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

Subcortical brain volume differences of participants with ADHD across the lifespan: an ENIGMA collaboration

PubMed Central

Hoogman, Martine; Bralten, Janita; Hibar, Derrek P.; Mennes, Maarten; Zwiers, Marcel P.; Schweren, Lizanne; van Hulzen, Kimm J.E.; Medland, Sarah E.; Shumskaya, Elena; Jahanshad, Neda; de Zeeuw, Patrick; Szekely, Eszter; Sudre, Gustavo; Wolfers, Thomas; Onnink, Alberdingk M.H.; Dammers, Janneke T.; Mostert, Jeanette C.; Vives-Gilabert, Yolanda; Kohls, Gregor; Oberwelland, Eileen; Seitz, Jochen; Schulte-Rüther, Martin; di Bruttopilo, Sara Ambrosino; Doyle, Alysa E.; Høvik, Marie F.; Dramsdahl, Margaretha; Tamm, Leanne; van Erp, Theo G.M.; Dale, Anders; Schork, Andrew; Conzelmann, Annette; Zierhut, Kathrin; Baur, Ramona; McCarthy, Hazel; Yoncheva, Yuliya N.; Cubillo, Ana; Chantiluke, Kaylita; Mehta, Mitul A.; Paloyelis, Yannis; Hohmann, Sarah; Baumeister, Sarah; Bramati, Ivanei; Mattos, Paulo; Tovar-Moll, Fernanda; Douglas, Pamela; Banaschewski, Tobias; Brandeis, Daniel; Kuntsi, Jonna; Asherson, Phil; Rubia, Katya; Kelly, Clare; Di Martino, Adriana; Milham, Michael P.; Castellanos, Francisco X.; Frodl, Thomas; Zentis, Mariam; Lesch, Klaus-Peter; Reif, Andreas; Pauli, Paul; Jernigan, Terry; Haavik, Jan; Plessen, Kerstin J.; Lundervold, Astri J.; Hugdahl, Kenneth; Seidman, Larry J.; Biederman, Joseph; Rommelse, Nanda; Heslenfeld, Dirk J.; Hartman, Catharina; Hoekstra, Pieter J.; Oosterlaan, Jaap; von Polier, Georg; Konrad, Kerstin; Vilarroya, Oscar; Ramos-Quiroga, Josep-Antoni; Soliva, Joan Carles; Durston, Sarah; Buitelaar, Jan K.; Faraone, Stephen V.; Shaw, Philip; Thompson, Paul; Franke, Barbara

2017-01-01

BACKGROUND Neuroimaging studies show structural alterations in several brain regions in children and adults with attention-deficit/hyperactivity disorder (ADHD). Through the formation of the worldwide ENIGMA ADHD Working Group, we addressed weaknesses of prior imaging studies and meta-analyses in sample size and methodological heterogeneity. METHODS Our sample comprised 1713 participants with ADHD and 1529 controls from 23 sites (age range: 4–63 years; 66% males). Individual sites analyzed magnetic resonance imaging brain scans with harmonized protocols. Case-control differences in subcortical structures and intracranial volume (ICV) were assessed through mega-and meta-analysis. FINDINGS The volumes of the accumbens (Cohen’s d=−0.15), amygdala (d=−0.19), caudate (d=−0.11), hippocampus (d=−0.11), putamen (d=−0.14), and ICV (d=−0.10) were found to be smaller in cases relative to controls. Effect sizes were highest in children, case-control differences were not present in adults. Explorative lifespan modeling suggested a delay of maturation and a delay of degeneration. Psychostimulant medication use or presence of comorbid psychiatric disorders did not influence results, nor did symptom scores correlate with brain volume. INTERPRETATION Using the largest data set to date, we extend the brain maturation delay theory for ADHD to include subcortical structures and refute medication effects on brain volume suggested by earlier meta-analyses. We add new knowledge about bilateral amygdala, accumbens, and hippocampus reductions in ADHD, and provide unprecedented precision in effect size estimates. Lifespan analyses suggest that, in the absence of well-powered longitudinal studies, the ENIGMA cross-sectional sample across six decades of life provides a means to generate hypotheses about lifespan trajectories in brain phenotypes. FUNDING National Institutes of Health PMID:28219628

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.

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.

Traumatic brain injury and hemorrhagic shock: evaluation of different resuscitation strategies in a large animal model of combined insults.

PubMed

Jin, Guang; DeMoya, Marc A; Duggan, Michael; Knightly, Thomas; Mejaddam, Ali Y; Hwabejire, John; Lu, Jennifer; Smith, William Michael; Kasotakis, Georgios; Velmahos, George C; Socrate, Simona; Alam, Hasan B

2012-07-01

Traumatic brain injury (TBI) and hemorrhagic shock (HS) are the leading causes of trauma-related mortality and morbidity. Combination of TBI and HS (TBI + HS) is highly lethal, and the optimal resuscitation strategy for this combined insult remains unclear. A critical limitation is the lack of suitable large animal models to test different treatment strategies. We have developed a clinically relevant large animal model of TBI + HS, which was used to evaluate the impact of different treatments on brain lesion size and associated edema. Yorkshire swine (42-50 kg) were instrumented to measure hemodynamic parameters and intracranial pressure. A computer-controlled cortical impact device was used to create a TBI through a 20-mm craniotomy: 15-mm cylindrical tip impactor at 4 m/s velocity, 100-ms dwell time, and 12-mm penetration depth. Volume-controlled hemorrhage was started (40% blood volume) concurrent with the TBI. After 2 h of shock, animals were randomized to one of three resuscitation groups (n = 5/group): (a) normal saline (NS); (b) 6% hetastarch, Hextend (Hex); and (c) fresh frozen plasma (FFP). Volumes of Hex and FFP matched the shed blood, whereas NS was three times the volume. After 6 h of postresuscitation monitoring, brains were sectioned into 5-mm slices and stained with TTC (2,3,5-triphenyltetrazolium chloride) to quantify the lesion size and brain swelling. Combination of 40% blood loss with cortical impact and a period of shock (2 h) resulted in a highly reproducible brain injury. Total fluid requirements were lower in the Hex and FFP groups. Lesion size and brain swelling in the FFP group (2,160 ± 202.63 mm and 22% ± 1.0%, respectively) were significantly smaller than those in the NS group (3,285 ± 130.8 mm3 and 37% ± 1.6%, respectively) (P < 0.05). Hex treatment decreased the swelling (29% ± 1.6%) without reducing the lesion size. Early administration of FFP reduces the size of brain lesion and associated swelling in a large animal model of TBI + HS. In contrast, artificial colloid (Hex) decreases swelling without reducing the actual size of the brain lesion.

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…

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

Adolescents who were born very preterm have decreased brain volumes.

PubMed

Nosarti, Chiara; Al-Asady, Mazin H S; Frangou, Sophia; Stewart, Ann L; Rifkin, Larry; Murray, Robin M

2002-07-01

Infants born very preterm have an increased risk of brain injury. Given the great increase in the number of such infants that are surviving, it is important to establish whether any resultant brain abnormalities persist into adolescence and adult life. We therefore examined in vivo whole brain, grey matter, white matter and hippocampal volumes, ventricular size and grey/white matter ratios in a series of adolescents who had been born very preterm, and an age-matched full-term control group. Structural MRI was carried out on a cohort of 72 adolescents (mean age 15 years) who were born before 33 weeks, and 48 age-matched full-term controls. Brain measurements were made blind to group affiliation using stereological principles. After controlling for gender and height, the very preterm subjects showed a 6.0% decrease in whole brain volume, and an 11.8% decrease in cortical grey matter volume, as well as a 15.6% decrease in right and a 12.1% decrease in left hippocampal volumes; they also had a 42.0% increase in the size of the lateral ventricles. Therefore, individuals who were born very preterm continue to show noticeable decrements in brain volumes and striking increases in lateral ventricular volume into adolescence. The functional significance of these abnormalities merits further investigation.

Neuron number and size in prefrontal cortex of children with autism.

PubMed

Courchesne, Eric; Mouton, Peter R; Calhoun, Michael E; Semendeferi, Katerina; Ahrens-Barbeau, Clelia; Hallet, Melodie J; Barnes, Cynthia Carter; Pierce, Karen

2011-11-09

Autism often involves early brain overgrowth, including the prefrontal cortex (PFC). Although prefrontal abnormality has been theorized to underlie some autistic symptoms, the cellular defects that cause abnormal overgrowth remain unknown. To investigate whether early brain overgrowth in children with autism involves excess neuron numbers in the PFC. DESIGN, SETTING, AND CASES: Postmortem prefrontal tissue from 7 autistic and 6 control male children aged 2 to 16 years was examined by expert anatomists who were blinded to diagnostic status. Number and size of neurons were quantified using stereological methods within the dorsolateral (DL-PFC) and mesial (M-PFC) subdivisions of the PFC. Cases were from the eastern and southeastern United States and died between 2000 and 2006. Mean neuron number and size in the DL-PFC and M-PFC were compared between autistic and control postmortem cases. Correlations of neuron number with deviation in brain weight from normative values for age were also performed. Children with autism had 67% more neurons in the PFC (mean, 1.94 billion; 95% CI, 1.57-2.31) compared with control children (1.16 billion; 95% CI, 0.90-1.42; P = .002), including 79% more in DL-PFC (1.57 billion; 95% CI, 1.20-1.94 in autism cases vs 0.88 billion; 95% CI, 0.66-1.10 in controls; P = .003) and 29% more in M-PFC (0.36 billion; 95% CI, 0.33-0.40 in autism cases vs 0.28 billion; 95% CI, 0.23-0.34 in controls; P = .009). Brain weight in the autistic cases differed from normative mean weight for age by a mean of 17.6% (95% CI, 10.2%-25.0%; P = .001), while brains in controls differed by a mean of 0.2% (95% CI, -8.7% to 9.1%; P = .96). Plots of counts by weight showed autistic children had both greater total prefrontal neuron counts and brain weight for age than control children. In this small preliminary study, brain overgrowth in males with autism involved an abnormal excess number of neurons in the PFC.

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 Cortical Thickness Differences in Adolescent Females with Substance Use Disorders.

PubMed

Boulos, Peter K; Dalwani, Manish S; Tanabe, Jody; Mikulich-Gilbertson, Susan K; Banich, Marie T; Crowley, Thomas J; Sakai, Joseph T

2016-01-01

We recruited right-handed female patients, 14-19 years of age, from a university-based treatment program for youths with substance use disorders and community controls similar for age, race and zip code of residence. We obtained 43 T1-weighted structural brain images (22 patients and 21 controls) to examine group differences in cortical thickness across the entire brain as well as six a priori regions-of-interest: 1) medial orbitofrontal cortex; 2) rostral anterior cingulate cortex; and 3) middle frontal cortex, in each hemisphere. Age and IQ were entered as nuisance factors for all analyses. A priori region-of-interest analyses yielded no significant differences. However, whole-brain group comparisons revealed that the left pregenual rostral anterior cingulate cortex extending into the left medial orbitofrontal region (355.84 mm2 in size), a subset of two of our a priori regions-of-interest, was significantly thinner in patients compared to controls (vertex-level threshold p = 0.005 and cluster-level family wise error corrected threshold p = 0.05). The whole-brain group differences did not survive after adjusting for depression or externalizing scores. Whole-brain within-patient analyses demonstrated a positive association between cortical thickness in the left precuneus and behavioral disinhibition scores (458.23 mm2 in size). Adolescent females with substance use disorders have significant differences in brain cortical thickness in regions engaged by the default mode network and that have been associated with problems of emotional dysregulation, inhibition, and behavioral control in past studies.

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.

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.

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

Evolution of brain region volumes during artificial selection for relative brain size.

