms can be applied because of the size constraints. In the case of diffusion MRI-based structural human brain imaging, the effective vertex number of the connectomes, or brain graphs derived from the data is on the scale of several hundred today. That size facilitates applying strict mathematical graph algorithms even for some hard-to-compute (or NP-hard) quantities like vertex cover or balanced minimum cut. In the present work we have examined brain graphs, computed from the data of the Human Connectome Project, recorded from male and female subjects between ages 22 and 35. Significant differences were found between the male and female structural brain graphs: we show that the average female connectome has more edges, is a better expander graph, has larger minimal bisection width, and has more spanning trees than the average male connectome. Since the average female brain weighs less than the brain of males, these properties show that the female brain has better graph theoretical properties, in a sense, than the brain of males. It is known that the female brain has a smaller gray matter/white matter ratio than males, that is, a larger white matter/gray matter ratio than the brain of males; this observation is in line with our findings concerning the number of edges, since the white matter consists of myelinated axons, which, in turn, roughly correspond to the connections in the brain graph. We have also found that the minimum bisection width, normalized with the edge number, is also significantly larger in the right and the left hemispheres in females: therefore, the differing bisection widths are independent from the difference in the number of edges.

Graph Theoretical Analysis Reveals: Women’s Brains Are Better Connected than Men’s

PubMed Central

Szalkai, Balázs; Varga, Bálint; Grolmusz, Vince

2015-01-01

Deep graph-theoretic ideas in the context with the graph of the World Wide Web led to the definition of Google’s PageRank and the subsequent rise of the most popular search engine to date. Brain graphs, or connectomes, are being widely explored today. We believe that non-trivial graph theoretic concepts, similarly as it happened in the case of the World Wide Web, will lead to discoveries enlightening the structural and also the functional details of the animal and human brains. When scientists examine large networks of tens or hundreds of millions of vertices, only fast algorithms can be applied because of the size constraints. In the case of diffusion MRI-based structural human brain imaging, the effective vertex number of the connectomes, or brain graphs derived from the data is on the scale of several hundred today. That size facilitates applying strict mathematical graph algorithms even for some hard-to-compute (or NP-hard) quantities like vertex cover or balanced minimum cut. In the present work we have examined brain graphs, computed from the data of the Human Connectome Project, recorded from male and female subjects between ages 22 and 35. Significant differences were found between the male and female structural brain graphs: we show that the average female connectome has more edges, is a better expander graph, has larger minimal bisection width, and has more spanning trees than the average male connectome. Since the average female brain weighs less than the brain of males, these properties show that the female brain has better graph theoretical properties, in a sense, than the brain of males. It is known that the female brain has a smaller gray matter/white matter ratio than males, that is, a larger white matter/gray matter ratio than the brain of males; this observation is in line with our findings concerning the number of edges, since the white matter consists of myelinated axons, which, in turn, roughly correspond to the connections in the brain graph. We have also found that the minimum bisection width, normalized with the edge number, is also significantly larger in the right and the left hemispheres in females: therefore, the differing bisection widths are independent from the difference in the number of edges. PMID:26132764

New insights into differences in brain organization between Neanderthals and anatomically modern humans

PubMed Central

Pearce, Eiluned; Stringer, Chris; Dunbar, R. I. M.

2013-01-01

Previous research has identified morphological differences between the brains of Neanderthals and anatomically modern humans (AMHs). However, studies using endocasts or the cranium itself are limited to investigating external surface features and the overall size and shape of the brain. A complementary approach uses comparative primate data to estimate the size of internal brain areas. Previous attempts to do this have generally assumed that identical total brain volumes imply identical internal organization. Here, we argue that, in the case of Neanderthals and AMHs, differences in the size of the body and visual system imply differences in organization between the same-sized brains of these two taxa. We show that Neanderthals had significantly larger visual systems than contemporary AMHs (indexed by orbital volume) and that when this, along with their greater body mass, is taken into account, Neanderthals have significantly smaller adjusted endocranial capacities than contemporary AMHs. We discuss possible implications of differing brain organization in terms of social cognition, and consider these in the context of differing abilities to cope with fluctuating resources and cultural maintenance. PMID:23486442

Differential investment in visual and olfactory brain areas reflects behavioural choices in hawk moths

PubMed Central

Stöckl, Anna; Heinze, Stanley; Charalabidis, Alice; el Jundi, Basil; Warrant, Eric; Kelber, Almut

2016-01-01

Nervous tissue is one of the most metabolically expensive animal tissues, thus evolutionary investments that result in enlarged brain regions should also result in improved behavioural performance. Indeed, large-scale comparative studies in vertebrates and invertebrates have successfully linked differences in brain anatomy to differences in ecology and behaviour, but their precision can be limited by the detail of the anatomical measurements, or by only measuring behaviour indirectly. Therefore, detailed case studies are valuable complements to these investigations, and have provided important evidence linking brain structure to function in a range of higher-order behavioural traits, such as foraging experience or aggressive behaviour. Here, we show that differences in the size of both lower and higher-order sensory brain areas reflect differences in the relative importance of these senses in the foraging choices of hawk moths, as suggested by previous anatomical work in Lepidopterans. To this end we combined anatomical and behavioural quantifications of the relative importance of vision and olfaction in two closely related hawk moth species. We conclude that differences in sensory brain volume in these hawk moths can indeed be interpreted as differences in the importance of these senses for the animal’s behaviour. PMID:27185464

Structural growth trajectories and rates of change in the first 3 months of infant brain development.

PubMed

Holland, Dominic; Chang, Linda; Ernst, Thomas M; Curran, Megan; Buchthal, Steven D; Alicata, Daniel; Skranes, Jon; Johansen, Heather; Hernandez, Antonette; Yamakawa, Robyn; Kuperman, Joshua M; Dale, Anders M

2014-10-01

The very early postnatal period witnesses extraordinary rates of growth, but structural brain development in this period has largely not been explored longitudinally. Such assessment may be key in detecting and treating the earliest signs of neurodevelopmental disorders. To assess structural growth trajectories and rates of change in the whole brain and regions of interest in infants during the first 3 months after birth. Serial structural T1-weighted and/or T2-weighted magnetic resonance images were obtained for 211 time points from 87 healthy term-born or term-equivalent preterm-born infants, aged 2 to 90 days, between October 5, 2007, and June 12, 2013. We segmented whole-brain and multiple subcortical regions of interest using a novel application of Bayesian-based methods. We modeled growth and rate of growth trajectories nonparametrically and assessed left-right asymmetries and sexual dimorphisms. Whole-brain volume at birth was approximately one-third of healthy elderly brain volume, and did not differ significantly between male and female infants (347 388 mm3 and 335 509 mm3, respectively, P = .12). The growth rate was approximately 1%/d, slowing to 0.4%/d by the end of the first 3 months, when the brain reached just more than half of elderly adult brain volume. Overall growth in the first 90 days was 64%. There was a significant age-by-sex effect leading to widening separation in brain sizes with age between male and female infants (with male infants growing faster than females by 200.4 mm3/d, SE = 67.2, P = .003). Longer gestation was associated with larger brain size (2215 mm3/d, SE = 284, P = 4×10-13). The expected brain size of an infant born one week earlier than average was 5% smaller than average; at 90 days it will not have caught up, being 2% smaller than average. The cerebellum grew at the highest rate, more than doubling in 90 days, and the hippocampus grew at the slowest rate, increasing by 47% in 90 days. There was left-right asymmetry in multiple regions of interest, particularly the lateral ventricles where the left was larger than the right by 462 mm3 on average (approximately 5% of lateral ventricular volume at 2 months). We calculated volume-by-age percentile plots for assessing individual development. Normative trajectories for early postnatal brain structural development can be determined from magnetic resonance imaging and could be used to improve the detection of deviant maturational patterns indicative of neurodevelopmental disorders.

Structural Growth Trajectories and Rates of Change in the First 3 Months of Infant Brain Development

PubMed Central

Holland, Dominic; Chang, Linda; Ernst, Thomas M.; Curran, Megan; Buchthal, Steven D.; Alicata, Daniel; Skranes, Jon; Johansen, Heather; Hernandez, Antonette; Yamakawa, Robyn; Kuperman, Joshua M.; Dale, Anders M.

2016-01-01

IMPORTANCE The very early postnatal period witnesses extraordinary rates of growth, but structural brain development in this period has largely not been explored longitudinally. Such assessment may be key in detecting and treating the earliest signs of neurodevelopmental disorders. OBJECTIVE To assess structural growth trajectories and rates of change in the whole brain and regions of interest in infants during the first 3 months after birth. DESIGN, SETTING, AND PARTICIPANTS Serial structural T1-weighted and/or T2-weighted magnetic resonance images were obtained for 211 time points from 87 healthy term-born or term-equivalent preterm-born infants, aged 2 to 90 days, between October 5, 2007, and June 12, 2013. MAIN OUTCOMES AND MEASURES We segmented whole-brain and multiple subcortical regions of interest using a novel application of Bayesian-based methods. We modeled growth and rate of growth trajectories nonparametrically and assessed left-right asymmetries and sexual dimorphisms. RESULTS Whole-brain volume at birth was approximately one-third of healthy elderly brain volume, and did not differ significantly between male and female infants (347 388 mm3 and 335 509 mm3, respectively, P = .12). The growth rate was approximately 1%/d, slowing to 0.4%/d by the end of the first 3 months, when the brain reached just more than half of elderly adult brain volume. Overall growth in the first 90 days was 64%. There was a significant age-by-sex effect leading to widening separation in brain sizes with age between male and female infants (with male infants growing faster than females by 200.4 mm3/d, SE = 67.2, P = .003). Longer gestation was associated with larger brain size (2215 mm3/d, SE = 284, P = 4×10−13). The expected brain size of an infant born one week earlier than average was 5% smaller than average; at 90 days it will not have caught up, being 2% smaller than average. The cerebellum grew at the highest rate, more than doubling in 90 days, and the hippocampus grew at the slowest rate, increasing by 47% in 90 days. There was left-right asymmetry in multiple regions of interest, particularly the lateral ventricles where the left was larger than the right by 462 mm3 on average (approximately 5% of lateral ventricular volume at 2 months). We calculated volume-by-age percentile plots for assessing individual development. CONCLUSIONS AND RELEVANCE Normative trajectories for early postnatal brain structural development can be determined from magnetic resonance imaging and could be used to improve the detection of deviant maturational patterns indicative of neurodevelopmental disorders. PMID:25111045

Phylogenetic signal, feeding behaviour and brain volume in Neotropical bats.

PubMed

Rojas, D; Mancina, C A; Flores-Martínez, J J; Navarro, L

2013-09-01

Comparative correlational studies of brain size and ecological traits (e.g. feeding habits and habitat complexity) have increased our knowledge about the selective pressures on brain evolution. Studies conducted in bats as a model system assume that shared evolutionary history has a maximum effect on the traits. However, this effect has not been quantified. In addition, the effect of levels of diet specialization on brain size remains unclear. We examined the role of diet on the evolution of brain size in Mormoopidae and Phyllostomidae using two comparative methods. Body mass explained 89% of the variance in brain volume. The effect of feeding behaviour (either characterized as feeding habits, as levels of specialization on a type of item or as handling behaviour) on brain volume was also significant albeit not consistent after controlling for body mass and the strength of the phylogenetic signal (λ). Although the strength of the phylogenetic signal of brain volume and body mass was high when tested individually, λ values in phylogenetic generalized least squares models were significantly different from 1. This suggests that phylogenetic independent contrasts models are not always the best approach for the study of ecological correlates of brain size in New World bats. © 2013 The Authors. Journal of Evolutionary Biology © 2013 European Society For Evolutionary Biology.

Assessing Relevance of External Cognitive Measures.

PubMed

Cairó, Osvaldo

2017-01-01

The arrival of modern brain imaging technologies has provided new opportunities for examining the biological essence of human intelligence as well as the relationship between brain size and cognition. Thanks to these advances, we can now state that the relationship between brain size and intelligence has never been well understood. This view is supported by findings showing that cognition is correlated more with brain tissues than sheer brain size. The complexity of cellular and molecular organization of neural connections actually determines the computational capacity of the brain. In this review article, we determine that while genotypes are responsible for defining the theoretical limits of intelligence, what is primarily responsible for determining whether those limits are reached or exceeded is experience (environmental influence). Therefore, we contend that the gene-environment interplay defines the intelligent quotient of an individual.

Neuroanatomical phenotyping of the mouse brain with three-dimensional autofluorescence imaging

PubMed Central

Wong, Michael D.; Dazai, Jun; Altaf, Maliha; Mark Henkelman, R.; Lerch, Jason P.; Nieman, Brian J.

2012-01-01

The structural organization of the brain is important for normal brain function and is critical to understand in order to evaluate changes that occur during disease processes. Three-dimensional (3D) imaging of the mouse brain is necessary to appreciate the spatial context of structures within the brain. In addition, the small scale of many brain structures necessitates resolution at the ∼10 μm scale. 3D optical imaging techniques, such as optical projection tomography (OPT), have the ability to image intact large specimens (1 cm3) with ∼5 μm resolution. In this work we assessed the potential of autofluorescence optical imaging methods, and specifically OPT, for phenotyping the mouse brain. We found that both specimen size and fixation methods affected the quality of the OPT image. Based on these findings we developed a specimen preparation method to improve the images. Using this method we assessed the potential of optical imaging for phenotyping. Phenotypic differences between wild-type male and female mice were quantified using computer-automated methods. We found that optical imaging of the endogenous autofluorescence in the mouse brain allows for 3D characterization of neuroanatomy and detailed analysis of brain phenotypes. This will be a powerful tool for understanding mouse models of disease and development and is a technology that fits easily within the workflow of biology and neuroscience labs. PMID:22718750

COMPARISON OF VOLUMETRIC REGISTRATION ALGORITHMS FOR TENSOR-BASED MORPHOMETRY

PubMed Central

Villalon, Julio; Joshi, Anand A.; Toga, Arthur W.; Thompson, Paul M.

2015-01-01

Nonlinear registration of brain MRI scans is often used to quantify morphological differences associated with disease or genetic factors. Recently, surface-guided fully 3D volumetric registrations have been developed that combine intensity-guided volume registrations with cortical surface constraints. In this paper, we compare one such algorithm to two popular high-dimensional volumetric registration methods: large-deformation viscous fluid registration, formulated in a Riemannian framework, and the diffeomorphic “Demons” algorithm. We performed an objective morphometric comparison, by using a large MRI dataset from 340 young adult twin subjects to examine 3D patterns of correlations in anatomical volumes. Surface-constrained volume registration gave greater effect sizes for detecting morphometric associations near the cortex, while the other two approaches gave greater effects sizes subcortically. These findings suggest novel ways to combine the advantages of multiple methods in the future. PMID:26925198

BDNF Polymorphism–Dependent OFC and DLPFC Plasticity Differentially Moderates Implicit and Explicit Bias

PubMed Central

Poore, Joshua C.; Barbey, Aron K.; Krueger, Frank; Solomon, Jeffrey; Lipsky, Robert H.; Hodgkinson, Colin A.; Goldman, David; Grafman, Jordan

2012-01-01

This study examined the role of orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (DLPFC) plasticity in controlling implicit and explicit social biases. Normal controls and patients with varied OFC and DLPFC lesion size and single nucleotide polymorphisms (SNPs) in the brain-derived neurotrophic factor (BDNF) gene, which promotes (methionine–valine [Met/Val] SNP) or stifles (valine–valine [Val/Val] SNP) plasticity in damaged PFC regions, completed measures of implicit and explicit social bias. Patients and controls demonstrated comparable levels of implicit bias, but patients with Met/Val SNPs exhibited less implicit bias when they had smaller OFC lesions compared with Val/Val patients with similar size lesions and those with large OFC lesions. Both patients and controls demonstrated patterns of explicit bias consistent with hypotheses. Patients with Met/Val SNPs exhibited less explicit bias when they had smaller DLPFC lesions sizes compared with Val/Val patients with similar size lesions and those with large DLPFC lesions. OFC lesion size and BDNF SNP type did not moderate explicit bias; DLPFC lesion size and BDNF SNP type did not moderate implicit bias (nor did other medial or lateral regions). Findings suggest that plasticity within specific PFC regions modulates the type and degree of social bias that individuals’ exhibit. PMID:22123938

In monkeys making value-based decisions, amygdala neurons are sensitive to cue value as distinct from cue salience.

PubMed

Leathers, Marvin L; Olson, Carl R

2017-04-01

Neurons in the lateral intraparietal (LIP) area of macaque monkey parietal cortex respond to cues predicting rewards and penalties of variable size in a manner that depends on the motivational salience of the predicted outcome (strong for both large reward and large penalty) rather than on its value (positive for large reward and negative for large penalty). This finding suggests that LIP mediates the capture of attention by salient events and does not encode value in the service of value-based decision making. It leaves open the question whether neurons elsewhere in the brain encode value in the identical task. To resolve this issue, we recorded neuronal activity in the amygdala in the context of the task employed in the LIP study. We found that responses to reward-predicting cues were similar between areas, with the majority of reward-sensitive neurons responding more strongly to cues that predicted large reward than to those that predicted small reward. Responses to penalty-predicting cues were, however, markedly different. In the amygdala, unlike LIP, few neurons were sensitive to penalty size, few penalty-sensitive neurons favored large over small penalty, and the dependence of firing rate on penalty size was negatively correlated with its dependence on reward size. These results indicate that amygdala neurons encoded cue value under circumstances in which LIP neurons exhibited sensitivity to motivational salience. However, the representation of negative value, as reflected in sensitivity to penalty size, was weaker than the representation of positive value, as reflected in sensitivity to reward size. NEW & NOTEWORTHY This is the first study to characterize amygdala neuronal responses to cues predicting rewards and penalties of variable size in monkeys making value-based choices. Manipulating reward and penalty size allowed distinguishing activity dependent on motivational salience from activity dependent on value. This approach revealed in a previous study that neurons of the lateral intraparietal (LIP) area encode motivational salience. Here, it reveals that amygdala neurons encode value. The results establish a sharp functional distinction between the two areas. Copyright © 2017 the American Physiological Society.

Sex-dependent association of common variants of microcephaly genes with brain structure.

PubMed

Rimol, Lars M; Agartz, Ingrid; Djurovic, Srdjan; Brown, Andrew A; Roddey, J Cooper; Kähler, Anna K; Mattingsdal, Morten; Athanasiu, Lavinia; Joyner, Alexander H; Schork, Nicholas J; Halgren, Eric; Sundet, Kjetil; Melle, Ingrid; Dale, Anders M; Andreassen, Ole A

2010-01-05

Loss-of-function mutations in the genes associated with primary microcephaly (MCPH) reduce human brain size by about two-thirds, without producing gross abnormalities in brain organization or physiology and leaving other organs largely unaffected [Woods CG, et al. (2005) Am J Hum Genet 76:717-728]. There is also evidence suggesting that MCPH genes have evolved rapidly in primates and humans and have been subjected to selection in recent human evolution [Vallender EJ, et al. (2008) Trends Neurosci 31:637-644]. Here, we show that common variants of MCPH genes account for some of the common variation in brain structure in humans, independently of disease status. We investigated the correlations of SNPs from four MCPH genes with brain morphometry phenotypes obtained with MRI. We found significant, sex-specific associations between common, nonexonic, SNPs of the genes CDK5RAP2, MCPH1, and ASPM, with brain volume or cortical surface area in an ethnically homogenous Norwegian discovery sample (n = 287), including patients with mental illness. The most strongly associated SNP findings were replicated in an independent North American sample (n = 656), which included patients with dementia. These results are consistent with the view that common variation in brain structure is associated with genetic variants located in nonexonic, presumably regulatory, regions.

Internal benchmarking of a human blood-brain barrier cell model for screening of nanoparticle uptake and transcytosis.

PubMed

Ragnaill, Michelle Nic; Brown, Meredith; Ye, Dong; Bramini, Mattia; Callanan, Sean; Lynch, Iseult; Dawson, Kenneth A

2011-04-01

Transport of drugs across the blood-brain barrier, which protects the brain from harmful agents, is considered the holy grail of targeted delivery, due to the extreme effectiveness of this barrier at preventing passage of non-essential molecules through to the brain. This has caused severe limitations for therapeutics for many brain-associated diseases, such as HIV and neurodegenerative diseases. Nanomaterials, as a result of their small size (in the order of many protein-lipid clusters routinely transported by cells) and their large surface area (which acts as a scaffold for proteins thereby rendering nanoparticles as biological entities) offer great promise for neuro-therapeutics. However, in parallel with developing neuro-therapeutic applications based on nanotechnology, it is essential to ensure their safety and long-term consequences upon reaching the brain. One approach to determining safe application of nanomaterials in biology is to obtain a deep mechanistic understanding of the interactions between nanomaterials and living systems (bionanointeractions). To this end, we report here on the establishment and internal round robin validation of a human cell model of the blood-brain barrier for use as a tool for screening nanoparticles interactions, and assessing the critical nanoscale parameters that determine transcytosis. Copyright © 2011 Elsevier B.V. All rights reserved.

Automated voxel classification used with atlas-guided diffuse optical tomography for assessment of functional brain networks in young and older adults.

PubMed

Li, Lin; Cazzell, Mary; Babawale, Olajide; Liu, Hanli

2016-10-01

Atlas-guided diffuse optical tomography (atlas-DOT) is a computational means to image changes in cortical hemodynamic signals during human brain activities. Graph theory analysis (GTA) is a network analysis tool commonly used in functional neuroimaging to study brain networks. Atlas-DOT has not been analyzed with GTA to derive large-scale brain connectivity/networks based on near-infrared spectroscopy (NIRS) measurements. We introduced an automated voxel classification (AVC) method that facilitated the use of GTA with atlas-DOT images by grouping unequal-sized finite element voxels into anatomically meaningful regions of interest within the human brain. The overall approach included volume segmentation, AVC, and cross-correlation. To demonstrate the usefulness of AVC, we applied reproducibility analysis to resting-state functional connectivity measurements conducted from 15 young adults in a two-week period. We also quantified and compared changes in several brain network metrics between young and older adults, which were in agreement with those reported by a previous positron emission tomography study. Overall, this study demonstrated that AVC is a useful means for facilitating integration or combination of atlas-DOT with GTA and thus for quantifying NIRS-based, voxel-wise resting-state functional brain networks.

MultiMap: A Tool to Automatically Extract and Analyse Spatial Microscopic Data From Large Stacks of Confocal Microscopy Images

PubMed Central

Varando, Gherardo; Benavides-Piccione, Ruth; Muñoz, Alberto; Kastanauskaite, Asta; Bielza, Concha; Larrañaga, Pedro; DeFelipe, Javier

2018-01-01

The development of 3D visualization and reconstruction methods to analyse microscopic structures at different levels of resolutions is of great importance to define brain microorganization and connectivity. MultiMap is a new tool that allows the visualization, 3D segmentation and quantification of fluorescent structures selectively in the neuropil from large stacks of confocal microscopy images. The major contribution of this tool is the posibility to easily navigate and create regions of interest of any shape and size within a large brain area that will be automatically 3D segmented and quantified to determine the density of puncta in the neuropil. As a proof of concept, we focused on the analysis of glutamatergic and GABAergic presynaptic axon terminals in the mouse hippocampal region to demonstrate its use as a tool to provide putative excitatory and inhibitory synaptic maps. The segmentation and quantification method has been validated over expert labeled images of the mouse hippocampus and over two benchmark datasets, obtaining comparable results to the expert detections. PMID:29875639

MultiMap: A Tool to Automatically Extract and Analyse Spatial Microscopic Data From Large Stacks of Confocal Microscopy Images.

PubMed

Varando, Gherardo; Benavides-Piccione, Ruth; Muñoz, Alberto; Kastanauskaite, Asta; Bielza, Concha; Larrañaga, Pedro; DeFelipe, Javier

2018-01-01

The development of 3D visualization and reconstruction methods to analyse microscopic structures at different levels of resolutions is of great importance to define brain microorganization and connectivity. MultiMap is a new tool that allows the visualization, 3D segmentation and quantification of fluorescent structures selectively in the neuropil from large stacks of confocal microscopy images. The major contribution of this tool is the posibility to easily navigate and create regions of interest of any shape and size within a large brain area that will be automatically 3D segmented and quantified to determine the density of puncta in the neuropil. As a proof of concept, we focused on the analysis of glutamatergic and GABAergic presynaptic axon terminals in the mouse hippocampal region to demonstrate its use as a tool to provide putative excitatory and inhibitory synaptic maps. The segmentation and quantification method has been validated over expert labeled images of the mouse hippocampus and over two benchmark datasets, obtaining comparable results to the expert detections.

Inference in the age of big data: Future perspectives on neuroscience.

PubMed

Bzdok, Danilo; Yeo, B T Thomas

2017-07-15

Neuroscience is undergoing faster changes than ever before. Over 100 years our field qualitatively described and invasively manipulated single or few organisms to gain anatomical, physiological, and pharmacological insights. In the last 10 years neuroscience spawned quantitative datasets of unprecedented breadth (e.g., microanatomy, synaptic connections, and optogenetic brain-behavior assays) and size (e.g., cognition, brain imaging, and genetics). While growing data availability and information granularity have been amply discussed, we direct attention to a less explored question: How will the unprecedented data richness shape data analysis practices? Statistical reasoning is becoming more important to distill neurobiological knowledge from healthy and pathological brain measurements. We argue that large-scale data analysis will use more statistical models that are non-parametric, generative, and mixing frequentist and Bayesian aspects, while supplementing classical hypothesis testing with out-of-sample predictions. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Molecular Magnetic Resonance Imaging of Endothelial Activation in the Central Nervous System

PubMed Central

Gauberti, Maxime; Fournier, Antoine P.; Docagne, Fabian; Vivien, Denis; Martinez de Lizarrondo, Sara

2018-01-01

Endothelial cells of the central nervous system over-express surface proteins during neurological disorders, either as a cause, or a consequence, of the disease. Since the cerebral vasculature is easily accessible by large contrast-carrying particles, it constitutes a target of choice for molecular magnetic resonance imaging (MRI). In this review, we highlight the most recent advances in molecular MRI of brain endothelial activation and focus on the development of micro-sized particles of iron oxide (MPIO) targeting adhesion molecules including intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), P-Selectin and E-Selectin. We also discuss the perspectives and challenges for the clinical application of this technology in neurovascular disorders (ischemic stroke, intracranial hemorrhage, subarachnoid hemorrhage, diabetes mellitus), neuroinflammatory disorders (multiple sclerosis, brain infectious diseases, sepsis), neurodegenerative disorders (Alzheimer's disease, vascular dementia, aging) and brain cancers (primitive neoplasms, metastasis). PMID:29507614

Relative Brain and Brain Part Sizes Provide Only Limited Evidence that Machiavellian Behaviour in Cleaner Wrasse Is Cognitively Demanding

PubMed Central

Chojnacka, Dominika; Isler, Karin; Barski, Jaroslaw Jerzy; Bshary, Redouan

2015-01-01

It is currently widely accepted that the complexity of a species’ social life is a major determinant of its brain complexity, as predicted by the social brain hypothesis. However, it remains a challenge to explain what social complexity exactly is and what the best corresponding measures of brain anatomy are. Absolute and relative size of the brain and of the neocortex have often been used as a proxy to predict cognitive performance. Here, we apply the logic of the social brain hypothesis to marine cleaning mutualism involving the genus Labroides. These wrasses remove ectoparasites from ‘client’ reef fish. Conflict occurs as wrasse prefer client mucus over ectoparasites, where mucus feeding constitutes cheating. As a result of this conflict, cleaner wrasse show remarkable Machiavellian-like behaviour. Using own data as well as available data from the literature, we investigated whether the general brain anatomy of Labroides provides any indication that their Machiavellian behaviour is associated with a more complex brain. Neither data set provided evidence for an increased encephalisation index compared to other wrasse species. Published data on relative sizes of brain parts in 25 species of the order Perciformes suggests that only the diencephalon is relatively enlarged in Labroides dimidiatus. This part contains various nuclei of the social decision making network. In conclusion, gross brain anatomy yields little evidence for the hypothesis that strategic behaviour in cleaning selects for larger brains, while future research should focus on more detailed aspects like the sizes of specific nuclei as well as their cryoarchitectonic structure and connectivity. PMID:26263490

Relative Brain and Brain Part Sizes Provide Only Limited Evidence that Machiavellian Behaviour in Cleaner Wrasse Is Cognitively Demanding.

PubMed

Chojnacka, Dominika; Isler, Karin; Barski, Jaroslaw Jerzy; Bshary, Redouan

2015-01-01

It is currently widely accepted that the complexity of a species' social life is a major determinant of its brain complexity, as predicted by the social brain hypothesis. However, it remains a challenge to explain what social complexity exactly is and what the best corresponding measures of brain anatomy are. Absolute and relative size of the brain and of the neocortex have often been used as a proxy to predict cognitive performance. Here, we apply the logic of the social brain hypothesis to marine cleaning mutualism involving the genus Labroides. These wrasses remove ectoparasites from 'client' reef fish. Conflict occurs as wrasse prefer client mucus over ectoparasites, where mucus feeding constitutes cheating. As a result of this conflict, cleaner wrasse show remarkable Machiavellian-like behaviour. Using own data as well as available data from the literature, we investigated whether the general brain anatomy of Labroides provides any indication that their Machiavellian behaviour is associated with a more complex brain. Neither data set provided evidence for an increased encephalisation index compared to other wrasse species. Published data on relative sizes of brain parts in 25 species of the order Perciformes suggests that only the diencephalon is relatively enlarged in Labroides dimidiatus. This part contains various nuclei of the social decision making network. In conclusion, gross brain anatomy yields little evidence for the hypothesis that strategic behaviour in cleaning selects for larger brains, while future research should focus on more detailed aspects like the sizes of specific nuclei as well as their cryoarchitectonic structure and connectivity.

Assessing Relevance of External Cognitive Measures

PubMed Central

Cairó, Osvaldo

2017-01-01

The arrival of modern brain imaging technologies has provided new opportunities for examining the biological essence of human intelligence as well as the relationship between brain size and cognition. Thanks to these advances, we can now state that the relationship between brain size and intelligence has never been well understood. This view is supported by findings showing that cognition is correlated more with brain tissues than sheer brain size. The complexity of cellular and molecular organization of neural connections actually determines the computational capacity of the brain. In this review article, we determine that while genotypes are responsible for defining the theoretical limits of intelligence, what is primarily responsible for determining whether those limits are reached or exceeded is experience (environmental influence). Therefore, we contend that the gene-environment interplay defines the intelligent quotient of an individual. PMID:28270753

Brain size and thermoregulation during the evolution of the genus Homo.

PubMed

Naya, Daniel E; Naya, Hugo; Lessa, Enrique P

2016-01-01

Several hypotheses have been proposed to explain the evolution of an energetically costly brain in the genus Homo. Some of these hypotheses are based on the correlation between climatic factors and brain size recorded for this genus during the last millions of years. In this study, we propose a complementary climatic hypothesis that is based on the mechanistic connection between temperature, thermoregulation, and size of internal organs in endothermic species. We hypothesized that global cooling during the last 3.2 my may have imposed an increased energy expenditure for thermoregulation, which in the case of hominids could represent a driver for the evolution of an expanded brain, or at least, it could imply the relaxation of a negative selection pressure acting upon this costly organ. To test this idea, here we (1) assess variation in the energetic costs of thermoregulation and brain maintenance for the last 3.2 my, and (2) evaluate the relationship between Earth temperature and brain maintenance cost for the same period, taking into account the effects of body mass and fossil age. We found that: (1) the energetic cost associated with brain enlargement represents an important fraction (between 47.5% and 82.5%) of the increase in energy needed for thermoregulation; (2) fossil age is a better predictor of brain maintenance cost than Earth temperature, suggesting that (at least) another factor correlated with time was more relevant than ambient temperature in brain size evolution; and (3) there is a significant negative correlation between the energetic cost of brain and Earth temperature, even after accounting for the effect of body mass and fossil age. Thus, our results expand the current energetic framework for the study of brain size evolution in our lineage by suggesting that a fall in Earth temperature during the last millions of years may have facilitated brain enlargement. Copyright © 2015 Elsevier Inc. All rights reserved.

Expensive Brains: "Brainy" Rodents have Higher Metabolic Rate.

PubMed

Sobrero, Raúl; May-Collado, Laura J; Agnarsson, Ingi; Hernández, Cristián E

2011-01-01

Brains are the centers of the nervous system of animals, controlling the organ systems of the body and coordinating responses to changes in the ecological and social environment. The evolution of traits that correlate with cognitive ability, such as relative brain size is thus of broad interest. Brain mass relative to body mass (BM) varies among mammals, and diverse factors have been proposed to explain this variation. A recent study provided evidence that energetics play an important role in brain evolution (Isler and van Schaik, 2006). Using composite phylogenies and data drawn from multiple sources, these authors showed that basal metabolic rate (BMR) correlates with brain mass across mammals. However, no such relationship was found within rodents. Here we re-examined the relationship between BMR and brain mass within Rodentia using a novel species-level phylogeny. Our results are sensitive to parameter evaluation; in particular how species mass is estimated. We detect no pattern when applying an approach used by previous studies, where each species BM is represented by two different numbers, one being the individual that happened to be used for BMR estimates of that species. However, this approach may compromise the analysis. When using a single value of BM for each species, whether representing a single individual, or available species mean, our findings provide evidence that brain mass (independent of BM) and BMR are correlated. These findings are thus consistent with the hypothesis that large brains evolve when the payoff for increased brain mass is greater than the energetic cost they incur.

A New Variational Method for Bias Correction and Its Applications to Rodent Brain Extraction.

PubMed

Chang, Huibin; Huang, Weimin; Wu, Chunlin; Huang, Su; Guan, Cuntai; Sekar, Sakthivel; Bhakoo, Kishore Kumar; Duan, Yuping

2017-03-01

Brain extraction is an important preprocessing step for further analysis of brain MR images. Significant intensity inhomogeneity can be observed in rodent brain images due to the high-field MRI technique. Unlike most existing brain extraction methods that require bias corrected MRI, we present a high-order and L 0 regularized variational model for bias correction and brain extraction. The model is composed of a data fitting term, a piecewise constant regularization and a smooth regularization, which is constructed on a 3-D formulation for medical images with anisotropic voxel sizes. We propose an efficient multi-resolution algorithm for fast computation. At each resolution layer, we solve an alternating direction scheme, all subproblems of which have the closed-form solutions. The method is tested on three T2 weighted acquisition configurations comprising a total of 50 rodent brain volumes, which are with the acquisition field strengths of 4.7 Tesla, 9.4 Tesla and 17.6 Tesla, respectively. On one hand, we compare the results of bias correction with N3 and N4 in terms of the coefficient of variations on 20 different tissues of rodent brain. On the other hand, the results of brain extraction are compared against manually segmented gold standards, BET, BSE and 3-D PCNN based on a number of metrics. With the high accuracy and efficiency, our proposed method can facilitate automatic processing of large-scale brain studies.

No evidence of early head circumference enlargements in children later diagnosed with autism in Israel.

PubMed

Dinstein, Ilan; Haar, Shlomi; Atsmon, Shir; Schtaerman, Hen

2017-01-01

Large controversy exists regarding the potential existence and clinical significance of larger brain volumes in toddlers who later develop autism. Assessing this relationship is important for determining the clinical utility of early head circumference (HC) measures and for assessing the validity of the early overgrowth hypothesis of autism, which suggests that early accelerated brain development may be a hallmark of the disorder. We performed a retrospective comparison of HC, height, and weight measurements between 66 toddlers who were later diagnosed with autism and 66 matched controls. These toddlers represent an unbiased regional sample from a single health service provider in the southern district of Israel. On average, participating toddlers had >8 measurements between birth and the age of two, which enabled us to characterize individual HC, height, and weight development with high precision and fit a negative exponential growth model to the data of each toddler with exceptional accuracy. The analyses revealed that HC sizes and growth rates were not significantly larger in toddlers with autism even when stratifying the autism group based on verbal capabilities at the time of diagnosis. In addition, there were no significant correlations between ADOS scores at the time of diagnosis and HC at any time-point during the first 2 years of life. These negative results add to accumulating evidence, which suggest that brain volume is not necessarily larger in toddlers who develop autism. We believe that conflicting results reported in other studies are due to small sample sizes, use of misleading population norms, changes in the clinical definition of autism over time, and/or inclusion of individuals with syndromic autism. While abnormally large brains may be evident in some individuals with autism and more clearly visible in MRI scans, converging evidence from this and other studies suggests that enlarged HC is not a common etiology of the entire autism population. Early HC measures, therefore, offer very limited clinical utility for assessment of autism risk in the general population.

Understanding the evolution of Mammalian brain structures; the need for a (new) cerebrotype approach.

PubMed

Willemet, Romain

2012-05-18

The mammalian brain varies in size by a factor of 100,000 and is composed of anatomically and functionally distinct structures. Theoretically, the manner in which brain composition can evolve is limited, ranging from highly modular ("mosaic evolution") to coordinated changes in brain structure size ("concerted evolution") or anything between these two extremes. There is a debate about the relative importance of these distinct evolutionary trends. It is shown here that the presence of taxa-specific allometric relationships between brain structures makes a taxa-specific approach obligatory. In some taxa, the evolution of the size of brain structures follows a unique, coordinated pattern, which, in addition to other characteristics at different anatomical levels, defines what has been called here a "taxon cerebrotype". In other taxa, no clear pattern is found, reflecting heterogeneity of the species' lifestyles. These results suggest that the evolution of brain size and composition depends on the complex interplay between selection pressures and constraints that have changed constantly during mammalian evolution. Therefore the variability in brain composition between species should not be considered as deviations from the normal, concerted mammalian trend, but in taxa and species-specific versions of the mammalian brain. Because it forms homogenous groups of species within this complex "space" of constraints and selection pressures, the cerebrotype approach developed here could constitute an adequate level of analysis for evo-devo studies, and by extension, for a wide range of disciplines related to brain evolution.

Understanding the Evolution of Mammalian Brain Structures; the Need for a (New) Cerebrotype Approach

PubMed Central

Willemet, Romain

2012-01-01

The mammalian brain varies in size by a factor of 100,000 and is composed of anatomically and functionally distinct structures. Theoretically, the manner in which brain composition can evolve is limited, ranging from highly modular (“mosaic evolution”) to coordinated changes in brain structure size (“concerted evolution”) or anything between these two extremes. There is a debate about the relative importance of these distinct evolutionary trends. It is shown here that the presence of taxa-specific allometric relationships between brain structures makes a taxa-specific approach obligatory. In some taxa, the evolution of the size of brain structures follows a unique, coordinated pattern, which, in addition to other characteristics at different anatomical levels, defines what has been called here a “taxon cerebrotype”. In other taxa, no clear pattern is found, reflecting heterogeneity of the species’ lifestyles. These results suggest that the evolution of brain size and composition depends on the complex interplay between selection pressures and constraints that have changed constantly during mammalian evolution. Therefore the variability in brain composition between species should not be considered as deviations from the normal, concerted mammalian trend, but in taxa and species-specific versions of the mammalian brain. Because it forms homogenous groups of species within this complex “space” of constraints and selection pressures, the cerebrotype approach developed here could constitute an adequate level of analysis for evo-devo studies, and by extension, for a wide range of disciplines related to brain evolution. PMID:24962772

Network analysis of functional brain connectivity in borderline personality disorder using resting-state fMRI

PubMed Central

Xu, Tingting; Cullen, Kathryn R.; Mueller, Bryon; Schreiner, Mindy W.; Lim, Kelvin O.; Schulz, S. Charles; Parhi, Keshab K.

2016-01-01

Borderline personality disorder (BPD) is associated with symptoms such as affect dysregulation, impaired sense of self, and self-harm behaviors. Neuroimaging research on BPD has revealed structural and functional abnormalities in specific brain regions and connections. However, little is known about the topological organizations of brain networks in BPD. We collected resting-state functional magnetic resonance imaging (fMRI) data from 20 patients with BPD and 10 healthy controls, and constructed frequency-specific functional brain networks by correlating wavelet-filtered fMRI signals from 82 cortical and subcortical regions. We employed graph-theory based complex network analysis to investigate the topological properties of the brain networks, and employed network-based statistic to identify functional dysconnections in patients. In the 0.03–0.06 Hz frequency band, compared to controls, patients with BPD showed significantly larger measures of global network topology, including the size of largest connected graph component, clustering coefficient, small-worldness, and local efficiency, indicating increased local cliquishness of the functional brain network. Compared to controls, patients showed lower nodal centrality at several hub nodes but greater centrality at several non-hub nodes in the network. Furthermore, an interconnected subnetwork in 0.03–0.06 Hz frequency band was identified that showed significantly lower connectivity in patients. The links in the subnetwork were mainly long-distance connections between regions located at different lobes; and the mean connectivity of this subnetwork was negatively correlated with the increased global topology measures. Lastly, the key network measures showed high correlations with several clinical symptom scores, and classified BPD patients against healthy controls with high accuracy based on linear discriminant analysis. The abnormal topological properties and connectivity found in this study may add new knowledge to the current understanding of functional brain networks in BPD. However, due to limitation of small sample sizes, the results of the current study should be viewed as exploratory and need to be validated on large samples in future works. PMID:26977400

Network analysis of functional brain connectivity in borderline personality disorder using resting-state fMRI.

PubMed

Xu, Tingting; Cullen, Kathryn R; Mueller, Bryon; Schreiner, Mindy W; Lim, Kelvin O; Schulz, S Charles; Parhi, Keshab K

2016-01-01

Borderline personality disorder (BPD) is associated with symptoms such as affect dysregulation, impaired sense of self, and self-harm behaviors. Neuroimaging research on BPD has revealed structural and functional abnormalities in specific brain regions and connections. However, little is known about the topological organizations of brain networks in BPD. We collected resting-state functional magnetic resonance imaging (fMRI) data from 20 patients with BPD and 10 healthy controls, and constructed frequency-specific functional brain networks by correlating wavelet-filtered fMRI signals from 82 cortical and subcortical regions. We employed graph-theory based complex network analysis to investigate the topological properties of the brain networks, and employed network-based statistic to identify functional dysconnections in patients. In the 0.03-0.06 Hz frequency band, compared to controls, patients with BPD showed significantly larger measures of global network topology, including the size of largest connected graph component, clustering coefficient, small-worldness, and local efficiency, indicating increased local cliquishness of the functional brain network. Compared to controls, patients showed lower nodal centrality at several hub nodes but greater centrality at several non-hub nodes in the network. Furthermore, an interconnected subnetwork in 0.03-0.06 Hz frequency band was identified that showed significantly lower connectivity in patients. The links in the subnetwork were mainly long-distance connections between regions located at different lobes; and the mean connectivity of this subnetwork was negatively correlated with the increased global topology measures. Lastly, the key network measures showed high correlations with several clinical symptom scores, and classified BPD patients against healthy controls with high accuracy based on linear discriminant analysis. The abnormal topological properties and connectivity found in this study may add new knowledge to the current understanding of functional brain networks in BPD. However, due to limitation of small sample sizes, the results of the current study should be viewed as exploratory and need to be validated on large samples in future works.

Brain Size and Cerebral Glucose Metabolic Rate in Nonspecific Retardation and Down Syndrome.

ERIC Educational Resources Information Center

Haier, Richard J.; And Others

1995-01-01

Brain size and cerebral glucose metabolic rate were determined for 10 individuals with mild mental retardation (MR), 7 individuals with Down syndrome (DS), and 10 matched controls. MR and DS groups both had brain volumes of about 80% compared to controls, with variance greatest within the MR group. (SLD)

Individualized statistical learning from medical image databases: application to identification of brain lesions.

PubMed

Erus, Guray; Zacharaki, Evangelia I; Davatzikos, Christos

2014-04-01

This paper presents a method for capturing statistical variation of normal imaging phenotypes, with emphasis on brain structure. The method aims to estimate the statistical variation of a normative set of images from healthy individuals, and identify abnormalities as deviations from normality. A direct estimation of the statistical variation of the entire volumetric image is challenged by the high-dimensionality of images relative to smaller sample sizes. To overcome this limitation, we iteratively sample a large number of lower dimensional subspaces that capture image characteristics ranging from fine and localized to coarser and more global. Within each subspace, a "target-specific" feature selection strategy is applied to further reduce the dimensionality, by considering only imaging characteristics present in a test subject's images. Marginal probability density functions of selected features are estimated through PCA models, in conjunction with an "estimability" criterion that limits the dimensionality of estimated probability densities according to available sample size and underlying anatomy variation. A test sample is iteratively projected to the subspaces of these marginals as determined by PCA models, and its trajectory delineates potential abnormalities. The method is applied to segmentation of various brain lesion types, and to simulated data on which superiority of the iterative method over straight PCA is demonstrated. Copyright © 2014 Elsevier B.V. All rights reserved.

A conserved pattern of differential expansion of cortical areas in simian primates.

PubMed

Chaplin, Tristan A; Yu, Hsin-Hao; Soares, Juliana G M; Gattass, Ricardo; Rosa, Marcello G P

2013-09-18

The layout of areas in the cerebral cortex of different primates is quite similar, despite significant variations in brain size. However, it is clear that larger brains are not simply scaled up versions of smaller brains: some regions of the cortex are disproportionately large in larger species. It is currently debated whether these expanded areas arise through natural selection pressures for increased cognitive capacity or as a result of the application of a common developmental sequence on different scales. Here, we used computational methods to map and quantify the expansion of the cortex in simian primates of different sizes to investigate whether there is any common pattern of cortical expansion. Surface models of the marmoset, capuchin, and macaque monkey cortex were registered using the software package CARET and the spherical landmark vector difference algorithm. The registration was constrained by the location of identified homologous cortical areas. When comparing marmosets with both capuchins and macaques, we found a high degree of expansion in the temporal parietal junction, the ventrolateral prefrontal cortex, and the dorsal anterior cingulate cortex, all of which are high-level association areas typically involved in complex cognitive and behavioral functions. These expanded maps correlated well with previously published macaque to human registrations, suggesting that there is a general pattern of primate cortical scaling.

A Drosophila model for fetal alcohol syndrome disorders: role for the insulin pathway

PubMed Central

McClure, Kimberly D.; French, Rachael L.; Heberlein, Ulrike

2011-01-01

SUMMARY Prenatal exposure to ethanol in humans results in a wide range of developmental abnormalities, including growth deficiency, developmental delay, reduced brain size, permanent neurobehavioral abnormalities and fetal death. Here we describe the use of Drosophila melanogaster as a model for exploring the effects of ethanol exposure on development and behavior. We show that developmental ethanol exposure causes reduced viability, developmental delay and reduced adult body size. We find that flies reared on ethanol-containing food have smaller brains and imaginal discs, which is due to reduced cell division rather than increased apoptosis. Additionally, we show that, as in mammals, flies reared on ethanol have altered responses to ethanol vapor exposure as adults, including increased locomotor activation, resistance to the sedating effects of the drug and reduced tolerance development upon repeated ethanol exposure. We have found that the developmental and behavioral defects are largely due to the effects of ethanol on insulin signaling; specifically, a reduction in Drosophila insulin-like peptide (Dilp) and insulin receptor expression. Transgenic expression of Dilp proteins in the larval brain suppressed both the developmental and behavioral abnormalities displayed by ethanol-reared adult flies. Our results thus establish Drosophila as a useful model system to uncover the complex etiology of fetal alcohol syndrome. PMID:21303840

Individualized Statistical Learning from Medical Image Databases: Application to Identification of Brain Lesions

PubMed Central

Erus, Guray; Zacharaki, Evangelia I.; Davatzikos, Christos

2014-01-01

This paper presents a method for capturing statistical variation of normal imaging phenotypes, with emphasis on brain structure. The method aims to estimate the statistical variation of a normative set of images from healthy individuals, and identify abnormalities as deviations from normality. A direct estimation of the statistical variation of the entire volumetric image is challenged by the high-dimensionality of images relative to smaller sample sizes. To overcome this limitation, we iteratively sample a large number of lower dimensional subspaces that capture image characteristics ranging from fine and localized to coarser and more global. Within each subspace, a “target-specific” feature selection strategy is applied to further reduce the dimensionality, by considering only imaging characteristics present in a test subject’s images. Marginal probability density functions of selected features are estimated through PCA models, in conjunction with an “estimability” criterion that limits the dimensionality of estimated probability densities according to available sample size and underlying anatomy variation. A test sample is iteratively projected to the subspaces of these marginals as determined by PCA models, and its trajectory delineates potential abnormalities. The method is applied to segmentation of various brain lesion types, and to simulated data on which superiority of the iterative method over straight PCA is demonstrated. PMID:24607564

Postoperative stereotactic radiosurgery for resected brain metastases: A comparison of outcomes for large resection cavities.

PubMed

Zhong, Jim; Ferris, Matthew J; Switchenko, Jeffrey; Press, Robert H; Buchwald, Zachary; Olson, Jeffrey J; Eaton, Bree R; Curran, Walter J; Shu, Hui-Kuo G; Crocker, Ian R; Patel, Kirtesh R

Although historical trials have established the role of surgical resection followed by whole brain irradiation (WBRT) for brain metastases, WBRT has recently been shown to cause significant neurocognitive decline. Many practitioners have employed postoperative stereotactic radiosurgery (SRS) to tumor resection cavities to increase local control without causing significant neurocognitive sequelae. However, studies analyzing outcomes of large brain metastases treated with resection and postoperative SRS are lacking. Here we compare outcomes in patients with large brain metastases >4 cm to those with smaller metastases ≤4 cm treated with surgical resection followed by SRS to the resection cavity. Consecutive patients with brain metastases treated at our institution with surgical resection and postoperative SRS were retrospectively reviewed. Patients were stratified into ≤4 cm and >4 cm cohorts based on preoperative maximal tumor dimension. Cumulative incidence of local failure, radiation necrosis, and death were analyzed for the 2 cohorts using a competing-risk model, defined as the time from SRS treatment date to the measured event, death, or last follow-up. A total of 117 consecutive cases were identified. Of these patients, 90 (77%) had preoperative tumors ≤4 cm, and 27 (23%) >4 cm in greatest dimension. The only significant baseline difference between the 2 groups was a higher proportion of patients who underwent gross total resection in the ≤4 cm compared with the >4 cm cohort, 76% versus 48%, respectively (P <.01). The 1-year rates of local failure, radiation necrosis, and overall survival for the ≤4 cm and >4 cm cohorts were 12.3% and 16.0%, 26.9% and 28.4%, and 80.6% and 67.6%, respectively (all P >.05). The rates of local failure and radiation necrosis were not statistically different on multivariable analysis based on tumor size. Brain metastases >4 cm in largest dimension managed by resection and radiosurgery to the tumor cavity have promising local control rates without a significant increase in radiation necrosis on our retrospective review. Copyright © 2017 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

FGFR3 regulates brain size by controlling progenitor cell proliferation and apoptosis during embryonic development.