PubMed

Kotrschal, Alexander; Zeng, Hong-Li; van der Bijl, Wouter; Öhman-Mägi, Caroline; Kotrschal, Kurt; Pelckmans, Kristiaan; Kolm, Niclas

2017-12-01

The vertebrate brain shows an extremely conserved layout across taxa. Still, the relative sizes of separate brain regions vary markedly between species. One interesting pattern is that larger brains seem associated with increased relative sizes only of certain brain regions, for instance telencephalon and cerebellum. Till now, the evolutionary association between separate brain regions and overall brain size is based on comparative evidence and remains experimentally untested. Here, we test the evolutionary response of brain regions to directional selection on brain size in guppies (Poecilia reticulata) selected for large and small relative brain size. In these animals, artificial selection led to a fast response in relative brain size, while body size remained unchanged. We use microcomputer tomography to investigate how the volumes of 11 main brain regions respond to selection for larger versus smaller brains. We found no differences in relative brain region volumes between large- and small-brained animals and only minor sex-specific variation. Also, selection did not change allometric scaling between brain and brain region sizes. Our results suggest that brain regions respond similarly to strong directional selection on relative brain size, which indicates that brain anatomy variation in contemporary species most likely stem from direct selection on key regions. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Brain nuclei in actively courting red-sided garter snakes: a paradigm of neural trimorphism.

PubMed

Krohmer, Randolph W; DeMarchi, Geno A; Baleckaitis, Daniel D; Lutterschmidt, Deborah I; Mason, Robert T

2011-03-28

During the breeding season, two distinct male phenotypes are exhibited by red-sided garter snakes (Thamnophis sirtalis parietalis), with courtship behavior being directed not only toward females, but also toward a sub-population of males called she-males. She-males are morphologically identical to other males except for a circulating androgen level three times that of normal males and their ability to produce a female-like pheromone. As in other vertebrates, limbic nuclei in the red-sided garter snake brain are involved in the control of sexual behaviors. For example, an intact anterior hypothalamus pre-optic area (AHPOA) is essential for the initiation and maintenance of reproduction. To determine if brain morphology varies among the three behavioral phenotypes (i.e., males, she-males, and females) during the breeding season, we examined the volume, cell size and cell density of the AHPOA as well as a control region, the external nucleus of the optic tract (ENOT). We used Luxol Fast Blue and Ziehl's Fuchsin to visualize neurons and glial cells, respectively. No significant differences were observed among the three behavioral phenotypes in the volume, cell size or density in the control region. In contrast, the volume, cell size and density of the AHPOA of she-males were significantly greater than those of both male and female snakes. While the volume of the AHPOA was significantly greater in females compared to males, no differences were observed in cell size or density. These differences in brain morphology suggest a possible underlying mechanism for phenotypic-specific behavioral patterns. Copyright © 2010 Elsevier Inc. All rights reserved.

Brain structure and executive functions in children with cerebral palsy: a systematic review.

PubMed

Weierink, Lonneke; Vermeulen, R Jeroen; Boyd, Roslyn N

2013-05-01

This systematic review aimed to establish the current knowledge about brain structure and executive function (EF) in children with cerebral palsy (CP). Five databases were searched (up till July 2012). Six articles met the inclusion criteria, all included structural brain imaging though no functional brain imaging. Study quality was assessed using the STROBE checklist. All articles scored between 58.7% and 70.5% for quality (100% is the maximum score). The included studies all reported poorer performance on EF tasks for children with CP compared to children without CP. For the selected EF measures non-significant effect sizes were found for the CP group compared to a semi-control group (children without cognitive deficits but not included in a control group). This could be due to the small sample sizes, group heterogeneity and lack of comparison of the CP group to typically developing children. The included studies did not consider specific brain areas associated with EF performance. To conclude, there is a paucity of brain imaging studies focused on EF in children with CP, especially of studies that include functional brain imaging. Outcomes of the present studies are difficult to compare as each study included different EF measures and cortical abnormality measures. Copyright © 2013 Elsevier Ltd. All rights reserved.

Postoperative Stereotactic Radiosurgery Without Whole-Brain Radiation Therapy for Brain Metastases: Potential Role of Preoperative Tumor Size

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

Hartford, Alan C., E-mail: Alan.C.Hartford@Hitchcock.org; Paravati, Anthony J.; Spire, William J.

2013-03-01

Purpose: Radiation therapy following resection of a brain metastasis increases the probability of disease control at the surgical site. We analyzed our experience with postoperative stereotactic radiosurgery (SRS) as an alternative to whole-brain radiotherapy (WBRT), with an emphasis on identifying factors that might predict intracranial disease control and overall survival (OS). Methods and Materials: We retrospectively reviewed all patients through December 2008, who, after surgical resection, underwent SRS to the tumor bed, deferring WBRT. Multiple factors were analyzed for time to intracranial recurrence (ICR), whether local recurrence (LR) at the surgical bed or “distant” recurrence (DR) in the brain, formore » time to WBRT, and for OS. Results: A total of 49 lesions in 47 patients were treated with postoperative SRS. With median follow-up of 9.3 months (range, 1.1-61.4 months), local control rates at the resection cavity were 85.5% at 1 year and 66.9% at 2 years. OS rates at 1 and 2 years were 52.5% and 31.7%, respectively. On univariate analysis (preoperative) tumors larger than 3.0 cm exhibited a significantly shorter time to LR. At a cutoff of 2.0 cm, larger tumors resulted in significantly shorter times not only for LR but also for DR, ICR, and salvage WBRT. While multivariate Cox regressions showed preoperative size to be significant for times to DR, ICR, and WBRT, in similar multivariate analysis for OS, only the graded prognostic assessment proved to be significant. However, the number of intracranial metastases at presentation was not significantly associated with OS nor with other outcome variables. Conclusions: Larger tumor size was associated with shorter time to recurrence and with shorter time to salvage WBRT; however, larger tumors were not associated with decrements in OS, suggesting successful salvage. SRS to the tumor bed without WBRT is an effective treatment for resected brain metastases, achieving local control particularly for tumors up to 3.0 cm diameter.« less

Pupillary and Heart Rate Reactivity in Children with Minimal Brain Dysfunction

ERIC Educational Resources Information Center

Zahn, Theodore P.; And Others

1978-01-01

In an attempt to replicate and extend previous findings on autonomic arousal and responsivity in children with minimal brain dysfunction (MBD), pupil size, heart rate, skin conductance, and skin temperature were recorded from 32 MBD and 45 control children (6-13 years old). (Author/CL)

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

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

Brain structure characteristics in intellectually superior schizophrenia.

PubMed

Vaskinn, Anja; Hartberg, Cecilie B; Sundet, Kjetil; Westlye, Lars T; Andreassen, Ole A; Melle, Ingrid; Agartz, Ingrid

2015-04-30

The current study aims to fill a gap in the knowledge base by investigating the structural brain characteristics of individuals with schizophrenia and superior intellectual abilities. Subcortical volumes, cortical thickness and cortical surface area were examined in intellectually normal and intellectually superior participants with schizophrenia and their IQ-matched healthy controls, as well as in intellectually low schizophrenia participants. We replicated significant diagnostic group effects on hippocampal and ventricular size after correction for multiple comparisons. There were no statistically significant effects of intellectual level or of the interaction between diagnostic group and intellectual level. Effect sizes indicated that differences between schizophrenia and healthy control participants were of similar magnitude at both intellectual levels for all three types of morphological data. A secondary analysis within the schizophrenia group, including participants with low intellectual abilities, yielded numerical, but no statistically significant differences on any structural brain measure. The present findings indicate that the brain structure abnormalities in schizophrenia are present at all intellectual levels, and individuals with schizophrenia and superior intellectual abilities have brain structure abnormalities of the same magnitude as individuals with schizophrenia and normal intellectual abilities. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Pancreatic signals controlling food intake; insulin, glucagon and amylin

PubMed Central

Woods, Stephen C; Lutz, Thomas A; Geary, Nori; Langhans, Wolfgang

2006-01-01

The control of food intake and body weight by the brain relies upon the detection and integration of signals reflecting energy stores and fluxes, and their interaction with many different inputs related to food palatability and gastrointestinal handling as well as social, emotional, circadian, habitual and other situational factors. This review focuses upon the role of hormones secreted by the endocrine pancreas: hormones, which individually and collectively influence food intake, with an emphasis upon insulin, glucagon and amylin. Insulin and amylin are co-secreted by B-cells and provide a signal that reflects both circulating energy in the form of glucose and stored energy in the form of visceral adipose tissue. Insulin acts directly at the liver to suppress the synthesis and secretion of glucose, and some plasma insulin is transported into the brain and especially the mediobasal hypothalamus where it elicits a net catabolic response, particularly reduced food intake and loss of body weight. Amylin reduces meal size by stimulating neurons in the hindbrain, and there is evidence that amylin additionally functions as an adiposity signal controlling body weight as well as meal size. Glucagon is secreted from A-cells and increases glucose secretion from the liver. Glucagon acts in the liver to reduce meal size, the signal being relayed to the brain via the vagus nerves. To summarize, hormones of the endocrine pancreas are collectively at the crossroads of many aspects of energy homeostasis. Glucagon and amylin act in the short term to reduce meal size, and insulin sensitizes the brain to short-term meal-generated satiety signals; and insulin and perhaps amylin as well act over longer intervals to modulate the amount of fat maintained and defended by the brain. Hormones of the endocrine pancreas interact with receptors at many points along the gut–brain axis, from the liver to the sensory vagus nerve to the hindbrain to the hypothalamus; and their signals are conveyed both neurally and humorally. Finally, their actions include gastrointestinal and metabolic as well as behavioural effects. PMID:16815800

Volumetric and Voxel-Based Morphometry Findings in Autism Subjects With and Without Macrocephaly

PubMed Central

Bigler, Erin D.; Abildskov, Tracy J.; Petrie, Jo Ann; Johnson, Michael; Lange, Nicholas; Chipman, Jonathan; Lu, Jeffrey; McMahon, William; Lainhart, Janet E.

2015-01-01

This study sought to replicate Herbert et al. (2003a), which found increased overall white matter (WM) volume in subjects with autism, even after controlling for head size differences. To avoid the possibility that greater WM volume in autism is merely an epiphenomena of macrocephaly over-representation associated with the disorder, the current study included control subjects with benign macrocephaly. The control group also included subjects with a reading disability to insure cognitive heterogeneity. WM volume in autism was significantly larger, even when controlling for brain volume, rate of macrocephaly, and other demographic variables. Autism and controls differed little on whole-brain WM voxel-based morphometry (VBM) analyses suggesting that the overall increase in WM volume was non-localized. Autism subjects exhibited a differential pattern of IQ relationships with brain volumetry findings from controls. Current theories of brain overgrowth and their importance in the development of autism are discussed in the context of these findings. PMID:20446133

Sex dependence of brain size and shape in bipolar disorder: an exploratory study.

PubMed

Mackay, Clare E; Roddick, Elina; Barrick, Thomas R; Lloyd, Adrian J; Roberts, Neil; Crow, Tim J; Young, Allan H; Ferrier, I Nicol

2010-05-01

Anomalies of asymmetry and sex differences in brain structure have frequently been described in schizophrenic illnesses but have seldom been explored in bipolar disorder. We measured volumes of the left and right frontal, temporal, parietal, and occipital lobes and computed the magnitude of brain torque (i.e., rightward frontal and leftward occipital asymmetry) for 49 patients with bipolar disorder and 47 healthy controls and performed an exploratory analysis of sex differences in patients and controls. Patients had significantly greater cerebrospinal fluid volume than controls, but no difference in total brain volume. There were no main effects of diagnosis in gray matter lobe volume or brain torque, but when analyses were performed separately for male and female subjects, significant sex-by-diagnosis interactions were found in the volume of the left frontal, left temporal, right parietal, and right occipital lobes, such that male patients with bipolar disorder tend toward larger, more symmetric brains than male controls, whereas female patients tend toward smaller, more asymmetric brains than female controls. The lateralised nature of these interactions was such that the normal sex difference in volume was significantly accentuated, whilst the normal sex difference in asymmetry tended to be diminished in patients with bipolar disorder. We conclude that bipolar disorder in part reflects an interaction between brain growth and sex along the anterior-posterior axis of the human brain.

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.

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.

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.

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.

Hyperforin changes the zinc-storage capacities of brain cells.