PubMed

Inglis-Broadgate, Suzanne L; Thomson, Rachel E; Pellicano, Francesca; Tartaglia, Michael A; Pontikis, Charlie C; Cooper, Jonathan D; Iwata, Tomoko

2005-03-01

Mice with the K644E kinase domain mutation in fibroblast growth factor receptor 3 (Fgfr3) (EIIa;Fgfr3(+/K644E)) exhibited a marked enlargement of the brain. The brain size was increased as early as E11.5, not secondary to the possible effect of Fgfr3 activity in the skeleton. Furthermore, the mutant brains showed a dramatic increase in cortical thickness, a phenotype opposite to that in FGF2 knockout mice. Despite this increased thickness, cortical layer formation was largely unaffected and no cortical folding was observed during embryonic days 11.5-18.5 (E11.5-E18.5). Measurement of cortical thickness revealed an increase of 38.1% in the EIIa;Fgfr3(+/K644E) mice at E14.5 and the advanced appearance of the cortical plate was frequently observed at this stage. Unbiased stereological analysis revealed that the volume of the ventricular zone (VZ) was increased by more than two fold in the EIIa;Fgfr3(+/K644E) mutants at E14.5. A relatively mild increase in progenitor cell proliferation and a profound decrease in developmental apoptosis during E11.5-E14.5 most likely accounts for the dramatic increase in total telecephalic cell number. Taken together, our data suggest a novel function of Fgfr3 in controlling the development of the cortex, by regulating proliferation and apoptosis of cortical progenitors.

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

PubMed Central

Solomon, Gregory; Gersch, William; Yoon, Young-Ho; Collura, Randall; Ruvolo, Maryellen; Barrett, J. Carl; Woods, C. Geoffrey; Walsh, Christopher A

2004-01-01

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. PMID:15045028

The devil is in the detail: brain dynamics in preparation for a global-local task.

PubMed

Leaver, Echo E; Low, Kathy A; DiVacri, Assunta; Merla, Arcangelo; Fabiani, Monica; Gratton, Gabriele

2015-08-01

When analyzing visual scenes, it is sometimes important to determine the relevant "grain" size. Attention control mechanisms may help direct our processing to the intended grain size. Here we used the event-related optical signal, a method possessing high temporal and spatial resolution, to examine the involvement of brain structures within the dorsal attention network (DAN) and the visual processing network (VPN) in preparation for the appropriate level of analysis. Behavioral data indicate that the small features of a hierarchical stimulus (local condition) are more difficult to process than the large features (global condition). Consistent with this finding, cues predicting a local trial were associated with greater DAN activation. This activity was bilateral but more pronounced in the left hemisphere, where it showed a frontal-to-parietal progression over time. Furthermore, the amount of DAN activation, especially in the left hemisphere and in parietal regions, was predictive of subsequent performance. Although local cues elicited left-lateralized DAN activity, no preponderantly right activity was observed for global cues; however, the data indicated an interaction between level of analysis (local vs. global) and hemisphere in VPN. They further showed that local processing involves structures in the ventral VPN, whereas global processing involves structures in the dorsal VPN. These results indicate that in our study preparation for analyzing different size features is an asymmetric process, in which greater preparation is required to focus on small rather than large features, perhaps because of their lesser salience. This preparation involves the same DAN used for other attention control operations.

Brain and sense organ anatomy and histology of the Falkland Islands mullet, Eleginops maclovinus (Eleginopidae), the sister group of the Antarctic notothenioid fishes (Perciformes: Notothenioidei).

PubMed

Eastman, Joseph T; Lannoo, Michael J

2008-01-01

The perciform notothenioid fish Eleginops maclovinus, representing the monotypic family Eleginopidae, has a non-Antarctic distribution in the Falkland Islands and southern South America. It is the sister group of the five families and 103 species of Antarctic notothenioids that dominate the cold shelf waters of Antarctica. Eleginops is the ideal subject for documenting the ancestral morphology of nervous and sensory systems that have not had historical exposure to the unusual Antarctic thermal and light regimes, and for comparing these systems with those of the phyletically derived Antarctic species. We present a detailed description of the brain and cranial nerves of Eleginops and ask how does the neural and sensory morphology of this non-Antarctic notothenioid differ from that seen in the phyletically derived Antarctic notothenioids? The brain of Eleginops is similar to those of visually oriented temperate and tropical perciforms. The tectum is smaller but it has well-developed olfactory and mechanoreceptive lateral line areas and a large, caudally projecting corpus cerebellum. Eye diameter is about twofold smaller in Eleginops than in many Antarctic species. Eleginops has a duplex (rod and cone) retina with single and occasional twin cones conspicuous centrally. Ocular vascular structures include a large choroid rete mirabile and a small lentiform body; a falciform process and hyaloid arteries are absent. The olfactory rosette is oval with 50-55 lamellae, a large number for notothenioids. The inconspicuous bony canals of the cephalic lateral line system are simple with membranous secondary branches that lack neuromasts. In Antarctic species, the corpus cerebellum is the most variable brain region, ranging in size from large and caudally projecting to small and round. "Stalked" brains showing reduction in the size of the telencephalon, tectum, and corpus cerebellum are present in the deep-living artedidraconid Dolloidraco longedorsalis and in most of the deep-living members of the Bathydraconini. Eye diameter is generally larger in Antarctic species but there is a phylogenetic loss of cellularity in the retina, including cone photoreceptors. Some deep-living Antarctic species have lost most of their cones. Mechanosensation is expanded in some species, most notably the nototheniid Pleuragramma antarcticum, the artedidraconid genera Dolloidraco and Pogonophryne, and the deep living members of the bathydraconid tribe Bathydraconini. Reduction in retinal cellularity, expansion of mechanoreception, and stalking are the most noteworthy departures from the morphology seen in Eleginops. These features reflect a modest depth or deep-sea effect, and they are not uniquely "Antarctic" attributes. Thus, at the level of organ system morphology, perciform brain and sensory systems are suitable for conditions on the Antarctic shelf, with only minor alterations in structure in directions exhibited by other fish groups inhabiting deep water. Notothenioids retain a relative balance among their array of senses that reflects their heritage as inshore perciforms. (c) 2007 Wiley-Liss, Inc.

New tyrannosaur from the mid-Cretaceous of Uzbekistan clarifies evolution of giant body sizes and advanced senses in tyrant dinosaurs.

PubMed

Brusatte, Stephen L; Averianov, Alexander; Sues, Hans-Dieter; Muir, Amy; Butler, Ian B

2016-03-29

Tyrannosaurids--the familiar group of carnivorous dinosaurs including Tyrannosaurus and Albertosaurus--were the apex predators in continental ecosystems in Asia and North America during the latest Cretaceous (ca. 80-66 million years ago). Their colossal sizes and keen senses are considered key to their evolutionary and ecological success, but little is known about how these features developed as tyrannosaurids evolved from smaller basal tyrannosauroids that first appeared in the fossil record in the Middle Jurassic (ca. 170 million years ago). This is largely because of a frustrating 20+ million-year gap in the mid-Cretaceous fossil record, when tyrannosauroids transitioned from small-bodied hunters to gigantic apex predators but from which no diagnostic specimens are known. We describe the first distinct tyrannosauroid species from this gap, based on a highly derived braincase and a variety of other skeletal elements from the Turonian (ca. 90-92 million years ago) of Uzbekistan. This taxon is phylogenetically intermediate between the oldest basal tyrannosauroids and the latest Cretaceous forms. It had yet to develop the giant size and extensive cranial pneumaticity of T. rex and kin but does possess the highly derived brain and inner ear characteristic of the latest Cretaceous species. Tyrannosauroids apparently developed huge size rapidly during the latest Cretaceous, and their success in the top predator role may have been enabled by their brain and keen senses that first evolved at smaller body size.

New tyrannosaur from the mid-Cretaceous of Uzbekistan clarifies evolution of giant body sizes and advanced senses in tyrant dinosaurs

PubMed Central

Brusatte, Stephen L.; Averianov, Alexander; Sues, Hans-Dieter; Muir, Amy; Butler, Ian B.

2016-01-01

Tyrannosaurids—the familiar group of carnivorous dinosaurs including Tyrannosaurus and Albertosaurus—were the apex predators in continental ecosystems in Asia and North America during the latest Cretaceous (ca. 80–66 million years ago). Their colossal sizes and keen senses are considered key to their evolutionary and ecological success, but little is known about how these features developed as tyrannosaurids evolved from smaller basal tyrannosauroids that first appeared in the fossil record in the Middle Jurassic (ca. 170 million years ago). This is largely because of a frustrating 20+ million-year gap in the mid-Cretaceous fossil record, when tyrannosauroids transitioned from small-bodied hunters to gigantic apex predators but from which no diagnostic specimens are known. We describe the first distinct tyrannosauroid species from this gap, based on a highly derived braincase and a variety of other skeletal elements from the Turonian (ca. 90–92 million years ago) of Uzbekistan. This taxon is phylogenetically intermediate between the oldest basal tyrannosauroids and the latest Cretaceous forms. It had yet to develop the giant size and extensive cranial pneumaticity of T. rex and kin but does possess the highly derived brain and inner ear characteristic of the latest Cretaceous species. Tyrannosauroids apparently developed huge size rapidly during the latest Cretaceous, and their success in the top predator role may have been enabled by their brain and keen senses that first evolved at smaller body size. PMID:26976562

New tyrannosaur from the mid-Cretaceous of Uzbekistan clarifies evolution of giant body sizes and advanced senses in tyrant dinosaurs

NASA Astrophysics Data System (ADS)

Brusatte, Stephen L.; Averianov, Alexander; Sues, Hans-Dieter; Muir, Amy; Butler, Ian B.

2016-03-01

Tyrannosaurids-the familiar group of carnivorous dinosaurs including Tyrannosaurus and Albertosaurus-were the apex predators in continental ecosystems in Asia and North America during the latest Cretaceous (ca. 80-66 million years ago). Their colossal sizes and keen senses are considered key to their evolutionary and ecological success, but little is known about how these features developed as tyrannosaurids evolved from smaller basal tyrannosauroids that first appeared in the fossil record in the Middle Jurassic (ca. 170 million years ago). This is largely because of a frustrating 20+ million-year gap in the mid-Cretaceous fossil record, when tyrannosauroids transitioned from small-bodied hunters to gigantic apex predators but from which no diagnostic specimens are known. We describe the first distinct tyrannosauroid species from this gap, based on a highly derived braincase and a variety of other skeletal elements from the Turonian (ca. 90-92 million years ago) of Uzbekistan. This taxon is phylogenetically intermediate between the oldest basal tyrannosauroids and the latest Cretaceous forms. It had yet to develop the giant size and extensive cranial pneumaticity of T. rex and kin but does possess the highly derived brain and inner ear characteristic of the latest Cretaceous species. Tyrannosauroids apparently developed huge size rapidly during the latest Cretaceous, and their success in the top predator role may have been enabled by their brain and keen senses that first evolved at smaller body size.

A geometrically adjustable receive array for imaging marmoset cohorts.

PubMed

Gilbert, Kyle M; Gati, Joseph S; Klassen, L Martyn; Zeman, Peter; Schaeffer, David J; Everling, Stefan; Menon, Ravi S

2017-08-01

The common marmoset (Callithrix jacchus) is an increasingly popular animal model for translational neuroscience studies, during which anatomical and functional MRI can be useful investigative tools. To attain the requisite SNR for high-resolution acquisitions, the radiofrequency coil must be optimized for the marmoset; however, relatively few custom coils have been developed that maximize SNR and are compatible with accelerated acquisitions. For the study of large populations of animals, the heterogeneity in animal size reduces the effectiveness of a "one size fits all" approach to coil sizing and makes coils tailored to individual animals cost and time prohibitive. The approach taken in this study was to create an 8-channel phased-array receive coil that was adjustable to the width of the marmoset head, thereby negating the need for tailored coils while still maintaining high SNR. Two marmosets of different size were imaged on a 9.4-T small-animal scanner. Consistent SNR was achieved in the periphery of the brain between head sizes. When compared to a 15-channel, "one size fits all" receive coil, the adjustable coil achieved 57% higher SNR in the superior frontal and parietal cortices and 29% higher SNR in the centre of the brain. The mean geometry factor of the adjustable coil was less than 1.2 for a 2-fold reduction factor in the left-right and anterior-posterior directions. Geometry factors were compared to the 15-channel coil to guide future designs. The adjustable coil was shown to be a practical means for anatomical and echo-planar imaging of marmoset cohorts. Copyright © 2017 Elsevier Inc. All rights reserved.

Transferrin liposomes of docetaxel for brain-targeted cancer applications: formulation and brain theranostics.

PubMed

Sonali; Singh, Rahul Pratap; Singh, Nitesh; Sharma, Gunjan; Vijayakumar, Mahalingam R; Koch, Biplob; Singh, Sanjay; Singh, Usha; Dash, Debabrata; Pandey, Bajarangprasad L; Muthu, Madaswamy S

2016-05-01

Diagnosis and therapy of brain cancer was often limited due to low permeability of delivery materials across the blood-brain barrier (BBB) and their poor penetration into the brain tissue. This study explored the possibility of utilizing theranostic d-alpha-tocopheryl polyethylene glycol 1000 succinate mono-ester (TPGS) liposomes as nanocarriers for minimally invasive brain-targeted imaging and therapy (brain theranostics). The aim of this work was to formulate transferrin conjugated TPGS coated theranostic liposomes, which contain both docetaxel and quantum dots (QDs) for imaging and therapy of brain cancer. The theranostic liposomes with and without transferrin decoration were prepared and characterized for their particle size, polydispersity, morphology, drug encapsulation efficiency, in-vitro release study and brain theranostics. The particle sizes of the non-targeted and targeted theranostic liposomes were found below 200 nm. Nearly, 71% of drug encapsulation efficiency was achieved with liposomes. The drug release from transferrin conjugated theranostic liposomes was sustained for more than 72 h with 70% of drug release. The in-vivo results indicated that transferrin receptor-targeted theranostic liposomes could be a promising carrier for brain theranostics due to nano-sized delivery and its permeability which provided an improved and prolonged brain targeting of docetaxel and QDs in comparison to the non-targeted preparations.

Large Soluble Oligomers of Amyloid β-Protein from Alzheimer Brain Are Far Less Neuroactive Than the Smaller Oligomers to Which They Dissociate

PubMed Central

Yang, Ting; Li, Shaomin; Xu, Huixin

2017-01-01

Soluble oligomers of amyloid β-protein (oAβ) isolated from the brains of Alzheimer's disease (AD) patients have been shown experimentally (in the absence of amyloid plaques) to impair hippocampal synaptic plasticity, decrease synapses, induce tau hyperphosphorylation and neuritic dystrophy, activate microglial inflammation, and impair memory in normal adult rodents. Nevertheless, there has been controversy about what types of oligomers actually confer these AD-like phenotypes. Here, we show that the vast majority of soluble Aβ species obtained from brains of humans who died with confirmed AD elute at high molecular weight (HMW) on nondenaturing size-exclusion chromatography. These species have little or no cytotoxic activity in several bioassays. However, incubation of HMW oAβ in mildly alkaline buffer led to their quantitative dissociation into low molecular weight oligomers (∼8–70 kDa), and these were now far more bioactive: they impaired hippocampal LTP, decreased neuronal levels of β2-adrenergic receptors, and activated microglia in wt mice in vivo. Thus, most soluble Aβ assemblies in AD cortex are large and inactive but under certain circumstances can dissociate into smaller, highly bioactive species. Insoluble amyloid plaques likely sequester soluble HMW oligomers, limiting their potential to dissociate. We conclude that conditions that destabilize HMW oligomers or retard the sequestration of their smaller, more bioactive components are important drivers of Aβ toxicity. Selectively targeting these small, cytotoxic forms should be therapeutically beneficial. SIGNIFICANCE STATEMENT Oligomers of amyloid β-protein (oAβ) are tought to play an important role in Alzheimer's disease (AD), but there is confusion and controversy about what types and sizes of oligomers have disease-relevant activity. Using size-exclusion chromatography and three distinct measures of bioactivity, we show that the predominant forms of Aβ in aqueous extracts of AD brain are high molecular weight (HMW) and relatively inactive. Importantly, under certain conditions, the abundant HMW oAβ can dissociate into low molecular weight species, and these low molecular weight oligomers are significantly more bioactive on synapses and microglia than the HMW species from which they are derived. We conclude that conditions that destabilize HMW oAβ or retard the sequestration of smaller, more bioactive components are important drivers of Aβ toxicity. PMID:28053038

Cortical Enhanced Tissue Segmentation of Neonatal Brain MR Images Acquired by a Dedicated Phased Array Coil

PubMed Central

Shi, Feng; Yap, Pew-Thian; Fan, Yong; Cheng, Jie-Zhi; Wald, Lawrence L.; Gerig, Guido; Lin, Weili; Shen, Dinggang

2010-01-01

The acquisition of high quality MR images of neonatal brains is largely hampered by their characteristically small head size and low tissue contrast. As a result, subsequent image processing and analysis, especially for brain tissue segmentation, are often hindered. To overcome this problem, a dedicated phased array neonatal head coil is utilized to improve MR image quality by effectively combing images obtained from 8 coil elements without lengthening data acquisition time. In addition, a subject-specific atlas based tissue segmentation algorithm is specifically developed for the delineation of fine structures in the acquired neonatal brain MR images. The proposed tissue segmentation method first enhances the sheet-like cortical gray matter (GM) structures in neonatal images with a Hessian filter for generation of cortical GM prior. Then, the prior is combined with our neonatal population atlas to form a cortical enhanced hybrid atlas, which we refer to as the subject-specific atlas. Various experiments are conducted to compare the proposed method with manual segmentation results, as well as with additional two population atlas based segmentation methods. Results show that the proposed method is capable of segmenting the neonatal brain with the highest accuracy, compared to other two methods. PMID:20862268

Cognitive Effects of ThinkRx Cognitive Rehabilitation Training for Eleven Soldiers with Brain Injury: A Retrospective Chart Review

PubMed Central

Ledbetter, Christina; Moore, Amy Lawson; Mitchell, Tanya

2017-01-01

Cognitive rehabilitation training is a promising technique for remediating the cognitive deficits associated with brain injury. Extant research is dominated by computer-based interventions with varied results. Results from clinician-delivered cognitive rehabilitation are notably lacking in the literature. The current study examined the cognitive outcomes following ThinkRx, a clinician-delivered cognitive rehabilitation training program for soldiers recovering from traumatic brain injury and acquired brain injury. In a retrospective chart review, we examined cognitive outcomes of 11 cases who had completed an average of 80 h of ThinkRx cognitive rehabilitation training delivered by clinicians and supplemented with digital training exercises. Outcome measures included scores from six cognitive skill batteries on the Woodcock Johnson – III Tests of Cognitive Abilities. Participants achieved gains in all cognitive skills tested and achieved statistically significant changes in long-term memory, processing speed, auditory processing, and fluid reasoning with very large effect sizes. Clinically significant changes in multiple cognitive skills were also noted across cases. Results of the study suggest that ThinkRx clinician-delivered cognitive training supplemented with digital exercises may be a viable method for targeting the cognitive deficits associated with brain injury. PMID:28588534

Using Structural Equation Modeling to Assess Functional Connectivity in the Brain: Power and Sample Size Considerations

ERIC Educational Resources Information Center

Sideridis, Georgios; Simos, Panagiotis; Papanicolaou, Andrew; Fletcher, Jack

2014-01-01

The present study assessed the impact of sample size on the power and fit of structural equation modeling applied to functional brain connectivity hypotheses. The data consisted of time-constrained minimum norm estimates of regional brain activity during performance of a reading task obtained with magnetoencephalography. Power analysis was first…

The Evolution of Human Intelligence and the Coefficient of Additive Genetic Variance in Human Brain Size

ERIC Educational Resources Information Center

Miller, Geoffrey F.; Penke, Lars

2007-01-01

Most theories of human mental evolution assume that selection favored higher intelligence and larger brains, which should have reduced genetic variance in both. However, adult human intelligence remains highly heritable, and is genetically correlated with brain size. This conflict might be resolved by estimating the coefficient of additive genetic…

Uptake and bio-reactivity of polystyrene nanoparticles is affected by surface modifications, ageing and LPS adsorption: in vitro studies on neural tissue cells

NASA Astrophysics Data System (ADS)

Murali, Kumarasamy; Kenesei, Kata; Li, Yang; Demeter, Kornél; Környei, Zsuzsanna; Madarász, Emilia

2015-02-01

Because of their capacity of crossing an intact blood-brain barrier and reaching the brain through an injured barrier or via the nasal epithelium, nanoparticles have been considered as vehicles to deliver drugs and as contrast materials for brain imaging. The potential neurotoxicity of nanoparticles, however, is not fully explored. Using particles with a biologically inert polystyrene core material, we investigated the role of the chemical composition of particle surfaces in the in vitro interaction with different neural cell types. PS NPs within a size-range of 45-70 nm influenced the metabolic activity of cells depending on the cell-type, but caused toxicity only at extremely high particle concentrations. Neurons did not internalize particles, while microglial cells ingested a large amount of carboxylated but almost no PEGylated NPs. PEGylation reduced the protein adsorption, toxicity and cellular uptake of NPs. After storage (shelf-life >6 months), the toxicity and cellular uptake of NPs increased. The altered biological activity of ``aged'' NPs was due to particle aggregation and due to the adsorption of bioactive compounds on NP surfaces. Aggregation by increasing the size and sedimentation velocity of NPs results in increased cell-targeted NP doses. The ready endotoxin adsorption which cannot be prevented by PEG coating, can render the particles toxic. The age-dependent changes in otherwise harmless NPs could be the important sources for variability in the effects of NPs, and could explain the contradictory data obtained with ``identical'' NPs.Because of their capacity of crossing an intact blood-brain barrier and reaching the brain through an injured barrier or via the nasal epithelium, nanoparticles have been considered as vehicles to deliver drugs and as contrast materials for brain imaging. The potential neurotoxicity of nanoparticles, however, is not fully explored. Using particles with a biologically inert polystyrene core material, we investigated the role of the chemical composition of particle surfaces in the in vitro interaction with different neural cell types. PS NPs within a size-range of 45-70 nm influenced the metabolic activity of cells depending on the cell-type, but caused toxicity only at extremely high particle concentrations. Neurons did not internalize particles, while microglial cells ingested a large amount of carboxylated but almost no PEGylated NPs. PEGylation reduced the protein adsorption, toxicity and cellular uptake of NPs. After storage (shelf-life >6 months), the toxicity and cellular uptake of NPs increased. The altered biological activity of ``aged'' NPs was due to particle aggregation and due to the adsorption of bioactive compounds on NP surfaces. Aggregation by increasing the size and sedimentation velocity of NPs results in increased cell-targeted NP doses. The ready endotoxin adsorption which cannot be prevented by PEG coating, can render the particles toxic. The age-dependent changes in otherwise harmless NPs could be the important sources for variability in the effects of NPs, and could explain the contradictory data obtained with ``identical'' NPs. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr06849a

A Virtual Reality Visualization Tool for Neuron Tracing

PubMed Central

Usher, Will; Klacansky, Pavol; Federer, Frederick; Bremer, Peer-Timo; Knoll, Aaron; Angelucci, Alessandra; Pascucci, Valerio

2017-01-01

Tracing neurons in large-scale microscopy data is crucial to establishing a wiring diagram of the brain, which is needed to understand how neural circuits in the brain process information and generate behavior. Automatic techniques often fail for large and complex datasets, and connectomics researchers may spend weeks or months manually tracing neurons using 2D image stacks. We present a design study of a new virtual reality (VR) system, developed in collaboration with trained neuroanatomists, to trace neurons in microscope scans of the visual cortex of primates. We hypothesize that using consumer-grade VR technology to interact with neurons directly in 3D will help neuroscientists better resolve complex cases and enable them to trace neurons faster and with less physical and mental strain. We discuss both the design process and technical challenges in developing an interactive system to navigate and manipulate terabyte-sized image volumes in VR. Using a number of different datasets, we demonstrate that, compared to widely used commercial software, consumer-grade VR presents a promising alternative for scientists. PMID:28866520

Different brains process numbers differently: structural bases of individual differences in spatial and nonspatial number representations.

PubMed

Krause, Florian; Lindemann, Oliver; Toni, Ivan; Bekkering, Harold

2014-04-01

A dominant hypothesis on how the brain processes numerical size proposes a spatial representation of numbers as positions on a "mental number line." An alternative hypothesis considers numbers as elements of a generalized representation of sensorimotor-related magnitude, which is not obligatorily spatial. Here we show that individuals' relative use of spatial and nonspatial representations has a cerebral counterpart in the structural organization of the posterior parietal cortex. Interindividual variability in the linkage between numbers and spatial responses (faster left responses to small numbers and right responses to large numbers; spatial-numerical association of response codes effect) correlated with variations in gray matter volume around the right precuneus. Conversely, differences in the disposition to link numbers to force production (faster soft responses to small numbers and hard responses to large numbers) were related to gray matter volume in the left angular gyrus. This finding suggests that numerical cognition relies on multiple mental representations of analogue magnitude using different neural implementations that are linked to individual traits.

A sparse structure learning algorithm for Gaussian Bayesian Network identification from high-dimensional data.

PubMed

Huang, Shuai; Li, Jing; Ye, Jieping; Fleisher, Adam; Chen, Kewei; Wu, Teresa; Reiman, Eric

2013-06-01

Structure learning of Bayesian Networks (BNs) is an important topic in machine learning. Driven by modern applications in genetics and brain sciences, accurate and efficient learning of large-scale BN structures from high-dimensional data becomes a challenging problem. To tackle this challenge, we propose a Sparse Bayesian Network (SBN) structure learning algorithm that employs a novel formulation involving one L1-norm penalty term to impose sparsity and another penalty term to ensure that the learned BN is a Directed Acyclic Graph--a required property of BNs. Through both theoretical analysis and extensive experiments on 11 moderate and large benchmark networks with various sample sizes, we show that SBN leads to improved learning accuracy, scalability, and efficiency as compared with 10 existing popular BN learning algorithms. We apply SBN to a real-world application of brain connectivity modeling for Alzheimer's disease (AD) and reveal findings that could lead to advancements in AD research.

A Virtual Reality Visualization Tool for Neuron Tracing.

PubMed

Usher, Will; Klacansky, Pavol; Federer, Frederick; Bremer, Peer-Timo; Knoll, Aaron; Yarch, Jeff; Angelucci, Alessandra; Pascucci, Valerio

2018-01-01

Tracing neurons in large-scale microscopy data is crucial to establishing a wiring diagram of the brain, which is needed to understand how neural circuits in the brain process information and generate behavior. Automatic techniques often fail for large and complex datasets, and connectomics researchers may spend weeks or months manually tracing neurons using 2D image stacks. We present a design study of a new virtual reality (VR) system, developed in collaboration with trained neuroanatomists, to trace neurons in microscope scans of the visual cortex of primates. We hypothesize that using consumer-grade VR technology to interact with neurons directly in 3D will help neuroscientists better resolve complex cases and enable them to trace neurons faster and with less physical and mental strain. We discuss both the design process and technical challenges in developing an interactive system to navigate and manipulate terabyte-sized image volumes in VR. Using a number of different datasets, we demonstrate that, compared to widely used commercial software, consumer-grade VR presents a promising alternative for scientists.

A Sparse Structure Learning Algorithm for Gaussian Bayesian Network Identification from High-Dimensional Data

PubMed Central

Huang, Shuai; Li, Jing; Ye, Jieping; Fleisher, Adam; Chen, Kewei; Wu, Teresa; Reiman, Eric

2014-01-01

Structure learning of Bayesian Networks (BNs) is an important topic in machine learning. Driven by modern applications in genetics and brain sciences, accurate and efficient learning of large-scale BN structures from high-dimensional data becomes a challenging problem. To tackle this challenge, we propose a Sparse Bayesian Network (SBN) structure learning algorithm that employs a novel formulation involving one L1-norm penalty term to impose sparsity and another penalty term to ensure that the learned BN is a Directed Acyclic Graph (DAG)—a required property of BNs. Through both theoretical analysis and extensive experiments on 11 moderate and large benchmark networks with various sample sizes, we show that SBN leads to improved learning accuracy, scalability, and efficiency as compared with 10 existing popular BN learning algorithms. We apply SBN to a real-world application of brain connectivity modeling for Alzheimer’s disease (AD) and reveal findings that could lead to advancements in AD research. PMID:22665720

Pathology of non-thermal irreversible electroporation (N-TIRE)-induced ablation of the canine brain.

PubMed

Rossmeisl, John H; Garcia, Paulo A; Roberston, John L; Ellis, Thomas L; Davalos, Rafael V

2013-01-01

This study describes the neuropathologic features of normal canine brain ablated with non-thermal irreversible electroporation (N-TIRE). The parietal cerebral cortices of four dogs were treated with N-TIRE using a dose-escalation protocol with an additional dog receiving sham treatment. Animals were allowed to recover following N-TIRE ablation and the effects of treatment were monitored with clinical and magnetic resonance imaging examinations. Brains were subjected to histopathologic and ultrastructural assessment along with Bcl-2, caspase-3, and caspase-9 immunohistochemical staining following sacrifice 72 h post-treatment. Adverse clinical effects of N-TIRE were only observed in the dog treated at the upper energy tier. MRI and neuropathologic examinations indicated that N-TIRE ablation resulted in focal regions of severe cytoarchitectural and blood-brain-barrier disruption. Lesion size correlated to the intensity of the applied electrical field. N-TIRE-induced lesions were characterized by parenchymal necrosis and hemorrhage; however, large blood vessels were preserved. A transition zone containing parenchymal edema, perivascular inflammatory cuffs, and reactive gliosis was interspersed between the necrotic focus and normal neuropil. Apoptotic labeling indices were not different between the N-TIRE-treated and control brains. This study identified N-TIRE pulse parameters that can be used to safely create circumscribed foci of brain necrosis while selectively preserving major vascular structures.

The early development and evolution of the human brain.

PubMed

Crawford, M A

1990-01-01

THE CHEMISTRY OF THE BRAIN: The brain and nervous system is characterised by a heavy investment in lipid chemistry which accounts for up to 60% of its structural material. In the different mammalian species so far studied, only the 20 and 22 carbon chain length polyenoic fatty acids were present and the balance of the n-3 to n-6 fatty acids was consistently 1:1. The difference observed between species, was not in the chemistry but in the extent to which the brain is developed. This paper discusses the possibility that essential fatty acids may have played a part in it evolution. THE ORIGIN OF AIR BREATHING ANIMALS: The first phase of the planet's existence indulged in high temperature reactions in which oxygen combined with everything feasible: from silicon to make rocks to hydrogen to make water. Once the planet's temperature dropped to a point at which water could condense on the surface allowing chemical reactions to take place in it. The atmosphere was at that time devoid of oxygen so life evolved in a reducing atmosphere. Oxygen was liberated by photolysis of water and as a by-product of the blue-green algae through photosynthesis. When the point was reached at which oxidative metabolism became thermodynamically possible, animal life evolved with all the principle phyla establishing themselves within a relatively short space of geological time. (Bernal 1973). DHA and nerve cell membranes DHA AND NERVE CELL MEMBRANES: From the chemistry of contemporary algae it is likely that animal life evolved in an n-3 rich environment although not exclusively so as smaller amounts of n-6 fatty acids would have been present. A key feature of the first animals was the evolution of the photoreceptor: in examples of marine, amphibian and modern mammalian species, it has been found to use docosahexaenoic acid (DHA) as the principle membrane fatty acid in the phosphoglycerides. It is likely that the first animals did so as well. Coincidentally, the synaptic membranes involved in signal transduction also use high proportions of n-3 fatty acids. However, the n-6 fatty acids also find a place, in the inositol phosphoglyceride (IPG) which appears to be involved with calcium ion transport and hence signal activation and reception. Even in the photoreceptor, the IPG is an arachidonic acid rich phosphoglyceride. THE EVOLUTION OF MAMMALS AND THE LARGE BRAIN: The dominance of n-3 fatty acids in the food chain, persisted until the end of the Cretaceous period when the flowering plants followed on the disappearance of the giant cycads and ferns. A new set of species, the mammals, then evolved with a requirement for n-6 fatty acids for reproduction. This dependance was coincident with the flowering plants which for the first time produced protected seeds: these introduced a rich source of n-6 fatty acids. The brain size of the mammals tended to be relatively larger (that is in relation to body size) by comparison with the previous reptilian or egg laying systems. This process led to the large human brain. A crucial difference between man and other animals, is undoubtedly the extent to which the brain and its peripheral attributes have been developed. This paper will address the possibility that the potential for the evolution of the large human brain may have been released by the evolving human primate occupying an ecological niche which offered a rich source of those nutrients specifically required for the brain. That niche is at the land/water interface.

Specificity, Size, and Frequency of Spaces That Characterize the Mechanism of Bulk Transepithelial Transport of Prions in the Nasal Cavities of Hamsters and Mice

PubMed Central

Ayers, J. I.; Bartz, J. C.

2016-01-01

ABSTRACT Inhalation of infected brain homogenate results in transepithelial transport of prions across the nasal mucosa of hamsters, some of which occurs rapidly in relatively large amounts between cells (A. E. Kincaid, K. F. Hudson, M. W. Richey, and J. C. Bartz, J. Virol 86:12731–12740, 2012, doi:http://dx.doi.org/10.1128/JVI.01930-12). Bulk transepithelial transport in the nasal cavity has not been studied to date. In the present study, we characterized the frequency, size, and specificity of the intercellular spaces that mediate the bulk transport of inhaled prions between cells of mice or hamsters following extranasal inoculation with mock-infected brain homogenate, different strains of prion-infected brain homogenate, or brain homogenate mixed with India ink. Infected or mock-infected inoculum was identified within lymphatic vessels of the lamina propria and in spaces of >5 μm between a small number of cells of the nasal mucosa in >90% of animals from 5 to 60 min after inhalation. The width of the spaces between cells, the amount of the inoculum within the lumen of lymphatic vessels, and the timing of the transport indicate that this type of transport was taking place through preexisting spaces in the nasal cavity that were orders of magnitude wider than what is normally reported for paracellular transport. The indiscriminate rapid bulk transport of brain homogenate in the nasal cavity results in immediate entry into nasal cavity lymphatics following inhalation. This novel mechanism may underlie the recent report of the early detection of prions in blood following inhalation and has implications for horizontal prion transmission. IMPORTANCE The results of these studies demonstrate that the nasal mucosa of mice and hamsters is not an absolute anatomical barrier to inhaled prion-infected or uninfected brain homogenate. Relatively large amounts of infected and uninfected brain homogenate rapidly cross the nasal mucosa and enter the lumen of lymphatic vessels following inhalation. These bulk transepithelial transport events were relatively rare but present in >90% of animals 5 to 60 min following inhalation. This novel mechanism of bulk transepithelial transport was seen in experimental and control hamsters and mice, indicating that it was not species specific or in response to prion exposure. The indiscriminate bulk intercellular transport of inhaled pathogens across the nasal mucosa followed by entry into the lymphatic system may be a mechanism that underlies the entry and spread of other toxins and pathogens in olfactory system-driven animals. PMID:27384659

The circuit architecture of whole brains at the mesoscopic scale.

PubMed

Mitra, Partha P

2014-09-17

Vertebrate brains of even moderate size are composed of astronomically large numbers of neurons and show a great degree of individual variability at the microscopic scale. This variation is presumably the result of phenotypic plasticity and individual experience. At a larger scale, however, relatively stable species-typical spatial patterns are observed in neuronal architecture, e.g., the spatial distributions of somata and axonal projection patterns, probably the result of a genetically encoded developmental program. The mesoscopic scale of analysis of brain architecture is the transitional point between a microscopic scale where individual variation is prominent and the macroscopic level where a stable, species-typical neural architecture is observed. The empirical existence of this scale, implicit in neuroanatomical atlases, combined with advances in computational resources, makes studying the circuit architecture of entire brains a practical task. A methodology has previously been proposed that employs a shotgun-like grid-based approach to systematically cover entire brain volumes with injections of neuronal tracers. This methodology is being employed to obtain mesoscale circuit maps in mouse and should be applicable to other vertebrate taxa. The resulting large data sets raise issues of data representation, analysis, and interpretation, which must be resolved. Even for data representation the challenges are nontrivial: the conventional approach using regional connectivity matrices fails to capture the collateral branching patterns of projection neurons. Future success of this promising research enterprise depends on the integration of previous neuroanatomical knowledge, partly through the development of suitable computational tools that encapsulate such expertise. Copyright © 2014 Elsevier Inc. All rights reserved.

Focused ultrasound-facilitated brain drug delivery using optimized nanodroplets: vaporization efficiency dictates large molecular delivery

NASA Astrophysics Data System (ADS)

Wu, Shih-Ying; Fix, Samantha M.; Arena, Christopher B.; Chen, Cherry C.; Zheng, Wenlan; Olumolade, Oluyemi O.; Papadopoulou, Virginie; Novell, Anthony; Dayton, Paul A.; Konofagou, Elisa E.

2018-02-01

Focused ultrasound with nanodroplets could facilitate localized drug delivery after vaporization with potentially improved in vivo stability, drug payload, and minimal interference outside of the focal zone compared with microbubbles. While the feasibility of blood-brain barrier (BBB) opening using nanodroplets has been previously reported, characterization of the associated delivery has not been achieved. It was hypothesized that the outcome of drug delivery was associated with the droplet’s sensitivity to acoustic energy, and can be modulated with the boiling point of the liquid core. Therefore, in this study, octafluoropropane (OFP) and decafluorobutane (DFB) nanodroplets were used both in vitro for assessing their relative vaporization efficiency with high-speed microscopy, and in vivo for delivering molecules with a size relevant to proteins (40 kDa dextran) to the murine brain. It was found that at low pressures (300-450 kPa), OFP droplets vaporized into a greater number of microbubbles compared to DFB droplets at higher pressures (750-900 kPa) in the in vitro study. In the in vivo study, successful delivery was achieved with OFP droplets at 300 kPa and 450 kPa without evidence of cavitation damage using ¼ dosage, compared to DFB droplets at 900 kPa where histology indicated tissue damage due to inertial cavitation. In conclusion, the vaporization efficiency of nanodroplets positively impacted the amount of molecules delivered to the brain. The OFP droplets due to the higher vaporization efficiency served as better acoustic agents to deliver large molecules efficiently to the brain compared with the DFB droplets.

In vitro large-scale experimental and theoretical studies for the realization of bi-directional brain-prostheses.

PubMed

Bonifazi, Paolo; Difato, Francesco; Massobrio, Paolo; Breschi, Gian L; Pasquale, Valentina; Levi, Timothée; Goldin, Miri; Bornat, Yannick; Tedesco, Mariateresa; Bisio, Marta; Kanner, Sivan; Galron, Ronit; Tessadori, Jacopo; Taverna, Stefano; Chiappalone, Michela

2013-01-01

Brain-machine interfaces (BMI) were born to control "actions from thoughts" in order to recover motor capability of patients with impaired functional connectivity between the central and peripheral nervous system. The final goal of our studies is the development of a new proof-of-concept BMI-a neuromorphic chip for brain repair-to reproduce the functional organization of a damaged part of the central nervous system. To reach this ambitious goal, we implemented a multidisciplinary "bottom-up" approach in which in vitro networks are the paradigm for the development of an in silico model to be incorporated into a neuromorphic device. In this paper we present the overall strategy and focus on the different building blocks of our studies: (i) the experimental characterization and modeling of "finite size networks" which represent the smallest and most general self-organized circuits capable of generating spontaneous collective dynamics; (ii) the induction of lesions in neuronal networks and the whole brain preparation with special attention on the impact on the functional organization of the circuits; (iii) the first production of a neuromorphic chip able to implement a real-time model of neuronal networks. A dynamical characterization of the finite size circuits with single cell resolution is provided. A neural network model based on Izhikevich neurons was able to replicate the experimental observations. Changes in the dynamics of the neuronal circuits induced by optical and ischemic lesions are presented respectively for in vitro neuronal networks and for a whole brain preparation. Finally the implementation of a neuromorphic chip reproducing the network dynamics in quasi-real time (10 ns precision) is presented.

Body mass dependence of glycogen stores in the anoxia-tolerant crucian carp ( Carassius carassius L.)

NASA Astrophysics Data System (ADS)

Vornanen, Matti; Asikainen, Juha; Haverinen, Jaakko

2011-03-01

Glycogen is a vital energy substrate for anaerobic organisms, and the size of glycogen stores can be a limiting factor for anoxia tolerance of animals. To this end, glycogen stores in 12 different tissues of the crucian carp ( Carassius carassius L.), an anoxia-tolerant fish species, were examined. Glycogen content of different tissues was 2-10 times higher in winter (0.68-18.20% of tissue wet weight) than in summer (0.12-4.23%). In scale, bone and brain glycogen stores were strongly dependent on body mass (range between 0.6 and 785 g), small fish having significantly more glycogen than large fish ( p < 0.05). In fin and skin, size dependence was evident in winter, but not in summer, while in other tissues (ventricle, atrium, intestine, liver, muscle, and spleen), no size dependence was found. The liver was much bigger in small than large fish ( p < 0.001), and there was a prominent enlargement of the liver in winter irrespective of fish size. As a consequence, the whole body glycogen reserves, measured as a sum of glycogen from different tissues, varied from 6.1% of the body mass in the 1-g fish to 2.0% in the 800-g fish. Since anaerobic metabolic rate scales down with body size, the whole body glycogen reserves could provide energy for approximately 79 and 88 days of anoxia in small and large fish, respectively. There was, however, a drastic difference in tissue distribution of glycogen between large and small fish: in the small fish, the liver was the major glycogen store (68% of the stores), while in the large fish, the white myotomal muscle was the principal deposit of glycogen (57%). Since muscle glycogen is considered to be unavailable for blood glucose regulation, its usefulness in anoxia tolerance of the large crucian carp might be limited, although not excluded. Therefore, mobilization of muscle glycogen under anoxia needs to be rigorously tested.

Brain invasion assessability in meningiomas is related to meningioma size and grade, and can be improved by extensive sampling of the surgically removed meningioma specimen.

PubMed

Pizem, Joze; Velnar, Tomaz; Prestor, Borut; Mlakar, Jernej; Popovic, Mara

2014-01-01

Despite the important prognostic value of brain invasion in meningiomas, little attention has been paid to its massessment, and the parameters associated with brain invasion assessability (identification of brain tissue in the surgical specimen) are not well characterized. The aim of our study was to determine the parameters that are associated with brain invasion assessability and brain invasion in meningiomas. By binary logistic regression analysis, we studied the association of various clinical and pathologic parameters with brain invasion assessabilitym and brain invasion in 294 meningiomas: 149 unselected consecutive meningiomas with extensive sampling, diagnosed in 2009 and 2010, collected prospectively, and 145 meningiomas diagnosed in 1999 and 2000 when little attention was paid to brain invasion assessment. Meningioma grade, size and number of tissue blocks were independent predictors of brain invasion assessability. Brain tissue was identified in 78 of 233 (33%) benign, 33 of 51 (65%) atypical, and 10 of 10 (100%) malignant meningiomas. In univariate analysis, group (prospective vs.retrospective), type (recurrent vs. primary), cleavability, meningioma grade and mitotic count were predictors of brain invasion, while only meningioma grade, and group retained predictive value in multivariate analysis. Brain invasion, when assessable, was identified in 22 of 78 (28%) benign, 21 of 33 (64%) atypical, and 10 of 10 (100%) malignant meningiomas. Brain invasion assessability is related to meningioma grade and size and can be improved by extensive sampling of meningioma surgical.

Opposing Brain Differences in 16p11.2 Deletion and Duplication Carriers

PubMed Central

Qureshi, Abid Y.; Mueller, Sophia; Snyder, Abraham Z.; Mukherjee, Pratik; Berman, Jeffrey I.; Roberts, Timothy P.L.; Nagarajan, Srikantan S.; Spiro, John E.; Chung, Wendy K.; Sherr, Elliott H.

2014-01-01

Deletions and duplications of the recurrent ∼600 kb chromosomal BP4–BP5 region of 16p11.2 are associated with a broad variety of neurodevelopmental outcomes including autism spectrum disorder. A clue to the pathogenesis of the copy number variant (CNV)'s effect on the brain is that the deletion is associated with a head size increase, whereas the duplication is associated with a decrease. Here we analyzed brain structure in a clinically ascertained group of human deletion (N = 25) and duplication (N = 17) carriers from the Simons Variation in Individuals Project compared with age-matched controls (N = 29 and 33, respectively). Multiple brain measures showed increased size in deletion carriers and reduced size in duplication carriers. The effects spanned global measures of intracranial volume, brain size, compartmental measures of gray matter and white matter, subcortical structures, and the cerebellum. Quantitatively, the largest effect was on the thalamus, but the collective results suggest a pervasive rather than a selective effect on the brain. Detailed analysis of cortical gray matter revealed that cortical surface area displays a strong dose-dependent effect of CNV (deletion > control > duplication), whereas average cortical thickness is less affected. These results suggest that the CNV may exert its opposing influences through mechanisms that influence early stages of embryonic brain development. PMID:25143601

High-resolution detection of 13C multiplets from the conscious mouse brain by ex vivo NMR spectroscopy

PubMed Central

Marin-Valencia, Isaac; Good, Levi B.; Ma, Qian; Jeffrey, F. Mark; Malloy, Craig R.; Pascual, Juan M.

2011-01-01

Glucose readily supplies the brain with the majority of carbon needed to sustain neurotransmitter production and utilization., The rate of brain glucose metabolism can be computed using 13C nuclear magnetic resonance (NMR) spectroscopy by detecting changes in 13C contents of products generated by cerebral metabolism. As previously observed, scalar coupling between adjacent 13C carbons (multiplets) can provide additional information to 13C contents for the computation of metabolic rates. Most NMR studies have been conducted in large animals (often under anesthesia) because the mass of the target organ is a limiting factor for NMR. Yet, despite the challengingly small size of the mouse brain, NMR studies are highly desirable because the mouse constitutes a common animal model for human neurological disorders. We have developed a method for the ex vivo resolution of NMR multiplets arising from the brain of an awake mouse after the infusion of [1,6-13C2]glucose. NMR spectra obtained by this method display favorable signal-to-noise ratios. With this protocol, the 13C multiplets of glutamate, glutamine, GABA and aspartate achieved steady state after 150 min. The method enables the accurate resolution of multiplets over time in the awake mouse brain. We anticipate that this method can be broadly applicable to compute brain fluxes in normal and transgenic mouse models of neurological disorders. PMID:21946227

Fully integrated silicon probes for high-density recording of neural activity.

PubMed

Jun, James J; Steinmetz, Nicholas A; Siegle, Joshua H; Denman, Daniel J; Bauza, Marius; Barbarits, Brian; Lee, Albert K; Anastassiou, Costas A; Andrei, Alexandru; Aydın, Çağatay; Barbic, Mladen; Blanche, Timothy J; Bonin, Vincent; Couto, João; Dutta, Barundeb; Gratiy, Sergey L; Gutnisky, Diego A; Häusser, Michael; Karsh, Bill; Ledochowitsch, Peter; Lopez, Carolina Mora; Mitelut, Catalin; Musa, Silke; Okun, Michael; Pachitariu, Marius; Putzeys, Jan; Rich, P Dylan; Rossant, Cyrille; Sun, Wei-Lung; Svoboda, Karel; Carandini, Matteo; Harris, Kenneth D; Koch, Christof; O'Keefe, John; Harris, Timothy D

2017-11-08

Sensory, motor and cognitive operations involve the coordinated action of large neuronal populations across multiple brain regions in both superficial and deep structures. Existing extracellular probes record neural activity with excellent spatial and temporal (sub-millisecond) resolution, but from only a few dozen neurons per shank. Optical Ca 2+ imaging offers more coverage but lacks the temporal resolution needed to distinguish individual spikes reliably and does not measure local field potentials. Until now, no technology compatible with use in unrestrained animals has combined high spatiotemporal resolution with large volume coverage. Here we design, fabricate and test a new silicon probe known as Neuropixels to meet this need. Each probe has 384 recording channels that can programmably address 960 complementary metal-oxide-semiconductor (CMOS) processing-compatible low-impedance TiN sites that tile a single 10-mm long, 70 × 20-μm cross-section shank. The 6 × 9-mm probe base is fabricated with the shank on a single chip. Voltage signals are filtered, amplified, multiplexed and digitized on the base, allowing the direct transmission of noise-free digital data from the probe. The combination of dense recording sites and high channel count yielded well-isolated spiking activity from hundreds of neurons per probe implanted in mice and rats. Using two probes, more than 700 well-isolated single neurons were recorded simultaneously from five brain structures in an awake mouse. The fully integrated functionality and small size of Neuropixels probes allowed large populations of neurons from several brain structures to be recorded in freely moving animals. This combination of high-performance electrode technology and scalable chip fabrication methods opens a path towards recording of brain-wide neural activity during behaviour.

Fully Integrated Silicon Probes for High-Density Recording of Neural Activity

PubMed Central

Jun, James J.; Steinmetz, Nicholas A.; Siegle, Joshua H.; Denman, Daniel J.; Bauza, Marius; Barbarits, Brian; Lee, Albert K.; Anastassiou, Costas A.; Andrei, Alexandru; Aydın, Çağatay; Barbic, Mladen; Blanche, Timothy J.; Bonin, Vincent; Couto, João; Dutta, Barundeb; Gratiy, Sergey L.; Gutnisky, Diego A.; Häusser, Michael; Karsh, Bill; Ledochowitsch, Peter; Lopez, Carolina Mora; Mitelut, Catalin; Musa, Silke; Okun, Michael; Pachitariu, Marius; Putzeys, Jan; Rich, P. Dylan; Rossant, Cyrille; Sun, Wei-lung; Svoboda, Karel; Carandini, Matteo; Harris, Kenneth D.; Koch, Christof; O'Keefe, John; Harris, Timothy D.

2018-01-01

Summary Paragraph Sensory, motor, and cognitive operations involve the coordinated action of large neuronal populations across multiple brain regions in both superficial and deep structures1,2. Existing extracellular probes record neural activity with excellent spatial and temporal (sub-millisecond) resolution but from only a few dozen neurons per shank. Optical Ca2+ imaging3–5 offers more coverage but lacks the temporal resolution to reliably distinguish individual spikes and does not measure local field potentials. To date, no technology compatible with unrestrained animals has combined high spatiotemporal resolution with large volume coverage. To satisfy this need, we designed, fabricated, and tested a new silicon probe called Neuropixels. Each probe has 384 recording channels that can programmably address 960 CMOS processing-compatible low-impedance TiN6 sites that tile a single 10 mm long, 70x20 µm cross section shank. The 6x9 mm probe base is fabricated with the shank on a single chip. Voltage signals are filtered, amplified, multiplexed, and digitized on the base, allowing noise-free digital data transmission directly from the probe. The combination of dense recording sites and high channel count yielded well-isolated spiking activity from hundreds of neurons per probe implanted in mice and rats. Using two probes, more than 700 well-isolated single neurons were simultaneously recorded from five brain structures in an awake mouse. The fully integrated functionality and small size of Neuropixels probes allowed recording large populations of neurons from multiple brain structures in freely moving animals. This combination of high-performance electrode technology and scalable chip fabrication methods opens the path to record brain-wide neural activity during behavior. PMID:29120427

The evolution of cerebrotypes in birds.

PubMed

Iwaniuk, Andrew N; Hurd, Peter L

2005-01-01

Multivariate analyses of brain composition in mammals, amphibians and fish have revealed the evolution of 'cerebrotypes' that reflect specific niches and/or clades. Here, we present the first demonstration of similar cerebrotypes in birds. Using principal component analysis and hierarchical clustering methods to analyze a data set of 67 species, we demonstrate that five main cerebrotypes can be recognized. One type is dominated by galliforms and pigeons, among other species, that all share relatively large brainstems, but can be further differentiated by the proportional size of the cerebellum and telencephalic regions. The second cerebrotype contains a range of species that all share relatively large cerebellar and small nidopallial volumes. A third type is composed of two species, the tawny frogmouth (Podargus strigoides) and an owl, both of which share extremely large Wulst volumes. Parrots and passerines, the principal members of the fourth group, possess much larger nidopallial, mesopallial and striatopallidal proportions than the other groups. The fifth cerebrotype contains species such as raptors and waterfowl that are not found at the extremes for any of the brain regions and could therefore be classified as 'generalist' brains. Overall, the clustering of species does not directly reflect the phylogenetic relationships among species, but there is a tendency for species within an order to clump together. There may also be a weak relationship between cerebrotype and developmental differences, but two of the main clusters contained species with both altricial and precocial developmental patterns. As a whole, the groupings do agree with behavioral and ecological similarities among species. Most notably, species that share similarities in locomotor behavior, mode of prey capture or cognitive ability are clustered together. The relationship between cerebrotype and behavior/ecology in birds suggests that future comparative studies of brain-behavior relationships will benefit from adopting a multivariate approach. Copyright 2005 S. Karger AG, Basel.

Postmortem changes in the neuroanatomical characteristics of the primate brain: the hippocampal formation

PubMed Central

Lavenex, Pierre; Lavenex, Pamela Banta; Bennett, Jeffrey L.; Amaral, David G.

2009-01-01

Comparative studies of the structural organization of the brain are fundamental to our understanding of human brain function. However, whereas brains of experimental animals are fixed by perfusion of a fixative through the vasculature, human or ape brains are fixed by immersion after varying postmortem intervals. Although differential treatments might affect the fundamental characteristics of the tissue, this question has not been evaluated empirically in primate brains. Monkey brains were either perfused, or acquired after varying postmortem intervals before immersion-fixation in 4% paraformaldehyde. We found that the fixation method affected the neuroanatomical characteristics of the monkey hippocampal formation. Soma size was smaller in Nissl-stained, immersion-fixed tissue, although overall brain volume was larger, as compared to perfusion-fixed tissue. Non-phosphorylated high-molecular-weight neurofilament immunoreactivity was lower in CA3 pyramidal neurons, dentate mossy cells and the entorhinal cortex, whereas it was higher in the mossy fiber pathway in immersion-fixed tissue. Serotonin-immunoreactive fibers were well-stained in perfused tissue but were undetectable in immersion-fixed tissue. Although regional immunoreactivity patterns for calcium-binding proteins were not affected, intracellular staining degraded with increasing postmortem intervals. Somatostatin-immunoreactive clusters of large axonal varicosities, previously reported only in humans, were observed in immersion-fixed monkey tissue. In addition, calretinin-immunoreactive multipolar neurons, previously observed only in rodents, were found in the rostral dentate gyrus in both perfused and immersion-fixed brains. In conclusion, comparative studies of the brain must evaluate the effects of fixation on the staining pattern of each marker in every structure of interest before drawing conclusions about species differences. PMID:18972553

Postmortem changes in the neuroanatomical characteristics of the primate brain: hippocampal formation.

PubMed

Lavenex, Pierre; Lavenex, Pamela Banta; Bennett, Jeffrey L; Amaral, David G

2009-01-01

Comparative studies of the structural organization of the brain are fundamental to our understanding of human brain function. However, whereas brains of experimental animals are fixed by perfusion of a fixative through the vasculature, human or ape brains are fixed by immersion after varying postmortem intervals. Although differential treatments might affect the fundamental characteristics of the tissue, this question has not been evaluated empirically in primate brains. Monkey brains were either perfused or acquired after varying postmortem intervals before immersion-fixation in 4% paraformaldehyde. We found that the fixation method affected the neuroanatomical characteristics of the monkey hippocampal formation. Soma size was smaller in Nissl-stained, immersion-fixed tissue, although overall brain volume was larger as compared to perfusion-fixed tissue. Nonphosphorylated high-molecular-weight neurofilament immunoreactivity was lower in CA3 pyramidal neurons, dentate mossy cells, and the entorhinal cortex, whereas it was higher in the mossy fiber pathway in immersion-fixed tissue. Serotonin-immunoreactive fibers were well stained in perfused tissue but were undetectable in immersion-fixed tissue. Although regional immunoreactivity patterns for calcium-binding proteins were not affected, intracellular staining degraded with increasing postmortem intervals. Somatostatin-immunoreactive clusters of large axonal varicosities, previously reported only in humans, were observed in immersion-fixed monkey tissue. In addition, calretinin-immunoreactive multipolar neurons, previously observed only in rodents, were found in the rostral dentate gyrus in both perfused and immersion-fixed brains. In conclusion, comparative studies of the brain must evaluate the effects of fixation on the staining pattern of each marker in every structure of interest before drawing conclusions about species differences.

A pilot investigation of the potential for incorporating lifelog technology into executive function rehabilitation for enhanced transfer of self-regulation skills to everyday life.

PubMed

Cuberos-Urbano, Gustavo; Caracuel, Alfonso; Valls-Serrano, Carlos; García-Mochón, Leticia; Gracey, Fergus; Verdejo-García, Antonio

2018-06-01

The objective of the study was to identify the potential target and effect size of goal management training (GMT) enhanced with life-logging technology compared with standard GMT on a range of possible primary outcomes reflecting cognitive and ecological aspects of executive functioning and quality of life. Sixteen patients with acquired brain injury involving executive dysfunction were randomly allocated to one of the two interventions: seven weeks of GMT (n = 8), or seven weeks of GMT+Lifelog (n = 8). Outcome measures included a battery of executive function tests, the Dysexecutive Questionnaire (DEX) and the Quality of Life after Brain Injury scale (QOLIBRI), measured pre- and post-interventions. Within-group changes were assessed with related-samples t-tests and estimation of effect sizes. GMT+Lifelog was associated with significant changes, of medium to large effect size, in response inhibition (Stroop), multitasking (Strategy Application and Multiple Errand tests), DEX Intentionality and Positive Affect subscales and QOLIBRI Daily Life and Autonomy, subscales. GMT alone was associated with significant changes of overall quality of life. It was concluded that GMT+Lifelog holds promise to optimise the impact of GMT on executive dysfunction and quality of life.

An Allometric Analysis of Sex and Sex Chromosome Dosage Effects on Subcortical Anatomy in Humans

PubMed Central

Clasen, Liv; Giedd, Jay N.; Blumenthal, Jonathan; Lerch, Jason P.; Chakravarty, M. Mallar; Raznahan, Armin

2016-01-01

Structural neuroimaging of humans with typical and atypical sex-chromosome complements has established the marked influence of both Yand X-/Y-chromosome dosage on total brain volume (TBV) and identified potential cortical substrates for the psychiatric phenotypes associated with sex-chromosome aneuploidy (SCA). Here, in a cohort of 354 humans with varying karyotypes (XX, XY, XXX, XXY, XYY, XXYY, XXXXY), we investigate sex and SCA effects on subcortical size and shape; focusing on the striatum, pallidum and thalamus. We find large effect-size differences in the volume and shape of all three structures as a function of sex and SCA. We correct for TBV effects with a novel allometric method harnessing normative scaling rules for subcortical size and shape in humans, which we derive here for the first time. We show that all three subcortical volumes scale sublinearly with TBV among healthy humans, mirroring known relationships between subcortical volume and TBV among species. Traditional TBV correction methods assume linear scaling and can therefore invert or exaggerate sex and SCA effects on subcortical anatomy. Allometric analysis restricts sex-differences to: (1) greater pallidal volume (PV) in males, and (2) relative caudate head expansion and ventral striatum contraction in females. Allometric analysis of SCA reveals that supernumerary X- and Y-chromosomes both cause disproportionate reductions in PV, and coordinated deformations of striatopallidal shape. Our study provides a novel understanding of sex and sex-chromosome dosage effects on subcortical organization, using an allometric approach that can be generalized to other basic and clinical structural neuroimaging settings. SIGNIFICANCE STATEMENT Sex and sex-chromosome dosage (SCD) are known to modulate human brain size and cortical anatomy, but very little is known regarding their impact on subcortical structures that work with the cortex to subserve a range of behaviors in health and disease. Moreover, regional brain allometry (nonlinear scaling) poses largely unaddressed methodological and theoretical challenges for such research. We build the first set of allometric norms for global and regional subcortical anatomy, and use these to dissect out the complex, distributed and topologically organized patterns of areal contraction and expansion, which characterize sex and SCD effects on subcortical anatomy. Our data inform basic research into the patterning of neuroanatomical variation, and the clinical neuroscience of sex-chromosome aneuploidy. PMID:26911691

Mosaic evolution and adaptive brain component alteration under domestication seen on the background of evolutionary theory.

PubMed

Rehkämper, Gerd; Frahm, Heiko D; Cnotka, Julia

2008-01-01

Brain sizes and brain component sizes of five domesticated pigeon breeds including homing (racing) pigeons are compared with rock doves (Columba livia) based on an allometric approach to test the influence of domestication on brain and brain component size. Net brain volume, the volumes of cerebellum and telencephalon as a whole are significantly smaller in almost all domestic pigeons. Inside the telencephalon, mesopallium, nidopallium (+ entopallium + arcopallium) and septum are smaller as well. The hippocampus is significantly larger, particularly in homing pigeons. This finding is in contrast to the predictions of the 'regression hypothesis' of brain alteration under domestication. Among the domestic pigeons homing pigeons have significantly larger olfactory bulbs. These data are interpreted as representing a functional adaptation to homing that is based on spatial cognition and sensory integration. We argue that domestication as seen in domestic pigeons is not principally different from evolution in the wild, but represents a heuristic model to understand the evolutionary process in terms of adaptation and optimization. Copyright 2007 S. Karger AG, Basel.

Strategy for an Association Study of the Intestinal Microbiome and Brain Metabolome Across the Lifespan of Rats.

PubMed

Chen, Tianlu; You, Yijun; Xie, Guoxiang; Zheng, Xiaojiao; Zhao, Aihua; Liu, Jiajian; Zhao, Qing; Wang, Shouli; Huang, Fengjie; Rajani, Cynthia; Wang, Congcong; Chen, Shaoqiu; Ni, Yan; Yu, Herbert; Deng, Youping; Wang, Xiaoyan; Jia, Wei

2018-02-20

There is increased appreciation for the diverse roles of the microbiome-gut-brain axis on mammalian growth and health throughout the lifespan. Numerous studies have demonstrated that the gut microbiome and their metabolites are extensively involved in the communication between brain and gut. Association study of brain metabolome and gut microbiome is an active field offering large amounts of information on the interaction of microbiome, brain and gut but data size and complicated hierarchical relationships were found to be major obstacles to the formation of significant, reproducible conclusions. This study addressed a two-level strategy of brain metabolome and gut microbiome association analysis of male Wistar rats in the process of growth, employing several analytical platforms and various bioinformatics methods. Trajectory analysis showed that the age-related brain metabolome and gut microbiome had similarity in overall alteration patterns. Four high taxonomical level correlated pairs of "metabolite type-bacterial phylum", including "lipids-Spirochaetes", "free fatty acids (FFAs)-Firmicutes", "bile acids (BAs)-Firmicutes", and "Neurotransmitters-Bacteroidetes", were screened out based on unit- and multivariant correlation analysis and function analysis. Four groups of specific "metabolite-bacterium" association pairs from within the above high level key pairs were further identified. The key correlation pairs were validated by an independent animal study. This two-level strategy is effective in identifying principal correlations in big data sets obtained from the systematic multiomics study, furthering our understanding on the lifelong connection between brain and gut.

Live imaging of mitosis in the developing mouse embryonic cortex.

PubMed

Pilaz, Louis-Jan; Silver, Debra L

2014-06-04

Although of short duration, mitosis is a complex and dynamic multi-step process fundamental for development of organs including the brain. In the developing cerebral cortex, abnormal mitosis of neural progenitors can cause defects in brain size and function. Hence, there is a critical need for tools to understand the mechanisms of neural progenitor mitosis. Cortical development in rodents is an outstanding model for studying this process. Neural progenitor mitosis is commonly examined in fixed brain sections. This protocol will describe in detail an approach for live imaging of mitosis in ex vivo embryonic brain slices. We will describe the critical steps for this procedure, which include: brain extraction, brain embedding, vibratome sectioning of brain slices, staining and culturing of slices, and time-lapse imaging. We will then demonstrate and describe in detail how to perform post-acquisition analysis of mitosis. We include representative results from this assay using the vital dye Syto11, transgenic mice (histone H2B-EGFP and centrin-EGFP), and in utero electroporation (mCherry-α-tubulin). We will discuss how this procedure can be best optimized and how it can be modified for study of genetic regulation of mitosis. Live imaging of mitosis in brain slices is a flexible approach to assess the impact of age, anatomy, and genetic perturbation in a controlled environment, and to generate a large amount of data with high temporal and spatial resolution. Hence this protocol will complement existing tools for analysis of neural progenitor mitosis.

The effect of alcohol consumption on the adolescent brain: A systematic review of MRI and fMRI studies of alcohol-using youth

PubMed Central

Feldstein Ewing, Sarah W.; Sakhardande, Ashok; Blakemore, Sarah-Jayne

2014-01-01

Background A large proportion of adolescents drink alcohol, with many engaging in high-risk patterns of consumption, including binge drinking. Here, we systematically review and synthesize the existing empirical literature on how consuming alcohol affects the developing human brain in alcohol-using (AU) youth. Methods For this systematic review, we began by conducting a literature search using the PubMED database to identify all available peer-reviewed magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI) studies of AU adolescents (aged 19 and under). All studies were screened against a strict set of criteria designed to constrain the impact of confounding factors, such as co-occurring psychiatric conditions. Results Twenty-one studies (10 MRI and 11 fMRI) met the criteria for inclusion. A synthesis of the MRI studies suggested that overall, AU youth showed regional differences in brain structure as compared with non-AU youth, with smaller grey matter volumes and lower white matter integrity in relevant brain areas. In terms of fMRI outcomes, despite equivalent task performance between AU and non-AU youth, AU youth showed a broad pattern of lower task-relevant activation, and greater task-irrelevant activation. In addition, a pattern of gender differences was observed for brain structure and function, with particularly striking effects among AU females. Conclusions Alcohol consumption during adolescence was associated with significant differences in structure and function in the developing human brain. However, this is a nascent field, with several limiting factors (including small sample sizes, cross-sectional designs, presence of confounding factors) within many of the reviewed studies, meaning that results should be interpreted in light of the preliminary state of the field. Future longitudinal and large-scale studies are critical to replicate the existing findings, and to provide a more comprehensive and conclusive picture of the effect of alcohol consumption on the developing brain. PMID:26958467

The effect of alcohol consumption on the adolescent brain: A systematic review of MRI and fMRI studies of alcohol-using youth.

PubMed

Ewing, Sarah W Feldstein; Sakhardande, Ashok; Blakemore, Sarah-Jayne

2014-01-01

A large proportion of adolescents drink alcohol, with many engaging in high-risk patterns of consumption, including binge drinking. Here, we systematically review and synthesize the existing empirical literature on how consuming alcohol affects the developing human brain in alcohol-using (AU) youth. For this systematic review, we began by conducting a literature search using the PubMED database to identify all available peer-reviewed magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI) studies of AU adolescents (aged 19 and under). All studies were screened against a strict set of criteria designed to constrain the impact of confounding factors, such as co-occurring psychiatric conditions. Twenty-one studies (10 MRI and 11 fMRI) met the criteria for inclusion. A synthesis of the MRI studies suggested that overall, AU youth showed regional differences in brain structure as compared with non-AU youth, with smaller grey matter volumes and lower white matter integrity in relevant brain areas. In terms of fMRI outcomes, despite equivalent task performance between AU and non-AU youth, AU youth showed a broad pattern of lower task-relevant activation, and greater task-irrelevant activation. In addition, a pattern of gender differences was observed for brain structure and function, with particularly striking effects among AU females. Alcohol consumption during adolescence was associated with significant differences in structure and function in the developing human brain. However, this is a nascent field, with several limiting factors (including small sample sizes, cross-sectional designs, presence of confounding factors) within many of the reviewed studies, meaning that results should be interpreted in light of the preliminary state of the field. Future longitudinal and large-scale studies are critical to replicate the existing findings, and to provide a more comprehensive and conclusive picture of the effect of alcohol consumption on the developing brain.

Neuroprotective Effect of TAT-14-3-3ε Fusion Protein against Cerebral Ischemia/Reperfusion Injury in Rats

PubMed Central

Liu, Xiaoyan; Hu, Wenhui; Wang, Yinye

2014-01-01

Stroke is the major cause of death and disability worldwide, and the thrombolytic therapy currently available was unsatisfactory. 14-3-3ε is a well characterized member of 14-3-3 family, and has been reported to protect neurons against apoptosis in cerebral ischemia. However, it cannot transverse blood brain barrier (BBB) due to its large size. A protein transduction domain (PTD) of HIV TAT protein, is capable of delivering a large variety of proteins into the brain. In this study, we generated a fusion protein TAT-14-3-3ε, and evaluated its potential neuroprotective effect in rat focal ischemia/reperfusion (I/R) model. Western blot analysis validated the efficient transduction of TAT-14-3-3ε fusion protein into brain via a route of intravenous injection. TAT-14-3-3ε pre-treatment 2 h before ischemia significantly reduced cerebral infarction volume and improved neurologic score, while post-treatment 2 h after ischemia was less effective. Importantly, pre- or post-ischemic treatment with TAT-14-3-3ε significantly increased the number of surviving neurons as determined by Nissl staining, and attenuated I/R-induced neuronal apoptosis as showed by the decrease in apoptotic cell numbers and the inhibition of caspase-3 activity. Moreover, the introduction of 14-3-3ε into brain by TAT-mediated delivering reduced the formation of autophagosome, attenuated LC3B-II upregulation and reversed p62 downregulation induced by ischemic injury. Such inhibition of autophagy was reversed by treatment with an autophagy inducer rapamycin (RAP), which also attenuated the neuroprotective effect of TAT-14-3-3ε. Conversely, autophagy inhibitor 3-methyladenine (3-MA) inhibited I/R-induced the increase in autophagic activity, and attenuated I/R-induced brain infarct. These results suggest that TAT-14-3-3ε can be efficiently transduced into brain and exert significantly protective effect against brain ischemic injury through inhibiting neuronal apoptosis and autophagic activation. PMID:24671253

A prospective study to evaluate a residential community reintegration program for patients with chronic acquired brain injury.

PubMed

Geurtsen, Gert J; van Heugten, Caroline M; Martina, Juan D; Rietveld, Antonius C; Meijer, Ron; Geurts, Alexander C

2011-05-01

To examine the effects of a residential community reintegration program on independent living, societal participation, emotional well-being, and quality of life in patients with chronic acquired brain injury and psychosocial problems hampering societal participation. A prospective cohort study with a 3-month waiting list control period and 1-year follow up. A tertiary rehabilitation center for acquired brain injury. Patients (N=70) with acquired brain injury (46 men; mean age, 25.1y; mean time post-onset, 5.2y; at follow up n=67). A structured residential treatment program was offered directed at improving independence in domestic life, work, leisure time, and social interactions. Community Integration Questionnaire (CIQ), Employability Rating Scale, living situation, school, work situation, work hours, Center for Epidemiological Studies Depression Scale, EuroQOL quality of life scale (2 scales), World Health Organization Quality of Life Scale Abbreviated (WHOQOL-BREF; 5 scales), and the Global Assessment of Functioning (GAF) scale. There was an overall significant time effect for all outcome measures (multiple analysis of variance T(2)=26.16; F(36,557) 134.9; P=.000). There was no spontaneous recovery during the waiting-list period. The effect sizes for the CIQ, Employability Rating Scale, work hours, and GAF were large (partial η(2)=0.25, 0.35, 0.22, and 0.72, respectively). The effect sizes were moderate for 7 of the 8 emotional well-being and quality of life (sub)scales (partial η(2)=0.11-0.20). The WHOQOL-BREF environment subscale showed a small effect size (partial η(2)=0.05). Living independently rose from 25.4% before treatment to 72.4% after treatment and was still 65.7% at follow up. This study shows that a residential community reintegration program leads to significant and relevant improvements of independent living, societal participation, emotional well-being, and quality of life in patients with chronic acquired brain injury and psychosocial problems hampering societal participation. Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Brain size and encephalization in early to Mid-Pleistocene Homo.

PubMed

Rightmire, G Philip

2004-06-01

Important changes in the brain have occurred during the course of human evolution. Both absolute and relative size increases can be documented for species of Homo, culminating in the appearance of modern humans. One species that is particularly well-represented by fossil crania is Homo erectus. The mean capacity for 30 individuals is 973 cm(3). Within this group there is substantial variation, but brain size increases slightly in specimens from later time periods. Other Middle Pleistocene crania differ from those of Homo erectus. Characters of the facial skeleton, vault, and cranial base suggest that fossils from sites such as Arago Cave in France, the Sima de los Huesos in Spain, Bodo in Ethiopia, Broken Hill in Zambia, and perhaps Dali in China belong to the taxon Homo heidelbergensis. Ten of these mid-Quaternary hominins have brains averaging 1,206 cm(3) in volume, and many fall beyond the limits of size predicted for Homo erectus of equivalent age. When orbit height is used to construct an index of relative brain size, it is apparent that the (significant) increase in volume documented for the Middle Pleistocene individuals is not simply a consequence of larger body mass. Encephalization quotient values confirm this finding. These changes in absolute and relative brain size can be taken as further corroborative evidence for a speciation event, in which Homo erectus produced a daughter lineage. It is probable that Homo heidelbergensis originated in Africa or western Eurasia and then ranged widely across the Old World. Archaeological traces indicate that these populations differed in their technology and behavior from earlier hominins. Copyright 2003 Wiley-Liss, Inc.

Designing a compact high performance brain PET scanner—simulation study

NASA Astrophysics Data System (ADS)

Gong, Kuang; Majewski, Stan; Kinahan, Paul E.; Harrison, Robert L.; Elston, Brian F.; Manjeshwar, Ravindra; Dolinsky, Sergei; Stolin, Alexander V.; Brefczynski-Lewis, Julie A.; Qi, Jinyi

2016-05-01

The desire to understand normal and disordered human brain function of upright, moving persons in natural environments motivates the development of the ambulatory micro-dose brain PET imager (AMPET). An ideal system would be light weight but with high sensitivity and spatial resolution, although these requirements are often in conflict with each other. One potential approach to meet the design goals is a compact brain-only imaging device with a head-sized aperture. However, a compact geometry increases parallax error in peripheral lines of response, which increases bias and variance in region of interest (ROI) quantification. Therefore, we performed simulation studies to search for the optimal system configuration and to evaluate the potential improvement in quantification performance over existing scanners. We used the Cramér-Rao variance bound to compare the performance for ROI quantification using different scanner geometries. The results show that while a smaller ring diameter can increase photon detection sensitivity and hence reduce the variance at the center of the field of view, it can also result in higher variance in peripheral regions when the length of detector crystal is 15 mm or more. This variance can be substantially reduced by adding depth-of-interaction (DOI) measurement capability to the detector modules. Our simulation study also shows that the relative performance depends on the size of the ROI, and a large ROI favors a compact geometry even without DOI information. Based on these results, we propose a compact ‘helmet’ design using detectors with DOI capability. Monte Carlo simulations show the helmet design can achieve four-fold higher sensitivity and resolve smaller features than existing cylindrical brain PET scanners. The simulations also suggest that improving TOF timing resolution from 400 ps to 200 ps also results in noticeable improvement in image quality, indicating better timing resolution is desirable for brain imaging.

Designing a compact high performance brain PET scanner—simulation study

PubMed Central

Gong, Kuang; Majewski, Stan; Kinahan, Paul E; Harrison, Robert L; Elston, Brian F; Manjeshwar, Ravindra; Dolinsky, Sergei; Stolin, Alexander V; Brefczynski-Lewis, Julie A; Qi, Jinyi

2016-01-01

The desire to understand normal and disordered human brain function of upright, moving persons in natural environments motivates the development of the ambulatory micro-dose brain PET imager (AMPET). An ideal system would be light weight but with high sensitivity and spatial resolution, although these requirements are often in conflict with each other. One potential approach to meet the design goals is a compact brain-only imaging device with a head-sized aperture. However, a compact geometry increases parallax error in peripheral lines of response, which increases bias and variance in region of interest (ROI) quantification. Therefore, we performed simulation studies to search for the optimal system configuration and to evaluate the potential improvement in quantification performance over existing scanners. We used the Cramér–Rao variance bound to compare the performance for ROI quantification using different scanner geometries. The results show that while a smaller ring diameter can increase photon detection sensitivity and hence reduce the variance at the center of the field of view, it can also result in higher variance in peripheral regions when the length of detector crystal is 15 mm or more. This variance can be substantially reduced by adding depth-of- interaction (DOI) measurement capability to the detector modules. Our simulation study also shows that the relative performance depends on the size of the ROI, and a large ROI favors a compact geometry even without DOI information. Based on these results, we propose a compact ‘helmet’ design using detectors with DOI capability. Monte Carlo simulations show the helmet design can achieve four-fold higher sensitivity and resolve smaller features than existing cylindrical brain PET scanners. The simulations also suggest that improving TOF timing resolution from 400 ps to 200 ps also results in noticeable improvement in image quality, indicating better timing resolution is desirable for brain imaging. PMID:27081753

Scaling of cerebral blood perfusion in primates and marsupials.

PubMed

Seymour, Roger S; Angove, Sophie E; Snelling, Edward P; Cassey, Phillip

2015-08-01

The evolution of primates involved increasing body size, brain size and presumably cognitive ability. Cognition is related to neural activity, metabolic rate and rate of blood flow to the cerebral cortex. These parameters are difficult to quantify in living animals. This study shows that it is possible to determine the rate of cortical brain perfusion from the size of the internal carotid artery foramina in skulls of certain mammals, including haplorrhine primates and diprotodont marsupials. We quantify combined blood flow rate in both internal carotid arteries as a proxy of brain metabolism in 34 species of haplorrhine primates (0.116-145 kg body mass) and compare it to the same analysis for 19 species of diprotodont marsupials (0.014-46 kg). Brain volume is related to body mass by essentially the same exponent of 0.70 in both groups. Flow rate increases with haplorrhine brain volume to the 0.95 power, which is significantly higher than the exponent (0.75) expected for most organs according to 'Kleiber's Law'. By comparison, the exponent is 0.73 in marsupials. Thus, the brain perfusion rate increases with body size and brain size much faster in primates than in marsupials. The trajectory of cerebral perfusion in primates is set by the phylogenetically older groups (New and Old World monkeys, lesser apes) and the phylogenetically younger groups (great apes, including humans) fall near the line, with the highest perfusion. This may be associated with disproportionate increases in cortical surface area and mental capacity in the highly social, larger primates. © 2015. Published by The Company of Biologists Ltd.

The corpus callosum in primates: processing speed of axons and the evolution of hemispheric asymmetry

PubMed Central

Phillips, Kimberley A.; Stimpson, Cheryl D.; Smaers, Jeroen B.; Raghanti, Mary Ann; Jacobs, Bob; Popratiloff, Anastas; Hof, Patrick R.; Sherwood, Chet C.

2015-01-01

Interhemispheric communication may be constrained as brain size increases because of transmission delays in action potentials over the length of axons. Although one might expect larger brains to have progressively thicker axons to compensate, spatial packing is a limiting factor. Axon size distributions within the primate corpus callosum (CC) may provide insights into how these demands affect conduction velocity. We used electron microscopy to explore phylogenetic variation in myelinated axon density and diameter of the CC from 14 different anthropoid primate species, including humans. The majority of axons were less than 1 µm in diameter across all species, indicating that conduction velocity for most interhemispheric communication is relatively constant regardless of brain size. The largest axons within the upper 95th percentile scaled with a progressively higher exponent than the median axons towards the posterior region of the CC. While brain mass among the primates in our analysis varied by 97-fold, estimates of the fastest cross-brain conduction times, as conveyed by axons at the 95th percentile, varied within a relatively narrow range between 3 and 9 ms across species, whereas cross-brain conduction times for the median axon diameters differed more substantially between 11 and 38 ms. Nonetheless, for both size classes of axons, an increase in diameter does not entirely compensate for the delay in interhemispheric transmission time that accompanies larger brain size. Such biophysical constraints on the processing speed of axons conveyed by the CC may play an important role in the evolution of hemispheric asymmetry. PMID:26511047

Functional connectomics from a "big data" perspective.

PubMed

Xia, Mingrui; He, Yong

2017-10-15

In the last decade, explosive growth regarding functional connectome studies has been observed. Accumulating knowledge has significantly contributed to our understanding of the brain's functional network architectures in health and disease. With the development of innovative neuroimaging techniques, the establishment of large brain datasets and the increasing accumulation of published findings, functional connectomic research has begun to move into the era of "big data", which generates unprecedented opportunities for discovery in brain science and simultaneously encounters various challenging issues, such as data acquisition, management and analyses. Big data on the functional connectome exhibits several critical features: high spatial and/or temporal precision, large sample sizes, long-term recording of brain activity, multidimensional biological variables (e.g., imaging, genetic, demographic, cognitive and clinic) and/or vast quantities of existing findings. We review studies regarding functional connectomics from a big data perspective, with a focus on recent methodological advances in state-of-the-art image acquisition (e.g., multiband imaging), analysis approaches and statistical strategies (e.g., graph theoretical analysis, dynamic network analysis, independent component analysis, multivariate pattern analysis and machine learning), as well as reliability and reproducibility validations. We highlight the novel findings in the application of functional connectomic big data to the exploration of the biological mechanisms of cognitive functions, normal development and aging and of neurological and psychiatric disorders. We advocate the urgent need to expand efforts directed at the methodological challenges and discuss the direction of applications in this field. Copyright © 2017 Elsevier Inc. All rights reserved.

Simultaneous Control of Error Rates in fMRI Data Analysis

PubMed Central

Kang, Hakmook; Blume, Jeffrey; Ombao, Hernando; Badre, David

2015-01-01

The key idea of statistical hypothesis testing is to fix, and thereby control, the Type I error (false positive) rate across samples of any size. Multiple comparisons inflate the global (family-wise) Type I error rate and the traditional solution to maintaining control of the error rate is to increase the local (comparison-wise) Type II error (false negative) rates. However, in the analysis of human brain imaging data, the number of comparisons is so large that this solution breaks down: the local Type II error rate ends up being so large that scientifically meaningful analysis is precluded. Here we propose a novel solution to this problem: allow the Type I error rate to converge to zero along with the Type II error rate. It works because when the Type I error rate per comparison is very small, the accumulation (or global) Type I error rate is also small. This solution is achieved by employing the Likelihood paradigm, which uses likelihood ratios to measure the strength of evidence on a voxel-by-voxel basis. In this paper, we provide theoretical and empirical justification for a likelihood approach to the analysis of human brain imaging data. In addition, we present extensive simulations that show the likelihood approach is viable, leading to ‘cleaner’ looking brain maps and operationally superiority (lower average error rate). Finally, we include a case study on cognitive control related activation in the prefrontal cortex of the human brain. PMID:26272730

Artificial selection on male genitalia length alters female brain size.

PubMed

Buechel, Séverine D; Booksmythe, Isobel; Kotrschal, Alexander; Jennions, Michael D; Kolm, Niclas

2016-11-30

Male harassment is a classic example of how sexual conflict over mating leads to sex-specific behavioural adaptations. Females often suffer significant costs from males attempting forced copulations, and the sexes can be in an arms race over male coercion. Yet, despite recent recognition that divergent sex-specific interests in reproduction can affect brain evolution, sexual conflict has not been addressed in this context. Here, we investigate whether artificial selection on a correlate of male success at coercion, genital length, affects brain anatomy in males and females. We analysed the brains of eastern mosquitofish (Gambusia holbrooki), which had been artificially selected for long or short gonopodium, thereby mimicking selection arising from differing levels of male harassment. By analogy to how prey species often have relatively larger brains than their predators, we found that female, but not male, brain size was greater following selection for a longer gonopodium. Brain subregion volumes remained unchanged. These results suggest that there is a positive genetic correlation between male gonopodium length and female brain size, which is possibly linked to increased female cognitive ability to avoid male coercion. We propose that sexual conflict is an important factor in the evolution of brain anatomy and cognitive ability. © 2016 The Author(s).

Reconstructing the ups and downs of primate brain evolution: implications for adaptive hypotheses and Homo floresiensis

PubMed Central

2010-01-01

Background Brain size is a key adaptive trait. It is often assumed that increasing brain size was a general evolutionary trend in primates, yet recent fossil discoveries have documented brain size decreases in some lineages, raising the question of how general a trend there was for brains to increase in mass over evolutionary time. We present the first systematic phylogenetic analysis designed to answer this question. Results We performed ancestral state reconstructions of three traits (absolute brain mass, absolute body mass, relative brain mass) using 37 extant and 23 extinct primate species and three approaches to ancestral state reconstruction: parsimony, maximum likelihood and Bayesian Markov-chain Monte Carlo. Both absolute and relative brain mass generally increased over evolutionary time, but body mass did not. Nevertheless both absolute and relative brain mass decreased along several branches. Applying these results to the contentious case of Homo floresiensis, we find a number of scenarios under which the proposed evolution of Homo floresiensis' small brain appears to be consistent with patterns observed along other lineages, dependent on body mass and phylogenetic position. Conclusions Our results confirm that brain expansion began early in primate evolution and show that increases occurred in all major clades. Only in terms of an increase in absolute mass does the human lineage appear particularly striking, with both the rate of proportional change in mass and relative brain size having episodes of greater expansion elsewhere on the primate phylogeny. However, decreases in brain mass also occurred along branches in all major clades, and we conclude that, while selection has acted to enlarge primate brains, in some lineages this trend has been reversed. Further analyses of the phylogenetic position of Homo floresiensis and better body mass estimates are required to confirm the plausibility of the evolution of its small brain mass. We find that for our dataset the Bayesian analysis for ancestral state reconstruction is least affected by inclusion of fossil data suggesting that this approach might be preferable for future studies on other taxa with a poor fossil record. PMID:20105283

Robust regression for large-scale neuroimaging studies.

PubMed

Fritsch, Virgile; Da Mota, Benoit; Loth, Eva; Varoquaux, Gaël; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Brühl, Rüdiger; Butzek, Brigitte; Conrod, Patricia; Flor, Herta; Garavan, Hugh; Lemaitre, Hervé; Mann, Karl; Nees, Frauke; Paus, Tomas; Schad, Daniel J; Schümann, Gunter; Frouin, Vincent; Poline, Jean-Baptiste; Thirion, Bertrand

2015-05-01

Multi-subject datasets used in neuroimaging group studies have a complex structure, as they exhibit non-stationary statistical properties across regions and display various artifacts. While studies with small sample sizes can rarely be shown to deviate from standard hypotheses (such as the normality of the residuals) due to the poor sensitivity of normality tests with low degrees of freedom, large-scale studies (e.g. >100 subjects) exhibit more obvious deviations from these hypotheses and call for more refined models for statistical inference. Here, we demonstrate the benefits of robust regression as a tool for analyzing large neuroimaging cohorts. First, we use an analytic test based on robust parameter estimates; based on simulations, this procedure is shown to provide an accurate statistical control without resorting to permutations. Second, we show that robust regression yields more detections than standard algorithms using as an example an imaging genetics study with 392 subjects. Third, we show that robust regression can avoid false positives in a large-scale analysis of brain-behavior relationships with over 1500 subjects. Finally we embed robust regression in the Randomized Parcellation Based Inference (RPBI) method and demonstrate that this combination further improves the sensitivity of tests carried out across the whole brain. Altogether, our results show that robust procedures provide important advantages in large-scale neuroimaging group studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Opposing brain differences in 16p11.2 deletion and duplication carriers.

PubMed

Qureshi, Abid Y; Mueller, Sophia; Snyder, Abraham Z; Mukherjee, Pratik; Berman, Jeffrey I; Roberts, Timothy P L; Nagarajan, Srikantan S; Spiro, John E; Chung, Wendy K; Sherr, Elliott H; Buckner, Randy L

2014-08-20

Deletions and duplications of the recurrent ~600 kb chromosomal BP4-BP5 region of 16p11.2 are associated with a broad variety of neurodevelopmental outcomes including autism spectrum disorder. A clue to the pathogenesis of the copy number variant (CNV)'s effect on the brain is that the deletion is associated with a head size increase, whereas the duplication is associated with a decrease. Here we analyzed brain structure in a clinically ascertained group of human deletion (N = 25) and duplication (N = 17) carriers from the Simons Variation in Individuals Project compared with age-matched controls (N = 29 and 33, respectively). Multiple brain measures showed increased size in deletion carriers and reduced size in duplication carriers. The effects spanned global measures of intracranial volume, brain size, compartmental measures of gray matter and white matter, subcortical structures, and the cerebellum. Quantitatively, the largest effect was on the thalamus, but the collective results suggest a pervasive rather than a selective effect on the brain. Detailed analysis of cortical gray matter revealed that cortical surface area displays a strong dose-dependent effect of CNV (deletion > control > duplication), whereas average cortical thickness is less affected. These results suggest that the CNV may exert its opposing influences through mechanisms that influence early stages of embryonic brain development. Copyright © 2014 the authors 0270-6474/14/3411199-13$15.00/0.

Spinal cord evolution in early Homo.

PubMed

Meyer, Marc R; Haeusler, Martin

2015-11-01

The discovery at Nariokotome of the Homo erectus skeleton KNM-WT 15000, with a narrow spinal canal, seemed to show that this relatively large-brained hominin retained the primitive spinal cord size of African apes and that brain size expansion preceded postcranial neurological evolution. Here we compare the size and shape of the KNM-WT 15000 spinal canal with modern and fossil taxa including H. erectus from Dmanisi, Homo antecessor, the European middle Pleistocene hominins from Sima de los Huesos, and Pan troglodytes. In terms of shape and absolute and relative size of the spinal canal, we find all of the Dmanisi and most of the vertebrae of KNM-WT 15000 are within the human range of variation except for the C7, T2, and T3 of KNM-WT 15000, which are constricted, suggesting spinal stenosis. While additional fossils might definitively indicate whether H. erectus had evolved a human-like enlarged spinal canal, the evidence from the Dmanisi spinal canal and the unaffected levels of KNM-WT 15000 show that unlike Australopithecus, H. erectus had a spinal canal size and shape equivalent to that of modern humans. Subadult status is unlikely to affect our results, as spinal canal growth is complete in both individuals. We contest the notion that vertebrae yield information about respiratory control or language evolution, but suggest that, like H. antecessor and European middle Pleistocene hominins from Sima de los Huesos, early Homo possessed a postcranial neurological endowment roughly commensurate to modern humans, with implications for neurological, structural, and vascular improvements over Pan and Australopithecus. Copyright © 2015 Elsevier Ltd. All rights reserved.

Influence of the Laser Spot Size, Focal Beam Profile, and Tissue Type on the Lipid Signals Obtained by MALDI-MS Imaging in Oversampling Mode

NASA Astrophysics Data System (ADS)

Wiegelmann, Marcel; Dreisewerd, Klaus; Soltwisch, Jens

2016-12-01

To improve the lateral resolution in matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) beyond the dimensions of the focal laser spot oversampling techniques are employed. However, few data are available on the effect of the laser spot size and its focal beam profile on the ion signals recorded in oversampling mode. To investigate these dependencies, we produced 2 times six spots with dimensions between 30 and 200 μm. By optional use of a fundamental beam shaper, square flat-top and Gaussian beam profiles were compared. MALDI-MSI data were collected using a fixed pixel size of 20 μm and both pixel-by-pixel and continuous raster oversampling modes on a QSTAR mass spectrometer. Coronal mouse brain sections coated with 2,5-dihydroxybenzoic acid matrix were used as primary test systems. Sizably higher phospholipid ion signals were produced with laser spots exceeding a dimension of 100 μm, although the same amount of material was essentially ablated from the 20 μm-wide oversampling pixel at all spot size settings. Only on white matter areas of the brain these effects were less apparent to absent. Scanning electron microscopy images showed that these findings can presumably be attributed to different matrix morphologies depending on tissue type. We propose that a transition in the material ejection mechanisms from a molecular desorption at large to ablation at smaller spot sizes and a concomitant reduction in ion yields may be responsible for the observed spot size effects. The combined results indicate a complex interplay between tissue type, matrix crystallization, and laser-derived desorption/ablation and finally analyte ionization.

Influence of the Laser Spot Size, Focal Beam Profile, and Tissue Type on the Lipid Signals Obtained by MALDI-MS Imaging in Oversampling Mode.

PubMed

Wiegelmann, Marcel; Dreisewerd, Klaus; Soltwisch, Jens

2016-12-01

To improve the lateral resolution in matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) beyond the dimensions of the focal laser spot oversampling techniques are employed. However, few data are available on the effect of the laser spot size and its focal beam profile on the ion signals recorded in oversampling mode. To investigate these dependencies, we produced 2 times six spots with dimensions between ~30 and 200 μm. By optional use of a fundamental beam shaper, square flat-top and Gaussian beam profiles were compared. MALDI-MSI data were collected using a fixed pixel size of 20 μm and both pixel-by-pixel and continuous raster oversampling modes on a QSTAR mass spectrometer. Coronal mouse brain sections coated with 2,5-dihydroxybenzoic acid matrix were used as primary test systems. Sizably higher phospholipid ion signals were produced with laser spots exceeding a dimension of ~100 μm, although the same amount of material was essentially ablated from the 20 μm-wide oversampling pixel at all spot size settings. Only on white matter areas of the brain these effects were less apparent to absent. Scanning electron microscopy images showed that these findings can presumably be attributed to different matrix morphologies depending on tissue type. We propose that a transition in the material ejection mechanisms from a molecular desorption at large to ablation at smaller spot sizes and a concomitant reduction in ion yields may be responsible for the observed spot size effects. The combined results indicate a complex interplay between tissue type, matrix crystallization, and laser-derived desorption/ablation and finally analyte ionization. Graphical Abstract ᅟ.

Sex differences in the relationship between planum temporale asymmetry and corpus callosum morphology in chimpanzees (Pan troglodytes): A combined MRI and DTI analysis.

PubMed

Hopkins, William D; Hopkins, Anna M; Misiura, Maria; Latash, Elitaveta M; Mareno, Mary Catherine; Schapiro, Steven J; Phillips, Kimberley A

2016-12-01

Increases brain size has been hypothesized to be inversely associated with the expression of behavioral and brain asymmetries within and between species. We tested this hypothesis by analyzing the relation between asymmetries in the planum temporale (PT) and different measures of the corpus callosum (CC) including surface area, streamline count as measured from diffusion tensor imaging, fractional anisotropy values and the ratio in the number of fibers to surface area in a sample of chimpanzees. We found that chimpanzees with larger PT asymmetries in absolute terms had smaller CC surface areas, fewer streamlines and a smaller ratio of fibers to surface area. These results were largely specific to male but not female chimpanzees. Our results partially support the hypothesis that brain asymmetries are linked to variation in corpus callosum morphology, although these associations may be sex-dependent. Copyright © 2016 Elsevier Ltd. All rights reserved.

Novel genetic loci underlying human intracranial volume identified through genome-wide association

PubMed Central

Adams, Hieab HH; Hibar, Derrek P; Chouraki, Vincent; Stein, Jason L; Nyquist, Paul A; Rentería, Miguel E; Trompet, Stella; Arias-Vasquez, Alejandro; Seshadri, Sudha; Desrivières, Sylvane; Beecham, Ashley H; Jahanshad, Neda; Wittfeld, Katharina; Van der Lee, Sven J; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S; Armstrong, Nicola J; Athanasiu, Lavinia; Axelsson, Tomas; Beiser, Alexa; Bernard, Manon; Bis, Joshua C; Blanken, Laura ME; Blanton, Susan H; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brickman, Adam M; Carmichael, Owen; Chakravarty, M Mallar; Chauhan, Ganesh; Chen, Qiang; Ching, Christopher RK; Cuellar-Partida, Gabriel; Den Braber, Anouk; Doan, Nhat Trung; Ehrlich, Stefan; Filippi, Irina; Ge, Tian; Giddaluru, Sudheer; Goldman, Aaron L; Gottesman, Rebecca F; Greven, Corina U; Grimm, Oliver; Griswold, Michael E; Guadalupe, Tulio; Hass, Johanna; Haukvik, Unn K; Hilal, Saima; Hofer, Edith; Hoehn, David; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Liao, Jiemin; Liewald, David CM; Lopez, Lorna M; Luciano, Michelle; Macare, Christine; Marquand, Andre; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; Mazoyer, Bernard; McKay, David R; McWhirter, Rebekah; Milaneschi, Yuri; Mirza-Schreiber, Nazanin; Muetzel, Ryan L; Maniega, Susana Muñoz; Nho, Kwangsik; Nugent, Allison C; Olde Loohuis, Loes M; Oosterlaan, Jaap; Papmeyer, Martina; Pappa, Irene; Pirpamer, Lukas; Pudas, Sara; Pütz, Benno; Rajan, Kumar B; Ramasamy, Adaikalavan; Richards, Jennifer S; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rommelse, Nanda; Rose, Emma J; Royle, Natalie A; Rundek, Tatjana; Sämann, Philipp G; Satizabal, Claudia L; Schmaal, Lianne; Schork, Andrew J; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V; Sprooten, Emma; Strike, Lachlan T; Teumer, Alexander; Thomson, Russell; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Meer, Dennis; Van Donkelaar, Marjolein MJ; Van Eijk, Kristel R; Van Erp, Theo GM; Van Rooij, Daan; Walton, Esther; Westlye, Lars T; Whelan, Christopher D; Windham, Beverly G; Winkler, Anderson M; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Xu, Bing; Yanek, Lisa R; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P; Agartz, Ingrid; Aggarwal, Neelum T; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A; Arepalli, Sampath; Assareh, Amelia A; Barral, Sandra; Bastin, Mark E; Becker, Diane M; Becker, James T; Bennett, David A; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I; Brodaty, Henry; Brouwer, Rachel M; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bulayeva, Kazima B; Cahn, Wiepke; Calhoun, Vince D; Cannon, Dara M; Cavalleri, Gianpiero L; Chen, Christopher; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Dale, Anders M; Davies, Gareth E; De Geus, Eco JC; De Jager, Philip L; de Zubicaray, Greig I; Delanty, Norman; Depondt, Chantal; DeStefano, Anita L; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Espeseth, Thomas; Evans, Denis A; Fedko, Iryna O; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E; Fleischman, Debra A; Ford, Ian; Foroud, Tatiana M; Fox, Peter T; Francks, Clyde; Fukunaga, Masaki; Gibbs, J Raphael; Glahn, David C; Gollub, Randy L; Göring, Harald HH; Grabe, Hans J; Green, Robert C; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Hansell, Narelle K; Hardy, John; Hartman, Catharina A; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G; Heslenfeld, Dirk J; Ho, Beng-Choon; Hoekstra, Pieter J; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Hulshoff Pol, Hilleke E; Ikeda, Masashi; Ikram, M Kamran; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G; Jukema, J Wouter; Kahn, René S; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L; Longstreth, WT; Lopez, Oscar L; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S; McDonald, Colm; McIntosh, Andrew M; McMahon, Katie L; McMahon, Francis J; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W; Morris, Derek W; Mosley, Thomas H; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Nalls, Michael A; Nauck, Matthias; Nichols, Thomas E; Niessen, Wiro J; Nöthen, Markus M; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L; Ophoff, Roel A; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda WJH; Pike, G Bruce; Potkin, Steven G; Psaty, Bruce M; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L; Romanczuk-Seiferth, Nina; Rotter, Jerome I; Ryten, Mina; Sacco, Ralph L; Sachdev, Perminder S; Saykin, Andrew J; Schmidt, Reinhold; Schofield, Peter R; Sigurdsson, Sigurdur; Simmons, Andy; Singleton, Andrew; Sisodiya, Sanjay M; Smith, Colin; Smoller, Jordan W; Soininen, Hilkka; Srikanth, Velandai; Steen, Vidar M; Stott, David J; Sussmann, Jessika E; Thalamuthu, Anbupalam; Tiemeier, Henning; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Tzourio, Christophe; Uitterlinden, Andre G; Valdés Hernández, Maria C; Van der Brug, Marcel; Van der Lugt, Aad; Van der Wee, Nic JA; Van Duijn, Cornelia M; Van Haren, Neeltje EM; Van 't Ent, Dennis; Van Tol, Marie-Jose; Vardarajan, Badri N; Veltman, Dick J; Vernooij, Meike W; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M; Wassink, Thomas H; Weale, Michael E; Weinberger, Daniel R; Weiner, Michael W; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y; Wright, Clinton B; Zielke, H Ronald; Zonderman, Alan B; Deary, Ian J; DeCarli, Charles; Schmidt, Helena; Martin, Nicholas G; De Craen, Anton JM; Wright, Margaret J; Launer, Lenore J; Schumann, Gunter; Fornage, Myriam; Franke, Barbara; Debette, Stéphanie; Medland, Sarah E; Ikram, M Arfan; Thompson, Paul M

2016-01-01

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth. PMID:27694991

Therapeutic approaches for HER2-positive brain metastases: Circumventing the blood–brain barrier

PubMed Central

Mehta, Ankit I.; Brufsky, Adam M.; Sampson, John H.