PubMed

Gibon, Julien; Richaud, Pierre; Bouron, Alexandre

2011-12-01

In vitro and in vivo experiments were carried out to investigate the consequences on brain cells of a chronic treatment with hyperforin, a plant extract known to dissipate the mitochondrial membrane potential and to release Zn(2+) and Ca(2+) from these organelles. Dissociated cortical neurons were grown in a culture medium supplemented with 1 μM hyperforin. Live-cell imaging experiments with the fluorescent probes FluoZin-3 and Fluo-4 show that a 3 day-hyperforin treatment diminishes the size of the hyperforin-sensitive pools of Ca(2+) and Zn(2+) whereas it increases the size of the DTDP-sensitive pool of Zn(2+) without affecting the ionomycin-sensitive pool of Ca(2+). When assayed by quantitative PCR the levels of mRNA coding for metallothioneins (MTs) I, II and III were increased in cortical neurons after a 3 day-hyperforin treatment. This was prevented by the zinc chelator TPEN, indicating that the plant extract controls the expression of MTs in a zinc-dependent manner. Brains of adult mice who received a daily injection (i.p.) of hyperforin (4 mg/kg/day) for 4 weeks had a higher sulphur content than control animals. They also exhibited an enhanced expression of the genes coding for MTs. However, the long-term treatment did not affect the brain levels of calcium and zinc. Based on these results showing that hyperforin influences the size of the internal pools of Zn(2+), the expression of MTs and the brain cellular sulphur content, it is proposed that hyperforin changes the Zn-storage capacity of brain cells and interferes with their thiol status. Copyright © 2011 Elsevier Ltd. All rights reserved.

Developing brain networks of attention.

PubMed

Posner, Michael I; Rothbart, Mary K; Voelker, Pascale

2016-12-01

Attention is a primary cognitive function critical for perception, language, and memory. We provide an update on brain networks related to attention, their development, training, and pathologies. An executive attention network, also called the cingulo-opercular network, allows voluntary control of behavior in accordance with goals. Individual differences among children in self-regulation have been measured by a higher order factor called effortful control, which is related to the executive network and to the size of the anterior cingulate cortex. Brain networks of attention arise in infancy and are related to individual differences, including pathology during childhood. Methods of training attention may improve performance and ameliorate pathology.

Structural imaging of the brain reveals decreased total brain and total gray matter volumes in obese but not in lean women with polycystic ovary syndrome compared to body mass index-matched counterparts.

PubMed

Ozgen Saydam, Basak; Has, Arzu Ceylan; Bozdag, Gurkan; Oguz, Kader Karli; Yildiz, Bulent Okan

2017-07-01

To detect differences in global brain volumes and identify relations between brain volume and appetite-related hormones in women with polycystic ovary syndrome (PCOS) compared to body mass index-matched controls. Forty subjects participated in this study. Cranial magnetic resonance imaging and measurements of fasting ghrelin, leptin and glucagon-like peptide 1 (GLP-1), as well as GLP-1 levels during mixed-meal tolerance test (MTT), were performed. Total brain volume and total gray matter volume (GMV) were decreased in obese PCOS compared to obese controls (p < 0.05 for both) whereas lean PCOS and controls did not show a significant difference. Secondary analyses of regional brain volumes showed decreases in GMV of the caudate nucleus, ventral diencephalon and hippocampus in obese PCOS compared to obese controls (p < 0.05 for all), whereas lean patients with PCOS had lower GMV in the amygdala than lean controls (p < 0.05). No significant relations were detected between structural differences and measured hormone levels at baseline or during MTT. This study, investigating structural brain alterations in PCOS, suggests volumetric reductions in global brain areas in obese women with PCOS. Functional studies with larger sample size are needed to determine physiopathological roles of these changes and potential effects of long-term medical management on brain structure of PCOS.

Artificial selection on relative brain size in the guppy reveals costs and benefits of evolving a larger brain.

PubMed

Kotrschal, Alexander; Rogell, Björn; Bundsen, Andreas; Svensson, Beatrice; Zajitschek, Susanne; Brännström, Ioana; Immler, Simone; Maklakov, Alexei A; Kolm, Niclas

2013-01-21

The large variation in brain size that exists in the animal kingdom has been suggested to have evolved through the balance between selective advantages of greater cognitive ability and the prohibitively high energy demands of a larger brain (the "expensive-tissue hypothesis"). Despite over a century of research on the evolution of brain size, empirical support for the trade-off between cognitive ability and energetic costs is based exclusively on correlative evidence, and the theory remains controversial. Here we provide experimental evidence for costs and benefits of increased brain size. We used artificial selection for large and small brain size relative to body size in a live-bearing fish, the guppy (Poecilia reticulata), and found that relative brain size evolved rapidly in response to divergent selection in both sexes. Large-brained females outperformed small-brained females in a numerical learning assay designed to test cognitive ability. Moreover, large-brained lines, especially males, developed smaller guts, as predicted by the expensive-tissue hypothesis, and produced fewer offspring. We propose that the evolution of brain size is mediated by a functional trade-off between increased cognitive ability and reproductive performance and discuss the implications of these findings for vertebrate brain evolution. Copyright © 2013 Elsevier Ltd. All rights reserved.

Neuroprotective effects of yoga practice: age-, experience-, and frequency-dependent plasticity

PubMed Central

Villemure, Chantal; Čeko, Marta; Cotton, Valerie A.; Bushnell, M. Catherine

2015-01-01

Yoga combines postures, breathing, and meditation. Despite reported health benefits, yoga’s effects on the brain have received little study. We used magnetic resonance imaging to compare age-related gray matter (GM) decline in yogis and controls. We also examined the effect of increasing yoga experience and weekly practice on GM volume and assessed which aspects of weekly practice contributed most to brain size. Controls displayed the well documented age-related global brain GM decline while yogis did not, suggesting that yoga contributes to protect the brain against age-related decline. Years of yoga experience correlated mostly with GM volume differences in the left hemisphere (insula, frontal operculum, and orbitofrontal cortex) suggesting that yoga tunes the brain toward a parasympatically driven mode and positive states. The number of hours of weekly practice correlated with GM volume in the primary somatosensory cortex/superior parietal lobule (S1/SPL), precuneus/posterior cingulate cortex (PCC), hippocampus, and primary visual cortex (V1). Commonality analyses indicated that the combination of postures and meditation contributed the most to the size of the hippocampus, precuneus/PCC, and S1/SPL while the combination of meditation and breathing exercises contributed the most to V1 volume. Yoga’s potential neuroprotective effects may provide a neural basis for some of its beneficial effects. PMID:26029093

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.

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.

Inference of ecological and social drivers of human brain-size evolution.

PubMed

González-Forero, Mauricio; Gardner, Andy

2018-05-01

The human brain is unusually large. It has tripled in size from Australopithecines to modern humans 1 and has become almost six times larger than expected for a placental mammal of human size 2 . Brains incur high metabolic costs 3 and accordingly a long-standing question is why the large human brain has evolved 4 . The leading hypotheses propose benefits of improved cognition for overcoming ecological 5-7 , social 8-10 or cultural 11-14 challenges. However, these hypotheses are typically assessed using correlative analyses, and establishing causes for brain-size evolution remains difficult 15,16 . Here we introduce a metabolic approach that enables causal assessment of social hypotheses for brain-size evolution. Our approach yields quantitative predictions for brain and body size from formalized social hypotheses given empirical estimates of the metabolic costs of the brain. Our model predicts the evolution of adult Homo sapiens-sized brains and bodies when individuals face a combination of 60% ecological, 30% cooperative and 10% between-group competitive challenges, and suggests that between-individual competition has been unimportant for driving human brain-size evolution. Moreover, our model indicates that brain expansion in Homo was driven by ecological rather than social challenges, and was perhaps strongly promoted by culture. Our metabolic approach thus enables causal assessments that refine, refute and unify hypotheses of brain-size evolution.

Brain plasticity and functional losses in the aged: scientific bases for a novel intervention.

PubMed

Mahncke, Henry W; Bronstone, Amy; Merzenich, Michael M

2006-01-01

Aging is associated with progressive losses in function across multiple systems, including sensation, cognition, memory, motor control, and affect. The traditional view has been that functional decline in aging is unavoidable because it is a direct consequence of brain machinery wearing down over time. In recent years, an alternative perspective has emerged, which elaborates on this traditional view of age-related functional decline. This new viewpoint--based upon decades of research in neuroscience, experimental psychology, and other related fields--argues that as people age, brain plasticity processes with negative consequences begin to dominate brain functioning. Four core factors--reduced schedules of brain activity, noisy processing, weakened neuromodulatory control, and negative learning--interact to create a self-reinforcing downward spiral of degraded brain function in older adults. This downward spiral might begin from reduced brain activity due to behavioral change, from a loss in brain function driven by aging brain machinery, or more likely from both. In aggregate, these interrelated factors promote plastic changes in the brain that result in age-related functional decline. This new viewpoint on the root causes of functional decline immediately suggests a remedial approach. Studies of adult brain plasticity have shown that substantial improvement in function and/or recovery from losses in sensation, cognition, memory, motor control, and affect should be possible, using appropriately designed behavioral training paradigms. Driving brain plasticity with positive outcomes requires engaging older adults in demanding sensory, cognitive, and motor activities on an intensive basis, in a behavioral context designed to re-engage and strengthen the neuromodulatory systems that control learning in adults, with the goal of increasing the fidelity, reliability, and power of cortical representations. Such a training program would serve a substantial unmet need in aging adults. Current treatments directed at age-related functional losses are limited in important ways. Pharmacological therapies can target only a limited number of the many changes believed to underlie functional decline. Behavioral approaches focus on teaching specific strategies to aid higher order cognitive functions, and do not usually aspire to fundamentally change brain function. A brain-plasticity-based training program would potentially be applicable to all aging adults with the promise of improving their operational capabilities. We have constructed such a brain-plasticity-based training program and conducted an initial randomized controlled pilot study to evaluate the feasibility of its use by older adults. A main objective of this initial study was to estimate the effect size on standardized neuropsychological measures of memory. We found that older adults could learn the training program quickly, and could use it entirely unsupervised for the majority of the time required. Pre- and posttesting documented a significant improvement in memory within the training group (effect size 0.41, p<0.0005), with no significant within-group changes in a time-matched computer using active control group, or in a no-contact control group. Thus, a brain-plasticity-based intervention targeting normal age-related cognitive decline may potentially offer benefit to a broad population of older adults.

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

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

Social behavioral testing and brain magnetic resonance imaging in chicks exposed to mobile phone radiation during development.

PubMed

Zhou, Zien; Shan, Jiehui; Zu, Jinyan; Chen, Zengai; Ma, Weiwei; Li, Lei; Xu, Jianrong

2016-06-10

The potential adverse effect of mobile phone radiation is currently an area of great concern in the field of public health. In the present study, we aimed to investigate the effect of mobile phone radiation (900 MHz radiofrequency) during hatching on postnatal social behaviors in chicks, as well as the effect on brain size and structural maturity estimated using 3.0 T magnetic resonance imaging. At day 4 of incubation, 76 normally developing chick embryos were divided into the control group (n = 39) and the radiation group (n = 37). Eggs in the radiation group were exposed to mobile phone radiation for 10 h each day from day 4 to 19 of incubation. Behavioral tests were performed 4 days after hatching. T2-weighted MR imaging and diffusion tensor imaging (DTI) were subsequently performed. The size of different brain subdivisions (telencephalon, optic lobe, brain stem, and cerebellum) and corresponding DTI parameters were measured. The Chi-square test and the student's t test were used for statistical analysis. P < 0.05 was considered statistically significant. Compared with controls, chicks in the radiation group showed significantly slower aggregation responses (14.87 ± 10.06 vs. 7.48 ± 4.31 s, respectively; P < 0.05), lower belongingness (23.71 ± 8.72 vs. 11.45 ± 6.53 s, respectively; P < 0.05), and weaker vocalization (53.23 ± 8.60 vs. 60.01 ± 10.45 dB/30 s, respectively; P < 0.05). No significant differences were found between the radiation and control group for brain size and structural maturity, except for cerebellum size, which was significantly smaller in the radiation group (28.40 ± 1.95 vs. 29.95 ± 1.41 cm(2), P < 0.05). The hatching and heteroplasia rates were also calculated and no significant difference was found between the two groups. Mobile phone radiation exposure during chick embryogenesis impaired social behaviors after hatching and possibly induced cerebellar retardation. This indicates potential adverse effects of mobile phone radiation on brain development.

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.

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

Controlled single bubble cavitation collapse results in jet-induced injury in brain tissue.