2015-01-01

We aim to summarize data from studies of trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and brain metastasis and to describe novel methods being developed to circumvent the blood–brain barrier (BBB). A literature search was conducted to obtain data on the clinical efficacy of trastuzumab and lapatinib in patients with HER2-positive MBC and brain metastasis, as well as the transport of therapeutic molecules across the BBB. Trastuzumab-based therapy is the standard of care for patients with HER2-positive MBC. Post hoc and retrospective analyses show that trastuzumab significantly prolongs overall survival when given after the diagnosis of central nervous system (CNS) metastasis; this is probably attributable to its control of extracranial disease, although trastuzumab may have a direct effect on CNS disease in patients with local or general perturbation of the BBB. In patients without a compromised BBB, trastuzumab is thought to have limited access to the brain, because of its relatively large molecular size. Several approaches are being developed to enhance the delivery of therapeutic agents to the brain. These include physical or pharmacologic disruption of the BBB, direct intracerebral drug delivery, drug manipulation, and coupling drugs to transport vectors. Available data suggest that trastuzumab extends survival in patients with HER2-positive MBC and brain metastasis. Novel methods for delivery of therapeutic agents into the brain could be used in the future to enhance access to the CNS by trastuzumab, thereby improving its efficacy in this setting. PMID:22727691

Island Rule, quantitative genetics and brain-body size evolution in Homo floresiensis.

PubMed

Diniz-Filho, José Alexandre Felizola; Raia, Pasquale

2017-06-28

Colonization of islands often activate a complex chain of adaptive events that, over a relatively short evolutionary time, may drive strong shifts in body size, a pattern known as the Island Rule. It is arguably difficult to perform a direct analysis of the natural selection forces behind such a change in body size. Here, we used quantitative evolutionary genetic models, coupled with simulations and pattern-oriented modelling, to analyse the evolution of brain and body size in Homo floresiensis , a diminutive hominin species that appeared around 700 kya and survived up to relatively recent times (60-90 kya) on Flores Island, Indonesia. The hypothesis of neutral evolution was rejected in 97% of the simulations, and estimated selection gradients are within the range found in living natural populations. We showed that insularity may have triggered slightly different evolutionary trajectories for body and brain size, which means explaining the exceedingly small cranial volume of H. floresiensis requires additional selective forces acting on brain size alone. Our analyses also support previous conclusions that H. floresiensis may be most likely derived from an early Indonesian H. erectus , which is coherent with currently accepted biogeographical scenario for Homo expansion out of Africa. © 2017 The Author(s).

Ultrasound effects on brain-targeting mannosylated liposomes: in vitro and blood-brain barrier transport investigations.

PubMed

Zidan, Ahmed S; Aldawsari, Hibah

2015-01-01

Delivering drugs to intracerebral regions can be accomplished by improving the capacity of transport through blood-brain barrier. Using sertraline as model drug for brain targeting, the current study aimed at modifying its liposomal vesicles with mannopyranoside. Box-Behnken design was employed to statistically optimize the ultrasound parameters, namely ultrasound amplitude, time, and temperature, for maximum mannosylation capacity, sertraline entrapment, and surface charge while minimizing vesicular size. Moreover, in vitro blood-brain barrier transport model was established to assess the transendothelial capacity of the optimized mannosylated vesicles. Results showed a dependence of vesicular size, mannosylation capacity, and sertraline entrapment on cavitation and bubble implosion events that were related to ultrasound power amplitude, temperature. However, short ultrasound duration was required to achieve >90% mannosylation with nanosized vesicles (<200 nm) of narrow size distribution. Optimized ultrasound parameters of 65°C, 27%, and 59 seconds for ultrasound temperature, amplitude, and time were elucidated to produce 81.1%, 46.6 nm, and 77.6% sertraline entrapment, vesicular size, and mannosylation capacity, respectively. Moreover, the transendothelial ability was significantly increased by 2.5-fold by mannosylation through binding with glucose transporters. Hence, mannosylated liposomes processed by ultrasound could be a promising approach for manufacturing and scale-up of brain-targeting liposomes.

What can volumes reveal about human brain evolution? A framework for bridging behavioral, histometric, and volumetric perspectives

PubMed Central

de Sousa, Alexandra A.; Proulx, Michael J.

2014-01-01

An overall relationship between brain size and cognitive ability exists across primates. Can more specific information about neural function be gleaned from cortical area volumes? Numerous studies have found significant relationships between brain structures and behaviors. However, few studies have speculated about brain structure-function relationships from the microanatomical to the macroanatomical level. Here we address this problem in comparative neuroanatomy, where the functional relevance of overall brain size and the sizes of cortical regions have been poorly understood, by considering comparative psychology, with measures of visual acuity and the perception of visual illusions. We outline a model where the macroscopic size (volume or surface area) of a cortical region (such as the primary visual cortex, V1) is related to the microstructure of discrete brain regions. The hypothesis developed here is that an absolutely larger V1 can process more information with greater fidelity due to having more neurons to represent a field of space. This is the first time that the necessary comparative neuroanatomical research at the microstructural level has been brought to bear on the issue. The evidence suggests that as the size of V1 increases: the number of neurons increases, the neuron density decreases, and the density of neuronal connections increases. Thus, we describe how information about gross neuromorphology, using V1 as a model for the study of other cortical areas, may permit interpretations of cortical function. PMID:25009469

Sensitivity to prediction error in reach adaptation

PubMed Central

Haith, Adrian M.; Harran, Michelle D.; Shadmehr, Reza

2012-01-01

It has been proposed that the brain predicts the sensory consequences of a movement and compares it to the actual sensory feedback. When the two differ, an error signal is formed, driving adaptation. How does an error in one trial alter performance in the subsequent trial? Here we show that the sensitivity to error is not constant but declines as a function of error magnitude. That is, one learns relatively less from large errors compared with small errors. We performed an experiment in which humans made reaching movements and randomly experienced an error in both their visual and proprioceptive feedback. Proprioceptive errors were created with force fields, and visual errors were formed by perturbing the cursor trajectory to create a visual error that was smaller, the same size, or larger than the proprioceptive error. We measured single-trial adaptation and calculated sensitivity to error, i.e., the ratio of the trial-to-trial change in motor commands to error size. We found that for both sensory modalities sensitivity decreased with increasing error size. A reanalysis of a number of previously published psychophysical results also exhibited this feature. Finally, we asked how the brain might encode sensitivity to error. We reanalyzed previously published probabilities of cerebellar complex spikes (CSs) and found that this probability declined with increasing error size. From this we posit that a CS may be representative of the sensitivity to error, and not error itself, a hypothesis that may explain conflicting reports about CSs and their relationship to error. PMID:22773782

Functional Implications of Species Differences in the Size and Morphology of the Isthmo Optic Nucleus (ION) in Birds

PubMed Central

Gutiérrez-Ibáñez, Cristián; Iwaniuk, Andrew N.; Lisney, Thomas J.; Faunes, Macarena; Marín, Gonzalo J.; Wylie, Douglas R.

2012-01-01

In birds, there is a retinofugal projection from the brain to the retina originating from the isthmo optic nucleus (ION) in the midbrain. Despite a large number of anatomical, physiological and histochemical studies, the function of this retinofugal system remains unclear. Several functions have been proposed including: gaze stabilization, pecking behavior, dark adaptation, shifting attention, and detection of aerial predators. This nucleus varies in size and organization among some species, but the relative size and morphology of the ION has not been systematically studied. Here, we present a comparison of the relative size and morphology of the ION in 81 species of birds, representing 17 different orders. Our results show that several orders of birds, besides those previously reported, have a large, well-organized ION, including: hummingbirds, woodpeckers, coots and allies, and kingfishers. At the other end of the spectrum, parrots, herons, waterfowl, owls and diurnal raptors have relatively small ION volumes. ION also appears to be absent or unrecognizable is several taxa, including one of the basal avian groups, the tinamous, which suggests that the ION may have evolved only in the more modern group of birds, Neognathae. Finally, we demonstrate that evolutionary changes in the relative size and the cytoarchitectonic organization of ION have occurred largely independent of phylogeny. The large relative size of the ION in orders with very different lifestyles and feeding behaviors suggest there is no clear association with pecking behavior or predator detection. Instead, our results suggest that the ION is more complex and enlarged in birds that have eyes that are emmetropic in some parts of the visual field and myopic in others. We therefore posit that the ION is involved in switching attention between two parts of the retina i.e. from an emmetropic to a myopic part of the retina. PMID:22666395

Alzheimer’s Disease Susceptibility Genes APOE and TOMM40, and Hippocampal Volumes in the Lothian Birth Cohort 1936

PubMed Central

Lyall, Donald M.; Royle, Natalie A.; Harris, Sarah E.; Bastin, Mark E.; Maniega, Susana Muñoz; Murray, Catherine; Lutz, Michael W.; Saunders, Ann M.; Roses, Allen D.; del Valdés Hernández, Maria C.; Starr, John M.; Porteous, David. J.; Wardlaw, Joanna M.; Deary, Ian J.

2013-01-01

The APOE ε and TOMM40 rs10524523 (‘523’) variable length poly-T repeat gene loci have been significantly and independently associated with Alzheimer’s disease (AD) related phenotypes such as age of clinical onset. Hippocampal atrophy has been significantly associated with memory impairment, a characteristic of AD. The current study aimed to test for independent effects of APOE ε and TOMM40 ‘523’ genotypes on hippocampal volumes as assessed by brain structural MRI in a relatively large sample of community-dwelling older adults. As part of a longitudinal study of cognitive ageing, participants in the Lothian Birth Cohort 1936 underwent genotyping for APOE ε2/ε3/ε4 status and TOMM40 ‘523’ poly-T repeat length, and detailed structural brain MRI at a mean age of 72.7 years (standard deviation = 0.7, N range = 624 to 636). No significant effects of APOE ε or TOMM40 523 genotype were found on hippocampal volumes when analysed raw, or when adjusted for either intracranial or total brain tissue volumes. In summary, in a large community-dwelling sample of older adults, we found no effects of APOE ε or TOMM40 523 genotypes on hippocampal volumes. This is discrepant with some previous reports of significant association between APOE and left/right hippocampal volumes, and instead echoes other reports that found no association. Previous significant findings may partly reflect type 1 error. Future studies should carefully consider: 1) their specific techniques in adjusting for brain size; 2) assessing more detailed sub-divisions of the hippocampal formation; and 3) testing whether significant APOE-hippocampal associations are independent of generalised brain atrophy. PMID:24260406

Alzheimer's disease susceptibility genes APOE and TOMM40, and hippocampal volumes in the Lothian birth cohort 1936.

PubMed

Lyall, Donald M; Royle, Natalie A; Harris, Sarah E; Bastin, Mark E; Maniega, Susana Muñoz; Murray, Catherine; Lutz, Michael W; Saunders, Ann M; Roses, Allen D; del Valdés Hernández, Maria C; Starr, John M; Porteous, David J; Wardlaw, Joanna M; Deary, Ian J

2013-01-01

The APOE ε and TOMM40 rs10524523 ('523') variable length poly-T repeat gene loci have been significantly and independently associated with Alzheimer's disease (AD) related phenotypes such as age of clinical onset. Hippocampal atrophy has been significantly associated with memory impairment, a characteristic of AD. The current study aimed to test for independent effects of APOE ε and TOMM40 '523' genotypes on hippocampal volumes as assessed by brain structural MRI in a relatively large sample of community-dwelling older adults. As part of a longitudinal study of cognitive ageing, participants in the Lothian Birth Cohort 1936 underwent genotyping for APOE ε2/ε3/ε4 status and TOMM40 '523' poly-T repeat length, and detailed structural brain MRI at a mean age of 72.7 years (standard deviation = 0.7, N range = 624 to 636). No significant effects of APOE ε or TOMM40 523 genotype were found on hippocampal volumes when analysed raw, or when adjusted for either intracranial or total brain tissue volumes. In summary, in a large community-dwelling sample of older adults, we found no effects of APOE ε or TOMM40 523 genotypes on hippocampal volumes. This is discrepant with some previous reports of significant association between APOE and left/right hippocampal volumes, and instead echoes other reports that found no association. Previous significant findings may partly reflect type 1 error. Future studies should carefully consider: 1) their specific techniques in adjusting for brain size; 2) assessing more detailed sub-divisions of the hippocampal formation; and 3) testing whether significant APOE-hippocampal associations are independent of generalised brain atrophy.

FRIEND: a brain-monitoring agent for adaptive and assistive systems.

PubMed

Morris, Alexis; Ulieru, Mihaela

2012-01-01

This paper presents an architectural design for adaptive-systems agents (FRIEND) that use brain state information to make more effective decisions on behalf of a user; measuring brain context versus situational demands. These systems could be useful for alerting users to cognitive workload levels or fatigue, and could attempt to compensate for higher cognitive activity by filtering noise information. In some cases such systems could also share control of devices, such as pulling over in an automated vehicle. These aim to assist people in everyday systems to perform tasks better and be more aware of internal states. Achieving a functioning system of this sort is a challenge, involving a unification of brain- computer-interfaces, human-computer-interaction, soft-computin deliberative multi-agent systems disciplines. Until recently, these were not able to be combined into a usable platform due largely to technological limitations (e.g., size, cost, and processing speed), insufficient research on extracting behavioral states from EEG signals, and lack of low-cost wireless sensing headsets. We aim to surpass these limitations and develop control architectures for making sense of brain state in applications by realizing an agent architecture for adaptive (human-aware) technology. In this paper we present an early, high-level design towards implementing a multi-purpose brain-monitoring agent system to improve user quality of life through the assistive applications of psycho-physiological monitoring, noise-filtering, and shared system control.

Parietal cortex mediates perceptual Gestalt grouping independent of stimulus size.

PubMed

Grassi, Pablo R; Zaretskaya, Natalia; Bartels, Andreas

2016-06-01

The integration of local moving elements into a unified gestalt percept has previously been linked to the posterior parietal cortex. There are two possible interpretations for the lack of involvement of other occipital regions. The first is that parietal cortex is indeed uniquely functionally specialized to perform grouping. Another possibility is that other visual regions can perform grouping as well, but that the large spatial separation of the local elements used previously exceeded their neurons' receptive field (RF) sizes, preventing their involvement. In this study we distinguished between these two alternatives. We measured whole-brain activity using fMRI in response to a bistable motion illusion that induced mutually exclusive percepts of either an illusory global Gestalt or of local elements. The stimulus was presented in two sizes, a large version known to activate IPS only, and a version sufficiently small to fit into the RFs of mid-level dorsal regions such as V5/MT. We found that none of the separately localized motion regions apart from parietal cortex showed a preference for global Gestalt perception, even for the smaller version of the stimulus. This outcome suggests that grouping-by-motion is mediated by a specialized size-invariant mechanism with parietal cortex as its anatomical substrate. Copyright © 2016 Elsevier Inc. All rights reserved.

Parasitoidism, not sociality, is associated with the evolution of elaborate mushroom bodies in the brains of hymenopteran insects.

PubMed

Farris, Sarah M; Schulmeister, Susanne

2011-03-22

The social brain hypothesis posits that the cognitive demands of social behaviour have driven evolutionary expansions in brain size in some vertebrate lineages. In insects, higher brain centres called mushroom bodies are enlarged and morphologically elaborate (having doubled, invaginated and subcompartmentalized calyces that receive visual input) in social species such as the ants, bees and wasps of the aculeate Hymenoptera, suggesting that the social brain hypothesis may also apply to invertebrate animals. In a quantitative and qualitative survey of mushroom body morphology across the Hymenoptera, we demonstrate that large, elaborate mushroom bodies arose concurrent with the acquisition of a parasitoid mode of life at the base of the Euhymenopteran (Orussioidea + Apocrita) lineage, approximately 90 Myr before the evolution of sociality in the Aculeata. Thus, sociality could not have driven mushroom body elaboration in the Hymenoptera. Rather, we propose that the cognitive demands of host-finding behaviour in parasitoids, particularly the capacity for associative and spatial learning, drove the acquisition of this evolutionarily novel mushroom body architecture. These neurobehavioural modifications may have served as pre-adaptations for central place foraging, a spatial learning-intensive behaviour that is widespread across the Aculeata and may have contributed to the multiple acquisitions of sociality in this taxon.

Revisiting the cognitive buffer hypothesis for the evolution of large brains

PubMed Central

Sol, Daniel

2008-01-01

Why have some animals evolved large brains despite substantial energetic and developmental costs? A classic answer is that a large brain facilitates the construction of behavioural responses to unusual, novel or complex socioecological challenges. This buffer effect should increase survival rates and favour a longer reproductive life, thereby compensating for the costs of delayed reproduction. Although still limited, evidence in birds and mammals is accumulating that a large brain facilitates the construction of novel and altered behavioural patterns and that this ability helps dealing with new ecological challenges more successfully, supporting the cognitive-buffer interpretation of the evolution of large brains. PMID:19049952

Neuroscientists’ Classroom Visits Positively Impact Student Attitudes

PubMed Central

Fitzakerley, Janet L.; Michlin, Michael L.; Paton, John; Dubinsky, Janet M.

2013-01-01

The primary recommendation of the 2010 President’s Council of Advisors on Science and Technology report on K-12 education was to inspire more students so that they are motivated to study science. Scientists’ visits to classrooms are intended to inspire learners and increase their interest in science, but verifications of this impact are largely qualitative. Our primary goal was to evaluate the impact of a longstanding Brain Awareness classroom visit program focused on increasing learners understanding of their own brains. Educational psychologists have established that neuroscience training sessions can improve academic performance and shift attitudes of students from a fixed mindset to a growth mindset. Our secondary goal was to determine whether short interactive Brain Awareness scientist-in-the-classroom sessions could similarly alter learners’ perceptions of their own potential to learn. Teacher and student surveys were administered in 4th-6th grade classrooms throughout Minnesota either before or after one-hour Brain Awareness sessions that engaged students in activities related to brain function. Teachers rated the Brain Awareness program as very valuable and said that the visits stimulated students’ interest in the brain and in science. Student surveys probed general attitudes towards science and their knowledge of neuroscience concepts (particularly the ability of the brain to change). Significant favorable improvements were found on 10 of 18 survey statements. Factor analyses of 4805 responses demonstrated that Brain Awareness presentations increased positive attitudes toward science and improved agreement with statements related to growth mindset. Overall effect sizes were small, consistent with the short length of the presentations. Thus, the impact of Brain Awareness presentations was positive and proportional to the efforts expended, demonstrating that short, scientist-in-the-classroom visits can make a positive contribution to primary school students’ attitudes toward science and learning. PMID:24358325

Neuroscientists' classroom visits positively impact student attitudes.

PubMed

Fitzakerley, Janet L; Michlin, Michael L; Paton, John; Dubinsky, Janet M

2013-01-01

The primary recommendation of the 2010 President's Council of Advisors on Science and Technology report on K-12 education was to inspire more students so that they are motivated to study science. Scientists' visits to classrooms are intended to inspire learners and increase their interest in science, but verifications of this impact are largely qualitative. Our primary goal was to evaluate the impact of a longstanding Brain Awareness classroom visit program focused on increasing learners understanding of their own brains. Educational psychologists have established that neuroscience training sessions can improve academic performance and shift attitudes of students from a fixed mindset to a growth mindset. Our secondary goal was to determine whether short interactive Brain Awareness scientist-in-the-classroom sessions could similarly alter learners' perceptions of their own potential to learn. Teacher and student surveys were administered in 4(th)-6(th) grade classrooms throughout Minnesota either before or after one-hour Brain Awareness sessions that engaged students in activities related to brain function. Teachers rated the Brain Awareness program as very valuable and said that the visits stimulated students' interest in the brain and in science. Student surveys probed general attitudes towards science and their knowledge of neuroscience concepts (particularly the ability of the brain to change). Significant favorable improvements were found on 10 of 18 survey statements. Factor analyses of 4805 responses demonstrated that Brain Awareness presentations increased positive attitudes toward science and improved agreement with statements related to growth mindset. Overall effect sizes were small, consistent with the short length of the presentations. Thus, the impact of Brain Awareness presentations was positive and proportional to the efforts expended, demonstrating that short, scientist-in-the-classroom visits can make a positive contribution to primary school students' attitudes toward science and learning.

Male criminals with organic brain syndrome: two distinct types based on age at first arrest.

PubMed

Grekin, E R; Brennan, P A; Hodgins, S; Mednick, S A

2001-07-01

This study examined whether criminals with organic brain syndrome could be divided into two distinct types. The authors proposed that early starters (onset of criminal activity by age 18) would display a persistent, long-lasting pattern of deviance that was largely independent of their brain disorder, whereas late starters (onset at age 19 or after) would exhibit deviant behaviors that began late in life and were more directly related to their brain disorder. Subjects were 1,130 male criminal offenders drawn from a birth cohort of all individuals born between January 1, 1944, and December 31, 1947, in Denmark. The main study group included all men with both a history of criminal arrest and a hospitalization for organic brain syndrome (N=565). In addition, for a subset of analyses, the authors examined a randomly selected, same-size comparison group of men with a history of criminal arrest who were not hospitalized for organic brain syndrome. Data were available on all arrests and all psychiatric hospitalizations for individuals in this cohort through the age of 44. Among those with organic brain syndrome, early starters were significantly more likely than late starters to 1) be arrested before the onset of organic brain syndrome, 2) show a higher rate of offending before but not after the onset of organic brain syndrome, 3) be both recidivists and violent recidivists, and 4) have a diagnosis of antisocial personality disorder. Male criminals with organic brain syndrome can be meaningfully divided into two distinct types on the basis of age at first arrest. Early starters show a more global, persistent, and stable pattern of offending than late starters. These results have implications for treatment and risk assessment.

Neural Plasticity and Neurorehabilitation Following Traumatic Brain Injury

DTIC Science & Technology

2009-10-01

Nissl . Using the Nissl stained sections, Dorothy Kozlowski’s lab has analyzed the size of the contusions. Previous studies have shown that if...brains, staining one set with Nissl , saving the remaining sets for Immunohistochemical staining . • Dr. Kozlowski’s lab is analyzing contusion size...serially and coronaly into sets and immunohistochemically analyzed for the following: contusion size estimated as volume of remaining tissue in Nissl

Fuzzy object models for newborn brain MR image segmentation

NASA Astrophysics Data System (ADS)

Kobashi, Syoji; Udupa, Jayaram K.

2013-03-01

Newborn brain MR image segmentation is a challenging problem because of variety of size, shape and MR signal although it is the fundamental study for quantitative radiology in brain MR images. Because of the large difference between the adult brain and the newborn brain, it is difficult to directly apply the conventional methods for the newborn brain. Inspired by the original fuzzy object model introduced by Udupa et al. at SPIE Medical Imaging 2011, called fuzzy shape object model (FSOM) here, this paper introduces fuzzy intensity object model (FIOM), and proposes a new image segmentation method which combines the FSOM and FIOM into fuzzy connected (FC) image segmentation. The fuzzy object models are built from training datasets in which the cerebral parenchyma is delineated by experts. After registering FSOM with the evaluating image, the proposed method roughly recognizes the cerebral parenchyma region based on a prior knowledge of location, shape, and the MR signal given by the registered FSOM and FIOM. Then, FC image segmentation delineates the cerebral parenchyma using the fuzzy object models. The proposed method has been evaluated using 9 newborn brain MR images using the leave-one-out strategy. The revised age was between -1 and 2 months. Quantitative evaluation using false positive volume fraction (FPVF) and false negative volume fraction (FNVF) has been conducted. Using the evaluation data, a FPVF of 0.75% and FNVF of 3.75% were achieved. More data collection and testing are underway.

The evolution of the complex sensory and motor systems of the human brain.

PubMed

Kaas, Jon H

2008-03-18

Inferences about how the complex sensory and motor systems of the human brain evolved are based on the results of comparative studies of brain organization across a range of mammalian species, and evidence from the endocasts of fossil skulls of key extinct species. The endocasts of the skulls of early mammals indicate that they had small brains with little neocortex. Evidence from comparative studies of cortical organization from small-brained mammals of the six major branches of mammalian evolution supports the conclusion that the small neocortex of early mammals was divided into roughly 20-25 cortical areas, including primary and secondary sensory fields. In early primates, vision was the dominant sense, and cortical areas associated with vision in temporal and occipital cortex underwent a significant expansion. Comparative studies indicate that early primates had 10 or more visual areas, and somatosensory areas with expanded representations of the forepaw. Posterior parietal cortex was also expanded, with a caudal half dominated by visual inputs, and a rostral half dominated by somatosensory inputs with outputs to an array of seven or more motor and visuomotor areas of the frontal lobe. Somatosensory areas and posterior parietal cortex became further differentiated in early anthropoid primates. As larger brains evolved in early apes and in our hominin ancestors, the number of cortical areas increased to reach an estimated 200 or so in present day humans, and hemispheric specializations emerged. The large human brain grew primarily by increasing neuron number rather than increasing average neuron size.

Brain-computer interfaces for post-stroke motor rehabilitation: a meta-analysis.

PubMed

Cervera, María A; Soekadar, Surjo R; Ushiba, Junichi; Millán, José Del R; Liu, Meigen; Birbaumer, Niels; Garipelli, Gangadhar

2018-05-01

Brain-computer interfaces (BCIs) can provide sensory feedback of ongoing brain oscillations, enabling stroke survivors to modulate their sensorimotor rhythms purposefully. A number of recent clinical studies indicate that repeated use of such BCIs might trigger neurological recovery and hence improvement in motor function. Here, we provide a first meta-analysis evaluating the clinical effectiveness of BCI-based post-stroke motor rehabilitation. Trials were identified using MEDLINE, CENTRAL, PEDro and by inspection of references in several review articles. We selected randomized controlled trials that used BCIs for post-stroke motor rehabilitation and provided motor impairment scores before and after the intervention. A random-effects inverse variance method was used to calculate the summary effect size. We initially identified 524 articles and, after removing duplicates, we screened titles and abstracts of 473 articles. We found 26 articles corresponding to BCI clinical trials, of these, there were nine studies that involved a total of 235 post-stroke survivors that fulfilled the inclusion criterion (randomized controlled trials that examined motor performance as an outcome measure) for the meta-analysis. Motor improvements, mostly quantified by the upper limb Fugl-Meyer Assessment (FMA-UE), exceeded the minimal clinically important difference (MCID=5.25) in six BCI studies, while such improvement was reached only in three control groups. Overall, the BCI training was associated with a standardized mean difference of 0.79 (95% CI: 0.37 to 1.20) in FMA-UE compared to control conditions, which is in the range of medium to large summary effect size. In addition, several studies indicated BCI-induced functional and structural neuroplasticity at a subclinical level. This suggests that BCI technology could be an effective intervention for post-stroke upper limb rehabilitation. However, more studies with larger sample size are required to increase the reliability of these results.

Tracking the Spatiotemporal Neural Dynamics of Real-world Object Size and Animacy in the Human Brain.

PubMed

Khaligh-Razavi, Seyed-Mahdi; Cichy, Radoslaw Martin; Pantazis, Dimitrios; Oliva, Aude

2018-06-07

Animacy and real-world size are properties that describe any object and thus bring basic order into our perception of the visual world. Here, we investigated how the human brain processes real-world size and animacy. For this, we applied representational similarity to fMRI and MEG data to yield a view of brain activity with high spatial and temporal resolutions, respectively. Analysis of fMRI data revealed that a distributed and partly overlapping set of cortical regions extending from occipital to ventral and medial temporal cortex represented animacy and real-world size. Within this set, parahippocampal cortex stood out as the region representing animacy and size stronger than most other regions. Further analysis of the detailed representational format revealed differences among regions involved in processing animacy. Analysis of MEG data revealed overlapping temporal dynamics of animacy and real-world size processing starting at around 150 msec and provided the first neuromagnetic signature of real-world object size processing. Finally, to investigate the neural dynamics of size and animacy processing simultaneously in space and time, we combined MEG and fMRI with a novel extension of MEG-fMRI fusion by representational similarity. This analysis revealed partly overlapping and distributed spatiotemporal dynamics, with parahippocampal cortex singled out as a region that represented size and animacy persistently when other regions did not. Furthermore, the analysis highlighted the role of early visual cortex in representing real-world size. A control analysis revealed that the neural dynamics of processing animacy and size were distinct from the neural dynamics of processing low-level visual features. Together, our results provide a detailed spatiotemporal view of animacy and size processing in the human brain.

Meta-analysis of associations between human brain volume and intelligence differences: How strong are they and what do they mean?

PubMed

Pietschnig, Jakob; Penke, Lars; Wicherts, Jelte M; Zeiler, Michael; Voracek, Martin

2015-10-01

Positive associations between human intelligence and brain size have been suspected for more than 150 years. Nowadays, modern non-invasive measures of in vivo brain volume (Magnetic Resonance Imaging) make it possible to reliably assess associations with IQ. By means of a systematic review of published studies and unpublished results obtained by personal communications with researchers, we identified 88 studies examining effect sizes of 148 healthy and clinical mixed-sex samples (>8000 individuals). Our results showed significant positive associations of brain volume and IQ (r=.24, R(2)=.06) that generalize over age (children vs. adults), IQ domain (full-scale, performance, and verbal IQ), and sex. Application of a number of methods for detection of publication bias indicates that strong and positive correlation coefficients have been reported frequently in the literature whilst small and non-significant associations appear to have been often omitted from reports. We show that the strength of the positive association of brain volume and IQ has been overestimated in the literature, but remains robust even when accounting for different types of dissemination bias, although reported effects have been declining over time. While it is tempting to interpret this association in the context of human cognitive evolution and species differences in brain size and cognitive ability, we show that it is not warranted to interpret brain size as an isomorphic proxy of human intelligence differences. Copyright © 2015 Elsevier Ltd. All rights reserved.

Endocranial morphology of Palaeocene Plesiadapis tricuspidens and evolution of the early primate brain.

PubMed

Orliac, Maeva J; Ladevèze, Sandrine; Gingerich, Philip D; Lebrun, Renaud; Smith, Thierry

2014-04-22

Expansion of the brain is a key feature of primate evolution. The fossil record, although incomplete, allows a partial reconstruction of changes in primate brain size and morphology through time. Palaeogene plesiadapoids, closest relatives of Euprimates (or crown-group primates), are crucial for understanding early evolution of the primate brain. However, brain morphology of this group remains poorly documented, and major questions remain regarding the initial phase of euprimate brain evolution. Micro-CT investigation of the endocranial morphology of Plesiadapis tricuspidens from the Late Palaeocene of Europe--the most complete plesiadapoid cranium known--shows that plesiadapoids retained a very small and simple brain. Plesiadapis has midbrain exposure, and minimal encephalization and neocorticalization, making it comparable with that of stem rodents and lagomorphs. However, Plesiadapis shares a domed neocortex and downwardly shifted olfactory-bulb axis with Euprimates. If accepted phylogenetic relationships are correct, then this implies that the euprimate brain underwent drastic reorganization during the Palaeocene, and some changes in brain structure preceded brain size increase and neocortex expansion during evolution of the primate brain.

Prenatal famine exposure has sex-specific effects on brain size.

PubMed

de Rooij, Susanne R; Caan, Matthan W A; Swaab, Dick F; Nederveen, Aart J; Majoie, Charles B; Schwab, Matthias; Painter, Rebecca C; Roseboom, Tessa J

2016-08-01

Early nutritional deprivation might cause irreversible damage to the brain. Prenatal exposure to undernutrition has been shown to be associated with increased central nervous system anomalies at birth and decreased cognitive function in adulthood. Little is known about the potential effect on the brain in older age. We investigated brain size and structure at age 68 years after prenatal famine exposure. T1-weighted structural magnetic resonance images of the brain were made in 118 Dutch famine birth cohort members. Of these 118 (44% male, age range 65-69 years), 41 had been exposed to famine in early gestation and 77 had been prenatally unexposed. Structural volumes were automatically assessed using FreeSurfer. Diffusion tensor imaging was performed and anisotropy and diffusivity were computed. Fluid attenuated inversion recovery was performed to assess white matter hyperintensities. Exposure to famine in early gestation was associated with smaller intracranial volume in males, but not females. Volumes of total brain, grey and white matter were also smaller in early exposed males, but these differences disappeared after adjusting for intracranial volume. Prenatally exposed males but not females, had a smaller intracranial and total brain volume compared to unexposed subjects. Our findings show that prenatal undernutrition permanently affected brain size.media-1vid110.1093/brain/aww132_video_abstractaww132_video_abstract. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Scaling of Brain Metabolism with a Fixed Energy Budget per Neuron: Implications for Neuronal Activity, Plasticity and Evolution

PubMed Central

Herculano-Houzel, Suzana

2011-01-01

It is usually considered that larger brains have larger neurons, which consume more energy individually, and are therefore accompanied by a larger number of glial cells per neuron. These notions, however, have never been tested. Based on glucose and oxygen metabolic rates in awake animals and their recently determined numbers of neurons, here I show that, contrary to the expected, the estimated glucose use per neuron is remarkably constant, varying only by 40% across the six species of rodents and primates (including humans). The estimated average glucose use per neuron does not correlate with neuronal density in any structure. This suggests that the energy budget of the whole brain per neuron is fixed across species and brain sizes, such that total glucose use by the brain as a whole, by the cerebral cortex and also by the cerebellum alone are linear functions of the number of neurons in the structures across the species (although the average glucose consumption per neuron is at least 10× higher in the cerebral cortex than in the cerebellum). These results indicate that the apparently remarkable use in humans of 20% of the whole body energy budget by a brain that represents only 2% of body mass is explained simply by its large number of neurons. Because synaptic activity is considered the major determinant of metabolic cost, a conserved energy budget per neuron has several profound implications for synaptic homeostasis and the regulation of firing rates, synaptic plasticity, brain imaging, pathologies, and for brain scaling in evolution. PMID:21390261

Scaling of brain metabolism with a fixed energy budget per neuron: implications for neuronal activity, plasticity and evolution.

PubMed

Herculano-Houzel, Suzana

2011-03-01

It is usually considered that larger brains have larger neurons, which consume more energy individually, and are therefore accompanied by a larger number of glial cells per neuron. These notions, however, have never been tested. Based on glucose and oxygen metabolic rates in awake animals and their recently determined numbers of neurons, here I show that, contrary to the expected, the estimated glucose use per neuron is remarkably constant, varying only by 40% across the six species of rodents and primates (including humans). The estimated average glucose use per neuron does not correlate with neuronal density in any structure. This suggests that the energy budget of the whole brain per neuron is fixed across species and brain sizes, such that total glucose use by the brain as a whole, by the cerebral cortex and also by the cerebellum alone are linear functions of the number of neurons in the structures across the species (although the average glucose consumption per neuron is at least 10× higher in the cerebral cortex than in the cerebellum). These results indicate that the apparently remarkable use in humans of 20% of the whole body energy budget by a brain that represents only 2% of body mass is explained simply by its large number of neurons. Because synaptic activity is considered the major determinant of metabolic cost, a conserved energy budget per neuron has several profound implications for synaptic homeostasis and the regulation of firing rates, synaptic plasticity, brain imaging, pathologies, and for brain scaling in evolution.

Stereoplotting Hominid Brain Endocasts : Some Preliminary Results

NASA Astrophysics Data System (ADS)

Holloway, Ralph L.

1980-07-01

To objectively and quantitatively demonstrate regional differences in brain endocast morphology, traditional anthropometric caliper measurements must be replaced by a system providing not only localness, but homology and reasonable freedom from allometric distortion. Stereoplotting the radial distances from endocast surface (the closest point to the once underlying brain cortex) to a homologous center every ten degrees provides some 300+ data points for each dorsal endocast surface, thus giving the requisite localness. These measurements provide a large matrix of data suitable for a number of multivariate statistical techniques, and the translation of such data and analyses to readily visualized maps, which can then be compared in relation to both taxonomic and functional knowledge about the cerebral surface. This paper descri-bes some preliminary results from using such methods on a sample of 64 undistorted endocasts composed of both pongids and fossil hominids. While sample sizes within taxonomic groups need to be augmented, the preliminary and tentative pilot studies conducted so far suggest that the method has excellent potential, and that two major areas of the brain endocast surface show the greatest shape changes : 1) the posterior association areas (inferior parietal lobule); 2) the anterior prefrontal areas.

In vivo measurement of apolipoprotein E from the brain interstitial fluid using microdialysis

PubMed Central

2013-01-01

Background The APOE4 allele variant is the strongest known genetic risk factor for developing late-onset Alzheimer’s disease. The link between apolipoprotein E (apoE) and Alzheimer’s disease is likely due in large part to the impact of apoE on the metabolism of amyloid β (Aβ) within the brain. Manipulation of apoE levels and lipidation within the brain has been proposed as a therapeutic target for the treatment of Alzheimer’s disease. However, we know little about the dynamic regulation of apoE levels and lipidation within the central nervous system. We have developed an assay to measure apoE levels in the brain interstitial fluid of awake and freely moving mice using large molecular weight cut-off microdialysis probes. Results We were able to recover apoE using microdialysis from human cerebrospinal fluid (CSF) in vitro and mouse brain parenchyma in vivo. Microdialysis probes were inserted into the hippocampus of wild-type mice and interstitial fluid was collected for 36 hours. Levels of apoE within the microdialysis samples were determined by ELISA. The levels of apoE were found to be relatively stable over 36 hours. No apoE was detected in microdialysis samples from apoE KO mice. Administration of the RXR agonist bexarotene increased ISF apoE levels while ISF Aβ levels were decreased. Extrapolation to zero-flow analysis allowed us to determine the absolute recoverable concentration of apoE3 in the brain ISF of apoE3 KI mice. Furthermore, analysis of microdialysis samples by non-denaturing gel electrophoresis determined lipidated apoE particles in microdialysis samples were consistent in size with apoE particles from CSF. Finally, we found that the concentration of apoE in the brain ISF was dependent upon apoE isoform in human apoE KI mice, following the pattern apoE2>apoE3>apoE4. Conclusions We are able to collect lipidated apoE from the brain of awake and freely moving mice and monitor apoE levels over the course of several hours from a single mouse. Our technique enables assessment of brain apoE dynamics under physiological and pathophysiological conditions and in response to therapeutic interventions designed to affect apoE levels and lipidation within the brain. PMID:23601557

Chlorpyrifos and Malathion have opposite effects on behaviors and brain size that are not correlated to changes in AChE activity

PubMed Central

Richendrfer, Holly; Creton, Robbert

2015-01-01

Organophosphates, a type of neurotoxicant pesticide, are used globally for the treatment of pests on croplands and are therefore found in a large number of conventional foods. These pesticides are harmful and potentially deadly if ingested or inhaled in large quantities by causing a significant reduction in acetylcholinesterase (AChE) activity in the central and peripheral nervous system. However, much less is known about the effects of exposure to small quantities of the pesticides on neural systems and behavior during development. In the current study we used zebrafish larvae in order to determine the effects of two of the most widely used organophosphates, chlorpyrifos and malathion, on zebrafish behavior and AChE activity. Embryos and larvae were exposed to the organophosphates during different time points in development and then tested at 5 days post-fertilization for behavioral, neurodevelopmental and AChE abnormalities. The results of the study indicate that chlorpyrifos and malathion cause opposing behaviors in the larvae such as swim speed (hypoactivity vs. hyperactivity) and rest. Additionally, the pesticides affect only certain behaviors, such as thigmotaxis, during specific time points in development that are unrelated to changes in AChE activity. Larvae treated with malathion but not chlorpyrifos also had significantly smaller forebrain and hindbrain regions compared to controls by 5 days post-fertilization. We conclude that exposure to very low concentrations of organophosphate pesticides during development cause abnormalities in behavior and brain size. PMID:25983063

First trimester size charts of embryonic brain structures.

PubMed

Gijtenbeek, M; Bogers, H; Groenenberg, I A L; Exalto, N; Willemsen, S P; Steegers, E A P; Eilers, P H C; Steegers-Theunissen, R P M

2014-02-01

Can reliable size charts of human embryonic brain structures be created from three-dimensional ultrasound (3D-US) visualizations? Reliable size charts of human embryonic brain structures can be created from high-quality images. Previous studies on the visualization of both the cavities and the walls of the brain compartments were performed using 2D-US, 3D-US or invasive intrauterine sonography. However, the walls of the diencephalon, mesencephalon and telencephalon have not been measured non-invasively before. Last-decade improvements in transvaginal ultrasound techniques allow a better visualization and offer the tools to measure these human embryonic brain structures with precision. This study is embedded in a prospective periconceptional cohort study. A total of 141 pregnancies were included before the sixth week of gestation and were monitored until delivery to assess complications and adverse outcomes. For the analysis of embryonic growth, 596 3D-US scans encompassing the entire embryo were obtained from 106 singleton non-malformed live birth pregnancies between 7(+0) and 12(+6) weeks' gestational age (GA). Using 4D View (3D software) the measured embryonic brain structures comprised thickness of the diencephalon, mesencephalon and telencephalon, and the total diameter of the diencephalon and mesencephalon. Of 596 3D scans, 161 (27%) high-quality scans of 79 pregnancies were eligible for analysis. The reliability of all embryonic brain structure measurements, based on the intra-class correlation coefficients (ICCs) (all above 0.98), was excellent. Bland-Altman plots showed moderate agreement for measurements of the telencephalon, but for all other measurements the agreement was good. Size charts were constructed according to crown-rump length (CRL). The percentage of high-quality scans suitable for analysis of these brain structures was low (27%).  The size charts of human embryonic brain structures can be used to study normal and abnormal development of brain development in future. Also, the effects of periconceptional maternal exposures, such as folic acid supplement use and smoking, on human embryonic brain development can be a topic of future research. This study was supported by the Department of Obstetrics and Gynaecology of the Erasmus University Medical Center. M.G. was supported by an additional grant from the Sophia Foundation for Medical Research (SSWO grant number 644). No competing interests are declared.

Half brain irradiation in a murine model of breast cancer brain metastasis: magnetic resonance imaging and histological assessments of dose-response.

PubMed

Zarghami, Niloufar; Murrell, Donna H; Jensen, Michael D; Dick, Frederick A; Chambers, Ann F; Foster, Paula J; Wong, Eugene

2018-06-01

Brain metastasis is becoming increasingly prevalent in breast cancer due to improved extra-cranial disease control. With emerging availability of modern image-guided radiation platforms, mouse models of brain metastases and small animal magnetic resonance imaging (MRI), we examined brain metastases' responses from radiotherapy in the pre-clinical setting. In this study, we employed half brain irradiation to reduce inter-subject variability in metastases dose-response evaluations. Half brain irradiation was performed on a micro-CT/RT system in a human breast cancer (MDA-MB-231-BR) brain metastasis mouse model. Radiation induced DNA double stranded breaks in tumors and normal mouse brain tissue were quantified using γ-H2AX immunohistochemistry at 30 min (acute) and 11 days (longitudinal) after half-brain treatment for doses of 8, 16 and 24 Gy. In addition, tumor responses were assessed volumetrically with in-vivo longitudinal MRI and histologically for tumor cell density and nuclear size. In the acute setting, γ-H2AX staining in tumors saturated at higher doses while normal mouse brain tissue continued to increase linearly in the phosphorylation of H2AX. While γ-H2AX fluorescence intensities returned to the background level in the brain 11 days after treatment, the residual γ-H2AX phosphorylation in the radiated tumors remained elevated compared to un-irradiated contralateral tumors. With radiation, MRI-derived relative tumor growth was significantly reduced compared to the un-irradiated side. While there was no difference in MRI tumor volume growth between 16 and 24 Gy, there was a significant reduction in tumor cell density from histology with increasing dose. In the longitudinal study, nuclear size in the residual tumor cells increased significantly as the radiation dose was increased. Radiation damages to the DNAs in the normal brain parenchyma are resolved over time, but remain unrepaired in the treated tumors. Furthermore, there is a radiation dose response in nuclear size of surviving tumor cells. Increase in nuclear size together with unrepaired DNA damage indicated that the surviving tumor cells post radiation had continued to progress in the cell cycle with DNA replication, but failed cytokinesis. Half brain irradiation provides efficient evaluation of dose-response for cancer cell lines, a pre-requisite to perform experiments to understand radio-resistance in brain metastases.

Structural brain development between childhood and adulthood: Convergence across four longitudinal samples.

PubMed

Mills, Kathryn L; Goddings, Anne-Lise; Herting, Megan M; Meuwese, Rosa; Blakemore, Sarah-Jayne; Crone, Eveline A; Dahl, Ronald E; Güroğlu, Berna; Raznahan, Armin; Sowell, Elizabeth R; Tamnes, Christian K

2016-11-01

Longitudinal studies including brain measures acquired through magnetic resonance imaging (MRI) have enabled population models of human brain development, crucial for our understanding of typical development as well as neurodevelopmental disorders. Brain development in the first two decades generally involves early cortical grey matter volume (CGMV) increases followed by decreases, and monotonic increases in cerebral white matter volume (CWMV). However, inconsistencies regarding the precise developmental trajectories call into question the comparability of samples. This issue can be addressed by conducting a comprehensive study across multiple datasets from diverse populations. Here, we present replicable models for gross structural brain development between childhood and adulthood (ages 8-30years) by repeating analyses in four separate longitudinal samples (391 participants; 852 scans). In addition, we address how accounting for global measures of cranial/brain size affect these developmental trajectories. First, we found evidence for continued development of both intracranial volume (ICV) and whole brain volume (WBV) through adolescence, albeit following distinct trajectories. Second, our results indicate that CGMV is at its highest in childhood, decreasing steadily through the second decade with deceleration in the third decade, while CWMV increases until mid-to-late adolescence before decelerating. Importantly, we show that accounting for cranial/brain size affects models of regional brain development, particularly with respect to sex differences. Our results increase confidence in our knowledge of the pattern of brain changes during adolescence, reduce concerns about discrepancies across samples, and suggest some best practices for statistical control of cranial volume and brain size in future studies. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The synganglion of the jumping spider Marpissa muscosa (Arachnida: Salticidae): Insights from histology, immunohistochemistry and microCT analysis.

PubMed

Steinhoff, Philip O M; Sombke, Andy; Liedtke, Jannis; Schneider, Jutta M; Harzsch, Steffen; Uhl, Gabriele

2017-03-01

Jumping spiders are known for their extraordinary cognitive abilities. The underlying nervous system structures, however, are largely unknown. Here, we explore and describe the anatomy of the brain in the jumping spider Marpissa muscosa (Clerck, 1757) by means of paraffin histology, X-ray microCT analysis and immunohistochemistry as well as three-dimensional reconstruction. In the prosoma, the CNS is a clearly demarcated mass that surrounds the esophagus. The anteriormost neuromere, the protocerebrum, comprises nine bilaterally paired neuropils, including the mushroom bodies and one unpaired midline neuropil, the arcuate body. Further ventrally, the synganglion comprises the cheliceral (deutocerebrum) and pedipalpal neuropils (tritocerebrum). Synapsin-immunoreactivity in all neuropils is generally strong, while allatostatin-immunoreactivity is mostly present in association with the arcuate body and the stomodeal bridge. The most prominent neuropils in the spider brain, the mushroom bodies and the arcuate body, were suggested to be higher integrating centers of the arthropod brain. The mushroom body in M. muscosa is connected to first and second order visual neuropils of the lateral eyes, and the arcuate body to the second order neuropils of the anterior median eyes (primary eyes) through a visual tract. The connection of both, visual neuropils and eyes and arcuate body, as well as their large size corroborates the hypothesis that these neuropils play an important role in cognition and locomotion control of jumping spiders. In addition, we show that the architecture of the brain of M. muscosa and some previously investigated salticids differs significantly from that of the wandering spider Cupiennius salei, especially with regard to structure and arrangement of visual neuropils and mushroom body. Thus, we need to explore the anatomical conformities and specificities of the brains of different spider taxa in order to understand evolutionary transformations of the arthropod brain. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lateralized Feeding Behavior is Associated with Asymmetrical Neuroanatomy and Lateralized Gene Expressions in the Brain in Scale-Eating Cichlid Fish

PubMed Central

Lee, Hyuk Je; Schneider, Ralf F; Manousaki, Tereza; Kang, Ji Hyoun; Lein, Etienne; Franchini, Paolo

2017-01-01

Abstract Lateralized behavior (“handedness”) is unusual, but consistently found across diverse animal lineages, including humans. It is thought to reflect brain anatomical and/or functional asymmetries, but its neuro-molecular mechanisms remain largely unknown. Lake Tanganyika scale-eating cichlid fish, Perissodus microlepis show pronounced asymmetry in their jaw morphology as well as handedness in feeding behavior—biting scales preferentially only from one or the other side of their victims. This makes them an ideal model in which to investigate potential laterality in neuroanatomy and transcription in the brain in relation to behavioral handedness. After determining behavioral handedness in P. microlepis (preferred attack side), we estimated the volume of the hemispheres of brain regions and captured their gene expression profiles. Our analyses revealed that the degree of behavioral handedness is mirrored at the level of neuroanatomical asymmetry, particularly in the tectum opticum. Transcriptome analyses showed that different brain regions (tectum opticum, telencephalon, hypothalamus, and cerebellum) display distinct expression patterns, potentially reflecting their developmental interrelationships. For numerous genes in each brain region, their extent of expression differences between hemispheres was found to be correlated with the degree of behavioral lateralization. Interestingly, the tectum opticum and telencephalon showed divergent biases on the direction of up- or down-regulation of the laterality candidate genes (e.g., grm2) in the hemispheres, highlighting the connection of handedness with gene expression profiles and the different roles of these brain regions. Hence, handedness in predation behavior may be caused by asymmetric size of brain hemispheres and also by lateralized gene expressions in the brain. PMID:29069363

Lateralized Feeding Behavior is Associated with Asymmetrical Neuroanatomy and Lateralized Gene Expressions in the Brain in Scale-Eating Cichlid Fish.

PubMed

Lee, Hyuk Je; Schneider, Ralf F; Manousaki, Tereza; Kang, Ji Hyoun; Lein, Etienne; Franchini, Paolo; Meyer, Axel

2017-11-01

Lateralized behavior ("handedness") is unusual, but consistently found across diverse animal lineages, including humans. It is thought to reflect brain anatomical and/or functional asymmetries, but its neuro-molecular mechanisms remain largely unknown. Lake Tanganyika scale-eating cichlid fish, Perissodus microlepis show pronounced asymmetry in their jaw morphology as well as handedness in feeding behavior-biting scales preferentially only from one or the other side of their victims. This makes them an ideal model in which to investigate potential laterality in neuroanatomy and transcription in the brain in relation to behavioral handedness. After determining behavioral handedness in P. microlepis (preferred attack side), we estimated the volume of the hemispheres of brain regions and captured their gene expression profiles. Our analyses revealed that the degree of behavioral handedness is mirrored at the level of neuroanatomical asymmetry, particularly in the tectum opticum. Transcriptome analyses showed that different brain regions (tectum opticum, telencephalon, hypothalamus, and cerebellum) display distinct expression patterns, potentially reflecting their developmental interrelationships. For numerous genes in each brain region, their extent of expression differences between hemispheres was found to be correlated with the degree of behavioral lateralization. Interestingly, the tectum opticum and telencephalon showed divergent biases on the direction of up- or down-regulation of the laterality candidate genes (e.g., grm2) in the hemispheres, highlighting the connection of handedness with gene expression profiles and the different roles of these brain regions. Hence, handedness in predation behavior may be caused by asymmetric size of brain hemispheres and also by lateralized gene expressions in the brain. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Critical dynamics on a large human Open Connectome network

NASA Astrophysics Data System (ADS)

Ódor, Géza

2016-12-01

Extended numerical simulations of threshold models have been performed on a human brain network with N =836 733 connected nodes available from the Open Connectome Project. While in the case of simple threshold models a sharp discontinuous phase transition without any critical dynamics arises, variable threshold models exhibit extended power-law scaling regions. This is attributed to fact that Griffiths effects, stemming from the topological or interaction heterogeneity of the network, can become relevant if the input sensitivity of nodes is equalized. I have studied the effects of link directness, as well as the consequence of inhibitory connections. Nonuniversal power-law avalanche size and time distributions have been found with exponents agreeing with the values obtained in electrode experiments of the human brain. The dynamical critical region occurs in an extended control parameter space without the assumption of self-organized criticality.

Reconstructing the Neanderthal brain using computational anatomy.

PubMed

Kochiyama, Takanori; Ogihara, Naomichi; Tanabe, Hiroki C; Kondo, Osamu; Amano, Hideki; Hasegawa, Kunihiro; Suzuki, Hiromasa; Ponce de León, Marcia S; Zollikofer, Christoph P E; Bastir, Markus; Stringer, Chris; Sadato, Norihiro; Akazawa, Takeru

2018-04-26

The present study attempted to reconstruct 3D brain shape of Neanderthals and early Homo sapiens based on computational neuroanatomy. We found that early Homo sapiens had relatively larger cerebellar hemispheres but a smaller occipital region in the cerebrum than Neanderthals long before the time that Neanderthals disappeared. Further, using behavioural and structural imaging data of living humans, the abilities such as cognitive flexibility, attention, the language processing, episodic and working memory capacity were positively correlated with size-adjusted cerebellar volume. As the cerebellar hemispheres are structured as a large array of uniform neural modules, a larger cerebellum may possess a larger capacity for cognitive information processing. Such a neuroanatomical difference in the cerebellum may have caused important differences in cognitive and social abilities between the two species and might have contributed to the replacement of Neanderthals by early Homo sapiens.

Task Dependence, Tissue Specificity, and Spatial Distribution of Widespread Activations in Large Single-Subject Functional MRI Datasets at 7T

PubMed Central

Gonzalez-Castillo, Javier; Hoy, Colin W.; Handwerker, Daniel A.; Roopchansingh, Vinai; Inati, Souheil J.; Saad, Ziad S.; Cox, Robert W.; Bandettini, Peter A.

2015-01-01

It was recently shown that when large amounts of task-based blood oxygen level–dependent (BOLD) data are combined to increase contrast- and temporal signal-to-noise ratios, the majority of the brain shows significant hemodynamic responses time-locked with the experimental paradigm. Here, we investigate the biological significance of such widespread activations. First, the relationship between activation extent and task demands was investigated by varying cognitive load across participants. Second, the tissue specificity of responses was probed using the better BOLD signal localization capabilities of a 7T scanner. Finally, the spatial distribution of 3 primary response types—namely positively sustained (pSUS), negatively sustained (nSUS), and transient—was evaluated using a newly defined voxel-wise waveshape index that permits separation of responses based on their temporal signature. About 86% of gray matter (GM) became significantly active when all data entered the analysis for the most complex task. Activation extent scaled with task load and largely followed the GM contour. The most common response type was nSUS BOLD, irrespective of the task. Our results suggest that widespread activations associated with extremely large single-subject functional magnetic resonance imaging datasets can provide valuable information about the functional organization of the brain that goes undetected in smaller sample sizes. PMID:25405938

Feedback associated with expectation for larger-reward improves visuospatial working memory performances in children with ADHD.

PubMed

Hammer, Rubi; Tennekoon, Michael; Cooke, Gillian E; Gayda, Jessica; Stein, Mark A; Booth, James R

2015-08-01

We tested the interactive effect of feedback and reward on visuospatial working memory in children with ADHD. Seventeen boys with ADHD and 17 Normal Control (NC) boys underwent functional magnetic resonance imaging (fMRI) while performing four visuospatial 2-back tasks that required monitoring the spatial location of letters presented on a display. Tasks varied in reward size (large; small) and feedback availability (no-feedback; feedback). While the performance of NC boys was high in all conditions, boys with ADHD exhibited higher performance (similar to those of NC boys) only when they received feedback associated with large-reward. Performance pattern in both groups was mirrored by neural activity in an executive function neural network comprised of few distinct frontal brain regions. Specifically, neural activity in the left and right middle frontal gyri of boys with ADHD became normal-like only when feedback was available, mainly when feedback was associated with large-reward. When feedback was associated with small-reward, or when large-reward was expected but feedback was not available, boys with ADHD exhibited altered neural activity in the medial orbitofrontal cortex and anterior insula. This suggests that contextual support normalizes activity in executive brain regions in children with ADHD, which results in improved working memory. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Toward brain correlates of natural behavior: fMRI during violent video games.

PubMed

Mathiak, Klaus; Weber, René

2006-12-01

Modern video games represent highly advanced virtual reality simulations and often contain virtual violence. In a significant amount of young males, playing video games is a quotidian activity, making it an almost natural behavior. Recordings of brain activation with functional magnetic resonance imaging (fMRI) during gameplay may reflect neuronal correlates of real-life behavior. We recorded 13 experienced gamers (18-26 years; average 14 hrs/week playing) while playing a violent first-person shooter game (a violent computer game played in self-perspective) by means of distortion and dephasing reduced fMRI (3 T; single-shot triple-echo echo-planar imaging [EPI]). Content analysis of the video and sound with 100 ms time resolution achieved relevant behavioral variables. These variables explained significant signal variance across large distributed networks. Occurrence of violent scenes revealed significant neuronal correlates in an event-related design. Activation of dorsal and deactivation of rostral anterior cingulate and amygdala characterized the mid-frontal pattern related to virtual violence. Statistics and effect sizes can be considered large at these areas. Optimized imaging strategies allowed for single-subject and for single-trial analysis with good image quality at basal brain structures. We propose that virtual environments can be used to study neuronal processes involved in semi-naturalistic behavior as determined by content analysis. Importantly, the activation pattern reflects brain-environment interactions rather than stimulus responses as observed in classical experimental designs. We relate our findings to the general discussion on social effects of playing first-person shooter games. (c) 2006 Wiley-Liss, Inc.

Mindcontrol: A web application for brain segmentation quality control.

PubMed

Keshavan, Anisha; Datta, Esha; M McDonough, Ian; Madan, Christopher R; Jordan, Kesshi; Henry, Roland G

2018-04-15

Tissue classification plays a crucial role in the investigation of normal neural development, brain-behavior relationships, and the disease mechanisms of many psychiatric and neurological illnesses. Ensuring the accuracy of tissue classification is important for quality research and, in particular, the translation of imaging biomarkers to clinical practice. Assessment with the human eye is vital to correct various errors inherent to all currently available segmentation algorithms. Manual quality assurance becomes methodologically difficult at a large scale - a problem of increasing importance as the number of data sets is on the rise. To make this process more efficient, we have developed Mindcontrol, an open-source web application for the collaborative quality control of neuroimaging processing outputs. The Mindcontrol platform consists of a dashboard to organize data, descriptive visualizations to explore the data, an imaging viewer, and an in-browser annotation and editing toolbox for data curation and quality control. Mindcontrol is flexible and can be configured for the outputs of any software package in any data organization structure. Example configurations for three large, open-source datasets are presented: the 1000 Functional Connectomes Project (FCP), the Consortium for Reliability and Reproducibility (CoRR), and the Autism Brain Imaging Data Exchange (ABIDE) Collection. These demo applications link descriptive quality control metrics, regional brain volumes, and thickness scalars to a 3D imaging viewer and editing module, resulting in an easy-to-implement quality control protocol that can be scaled for any size and complexity of study. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Large national series of patients with Xq28 duplication involving MECP2: Delineation of brain MRI abnormalities in 30 affected patients.

PubMed

El Chehadeh, Salima; Faivre, Laurence; Mosca-Boidron, Anne-Laure; Malan, Valérie; Amiel, Jeanne; Nizon, Mathilde; Touraine, Renaud; Prieur, Fabienne; Pasquier, Laurent; Callier, Patrick; Lefebvre, Mathilde; Marle, Nathalie; Dubourg, Christèle; Julia, Sophie; Sarret, Catherine; Francannet, Christine; Laffargue, Fanny; Boespflug-Tanguy, Odile; David, Albert; Isidor, Bertrand; Le Caignec, Cédric; Vigneron, Jacqueline; Leheup, Bruno; Lambert, Laetitia; Philippe, Christophe; Cuisset, Jean-Marie; Andrieux, Joris; Plessis, Ghislaine; Toutain, Annick; Goldenberg, Alice; Cormier-Daire, Valérie; Rio, Marlène; Bonnefont, Jean-Paul; Thevenon, Julien; Echenne, Bernard; Journel, Hubert; Afenjar, Alexandra; Burglen, Lydie; Bienvenu, Thierry; Addor, Marie-Claude; Lebon, Sébastien; Martinet, Danièle; Baumann, Clarisse; Perrin, Laurence; Drunat, Séverine; Jouk, Pierre-Simon; Devillard, Françoise; Coutton, Charles; Lacombe, Didier; Delrue, Marie-Ange; Philip, Nicole; Moncla, Anne; Badens, Catherine; Perreton, Nathalie; Masurel, Alice; Thauvin-Robinet, Christel; Des Portes, Vincent; Guibaud, Laurent

2016-01-01

Xq28 duplications encompassing MECP2 have been described in male patients with a severe neurodevelopmental disorder associated with hypotonia and spasticity, severe learning disability, stereotyped movements, and recurrent pulmonary infections. We report on standardized brain magnetic resonance imaging (MRI) data of 30 affected patients carrying an Xq28 duplication involving MECP2 of various sizes (228 kb to 11.7 Mb). The aim of this study was to seek recurrent malformations and attempt to determine whether variations in imaging features could be explained by differences in the size of the duplications. We showed that 93% of patients had brain MRI abnormalities such as corpus callosum abnormalities (n = 20), reduced volume of the white matter (WM) (n = 12), ventricular dilatation (n = 9), abnormal increased hyperintensities on T2-weighted images involving posterior periventricular WM (n = 6), and vermis hypoplasia (n = 5). The occipitofrontal circumference varied considerably between >+2SD in five patients and <-2SD in four patients. Among the nine patients with dilatation of the lateral ventricles, six had a duplication involving L1CAM. The only patient harboring bilateral posterior subependymal nodular heterotopia also carried an FLNA gene duplication. We could not demonstrate a correlation between periventricular WM hyperintensities/delayed myelination and duplication of the IKBKG gene. We thus conclude that patients with an Xq28 duplication involving MECP2 share some similar but non-specific brain abnormalities. These imaging features, therefore, could not constitute a diagnostic clue. The genotype-phenotype correlation failed to demonstrate a relationship between the presence of nodular heterotopia, ventricular dilatation, WM abnormalities, and the presence of FLNA, L1CAM, or IKBKG, respectively, in the duplicated segment. © 2015 Wiley Periodicals, Inc.

Maternal-fetal unit interactions and eutherian neocortical development and evolution

PubMed Central

Montiel, Juan F.; Kaune, Heidy; Maliqueo, Manuel

2013-01-01

The conserved brain design that primates inherited from early mammals differs from the variable adult brain size and species-specific brain dominances observed across mammals. This variability relies on the emergence of specialized cerebral cortical regions and sub-compartments, triggering an increase in brain size, areal interconnectivity and histological complexity that ultimately lies on the activation of developmental programs. Structural placental features are not well correlated with brain enlargement; however, several endocrine pathways could be tuned with the activation of neuronal progenitors in the proliferative neocortical compartments. In this article, we reviewed some mechanisms of eutherians maternal–fetal unit interactions associated with brain development and evolution. We propose a hypothesis of brain evolution where proliferative compartments in primates become activated by “non-classical” endocrine placental signals participating in different steps of corticogenesis. Changes in the inner placental structure, along with placenta endocrine stimuli over the cortical proliferative activity would allow mammalian brain enlargement with a concomitant shorter gestation span, as an evolutionary strategy to escape from parent-offspring conflict. PMID:23882189

Characteristics of voxel prediction power in full-brain Granger causality analysis of fMRI data

NASA Astrophysics Data System (ADS)

Garg, Rahul; Cecchi, Guillermo A.; Rao, A. Ravishankar

2011-03-01

Functional neuroimaging research is moving from the study of "activations" to the study of "interactions" among brain regions. Granger causality analysis provides a powerful technique to model spatio-temporal interactions among brain regions. We apply this technique to full-brain fMRI data without aggregating any voxel data into regions of interest (ROIs). We circumvent the problem of dimensionality using sparse regression from machine learning. On a simple finger-tapping experiment we found that (1) a small number of voxels in the brain have very high prediction power, explaining the future time course of other voxels in the brain; (2) these voxels occur in small sized clusters (of size 1-4 voxels) distributed throughout the brain; (3) albeit small, these clusters overlap with most of the clusters identified with the non-temporal General Linear Model (GLM); and (4) the method identifies clusters which, while not determined by the task and not detectable by GLM, still influence brain activity.

Brain Stimulation in Alzheimer's Disease.

PubMed

Chang, Chun-Hung; Lane, Hsien-Yuan; Lin, Chieh-Hsin

2018-01-01

Brain stimulation techniques can modulate cognitive functions in many neuropsychiatric diseases. Pilot studies have shown promising effects of brain stimulations on Alzheimer's disease (AD). Brain stimulations can be categorized into non-invasive brain stimulation (NIBS) and invasive brain stimulation (IBS). IBS includes deep brain stimulation (DBS), and invasive vagus nerve stimulation (VNS), whereas NIBS includes transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), electroconvulsive treatment (ECT), magnetic seizure therapy (MST), cranial electrostimulation (CES), and non-invasive VNS. We reviewed the cutting-edge research on these brain stimulation techniques and discussed their therapeutic effects on AD. Both IBS and NIBS may have potential to be developed as novel treatments for AD; however, mixed findings may result from different study designs, patients selection, population, or samples sizes. Therefore, the efficacy of NIBS and IBS in AD remains uncertain, and needs to be further investigated. Moreover, more standardized study designs with larger sample sizes and longitudinal follow-up are warranted for establishing a structural guide for future studies and clinical application.

Size-weight illusion and anticipatory grip force scaling following unilateral cortical brain lesion.

PubMed

Li, Yong; Randerath, Jennifer; Goldenberg, Georg; Hermsdörfer, Joachim

2011-04-01

The prediction of object weight from its size is an important prerequisite of skillful object manipulation. Grip and load forces anticipate object size during early phases of lifting an object. A mismatch between predicted and actual weight when two different sized objects have the same weight results in the size-weight illusion (SWI), the small object feeling heavier. This study explores whether lateralized brain lesions in patients with or without apraxia alter the size-weight illusion and impair anticipatory finger force scaling. Twenty patients with left brain damage (LBD, 10 with apraxia, 10 without apraxia), ten patients with right brain damage (RBD), and matched control subjects lifted two different-sized boxes in alternation. All subjects experienced a similar size-weight illusion. The anticipatory force scaling of all groups was in correspondence with the size cue: higher forces and force rates were applied to the big box and lower forces and force rates to the small box during the first lifts. Within few lifts, forces were scaled to actual object weight. Despite the lack of significant differences at group level, 5 out of 20 LBD patients showed abnormal predictive scaling of grip forces. They differed from the LBD patients with normal predictive scaling by a greater incidence of posterior occipito-parietal lesions but not by a greater incidence of apraxia. The findings do not support a more general role for the motor-dominant left hemisphere, or an influence of apraxia per se, in the scaling of finger force according to object properties. However, damage in the vicinity of the parietal-occipital junction may be critical for deriving predictions of weight from size. Copyright © 2011 Elsevier Ltd. All rights reserved.

A biometric analysis of brain size in micrencephalics.

PubMed

Hofman, M A

1984-01-01

Brain weight and head circumference in micrencephalic patients were analysed as a function of age, height and sex in relation to normal human standards. A quantitative definition of micrencephaly is proposed, which is based on these analyses. Evidence is presented, furthermore, that micrencephalics have a significantly lower brain weight in adolescence than in early childhood, and that this cerebral dystrophy continues throughout adulthood, leading to death in more than 85% of the males and 78% of the females before they reach the age of 30 years. Since this decline in brain weight after approximately 3-5 years of age is not accompanied by a similar reduction in head circumference, the brains of elderly micrencephalic patients no longer occupy the entire cranial cavity. It is evident, therefore, that head circumference in the case of micrencephaly is an unsuitable parameter for estimating brain size.

Anti-cancer Antibody Trastuzumab-Melanotransferrin Conjugate (BT2111) for the Treatment of Metastatic HER2+ Breast Cancer Tumors in the Brain: an In-Vivo Study.

PubMed

Nounou, Mohamed Ismail; Adkins, Chris E; Rubinchik, Evelina; Terrell-Hall, Tori B; Afroz, Mohamed; Vitalis, Tim; Gabathuler, Reinhard; Tian, Mei Mei; Lockman, Paul R

2016-12-01

The ability of human melanotransferrin (hMTf) to carry a therapeutic concentration of trastuzumab (BTA) in the brain after conjugation (in the form of trastuzumab-melanotransferrin conjugate, BT2111 conjugate) was investigated by measuring the reduction of the number and size of metastatic human HER 2+ breast cancer tumors in a preclinical model of brain metastases of breast cancer. Human metastatic brain seeking breast cancer cells were injected in NuNu mice (n = 6-12 per group) which then developed experimental brain metastases. Drug uptake was analyzed in relation to metastasis size and blood-tumor barrier permeability. To investigate in-vivo activity against brain metastases, equimolar doses of the conjugate, and relevant controls (hMTf and BTA) in separate groups were administered biweekly after intracardiac injection of the metastatic cancer cells. The trastuzumab-melanotransferrin conjugate (BT2111) reduced the number of preclinical human HER 2+ breast cancer metastases in the brain by 68% compared to control groups. Tumors which remained after treatment were 46% smaller than the control groups. In contrast, BTA alone had no effect on reducing number of metastases, and was associated with only a minimal reduction in metastasis size. The results suggest the novel trastuzumab-melanotransferrin conjugate (BT2111) may have utility in treating brain metastasis and validate hMTf as a potential vector for antibody transport across the Blood Brain Barrier (BBB).

Cortical and Subcortical Brain Morphometry Differences Between Patients With Autism Spectrum Disorder and Healthy Individuals Across the Lifespan: Results From the ENIGMA ASD Working Group.

PubMed

van Rooij, Daan; Anagnostou, Evdokia; Arango, Celso; Auzias, Guillaume; Behrmann, Marlene; Busatto, Geraldo F; Calderoni, Sara; Daly, Eileen; Deruelle, Christine; Di Martino, Adriana; Dinstein, Ilan; Duran, Fabio Luis Souza; Durston, Sarah; Ecker, Christine; Fair, Damien; Fedor, Jennifer; Fitzgerald, Jackie; Freitag, Christine M; Gallagher, Louise; Gori, Ilaria; Haar, Shlomi; Hoekstra, Liesbeth; Jahanshad, Neda; Jalbrzikowski, Maria; Janssen, Joost; Lerch, Jason; Luna, Beatriz; Martinho, Mauricio Moller; McGrath, Jane; Muratori, Filippo; Murphy, Clodagh M; Murphy, Declan G M; O'Hearn, Kirsten; Oranje, Bob; Parellada, Mara; Retico, Alessandra; Rosa, Pedro; Rubia, Katya; Shook, Devon; Taylor, Margot; Thompson, Paul M; Tosetti, Michela; Wallace, Gregory L; Zhou, Fengfeng; Buitelaar, Jan K

2018-04-01

Neuroimaging studies show structural differences in both cortical and subcortical brain regions in children and adults with autism spectrum disorder (ASD) compared with healthy subjects. Findings are inconsistent, however, and it is unclear how differences develop across the lifespan. The authors investigated brain morphometry differences between individuals with ASD and healthy subjects, cross-sectionally across the lifespan, in a large multinational sample from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) ASD working group. The sample comprised 1,571 patients with ASD and 1,651 healthy control subjects (age range, 2-64 years) from 49 participating sites. MRI scans were preprocessed at individual sites with a harmonized protocol based on a validated automated-segmentation software program. Mega-analyses were used to test for case-control differences in subcortical volumes, cortical thickness, and surface area. Development of brain morphometry over the lifespan was modeled using a fractional polynomial approach. The case-control mega-analysis demonstrated that ASD was associated with smaller subcortical volumes of the pallidum, putamen, amygdala, and nucleus accumbens (effect sizes [Cohen's d], 0.13 to -0.13), as well as increased cortical thickness in the frontal cortex and decreased thickness in the temporal cortex (effect sizes, -0.21 to 0.20). Analyses of age effects indicate that the development of cortical thickness is altered in ASD, with the largest differences occurring around adolescence. No age-by-ASD interactions were observed in the subcortical partitions. The ENIGMA ASD working group provides the largest study of brain morphometry differences in ASD to date, using a well-established, validated, publicly available analysis pipeline. ASD patients showed altered morphometry in the cognitive and affective parts of the striatum, frontal cortex, and temporal cortex. Complex developmental trajectories were observed for the different regions, with a developmental peak around adolescence. These findings suggest an interplay in the abnormal development of the striatal, frontal, and temporal regions in ASD across the lifespan.

MicroCT and microMRI imaging of a prenatal mouse model of increased brain size

NASA Astrophysics Data System (ADS)

López, Elisabeth K. N.; Stock, Stuart R.; Taketo, Makoto M.; Chenn, Anjen; Ravosa, Matthew J.

2008-08-01

There are surprisingly few experimental models of neural growth and cranial integration. This and the dearth of information regarding fetal brain development detract from a mechanistic understanding of cranial integration and its relevance to the patterning of skull form, specifically the role of encephalization on basicranial flexion. To address this shortcoming, our research uses transgenic mice expressing a stabilized form of β-catenin to isolate the effects of relative brain size on craniofacial development. These mice develop highly enlarged brains due to an increase in neural precursors, and differences between transgenic and wild-type mice are predicted to result solely from variation in brain size. Comparisons of wild-type and transgenic mice at several prenatal ages were performed using microCT (Scanco Medical MicroCT 40) and microMRI (Avance 600 WB MR spectrometer). Statistical analyses show that the larger brain of the transgenic mice is associated with a larger neurocranium and an altered basicranial morphology. However, body size and postcranial ossification do not seem to be affected by the transgene. Comparisons of the rate of postcranial and cranial ossification using microCT also point to an unexpected effect of neural growth on skull development: increased fetal encephalization may result in a compensatory decrease in the level of cranial ossification. Therefore, if other life history factors are held constant, the ontogeny of a metabolically costly structure such as a brain may occur at the expense of other cranial structures. These analyses indicate the benefits of a multifactorial approach to cranial integration using a mouse model.

Trace: a high-throughput tomographic reconstruction engine for large-scale datasets

DOE PAGES

Bicer, Tekin; Gursoy, Doga; Andrade, Vincent De; ...

2017-01-28

Here, synchrotron light source and detector technologies enable scientists to perform advanced experiments. These scientific instruments and experiments produce data at such scale and complexity that large-scale computation is required to unleash their full power. One of the widely used data acquisition technique at light sources is Computed Tomography, which can generate tens of GB/s depending on x-ray range. A large-scale tomographic dataset, such as mouse brain, may require hours of computation time with a medium size workstation. In this paper, we present Trace, a data-intensive computing middleware we developed for implementation and parallelization of iterative tomographic reconstruction algorithms. Tracemore » provides fine-grained reconstruction of tomography datasets using both (thread level) shared memory and (process level) distributed memory parallelization. Trace utilizes a special data structure called replicated reconstruction object to maximize application performance. We also present the optimizations we have done on the replicated reconstruction objects and evaluate them using a shale and a mouse brain sinogram. Our experimental evaluations show that the applied optimizations and parallelization techniques can provide 158x speedup (using 32 compute nodes) over single core configuration, which decreases the reconstruction time of a sinogram (with 4501 projections and 22400 detector resolution) from 12.5 hours to less than 5 minutes per iteration.« less

Trace: a high-throughput tomographic reconstruction engine for large-scale datasets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bicer, Tekin; Gursoy, Doga; Andrade, Vincent De

Here, synchrotron light source and detector technologies enable scientists to perform advanced experiments. These scientific instruments and experiments produce data at such scale and complexity that large-scale computation is required to unleash their full power. One of the widely used data acquisition technique at light sources is Computed Tomography, which can generate tens of GB/s depending on x-ray range. A large-scale tomographic dataset, such as mouse brain, may require hours of computation time with a medium size workstation. In this paper, we present Trace, a data-intensive computing middleware we developed for implementation and parallelization of iterative tomographic reconstruction algorithms. Tracemore » provides fine-grained reconstruction of tomography datasets using both (thread level) shared memory and (process level) distributed memory parallelization. Trace utilizes a special data structure called replicated reconstruction object to maximize application performance. We also present the optimizations we have done on the replicated reconstruction objects and evaluate them using a shale and a mouse brain sinogram. Our experimental evaluations show that the applied optimizations and parallelization techniques can provide 158x speedup (using 32 compute nodes) over single core configuration, which decreases the reconstruction time of a sinogram (with 4501 projections and 22400 detector resolution) from 12.5 hours to less than 5 minutes per iteration.« less

Treatment of rats with a self-selected hyperlipidic diet, increases the lipid content of the main adipose tissue sites in a proportion similar to that of the lipids in the rest of organs and tissues.

PubMed

Romero, María Del Mar; Roy, Stéphanie; Pouillot, Karl; Feito, Marisol; Esteve, Montserrat; Grasa, María Del Mar; Fernández-López, José-Antonio; Alemany, Marià; Remesar, Xavier

2014-01-01

Adipose tissue (AT) is distributed as large differentiated masses, and smaller depots covering vessels, and organs, as well as interspersed within them. The differences between types and size of cells makes AT one of the most disperse and complex organs. Lipid storage is partly shared by other tissues such as muscle and liver. We intended to obtain an approximate estimation of the size of lipid reserves stored outside the main fat depots. Both male and female rats were made overweight by 4-weeks feeding of a cafeteria diet. Total lipid content was analyzed in brain, liver, gastrocnemius muscle, four white AT sites: subcutaneous, perigonadal, retroperitoneal and mesenteric, two brown AT sites (interscapular and perirenal) and in a pool of the rest of organs and tissues (after discarding gut contents). Organ lipid content was estimated and tabulated for each individual rat. Food intake was measured daily. There was a surprisingly high proportion of lipid not accounted for by the main macroscopic AT sites, even when brain, liver and BAT main sites were discounted. Muscle contained about 8% of body lipids, liver 1-1.4%, four white AT sites lipid 28-63% of body lipid, and the rest of the body (including muscle) 38-44%. There was a good correlation between AT lipid and body lipid, but lipid in "other organs" was highly correlated too with body lipid. Brain lipid was not. Irrespective of dietary intake, accumulation of body fat was uniform both for the main lipid storage and handling organs: large masses of AT (but also liver, muscle), as well as in the "rest" of tissues. These storage sites, in specialized (adipose) or not-specialized (liver, muscle) tissues reacted in parallel against a hyperlipidic diet challenge. We postulate that body lipid stores are handled and regulated coordinately, with a more centralized and overall mechanisms than usually assumed.

In vitro and in vivo studies on the transport of PEGylated silica nanoparticles across the blood-brain barrier.

PubMed

Liu, Dan; Lin, Bingqian; Shao, Wei; Zhu, Zhi; Ji, Tianhai; Yang, Chaoyong

2014-02-12

Transport of PEGylated silica nanoparticles (PSiNPs) with diameters of 100, 50, and 25 nm across the blood-brain barrier (BBB) was evaluated using an in vitro BBB model based on mouse cerebral endothelial cells (bEnd.3) cultured on transwell inserts within a chamber. In vivo animal experiments were further performed by noninvasive in vivo imaging and ex vivo optical imaging after injection via carotid artery. Confocal fluorescence studies were carried out to evaluate the uptake of PSiNPs by brain endothelial cells. The results showed that PSiNPs can traverse the BBB in vitro and in vivo. The transport efficiency of PSiNPs across BBB was found to be size-dependent, with increased particle size resulting in decreased efficiency. This work points to the potential application of small sized silica nanoparticles in brain imaging or drug delivery.

Evolution of the Genus Homo

NASA Astrophysics Data System (ADS)

Tattersall, Ian; Schwartz, Jeffrey H.

2009-05-01

Definition of the genus Homo is almost as fraught as the definition of Homo sapiens. We look at the evidence for “early Homo,” finding little morphological basis for extending our genus to any of the 2.5-1.6-myr-old fossil forms assigned to “early Homo” or Homo habilis/rudolfensis. We also point to heterogeneity among “early African Homo erectus,” and the lack of apomorphies linking these fossils to the Asian Homo erectus group, a cohesive regional clade that shows some internal variation, including brain size increase over time. The first truly cosmopolitan Homo species is Homo heidelbergensis, known from Africa, Europe, and China following 600 kyr ago. One species sympatric with it included the >500-kyr-old Sima de los Huesos fossils from Spain, clearly distinct from Homo heidelbergensis and the oldest hominids assignable to the clade additionally containing Homo neanderthalensis. This clade also shows evidence of brain size expansion with time; but although Homo neanderthalensis had a large brain, it left no unequivocal evidence of the symbolic consciousness that makes our species unique. Homo sapiens clearly originated in Africa, where it existed as a physical entity before it began (also in that continent) to show the first stirrings of symbolism. Most likely, the biological underpinnings of symbolic consciousness were exaptively acquired in the radical developmental reorganization that gave rise to the highly characteristic osteological structure of Homo sapiens, but lay fallow for tens of thousands of years before being “discovered” by a cultural stimulus, plausibly the invention of language.

Additional increased effects of mannitol-temozolomide combined treatment on blood-brain barrier permeability.

PubMed

Choi, Chunggab; Kim, Hye Min; Shon, Jeeheun; Park, Jiae; Kim, Hyeong-Taek; Oh, Seung-Hun; Kim, Nam Keun; Kim, Ok Joon

2018-03-04

The blood-brain barrier (BBB) is major obstacle in drug or stem cell treatment in chronic stroke. We hypothesized that adding mannitol to temozolomide (TMZ) is a practically applicable method for resolving the low efficacy of intravenous mannitol therapy. In this study, we investigated whether BBB permeability could be increased by this combined treatment. First, we established a chronic ischemic stroke rat model and examined changes in leakage of Evans blue dye within a lesion site, and in expression of tight junction proteins (TJPs), by this combined treatment. Additionally, in an in vitro BBB model using trans-wells, we analyzed changes in diffusion of a fluorescent tracer and in expression of TJPs. Mannitol-TMZ combined treatment not only increased the amount of Evans blue dye within the stroke lesion site, but also reduced occludin expression in rat brain microvessels. The in vitro study also showed that combined treatment increased the permeability for two different-sized fluorescent tracers, especially large size, and decreased expression of TJPs, such as occludin and ZO-1. Increased BBB permeability effects were more prominent with combined than with single treatments. Mannitol-TMZ combined treatment induced a decrease of TJPs with a consequent increase in BBB permeability. This combined treatment is clinically useful and might provide new therapeutic options by enabling efficient intracerebral delivery of various drugs that could not otherwise be used to treat many CNS diseases due to their inability to penetrate the BBB. Copyright © 2018 Elsevier Inc. All rights reserved.

Prenatal Nutrition and Later Education

ERIC Educational Resources Information Center

Evans, T. N.

1972-01-01

Text of an affidavit in the case, Kennedy v. Detroit Board of Education. Reports on a study which established that prenatal nutrition is directly related to brain size and volume determined at 48 hours of infancy and at eight months of age. Pinpoints the relationship between inadequate nutrition in pregnancy, infant brain size, and intellectual…

Metabolic acceleration and the evolution of human brain size and life history.

PubMed

Pontzer, Herman; Brown, Mary H; Raichlen, David A; Dunsworth, Holly; Hare, Brian; Walker, Kara; Luke, Amy; Dugas, Lara R; Durazo-Arvizu, Ramon; Schoeller, Dale; Plange-Rhule, Jacob; Bovet, Pascal; Forrester, Terrence E; Lambert, Estelle V; Thompson, Melissa Emery; Shumaker, Robert W; Ross, Stephen R

2016-05-19

Humans are distinguished from the other living apes in having larger brains and an unusual life history that combines high reproductive output with slow childhood growth and exceptional longevity. This suite of derived traits suggests major changes in energy expenditure and allocation in the human lineage, but direct measures of human and ape metabolism are needed to compare evolved energy strategies among hominoids. Here we used doubly labelled water measurements of total energy expenditure (TEE; kcal day(-1)) in humans, chimpanzees, bonobos, gorillas and orangutans to test the hypothesis that the human lineage has experienced an acceleration in metabolic rate, providing energy for larger brains and faster reproduction without sacrificing maintenance and longevity. In multivariate regressions including body size and physical activity, human TEE exceeded that of chimpanzees and bonobos, gorillas and orangutans by approximately 400, 635 and 820 kcal day(-1), respectively, readily accommodating the cost of humans' greater brain size and reproductive output. Much of the increase in TEE is attributable to humans' greater basal metabolic rate (kcal day(-1)), indicating increased organ metabolic activity. Humans also had the greatest body fat percentage. An increased metabolic rate, along with changes in energy allocation, was crucial in the evolution of human brain size and life history.

RB4CD12 epitope expression and heparan sulfate disaccharide composition in brain vasculature.

PubMed

Hosono-Fukao, Tomomi; Ohtake-Niimi, Shiori; Nishitsuji, Kazuchika; Hossain, Md Motarab; van Kuppevelt, Toin H; Michikawa, Makoto; Uchimura, Kenji

2011-11-01

RB4CD12 is a phage display antibody that recognizes a heparan sulfate (HS) glycosaminoglycan epitope. The epitope structure is proposed to contain a trisulfated disaccharide, [-IdoA(2-OSO(3))-GlcNSO(3) (6-OSO(3))-], which supports HS binding to various macromolecules such as growth factors and cytokines in central nervous tissues. Chemically modified heparins that lack the trisulfated disaccharides failed to inhibit the RB4CD12 recognition of HS chains. To determine the localization of the RB4CD12 anti-HS epitope in the brain, we performed an immunohistochemical analysis for cryocut sections of mouse brain. The RB4CD12 staining signals were colocalized with laminin and were detected abundantly in the vascular basement membrane. Bacterial heparinases eliminated the RB4CD12 staining signals. The RB4CD12 epitope localization was confirmed by immunoelectron microscopy. Western blotting analysis revealed that the size of a major RB4CD12-positive molecule is ∼460 kDa in a vessel-enriched fraction of the mouse brain. Disaccharide analysis with reversed-phase ion-pair HPLC showed that [-IdoA(2-OSO(3))-GlcNSO(3) (6-OSO(3))-] trisulfated disaccharide residues are present in HS purified from the vessel-enriched brain fraction. These results indicated that the RB4CD12 anti-HS epitope exists in large quantities in the brain vascular basement membrane. Copyright © 2011 Wiley-Liss, Inc.

Dynamic Repertoire of Intrinsic Brain States Is Reduced in Propofol-Induced Unconsciousness

PubMed Central

Liu, Xiping; Pillay, Siveshigan

2015-01-01

Abstract The richness of conscious experience is thought to scale with the size of the repertoire of causal brain states, and it may be diminished in anesthesia. We estimated the state repertoire from dynamic analysis of intrinsic functional brain networks in conscious sedated and unconscious anesthetized rats. Functional resonance images were obtained from 30-min whole-brain resting-state blood oxygen level-dependent (BOLD) signals at propofol infusion rates of 20 and 40 mg/kg/h, intravenously. Dynamic brain networks were defined at the voxel level by sliding window analysis of regional homogeneity (ReHo) or coincident threshold crossings (CTC) of the BOLD signal acquired in nine sagittal slices. The state repertoire was characterized by the temporal variance of the number of voxels with significant ReHo or positive CTC. From low to high propofol dose, the temporal variances of ReHo and CTC were reduced by 78%±20% and 76%±20%, respectively. Both baseline and propofol-induced reduction of CTC temporal variance increased from lateral to medial position. Group analysis showed a 20% reduction in the number of unique states at the higher propofol dose. Analysis of temporal variance in 12 anatomically defined regions of interest predicted that the largest changes occurred in visual cortex, parietal cortex, and caudate-putamen. The results suggest that the repertoire of large-scale brain states derived from the spatiotemporal dynamics of intrinsic networks is substantially reduced at an anesthetic dose associated with loss of consciousness. PMID:24702200

Feasibility of task-specific brain-machine interface training for upper-extremity paralysis in patients with chronic hemiparetic stroke.

PubMed

Nishimoto, Atsuko; Kawakami, Michiyuki; Fujiwara, Toshiyuki; Hiramoto, Miho; Honaga, Kaoru; Abe, Kaoru; Mizuno, Katsuhiro; Ushiba, Junichi; Liu, Meigen

2018-01-10

Brain-machine interface training was developed for upper-extremity rehabilitation for patients with severe hemiparesis. Its clinical application, however, has been limited because of its lack of feasibility in real-world rehabilitation settings. We developed a new compact task-specific brain-machine interface system that enables task-specific training, including reach-and-grasp tasks, and studied its clinical feasibility and effectiveness for upper-extremity motor paralysis in patients with stroke. Prospective beforeâ€"after study. Twenty-six patients with severe chronic hemiparetic stroke. Participants were trained with the brain-machine interface system to pick up and release pegs during 40-min sessions and 40 min of standard occupational therapy per day for 10 days. Fugl-Meyer upper-extremity motor (FMA) and Motor Activity Log-14 amount of use (MAL-AOU) scores were assessed before and after the intervention. To test its feasibility, 4 occupational therapists who operated the system for the first time assessed it with the Quebec User Evaluation of Satisfaction with assistive Technology (QUEST) 2.0. FMA and MAL-AOU scores improved significantly after brain-machine interface training, with the effect sizes being medium and large, respectively (p<0.01, d=0.55; p<0.01, d=0.88). QUEST effectiveness and safety scores showed feasibility and satisfaction in the clinical setting. Our newly developed compact brain-machine interface system is feasible for use in real-world clinical settings.

Innervation of Ventricular and Periventricular Brain Compartments

PubMed Central

Leak, Rehana K.; Moore, Robert Y.

2012-01-01

Synaptic transmission is divided into two broad categories on the basis of the distance over which neurotransmitters travel. Wiring transmission is the release of transmitter into synaptic clefts in close apposition to receptors. Volume transmission is the release of transmitters or modulators over varying distances before interacting with receptors. One case of volume transmission over potentially long distances involves release into cerebrospinal fluid (CSF). The CSF contains neuroactive substances that affect brain function and range in size from small molecule transmitters to peptides and large proteins. CSF-contacting neurons are a well-known and universal feature of non-mammalian vertebrates, but only supra- and subependymal serotonergic plexuses are a commonly studied feature in mammals. The origin of most other neuroactive substances in CSF is unknown. In order to determine which brain regions communicate with CSF, we describe the distribution of retrograde neuronal labeling in the rat brain following ventricular injection of Cholera toxin, β subunit (CTβ), a tracer frequently used in brain circuit analysis. Within 15 to 30 minutes following intraventricular injection, there is only diffuse, non-specific staining adjacent to the ventricular surface. Within 2 to 10 days, however, there is extensive labeling of neuronal perikarya in specific nuclear groups in the telencephalon, thalamus, hypothalamus and brainstem, many at a considerable distance from the ventricles. These observations support the view that ventricular CSF is a significant channel for volume transmission and identifies those brain regions most likely to be involved in this process. PMID:22575559

Size Matters: Cerebral Volume Influences Sex Differences in Neuroanatomy

PubMed Central

Towler, Stephen; Welcome, Suzanne; Halderman, Laura K.; Otto, Ron; Eckert, Mark A.; Chiarello, Christine

2008-01-01

Biological and behavioral differences between the sexes range from obvious to subtle or nonexistent. Neuroanatomical differences are particularly controversial, perhaps due to the implication that they might account for behavioral differences. In this sample of 200 men and women, large effect sizes (Cohen's d > 0.8) were found for sex differences in total cerebral gray and white matter, cerebellum, and gray matter proportion (women had a higher proportion of gray matter). The only one of these sex differences that survived adjustment for the effect of cerebral volume was gray matter proportion. Individual differences in cerebral volume accounted for 21% of the difference in gray matter proportion, while sex accounted for an additional 4%. The relative size of the corpus callosum was 5% larger in women, but this difference was completely explained by a negative relationship between relative callosal size and cerebral volume. In agreement with Jancke et al., individuals with higher cerebral volume tended to have smaller corpora callosa. There were few sex differences in the size of structures in Broca's and Wernicke's area. We conclude that individual differences in brain volume, in both men and women, account for apparent sex differences in relative size. PMID:18440950

Neural Networks: Making Connections about the Brain and about College while Monitoring Student Engagement in Second Graders

PubMed Central

Mead, Kristina S.

2010-01-01

This article describes a neuroscience outreach program developed by college undergraduates and aimed at second graders. Over a period of four weeks, twenty-five Denison students enrolled in a non-majors course on gender and the brain visited twenty-four second grade classrooms to engage a total of 464 students. We had a mission to both promote college awareness and to specifically bring some brain science into the classroom. The desire to engage students with the brain was in part a wish to celebrate brain awareness week and in part a wish to follow a feminist tenet of bridging theory and practice via activism. The college students chose six activities: a brain puzzle, a sock content guessing game, a jelly bean olfaction and taste test, mystery noises, a message transmission game, and a version of tag. During our outreach with the second graders, my students monitored student engagement and compared engagement between male and female second graders. Engagement was high for nearly all activities but girls were more engaged than boys during the brain puzzle and jelly bean activities. Effect sizes measured as Cohen’s “d” statistics were small to large (0.2 to 0.93). The other four activities (mystery socks, mystery noises, message transmission and neuron chain tag) showed no difference in engagement between male and female second graders. Our program benefited the Denison students as well, introducing many to community involvement and awakening in them an interest in teaching or working with kids. PMID:23494920

The evolution of the complex sensory and motor systems of the human brain

PubMed Central

Kaas, Jon H.

2008-01-01

Inferences about how the complex sensory and motor systems of the human brain evolved are based on the results of comparative studies of brain organization across a range of mammalian species, and evidence from the endocasts of fossil skulls of key extinct species. The endocasts of the skulls of early mammals indicate that they had small brains with little neocortex. Evidence from comparative studies of cortical organization from small-brained mammals of the six major branches of mammalian evolution supports the conclusion that the small neocortex of early mammals was divided into roughly 20–25 cortical areas, including primary and secondary sensory fields. In early primates, vision was the dominant sense, and cortical areas associated with vision in temporal and occipital cortex underwent a significant expansion. Comparative studies indicate that early primates had 10 or more visual areas, and somatosensory areas with expanded representations of the forepaw. Posterior parietal cortex was also expanded, with a caudal half dominated by visual inputs, and a rostral half dominated by somatosensory inputs with outputs to an array of seven or more motor and visuomotor areas of the frontal lobe. Somatosensory areas and posterior parietal cortex became further differentiated in early anthropoid primates. As larger brains evolved in early apes and in our hominin ancestors, the number of cortical areas increased to reach an estimated 200 or so in present day humans, and hemispheric specializations emerged. The large human brain grew primarily by increasing neuron number rather than increasing average neuron size. PMID:18331903

Intrinsic qualities of primate bones as predictors of skeletal element representation in modern and fossil carnivore feeding assemblages.

PubMed

Carlson, Kristian J; Pickering, Travis Rayne

2003-04-01

Plio-Pleistocene faunal assemblages from Swartkrans Cave (South Africa) preserve large numbers of primate remains. Brain, C.K., 1981. The Hunters or the Hunted? An Introduction to African Cave Taphonomy. University of Chicago Press, Chicago suggested that these primate subassemblages might have resulted from a focus by carnivores on primate predation and bone accumulation. Brain's hypothesis prompted us to investigate, in a previous study, this taphonomic issue as it relates to density-mediated destruction of primate bones (J. Archaeol. Sci. 29, 2002, 883). Here we extend our investigation of Brain's hypothesis by examining additional intrinsic qualities of baboon bones and their role as mediators of skeletal element representation in carnivore-created assemblages. Using three modern adult baboon skeletons, we collected data on four intrinsic bone qualities (bulk bone mineral density, maximum length, volume, and cross-sectional area) for approximately 81 bones per baboon skeleton. We investigated the relationship between these intrinsic bone qualities and a measure of skeletal part representation (the percentage minimum animal unit) for baboon bones in carnivore refuse and scat assemblages. Refuse assemblages consist of baboon bones not ingested during ten separate experimental feeding episodes in which individual baboon carcasses were fed to individual captive leopards and a spotted hyena. Scat assemblages consist of those baboon bones recovered in carnivore regurgitations and feces resulting from the feeding episodes. In refuse assemblages, volume (i.e., size) was consistently the best predictor of element representation, while cross-sectional area was the poorest predictor in the leopard refuse assemblage and bulk bone mineral density (i.e., a measure of the proportion of cortical to trabecular bone) was the poorest predictor in the hyena refuse assemblage. In light of previous documentation of carnivore-induced density-mediated destruction to bone assemblages, we interpret the current findings as suggestive of the secondary importance of bulk bone mineral density to other intrinsic qualities of skeletal elements (e.g., size, maximum dimension, and average cross-sectional area). It is only when skeletal elements are too large for consumption (e.g., many long bones) that they are fragmented following intra-element patterns of density-mediated carnivore destruction. There appears to be a size threshold beneath which bulk bone mineral density contributes little to mediating carnivore destruction of carcasses. Thus, depending on body size of the predator, body size of the prey, and specific size of the element, bulk bone mineral density may play little or no role of primary importance in mediating the destruction of skeletal elements. We compare patterns in modern comparative assemblages to patterns in primate fossil assemblages from Swartkrans. One of the fossil assemblages, Swartkrans Member 1, Hanging Remnant, most closely approximates a hyena (possibly refuse) assemblage pattern, while the Swartkrans Member 2 assemblage most closely approximates a leopard (possibly scat) assemblage pattern. The Swartkrans Member 1, Lower Bank, assemblage does not closely approximate any of our modern comparative assemblage patterns.

Transcranial cavitation-mediated ultrasound therapy at sub-MHz frequency via temporal interference modulation

NASA Astrophysics Data System (ADS)

Sun, Tao; Sutton, Jonathan T.; Power, Chanikarn; Zhang, Yongzhi; Miller, Eric L.; McDannold, Nathan J.

2017-10-01

Sub-megahertz transmission is not usually adopted in pre-clinical small animal experiments for focused ultrasound (FUS) brain therapy due to the large focal size. However, low frequency FUS is vital for preclinical evaluations due to the frequency-dependence of cavitation behavior. To maximize clinical relevance, a dual-aperture FUS system was designed for low-frequency (274.3 kHz) cavitation-mediated FUS therapy. Combining two spherically curved transducers provides significantly improved focusing in the axial direction while yielding an interference pattern with strong side lobes, leading to inhomogeneously distributed cavitation activities. By operating the two transducers at slightly offset frequencies to modulate this interference pattern over the period of sonication, the acoustic energy was redistributed and resulted in a spatially homogenous treatment profile. Simulation and pressure field measurements in water were performed to assess the beam profiles. In addition, the system performance was demonstrated in vivo in rats via drug delivery through microbubble-mediated blood-brain barrier disruption. This design resulted in a homogenous treatment profile that was fully contained within the rat brain at a clinically relevant acoustic frequency.

Systems neuroscience in Drosophila: Conceptual and technical advantages.

PubMed

Kazama, H

2015-06-18

The fruit fly Drosophila melanogaster is ideally suited for investigating the neural circuit basis of behavior. Due to the simplicity and genetic tractability of the fly brain, neurons and circuits are identifiable across animals. Additionally, a large set of transgenic lines has been developed with the aim of specifically labeling small subsets of neurons and manipulating them in sophisticated ways. Electrophysiology and imaging can be applied in behaving individuals to examine the computations performed by each neuron, and even the entire population of relevant neurons in a particular region, because of the small size of the brain. Moreover, a rich repertoire of behaviors that can be studied is expanding to include those requiring cognitive abilities. Thus, the fly brain is an attractive system in which to explore both computations and mechanisms underlying behavior at levels spanning from genes through neurons to circuits. This review summarizes the advantages Drosophila offers in achieving this objective. A recent neurophysiology study on olfactory behavior is also introduced to demonstrate the effectiveness of these advantages. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Quantification of traumatic meningeal injury using dynamic contrast enhanced (DCE) fluid-attenuated inversion recovery (FLAIR) imaging

NASA Astrophysics Data System (ADS)

Castro, Marcelo A.; Williford, Joshua P.; Cota, Martin R.; MacLaren, Judy M.; Dardzinski, Bernard J.; Latour, Lawrence L.; Pham, Dzung L.; Butman, John A.

2016-03-01

Traumatic meningeal injury is a novel imaging marker of traumatic brain injury, which appears as enhancement of the dura on post-contrast T2-weighted FLAIR images, and is likely associated with inflammation of the meninges. Dynamic Contrast Enhanced MRI provides a better discrimination of abnormally perfused regions. A method to properly identify those regions is presented. Images of seventeen patients scanned within 96 hours of head injury with positive traumatic meningeal injury were normalized and aligned. The difference between the pre- and last post-contrast acquisitions was segmented and voxels in the higher class were spatially clustered. Spatial and morphological descriptors were used to identify the regions of enhancement: a) centroid; b) distance to the brain mask from external voxels; c) distance from internal voxels; d) size; e) shape. The method properly identified thirteen regions among all patients. The method failed in one case due to the presence of a large brain lesion that altered the mask boundaries. Most false detections were correctly rejected resulting in a sensitivity and specificity of 92.9% and 93.6%, respectively.

Multiple imputation of missing fMRI data in whole brain analysis

PubMed Central

Vaden, Kenneth I.; Gebregziabher, Mulugeta; Kuchinsky, Stefanie E.; Eckert, Mark A.