PubMed

Canchi, Saranya; Kelly, Karen; Hong, Yu; King, Michael A; Subhash, Ghatu; Sarntinoranont, Malisa

2017-10-01

Multiscale damage due to cavitation is considered as a potential mechanism of traumatic brain injury (TBI) associated with explosion. In this study, we employed a TBI relevant hippocampal ex vivo slice model to induce bubble cavitation. Placement of single reproducible seed bubbles allowed control of size, number, and tissue location to visualize and measure deformation parameters. Maximum strain value was measured at 45 µs after bubble collapse, presented with a distinct contour and coincided temporally and spatially with the liquid jet. Composite injury maps combined this maximum strain value with maximum measured bubble size and location along with histological injury patterns. This facilitated the correlation of bubble location and subsequent jet direction to the corresponding regions of high strain which overlapped with regions of observed injury. A dynamic threshold strain range for tearing of cerebral cortex was estimated to be between 0.5 and 0.6. For a seed bubble placed underneath the hippocampus, cavitation induced damage was observed in hippocampus (local), proximal cerebral cortex (marginal) and the midbrain/forebrain (remote) upon histological evaluation. Within this test model, zone of cavitation injury was greater than the maximum radius of the bubble. Separation of apposed structures, tissue tearing, and disruption of cellular layers defined early injury patterns that were not detected in the blast-exposed half of the brain slice. Ultrastructural pathology of the neurons exposed to cavitation was characterized by disintegration of plasma membrane along with loss of cellular content. The developed test system provided a controlled experimental platform to study cavitation induced high strain deformations on brain tissue slice. The goal of the future studies will be to lower underpressure magnitude and cavitation bubble size for more sensitive evaluation of injury. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reduced amygdalar and hippocampal size in adults with generalized social phobia.

PubMed

Irle, Eva; Ruhleder, Mirjana; Lange, Claudia; Seidler-Brandler, Ulrich; Salzer, Simone; Dechent, Peter; Weniger, Godehard; Leibing, Eric; Leichsenring, Falk

2010-03-01

Structural and functional brain imaging studies suggest abnormalities of the amygdala and hippocampus in posttraumatic stress disorder and major depressive disorder. However, structural brain imaging studies in social phobia are lacking. In total, 24 patients with generalized social phobia (GSP) and 24 healthy controls underwent 3-dimensional structural magnetic resonance imaging of the amygdala and hippocampus and a clinical investigation. Compared with controls, GSP patients had significantly reduced amygdalar (13%) and hippocampal (8%) size. The reduction in the size of the amygdala was statistically significant for men but not women. Smaller right-sided hippocampal volumes of GSP patients were significantly related to stronger disorder severity. Our sample included only patients with the generalized subtype of social phobia. Because we excluded patients with comorbid depression, our sample may not be representative. We report for the first time volumetric results in patients with GSP. Future assessment of these patients will clarify whether these changes are reversed after successful treatment and whether they predict treatment response.

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

In vivo real-time fluorescence visualization and brain-targeting mechanisms of lipid nanocarriers with different fatty ester:oil ratios.

PubMed

Wen, Chih-Jen; Yen, Tzu-Chen; Al-Suwayeh, Saleh A; Chang, Hui-Wen; Fang, Jia-You

2011-11-01

The objective of the present work was to investigate the influence of the inner cores of lipid nanocarriers on the efficiency of brain targeting. Cetyl palmitate and squalene were respectively chosen as the solid lipid and liquid oil in the inner phase of the nanocarriers. Nanoparticulate systems with different cetyl palmitate/squalene ratios were compared by evaluating the size, zeta potential, molecular environment, and mobility of lipids in the systems. The particulate diameter ranged from 190 to 210 nm, with systems containing 100% cetyl palmitate in the matrix (solid lipid nanoparticles [SLN]) showing the smallest size, followed by systems with both cetyl palmitate and squalene (nanostructured lipid carriers [NLC]) and with 100% squalene (lipid emulsions [LE]). A cationic surfactant, Forestall, was used to produce a positive surface charge of 40-55 mW. The in vitro release was evaluated using various dyes located in different phases of the nanocarriers. The release of sulforhodamine B occurred in a sustained manner from the shell of the nanocarriers. The in vivo brain distribution of lipid nanosystems after an intravenous injection into rats was monitored by a real-time fluorescence imaging system. LE showed higher brain accumulation than SLN and NLC. NLC only exhibited a slightly higher brain accumulation compared with the aqueous control. Incorporation of sulforhodamine B into LE could prolong its retention in the brain from 20 to 50 min. The results were further confirmed by imaging the entire brain and brain slices. The specific association of lipid nanocarriers with rat brain endothelial cells (bEnd3) was demonstrated using fluorescence microscopy. The cellular uptake of LE and SLN was higher compared with NLC and the aqueous control. LE were observed to be internalized by cells through caveola-mediated and macropinocytotic energy-dependent endocytosis. The experimental profiles indicated that LE with moderate additives are a promising brain-targeting nanocarrier. The composition of the lipid matrix played a significant role in delivering compounds to the brain.

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

Why size matters: differences in brain volume account for apparent sex differences in callosal anatomy: the sexual dimorphism of the corpus callosum.

PubMed

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

2014-01-01

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. © 2013.

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

Stress and inflammation reduce brain-derived neurotrophic factor expression in first-episode psychosis: a pathway to smaller hippocampal volume.

PubMed

Mondelli, Valeria; Cattaneo, Annamaria; Murri, Martino Belvederi; Di Forti, Marta; Handley, Rowena; Hepgul, Nilay; Miorelli, Ana; Navari, Serena; Papadopoulos, Andrew S; Aitchison, Katherine J; Morgan, Craig; Murray, Robin M; Dazzan, Paola; Pariante, Carmine M

2011-12-01

Reduced brain-derived neurotrophic factor (BDNF) levels have been reported in the serum and plasma of patients with psychosis. The aim of this cross-sectional case-control study was to investigate potential causes and consequences of reduced BDNF expression in these patients by examining the association between BDNF levels and measures of stress, inflammation, and hippocampal volume in first-episode psychosis. Brain-derived neurotrophic factor, interleukin (IL)-6, and tumor necrosis factor (TNF)-α messenger RNA levels were measured in the leukocytes of 49 first-episode psychosis patients (DSM-IV criteria) and 30 healthy controls, all aged 18 to 65 years, recruited between January 2006 and December 2008. Patients were recruited from inpatient and outpatient units of the South London and Maudsley National Health Service Foundation Trust in London, United Kingdom, and the healthy controls were recruited from the same catchment area via advertisement and volunteer databases. In these same subjects, we measured salivary cortisol levels and collected information about psychosocial stressors (number of childhood traumas, number of recent stressors, and perceived stress). Finally, hippocampal volume was measured using brain magnetic resonance imaging in a subsample of 19 patients. Patients had reduced BDNF (effect size, d = 1.3; P < .001) and increased IL-6 (effect size, d = 1.1; P < .001) and TNF-α (effect size, d = 1.7; P < .001) gene expression levels when compared with controls, as well as higher levels of psychosocial stressors. A linear regression analysis in patients showed that a history of childhood trauma and high levels of recent stressors predicted lower BDNF expression through an inflammation-mediated pathway (adjusted R(2) = 0.23, P = .009). In turn, lower BDNF expression, increased IL-6 expression, and increased cortisol levels all significantly and independently predicted a smaller left hippocampal volume (adjusted R(2) = 0.71, P < .001). Biological changes activated by stress represent a significant factor influencing brain structure and function in first-episode psychosis through an effect on BDNF. © Copyright 2011 Physicians Postgraduate Press, Inc.

Dystrophic Serotonergic Axons in Neurodegenerative Diseases

PubMed Central

Azmitia, Efrain C.; Nixon, Ralph

2012-01-01

Neurodegenerative diseases such as Parkinson's disease (PD), frontal lobe dementia (FLD) and Diffuse Lewy-Body dementia (DLBD) have diverse neuropathologic features. Here we report that serotonin fibers are dystrophic in the brains of individuals with these three diseases. In neuropathologically normal (control) brains (n=3), serotonin axons immunoreactive (IR) with antibodies against the serotonin transporter (5-HTT) protein were widely distributed in cortex (entorhinal and dorsolateral prefrontal), hippocampus and rostral brainstem. 5-HTT-IR fibers of passage appeared thick, smooth, and un-branched in medial forebrain bundle, medial lemniscus and cortex white matter. The terminal branches were fine, highly branched and varicose in substantia nigra, hippocampus and cortical gray matter. In the diseased brains, however, 5-HTT-IR fibers in the forebrain were reduced in number and were frequently bulbous, splayed, tightly clustered and enlarged. Morphometric analysis revealed significant differences in the size distribution of the 5-HTT-IR profiles in dorsolateral prefrontal area between neurodegenerative diseases and controls. Our observations provide direct morphologic evidence for degeneration of human serotonergic axons in the brains of patients with neurodegenerative diseases despite the limited size (n=3 slices for each region (3) from each brain (4), total slices was n=36) and lack of extensive clinical characterization of the analyzed cohort. This is the first report of dystrophic 5-HTT-IR axons in postmortem human tissue PMID:18502405

Regional brain volumes and cognition in childhood epilepsy: does size really matter?

PubMed

Zelko, Frank A; Pardoe, Heath R; Blackstone, Sarah R; Jackson, Graeme D; Berg, Anne T

2014-05-01

Recent studies have correlated neurocognitive function and regional brain volumes in children with epilepsy. We tested whether brain volume differences between children with and without epilepsy explained differences in neurocognitive function. The study sample included 108 individuals with uncomplicated non-syndromic epilepsy (NSE) and 36 healthy age- and gender-matched controls. Participants received a standardized cognitive battery. Whole brain T1-weighted MRI was obtained and volumes analyzed with FreeSurfer (TM). Total brain volume (TBV) was significantly smaller in cases. After adjustment for TBV, cases had significantly larger regional grey matter volumes for total, frontal, parietal, and precentral cortex. Cases had poorer performance on neurocognitive indices of intelligence and variability of sustained attention. In cases, TBV showed small associations with intellectual indices of verbal and perceptual ability, working memory, and overall IQ. In controls, TBV showed medium associations with working memory and variability of sustained attention. In both groups, small associations were seen between some TBV-adjusted regional brain volumes and neurocognitive indices, but not in a consistent pattern. Brain volume differences did not account for cognitive differences between the groups. Patients with uncomplicated NSE have smaller brains than controls but areas of relative grey matter enlargement. That this relative regional enlargement occurs in the context of poorer overall neurocognitive functioning suggests that it is not adaptive. However, the lack of consistent associations between case-control differences in brain volumes and cognitive functioning suggests that brain volumes have limited explanatory value for cognitive functioning in childhood epilepsy. Copyright © 2014 Elsevier B.V. All rights reserved.

A Bayesian network meta-analysis of whole brain radiotherapy and stereotactic radiotherapy for brain metastasis.

PubMed

Yuan, Xi; Liu, Wen-Jie; Li, Bing; Shen, Ze-Tian; Shen, Jun-Shu; Zhu, Xi-Xu

2017-08-01

This study was conducted to compare the effects of whole brain radiotherapy (WBRT) and stereotactic radiotherapy (SRS) in treatment of brain metastasis.A systematical retrieval in PubMed and Embase databases was performed for relative literatures on the effects of WBRT and SRS in treatment of brain metastasis. A Bayesian network meta-analysis was performed by using the ADDIS software. The effect sizes included odds ratio (OR) and 95% confidence interval (CI). A random effects model was used for the pooled analysis for all the outcome measures, including 1-year distant control rate, 1-year local control rate, 1-year survival rate, and complication. The consistency was tested by using node-splitting analysis and inconsistency standard deviation. The convergence was estimated according to the Brooks-Gelman-Rubin method.A total of 12 literatures were included in this meta-analysis. WBRT + SRS showed higher 1-year distant control rate than SRS. WBRT + SRS was better for the 1-year local control rate than WBRT. SRS and WBRT + SRS had higher 1-year survival rate than the WBRT. In addition, there was no difference in complication among the three therapies.Comprehensively, WBRT + SRS might be the choice of treatment for brain metastasis.

Increased hippocampal, thalamus and amygdala volume in long-term lithium-treated bipolar I disorder patients compared with unmedicated patients and healthy subjects.