2012-01-01

Whole brain fMRI analyses rarely include the entire brain because of missing data that result from data acquisition limits and susceptibility artifact, in particular. This missing data problem is typically addressed by omitting voxels from analysis, which may exclude brain regions that are of theoretical interest and increase the potential for Type II error at cortical boundaries or Type I error when spatial thresholds are used to establish significance. Imputation could significantly expand statistical map coverage, increase power, and enhance interpretations of fMRI results. We examined multiple imputation for group level analyses of missing fMRI data using methods that leverage the spatial information in fMRI datasets for both real and simulated data. Available case analysis, neighbor replacement, and regression based imputation approaches were compared in a general linear model framework to determine the extent to which these methods quantitatively (effect size) and qualitatively (spatial coverage) increased the sensitivity of group analyses. In both real and simulated data analysis, multiple imputation provided 1) variance that was most similar to estimates for voxels with no missing data, 2) fewer false positive errors in comparison to mean replacement, and 3) fewer false negative errors in comparison to available case analysis. Compared to the standard analysis approach of omitting voxels with missing data, imputation methods increased brain coverage in this study by 35% (from 33,323 to 45,071 voxels). In addition, multiple imputation increased the size of significant clusters by 58% and number of significant clusters across statistical thresholds, compared to the standard voxel omission approach. While neighbor replacement produced similar results, we recommend multiple imputation because it uses an informed sampling distribution to deal with missing data across subjects that can include neighbor values and other predictors. Multiple imputation is anticipated to be particularly useful for 1) large fMRI data sets with inconsistent missing voxels across subjects and 2) addressing the problem of increased artifact at ultra-high field, which significantly limit the extent of whole brain coverage and interpretations of results. PMID:22500925

3D brain tumor localization and parameter estimation using thermographic approach on GPU.

PubMed

Bousselham, Abdelmajid; Bouattane, Omar; Youssfi, Mohamed; Raihani, Abdelhadi

2018-01-01

The aim of this paper is to present a GPU parallel algorithm for brain tumor detection to estimate its size and location from surface temperature distribution obtained by thermography. The normal brain tissue is modeled as a rectangular cube including spherical tumor. The temperature distribution is calculated using forward three dimensional Pennes bioheat transfer equation, it's solved using massively parallel Finite Difference Method (FDM) and implemented on Graphics Processing Unit (GPU). Genetic Algorithm (GA) was used to solve the inverse problem and estimate the tumor size and location by minimizing an objective function involving measured temperature on the surface to those obtained by numerical simulation. The parallel implementation of Finite Difference Method reduces significantly the time of bioheat transfer and greatly accelerates the inverse identification of brain tumor thermophysical and geometrical properties. Experimental results show significant gains in the computational speed on GPU and achieve a speedup of around 41 compared to the CPU. The analysis performance of the estimation based on tumor size inside brain tissue also presented. Copyright © 2017 Elsevier Ltd. All rights reserved.

C-type natriuretic peptide functions as an innate neuroprotectant in neonatal hypoxic-ischemic brain injury in mouse via natriuretic peptide receptor 2.

PubMed

Ma, Qingyi; Zhang, Lubo

2018-06-01

Neonatal hypoxia-ischemia (HI) is the most common cause of brain injury in neonates, which leads to high neonatal mortality and severe neurological morbidity in later life (Vannucci, 2000; Volpe, 2001). Yet the molecular mechanisms of neuronal death and brain damage induced by neonatal HI remain largely elusive. Herein, using both in vivo and in vitro models, we determine an endogenous neuroprotectant role of c-type natriuretic peptide (CNP) in preserving neuronal survival after HI brain injury in mouse pups. Postnatal day 7 (P7) mouse pups with CNP deficiency (Nppc lbab/lbab ) exhibit increased brain infarct size and worsened long-term locomotor function after neonatal HI compared with wildtype control (Nppc +/+ ). In isolated primary cortical neurons, recombinant CNP dose-dependently protects primary neurons from oxygen-glucose deprivation (OGD) insult. This neuroprotective effect appears to be mediated through its cognate natriuretic peptide receptor 2 (NPR2), in that antagonization of NPR2, but not NPR3, exacerbates neuronal death and counteracts the protective effect of CNP on primary neurons exposed to OGD insult. Immunoblot and confocal microscopy demonstrate the abundant expression of NPR2 in neurons of the neonatal brain and in isolated primary cortical neurons as well. Moreover, similar to CNP deficiency, administration of NPR2 antagonist P19 via intracerebroventricular injection prior to HI results in exacerbated neuronal death and brain injury after HI. Altogether, the present study indicates that CNP and its cognate receptor NPR2 mainly expressed in neurons represent an innate neuroprotective mechanism in neonatal HI brain injury. Copyright © 2018 Elsevier Inc. All rights reserved.

The PPARgamma agonist FMOC-L-leucine protects both mature and immature brain.

PubMed

Maurois, Pierre; Rocchi, Stéphane; Pages, Nicole; Bac, Pierre; Stables, James P; Gressens, Pierre; Vamecq, Joseph

2008-01-01

(N-[9-fluorenylmethoxycarbonyl]-)-L-leucine (FMOC-L-leucine) and rosiglitazone, two ligands of peroxisome proliferator-activated receptor gamma (PPARgamma), were evaluated in mature (adult mice) and immature (pups) brain injury models. In adult magnesium-deficient mice, a model responsive to both neuroprotective and anti-seizure compounds, FMOC-L-leucine, but not rosiglitazone, protected against audiogenic seizures. The protection afforded by FMOC-L-leucine was alleviated by the PPARgamma antagonist GW9662 (1-2 mg/kg) and was induced in 50% animals by 4.8+/-1.2 mg/kg. At this dose, FMOC-L-leucine modified audiogenic seizure phase durations in convulsing mice differently than prototype antiepileptic drugs did. FMOC-L-leucine (up to 100 mg/kg) was inactive in the 6 Hz seizure test, an adult animal model largely responsive to anti-seizure drugs. In a model of neonatal brain injury, FMOC-L-leucine (4 microg/kg) was neuroprotective against cerebral ibotenate toxicity. It reduced significantly the size of lesions in grey but not in white matter, while rosiglitazone (10 microg/kg) was inactive. Taken as a whole, the present data support neuroprotective potentialities of FMOC-L-leucine towards both mature and immature brain. The PPAR-based protection of immature brain is more important as it is known that classic adult brain protectants (GABA(A) activators, N-methyl-D-aspartate and sodium channel blockers) may be toxic for immature brain. The PPARgamma agonist FMOC-L-leucine is likely to be devoid of these classic protective mechanisms because of its inactivity in the 6 Hz seizure test, its activity in the audiogenic test being explained by neuroprotective rather than intrinsic anti-seizure mechanisms. Targeting PPARs might be thus a promising way to protect immature brain.

Life in the unthinking depths: energetic constraints on encephalization in marine fishes.

PubMed

Iglesias, T L; Dornburg, A; Brandley, M C; Alfaro, M E; Warren, D L

2015-05-01

Several hypotheses have been proposed to explain the limitation of brain size in vertebrates. Here, we test three hypotheses of brain size evolution using marine teleost fishes: the direct metabolic constraints hypothesis (DMCH), the expensive tissue hypothesis and the temperature-dependent hypothesis. Our analyses indicate that there is a robust positive correlation between encephalization and basal metabolic rate (BMR) that spans the full range of depths occupied by teleosts from the epipelagic (< 200 m), mesopelagic (200-1000 m) and bathypelagic (> 4000 m). Our results disentangle the effects of temperature and metabolic rate on teleost brain size evolution, supporting the DMCH. Our results agree with previous findings that teleost brain size decreases with depth; however, we also recover a negative correlation between trophic level and encephalization within the mesopelagic zone, a result that runs counter to the expectations of the expensive tissue hypothesis. We hypothesize that mesopelagic fishes at lower trophic levels may be investing more in neural tissue related to the detection of small prey items in a low-light environment. We recommend that comparative encephalization studies control for BMR in addition to controlling for body size and phylogeny. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

Sex-related difference in human white matter volumes studied: Inspection of the corpus callosum and other white matter by VBM

NASA Astrophysics Data System (ADS)

Shiino, Akihiko; Chen, Yen-Wei; Tanigaki, Kenji; Yamada, Atsushi; Vigers, Piers; Watanabe, Toshiyuki; Tooyama, Ikuo; Akiguchi, Ichiro

2017-01-01

It has been contended that any observed difference of the corpus callosum (CC) size between men and women is not sex-related but brain-size-related. A recent report, however, showed that the midsagittal CC area was significantly larger in women in 37 brain-size-matched pairs of normal young adults. Since this constituted strong evidence of sexual dimorphism and was obtained from publicly available data in OASIS, we examined volume differences within the CC and in other white matter using voxel-based morphometry (VBM). We created a three-dimensional region of interest of the CC and measured its volume. The VBM statistics were analyzed by permutation test and threshold-free cluster enhancement (TFCE) with the significance levels at FWER < 0.05. The CC volume was significantly larger in women in the same 37 brain-size-matched pairs. We found that the CC genu was the subregion showing the most significant sex-related difference. We also found that white matter in the bilateral anterior frontal regions and the left lateral white matter near to Broca’s area were larger in women, whereas there were no significant larger regions in men. Since we used brain-size-matched subjects, our results gave strong volumetric evidence of localized sexual dimorphism of white matter.

The effect of nanoparticle size on the ability to cross the blood-brain barrier: an in vivo study.

PubMed

Betzer, Oshra; Shilo, Malka; Opochinsky, Renana; Barnoy, Eran; Motiei, Menachem; Okun, Eitan; Yadid, Gal; Popovtzer, Rachela

2017-07-01

Our goal was to develop an efficient nanoparticle-based system that can overcome the restrictive mechanism of the blood-brain barrier (BBB) by targeting insulin receptors and would thus enable drug delivery to the brain. Insulin-coated gold nanoparticles (INS-GNPs) were synthesized to serve as a BBB transport system. The effect of nanoparticle size (20, 50 and 70 nm) on their ability to cross the BBB was quantitatively investigated in Balb/C mice. The most widespread biodistribution and highest accumulation within the brain were observed using 20 nm INS-GNPs, 2 h post injection. In vivo CT imaging revealed that particles migrated to specific brain regions, which are involved in neurodegenerative and neuropsychiatric disorders. These findings promote the optimization of nanovehicles for transport of drugs through the BBB. The insulin coating of the particles enabled targeting of specific brain regions, suggesting the potential use of INS-GNPs for delivery of various treatments for brain-related disorders.

Brain Dynamics of Word Familiarization in 20-Month-Olds: Effects of Productive Vocabulary Size

ERIC Educational Resources Information Center

Torkildsen, Janne von Koss; Hansen, Hanna Friis; Svangstu, Janne Mari; Smith, Lars; Simonsen, Hanne Gram; Moen, Inger; Lindgren, Magnus

2009-01-01

The present study investigated the brain mechanisms involved during young children's receptive familiarization with new words, and whether the dynamics of these mechanisms are related to the child's productive vocabulary size. To this end, we recorded event-related potentials (ERPs) from 20-month-old children in a pseudoword repetition task.…

Regulation of Cerebral Cortical Size and Neuron Number by Fibroblast Growth Factors: Implications for Autism

ERIC Educational Resources Information Center

Vaccarino, Flora M.; Grigorenko, Elena L.; Smith, Karen Muller; Stevens, Hanna E.

2009-01-01

Increased brain size is common in children with autism spectrum disorders. Here we propose that an increased number of cortical excitatory neurons may underlie the increased brain volume, minicolumn pathology and excessive network excitability, leading to sensory hyper-reactivity and seizures, which are often found in autism. We suggest that…

Glucocorticoids Protect Neonatal Rat Brain in Model of Hypoxic-Ischemic Encephalopathy (HIE)

PubMed Central

Harding, Benjamin; Conception, Katherine; Li, Yong; Zhang, Lubo

2016-01-01

Hypoxic-ischemic encephalopathy (HIE) resulting from asphyxia in the peripartum period is the most common cause of neonatal brain damage and can result in significant neurologic sequelae, including cerebral palsy. Currently therapeutic hypothermia is the only accepted treatment in addition to supportive care for infants with HIE, however, many additional neuroprotective therapies have been investigated. Of these, glucocorticoids have previously been shown to have neuroprotective effects. HIE is also frequently compounded by infectious inflammatory processes (sepsis) and as such, the infants may be more amenable to treatment with an anti-inflammatory agent. Thus, the present study investigated dexamethasone and hydrocortisone treatment given after hypoxic-ischemic (HI) insult in neonatal rats via intracerebroventricular (ICV) injection and intranasal administration. In addition, we examined the effects of hydrocortisone treatment in HIE after lipopolysaccharide (LPS) sensitization in a model of HIE and sepsis. We found that dexamethasone significantly reduced rat brain infarction size when given after HI treatment via ICV injection; however it did not demonstrate any neuroprotective effects when given intranasally. Hydrocortisone after HI insult also significantly reduced brain infarction size when given via ICV injection; and the intranasal administration showed to be protective of brain injury in male rats at a dose of 300 µg. LPS sensitization did significantly increase the brain infarction size compared to controls, and hydrocortisone treatment after LPS sensitization showed a significant decrease in brain infarction size when given via ICV injection, as well as intranasal administration in both genders at a dose of 300 µg. To conclude, these results show that glucocorticoids have significant neuroprotective effects when given after HI injury and that these effects may be even more pronounced when given in circumstances of additional inflammatory injury, such as neonatal sepsis. PMID:28025500

A Model of Penetrating Traumatic Brain Injury Using an Air Inflation Technique

DTIC Science & Technology

2003-06-01

work of Carey et al (1989, 1990) using the now-abandoned fired projectile feline model. This report contains the results of all of the above...parameters that come into play, and do not neglect the usual forces that act on the projectile such as gravity. Ammunition producers go through great pains ...focus of our investigations. Vt is compared to the size of the human brain and then scaled down by 672.5:1 for the rat’s brain size and designated as Vt

Toward 20 T magnetic resonance for human brain studies: opportunities for discovery and neuroscience rationale

PubMed Central

Bird, Mark D.; Frydman, Lucio; Long, Joanna R.; Mareci, Thomas H.; Rooney, William D.; Rosen, Bruce; Schenck, John F.; Schepkin, Victor D.; Sherry, A. Dean; Sodickson, Daniel K.; Springer, Charles S.; Thulborn, Keith R.; Uğurbil, Kamil; Wald, Lawrence L.

2017-01-01

An initiative to design and build magnetic resonance imaging (MRI) and spectroscopy (MRS) instruments at 14 T and beyond to 20 T has been underway since 2012. This initiative has been supported by 22 interested participants from the USA and Europe, of which 15 are authors of this review. Advances in high temperature superconductor materials, advances in cryocooling engineering, prospects for non-persistent mode stable magnets, and experiences gained from large-bore, high-field magnet engineering for the nuclear fusion endeavors support the feasibility of a human brain MRI and MRS system with 1 ppm homogeneity over at least a 16-cm diameter volume and a bore size of 68 cm. Twelve neuroscience opportunities are presented as well as an analysis of the biophysical and physiological effects to be investigated before exposing human subjects to the high fields of 14 T and beyond. PMID:27194154

Cognitive and academic achievement changes associated with day hospital rehabilitation in children with acquired brain injury.

PubMed

Goldstein, Gerald; Mayfield, Joan; Thaler, Nicholas S; Walker, Jon; Allen, Daniel N

2018-01-01

An evaluation was made of the outcome of a day hospital rehabilitation program for children who experienced an acquired neurological illness, mainly traumatic brain injury. Participants were administered neuropsychological and academic evaluations upon entry to the program, immediately upon discharge and several months after discharge Repeated measures ANOVA results for variables selected from the Reynolds Intellectual Assessment and the Delis-Kaplan Executive Function System found that comparisons showed significant (≥p < .01) improvement occurred between the first and second assessment, generally with large effect sizes. There were some nonsignificant decrements in performance between the discharge and follow-up assessments. A correlational analysis showed that while the association between cognitive function and academic achievement was robust, correlation coefficients did not differ in strength before and following rehabilitation. The study demonstrates significant improvement in children with acquired neurological disorders following rehabilitation.

Flexible Organic Electronics for Use in Neural Sensing

PubMed Central

Bink, Hank; Lai, Yuming; Saudari, Sangameshwar R.; Helfer, Brian; Viventi, Jonathan; Van der Spiegel, Jan; Litt, Brian; Kagan, Cherie

2016-01-01

Recent research in brain-machine interfaces and devices to treat neurological disease indicate that important network activity exists at temporal and spatial scales beyond the resolution of existing implantable devices. High density, active electrode arrays hold great promise in enabling high-resolution interface with the brain to access and influence this network activity. Integrating flexible electronic devices directly at the neural interface can enable thousands of multiplexed electrodes to be connected using many fewer wires. Active electrode arrays have been demonstrated using flexible, inorganic silicon transistors. However, these approaches may be limited in their ability to be cost-effectively scaled to large array sizes (8×8 cm). Here we show amplifiers built using flexible organic transistors with sufficient performance for neural signal recording. We also demonstrate a pathway for a fully integrated, amplified and multiplexed electrode array built from these devices. PMID:22255558

Toward 20 T magnetic resonance for human brain studies: opportunities for discovery and neuroscience rationale.

PubMed

Budinger, Thomas F; Bird, Mark D; Frydman, Lucio; Long, Joanna R; Mareci, Thomas H; Rooney, William D; Rosen, Bruce; Schenck, John F; Schepkin, Victor D; Sherry, A Dean; Sodickson, Daniel K; Springer, Charles S; Thulborn, Keith R; Uğurbil, Kamil; Wald, Lawrence L

2016-06-01

An initiative to design and build magnetic resonance imaging (MRI) and spectroscopy (MRS) instruments at 14 T and beyond to 20 T has been underway since 2012. This initiative has been supported by 22 interested participants from the USA and Europe, of which 15 are authors of this review. Advances in high temperature superconductor materials, advances in cryocooling engineering, prospects for non-persistent mode stable magnets, and experiences gained from large-bore, high-field magnet engineering for the nuclear fusion endeavors support the feasibility of a human brain MRI and MRS system with 1 ppm homogeneity over at least a 16-cm diameter volume and a bore size of 68 cm. Twelve neuroscience opportunities are presented as well as an analysis of the biophysical and physiological effects to be investigated before exposing human subjects to the high fields of 14 T and beyond.

Effect of Leukocyte Telomere Length on Total and Regional Brain Volumes in a Large Population-Based Cohort

PubMed Central

King, Kevin S.; Kozlitina, Julia; Rosenberg, Roger N.; Peshock, Ronald M.; McColl, Roderick W.; Garcia, Christine K.

2017-01-01

Importance Telomere length has been associated with dementia and psychological stress, but its relationship with human brain size is unknown. Objective To determine if peripheral blood telomere length is associated with brain volume. Design, Setting, and Participants Peripheral blood leukocyte telomere length and brain volumes were measured for 1960 individuals in the Dallas Heart Study, a population-based, probability sample of Dallas County, Texas, residents, with a median (25th-75th percentile) age of 50 (42-58) years. Global and 48 regional brain volumes were assessed from the automated analysis of magnetic resonance imaging. Main Outcomes and Measures Telomere length and global and regional brain volumes. Results Leukocyte telomere length was associated with total cerebral volume (β [SE], 0.06 [0.01], P <.001) including white and cortical gray matter volume (β [SE], 0.04 [0.01], P = .002; β [SE], 0.07 [0.02], P <.001, respectively), independent of age, sex, ethnicity, and total intracranial volume. While age was associated with the size of most subsegmental regions of the cerebral cortex, telomere length was associated with certain subsegmental regions. Compared with age, telomere length (TL) explained a sizeable proportion of the variance in volume of the hippocampus, amygdala, and inferior temporal region (hippocampus: βTL [SE], 0.08 [0.02], R2, 0.91% vs βage [SE], −0.16 [0.02], R2, 3.80%; amygdala: βTL [SE], 0.08 [0.02], R2, 0.78% vs βage [SE], −0.19 [0.02], R2,4.63%; inferior temporal: βTL [SE], 0.07 [0.02], R2, 0.92% vs βage [SE], −0.14 [0.02], R2, 3.98%) (P <.001 for all). The association of telomere length and the size of the inferior and superior parietal, hippocampus, and fusiform regions was stronger in individuals older than 50 years than younger individuals (inferior parietal: β>50 [SE], 0.13 [0.03], P <.001 vs β≤50 [SE], 0.02 [0.02], P = .51, P for interaction = .001; superior parietal: β>50 [SE], 0.11 [0.03], P <.001 vs β≤50 [SE], 0.01 [0.02], P = .71, P for interaction = .004; hippocampus: β>50 [SE], 0.10 [0.03], P = .004 vs β≤50 [SE], 0.05 [0.02], P = .07, P for interaction = .04; fusiform: β>50 [SE], 0.09 [0.03], P = .002, β≤50 [SE], 0.03 [0.02], P = .31, P for interaction = .03). The volume of the hippocampus, amygdala, superior and inferior temporal, precuneus, lateral orbitofrontal, posterior cingulate, thalamus and ventral diencephalon were independently associated with telomere length after adjustment for all covariates (age, gender, ethnicity, total intracranial volume, body mass index, blood pressure, diabetes, smoking status, and APOE genotype). Conclusions and Relevance To our knowledge, this is the first population-based study to date to evaluate telomere length as an independent predictor of global and regional brain size. Future studies are needed to determine how telomere length and anatomic structural changes are related to cognitive function, dementia, and psychological disease. PMID:25090243

Growth hormone deficiency after mild combat-related traumatic brain injury.

PubMed

Ioachimescu, Adriana G; Hampstead, Benjamin M; Moore, Anna; Burgess, Elizabeth; Phillips, Lawrence S

2015-08-01

Traumatic brain injury (TBI) has been recognized as a cause of growth hormone deficiency (GHD) in civilians. However, comparable data are sparse in veterans who incurred TBI during combat. Our objective was to determine the prevalence of GHD in veterans with a history of combat-related TBI, and its association with cognitive and psychosocial dysfunction. Single center prospective study. Twenty male veterans with mild TBI incurred during combat 8-72 months prior to enrollment. GHD was defined by a GH peak <3 μg/L during glucagon stimulation test. Differences in neuropsychological, emotional, and quality of life of the GHD Veterans were described using Cohen's d. Large effect sizes were considered meaningful. Mean age was 33.7 years (SD 7.8) and all subjects had normal thyroid hormone and cortisol levels. Five (25%) exhibited a subnormal response to glucagon. Sixteen participants (80%) provided sufficient effort for valid neuropsychological assessment (12 GH-sufficient, 4 GHD). There were large effect size differences in self-monitoring during memory testing (d = 1.46) and inhibitory control (d = 0.92), with worse performances in the GHD group. While fatigue and post-traumatic stress disorder were comparable, the GHD group reported more depression (d = 0.80) and lower quality of life (d = 0.64). Our study found a 25% prevalence of GHD in veterans with mild TBI as shown by glucagon stimulation. The neuropsychological findings raise the possibility that GHD has adverse effects on executive abilities and mood. Further studies are needed to determine whether GH replacement is an effective treatment in these patients.

Chlorpyrifos and malathion have opposite effects on behaviors and brain size that are not correlated to changes in AChE activity.

PubMed

Richendrfer, Holly; Creton, Robbert

2015-07-01

Organophosphates, a type of neurotoxicant pesticide, are used globally for the treatment of pests on croplands and are therefore found in a large number of conventional foods. These pesticides are harmful and potentially deadly if ingested or inhaled in large quantities by causing a significant reduction in acetylcholinesterase (AChE) activity in the central and peripheral nervous system. However, much less is known about the effects of exposure to small quantities of the pesticides on neural systems and behavior during development. In the current study we used zebrafish larvae in order to determine the effects of two of the most widely used organophosphates, chlorpyrifos and malathion, on zebrafish behavior and AChE activity. Embryos and larvae were exposed to the organophosphates during different time points in development and then tested at 5 days post-fertilization for behavioral, neurodevelopmental and AChE abnormalities. The results of the study indicate that chlorpyrifos and malathion cause opposing behaviors in the larvae such as swim speed (hypoactivity vs. hyperactivity) and rest. Additionally, the pesticides affect only certain behaviors, such as thigmotaxis, during specific time points in development that are unrelated to changes in AChE activity. Larvae treated with malathion but not chlorpyrifos also had significantly smaller forebrain and hindbrain regions compared to controls by 5 days post-fertilization. We conclude that exposure to very low concentrations of organophosphate pesticides during development cause abnormalities in behavior and brain size. Copyright © 2015 Elsevier Inc. All rights reserved.

An ERP study on whether semantic integration exists in processing ecologically unrelated audio-visual information.

PubMed

Liu, Baolin; Meng, Xianyao; Wang, Zhongning; Wu, Guangning

2011-11-14

In the present study, we used event-related potentials (ERPs) to examine whether semantic integration occurs for ecologically unrelated audio-visual information. Videos with synchronous audio-visual information were used as stimuli, where the auditory stimuli were sine wave sounds with different sound levels, and the visual stimuli were simple geometric figures with different areas. In the experiment, participants were shown an initial display containing a single shape (drawn from a set of 6 shapes) with a fixed size (14cm(2)) simultaneously with a 3500Hz tone of a fixed intensity (80dB). Following a short delay, another shape/tone pair was presented and the relationship between the size of the shape and the intensity of the tone varied across trials: in the V+A- condition, a large shape was paired with a soft tone; in the V+A+ condition, a large shape was paired with a loud tone, and so forth. The ERPs results revealed that N400 effect was elicited under the VA- condition (V+A- and V-A+) as compared to the VA+ condition (V+A+ and V-A-). It was shown that semantic integration would occur when simultaneous, ecologically unrelated auditory and visual stimuli enter the human brain. We considered that this semantic integration was based on semantic constraint of audio-visual information, which might come from the long-term learned association stored in the human brain and short-term experience of incoming information. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Between Scylla and Charybdis: renegotiating resolution of the ‘obstetric dilemma’ in response to ecological change

PubMed Central

Wells, Jonathan C. K.

2015-01-01

Hominin evolution saw the emergence of two traits—bipedality and encephalization—that are fundamentally linked because the fetal head must pass through the maternal pelvis at birth, a scenario termed the ‘obstetric dilemma’. While adaptive explanations for bipedality and large brains address adult phenotype, it is brain and pelvic growth that are subject to the obstetric dilemma. Many contemporary populations experience substantial maternal and perinatal morbidity/mortality from obstructed labour, yet there is increasing recognition that the obstetric dilemma is not fixed and is affected by ecological change. Ecological trends may affect growth of the pelvis and offspring brain to different extents, while the two traits also differ by a generation in the timing of their exposure. Two key questions arise: how can the fit between the maternal pelvis and the offspring brain be ‘renegotiated’ as the environment changes, and what nutritional signals regulate this process? I argue that the potential for maternal size to change across generations precludes birthweight being under strong genetic influence. Instead, fetal growth tracks maternal phenotype, which buffers short-term ecological perturbations. Nevertheless, rapid changes in nutritional supply between generations can generate antagonistic influences on maternal and offspring traits, increasing the risk of obstructed labour. PMID:25602071

Between Scylla and Charybdis: renegotiating resolution of the 'obstetric dilemma' in response to ecological change.

PubMed

Wells, Jonathan C K

2015-03-05

Hominin evolution saw the emergence of two traits-bipedality and encephalization-that are fundamentally linked because the fetal head must pass through the maternal pelvis at birth, a scenario termed the 'obstetric dilemma'. While adaptive explanations for bipedality and large brains address adult phenotype, it is brain and pelvic growth that are subject to the obstetric dilemma. Many contemporary populations experience substantial maternal and perinatal morbidity/mortality from obstructed labour, yet there is increasing recognition that the obstetric dilemma is not fixed and is affected by ecological change. Ecological trends may affect growth of the pelvis and offspring brain to different extents, while the two traits also differ by a generation in the timing of their exposure. Two key questions arise: how can the fit between the maternal pelvis and the offspring brain be 'renegotiated' as the environment changes, and what nutritional signals regulate this process? I argue that the potential for maternal size to change across generations precludes birthweight being under strong genetic influence. Instead, fetal growth tracks maternal phenotype, which buffers short-term ecological perturbations. Nevertheless, rapid changes in nutritional supply between generations can generate antagonistic influences on maternal and offspring traits, increasing the risk of obstructed labour. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

A finite element analysis of the effect of electrode area and inter-electrode distance on the spatial distribution of the current density in tDCS

NASA Astrophysics Data System (ADS)

Faria, Paula; Hallett, Mark; Cavaleiro Miranda, Pedro

2011-12-01

We investigated the effect of electrode area and inter-electrode distance on the spatial distribution of the current density in transcranial direct current stimulation (tDCS). For this purpose, we used the finite element method to compute the distribution of the current density in a four-layered spherical head model using various electrode montages, corresponding to a range of electrode sizes and inter-electrode distances. We found that smaller electrodes required slightly less current to achieve a constant value of the current density at a reference point on the brain surface located directly under the electrode center. Under these conditions, smaller electrodes also produced a more focal current density distribution in the brain, i.e. the magnitude of the current density fell more rapidly with distance from the reference point. The combination of two electrodes with different areas produced an asymmetric current distribution that could lead to more effective and localized neural modulation under the smaller electrode than under the larger one. Focality improved rapidly with decreasing electrode size when the larger electrode sizes were considered but the improvement was less marked for the smaller electrode sizes. Also, focality was not affected significantly by inter-electrode distance unless two large electrodes were placed close together. Increasing the inter-electrode distance resulted in decreased shunting of the current through the scalp and the cerebrospinal fluid, and decreasing electrode area resulted in increased current density on the scalp under the edges of the electrode. Our calculations suggest that when working with conventional electrodes (25-35 cm2), one of the electrodes should be placed just 'behind' the target relative to the other electrode, for maximum current density on the target. Also electrodes with areas in the range 3.5-12 cm2 may provide a better compromise between focality and current density in the scalp than the traditional electrodes. Finally, the use of multiple small return electrodes may be more efficient than the use of a single large return electrode.

Slow CCL2-dependent translocation of biopersistent particles from muscle to brain

PubMed Central

2013-01-01

Background Long-term biodistribution of nanomaterials used in medicine is largely unknown. This is the case for alum, the most widely used vaccine adjuvant, which is a nanocrystalline compound spontaneously forming micron/submicron-sized agglomerates. Although generally well tolerated, alum is occasionally detected within monocyte-lineage cells long after immunization in presumably susceptible individuals with systemic/neurologic manifestations or autoimmune (inflammatory) syndrome induced by adjuvants (ASIA). Methods On the grounds of preliminary investigations in 252 patients with alum-associated ASIA showing both a selective increase of circulating CCL2, the major monocyte chemoattractant, and a variation in the CCL2 gene, we designed mouse experiments to assess biodistribution of vaccine-derived aluminum and of alum-particle fluorescent surrogates injected in muscle. Aluminum was detected in tissues by Morin stain and particle induced X-ray emission) (PIXE) Both 500 nm fluorescent latex beads and vaccine alum agglomerates-sized nanohybrids (Al-Rho) were used. Results Intramuscular injection of alum-containing vaccine was associated with the appearance of aluminum deposits in distant organs, such as spleen and brain where they were still detected one year after injection. Both fluorescent materials injected into muscle translocated to draining lymph nodes (DLNs) and thereafter were detected associated with phagocytes in blood and spleen. Particles linearly accumulated in the brain up to the six-month endpoint; they were first found in perivascular CD11b+ cells and then in microglia and other neural cells. DLN ablation dramatically reduced the biodistribution. Cerebral translocation was not observed after direct intravenous injection, but significantly increased in mice with chronically altered blood-brain-barrier. Loss/gain-of-function experiments consistently implicated CCL2 in systemic diffusion of Al-Rho particles captured by monocyte-lineage cells and in their subsequent neurodelivery. Stereotactic particle injection pointed out brain retention as a factor of progressive particle accumulation. Conclusion Nanomaterials can be transported by monocyte-lineage cells to DLNs, blood and spleen, and, similarly to HIV, may use CCL2-dependent mechanisms to penetrate the brain. This occurs at a very low rate in normal conditions explaining good overall tolerance of alum despite its strong neurotoxic potential. However, continuously escalating doses of this poorly biodegradable adjuvant in the population may become insidiously unsafe, especially in the case of overimmunization or immature/altered blood brain barrier or high constitutive CCL-2 production. PMID:23557144

Slow CCL2-dependent translocation of biopersistent particles from muscle to brain.

PubMed

Khan, Zakir; Combadière, Christophe; Authier, François-Jérôme; Itier, Valérie; Lux, François; Exley, Christopher; Mahrouf-Yorgov, Meriem; Decrouy, Xavier; Moretto, Philippe; Tillement, Olivier; Gherardi, Romain K; Cadusseau, Josette

2013-04-04

Long-term biodistribution of nanomaterials used in medicine is largely unknown. This is the case for alum, the most widely used vaccine adjuvant, which is a nanocrystalline compound spontaneously forming micron/submicron-sized agglomerates. Although generally well tolerated, alum is occasionally detected within monocyte-lineage cells long after immunization in presumably susceptible individuals with systemic/neurologic manifestations or autoimmune (inflammatory) syndrome induced by adjuvants (ASIA). On the grounds of preliminary investigations in 252 patients with alum-associated ASIA showing both a selective increase of circulating CCL2, the major monocyte chemoattractant, and a variation in the CCL2 gene, we designed mouse experiments to assess biodistribution of vaccine-derived aluminum and of alum-particle fluorescent surrogates injected in muscle. Aluminum was detected in tissues by Morin stain and particle induced X-ray emission) (PIXE) Both 500 nm fluorescent latex beads and vaccine alum agglomerates-sized nanohybrids (Al-Rho) were used. Intramuscular injection of alum-containing vaccine was associated with the appearance of aluminum deposits in distant organs, such as spleen and brain where they were still detected one year after injection. Both fluorescent materials injected into muscle translocated to draining lymph nodes (DLNs) and thereafter were detected associated with phagocytes in blood and spleen. Particles linearly accumulated in the brain up to the six-month endpoint; they were first found in perivascular CD11b+ cells and then in microglia and other neural cells. DLN ablation dramatically reduced the biodistribution. Cerebral translocation was not observed after direct intravenous injection, but significantly increased in mice with chronically altered blood-brain-barrier. Loss/gain-of-function experiments consistently implicated CCL2 in systemic diffusion of Al-Rho particles captured by monocyte-lineage cells and in their subsequent neurodelivery. Stereotactic particle injection pointed out brain retention as a factor of progressive particle accumulation. Nanomaterials can be transported by monocyte-lineage cells to DLNs, blood and spleen, and, similarly to HIV, may use CCL2-dependent mechanisms to penetrate the brain. This occurs at a very low rate in normal conditions explaining good overall tolerance of alum despite its strong neurotoxic potential. However, continuously escalating doses of this poorly biodegradable adjuvant in the population may become insidiously unsafe, especially in the case of overimmunization or immature/altered blood brain barrier or high constitutive CCL-2 production.

Normalization of similarity-based individual brain networks from gray matter MRI and its association with neurodevelopment in infants with intrauterine growth restriction.

PubMed

Batalle, Dafnis; Muñoz-Moreno, Emma; Figueras, Francesc; Bargallo, Nuria; Eixarch, Elisenda; Gratacos, Eduard

2013-12-01

Obtaining individual biomarkers for the prediction of altered neurological outcome is a challenge of modern medicine and neuroscience. Connectomics based on magnetic resonance imaging (MRI) stands as a good candidate to exhaustively extract information from MRI by integrating the information obtained in a few network features that can be used as individual biomarkers of neurological outcome. However, this approach typically requires the use of diffusion and/or functional MRI to extract individual brain networks, which require high acquisition times and present an extreme sensitivity to motion artifacts, critical problems when scanning fetuses and infants. Extraction of individual networks based on morphological similarity from gray matter is a new approach that benefits from the power of graph theory analysis to describe gray matter morphology as a large-scale morphological network from a typical clinical anatomic acquisition such as T1-weighted MRI. In the present paper we propose a methodology to normalize these large-scale morphological networks to a brain network with standardized size based on a parcellation scheme. The proposed methodology was applied to reconstruct individual brain networks of 63 one-year-old infants, 41 infants with intrauterine growth restriction (IUGR) and 22 controls, showing altered network features in the IUGR group, and their association with neurodevelopmental outcome at two years of age by means of ordinal regression analysis of the network features obtained with Bayley Scale for Infant and Toddler Development, third edition. Although it must be more widely assessed, this methodology stands as a good candidate for the development of biomarkers for altered neurodevelopment in the pediatric population. © 2013 Elsevier Inc. All rights reserved.

SU-E-T-230: Creating a Large Number of Focused Beams with Variable Patient Head Tilt to Improve Dose Fall-Off for Brain Radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chiu, J; Ma, L

2015-06-15

Purpose: To develop a treatment delivery and planning strategy by increasing the number of beams to minimize dose to brain tissue surrounding a target, while maximizing dose coverage to the target. Methods: We analyzed 14 different treatment plans via Leksell PFX and 4C. For standardization, single tumor cases were chosen. Original treatment plans were compared with two optimized plans. The number of beams was increased in treatment plans by varying tilt angles of the patient head, while maintaining original isocenter and the beam positions in the x-, y- and z-axes, collimator size, and beam blocking. PFX optimized plans increased beammore » numbers with three pre-set tilt angles, 70, 90, 110, and 4C optimized plans increased beam numbers with tilt angles increasing arbitrarily from range of 30 to 150 degrees. Optimized treatment plans were compared dosimetrically with original treatment plans. Results: Comparing total normal tissue isodose volumes between original and optimized plans, the low-level percentage isodose volumes decreased in all plans. Despite the addition of multiple beams up to a factor of 25, beam-on times for 1 tilt angle versus 3 or more tilt angles were comparable (<1 min.). In 64% (9/14) of the studied cases, the volume percentage decrease by >5%, with the highest value reaching 19%. The addition of more tilt angles correlates to a greater decrease in normal brain irradiated volume. Selectivity and coverage for original and optimized plans remained comparable. Conclusion: Adding large number of additional focused beams with variable patient head tilt shows improvement for dose fall-off for brain radiosurgery. The study demonstrates technical feasibility of adding beams to decrease target volume.« less

3D variational brain tumor segmentation using Dirichlet priors on a clustered feature set.

PubMed

Popuri, Karteek; Cobzas, Dana; Murtha, Albert; Jägersand, Martin

2012-07-01

Brain tumor segmentation is a required step before any radiation treatment or surgery. When performed manually, segmentation is time consuming and prone to human errors. Therefore, there have been significant efforts to automate the process. But, automatic tumor segmentation from MRI data is a particularly challenging task. Tumors have a large diversity in shape and appearance with intensities overlapping the normal brain tissues. In addition, an expanding tumor can also deflect and deform nearby tissue. In our work, we propose an automatic brain tumor segmentation method that addresses these last two difficult problems. We use the available MRI modalities (T1, T1c, T2) and their texture characteristics to construct a multidimensional feature set. Then, we extract clusters which provide a compact representation of the essential information in these features. The main idea in this work is to incorporate these clustered features into the 3D variational segmentation framework. In contrast to previous variational approaches, we propose a segmentation method that evolves the contour in a supervised fashion. The segmentation boundary is driven by the learned region statistics in the cluster space. We incorporate prior knowledge about the normal brain tissue appearance during the estimation of these region statistics. In particular, we use a Dirichlet prior that discourages the clusters from the normal brain region to be in the tumor region. This leads to a better disambiguation of the tumor from brain tissue. We evaluated the performance of our automatic segmentation method on 15 real MRI scans of brain tumor patients, with tumors that are inhomogeneous in appearance, small in size and in proximity to the major structures in the brain. Validation with the expert segmentation labels yielded encouraging results: Jaccard (58%), Precision (81%), Recall (67%), Hausdorff distance (24 mm). Using priors on the brain/tumor appearance, our proposed automatic 3D variational segmentation method was able to better disambiguate the tumor from the surrounding tissue.

Neural decoding of collective wisdom with multi-brain computing.

PubMed

Eckstein, Miguel P; Das, Koel; Pham, Binh T; Peterson, Matthew F; Abbey, Craig K; Sy, Jocelyn L; Giesbrecht, Barry

2012-01-02

Group decisions and even aggregation of multiple opinions lead to greater decision accuracy, a phenomenon known as collective wisdom. Little is known about the neural basis of collective wisdom and whether its benefits arise in late decision stages or in early sensory coding. Here, we use electroencephalography and multi-brain computing with twenty humans making perceptual decisions to show that combining neural activity across brains increases decision accuracy paralleling the improvements shown by aggregating the observers' opinions. Although the largest gains result from an optimal linear combination of neural decision variables across brains, a simpler neural majority decision rule, ubiquitous in human behavior, results in substantial benefits. In contrast, an extreme neural response rule, akin to a group following the most extreme opinion, results in the least improvement with group size. Analyses controlling for number of electrodes and time-points while increasing number of brains demonstrate unique benefits arising from integrating neural activity across different brains. The benefits of multi-brain integration are present in neural activity as early as 200 ms after stimulus presentation in lateral occipital sites and no additional benefits arise in decision related neural activity. Sensory-related neural activity can predict collective choices reached by aggregating individual opinions, voting results, and decision confidence as accurately as neural activity related to decision components. Estimation of the potential for the collective to execute fast decisions by combining information across numerous brains, a strategy prevalent in many animals, shows large time-savings. Together, the findings suggest that for perceptual decisions the neural activity supporting collective wisdom and decisions arises in early sensory stages and that many properties of collective cognition are explainable by the neural coding of information across multiple brains. Finally, our methods highlight the potential of multi-brain computing as a technique to rapidly and in parallel gather increased information about the environment as well as to access collective perceptual/cognitive choices and mental states. Copyright © 2011 Elsevier Inc. All rights reserved.

2D and 3D Stem Cell Models of Primate Cortical Development Identify Species-Specific Differences in Progenitor Behavior Contributing to Brain Size.

PubMed

Otani, Tomoki; Marchetto, Maria C; Gage, Fred H; Simons, Benjamin D; Livesey, Frederick J

2016-04-07

Variation in cerebral cortex size and complexity is thought to contribute to differences in cognitive ability between humans and other animals. Here we compare cortical progenitor cell output in humans and three nonhuman primates using directed differentiation of pluripotent stem cells (PSCs) in adherent two-dimensional (2D) and organoid three-dimensional (3D) culture systems. Clonal lineage analysis showed that primate cortical progenitors proliferate for a protracted period of time, during which they generate early-born neurons, in contrast to rodents, where this expansion phase largely ceases before neurogenesis begins. The extent of this additional cortical progenitor expansion differs among primates, leading to differences in the number of neurons generated by each progenitor cell. We found that this mechanism for controlling cortical size is regulated cell autonomously in culture, suggesting that primate cerebral cortex size is regulated at least in part at the level of individual cortical progenitor cell clonal output. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Computed microtomography visualization and quantification of mouse ischemic brain lesion by nonionic radio contrast agents

PubMed Central

Dobrivojević, Marina; Bohaček, Ivan; Erjavec, Igor; Gorup, Dunja; Gajović, Srećko

2013-01-01

Aim To explore the possibility of brain imaging by microcomputed tomography (microCT) using x-ray contrasting methods to visualize mouse brain ischemic lesions after middle cerebral artery occlusion (MCAO). Methods Isolated brains were immersed in ionic or nonionic radio contrast agent (RCA) for 5 days and subsequently scanned using microCT scanner. To verify whether ex-vivo microCT brain images can be used to characterize ischemic lesions, they were compared to Nissl stained serial histological sections of the same brains. To verify if brains immersed in RCA may be used afterwards for other methods, subsequent immunofluorescent labeling with anti-NeuN was performed. Results Nonionic RCA showed better gray to white matter contrast in the brain, and therefore was selected for further studies. MicroCT measurement of ischemic lesion size and cerebral edema significantly correlated with the values determined by Nissl staining (ischemic lesion size: P=0.0005; cerebral edema: P=0.0002). Brain immersion in nonionic RCA did not affect subsequent immunofluorescent analysis and NeuN immunoreactivity. Conclusion MicroCT method was proven to be suitable for delineation of the ischemic lesion from the non-infarcted tissue, and quantification of lesion volume and cerebral edema. PMID:23444240

Computed microtomography visualization and quantification of mouse ischemic brain lesion by nonionic radio contrast agents.

PubMed

Dobrivojević, Marina; Bohaček, Ivan; Erjavec, Igor; Gorup, Dunja; Gajović, Srećko

2013-02-01

To explore the possibility of brain imaging by microcomputed tomography (microCT) using x-ray contrasting methods to visualize mouse brain ischemic lesions after middle cerebral artery occlusion (MCAO). Isolated brains were immersed in ionic or nonionic radio contrast agent (RCA) for 5 days and subsequently scanned using microCT scanner. To verify whether ex-vivo microCT brain images can be used to characterize ischemic lesions, they were compared to Nissl stained serial histological sections of the same brains. To verify if brains immersed in RCA may be used afterwards for other methods, subsequent immunofluorescent labeling with anti-NeuN was performed. Nonionic RCA showed better gray to white matter contrast in the brain, and therefore was selected for further studies. MicroCT measurement of ischemic lesion size and cerebral edema significantly correlated with the values determined by Nissl staining (ischemic lesion size: P=0.0005; cerebral edema: P=0.0002). Brain immersion in nonionic RCA did not affect subsequent immunofluorescent analysis and NeuN immunoreactivity. MicroCT method was proven to be suitable for delineation of the ischemic lesion from the non-infarcted tissue, and quantification of lesion volume and cerebral edema.

Brief Report: Abnormal Association between the Thalamus and Brain Size in Asperger's Disorder

ERIC Educational Resources Information Center

Hardan, Antonio Y.; Girgis, Ragy R.; Adams, Jason; Gilbert, Andrew R.; Melhem, Nadine M.; Keshavan, Matcheri S.; Minshew, Nancy J.

2008-01-01

The objective of this study was to examine the relationship between thalamic volume and brain size in individuals with Asperger's disorder (ASP). Volumetric measurements of the thalamus were performed on MRI scans obtained from 12 individuals with ASP (age range: 10-35 years) and 12 healthy controls (age range: 9-33 years). A positive correlation…

The Effect of Brain Based Learning on Academic Achievement: A Meta-Analytical Study

ERIC Educational Resources Information Center

Gozuyesil, Eda; Dikici, Ayhan

2014-01-01

This study's aim is to measure the effect sizes of the quantitative studies that examined the effectiveness of brain-based learning on students' academic achievement and to examine with the meta-analytical method if there is a significant difference in effect in terms of the factors of education level, subject matter, sampling size, and the…

Technologies for imaging neural activity in large volumes

PubMed Central

Ji, Na; Freeman, Jeremy; Smith, Spencer L.

2017-01-01

Neural circuitry has evolved to form distributed networks that act dynamically across large volumes. Collecting data from individual planes, conventional microscopy cannot sample circuitry across large volumes at the temporal resolution relevant to neural circuit function and behaviors. Here, we review emerging technologies for rapid volume imaging of neural circuitry. We focus on two critical challenges: the inertia of optical systems, which limits image speed, and aberrations, which restrict the image volume. Optical sampling time must be long enough to ensure high-fidelity measurements, but optimized sampling strategies and point spread function engineering can facilitate rapid volume imaging of neural activity within this constraint. We also discuss new computational strategies for the processing and analysis of volume imaging data of increasing size and complexity. Together, optical and computational advances are providing a broader view of neural circuit dynamics, and help elucidate how brain regions work in concert to support behavior. PMID:27571194

Robust Wireless Power Transmission to mm-Sized Free-Floating Distributed Implants.

PubMed

Mirbozorgi, S Abdollah; Yeon, Pyungwoo; Ghovanloo, Maysam

2017-06-01

This paper presents an inductive link for wireless power transmission (WPT) to mm-sized free-floating implants (FFIs) distributed in a large three-dimensional space in the neural tissue that is insensitive to the exact location of the receiver (Rx). The proposed structure utilizes a high-Q resonator on the target wirelessly powered plane that encompasses randomly positioned multiple FFIs, all powered by a large external transmitter (Tx). Based on resonant WPT fundamentals, we have devised a detailed method for optimization of the FFIs and explored design strategies and safety concerns, such as coil segmentation and specific absorption rate limits using realistic finite element simulation models in HFSS including head tissue layers, respectively. We have built several FFI prototypes to conduct accurate measurements and to characterize the performance of the proposed WPT method. Measurement results on 1-mm receivers operating at 60 MHz show power transfer efficiency and power delivered to the load at 2.4% and 1.3 mW, respectively, within 14-18 mm of Tx-Rx separation and 7 cm 2 of brain surface.

Co-Design Method and Wafer-Level Packaging Technique of Thin-Film Flexible Antenna and Silicon CMOS Rectifier Chips for Wireless-Powered Neural Interface Systems.

PubMed

Okabe, Kenji; Jeewan, Horagodage Prabhath; Yamagiwa, Shota; Kawano, Takeshi; Ishida, Makoto; Akita, Ippei

2015-12-16

In this paper, a co-design method and a wafer-level packaging technique of a flexible antenna and a CMOS rectifier chip for use in a small-sized implantable system on the brain surface are proposed. The proposed co-design method optimizes the system architecture, and can help avoid the use of external matching components, resulting in the realization of a small-size system. In addition, the technique employed to assemble a silicon large-scale integration (LSI) chip on the very thin parylene film (5 μm) enables the integration of the rectifier circuits and the flexible antenna (rectenna). In the demonstration of wireless power transmission (WPT), the fabricated flexible rectenna achieved a maximum efficiency of 0.497% with a distance of 3 cm between antennas. In addition, WPT with radio waves allows a misalignment of 185% against antenna size, implying that the misalignment has a less effect on the WPT characteristics compared with electromagnetic induction.

Co-Design Method and Wafer-Level Packaging Technique of Thin-Film Flexible Antenna and Silicon CMOS Rectifier Chips for Wireless-Powered Neural Interface Systems

PubMed Central

Okabe, Kenji; Jeewan, Horagodage Prabhath; Yamagiwa, Shota; Kawano, Takeshi; Ishida, Makoto; Akita, Ippei

2015-01-01

In this paper, a co-design method and a wafer-level packaging technique of a flexible antenna and a CMOS rectifier chip for use in a small-sized implantable system on the brain surface are proposed. The proposed co-design method optimizes the system architecture, and can help avoid the use of external matching components, resulting in the realization of a small-size system. In addition, the technique employed to assemble a silicon large-scale integration (LSI) chip on the very thin parylene film (5 μm) enables the integration of the rectifier circuits and the flexible antenna (rectenna). In the demonstration of wireless power transmission (WPT), the fabricated flexible rectenna achieved a maximum efficiency of 0.497% with a distance of 3 cm between antennas. In addition, WPT with radio waves allows a misalignment of 185% against antenna size, implying that the misalignment has a less effect on the WPT characteristics compared with electromagnetic induction. PMID:26694407

Insula and striatum activity in effort-related monetary reward processing in gambling disorder: the role of depressive symptomatology.