PubMed

López-Jaramillo, Carlos; Vargas, Cristian; Díaz-Zuluaga, Ana M; Palacio, Juan David; Castrillón, Gabriel; Bearden, Carrie; Vieta, Eduard

2017-02-01

Magnetic resonance imaging (MRI) studies in bipolar I disorder (BD-I) suggest that lithium is associated with increased volumes of cortico-limbic structures. However, more rigorous control of confounding factors is needed to obtain further support for this hypothesis. The aim of the present study was to assess differences in brain volumes among long-term lithium-treated BD-I patients, unmedicated BD-I patients, and healthy controls. This was a cross-sectional study with 32 euthymic BD-I patients (16 on lithium monotherapy for a mean of 180 months, and 16 receiving no medication for at least the 2 months prior to the study) and 20 healthy controls. Patients were euthymic (Hamilton Depression Rating Scale [HDRS] <6 and Young Mania Rating Scale [YMRS] <7) and had not taken psychotropic medications other than lithium for at least 6 months. Brain images were acquired on a 1.5 Tesla MRI (Phillips, Amsterdam, The Netherlands) and segmented to generate volumetric measures of cortical and subcortical brain areas, ventricles and global brain. Significant differences were found in the volumes of the left amygdala (P=.0003), right amygdala (P=.030), left hippocampus (P=.022), left thalamus (P=.022), and right thalamus (P=.019) in long-term lithium-treated BD-I patients, compared to unmedicated patients and controls, after multivariable adjustment. No differences were observed in global brain volume or in ventricular size among the three groups. Likewise, there was no correlation between serum lithium levels and the increase in size in the described brain areas. The structural differences found among the three groups, and specifically those between long-term lithium-treated and unmedicated BD-I patients, indicate increased limbic structure volumes in lithium-treated patients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

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).

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.

Effective Treatment of Solitary Pituitary Metastasis with Panhypopituitarism in HER2-Positive Breast Cancer by Lapatinib.

PubMed

Park, Youngmok; Kim, Hyemin; Kim, Eui-Hyun; Suh, Chang-Ok; Lee, Soohyeon

2016-01-01

Brain metastasis affects one third of patients with HER2-positive breast cancer after treatment with trastuzumab. Surgical resection and radiation therapy are often unsuccessful at accomplishing complete control of metastasis. Lapatinib is presumed to cross the blood-brain barrier, and exhibits clinical activities for treatment of HER2-positive breast cancer. A 43-year-old woman was treated for early breast carcinoma with total mastectomy, axillary lymph-node dissection, and adjuvant chemotherapy with cyclophosphamide plus doxorubicin. After the end of adjuvant trastuzumab therapy, she was diagnosed with panhypopituitarism due to pituitary metastasis. Surgical removal and whole brain radiation therapy were performed, but a portion of viable tumor remained. Only taking lapatinib, the size of the metastatic lesion began to shrink. Trastuzumab may have controlled the micro-metastasis of breast cancer, but it was unable to control its progression to the central nervous system. Lapatinib is a possible option for HER2-positive metastatic breast cancer patients with brain metastasis.

Flexible traffic control of the synfire-mode transmission by inhibitory modulation: Nonlinear noise reduction

NASA Astrophysics Data System (ADS)

Shinozaki, Takashi; Okada, Masato; Reyes, Alex D.; Câteau, Hideyuki

2010-01-01

Intermingled neural connections apparent in the brain make us wonder what controls the traffic of propagating activity in the brain to secure signal transmission without harmful crosstalk. Here, we reveal that inhibitory input but not excitatory input works as a particularly useful traffic controller because it controls the degree of synchrony of population firing of neurons as well as controlling the size of the population firing bidirectionally. Our dynamical system analysis reveals that the synchrony enhancement depends crucially on the nonlinear membrane potential dynamics and a hidden slow dynamical variable. Our electrophysiological study with rodent slice preparations show that the phenomenon happens in real neurons. Furthermore, our analysis with the Fokker-Planck equations demonstrates the phenomenon in a semianalytical manner.

Functional brain development in growth-restricted and constitutionally small fetuses: a fetal magnetoencephalography case-control study.

PubMed

Morin, E C; Schleger, F; Preissl, H; Braendle, J; Eswaran, H; Abele, H; Brucker, S; Kiefer-Schmidt, I

2015-08-01

Fetal magnetoencephalography records fetal brain activity non-invasively. Delayed brain responses were reported for fetuses weighing below the tenth percentile. To investigate whether this delay indicates delayed brain maturation resulting from placental insufficiency, this study distinguished two groups of fetuses below the tenth percentile: growth-restricted fetuses with abnormal umbilical artery Doppler velocity (IUGR) and constitutionally small-for-gestational-age fetuses with normal umbilical artery Doppler findings (SGA) were compared with fetuses of adequate weight for gestational age (AGA), matched for age and behavioural state. A case-control study of matched pairs. Fetal magnetoencephalography-Center at the University Hospital of Tuebingen. Fourteen IUGR fetuses and 23 SGA fetuses were matched for gestational age and fetal behavioural state with 37 healthy, normal-sized fetuses. A 156-channel fetal magentoencephalography system was used to record fetal brain activity. Light flashes as visual stimulation were applied to the fetus. The Student's t-test for paired groups was performed. Latency of fetal visual evoked magnetic responses (VER). The IUGR fetuses showed delayed VERs compared with controls (IUGR, 233.1 ms; controls, 184.6 ms; P = 0.032). SGA fetuses had similar evoked response latencies compared with controls (SGA, 216.1 ms; controls, 219.9 ms; P = 0.828). Behavioural states were similarly distributed. Visual evoked responses are delayed in IUGR fetuses, but not in SGA. Fetal behavioural state as an influencing factor of brain response latency was accounted for in the comparison. This reinforces that delayed brain maturation is the result of placental insufficiency. © 2015 Royal College of Obstetricians and Gynaecologists.

Computerized Cognitive Rehabilitation of Attention and Executive Function in Acquired Brain Injury: A Systematic Review.

PubMed

Bogdanova, Yelena; Yee, Megan K; Ho, Vivian T; Cicerone, Keith D

Comprehensive review of the use of computerized treatment as a rehabilitation tool for attention and executive function in adults (aged 18 years or older) who suffered an acquired brain injury. Systematic review of empirical research. Two reviewers independently assessed articles using the methodological quality criteria of Cicerone et al. Data extracted included sample size, diagnosis, intervention information, treatment schedule, assessment methods, and outcome measures. A literature review (PubMed, EMBASE, Ovid, Cochrane, PsychINFO, CINAHL) generated a total of 4931 publications. Twenty-eight studies using computerized cognitive interventions targeting attention and executive functions were included in this review. In 23 studies, significant improvements in attention and executive function subsequent to training were reported; in the remaining 5, promising trends were observed. Preliminary evidence suggests improvements in cognitive function following computerized rehabilitation for acquired brain injury populations including traumatic brain injury and stroke. Further studies are needed to address methodological issues (eg, small sample size, inadequate control groups) and to inform development of guidelines and standardized protocols.

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

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).

Distribution of polymer nanoparticles by convection-enhanced delivery to brain tumors.

PubMed

Saucier-Sawyer, Jennifer K; Seo, Young-Eun; Gaudin, Alice; Quijano, Elias; Song, Eric; Sawyer, Andrew J; Deng, Yang; Huttner, Anita; Saltzman, W Mark

2016-06-28

Glioblastoma multiforme (GBM) is a fatal brain tumor characterized by infiltration beyond the margins of the main tumor mass and local recurrence after surgery. The blood-brain barrier (BBB) poses the most significant hurdle to brain tumor treatment. Convection-enhanced delivery (CED) allows for local administration of agents, overcoming the restrictions of the BBB. Recently, polymer nanoparticles have been demonstrated to penetrate readily through the healthy brain when delivered by CED, and size has been shown to be a critical factor for nanoparticle penetration. Because these brain-penetrating nanoparticles (BPNPs) have high potential for treatment of intracranial tumors since they offer the potential for cell targeting and controlled drug release after administration, here we investigated the intratumoral CED infusions of PLGA BPNPs in animals bearing either U87 or RG2 intracranial tumors. We demonstrate that the overall volume of distribution of these BPNPs was similar to that observed in healthy brains; however, the presence of tumors resulted in asymmetric and heterogeneous distribution patterns, with substantial leakage into the peritumoral tissue. Together, our results suggest that CED of BPNPs should be optimized by accounting for tumor geometry, in terms of location, size and presence of necrotic regions, to determine the ideal infusion site and parameters for individual tumors. Copyright © 2016 Elsevier B.V. All rights reserved.

Clever birds are lousy: co-variation between avian innovation and the taxonomic richness of their amblyceran lice.

PubMed

Vas, Zoltán; Lefebvre, Louis; Johnson, Kevin P; Reiczigel, Jeno; Rózsa, Lajos

2011-10-01

Lice (Insecta: Phthiraptera) are ectoparasites that reduce host life expectancy and sexual attractiveness. Their taxonomic richness varies considerably among their hosts. Previous studies have already explored some important factors shaping louse diversity. An unexplored potential correlate of louse taxonomic richness is host behavioural flexibility. In this comparative study, we examine the relationship between louse generic richness, innovative capabilities (as a proxy for behavioural flexibility), and brain size while controlling for host species diversity, phylogeny, body size and research effort. Using data for 108 avian families, we found a highly significant positive relationship between host innovative capabilities and the taxonomic richness of amblyceran lice, but a lack of a similar relationship in ischnoceran lice. Host brain size had only a marginal impact on amblyceran diversity and no correlation with ischnoceran diversity. This suggests that the effect in Amblycera is not mediated by metabolic limitations due to the energetic costs of brain size and maintenance, rather directly caused by the ecological differences between hosts with differing cognitive capabilities. We propose four alternative and mutually non-exclusive hypotheses that may explain this phenomenon. Copyright © 2011 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Damage to Arousal-Promoting Brainstem Neurons with Traumatic Brain Injury.

PubMed

Valko, Philipp O; Gavrilov, Yuri V; Yamamoto, Mihoko; Noaín, Daniela; Reddy, Hasini; Haybaeck, Johannes; Weis, Serge; Baumann, Christian R; Scammell, Thomas E

2016-06-01

Coma and chronic sleepiness are common after traumatic brain injury (TBI). Here, we explored whether injury to arousal-promoting brainstem neurons occurs in patients with fatal TBI. Postmortem examination of 8 TBI patients and 10 controls. Compared to controls, TBI patients had 17% fewer serotonergic neurons in the dorsal raphe nucleus (effect size: 1.25), but the number of serotonergic neurons did not differ in the median raphe nucleus. TBI patients also had 29% fewer noradrenergic neurons in the locus coeruleus (effect size: 0.96). The number of cholinergic neurons in the pedunculopontine and laterodorsal tegmental nuclei (PPT/LDT) was similar in TBI patients and controls. TBI injures arousal-promoting neurons of the mesopontine tegmentum, but this injury is less severe than previously observed in hypothalamic arousal-promoting neurons. Most likely, posttraumatic arousal disturbances are not primarily caused by damage to these brainstem neurons, but arise from an aggregate of injuries, including damage to hypothalamic arousal nuclei and disruption of other arousal-related circuitries. © 2016 Associated Professional Sleep Societies, LLC.

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.

Damage to Arousal-Promoting Brainstem Neurons with Traumatic Brain Injury

PubMed Central

Valko, Philipp O.; Gavrilov, Yuri V.; Yamamoto, Mihoko; Noaín, Daniela; Reddy, Hasini; Haybaeck, Johannes; Weis, Serge; Baumann, Christian R.; Scammell, Thomas E.

2016-01-01

Study Objectives: Coma and chronic sleepiness are common after traumatic brain injury (TBI). Here, we explored whether injury to arousal-promoting brainstem neurons occurs in patients with fatal TBI. Methods: Postmortem examination of 8 TBI patients and 10 controls. Results: Compared to controls, TBI patients had 17% fewer serotonergic neurons in the dorsal raphe nucleus (effect size: 1.25), but the number of serotonergic neurons did not differ in the median raphe nucleus. TBI patients also had 29% fewer noradrenergic neurons in the locus coeruleus (effect size: 0.96). The number of cholinergic neurons in the pedunculopontine and laterodorsal tegmental nuclei (PPT/LDT) was similar in TBI patients and controls. Conclusions: TBI injures arousal-promoting neurons of the mesopontine tegmentum, but this injury is less severe than previously observed in hypothalamic arousal-promoting neurons. Most likely, posttraumatic arousal disturbances are not primarily caused by damage to these brainstem neurons, but arise from an aggregate of injuries, including damage to hypothalamic arousal nuclei and disruption of other arousal-related circuitries. Citation: Valko PO, Gavrilov YV, Yamamoto M, Noain D, Reddy H, Haybaeck J, Weis S, Baumann CR, Scammell TE. Damage to arousal-promoting brainstem neurons with traumatic brain injury. SLEEP 2016;39(6):1249–1252. PMID:27091531

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).

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)

International practice survey on the management of brain metastases: Third International Consensus Workshop on Palliative Radiotherapy and Symptom Control.

PubMed

Tsao, M N; Rades, D; Wirth, A; Lo, S S; Danielson, B L; Vichare, A; Hahn, C; Chang, E L

2012-08-01

To evaluate international patterns of practice for the management of metastatic disease to the brain. An online international practice survey was conducted from April to June 2010. Most of the survey questions were based on common management issues for which optimal management using level 1 evidence was lacking. The survey consisted of three sections: respondent demographics, 13 general questions regarding surgery, whole brain radiotherapy (WBRT) and radiosurgery and 13 questions related to specific scenarios. In total, 445 individuals responded to the survey over a 3 month period. Ninety per cent of respondents worked in a hospital-based setting. Ninety-three per cent of respondents were radiation oncologists. Thirty-seven per cent worked in an academic setting. Only three of 26 survey questions generated at least 70% agreement for a favoured response. Eighty-eight per cent of respondents chose comfort measures only for patients with multiple brain metastases who have been previously treated with WBRT and who now present 6 months later with two to four brain metastases (all less than 4 cm in size) with uncontrolled extracranial disease and bedridden state. Seventy-eight per cent of respondents would use WBRT alone for initial treatment in patients with two to four brain metastases (all less than 4 cm in size), with active, uncontrolled extracranial disease and a Karnofsky performance status of 70. Seventy-eight per cent of respondents chose surgical resection for an enlarging single brain metastasis that has been previously treated with radiosurgery. The enlarging single brain metastasis is in a surgically accessible site and is now symptomatic. The patient has controlled extracranial disease, good performance status and magnetic resonance spectroscopy was not diagnostic. There is a lack of uniform agreement for many common management issues (not well answered by level 1 evidence) in patients with metastatic disease to the brain. Copyright © 2012 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Gorilla and Orangutan Brains Conform to the Primate Cellular Scaling Rules: Implications for Human Evolution

PubMed Central

Herculano-Houzel, Suzana; Kaas, Jon H.

2011-01-01

Gorillas and orangutans are primates at least as large as humans, but their brains amount to about one third of the size of the human brain. This discrepancy has been used as evidence that the human brain is about 3 times larger than it should be for a primate species of its body size. In contrast to the view that the human brain is special in its size, we have suggested that it is the great apes that might have evolved bodies that are unusually large, on the basis of our recent finding that the cellular composition of the human brain matches that expected for a primate brain of its size, making the human brain a linearly scaled-up primate brain in its number of cells. To investigate whether the brain of great apes also conforms to the primate cellular scaling rules identified previously, we determine the numbers of neuronal and other cells that compose the orangutan and gorilla cerebella, use these numbers to calculate the size of the brain and of the cerebral cortex expected for these species, and show that these match the sizes described in the literature. Our results suggest that the brains of great apes also scale linearly in their numbers of neurons like other primate brains, including humans. The conformity of great apes and humans to the linear cellular scaling rules that apply to other primates that diverged earlier in primate evolution indicates that prehistoric Homo species as well as other hominins must have had brains that conformed to the same scaling rules, irrespective of their body size. We then used those scaling rules and published estimated brain volumes for various hominin species to predict the numbers of neurons that composed their brains. We predict that Homo heidelbergensis and Homo neanderthalensis had brains with approximately 80 billion neurons, within the range of variation found in modern Homo sapiens. We propose that while the cellular scaling rules that apply to the primate brain have remained stable in hominin evolution (since they apply to simians, great apes and modern humans alike), the Colobinae and Pongidae lineages favored marked increases in body size rather than brain size from the common ancestor with the Homo lineage, while the Homo lineage seems to have favored a large brain instead of a large body, possibly due to the metabolic limitations to having both. PMID:21228547

Gorilla and orangutan brains conform to the primate cellular scaling rules: implications for human evolution.

PubMed

Herculano-Houzel, Suzana; Kaas, Jon H

2011-01-01

Gorillas and orangutans are primates at least as large as humans, but their brains amount to about one third of the size of the human brain. This discrepancy has been used as evidence that the human brain is about 3 times larger than it should be for a primate species of its body size. In contrast to the view that the human brain is special in its size, we have suggested that it is the great apes that might have evolved bodies that are unusually large, on the basis of our recent finding that the cellular composition of the human brain matches that expected for a primate brain of its size, making the human brain a linearly scaled-up primate brain in its number of cells. To investigate whether the brain of great apes also conforms to the primate cellular scaling rules identified previously, we determine the numbers of neuronal and other cells that compose the orangutan and gorilla cerebella, use these numbers to calculate the size of the brain and of the cerebral cortex expected for these species, and show that these match the sizes described in the literature. Our results suggest that the brains of great apes also scale linearly in their numbers of neurons like other primate brains, including humans. The conformity of great apes and humans to the linear cellular scaling rules that apply to other primates that diverged earlier in primate evolution indicates that prehistoric Homo species as well as other hominins must have had brains that conformed to the same scaling rules, irrespective of their body size. We then used those scaling rules and published estimated brain volumes for various hominin species to predict the numbers of neurons that composed their brains. We predict that Homo heidelbergensis and Homo neanderthalensis had brains with approximately 80 billion neurons, within the range of variation found in modern Homo sapiens. We propose that while the cellular scaling rules that apply to the primate brain have remained stable in hominin evolution (since they apply to simians, great apes and modern humans alike), the Colobinae and Pongidae lineages favored marked increases in body size rather than brain size from the common ancestor with the Homo lineage, while the Homo lineage seems to have favored a large brain instead of a large body, possibly due to the metabolic limitations to having both. Copyright © 2011 S. Karger AG, Basel.

Neural systemic impairment from whole-body vibration.

PubMed

Yan, Ji-Geng; Zhang, Lin-ling; Agresti, Michael; LoGiudice, John; Sanger, James R; Matloub, Hani S; Havlik, Robert

2015-05-01

Insidious brain microinjury from motor vehicle-induced whole-body vibration (WBV) has not yet been investigated. For a long time we have believed that WBV would cause cumulative brain microinjury and impair cerebral function, which suggests an important risk factor for motor vehicle accidents and secondary cerebral vascular diseases. Fifty-six Sprague-Dawley rats were divided into seven groups (n = 8): 1) 2-week normal control group, 2) 2-week sham control group (restrained in the tube without vibration), 3) 2-week vibration group (exposed to whole-body vibration at 30 Hz and 0.5g acceleration for 4 hr/day, 5 days/week, for 2 weeks), 4) 4-week sham control group, 5) 4-week vibration group, 6) 8-week sham control group, and 7) 8-week vibration group. At the end point, all rats were evaluated in behavior, physiological, and brain histopathological studies. The cerebral injury from WBV is a cumulative process starting with vasospasm squeezing of the endothelial cells, followed by constriction of the cerebral arteries. After the 4-week vibration, brain neuron apoptosis started. After the 8-week vibration, vacuoles increased further in the brain arteries. Brain capillary walls thickened, mean neuron size was obviously reduced, neuron necrosis became prominent, and wide-ranging chronic cerebral edema was seen. These pathological findings are strongly correlated with neural functional impairments. © 2014 Wiley Periodicals, Inc.

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

p53 is required for brain growth but is dispensable for resistance to nutrient restriction during Drosophila larval development

PubMed Central

Contreras, Esteban G.; Sierralta, Jimena

2018-01-01

Background Animal growth is influenced by the genetic background and the environmental circumstances. How genes promote growth and coordinate adaptation to nutrient availability is still an open question. p53 is a transcription factor that commands the cellular response to different types of stresses. In adult Drosophila melanogaster, p53 regulates the metabolic adaptation to nutrient restriction that supports fly viability. Furthermore, the larval brain is protected from nutrient restriction in a phenomenon called ‘brain sparing’. Therefore, we hypothesised that p53 may regulate brain growth and show a protective role over brain development under nutrient restriction. Results Here, we studied the function of p53 during brain growth in normal conditions and in animals subjected to developmental nutrient restriction. We showed that p53 loss of function reduced animal growth and larval brain size. Endogenous p53 was expressed in larval neural stem cells, but its levels and activity were not affected by nutritional stress. Interestingly, p53 knockdown only in neural stem cells was sufficient to decrease larval brain growth. Finally, we showed that in p53 mutant larvae under nutrient restriction, the energy storage levels were not altered, and these larvae generated adults with brains of similar size than wild-type animals. Conclusions Using genetic approaches, we demonstrate that p53 is required for proper growth of the larval brain. This developmental role of p53 does not have an impact on animal resistance to nutritional stress since brain growth in p53 mutants under nutrient restriction is similar to control animals. PMID:29621246

p53 is required for brain growth but is dispensable for resistance to nutrient restriction during Drosophila larval development.

PubMed

Contreras, Esteban G; Sierralta, Jimena; Glavic, Alvaro

2018-01-01

Animal growth is influenced by the genetic background and the environmental circumstances. How genes promote growth and coordinate adaptation to nutrient availability is still an open question. p53 is a transcription factor that commands the cellular response to different types of stresses. In adult Drosophila melanogaster, p53 regulates the metabolic adaptation to nutrient restriction that supports fly viability. Furthermore, the larval brain is protected from nutrient restriction in a phenomenon called 'brain sparing'. Therefore, we hypothesised that p53 may regulate brain growth and show a protective role over brain development under nutrient restriction. Here, we studied the function of p53 during brain growth in normal conditions and in animals subjected to developmental nutrient restriction. We showed that p53 loss of function reduced animal growth and larval brain size. Endogenous p53 was expressed in larval neural stem cells, but its levels and activity were not affected by nutritional stress. Interestingly, p53 knockdown only in neural stem cells was sufficient to decrease larval brain growth. Finally, we showed that in p53 mutant larvae under nutrient restriction, the energy storage levels were not altered, and these larvae generated adults with brains of similar size than wild-type animals. Using genetic approaches, we demonstrate that p53 is required for proper growth of the larval brain. This developmental role of p53 does not have an impact on animal resistance to nutritional stress since brain growth in p53 mutants under nutrient restriction is similar to control animals.

Stereotactic radiotherapy following surgery for brain metastasis: Predictive factors for local control and radionecrosis.

PubMed

Doré, M; Martin, S; Delpon, G; Clément, K; Campion, L; Thillays, F

2017-02-01

To evaluate local control and adverse effects after postoperative hypofractionated stereotactic radiosurgery in patients with brain metastasis. We reviewed patients who had hypofractionated stereotactic radiosurgery (7.7Gy×3 prescribed to the 70% isodose line, with 2mm planning target volume margin) following resection from March 2008 to January 2014. The primary endpoint was local failure defined as recurrence within the surgical cavity. Secondary endpoints were distant failure rates and the occurrence of radionecrosis. Out of 95 patients, 39.2% had metastatic lesions from a non-small cell lung cancer primary tumour. The median Graded Prognostic Assessment score was 3 (48% of patients). One-year local control rates were 84%. Factors associated with improved local control were no cavity enhancement on pre-radiation MRI (P<0.00001), planning target volume less than 12cm 3 (P=0.005), Graded Prognostic Assessment score 2 or above (P=0.009). One-year distant cerebral control rates were 56%. Thirty-three percent of patients received whole brain radiation therapy. Histologically proven radionecrosis of brain tissue occurred in 7.2% of cases. The size of the preoperative lesion and the volume of healthy brain tissue receiving 21Gy (V 21 ) were both predictive of the incidence of radionecrosis (P=0.010 and 0.036, respectively). Adjuvant hypofractionated stereotactic radiosurgery to the postoperative cavity in patients with brain metastases results in excellent local control in selected patients, helps delay the use of whole brain radiation, and is associated with a relatively low risk of radionecrosis. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

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 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).