PubMed

Fauth-Bühler, Mira; Zois, Evangelos; Vollstädt-Klein, Sabine; Lemenager, Tagrid; Beutel, Martin; Mann, Karl

2014-01-01

The neurobiological underpinnings of effort-related monetary reward processing of gambling disorder have not been previously studied. To date neuroimaging studies lack in large sample sizes and as a consequence less attention has been given to brain reward processing that could potentially be attributed to comorbid conditions such as depressive mood state. We assessed monetary reward processing using an effort-dependent task during 3 tesla functional magnetic resonance imaging. We investigated a large sample of male, right-handed, slot-machine-playing disordered gamblers (DGs; N = 80) as well as age- and smoking-matched male healthy controls (HCs; N = 89). Depressive symptoms were assessed using the Beck Depression Inventory (BDI). DGs and HCs were divided into subgroups ("high" and "low") based on their BDI scores. Effort-related monetary reward processing did not differ between the complete groups of HCs and DGs. Brain activation during receipt of monetary reward though revealed a significant Group × BDI interaction: DGs with higher BDI scores compared to DGs with lower BDI scores showed greater brain activity in the right insula cortex and dorsal striatum while no differences were observed for HCs with higher versus lower BDI scores. Our results suggest that effort-related aspects of monetary motivation, i.e. when monetary output is tied to performance, are not altered in DG. Additionally, our findings strengthen the need for subgroup comparisons in future investigations of the disorder as part of a personalized medicine approach.

Dimorphism in the Size and Shape of the Birth Canal Across Anthropoid Primates.

PubMed

Moffett, Elizabeth A

2017-05-01

It has long been noted that the human female birth canal is well adapted to giving birth to large-brained neonates. However, several species of nonhuman primates give birth to large-headed neonates compared to the maternal birth canal. The presence of such large cephalopelvic proportions in nonhuman primates presents the question of whether dimorphism in the birth canals of these other species is related to obstetric demand, as such dimorphism is presumed to be in humans. In this study, the hypothesis that either the presence or magnitude of dimorphism in the birth canal is related to large cephalopelvic proportions among anthropoid primates is directly tested. This study shows that birth canal dimorphism is common among anthropoids regardless of cephalopelvic proportions, but taxa with large cephalopelvic proportions have a higher magnitude of dimorphism than those that give birth to relatively small-headed neonates. Furthermore, humans have exceptionally high levels of dimorphism that cannot be explained based on our large cephalopelvic proportions alone. Anat Rec, 300:870-889, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Island Rule, quantitative genetics and brain–body size evolution in Homo floresiensis

PubMed Central

2017-01-01

Colonization of islands often activate a complex chain of adaptive events that, over a relatively short evolutionary time, may drive strong shifts in body size, a pattern known as the Island Rule. It is arguably difficult to perform a direct analysis of the natural selection forces behind such a change in body size. Here, we used quantitative evolutionary genetic models, coupled with simulations and pattern-oriented modelling, to analyse the evolution of brain and body size in Homo floresiensis, a diminutive hominin species that appeared around 700 kya and survived up to relatively recent times (60–90 kya) on Flores Island, Indonesia. The hypothesis of neutral evolution was rejected in 97% of the simulations, and estimated selection gradients are within the range found in living natural populations. We showed that insularity may have triggered slightly different evolutionary trajectories for body and brain size, which means explaining the exceedingly small cranial volume of H. floresiensis requires additional selective forces acting on brain size alone. Our analyses also support previous conclusions that H. floresiensis may be most likely derived from an early Indonesian H. erectus, which is coherent with currently accepted biogeographical scenario for Homo expansion out of Africa. PMID:28637851

Unusual developmental pattern of brain lateralization in young boys with autism spectrum disorder: Power analysis with child-sized magnetoencephalography.

PubMed

Hiraishi, Hirotoshi; Kikuchi, Mitsuru; Yoshimura, Yuko; Kitagawa, Sachiko; Hasegawa, Chiaki; Munesue, Toshio; Takesaki, Natsumi; Ono, Yasuki; Takahashi, Tsutomu; Suzuki, Michio; Higashida, Haruhiro; Asada, Minoru; Minabe, Yoshio

2015-03-01

Autism spectrum disorder (ASD) is often described as comprising an unusual brain growth pattern and aberrant brain lateralization. Although it is important to study the pathophysiology of the developing ASD cortex, examples of physiological brain lateralization in young children with ASD have yet to be well examined. Thirty-eight boys with ASD (aged 3-7 years) and 38 typically developing (TD) boys (aged 3-8 years) concentrated on video programs and their brain activities were measured non-invasively. We employed a customized child-sized magnetoencephalography system in which the sensors were located as close to the brain as possible for optimal recording in young children. To produce a credible laterality index of the brain oscillations, we defined two clusters of sensors corresponding to the right and left hemispheres. We focused on the laterality index ([left - right]/[left+right]) of the relative power band in seven frequency bands. The TD group displayed significantly rightward lateralized brain oscillations in the theta-1 frequency bands compared to the ASD group. This is the first study to demonstrate unusual brain lateralization of brain oscillations measured by magnetoencephalography in young children with ASD. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

Supervised learning based multimodal MRI brain tumour segmentation using texture features from supervoxels.

PubMed

Soltaninejad, Mohammadreza; Yang, Guang; Lambrou, Tryphon; Allinson, Nigel; Jones, Timothy L; Barrick, Thomas R; Howe, Franklyn A; Ye, Xujiong

2018-04-01

Accurate segmentation of brain tumour in magnetic resonance images (MRI) is a difficult task due to various tumour types. Using information and features from multimodal MRI including structural MRI and isotropic (p) and anisotropic (q) components derived from the diffusion tensor imaging (DTI) may result in a more accurate analysis of brain images. We propose a novel 3D supervoxel based learning method for segmentation of tumour in multimodal MRI brain images (conventional MRI and DTI). Supervoxels are generated using the information across the multimodal MRI dataset. For each supervoxel, a variety of features including histograms of texton descriptor, calculated using a set of Gabor filters with different sizes and orientations, and first order intensity statistical features are extracted. Those features are fed into a random forests (RF) classifier to classify each supervoxel into tumour core, oedema or healthy brain tissue. The method is evaluated on two datasets: 1) Our clinical dataset: 11 multimodal images of patients and 2) BRATS 2013 clinical dataset: 30 multimodal images. For our clinical dataset, the average detection sensitivity of tumour (including tumour core and oedema) using multimodal MRI is 86% with balanced error rate (BER) 7%; while the Dice score for automatic tumour segmentation against ground truth is 0.84. The corresponding results of the BRATS 2013 dataset are 96%, 2% and 0.89, respectively. The method demonstrates promising results in the segmentation of brain tumour. Adding features from multimodal MRI images can largely increase the segmentation accuracy. The method provides a close match to expert delineation across all tumour grades, leading to a faster and more reproducible method of brain tumour detection and delineation to aid patient management. Copyright © 2018 Elsevier B.V. All rights reserved.

Local and long-range endogenous resting potential gradients antagonistically regulate apoptosis and proliferation in the embryonic CNS.

PubMed

Pai, Vaibhav P; Lemire, Joan M; Chen, Ying; Lin, Gufa; Levin, Michael

2015-01-01

Bioelectric signals, particularly transmembrane voltage potentials (Vmem), play an important role in large-scale patterning during embryonic development. Endogenous bioelectric gradients across tissues function as instructive factors during eye, brain, and other morphogenetic processes. An important and still poorly-understood aspect is the control of cell behaviors by the voltage states of distant cell groups. Here, experimental alteration of endogenous Vmem was induced in Xenopus laevis embryos by misexpression of well-characterized ion channel mRNAs, a strategy often used to identify functional roles of Vmem gradients during embryonic development and regeneration. Immunofluorescence analysis (for activated caspase 3 and phosphor-histone H3P) on embryonic sections was used to characterize apoptosis and proliferation. Disrupting local bioelectric signals (within the developing neural tube region) increased caspase 3 and decreased H3P in the brain, resulting in brain mispatterning. Disrupting remote (ventral, non-neural region) bioelectric signals decreased caspase 3 and highly increased H3P within the brain, with normal brain patterning. Disrupting both the local and distant bioelectric signals produced antagonistic effects on caspase 3 and H3P. Thus, two components of bioelectric signals regulate apoptosis-proliferation balance within the developing brain and spinal cord: local (developing neural tube region) and distant (ventral non-neural region). Together, the local and long-range bioelectric signals create a binary control system capable of fine-tuning apoptosis and proliferation with the brain and spinal cord to achieve correct pattern and size control. Our data suggest a roadmap for utilizing bioelectric state as a diagnostic modality and convenient intervention parameter for birth defects and degenerative disease states of the CNS.

A designed recombinant fusion protein for targeted delivery of siRNA to the mouse brain.

PubMed

Haroon, Mohamed Mohamed; Dar, Ghulam Hassan; Jeyalakshmi, Durga; Venkatraman, Uthra; Saba, Kamal; Rangaraj, Nandini; Patel, Anant Bahadur; Gopal, Vijaya

2016-04-28

RNA interference represents a novel therapeutic approach to modulate several neurodegenerative disease-related genes. However, exogenous delivery of siRNA restricts their transport into different tissues and specifically into the brain mainly due to its large size and the presence of the blood-brain barrier (BBB). To overcome these challenges, we developed here a strategy wherein a peptide known to target specific gangliosides was fused to a double-stranded RNA binding protein to deliver siRNA to the brain parenchyma. The designed fusion protein designated as TARBP-BTP consists of a double-stranded RNA-binding domain (dsRBD) of human Trans Activation response element (TAR) RNA Binding Protein (TARBP2) fused to a brain targeting peptide that binds to monosialoganglioside GM1. Conformation-specific binding of TARBP2 domain to siRNA led to the formation of homogenous serum-stable complex with targeting potential. Further, uptake of the complex in Neuro-2a, IMR32 and HepG2 cells analyzed by confocal microscopy and fluorescence activated cell sorting, revealed selective requirement of GM1 for entry. Remarkably, systemic delivery of the fluorescently labeled complex (TARBP-BTP:siRNA) in ΑβPP-PS1 mouse model of Alzheimer's disease (AD) led to distinctive localization in the cerebral hemisphere. Further, the delivery of siRNA mediated by TARBP-BTP led to significant knockdown of BACE1 in the brain, in both ΑβPP-PS1 mice and wild type C57BL/6. The study establishes the growing importance of fusion proteins in delivering therapeutic siRNA to brain tissues. Copyright © 2016 Elsevier B.V. All rights reserved.

Mind-Matter Interactions and the Frontal Lobes of the Brain: A Novel Neurobiological Model of Psi Inhibition.

PubMed

Freedman, Morris; Binns, Malcolm; Gao, Fuqiang; Holmes, Melissa; Roseborough, Austyn; Strother, Stephen; Vallesi, Antonino; Jeffers, Stanley; Alain, Claude; Whitehouse, Peter; Ryan, Jennifer D; Chen, Robert; Cusimano, Michael D; Black, Sandra E

Despite a large literature on psi, which encompasses a range of experiences including putative telepathy (mind-mind connections), clairvoyance (perceiving distant objects or events), precognition (perceiving future events), and mind-matter interactions, there has been insufficient focus on the brain in relation to this controversial phenomenon. In contrast, our research is based on a novel neurobiological model suggesting that frontal brain systems act as a filter to inhibit psi and that the inhibitory mechanisms may relate to self-awareness. To identify frontal brain regions that may inhibit psi. We used mind-matter interactions to study psi in two participants with frontal lobe damage. The experimental task was to influence numerical output of a Random Event Generator translated into movement of an arrow on a computer screen to the right or left. Brain MRI was analyzed to determine frontal volume loss. The primary area of lesion overlap between the participants was in the left medial middle frontal region, an area related to self-awareness, and involved Brodmann areas 9, 10, and 32. Both participants showed a significant effect in moving the arrow to the right, i.e., contralateral to the side of primary lesion overlap. Effect sizes were much larger compared to normal participants. The medial frontal lobes may act as a biological filter to inhibit psi through mechanisms related to self-awareness. Neurobiological studies with a focus on the brain may open new avenues of research on psi and may significantly advance the state of this poorly understood field. Copyright © 2018 Elsevier Inc. All rights reserved.

Brain shape in human microcephalics and Homo floresiensis.

PubMed

Falk, Dean; Hildebolt, Charles; Smith, Kirk; Morwood, M J; Sutikna, Thomas; Jatmiko; Saptomo, E Wayhu; Imhof, Herwig; Seidler, Horst; Prior, Fred

2007-02-13

Because the cranial capacity of LB1 (Homo floresiensis) is only 417 cm(3), some workers propose that it represents a microcephalic Homo sapiens rather than a new species. This hypothesis is difficult to assess, however, without a clear understanding of how brain shape of microcephalics compares with that of normal humans. We compare three-dimensional computed tomographic reconstructions of the internal braincases (virtual endocasts that reproduce details of external brain morphology, including cranial capacities and shape) from a sample of 9 microcephalic humans and 10 normal humans. Discriminant and canonical analyses are used to identify two variables that classify normal and microcephalic humans with 100% success. The classification functions classify the virtual endocast from LB1 with normal humans rather than microcephalics. On the other hand, our classification functions classify a pathological H. sapiens specimen that, like LB1, represents an approximately 3-foot-tall adult female and an adult Basuto microcephalic woman that is alleged to have an endocast similar to LB1's with the microcephalic humans. Although microcephaly is genetically and clinically variable, virtual endocasts from our highly heterogeneous sample share similarities in protruding and proportionately large cerebella and relatively narrow, flattened orbital surfaces compared with normal humans. These findings have relevance for hypotheses regarding the genetic substrates of hominin brain evolution and may have medical diagnostic value. Despite LB1's having brain shape features that sort it with normal humans rather than microcephalics, other shape features and its small brain size are consistent with its assignment to a separate species.

Selective targeting of a TNFR decoy receptor pharmaceutical to the primate brain as a receptor-specific IgG fusion protein.

PubMed

Boado, Ruben J; Hui, Eric Ka-Wai; Lu, Jeff Zhiqiang; Zhou, Qing-Hui; Pardridge, William M

2010-03-01

Decoy receptors, such as the human tumor necrosis factor receptor (TNFR), are potential new therapies for brain disorders. However, decoy receptors are large molecule drugs that are not transported across the blood-brain barrier (BBB). To enable BBB transport of a TNFR decoy receptor, the human TNFR-II extracellular domain was re-engineered as a fusion protein with a chimeric monoclonal antibody (MAb) against the human insulin receptor (HIR). The HIRMAb acts as a molecular Trojan horse to ferry the TNFR therapeutic decoy receptor across the BBB. The HIRMAb-TNFR fusion protein was expressed in stably transfected CHO cells, and was analyzed with electrophoresis, Western blotting, size exclusion chromatography, and binding assays for the HIR and TNFalpha. The HIRMAb-TNFR fusion protein was radio-labeled by trititation, in parallel with the radio-iodination of recombinant TNFR:Fc fusion protein, and the proteins were co-injected in the adult Rhesus monkey. The TNFR:Fc fusion protein did not cross the primate BBB in vivo, but the uptake of the HIRMAb-TNFR fusion protein was high and 3% of the injected dose was taken up by the primate brain. The TNFR was selectively targeted to brain, relative to peripheral organs, following fusion to the HIRMAb. This study demonstrates that decoy receptors may be re-engineered as IgG fusion proteins with a BBB molecular Trojan horse that selectively targets the brain, and enables penetration of the BBB in vivo. IgG-decoy receptor fusion proteins represent a new class of human neurotherapeutics. Copyright 2010 Elsevier B.V. All rights reserved.

Not all sharks are "swimming noses": variation in olfactory bulb size in cartilaginous fishes.

PubMed

Yopak, Kara E; Lisney, Thomas J; Collin, Shaun P

2015-03-01

Olfaction is a universal modality by which all animals sample chemical stimuli from their environment. In cartilaginous fishes, olfaction is critical for various survival tasks including localizing prey, avoiding predators, and chemosensory communication with conspecifics. Little is known, however, about interspecific variation in olfactory capability in these fishes, or whether the relative importance of olfaction in relation to other sensory systems varies with regard to ecological factors, such as habitat and lifestyle. In this study, we have addressed these questions by directly examining interspecific variation in the size of the olfactory bulbs (OB), the region of the brain that receives the primary sensory projections from the olfactory nerve, in 58 species of cartilaginous fishes. Relative OB size was compared among species occupying different ecological niches. Our results show that the OBs maintain a substantial level of allometric independence from the rest of the brain across cartilaginous fishes and that OB size is highly variable among species. These findings are supported by phylogenetic generalized least-squares models, which show that this variability is correlated with ecological niche, particularly habitat. The relatively largest OBs were found in pelagic-coastal/oceanic sharks, especially migratory species such as Carcharodon carcharias and Galeocerdo cuvier. Deep-sea species also possess large OBs, suggesting a greater reliance on olfaction in habitats where vision may be compromised. In contrast, the smallest OBs were found in the majority of reef-associated species, including sharks from the families Carcharhinidae and Hemiscyllidae and dasyatid batoids. These results suggest that there is great variability in the degree to which these fishes rely on olfactory cues. The OBs have been widely used as a neuroanatomical proxy for olfactory capability in vertebrates, and we speculate that differences in olfactory capabilities may be the result of functional rather than phylogenetic adaptations.

How number line estimation skills relate to neural activations in single digit subtraction problems

PubMed Central

Berteletti, I.; Man, G.; Booth, J.R.

2014-01-01

The Number Line (NL) task requires judging the relative numerical magnitude of a number and estimating its value spatially on a continuous line. Children's skill on this task has been shown to correlate with and predict future mathematical competence. Neurofunctionally, this task has been shown to rely on brain regions involved in numerical processing. However, there is no direct evidence that performance on the NL task is related to brain areas recruited during arithmetical processing and that these areas are domain-specific to numerical processing. In this study, we test whether 8- to 14-year-old's behavioral performance on the NL task is related to fMRI activation during small and large single-digit subtraction problems. Domain-specific areas for numerical processing were independently localized through a numerosity judgment task. Results show a direct relation between NL estimation performance and the amount of the activation in key areas for arithmetical processing. Better NL estimators showed a larger problem size effect than poorer NL estimators in numerical magnitude (i.e., intraparietal sulcus) and visuospatial areas (i.e., posterior superior parietal lobules), marked by less activation for small problems. In addition, the direction of the activation with problem size within the IPS was associated to differences in accuracies for small subtraction problems. This study is the first to show that performance in the NL task, i.e. estimating the spatial position of a number on an interval, correlates with brain activity observed during single-digit subtraction problem in regions thought to be involved numerical magnitude and spatial processes. PMID:25497398

Measuring and Validating the Levels of Brain-Derived Neurotrophic Factor in Human Serum

PubMed Central

Naegelin, Yvonne; Dingsdale, Hayley; Säuberli, Katharina; Schädelin, Sabine; Kappos, Ludwig

2018-01-01

Brain-derived neurotrophic factor (BDNF) secreted by neurons is a significant component of synaptic plasticity. In humans, it is also present in blood platelets where it accumulates following its biosynthesis in megakaryocytes. BDNF levels are thus readily detectable in human serum and it has been abundantly speculated that they may somehow serve as an indicator of brain function. However, there is a great deal of uncertainty with regard to the range of BDNF levels that can be considered normal, how stable these values are over time and even whether BDNF levels can be reliably measured in serum. Using monoclonal antibodies and a sandwich ELISA, this study reports on BDNF levels in the serum of 259 volunteers with a mean value of 32.69 ± 8.33 ng/ml (SD). The mean value for the same cohort after 12 months was not significantly different (N = 226, 32.97 ± 8.36 ng/ml SD, p = 0.19). Power analysis of these values indicates that relatively large cohorts are necessary to identify significant differences, requiring a group size of 60 to detect a 20% change. The levels determined by ELISA could be validated by Western blot analyses using a BDNF monoclonal antibody. While no association was observed with gender, a weak, positive correlation was found with age. The overall conclusions are that BDNF levels can be reliably measured in human serum, that these levels are quite stable over one year, and that comparisons between two populations may only be meaningful if cohorts of sufficient sizes are assembled. PMID:29662942

The Molecular Basis of Human Brain Evolution.

PubMed

Enard, Wolfgang

2016-10-24

Humans are a remarkable species, especially because of the remarkable properties of their brain. Since the split from the chimpanzee lineage, the human brain has increased three-fold in size and has acquired abilities for vocal learning, language and intense cooperation. To better understand the molecular basis of these changes is of great biological and biomedical interest. However, all the about 16 million fixed genetic changes that occurred during human evolution are fully correlated with all molecular, cellular, anatomical and behavioral changes that occurred during this time. Hence, as humans and chimpanzees cannot be crossed or genetically manipulated, no direct evidence for linking particular genetic and molecular changes to human brain evolution can be obtained. Here, I sketch a framework how indirect evidence can be obtained and review findings related to the molecular basis of human cognition, vocal learning and brain size. In particular, I discuss how a comprehensive comparative approach, leveraging cellular systems and genomic technologies, could inform the evolution of our brain in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Fast Method for the Segmentation of Synaptic Junctions and Mitochondria in Serial Electron Microscopic Images of the Brain.

PubMed

Márquez Neila, Pablo; Baumela, Luis; González-Soriano, Juncal; Rodríguez, Jose-Rodrigo; DeFelipe, Javier; Merchán-Pérez, Ángel

2016-04-01

Recent electron microscopy (EM) imaging techniques permit the automatic acquisition of a large number of serial sections from brain samples. Manual segmentation of these images is tedious, time-consuming and requires a high degree of user expertise. Therefore, there is considerable interest in developing automatic segmentation methods. However, currently available methods are computationally demanding in terms of computer time and memory usage, and to work properly many of them require image stacks to be isotropic, that is, voxels must have the same size in the X, Y and Z axes. We present a method that works with anisotropic voxels and that is computationally efficient allowing the segmentation of large image stacks. Our approach involves anisotropy-aware regularization via conditional random field inference and surface smoothing techniques to improve the segmentation and visualization. We have focused on the segmentation of mitochondria and synaptic junctions in EM stacks from the cerebral cortex, and have compared the results to those obtained by other methods. Our method is faster than other methods with similar segmentation results. Our image regularization procedure introduces high-level knowledge about the structure of labels. We have also reduced memory requirements with the introduction of energy optimization in overlapping partitions, which permits the regularization of very large image stacks. Finally, the surface smoothing step improves the appearance of three-dimensional renderings of the segmented volumes.

Multiscale CNNs for Brain Tumor Segmentation and Diagnosis.

PubMed

Zhao, Liya; Jia, Kebin

2016-01-01

Early brain tumor detection and diagnosis are critical to clinics. Thus segmentation of focused tumor area needs to be accurate, efficient, and robust. In this paper, we propose an automatic brain tumor segmentation method based on Convolutional Neural Networks (CNNs). Traditional CNNs focus only on local features and ignore global region features, which are both important for pixel classification and recognition. Besides, brain tumor can appear in any place of the brain and be any size and shape in patients. We design a three-stream framework named as multiscale CNNs which could automatically detect the optimum top-three scales of the image sizes and combine information from different scales of the regions around that pixel. Datasets provided by Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized by MICCAI 2013 are utilized for both training and testing. The designed multiscale CNNs framework also combines multimodal features from T1, T1-enhanced, T2, and FLAIR MRI images. By comparison with traditional CNNs and the best two methods in BRATS 2012 and 2013, our framework shows advances in brain tumor segmentation accuracy and robustness.

Opening of the blood-brain barrier with an unfocused ultrasound device in rabbits.

PubMed

Beccaria, Kevin; Canney, Michael; Goldwirt, Lauriane; Fernandez, Christine; Adam, Clovis; Piquet, Julie; Autret, Gwennhael; Clément, Olivier; Lafon, Cyril; Chapelon, Jean-Yves; Carpentier, Alexandre

2013-10-01

The blood-brain barrier (BBB) is a major impediment to the intracerebral diffusion of drugs used in the treatment of gliomas. Previous studies have demonstrated that pulsed focused ultrasound (US) in conjunction with a microbubble contrast agent can be used to open the BBB. To apply the US-induced opening of the BBB in clinical practice, the authors designed an innovative unfocused US device that can be implanted in the skull and used to transiently and repeatedly open the BBB during a standard chemotherapy protocol. The goal of this preliminary work was to study the opening of the BBB induced by the authors' small unfocused US transducer and to evaluate the effects of the sonications on brain parenchyma. Craniectomy was performed in 16 healthy New Zealand White rabbits; epidural application of a single-element planar ultrasonic transducer operating at 1 MHz was then used with a pulse-repetition frequency of 1 Hz, pulse lengths of 10-35 msec, in situ acoustic pressure levels of 0.3-0.8 MPa, and sonication for 60-120 seconds. SonoVue was intravenously injected during the US applications, and opening of the BBB was determined by detecting extravasation of Evans blue dye (EBD) in brain tissues, quantitative measurement of EBD with UV-visible spectrophotometry, and contrast enhancement after Gd injection in 4.7-T MRI. A histological study was performed to determine adverse effects. An opening of the BBB was observed over a large extent of the US beam in the brain corresponding to in situ pressures of greater than 0.2 MPa. The BBB opening observed was highly significant for both EBD (p < 0.01) and MRI Gd enhancement (p < 0.0001). The BBB opening was associated with minor adverse effects that included perivascular red blood cell extravasations that were less than 150 μm in size and not visible on MR images. Moderate edema was visible on FLAIR sequences and limited to the extent of the sonication field. The results demonstrate that the BBB can be opened in large areas of the brain in rabbits with low-power, pulsed, and unfocused US with limited damage to healthy tissue.

Voxelwise distribution of acute ischemic stroke lesions in patients with newly diagnosed atrial fibrillation: Trigger of arrhythmia or only target of embolism?

PubMed Central

Johnson, Timothy D.; Dittgen, Felix; Nichols, Thomas E.; Malzahn, Uwe; Veltkamp, Roland

2017-01-01

Objective Atrial fibrillation (AF) is frequently detected after ischemic stroke for the first time, and brain regions involved in autonomic control have been suspected to trigger AF. We examined whether specific brain regions are associated with newly detected AF after ischemic stroke. Methods Patients with acute cerebral infarctions on diffusion-weighted magnetic resonance imaging were included in this lesion mapping study. Lesions were mapped and modeled voxelwise using Bayesian Spatial Generalised Linear Mixed Modeling to determine differences in infarct locations between stroke patients with new AF, without AF and with AF already known before the stroke. Results 582 patients were included (median age 68 years; 63.2% male). AF was present in 109/582 patients [(18.7%); new AF: 39/109 (35.8%), known AF: 70/109 (64.2%)]. AF patients had larger infarct volumes than patients without AF (mean: 29.7 ± 45.8 ml vs. 15.2 ± 35.1 ml; p<0.001). Lesions in AF patients accumulated in the right central middle cerebral artery territory. Increasing stroke size predicted progressive cortical but not pontine and thalamic involvement. Patients with new AF had more frequently lesions in the right insula compared to patients without AF when stroke size was not accounted for, but no specific brain region was more frequently involved after adjustment for infarct volume. Controlled for stroke size, left parietal involvement was less likely for patients with new AF than for those without AF or with known AF. Conclusions In the search for brain areas potentially triggering cardiac arrhythmias infarct size should be accounted for. After controlling for infarct size, there is currently no evidence that ischemic stroke lesions of specific brain areas are associated with new AF compared to patients without AF. This challenges the neurogenic hypothesis of AF according to which a relevant proportion of new AF is triggered by ischemic brain lesions of particular locations. PMID:28542605

An analytical model for the calculation of the change in transmembrane potential produced by an ultrawideband electromagnetic pulse.

PubMed

Hart, Francis X; Easterly, Clay E

2004-05-01

The electric field pulse shape and change in transmembrane potential produced at various points within a sphere by an intense, ultrawideband pulse are calculated in a four stage, analytical procedure. Spheres of two sizes are used to represent the head of a human and the head of a rat. In the first stage, the pulse is decomposed into its Fourier components. In the second stage, Mie scattering analysis (MSA) is performed for a particular point in the sphere on each of the Fourier components, and the resulting electric field pulse shape is obtained for that point. In the third stage, the long wavelength approximation (LWA) is used to obtain the change in transmembrane potential in a cell at that point. In the final stage, an energy analysis is performed. These calculations are performed at 45 points within each sphere. Large electric fields and transmembrane potential changes on the order of a millivolt are produced within the brain, but on a time scale on the order of nanoseconds. The pulse shape within the brain differs considerably from that of the incident pulse. Comparison of the results for spheres of different sizes indicates that scaling of such pulses across species is complicated. Published 2004 Wiley-Liss, Inc.

The social brain: scale-invariant layering of Erdős-Rényi networks in small-scale human societies.

PubMed

Harré, Michael S; Prokopenko, Mikhail

2016-05-01

The cognitive ability to form social links that can bind individuals together into large cooperative groups for safety and resource sharing was a key development in human evolutionary and social history. The 'social brain hypothesis' argues that the size of these social groups is based on a neurologically constrained capacity for maintaining long-term stable relationships. No model to date has been able to combine a specific socio-cognitive mechanism with the discrete scale invariance observed in ethnographic studies. We show that these properties result in nested layers of self-organizing Erdős-Rényi networks formed by each individual's ability to maintain only a small number of social links. Each set of links plays a specific role in the formation of different social groups. The scale invariance in our model is distinct from previous 'scale-free networks' studied using much larger social groups; here, the scale invariance is in the relationship between group sizes, rather than in the link degree distribution. We also compare our model with a dominance-based hierarchy and conclude that humans were probably egalitarian in hunter-gatherer-like societies, maintaining an average maximum of four or five social links connecting all members in a largest social network of around 132 people. © 2016 The Author(s).

Brain size, innovative propensity and migratory behaviour in temperate Palaearctic birds

PubMed Central

Sol, Daniel; Lefebvre, Louis; Rodríguez-Teijeiro, J. Domingo

2005-01-01

The evolution of migration in birds remains an outstanding, unresolved question in evolutionary ecology. A particularly intriguing question is why individuals in some species have been selected to migrate, whereas in other species they have been selected to be sedentary. In this paper, we suggest that this diverging selection might partially result from differences among species in the behavioural flexibility of their responses to seasonal changes in the environment. This hypothesis is supported in a comparative analysis of Palaearctic passerines. First, resident species tend to rely more on innovative feeding behaviours in winter, when food is harder to find, than in other seasons. Second, species with larger brains, relative to their body size, and a higher propensity for innovative behaviours tend to be resident, while less flexible species tend to be migratory. Residence also appears to be less likely in species that occur in more northerly regions, exploit temporally available food sources, inhabit non-buffered habitats and have smaller bodies. Yet, the role of behavioural flexibility as a response to seasonal environments is largely independent of these other factors. Therefore, species with greater foraging flexibility seem to be able to cope with seasonal environments better, while less flexible species are forced to become migratory. PMID:16011917

3D variational brain tumor segmentation on a clustered feature set

NASA Astrophysics Data System (ADS)

Popuri, Karteek; Cobzas, Dana; Jagersand, Martin; Shah, Sirish L.; Murtha, Albert

2009-02-01

Tumor segmentation from MRI data is a particularly challenging and time consuming task. Tumors have a large diversity in shape and appearance with intensities overlapping the normal brain tissues. In addition, an expanding tumor can also deflect and deform nearby tissue. Our work addresses these last two difficult problems. We use the available MRI modalities (T1, T1c, T2) and their texture characteristics to construct a multi-dimensional feature set. Further, we extract clusters which provide a compact representation of the essential information in these features. The main idea in this paper is to incorporate these clustered features into the 3D variational segmentation framework. In contrast to the previous variational approaches, we propose a segmentation method that evolves the contour in a supervised fashion. The segmentation boundary is driven by the learned inside and outside region voxel probabilities in the cluster space. We incorporate prior knowledge about the normal brain tissue appearance, during the estimation of these region statistics. In particular, we use a Dirichlet prior that discourages the clusters in the ventricles to be in the tumor and hence better disambiguate the tumor from brain tissue. We show the performance of our method on real MRI scans. The experimental dataset includes MRI scans, from patients with difficult instances, with tumors that are inhomogeneous in appearance, small in size and in proximity to the major structures in the brain. Our method shows good results on these test cases.

Seeing the whole picture: A comprehensive imaging approach to functional mapping of circuits in behaving zebrafish.

PubMed

Feierstein, C E; Portugues, R; Orger, M B

2015-06-18

In recent years, the zebrafish has emerged as an appealing model system to tackle questions relating to the neural circuit basis of behavior. This can be attributed not just to the growing use of genetically tractable model organisms, but also in large part to the rapid advances in optical techniques for neuroscience, which are ideally suited for application to the small, transparent brain of the larval fish. Many characteristic features of vertebrate brains, from gross anatomy down to particular circuit motifs and cell-types, as well as conserved behaviors, can be found in zebrafish even just a few days post fertilization, and, at this early stage, the physical size of the brain makes it possible to analyze neural activity in a comprehensive fashion. In a recent study, we used a systematic and unbiased imaging method to record the pattern of activity dynamics throughout the whole brain of larval zebrafish during a simple visual behavior, the optokinetic response (OKR). This approach revealed the broadly distributed network of neurons that were active during the behavior and provided insights into the fine-scale functional architecture in the brain, inter-individual variability, and the spatial distribution of behaviorally relevant signals. Combined with mapping anatomical and functional connectivity, targeted electrophysiological recordings, and genetic labeling of specific populations, this comprehensive approach in zebrafish provides an unparalleled opportunity to study complete circuits in a behaving vertebrate animal. Copyright © 2014. Published by Elsevier Ltd.

Dynamics of scene representations in the human brain revealed by magnetoencephalography and deep neural networks

PubMed Central

Cichy, Radoslaw Martin; Khosla, Aditya; Pantazis, Dimitrios; Oliva, Aude

2017-01-01

Human scene recognition is a rapid multistep process evolving over time from single scene image to spatial layout processing. We used multivariate pattern analyses on magnetoencephalography (MEG) data to unravel the time course of this cortical process. Following an early signal for lower-level visual analysis of single scenes at ~100 ms, we found a marker of real-world scene size, i.e. spatial layout processing, at ~250 ms indexing neural representations robust to changes in unrelated scene properties and viewing conditions. For a quantitative model of how scene size representations may arise in the brain, we compared MEG data to a deep neural network model trained on scene classification. Representations of scene size emerged intrinsically in the model, and resolved emerging neural scene size representation. Together our data provide a first description of an electrophysiological signal for layout processing in humans, and suggest that deep neural networks are a promising framework to investigate how spatial layout representations emerge in the human brain. PMID:27039703

Does encephalization correlate with life history or metabolic rate in Carnivora?

PubMed

Finarelli, John A

2010-06-23

A recent analysis of brain size evolution reconstructed the plesiomorphic brain-body size allometry for the mammalian order Carnivora, providing an important reference frame for comparative analyses of encephalization (brain volume scaled to body mass). I performed phylogenetically corrected regressions to remove the effects of body mass, calculating correlations between residual values of encephalization with basal metabolic rate (BMR) and six life-history variables (gestation time, neonatal mass, weaning time, weaning mass, litter size, litters per year). No significant correlations were recovered between encephalization and any life-history variable or BMR, arguing against hypotheses relating encephalization to maternal energetic investment. However, after correcting for clade-specific adaptations, I recovered significant correlations for several variables, and further analysis revealed a conserved carnivoran reproductive strategy, linking degree of encephalization to the well-documented mammalian life-history trade-off between neonatal mass and litter size. This strategy of fewer, larger offspring correlating with increased encephalization remains intact even after independent changes in encephalization allometries in the evolutionary history of this clade.

SAFETY/TOXICITY ASSESSMENT OF CERIA (A MODEL ENGINEERED NP) TO THE BRAIN

EPA Science Inventory

The results will indicate the influence of the size, shape and various surface chemistry properties of ENMs on their entrance into BBB cells and the brain, compared to selected peripheral organs, the effects they produce in the brain, their biopersistence and biotransformation...

Surfactants, not size or zeta-potential influence blood-brain barrier passage of polymeric nanoparticles.

PubMed

Voigt, Nadine; Henrich-Noack, Petra; Kockentiedt, Sarah; Hintz, Werner; Tomas, Jürgen; Sabel, Bernhard A

2014-05-01

Nanoparticles (NP) can deliver drugs across the blood-brain barrier (BBB), but little is known which of the factors surfactant, size and zeta-potential are essential for allowing BBB passage. To this end we designed purpose-built fluorescent polybutylcyanoacrylate (PBCA) NP and imaged the NP's passage over the blood-retina barrier - which is a model of the BBB - in live animals. Rats received intravenous injections of fluorescent PBCA-NP fabricated by mini-emulsion polymerisation to obtain various NP's compositions that varied in surfactants (non-ionic, anionic, cationic), size (67-464nm) and zeta-potential. Real-time imaging of retinal blood vessels and retinal tissue was carried out with in vivo confocal neuroimaging (ICON) before, during and after NP's injection. Successful BBB passage with subsequent cellular labelling was achieved if NP were fabricated with non-ionic surfactants or cationic stabilizers but not when anionic compounds were added. NP's size and charge had no influence on BBB passage and cell labelling. This transport was not caused by an unspecific opening of the BBB because control experiments with injections of unlabelled NP and fluorescent dye (to test a "door-opener" effect) did not lead to parenchymal labelling. Thus, neither NP's size nor chemo-electric charge, but particle surface is the key factor determining BBB passage. This result has important implications for NP engineering in medicine: depending on the surfactant, NP can serve one of two opposite functions: while non-ionic tensides enhance brain up-take, addition of anionic tensides prevents it. NP can now be designed to specifically enhance drug delivery to the brain or, alternatively, to prevent brain penetration so to reduce unwanted psychoactive effects of drugs or prevent environmental nanoparticles from entering tissue of the central nervous system. Copyright © 2014 Elsevier B.V. All rights reserved.

Cluster-level statistical inference in fMRI datasets: The unexpected behavior of random fields in high dimensions.

PubMed

Bansal, Ravi; Peterson, Bradley S

2018-06-01

Identifying regional effects of interest in MRI datasets usually entails testing a priori hypotheses across many thousands of brain voxels, requiring control for false positive findings in these multiple hypotheses testing. Recent studies have suggested that parametric statistical methods may have incorrectly modeled functional MRI data, thereby leading to higher false positive rates than their nominal rates. Nonparametric methods for statistical inference when conducting multiple statistical tests, in contrast, are thought to produce false positives at the nominal rate, which has thus led to the suggestion that previously reported studies should reanalyze their fMRI data using nonparametric tools. To understand better why parametric methods may yield excessive false positives, we assessed their performance when applied both to simulated datasets of 1D, 2D, and 3D Gaussian Random Fields (GRFs) and to 710 real-world, resting-state fMRI datasets. We showed that both the simulated 2D and 3D GRFs and the real-world data contain a small percentage (<6%) of very large clusters (on average 60 times larger than the average cluster size), which were not present in 1D GRFs. These unexpectedly large clusters were deemed statistically significant using parametric methods, leading to empirical familywise error rates (FWERs) as high as 65%: the high empirical FWERs were not a consequence of parametric methods failing to model spatial smoothness accurately, but rather of these very large clusters that are inherently present in smooth, high-dimensional random fields. In fact, when discounting these very large clusters, the empirical FWER for parametric methods was 3.24%. Furthermore, even an empirical FWER of 65% would yield on average less than one of those very large clusters in each brain-wide analysis. Nonparametric methods, in contrast, estimated distributions from those large clusters, and therefore, by construct rejected the large clusters as false positives at the nominal FWERs. Those rejected clusters were outlying values in the distribution of cluster size but cannot be distinguished from true positive findings without further analyses, including assessing whether fMRI signal in those regions correlates with other clinical, behavioral, or cognitive measures. Rejecting the large clusters, however, significantly reduced the statistical power of nonparametric methods in detecting true findings compared with parametric methods, which would have detected most true findings that are essential for making valid biological inferences in MRI data. Parametric analyses, in contrast, detected most true findings while generating relatively few false positives: on average, less than one of those very large clusters would be deemed a true finding in each brain-wide analysis. We therefore recommend the continued use of parametric methods that model nonstationary smoothness for cluster-level, familywise control of false positives, particularly when using a Cluster Defining Threshold of 2.5 or higher, and subsequently assessing rigorously the biological plausibility of the findings, even for large clusters. Finally, because nonparametric methods yielded a large reduction in statistical power to detect true positive findings, we conclude that the modest reduction in false positive findings that nonparametric analyses afford does not warrant a re-analysis of previously published fMRI studies using nonparametric techniques. Copyright © 2018 Elsevier Inc. All rights reserved.

Inter-subject FDG PET Brain Networks Exhibit Multi-scale Community Structure with Different Normalization Techniques.

PubMed

Sperry, Megan M; Kartha, Sonia; Granquist, Eric J; Winkelstein, Beth A

2018-07-01

Inter-subject networks are used to model correlations between brain regions and are particularly useful for metabolic imaging techniques, like 18F-2-deoxy-2-(18F)fluoro-D-glucose (FDG) positron emission tomography (PET). Since FDG PET typically produces a single image, correlations cannot be calculated over time. Little focus has been placed on the basic properties of inter-subject networks and if they are affected by group size and image normalization. FDG PET images were acquired from rats (n = 18), normalized by whole brain, visual cortex, or cerebellar FDG uptake, and used to construct correlation matrices. Group size effects on network stability were investigated by systematically adding rats and evaluating local network connectivity (node strength and clustering coefficient). Modularity and community structure were also evaluated in the differently normalized networks to assess meso-scale network relationships. Local network properties are stable regardless of normalization region for groups of at least 10. Whole brain-normalized networks are more modular than visual cortex- or cerebellum-normalized network (p < 0.00001); however, community structure is similar at network resolutions where modularity differs most between brain and randomized networks. Hierarchical analysis reveals consistent modules at different scales and clustering of spatially-proximate brain regions. Findings suggest inter-subject FDG PET networks are stable for reasonable group sizes and exhibit multi-scale modularity.

Endocranial Morphology of the Extinct North American Lion (Panthera atrox).

PubMed

Cuff, Andrew R; Stockey, Christopher; Goswami, Anjali

2016-01-01

The extinct North American lion (Panthera atrox) is one of the largest felids (Mammalia, Carnivora) to have ever lived, and it is known from a plethora of incredibly well-preserved remains. Despite this abundance of material, there has been little research into its endocranial anatomy. CT scans of a skull of P. atrox from the Pleistocene La Brea Tar pits were used to generate the first virtual endocranium for this species and to elucidate previously unknown details of its brain size and gross structure, cranial nerves, and inner-ear morphology. Results show that its gross brain anatomy is broadly similar to that of other pantherines, although P. atrox displays less cephalic flexure than either extant lions or tigers, instead showing a brain shape that is reminiscent of earlier felids. Despite this unusual reduction in flexure, the estimated absolute brain size for this specimen is one of the largest reported for any felid, living or extinct. Its encephalization quotient (brain size as a fraction of the expected brain mass for a given body mass) is also larger than that of extant lions but similar to that of the other pantherines. The advent of CT scans has allowed nondestructive sampling of anatomy that cannot otherwise be studied in these extinct lions, leading to a more accurate reconstruction of endocranial morphology and its evolution. © 2017 S. Karger AG, Basel.

Assessing atrophy measurement techniques in dementia: Results from the MIRIAD atrophy challenge.

PubMed

Cash, David M; Frost, Chris; Iheme, Leonardo O; Ünay, Devrim; Kandemir, Melek; Fripp, Jurgen; Salvado, Olivier; Bourgeat, Pierrick; Reuter, Martin; Fischl, Bruce; Lorenzi, Marco; Frisoni, Giovanni B; Pennec, Xavier; Pierson, Ronald K; Gunter, Jeffrey L; Senjem, Matthew L; Jack, Clifford R; Guizard, Nicolas; Fonov, Vladimir S; Collins, D Louis; Modat, Marc; Cardoso, M Jorge; Leung, Kelvin K; Wang, Hongzhi; Das, Sandhitsu R; Yushkevich, Paul A; Malone, Ian B; Fox, Nick C; Schott, Jonathan M; Ourselin, Sebastien

2015-12-01

Structural MRI is widely used for investigating brain atrophy in many neurodegenerative disorders, with several research groups developing and publishing techniques to provide quantitative assessments of this longitudinal change. Often techniques are compared through computation of required sample size estimates for future clinical trials. However interpretation of such comparisons is rendered complex because, despite using the same publicly available cohorts, the various techniques have been assessed with different data exclusions and different statistical analysis models. We created the MIRIAD atrophy challenge in order to test various capabilities of atrophy measurement techniques. The data consisted of 69 subjects (46 Alzheimer's disease, 23 control) who were scanned multiple (up to twelve) times at nine visits over a follow-up period of one to two years, resulting in 708 total image sets. Nine participating groups from 6 countries completed the challenge by providing volumetric measurements of key structures (whole brain, lateral ventricle, left and right hippocampi) for each dataset and atrophy measurements of these structures for each time point pair (both forward and backward) of a given subject. From these results, we formally compared techniques using exactly the same dataset. First, we assessed the repeatability of each technique using rates obtained from short intervals where no measurable atrophy is expected. For those measures that provided direct measures of atrophy between pairs of images, we also assessed symmetry and transitivity. Then, we performed a statistical analysis in a consistent manner using linear mixed effect models. The models, one for repeated measures of volume made at multiple time-points and a second for repeated "direct" measures of change in brain volume, appropriately allowed for the correlation between measures made on the same subject and were shown to fit the data well. From these models, we obtained estimates of the distribution of atrophy rates in the Alzheimer's disease (AD) and control groups and of required sample sizes to detect a 25% treatment effect, in relation to healthy ageing, with 95% significance and 80% power over follow-up periods of 6, 12, and 24months. Uncertainty in these estimates, and head-to-head comparisons between techniques, were carried out using the bootstrap. The lateral ventricles provided the most stable measurements, followed by the brain. The hippocampi had much more variability across participants, likely because of differences in segmentation protocol and less distinct boundaries. Most methods showed no indication of bias based on the short-term interval results, and direct measures provided good consistency in terms of symmetry and transitivity. The resulting annualized rates of change derived from the model ranged from, for whole brain: -1.4% to -2.2% (AD) and -0.35% to -0.67% (control), for ventricles: 4.6% to 10.2% (AD) and 1.2% to 3.4% (control), and for hippocampi: -1.5% to -7.0% (AD) and -0.4% to -1.4% (control). There were large and statistically significant differences in the sample size requirements between many of the techniques. The lowest sample sizes for each of these structures, for a trial with a 12month follow-up period, were 242 (95% CI: 154 to 422) for whole brain, 168 (95% CI: 112 to 282) for ventricles, 190 (95% CI: 146 to 268) for left hippocampi, and 158 (95% CI: 116 to 228) for right hippocampi. This analysis represents one of the most extensive statistical comparisons of a large number of different atrophy measurement techniques from around the globe. The challenge data will remain online and publicly available so that other groups can assess their methods. Copyright © 2015. Published by Elsevier Inc.

Assessing atrophy measurement techniques in dementia: Results from the MIRIAD atrophy challenge

PubMed Central

Cash, David M.; Frost, Chris; Iheme, Leonardo O.; Ünay, Devrim; Kandemir, Melek; Fripp, Jurgen; Salvado, Olivier; Bourgeat, Pierrick; Reuter, Martin; Fischl, Bruce; Lorenzi, Marco; Frisoni, Giovanni B.; Pennec, Xavier; Pierson, Ronald K.; Gunter, Jeffrey L.; Senjem, Matthew L.; Jack, Clifford R.; Guizard, Nicolas; Fonov, Vladimir S.; Collins, D. Louis; Modat, Marc; Cardoso, M. Jorge; Leung, Kelvin K.; Wang, Hongzhi; Das, Sandhitsu R.; Yushkevich, Paul A.; Malone, Ian B.; Fox, Nick C.; Schott, Jonathan M.; Ourselin, Sebastien

2015-01-01

Structural MRI is widely used for investigating brain atrophy in many neurodegenerative disorders, with several research groups developing and publishing techniques to provide quantitative assessments of this longitudinal change. Often techniques are compared through computation of required sample size estimates for future clinical trials. However interpretation of such comparisons is rendered complex because, despite using the same publicly available cohorts, the various techniques have been assessed with different data exclusions and different statistical analysis models. We created the MIRIAD atrophy challenge in order to test various capabilities of atrophy measurement techniques. The data consisted of 69 subjects (46 Alzheimer's disease, 23 control) who were scanned multiple (up to twelve) times at nine visits over a follow-up period of one to two years, resulting in 708 total image sets. Nine participating groups from 6 countries completed the challenge by providing volumetric measurements of key structures (whole brain, lateral ventricle, left and right hippocampi) for each dataset and atrophy measurements of these structures for each time point pair (both forward and backward) of a given subject. From these results, we formally compared techniques using exactly the same dataset. First, we assessed the repeatability of each technique using rates obtained from short intervals where no measurable atrophy is expected. For those measures that provided direct measures of atrophy between pairs of images, we also assessed symmetry and transitivity. Then, we performed a statistical analysis in a consistent manner using linear mixed effect models. The models, one for repeated measures of volume made at multiple time-points and a second for repeated “direct” measures of change in brain volume, appropriately allowed for the correlation between measures made on the same subject and were shown to fit the data well. From these models, we obtained estimates of the distribution of atrophy rates in the Alzheimer's disease (AD) and control groups and of required sample sizes to detect a 25% treatment effect, in relation to healthy ageing, with 95% significance and 80% power over follow-up periods of 6, 12, and 24 months. Uncertainty in these estimates, and head-to-head comparisons between techniques, were carried out using the bootstrap. The lateral ventricles provided the most stable measurements, followed by the brain. The hippocampi had much more variability across participants, likely because of differences in segmentation protocol and less distinct boundaries. Most methods showed no indication of bias based on the short-term interval results, and direct measures provided good consistency in terms of symmetry and transitivity. The resulting annualized rates of change derived from the model ranged from, for whole brain: − 1.4% to − 2.2% (AD) and − 0.35% to − 0.67% (control), for ventricles: 4.6% to 10.2% (AD) and 1.2% to 3.4% (control), and for hippocampi: − 1.5% to − 7.0% (AD) and − 0.4% to − 1.4% (control). There were large and statistically significant differences in the sample size requirements between many of the techniques. The lowest sample sizes for each of these structures, for a trial with a 12 month follow-up period, were 242 (95% CI: 154 to 422) for whole brain, 168 (95% CI: 112 to 282) for ventricles, 190 (95% CI: 146 to 268) for left hippocampi, and 158 (95% CI: 116 to 228) for right hippocampi. This analysis represents one of the most extensive statistical comparisons of a large number of different atrophy measurement techniques from around the globe. The challenge data will remain online and publicly available so that other groups can assess their methods. PMID:26275383

Longitudinal assessment of chemotherapy-induced changes in brain and cognitive functioning: A systematic review.