Metabolic constraint imposes tradeoff between body size and number of brain neurons in human evolution

PubMed Central

Fonseca-Azevedo, Karina; Herculano-Houzel, Suzana

2012-01-01

Despite a general trend for larger mammals to have larger brains, humans are the primates with the largest brain and number of neurons, but not the largest body mass. Why are great apes, the largest primates, not also those endowed with the largest brains? Recently, we showed that the energetic cost of the brain is a linear function of its numbers of neurons. Here we show that metabolic limitations that result from the number of hours available for feeding and the low caloric yield of raw foods impose a tradeoff between body size and number of brain neurons, which explains the small brain size of great apes compared with their large body size. This limitation was probably overcome in Homo erectus with the shift to a cooked diet. Absent the requirement to spend most available hours of the day feeding, the combination of newly freed time and a large number of brain neurons affordable on a cooked diet may thus have been a major positive driving force to the rapid increased in brain size in human evolution. PMID:23090991

Metabolic constraint imposes tradeoff between body size and number of brain neurons in human evolution.

PubMed

Fonseca-Azevedo, Karina; Herculano-Houzel, Suzana

2012-11-06

Despite a general trend for larger mammals to have larger brains, humans are the primates with the largest brain and number of neurons, but not the largest body mass. Why are great apes, the largest primates, not also those endowed with the largest brains? Recently, we showed that the energetic cost of the brain is a linear function of its numbers of neurons. Here we show that metabolic limitations that result from the number of hours available for feeding and the low caloric yield of raw foods impose a tradeoff between body size and number of brain neurons, which explains the small brain size of great apes compared with their large body size. This limitation was probably overcome in Homo erectus with the shift to a cooked diet. Absent the requirement to spend most available hours of the day feeding, the combination of newly freed time and a large number of brain neurons affordable on a cooked diet may thus have been a major positive driving force to the rapid increased in brain size in human evolution.

Data-driven regions of interest for longitudinal change in frontotemporal lobar degeneration.

PubMed

Pankov, Aleksandr; Binney, Richard J; Staffaroni, Adam M; Kornak, John; Attygalle, Suneth; Schuff, Norbert; Weiner, Michael W; Kramer, Joel H; Dickerson, Bradford C; Miller, Bruce L; Rosen, Howard J

2016-01-01

Current research is investigating the potential utility of longitudinal measurement of brain structure as a marker of drug effect in clinical trials for neurodegenerative disease. Recent studies in Alzheimer's disease (AD) have shown that measurement of change in empirically derived regions of interest (ROIs) allows more reliable measurement of change over time compared with regions chosen a-priori based on known effects of AD on brain anatomy. Frontotemporal lobar degeneration (FTLD) is a devastating neurodegenerative disorder for which there are no approved treatments. The goal of this study was to identify an empirical ROI that maximizes the effect size for the annual rate of brain atrophy in FTLD compared with healthy age matched controls, and to estimate the effect size and associated power estimates for a theoretical study that would use change within this ROI as an outcome measure. Eighty six patients with FTLD were studied, including 43 who were imaged twice at 1.5 T and 43 at 3 T, along with 105 controls (37 imaged at 1.5 T and 67 at 3 T). Empirically-derived maps of change were generated separately for each field strength and included the bilateral insula, dorsolateral, medial and orbital frontal, basal ganglia and lateral and inferior temporal regions. The extent of regions included in the 3 T map was larger than that in the 1.5 T map. At both field strengths, the effect sizes for imaging were larger than for any clinical measures. At 3 T, the effect size for longitudinal change measured within the empirically derived ROI was larger than the effect sizes derived from frontal lobe, temporal lobe or whole brain ROIs. The effect size derived from the data-driven 1.5 T map was smaller than at 3 T, and was not larger than the effect size derived from a-priori ROIs. It was estimated that measurement of longitudinal change using 1.5 T MR systems requires approximately a 3-fold increase in sample size to obtain effect sizes equivalent to those seen at 3 T. While the results should be confirmed in additional datasets, these results indicate that empirically derived ROIs can reduce the number of subjects needed for a longitudinal study of drug effects in FTLD compared with a-priori ROIs. Field strength may have a significant impact on the utility of imaging for measuring longitudinal change.

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.

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

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.

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.

Development of acute hydrocephalus does not change brain tissue mechanical properties in adult rats, but in juvenile rats

PubMed Central

Pong, Alice C.; Jugé, Lauriane; Bilston, Lynne E.; Cheng, Shaokoon

2017-01-01

Introduction Regional changes in brain stiffness were previously demonstrated in an experimental obstructive hydrocephalus juvenile rat model. The open cranial sutures in the juvenile rats have influenced brain compression and mechanical properties during hydrocephalus development and the extent by which closed cranial sutures in adult hydrocephalic rat models affect brain stiffness in-vivo remains unclear. The aims of this study were to determine changes in brain tissue mechanical properties and brain structure size during hydrocephalus development in adult rat with fixed cranial volume and how these changes were related to brain tissue deformation. Methods Hydrocephalus was induced in 9 female ten weeks old Sprague-Dawley rats by injecting 60 μL of a kaolin suspension (25%) into the cisterna magna under anaesthesia. 6 sham-injected age-matched female SD rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before and then at 3 days post injection. T2-weighted anatomical MR images were collected to quantify ventricle and brain tissue cross-sectional areas. MR elastography (800 Hz) was used to measure the brain stiffness (G*, shear modulus). Results Brain tissue in the adult hydrocephalic rats was more compressed than the juvenile hydrocephalic rats because the skulls of the adult hydrocephalic rats were unable to expand like the juvenile rats. In the adult hydrocephalic rats, the cortical gray matter thickness and the caudate-putamen cross-sectional area decreased (Spearman, P < 0.001 for both) but there were no significant changes in cranial cross-sectional area (Spearman, P = 0.35), cortical gray matter stiffness (Spearman, P = 0.24) and caudate-putamen (Spearman, P = 0.11) stiffness. No significant changes in the size of brain structures were observed in the controls. Conclusions This study showed that although brain tissue in the adult hydrocephalic rats was severely compressed, their brain tissue stiffness did not change significantly. These results are in contrast with our previous findings in juvenile hydrocephalic rats which had significantly less brain compression (as the brain circumference was able to stretch with the cranium due to the open skull sutures) and had a significant increase in caudate putamen stiffness. These results suggest that change in brain mechanical properties in hydrocephalus is complex and is not solely dependent on brain tissue deformation. Further studies on the interactions between brain tissue stiffness, deformation, tissue oedema and neural damage are necessary before MRE can be used as a tool to track changes in brain biomechanics in hydrocephalus. PMID:28837671

Development of acute hydrocephalus does not change brain tissue mechanical properties in adult rats, but in juvenile rats.

PubMed

Pong, Alice C; Jugé, Lauriane; Bilston, Lynne E; Cheng, Shaokoon

2017-01-01

Regional changes in brain stiffness were previously demonstrated in an experimental obstructive hydrocephalus juvenile rat model. The open cranial sutures in the juvenile rats have influenced brain compression and mechanical properties during hydrocephalus development and the extent by which closed cranial sutures in adult hydrocephalic rat models affect brain stiffness in-vivo remains unclear. The aims of this study were to determine changes in brain tissue mechanical properties and brain structure size during hydrocephalus development in adult rat with fixed cranial volume and how these changes were related to brain tissue deformation. Hydrocephalus was induced in 9 female ten weeks old Sprague-Dawley rats by injecting 60 μL of a kaolin suspension (25%) into the cisterna magna under anaesthesia. 6 sham-injected age-matched female SD rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before and then at 3 days post injection. T2-weighted anatomical MR images were collected to quantify ventricle and brain tissue cross-sectional areas. MR elastography (800 Hz) was used to measure the brain stiffness (G*, shear modulus). Brain tissue in the adult hydrocephalic rats was more compressed than the juvenile hydrocephalic rats because the skulls of the adult hydrocephalic rats were unable to expand like the juvenile rats. In the adult hydrocephalic rats, the cortical gray matter thickness and the caudate-putamen cross-sectional area decreased (Spearman, P < 0.001 for both) but there were no significant changes in cranial cross-sectional area (Spearman, P = 0.35), cortical gray matter stiffness (Spearman, P = 0.24) and caudate-putamen (Spearman, P = 0.11) stiffness. No significant changes in the size of brain structures were observed in the controls. This study showed that although brain tissue in the adult hydrocephalic rats was severely compressed, their brain tissue stiffness did not change significantly. These results are in contrast with our previous findings in juvenile hydrocephalic rats which had significantly less brain compression (as the brain circumference was able to stretch with the cranium due to the open skull sutures) and had a significant increase in caudate putamen stiffness. These results suggest that change in brain mechanical properties in hydrocephalus is complex and is not solely dependent on brain tissue deformation. Further studies on the interactions between brain tissue stiffness, deformation, tissue oedema and neural damage are necessary before MRE can be used as a tool to track changes in brain biomechanics in hydrocephalus.

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

I.V. infusion of brain-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat.

PubMed

Nomura, T; Honmou, O; Harada, K; Houkin, K; Hamada, H; Kocsis, J D

2005-01-01

I.V. delivery of mesenchymal stem cells prepared from adult bone marrow reduces infarction size and ameliorates functional deficits in rat cerebral ischemia models. Administration of the brain-derived neurotrophic factor to the infarction site has also been demonstrated to be neuroprotective. To test the hypothesis that brain-derived neurotrophic factor contributes to the therapeutic benefits of mesenchymal stem cell delivery, we compared the efficacy of systemic delivery of human mesenchymal stem cells and human mesenchymal stem cells transfected with a fiber-mutant F/RGD adenovirus vector with a brain-derived neurotrophic factor gene (brain-derived neurotrophic factor-human mesenchymal stem cells). A permanent middle cerebral artery occlusion was induced by intraluminal vascular occlusion with a microfilament. Human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells were i.v. injected into the rats 6 h after middle cerebral artery occlusion. Lesion size was assessed at 6 h, 1, 3 and 7 days using MR imaging, and histological methods. Functional outcome was assessed using the treadmill stress test. Both human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells reduced lesion volume and elicited functional improvement compared with the control sham group, but the effect was greater in the brain-derived neurotrophic factor-human mesenchymal stem cell group. ELISA analysis of the infarcted hemisphere revealed an increase in brain-derived neurotrophic factor in the human mesenchymal stem cell groups, but a greater increase in the brain-derived neurotrophic factor-human mesenchymal stem cell group. These data support the hypothesis that brain-derived neurotrophic factor contributes to neuroprotection in cerebral ischemia and cellular delivery of brain-derived neurotrophic factor can be achieved by i.v. delivery of human mesenchymal stem cells.

Design and Rationale of the Cognitive Intervention to Improve Memory in Heart Failure Patients Study.

PubMed

Pressler, Susan J; Giordani, Bruno; Titler, Marita; Gradus-Pizlo, Irmina; Smith, Dean; Dorsey, Susan G; Gao, Sujuan; Jung, Miyeon

Memory loss is an independent predictor of mortality among heart failure patients. Twenty-three percent to 50% of heart failure patients have comorbid memory loss, but few interventions are available to treat the memory loss. The aims of this 3-arm randomized controlled trial were to (1) evaluate efficacy of computerized cognitive training intervention using BrainHQ to improve primary outcomes of memory and serum brain-derived neurotrophic factor levels and secondary outcomes of working memory, instrumental activities of daily living, and health-related quality of life among heart failure patients; (2) evaluate incremental cost-effectiveness of BrainHQ; and (3) examine depressive symptoms and genomic moderators of BrainHQ effect. A sample of 264 heart failure patients within 4 equal-sized blocks (normal/low baseline cognitive function and gender) will be randomly assigned to (1) BrainHQ, (2) active control computer-based crossword puzzles, and (3) usual care control groups. BrainHQ is an 8-week, 40-hour program individualized to each patient's performance. Data collection will be completed at baseline and at 10 weeks and 4 and 8 months. Descriptive statistics, mixed model analyses, and cost-utility analysis using intent-to-treat approach will be computed. This research will provide new knowledge about the efficacy of BrainHQ to improve memory and increase serum brain-derived neurotrophic factor levels in heart failure. If efficacious, the intervention will provide a new therapeutic approach that is easy to disseminate to treat a serious comorbid condition of heart failure.