PubMed

Li, Mingmei; Caeyenberghs, Karen

2018-05-20

In addition to the burden of a life-threatening diagnosis, cancer patients are struggling with adverse side-effects from cancer treatment. Chemotherapy has been linked to an array of cognitive impairments and alterations in brain structure and function ("chemobrain"). In this review, we summarized the existing evidence that evaluate the changes in cognitive functioning and brain with chemotherapy, as assessed using structural and functional MRI-based techniques in a longitudinal design. This review followed the latest PRISMA guidelines using Embase, Medline, PsychINFO, Scopus, and Web of Science databases with date restrictions from 2012-2017. Fourteen research articles met the key inclusion criteria: (i) the studies involved adult cancer patients (mean age≥18); (ii) the use of chemotherapy in the treatment of cancer; (iii) pre-post assessment of behavioral and brain-based outcomes; and (iv) abstracts written in English. Effect sizes of subjective and objective cognitive impairments from the reviewed studies were estimated using Cohen's d or z-scores. We calculated percentage of mean change or effect sizes for main neuroimaging findings when data were available. Strength of the correlations between brain alterations and cognitive changes was obtained using squared correlation coefficients. We showed small to medium effect sizes on individual tests of attention, processing speed, verbal memory, and executive control; and medium effect sizes on self-report questionnaires. Neuroimaging data showed reduced grey matter density in cancer patients in frontal, parietal, and temporal regions. Changes in brain function (brain activation and cerebral blood flow) were observed with cancer across functional networks involving (pre)frontal, parietal, occipital, temporal, and cerebellar regions. Data from diffusion-weighted MRI suggested reduced white matter integrity involving the superior longitudinal fasciculus, corpus callosum, forceps major, and corona radiate, and altered structural connectivity across the whole brain network. Finally, we observed moderate-to-strong correlations between worsening cognitive function and morphological changes in frontal brain regions. While MRI is a powerful tool for detection of longitudinal brain changes in the 'chemobrain', the underlying biological mechanisms are still unclear. Continued work in this field will hopefully detect MRI metrics to be used as biomarkers to help guide cognitive treatment at the individual cancer patient level. Copyright © 2018. Published by Elsevier Ltd.

Brain glucose content in fetuses of ethanol-fed rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pullen, G.; Singh, S.P.; Snyder, A.K.

1986-03-01

The authors have previously demonstrated impaired placental glucose transfer and fetal hypoglycemia in association with ethanol ingestion by pregnant rats. The present study examines the relationship between glucose availability and fetal brain growth under the same conditions. Rats (EF) were fed ethanol (30% of caloric intake) in liquid diet throughout gestation. Controls received isocaloric diet without ethanol by pair-feeding (PF) or ad libitum (AF). On the 22nd day of gestation fetuses were obtained by cesarean section. Fetal brains were removed and freeze-clamped. Brain weight was significantly reduced (p < 0.001) by maternal ethanol ingestion (206 +/- 2, 212 +/- 4more » and 194 +/- 2 mg in AF, FP and EF fetuses respectively). Similarly, fetal brain glucose content was lower (p < 0.05) in the EF group (14.3 +/- 0.9 mmoles/g dry weight) than in the PF (18.6 +/- 1.0) or the AF (16.2 +/- 0.9) groups. The protein: DNA ratio, an indicator of cell size, correlated positively (r = 0.371, p < 0.005) with brain glucose content. In conclusion, maternal ethanol ingestion resulted in lower brain weight and reduced brain glucose content. Glucose availability may be a significant factor in the determination of cell size in the fetal rat brain.« less

Brain organization and specialization in deep-sea chondrichthyans.

PubMed

Yopak, Kara E; Montgomery, John C

2008-01-01

Chondrichthyans occupy a basal place in vertebrate evolution and offer a relatively unexplored opportunity to study the evolution of vertebrate brains. This study examines the brain morphology of 22 species of deep-sea sharks and holocephalans, in relation to both phylogeny and ecology. Both relative brain size (expressed as residuals) and the relative development of the five major brain areas (telencephalon, diencephalon, mesencephalon, cerebellum, and medulla) were assessed. The cerebellar-like structures, which receive projections from the electroreceptive and lateral line organs, were also examined as a discrete part of the medulla. Although the species examined spanned three major chondrichthyan groupings (Squalomorphii, Galeomorphii, Holocephali), brain size and the relative development of the major brain areas did not track phylogenetic groupings. Rather, a hierarchical cluster analysis performed on the deep-sea sharks and holocephalans shows that these species all share the common characteristics of a relatively reduced telencephalon and smooth cerebellar corpus, as well as extreme relative enlargement of the medulla, specifically the cerebellar-like lobes. Although this study was not a functional analysis, it provides evidence that brain variation in deep-sea chondichthyans shows adaptive patterns in addition to underlying phylogenetic patterns, and that particular brain patterns might be interpreted as 'cerebrotypes'. (c) 2008 S. Karger AG, Basel

Internal carotid arterial canal size and scaling in Euarchonta: Re-assessing implications for arterial patency and phylogenetic relationships in early fossil primates.

PubMed

Boyer, Doug M; Kirk, E Christopher; Silcox, Mary T; Gunnell, Gregg F; Gilbert, Christopher C; Yapuncich, Gabriel S; Allen, Kari L; Welch, Emma; Bloch, Jonathan I; Gonzales, Lauren A; Kay, Richard F; Seiffert, Erik R

2016-08-01

Primate species typically differ from other mammals in having bony canals that enclose the branches of the internal carotid artery (ICA) as they pass through the middle ear. The presence and relative size of these canals varies among major primate clades. As a result, differences in the anatomy of the canals for the promontorial and stapedial branches of the ICA have been cited as evidence of either haplorhine or strepsirrhine affinities among otherwise enigmatic early fossil euprimates. Here we use micro X-ray computed tomography to compile the largest quantitative dataset on ICA canal sizes. The data suggest greater variation of the ICA canals within some groups than has been previously appreciated. For example, Lepilemur and Avahi differ from most other lemuriforms in having a larger promontorial canal than stapedial canal. Furthermore, various lemurids are intraspecifically variable in relative canal size, with the promontorial canal being larger than the stapedial canal in some individuals but not others. In species where the promontorial artery supplies the brain with blood, the size of the promontorial canal is significantly correlated with endocranial volume (ECV). Among species with alternate routes of encephalic blood supply, the promontorial canal is highly reduced relative to ECV, and correlated with both ECV and cranium size. Ancestral state reconstructions incorporating data from fossils suggest that the last common ancestor of living primates had promontorial and stapedial canals that were similar to each other in size and large relative to ECV. We conclude that the plesiomorphic condition for crown primates is to have a patent promontorial artery supplying the brain and a patent stapedial artery for various non-encephalic structures. This inferred ancestral condition is exhibited by treeshrews and most early fossil euprimates, while extant primates exhibit reduction in one canal or another. The only early fossils deviating from this plesiomorphic condition are Adapis parisiensis with a reduced promontorial canal, and Rooneyia and Mahgarita with reduced stapedial canals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Aging, Brain Size, and IQ.

ERIC Educational Resources Information Center

Bigler, Erin D.; And Others

1995-01-01

Whether cross-sectional rates of decline for brain volume and the Performance Intellectual Quotient of the Wechsler Adult Intelligence Scale-Revised were equivalent over the years 16 to 65 was studied with 196 volunteers. Results indicate remarkably similar rates of decline in perceptual-motor functions and aging brain volume loss. (SLD)

Glycogen distribution in the microwave-fixed mouse brain reveals heterogeneous astrocytic patterns.

PubMed

Oe, Yuki; Baba, Otto; Ashida, Hitoshi; Nakamura, Kouichi C; Hirase, Hajime

2016-09-01

In the brain, glycogen metabolism has been implied in synaptic plasticity and learning, yet the distribution of this molecule has not been fully described. We investigated cerebral glycogen of the mouse by immunohistochemistry (IHC) using two monoclonal antibodies that have different affinities depending on the glycogen size. The use of focused microwave irradiation yielded well-defined glycogen immunoreactive signals compared with the conventional periodic acid-Schiff method. The IHC signals displayed a punctate distribution localized predominantly in astrocytic processes. Glycogen immunoreactivity (IR) was high in the hippocampus, striatum, cortex, and cerebellar molecular layer, whereas it was low in the white matter and most of the subcortical structures. Additionally, glycogen distribution in the hippocampal CA3-CA1 and striatum had a 'patchy' appearance with glycogen-rich and glycogen-poor astrocytes appearing in alternation. The glycogen patches were more evident with large-molecule glycogen in young adult mice but they were hardly observable in aged mice (1-2 years old). Our results reveal brain region-dependent glycogen accumulation and possibly metabolic heterogeneity of astrocytes. GLIA 2016;64:1532-1545. © 2016 The Authors. Glia Published by Wiley Periodicals, Inc.

Function and regulation of AUTS2, a gene implicated in autism and human evolution.

PubMed

Oksenberg, Nir; Stevison, Laurie; Wall, Jeffrey D; Ahituv, Nadav

2013-01-01

Nucleotide changes in the AUTS2 locus, some of which affect only noncoding regions, are associated with autism and other neurological disorders, including attention deficit hyperactivity disorder, epilepsy, dyslexia, motor delay, language delay, visual impairment, microcephaly, and alcohol consumption. In addition, AUTS2 contains the most significantly accelerated genomic region differentiating humans from Neanderthals, which is primarily composed of noncoding variants. However, the function and regulation of this gene remain largely unknown. To characterize auts2 function, we knocked it down in zebrafish, leading to a smaller head size, neuronal reduction, and decreased mobility. To characterize AUTS2 regulatory elements, we tested sequences for enhancer activity in zebrafish and mice. We identified 23 functional zebrafish enhancers, 10 of which were active in the brain. Our mouse enhancer assays characterized three mouse brain enhancers that overlap an ASD-associated deletion and four mouse enhancers that reside in regions implicated in human evolution, two of which are active in the brain. Combined, our results show that AUTS2 is important for neurodevelopment and expose candidate enhancer sequences in which nucleotide variation could lead to neurological disease and human-specific traits.

SU-E-T-629: Feasibility Study of Treating Multiple Brain Tumors with Large Number of Noncoplanar IMRT Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dong, P; Ma, L

Purpose: To study the feasibility of treating multiple brain tumors withlarge number of noncoplanar IMRT beams. Methods: Thirty beams are selected from 390 deliverable beams separated by six degree in 4pi space. Beam selection optimization is based on a column generation algorithm. MLC leaf size is 2 mm. Dose matrices are calculated with collapsed cone convolution and superposition method in a 2 mm by 2mm by 2 mm grid. Twelve brain tumors of various shapes, sizes and locations are used to generate four plans treating 3, 6, 9 and 12 tumors. The radiation dose was 20 Gy prescribed to themore » 100% isodose line. Dose Volume Histograms for tumor and brain were compared. Results: All results are based on a 2 mm by 2 mm by 2 mm CT grid. For 3, 6, 9 and 12 tumor plans, minimum tumor doses are all 20 Gy. Mean tumor dose are 20.0, 20.1, 20.1 and 20.1 Gy. Maximum tumor dose are 23.3, 23.6, 25.4 and 25.4 Gy. Mean ventricles dose are 0.7, 1.7, 2.4 and 3.1 Gy.Mean subventricular zone dose are 0.8, 1.3, 2.2 and 3.2 Gy. Average Equivalent uniform dose (gEUD) values for tumor are 20.1, 20.1, 20.2 and 20.2 Gy. The conformity index (CI) values are close to 1 for all 4 plans. The gradient index (GI) values are 2.50, 2.05, 2.09 and 2.19. Conclusion: Compared with published Gamma Knife treatment studies, noncoplanar IMRT treatment plan is superior in terms of dose conformity. Due to maximum limit of beams per plan, Gamma knife has to treat multiple tumors separately in different plans. Noncoplanar IMRT plans theoretically can be delivered in a single plan on any modern linac with an automated couch and image guidance. This warrants further study of using noncoplanar IMRT as a viable treatment solution for multiple brain tumors.« less

Experimental Toxoplasmosis in Rats Induced Orally with Eleven Strains of Toxoplasma gondii of Seven Genotypes: Tissue Tropism, Tissue Cyst Size, Neural Lesions, Tissue Cyst Rupture without Reactivation, and Ocular Lesions.

PubMed

Dubey, Jitender P; Ferreira, Leandra R; Alsaad, Mohammad; Verma, Shiv K; Alves, Derron A; Holland, Gary N; McConkey, Glenn A

2016-01-01

The protozoan parasite Toxoplasma gondii is one of the most widely distributed and successful parasites. Toxoplasma gondii alters rodent behavior such that infected rodents reverse their fear of cat odor, and indeed are attracted rather than repelled by feline urine. The location of the parasite encysted in the brain may influence this behavior. However, most studies are based on the highly susceptible rodent, the mouse. Latent toxoplasmosis was induced in rats (10 rats per T. gondii strains) of the same age, strain, and sex, after oral inoculation with oocysts (natural route and natural stage of infection) of 11 T. gondii strains of seven genotypes. Rats were euthanized at two months post inoculation (p.i.) to investigate whether the parasite genotype affects the distribution, location, tissue cyst size, or lesions. Tissue cysts were enumerated in different regions of the brains, both in histological sections as well in saline homogenates. Tissue cysts were found in all regions of the brain. The tissue cyst density in different brain regions varied extensively between rats with many regions highly infected in some animals. Overall, the colliculus was most highly infected although there was a large amount of variability. The cerebral cortex, thalamus, and cerebellum had higher tissue cyst densities and two strains exhibited tropism for the colliculus and olfactory bulb. Histologically, lesions were confined to the brain and eyes. Tissue cyst rupture was frequent with no clear evidence for reactivation of tachyzoites. Ocular lesions were found in 23 (25%) of 92 rat eyes at two months p.i. The predominant lesion was focal inflammation in the retina. Tissue cysts were seen in the sclera of one and in the optic nerve of two rats. The choroid was not affected. Only tissue cysts, not active tachyzoite infections, were detected. Tissue cysts were seen in histological sections of tongue of 20 rats but not in myocardium and leg muscle. This study reevaluated in depth the rat model of toxoplasmosis visualizing cyst rupture and clarified many aspects of the biology of the parasite useful for future investigations.

Midsagittal Brain Variation among Non-Human Primates: Insights into Evolutionary Expansion of the Human Precuneus.

PubMed

Pereira-Pedro, Ana Sofia; Rilling, James K; Chen, Xu; Preuss, Todd M; Bruner, Emiliano

2017-01-01

The precuneus is a major element of the superior parietal lobule, positioned on the medial side of the hemisphere and reaching the dorsal surface of the brain. It is a crucial functional region for visuospatial integration, visual imagery, and body coordination. Previously, we argued that the precuneus expanded in recent human evolution, based on a combination of paleontological, comparative, and intraspecific evidence from fossil and modern human endocasts as well as from human and chimpanzee brains. The longitudinal proportions of this region are a major source of anatomical variation among adult humans and, being much larger in Homo sapiens, is the main characteristic differentiating human midsagittal brain morphology from that of our closest living primate relative, the chimpanzee. In the current shape analysis, we examine precuneus variation in non-human primates through landmark-based models, to evaluate the general pattern of variability in non-human primates, and to test whether precuneus proportions are influenced by allometric effects of brain size. Results show that precuneus proportions do not covary with brain size, and that the main difference between monkeys and apes involves a vertical expansion of the frontal and occipital regions in apes. Such differences might reflect differences in brain proportions or differences in cranial architecture. In this sample, precuneus variation is apparently not influenced by phylogenetic or allometric factors, but does vary consistently within species, at least in chimpanzees and macaques. This result further supports the hypothesis that precuneus expansion in modern humans is not merely a consequence of increasing brain size or of allometric scaling, but rather represents a species-specific morphological change in our lineage. © 2017 S. Karger AG, Basel.

Lycium barbarum Extracts Protect the Brain from Blood-Brain Barrier Disruption and Cerebral Edema in Experimental Stroke

PubMed Central

Yang, Di; Li, Suk-Yee; Yeung, Chung-Man; Chang, Raymond Chuen-Chung; So, Kwok-Fai; Wong, David; Lo, Amy C. Y.

2012-01-01

Background and Purpose Ischemic stroke is a destructive cerebrovascular disease and a leading cause of death. Yet, no ideal neuroprotective agents are available, leaving prevention an attractive alternative. The extracts from the fruits of Lycium barbarum (LBP), a Chinese anti-aging medicine and food supplement, showed neuroprotective function in the retina when given prophylactically. We aim to evaluate the protective effects of LBP pre-treatment in an experimental stroke model. Methods C57BL/6N male mice were first fed with either vehicle (PBS) or LBP (1 or 10 mg/kg) daily for 7 days. Mice were then subjected to 2-hour transient middle cerebral artery occlusion (MCAO) by the intraluminal method followed by 22-hour reperfusion upon filament removal. Mice were evaluated for neurological deficits just before sacrifice. Brains were harvested for infarct size estimation, water content measurement, immunohistochemical analysis, and Western blot experiments. Evans blue (EB) extravasation was determined to assess blood-brain barrier (BBB) disruption after MCAO. Results LBP pre-treatment significantly improved neurological deficits as well as decreased infarct size, hemispheric swelling, and water content. Fewer apoptotic cells were identified in LBP-treated brains by TUNEL assay. Reduced EB extravasation, fewer IgG-leaky vessels, and up-regulation of occludin expression were also observed in LBP-treated brains. Moreover, immunoreactivity for aquaporin-4 and glial fibrillary acidic protein were significantly decreased in LBP-treated brains. Conclusions Seven-day oral LBP pre-treatment effectively improved neurological deficits, decreased infarct size and cerebral edema as well as protected the brain from BBB disruption, aquaporin-4 up-regulation, and glial activation. The present study suggests that LBP may be used as a prophylactic neuroprotectant in patients at high risk for ischemic stroke. PMID:22438957

Irisin Peptide Protects Brain Against Ischemic Injury Through Reducing Apoptosis and Enhancing BDNF in a Rodent Model of Stroke.

PubMed

Asadi, Yasin; Gorjipour, Fazel; Behrouzifar, Sedigheh; Vakili, Abedin

2018-06-07

Evidence has shown therapeutic potential of irisin in cerebral stroke. The present study aimed to assess the effects of recombinant irisin on the infarct size, neurological outcomes, blood-brain barrier (BBB) permeability, apoptosis and brain-derived neurotrophic factor (BDNF) expression in a mouse model of stroke. Transient focal cerebral ischemia was established by middle cerebral artery occlusion (MCAO) for 45 min and followed reperfusion for 23 h in mice. Recombinant irisin was administrated at doses of 0.1, 0.5, 2.5, 7.5, and 15 µg/kg, intracerebroventricularly (ICV), on the MCAO beginning. Neurological outcomes, infarct size, brain edema and BBB permeability were evaluated by modified neurological severity score (mNSS), 2,3,5-triphenyltetrazolium chloride (TTC) staining and Evans blue (EB) extravasation methods, respectively, at 24 h after ischemia. Apoptotic cells and BDNF protein were detected by TUNEL assay and immunohistochemistry techniques. The levels of Bcl-2, Bax and caspase-3 proteins were measured by immunoblotting technique. ICV irisin administration at doses of 0.5, 2.5, 7.5 and 15 µg/kg, significantly reduced infarct size, whereas only in 7.5 and 15 µg/kg improved neurological outcome (P < 0.001). Treatment with irisin (7.5 µg/kg) reduced brain edema (P < 0.001) without changing BBB permeability (P > 0.05). Additionally, irisin (7.5 µg/kg) significantly diminished apoptotic cells and increased BDNF immunoreactivity in the ischemic brain cortex (P < 0.004). Irisin administration significantly downregulated the Bax and caspase-3 expression and upregulated the Bcl-2 protein. The present study indicated that irisin attenuates brain damage via reducing apoptosis and increasing BDNF protein of brain cortex in the experimental model of stroke in mice.

Intranasal mucoadhesive microemulsions of clonazepam: preliminary studies on brain targeting.

PubMed

Vyas, Tushar K; Babbar, A K; Sharma, R K; Singh, Shashi; Misra, Ambikanandan

2006-03-01

The aim of this investigation was to prepare clonazepam microemulsions (CME) for rapid drug delivery to the brain to treat acute status epileptic patients and to characterize and evaluate the performance of CME in vitro and in vivo in rats. The CME were prepared by the titration method and were characterized for globule size and size distribution, zeta potential, and drug content. CME was radiolabeled with (99m)Tc (technetium) and biodistribution of drug in the brain was studied in Swiss albino rats after intranasal and intravenous administrations. Brain scintigraphy imaging in rabbits was also performed to ascertain the uptake of the drug into the brain. Pre and postCME formulation treated human nasal mucosa was subjected to transmission electron microscopy to investigate the mechanism of drug uptake across the nasal mucosa. CME were transparent and stable with mean globule size of 15 +/- 10 nm and zeta potential of -30 mV to -40 mV. (99m)Tc-labeled clonazepam solution ((99m)Tc CS)/ clonazepam microemulsion (CME)/clonazepam mucoadhesive microemulsion (CMME) were found to be stable and suitable for in vivo studies. Brain/blood uptake ratios at 0.50 hour (h) following intranasal CMME, CME, clonazepam solution (CS), and intravenous CME administrations were found to be 0.67, 0.50, 0.48, and 0.13, respectively indicating more effective targeting with intranasal administration and best targeting of the brain with intranasal CMME. Brain/blood ratio at all sampling points up to 8 h following intranasal administration of CMME compared to intravenous was found to be twofold higher indicating larger extent of distribution of the drug in brain. Rabbit brain scintigraphy also showed higher intranasal uptake of the drug into the brain. Transmission electron microscopy revealed significant accretion of CMME within interstitial spaces and paracellular mode of transport due to stretching of the tight junctions present in the nasal mucosa. This investigation demonstrates a more rapid and larger extent of transport of clonazepam into the rat brain with intranasal CMME, which may prove useful in treating acute status epileptics. Copyright 2006 Wiley-Liss, Inc. and the American Pharmacists Association.

Segregated Systems of Human Brain Networks.

PubMed

Wig, Gagan S

2017-12-01

The organization of the brain network enables its function. Evaluation of this organization has revealed that large-scale brain networks consist of multiple segregated subnetworks of interacting brain areas. Descriptions of resting-state network architecture have provided clues for understanding the functional significance of these segregated subnetworks, many of which correspond to distinct brain systems. The present report synthesizes accumulating evidence to reveal how maintaining segregated brain systems renders the human brain network functionally specialized, adaptable to task demands, and largely resilient following focal brain damage. The organizational properties that support system segregation are harmonious with the properties that promote integration across the network, but confer unique and important features to the brain network that are central to its function and behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prenatal Exposure to Autism-Specific Maternal Autoantibodies Alters Proliferation of Cortical Neural Precursor Cells, Enlarges Brain, and Increases Neuronal Size in Adult Animals.

PubMed

Martínez-Cerdeño, Verónica; Camacho, Jasmin; Fox, Elizabeth; Miller, Elaine; Ariza, Jeanelle; Kienzle, Devon; Plank, Kaela; Noctor, Stephen C; Van de Water, Judy

2016-01-01

Autism spectrum disorders (ASDs) affect up to 1 in 68 children. Autism-specific autoantibodies directed against fetal brain proteins have been found exclusively in a subpopulation of mothers whose children were diagnosed with ASD or maternal autoantibody-related autism. We tested the impact of autoantibodies on brain development in mice by transferring human antigen-specific IgG directly into the cerebral ventricles of embryonic mice during cortical neurogenesis. We show that autoantibodies recognize radial glial cells during development. We also show that prenatal exposure to autism-specific maternal autoantibodies increased stem cell proliferation in the subventricular zone (SVZ) of the embryonic neocortex, increased adult brain size and weight, and increased the size of adult cortical neurons. We propose that prenatal exposure to autism-specific maternal autoantibodies directly affects radial glial cell development and presents a viable pathologic mechanism for the maternal autoantibody-related prenatal ASD risk factor. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

HAFNI-enabled largescale platform for neuroimaging informatics (HELPNI).

PubMed

Makkie, Milad; Zhao, Shijie; Jiang, Xi; Lv, Jinglei; Zhao, Yu; Ge, Bao; Li, Xiang; Han, Junwei; Liu, Tianming

Tremendous efforts have thus been devoted on the establishment of functional MRI informatics systems that recruit a comprehensive collection of statistical/computational approaches for fMRI data analysis. However, the state-of-the-art fMRI informatics systems are especially designed for specific fMRI sessions or studies of which the data size is not really big, and thus has difficulty in handling fMRI 'big data.' Given the size of fMRI data are growing explosively recently due to the advancement of neuroimaging technologies, an effective and efficient fMRI informatics system which can process and analyze fMRI big data is much needed. To address this challenge, in this work, we introduce our newly developed informatics platform, namely, 'HAFNI-enabled largescale platform for neuroimaging informatics (HELPNI).' HELPNI implements our recently developed computational framework of sparse representation of whole-brain fMRI signals which is called holistic atlases of functional networks and interactions (HAFNI) for fMRI data analysis. HELPNI provides integrated solutions to archive and process large-scale fMRI data automatically and structurally, to extract and visualize meaningful results information from raw fMRI data, and to share open-access processed and raw data with other collaborators through web. We tested the proposed HELPNI platform using publicly available 1000 Functional Connectomes dataset including over 1200 subjects. We identified consistent and meaningful functional brain networks across individuals and populations based on resting state fMRI (rsfMRI) big data. Using efficient sampling module, the experimental results demonstrate that our HELPNI system has superior performance than other systems for large-scale fMRI data in terms of processing and storing the data and associated results much faster.

HAFNI-enabled largescale platform for neuroimaging informatics (HELPNI).

PubMed

Makkie, Milad; Zhao, Shijie; Jiang, Xi; Lv, Jinglei; Zhao, Yu; Ge, Bao; Li, Xiang; Han, Junwei; Liu, Tianming

2015-12-01

Tremendous efforts have thus been devoted on the establishment of functional MRI informatics systems that recruit a comprehensive collection of statistical/computational approaches for fMRI data analysis. However, the state-of-the-art fMRI informatics systems are especially designed for specific fMRI sessions or studies of which the data size is not really big, and thus has difficulty in handling fMRI 'big data.' Given the size of fMRI data are growing explosively recently due to the advancement of neuroimaging technologies, an effective and efficient fMRI informatics system which can process and analyze fMRI big data is much needed. To address this challenge, in this work, we introduce our newly developed informatics platform, namely, 'HAFNI-enabled largescale platform for neuroimaging informatics (HELPNI).' HELPNI implements our recently developed computational framework of sparse representation of whole-brain fMRI signals which is called holistic atlases of functional networks and interactions (HAFNI) for fMRI data analysis. HELPNI provides integrated solutions to archive and process large-scale fMRI data automatically and structurally, to extract and visualize meaningful results information from raw fMRI data, and to share open-access processed and raw data with other collaborators through web. We tested the proposed HELPNI platform using publicly available 1000 Functional Connectomes dataset including over 1200 subjects. We identified consistent and meaningful functional brain networks across individuals and populations based on resting state fMRI (rsfMRI) big data. Using efficient sampling module, the experimental results demonstrate that our HELPNI system has superior performance than other systems for large-scale fMRI data in terms of processing and storing the data and associated results much faster.

Micro sized implantable ball lens-based fiber optic probe design

NASA Astrophysics Data System (ADS)

Cha, Jaepyeong; Kang, Jin U.

2014-02-01

A micro sized implantable ball lens-based fiber optic probe design is described for continuous monitoring of brain activity in freely behaving mice. A prototype uses a 500-micron ball lens and a highly flexible 350-micron-diameter fiber bundle, which are enclosed by a 21G stainless steel sheath. Several types and thickness of brain tissue, consisting of fluorescent probes such as GFP, GCaMP3 calcium indicator, are used to evaluate the performance of the imaging probe. Measured working distance is approximately 400-μm, but is long enough to detect neural activities from cortical and cerebellar tissues of mice brain.

Loss of Brain Aerobic Glycolysis in Normal Human Aging.

PubMed

Goyal, Manu S; Vlassenko, Andrei G; Blazey, Tyler M; Su, Yi; Couture, Lars E; Durbin, Tony J; Bateman, Randall J; Benzinger, Tammie L-S; Morris, John C; Raichle, Marcus E

2017-08-01

The normal aging human brain experiences global decreases in metabolism, but whether this affects the topography of brain metabolism is unknown. Here we describe PET-based measurements of brain glucose uptake, oxygen utilization, and blood flow in cognitively normal adults from 20 to 82 years of age. Age-related decreases in brain glucose uptake exceed that of oxygen use, resulting in loss of brain aerobic glycolysis (AG). Whereas the topographies of total brain glucose uptake, oxygen utilization, and blood flow remain largely stable with age, brain AG topography changes significantly. Brain regions with high AG in young adults show the greatest change, as do regions with prolonged developmental transcriptional features (i.e., neoteny). The normal aging human brain thus undergoes characteristic metabolic changes, largely driven by global loss and topographic changes in brain AG. Copyright © 2017 Elsevier Inc. All rights reserved.

Evolution of complex higher brain centers and behaviors: behavioral correlates of mushroom body elaboration in insects.

PubMed

Farris, Sarah M

2013-01-01

Large, complex higher brain centers have evolved many times independently within the vertebrates, but the selective pressures driving these acquisitions have been difficult to pinpoint. It is well established that sensory brain centers become larger and more structurally complex to accommodate processing of a particularly important sensory modality. When higher brain centers such as the cerebral cortex become greatly expanded in a particular lineage, it is likely to support the coordination and execution of more complex behaviors, such as those that require flexibility, learning, and social interaction, in response to selective pressures that made these new behaviors advantageous. Vertebrate studies have established a link between complex behaviors, particularly those associated with sociality, and evolutionary expansions of telencephalic higher brain centers. Enlarged higher brain centers have convergently evolved in groups such as the insects, in which multimodal integration and learning and memory centers called the mushroom bodies have become greatly elaborated in at least four independent lineages. Is it possible that similar selective pressures acting on equivalent behavioral outputs drove the evolution of large higher brain centers in all bilaterians? Sociality has greatly impacted brain evolution in vertebrates such as primates, but it has not been a major driver of higher brain center enlargement in insects. However, feeding behaviors requiring flexibility and learning are associated with large higher brain centers in both phyla. Selection for the ability to support behavioral flexibility appears to be a common thread underlying the evolution of large higher brain centers, but the precise nature of these computations and behaviors may vary. © 2013 S. Karger AG, Basel.

Abnormalities in the zinc-metalloprotease-BDNF axis may contribute to megalencephaly and cortical hyperconnectivity in young autism spectrum disorder patients.

PubMed

Koh, Jae-Young; Lim, Joon Seo; Byun, Hyae-Ran; Yoo, Min-Heui

2014-09-03

Whereas aberrant brain connectivity is likely the core pathology of autism-spectrum disorder (ASD), studies do not agree as to whether hypo- or hyper-connectivity is the main underlying problem. Recent functional imaging studies have shown that, in most young ASD patients, cerebral cortical regions appear hyperconnected, and cortical thickness/brain size is increased. Collectively, these findings indicate that developing ASD brains may exist in an altered neurotrophic milieu. Consistently, some ASD patients, as well as some animal models of ASD, show increased levels of brain-derived neurotrophic factor (BDNF). However, how BDNF is upregulated in ASD is unknown. To address this question, we propose the novel hypothesis that a putative zinc-metalloprotease-BDNF (ZMB) axis in the forebrain plays a pivotal role in the development of hyperconnectivity and megalencephaly in ASD. We have previously demonstrated that extracellular zinc at micromolar concentrations can rapidly increase BDNF levels and phosphorylate the receptor tyrosine kinase TrkB via the activation of metalloproteases. The role of metalloproteases in ASD is still uncertain, but in fragile X syndrome, a monogenic disease with an autistic phenotype, the levels of MMP are increased. Early exposure to lipopolysaccharides (LPS) and other MMP activators such as organic mercurials also have been implicated in ASD pathogenesis. The resultant increases in BDNF levels at synapses, especially those involved in the zinc-containing, associative glutamatergic system may produce abnormal brain circuit development. Various genetic mutations that lead to ASD are also known to affect BDNF signaling: some down-regulate, and others up-regulate it. We hypothesize that, although both up- and down-regulation of BDNF may induce autism symptoms, only BDNF up-regulation is associated with the hyperconnectivity and large brain size observed in most young idiopathic ASD patients. To test this hypothesis, we propose to examine the ZMB axis in animal models of ASD. Synaptic zinc can be examined by fluorescence zinc staining. MMP activation can be measured by in situ zymography and Western blot analysis. Finally, regional levels of BDNF can be measured. Validating this hypothesis may shed light on the central pathogenic mechanism of ASD and aid in the identification of useful biomarkers and the development of preventive/therapeutic strategies.

Abnormalities in the zinc-metalloprotease-BDNF axis may contribute to megalencephaly and cortical hyperconnectivity in young autism spectrum disorder patients

PubMed Central

2014-01-01

Whereas aberrant brain connectivity is likely the core pathology of autism-spectrum disorder (ASD), studies do not agree as to whether hypo- or hyper-connectivity is the main underlying problem. Recent functional imaging studies have shown that, in most young ASD patients, cerebral cortical regions appear hyperconnected, and cortical thickness/brain size is increased. Collectively, these findings indicate that developing ASD brains may exist in an altered neurotrophic milieu. Consistently, some ASD patients, as well as some animal models of ASD, show increased levels of brain-derived neurotrophic factor (BDNF). However, how BDNF is upregulated in ASD is unknown. To address this question, we propose the novel hypothesis that a putative zinc-metalloprotease-BDNF (ZMB) axis in the forebrain plays a pivotal role in the development of hyperconnectivity and megalencephaly in ASD. We have previously demonstrated that extracellular zinc at micromolar concentrations can rapidly increase BDNF levels and phosphorylate the receptor tyrosine kinase TrkB via the activation of metalloproteases. The role of metalloproteases in ASD is still uncertain, but in fragile X syndrome, a monogenic disease with an autistic phenotype, the levels of MMP are increased. Early exposure to lipopolysaccharides (LPS) and other MMP activators such as organic mercurials also have been implicated in ASD pathogenesis. The resultant increases in BDNF levels at synapses, especially those involved in the zinc-containing, associative glutamatergic system may produce abnormal brain circuit development. Various genetic mutations that lead to ASD are also known to affect BDNF signaling: some down-regulate, and others up-regulate it. We hypothesize that, although both up- and down-regulation of BDNF may induce autism symptoms, only BDNF up-regulation is associated with the hyperconnectivity and large brain size observed in most young idiopathic ASD patients. To test this hypothesis, we propose to examine the ZMB axis in animal models of ASD. Synaptic zinc can be examined by fluorescence zinc staining. MMP activation can be measured by in situ zymography and Western blot analysis. Finally, regional levels of BDNF can be measured. Validating this hypothesis may shed light on the central pathogenic mechanism of ASD and aid in the identification of useful biomarkers and the development of preventive/therapeutic strategies. PMID:25182223

Cerebral vessels segmentation for light-sheet microscopy image using convolutional neural networks

NASA Astrophysics Data System (ADS)

Hu, Chaoen; Hui, Hui; Wang, Shuo; Dong, Di; Liu, Xia; Yang, Xin; Tian, Jie

2017-03-01

Cerebral vessel segmentation is an important step in image analysis for brain function and brain disease studies. To extract all the cerebrovascular patterns, including arteries and capillaries, some filter-based methods are used to segment vessels. However, the design of accurate and robust vessel segmentation algorithms is still challenging, due to the variety and complexity of images, especially in cerebral blood vessel segmentation. In this work, we addressed a problem of automatic and robust segmentation of cerebral micro-vessels structures in cerebrovascular images acquired by light-sheet microscope for mouse. To segment micro-vessels in large-scale image data, we proposed a convolutional neural networks (CNNs) architecture trained by 1.58 million pixels with manual label. Three convolutional layers and one fully connected layer were used in the CNNs model. We extracted a patch of size 32x32 pixels in each acquired brain vessel image as training data set to feed into CNNs for classification. This network was trained to output the probability that the center pixel of input patch belongs to vessel structures. To build the CNNs architecture, a series of mouse brain vascular images acquired from a commercial light sheet fluorescence microscopy (LSFM) system were used for training the model. The experimental results demonstrated that our approach is a promising method for effectively segmenting micro-vessels structures in cerebrovascular images with vessel-dense, nonuniform gray-level and long-scale contrast regions.

Initial brain aging: heterogeneity of mitochondrial size is associated with decline in complex I-linked respiration in cortex and hippocampus.

PubMed

Thomsen, Kirsten; Yokota, Takashi; Hasan-Olive, Md Mahdi; Sherazi, Niloofar; Fakouri, Nima Borhan; Desler, Claus; Regnell, Christine Elisabeth; Larsen, Steen; Rasmussen, Lene Juel; Dela, Flemming; Bergersen, Linda Hildegard; Lauritzen, Martin

2018-01-01

Brain aging is accompanied by declining mitochondrial respiration. We hypothesized that mitochondrial morphology and dynamics would reflect this decline. Using hippocampus and frontal cortex of a segmental progeroid mouse model lacking Cockayne syndrome protein B (CSB m/m ) and C57Bl/6 (WT) controls and comparing young (2-5 months) to middle-aged mice (13-14 months), we found that complex I-linked state 3 respiration (CI) was reduced at middle age in CSB m/m hippocampus, but not in CSB m/m cortex or WT brain. In hippocampus of both genotypes, mitochondrial size heterogeneity increased with age. Notably, an inverse correlation between heterogeneity and CI was found in both genotypes, indicating that heterogeneity reflects mitochondrial dysfunction. The ratio between fission and fusion gene expression reflected age-related alterations in mitochondrial morphology but not heterogeneity. Mitochondrial DNA content was lower, and hypoxia-induced factor 1α mRNA was greater at both ages in CSB m/m compared to WT brain. Our findings show that decreased CI and increased mitochondrial size heterogeneity are highly associated and point to declining mitochondrial quality control as an initial event in brain aging. Copyright © 2017 Elsevier Inc. All rights reserved.

Fossil skulls reveal that blood flow rate to the brain increased faster than brain volume during human evolution

NASA Astrophysics Data System (ADS)

Seymour, Roger S.; Bosiocic, Vanya; Snelling, Edward P.

2016-08-01

The evolution of human cognition has been inferred from anthropological discoveries and estimates of brain size from fossil skulls. A more direct measure of cognition would be cerebral metabolic rate, which is proportional to cerebral blood flow rate (perfusion). The hominin cerebrum is supplied almost exclusively by the internal carotid arteries. The sizes of the foramina that transmitted these vessels in life can be measured in hominin fossil skulls and used to calculate cerebral perfusion rate. Perfusion in 11 species of hominin ancestors, from Australopithecus to archaic Homo sapiens, increases disproportionately when scaled against brain volume (the allometric exponent is 1.41). The high exponent indicates an increase in the metabolic intensity of cerebral tissue in later Homo species, rather than remaining constant (1.0) as expected by a linear increase in neuron number, or decreasing according to Kleiber's Law (0.75). During 3 Myr of hominin evolution, cerebral tissue perfusion increased 1.7-fold, which, when multiplied by a 3.5-fold increase in brain size, indicates a 6.0-fold increase in total cerebral blood flow rate. This is probably associated with increased interneuron connectivity, synaptic activity and cognitive function, which all ultimately depend on cerebral metabolic rate.

Oxaloacetate decreases the infarct size and attenuates the reduction in evoked responses after photothrombotic focal ischemia in the rat cortex.

PubMed

Nagy, David; Marosi, Mate; Kis, Zsolt; Farkas, Tamas; Rakos, Gabriella; Vecsei, Laszlo; Teichberg, Vivian I; Toldi, Jozsef

2009-09-01

A traumatic brain injury or a focal brain lesion is followed by acute excitotoxicity caused by the presence of abnormally high glutamate (Glu) levels in the cerebrospinal and interstitial fluids. It has recently been demonstrated that this excess Glu in the brain can be eliminated into the blood following the intravenous administration of oxaloacetate (OxAc), which, by scavenging the blood Glu, induces an enhanced and neuroprotective brain-to-blood Glu efflux. In this study, we subjected rats to a photothrombotic lesion and treated them after the illumination with a single 30-min-long administration of OxAc (1.2 mg/100 g, i.v.). Following induction of the lesion, we measured the infarct size and the amplitudes of the somatosensory evoked potentials (SEPs) as recorded from the skull surface. The photothrombotic lesion resulted in appreciably decreased amplitudes of the evoked potentials, but OxAc administration significantly attenuated this reduction, and also the infarct size assessed histologically. We suggest that the neuroprotective effects of OxAc are due to its blood Glu-scavenging activity, which, by increasing the brain-to-blood Glu efflux, reduces the excess Glu responsible for the anatomical and functional correlates of the ischemia, as evaluated by electrophysiological evoked potential (EP) measurements.

Moderate and late preterm birth: effect on brain size and maturation at term-equivalent age.

PubMed

Walsh, Jennifer M; Doyle, Lex W; Anderson, Peter J; Lee, Katherine J; Cheong, Jeanie L Y

2014-10-01

To compare the size of multiple brain structures, maturation in terms of both brain myelination and gyral development, and evidence of brain injury between moderate and late preterm (MLPT) and term-born infants at term-equivalent age. The study was approved by the human research ethics committees of the participating hospitals, and informed parental consent was obtained for all infants. One hundred ninety-nine MLPT and 50 term-born infants underwent 3-T magnetic resonance (MR) imaging brain examinations at 38-44 weeks of corrected gestational age. T1- and T2-weighted MR images were compared between groups for size of multiple cerebral structures, degree of myelination in the posterior limb of the internal capsule, gyral maturation, signal intensity abnormalities, and presence of cysts by a single assessor who was blinded to the gestational group and perinatal course of the infants. Group differences were compared by using linear regression for continuous variables and logistic regression for categorical variables, and interrater and intrarater reliability was assessed by using intraclass correlation coefficients. Compared with those in the term-born control group, measurements of brain biparietal diameter, corpus callosum, basal ganglia and thalami, and cerebellum were smaller in infants in the MLPT group (all P ≤ .01), while extracerebral space was larger (P < .0001). Myelination of the posterior limb of the internal capsule was less developed, and gyral maturation was delayed in the MLPT group (both P < .001). Signal intensity abnormalities and cysts were uncommon in both groups, with 13 (6.5%) MLPT infants and one (2%) term infant having abnormalities. Inter- and intrarater reliability was good for most measures, with intraclass correlation coefficients generally greater than 0.68. MLPT birth is associated with smaller brain size, less-developed myelination of the posterior limb of the internal capsule, and more immature gyral folding than those associated with full-term birth. These brain changes may form the basis of some of the long-term neurodevelopmental deficits observed in MLPT children. Online supplemental material is available for this article. © RSNA, 2014.

Avalanches and generalized memory associativity in a network model for conscious and unconscious mental functioning

NASA Astrophysics Data System (ADS)

Siddiqui, Maheen; Wedemann, Roseli S.; Jensen, Henrik Jeldtoft

2018-01-01

We explore statistical characteristics of avalanches associated with the dynamics of a complex-network model, where two modules corresponding to sensorial and symbolic memories interact, representing unconscious and conscious mental processes. The model illustrates Freud's ideas regarding the neuroses and that consciousness is related with symbolic and linguistic memory activity in the brain. It incorporates the Stariolo-Tsallis generalization of the Boltzmann Machine in order to model memory retrieval and associativity. In the present work, we define and measure avalanche size distributions during memory retrieval, in order to gain insight regarding basic aspects of the functioning of these complex networks. The avalanche sizes defined for our model should be related to the time consumed and also to the size of the neuronal region which is activated, during memory retrieval. This allows the qualitative comparison of the behaviour of the distribution of cluster sizes, obtained during fMRI measurements of the propagation of signals in the brain, with the distribution of avalanche sizes obtained in our simulation experiments. This comparison corroborates the indication that the Nonextensive Statistical Mechanics formalism may indeed be more well suited to model the complex networks which constitute brain and mental structure.

Large-scale brain networks in affective and social neuroscience: Towards an integrative functional architecture of the brain

PubMed Central

Barrett, Lisa Feldman; Satpute, Ajay

2013-01-01

Understanding how a human brain creates a human mind ultimately depends on mapping psychological categories and concepts to physical measurements of neural response. Although it has long been assumed that emotional, social, and cognitive phenomena are realized in the operations of separate brain regions or brain networks, we demonstrate that it is possible to understand the body of neuroimaging evidence using a framework that relies on domain general, distributed structure-function mappings. We review current research in affective and social neuroscience and argue that the emerging science of large-scale intrinsic brain networks provides a coherent framework for a domain-general functional architecture of the human brain. PMID:23352202

Brain Tumor Epidemiology: Consensus from the Brain Tumor Epidemiology Consortium (BTEC)

PubMed Central

Bondy, Melissa L.; Scheurer, Michael E.; Malmer, Beatrice; Barnholtz-Sloan, Jill S.; Davis, Faith G.; Il’yasova, Dora; Kruchko, Carol; McCarthy, Bridget J.; Rajaraman, Preetha; Schwartzbaum, Judith A.; Sadetzki, Siegal; Schlehofer, Brigitte; Tihan, Tarik; Wiemels, Joseph L.; Wrensch, Margaret; Buffler, Patricia A.

2010-01-01

Epidemiologists in the Brain Tumor Epidemiology Consortium (BTEC) have prioritized areas for further research. Although many risk factors have been examined over the past several decades, there are few consistent findings possibly due to small sample sizes in individual studies and differences between studies in subjects, tumor types, and methods of classification. Individual studies have generally lacked sufficient sample size to examine interactions. A major priority based on available evidence and technologies includes expanding research in genetics and molecular epidemiology of brain tumors. BTEC has taken an active role in promoting understudied groups such as pediatric brain tumors, the etiology of rare glioma subtypes, such as oligodendroglioma, and meningioma, which not uncommon, has only recently been systematically registered in the US. There is also a pressing need to bring more researchers, especially junior investigators, to study brain tumor epidemiology. However, relatively poor funding for brain tumor research has made it difficult to encourage careers in this area. We review the group’s consensus on the current state of scientific findings and present a consensus on research priorities to identify the important areas the science should move to address. PMID:18798534

The endocranial cast of an early miocene edentate, Hapalops indifferens Ameghino (Mammalia, Edentata, Tardigrada, Megatheriidae). Comparative study with brains of recent sloths.

PubMed

Dozo, M T

1987-01-01

A natural endocranial cast which represents a complete brain of a specimen of Hapalops indifferens is described. Comparing this cast to brains of actual Tardigrada, it shows a telencephalic morphology and a pattern of neocortical sulci that resemble more the brain of Bradypus rather than that of Choloepus. The neocortical sulci homologate the lateral or corono-lateral, suprasylvian and pseudosylvian sulci. Taking into account the studies of cortical maps in Bradypus and the notable similitude of the pattern of neocortical sulci between Bradypus and H. indifferens, the possible representation of the primary sensitive and motor somatic areas, secondary sensitive somatic area, visual and auditory areas are inferred. As in Bradypus, the primary sensitive and motor somatotopic organizations would be overlapped and would not be mirror images; they would show a predominance of the area of the forelimb. The relative brain size of H. indifferens is similar or higher than that of sloths of the genus Bradypus. The close resemblance between Bradypus and Hapalops, with respect to its brain morphology and relative brain size. is congruent with the current hypothesis of the phylogenetic relations between fossil and recent Tardigrada.

Multisite Reliability of Cognitive BOLD Data

PubMed Central

Brown, Gregory G.; Mathalon, Daniel H.; Stern, Hal; Ford, Judith; Mueller, Bryon; Greve, Douglas N.; McCarthy, Gregory; Voyvodic, Jim; Glover, Gary; Diaz, Michele; Yetter, Elizabeth; Burak Ozyurt, I.; Jorgensen, Kasper W.; Wible, Cynthia G.; Turner, Jessica A.; Thompson, Wesley K.; Potkin, Steven G.

2010-01-01

Investigators perform multi-site functional magnetic resonance imaging studies to increase statistical power, to enhance generalizability, and to improve the likelihood of sampling relevant subgroups. Yet undesired site variation in imaging methods could off-set these potential advantages. We used variance components analysis to investigate sources of variation in the blood oxygen level dependent (BOLD) signal across four 3T magnets in voxelwise and region of interest (ROI) analyses. Eighteen participants traveled to four magnet sites to complete eight runs of a working memory task involving emotional or neutral distraction. Person variance was more than 10 times larger than site variance for five of six ROIs studied. Person-by-site interactions, however, contributed sizable unwanted variance to the total. Averaging over runs increased between-site reliability, with many voxels showing good to excellent between-site reliability when eight runs were averaged and regions of interest showing fair to good reliability. Between-site reliability depended on the specific functional contrast analyzed in addition to the number of runs averaged. Although median effect size was correlated with between-site reliability, dissociations were observed for many voxels. Brain regions where the pooled effect size was large but between-site reliability was poor were associated with reduced individual differences. Brain regions where the pooled effect size was small but between-site reliability was excellent were associated with a balance of participants who displayed consistently positive or consistently negative BOLD responses. Although between-site reliability of BOLD data can be good to excellent, acquiring highly reliable data requires robust activation paradigms, ongoing quality assurance, and careful experimental control. PMID:20932915

Functional size of human visual area V1: a neural correlate of top-down attention.

PubMed

Verghese, Ashika; Kolbe, Scott C; Anderson, Andrew J; Egan, Gary F; Vidyasagar, Trichur R

2014-06-01

Heavy demands are placed on the brain's attentional capacity when selecting a target item in a cluttered visual scene, or when reading. It is widely accepted that such attentional selection is mediated by top-down signals from higher cortical areas to early visual areas such as the primary visual cortex (V1). Further, it has also been reported that there is considerable variation in the surface area of V1. This variation may impact on either the number or specificity of attentional feedback signals and, thereby, the efficiency of attentional mechanisms. In this study, we investigated whether individual differences between humans performing attention-demanding tasks can be related to the functional area of V1. We found that those with a larger representation in V1 of the central 12° of the visual field as measured using BOLD signals from fMRI were able to perform a serial search task at a faster rate. In line with recent suggestions of the vital role of visuo-spatial attention in reading, the speed of reading showed a strong positive correlation with the speed of visual search, although it showed little correlation with the size of V1. The results support the idea that the functional size of the primary visual cortex is an important determinant of the efficiency of selective spatial attention for simple tasks, and that the attentional processing required for complex tasks like reading are to a large extent determined by other brain areas and inter-areal connections. Copyright © 2014 Elsevier Inc. All rights reserved.