Polymorphisms in the vitamin D receptor and their associations with risk of schizophrenia and selected anthropometric measures.

PubMed

Handoko, H Y; Nancarrow, D J; Mowry, B J; McGrath, J J

2006-01-01

The association between vitamin D levels and skeletal growth has long been recognized. However, exposure to low levels of vitamin D during early life is also known to alter brain development, and is a candidate risk factor for schizophrenia. This study examines the association between four polymorphisms in the vitamin D receptor (VDR) and 1) risk of schizophrenia, and 2) three anthropometric variables (height, head size, and head shape). Four single-nucleotide polymorphisms (SNPs; rs10735810/FokI, rs1544410/BsmI, rs7975232/ApaI, and rs731236/TaqI) in the VDR gene were genotyped in 179 individuals with schizophrenia and 189 healthy controls. No significant associations were detected between any of the four VDR SNPs and risk of schizophrenia. Patients were slightly but significantly shorter compared to controls. Of the four SNPs, only rs10735810/FokI was associated with any of the anthropometric measures: the M4 isoform of this SNP was significantly associated with larger head size (P = 0.002). In light of the evidence demonstrating a role for vitamin D during brain development, the association between polymorphisms in VDR and brain development warrants closer scrutiny.

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.

Increased brain injury and vascular leakage after pretreatment with p38-inhibitor SB203580 in transient ischemia.

PubMed

Lennmyr, F; Ericsson, A; Gerwins, P; Ahlström, H; Terént, A

2003-11-01

Focal cerebral ischemia activates intracellular signaling pathways including the mitogen-activated protein kinase p38, which may be involved in the process of ischemic brain injury. In this study, the effect of pretreatment with the p38-inhibitor SB203580 on infarct size and blood-brain barrier (BBB) breakdown was investigated with magnetic resonance imaging (MRI). Rats were given SB203580 (n = 6) or vehicle (n = 6) in the right lateral ventricle prior to transient (90 min) middle cerebral artery occlusion (MCAO) on the left side. The rats were examined with serial MRI during MCAO, at reperfusion and after 1 and 4 days. The mean infarct size on T2-weighted images after 1 day was significantly higher in the SB203580-treated group than in controls (300 +/- 95 mm3 vs 126 +/- 75 mm3; P < 0.01). Vascular gadolinium leakage, indicating BBB breakdown, was significantly larger in the SB203580-treated group than in controls after 1 day (median leakage score 18.5; range 15-21 vs 6.5; 4-17; P < 0.05) and 4 days (11; 6-15 vs 3.5; 1-9; P < 0.05), although no significant difference was seen initially. Pretreatment with SB203580 may aggravate ischemic brain injury and cerebral vascular leakage in the present model of transient ischemia.

Experimental exposure to urban and pink noise affects brain development and song learning in zebra finches (Taenopygia guttata)

PubMed Central

Curcio, Michael T.; Swaddle, John P.; MacDougall-Shackleton, Scott A.

2016-01-01

Recently, numerous studies have observed changes in bird vocalizations—especially song—in urban habitats. These changes are often interpreted as adaptive, since they increase the active space of the signal in its environment. However, the proximate mechanisms driving cross-generational changes in song are still unknown. We performed a captive experiment to identify whether noise experienced during development affects song learning and the development of song-control brain regions. Zebra finches (Taeniopygia guttata) were bred while exposed, or not exposed, to recorded traffic urban noise (Study 1) or pink noise (Study 2). We recorded the songs of male offspring and compared these to fathers’ songs. We also measured baseline corticosterone and measured the size of song-control brain regions when the males reached adulthood (Study 1 only). While male zebra finches tended to copy syllables accurately from tutors regardless of noise environment, syntax (the ordering of syllables within songs) was incorrectly copied affected by juveniles exposed to noise. Noise did not affect baseline corticosterone, but did affect the size of brain regions associated with song learning: these regions were smaller in males that had been had been exposed to recorded traffic urban noise in early development. These findings provide a possible mechanism by which noise affects behaviour, leading to potential population differences between wild animals occupying noisier urban environments compared with those in quieter habitats. PMID:27602270

Experimental exposure to urban and pink noise affects brain development and song learning in zebra finches (Taenopygia guttata).

PubMed

Potvin, Dominique A; Curcio, Michael T; Swaddle, John P; MacDougall-Shackleton, Scott A

2016-01-01

Recently, numerous studies have observed changes in bird vocalizations-especially song-in urban habitats. These changes are often interpreted as adaptive, since they increase the active space of the signal in its environment. However, the proximate mechanisms driving cross-generational changes in song are still unknown. We performed a captive experiment to identify whether noise experienced during development affects song learning and the development of song-control brain regions. Zebra finches (Taeniopygia guttata) were bred while exposed, or not exposed, to recorded traffic urban noise (Study 1) or pink noise (Study 2). We recorded the songs of male offspring and compared these to fathers' songs. We also measured baseline corticosterone and measured the size of song-control brain regions when the males reached adulthood (Study 1 only). While male zebra finches tended to copy syllables accurately from tutors regardless of noise environment, syntax (the ordering of syllables within songs) was incorrectly copied affected by juveniles exposed to noise. Noise did not affect baseline corticosterone, but did affect the size of brain regions associated with song learning: these regions were smaller in males that had been had been exposed to recorded traffic urban noise in early development. These findings provide a possible mechanism by which noise affects behaviour, leading to potential population differences between wild animals occupying noisier urban environments compared with those in quieter habitats.

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

Differential effects of chronic intermittent and chronic constant hypoxia on postnatal growth and development.

PubMed

Farahani, Reza; Kanaan, Amjad; Gavrialov, Orit; Brunnert, Steven; Douglas, Robert M; Morcillo, Patrick; Haddad, Gabriel G

2008-01-01

Exposure to chronic constant or intermittent hypoxia (CCH or CIH) may have different effects on growth and development in early life. In this work, we exposed postnatal day 2 (P2) CD1 mice to CCH or CIH (11% O2) for 4 weeks and examined the effect of hypoxia on body and organ growth until P30. Regression analysis showed that weight increased in control, CCH and CIH cohorts with age with r2 values of 0.99, 0.97, and 0.94, respectively. Between days 2 and 30, slopes were 0.93+/-0.057, 0.76+/-0.108, and 0.63+/-0.061 (g/day, means+/-SEM) for control, CIH, and CCH, respectively and significantly different from each other (P<0.001). The slopes between P2 and P16 were 0.78+/-0.012, 0.46+/-0.002, and 0.47+/-0.019 for control, CCH and CIH, respectively. From P16 to 30, slopes were 1.12+/-0.033, 1.09+/-0.143, and 0.82+/-0.08 for control, CIH, and CCH, respectively with no significant difference from each other, suggesting a catch-up growth in the latter part of the hypoxic period. Slower weight gain resulted in a 12% and 23% lower body weight in CIH and CCH mice (P<0.001) by P30. Lung/body ratios were 0.010, 0.015, 0.015 for control, CIH, and CCH at P30, respectively. The decrease in liver, kidney, and brain weight were greater in CCH than CIH. Smaller liver weight was shown to be due to a reduction in cell size and cell number. Liver in CIH and CCH mice showed a 5% and 10% reduction in cell size (P<0.05) and a reduction of 28% in cell number (P<0.001) at P30. In contrast, CCH and CIH heart weight was 13% and 33% greater than control at P30 (P<0.05), respectively. This increase in the heart weight was due to an increase in the size of cardiomyocytes which showed an increase of 12% and 14% (P<0.001) for CIH and CCH, respectively as compared to control. Brain weight was 0.48 and 0.46 g for CIH and CCH, respectively (95% and 92% of normal). We concluded that (a) CIH and CCH follow different body and organ growth patterns; (b) mostly with CCH, the liver and kidneys are reduced in size in a proportionate way to body size but heart, lung, and brain are either spared or increased in size compared to body weight; and (c) the decrease in liver is secondary mostly to a decrease in cell number. Copyright (c) 2007 Wiley-Liss, Inc.

A multicenter, randomized trial on neuroprotection with remote ischemic per-conditioning during acute ischemic stroke: the REmote iSchemic Conditioning in acUtE BRAin INfarction study protocol.

PubMed

Pico, Fernando; Rosso, Charlotte; Meseguer, Elena; Chadenat, Marie-Laure; Cattenoy, Amina; Aegerter, Philippe; Deltour, Sandrine; Yeung, Jennifer; Hosseini, Hassan; Lambert, Yves; Smadja, Didier; Samson, Yves; Amarenco, Pierre

2016-10-01

Rationale Remote ischemic per-conditioning-causing transient limb ischemia to induce ischemic tolerance in other organs-reduces final infarct size in animal stroke models. Aim To evaluate whether remote ischemic per-conditioning during acute ischemic stroke (<6 h) reduces brain infarct size at 24 h. Methods and design This study is being performed in five French hospitals using a prospective randomized open blinded end-point design. Adults with magnetic resonance imaging confirmed ischemic stroke within 6 h of symptom onset and clinical deficit of 5-25 according to National Institutes of Health Stroke Scale will be randomized 1:1 to remote ischemic per-conditioning or control (stratified by center and intravenous fibrinolysis use). Remote ischemic per-conditioning will consist of four cycles of electronic tourniquet inflation (5 min) and deflation (5 min) to a thigh within 6 h of symptom onset. Magnetic resonance imaging is repeated 24 h after stroke onset. Sample size estimates For a difference of 15 cm 3 in brain infarct growth between groups, 200 patients will be included for 5% significance and 80% power. Study outcomes The primary outcome will be the difference in brain infarct growth from baseline to 24 h in the intervention versus control groups (by diffusion-weighted image magnetic resonance imaging). Secondary outcomes include: National Institutes of Health Stroke Scale score absolute difference between baseline and 24 h, three-month modified Rankin score and daily living activities, mortality, and tolerance and side effects of remote ischemic per-conditioning. Discussion The only remote ischemic per-conditioning trial in humans with stroke did not show remote ischemic per-conditioning to be effective. REmote iSchemic Conditioning in acUtE BRAin INfarction, which has important design differences, should provide more information on the use of this intervention in patients with acute ischemic stroke.

Do antipsychotic drugs affect brain structure? A systematic and critical review of MRI findings.

PubMed

Navari, S; Dazzan, P

2009-11-01

The potential effects of antipsychotic drugs on brain structure represent a key factor in understanding neuroanatomical changes in psychosis. This review addresses two issues: (1) do antipsychotic medications induce changes in total or regional human brain volumes and (2) do such effects depend on antipsychotic type? A systematic review of studies reporting structural brain magnetic resonance imaging (MRI) measures: (1) directly in association with antipsychotic use; and (2) in patients receiving lifetime treatment with antipsychotics in comparison with drug-naive patients or healthy controls. We searched Medline and EMBASE databases using the medical subject heading terms: 'antipsychotics' AND 'brain' AND (MRI NOT functional). The search included studies published up to 31 January 2007. Wherever possible, we reported the effect size of the difference observed. Thirty-three studies met our inclusion criteria. The results suggest that antipsychotics act regionally rather than globally on the brain. These volumetric changes are of a greater magnitude in association with typical than with atypical antipsychotic use. Indeed, there is evidence of a specific effect of antipsychotic type on the basal ganglia, with typicals specifically increasing the volume of these structures. Differential effects of antipsychotic type may also be present on the thalamus and the cortex, but data on these and other brain areas are more equivocal. Antipsychotic treatment potentially contributes to the brain structural changes observed in psychosis. Future research should take into account these potential effects, and use adequate sample sizes, to allow improved interpretation of neuroimaging findings in these disorders.

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.

Embracing covariation in brain evolution: Large brains, extended development, and flexible primate social systems

PubMed Central

Charvet, Christine J.; Finlay, Barbara L.

2012-01-01

Brain size, body size, developmental length, life span, costs of raising offspring, behavioral complexity, and social structures are correlated in mammals due to intrinsic life-history requirements. Dissecting variation and direction of causation in this web of relationships often draw attention away from the factors that correlate with basic life parameters. We consider the “social brain hypothesis,” which postulates that overall brain and the isocortex are selectively enlarged to confer social abilities in primates, as an example of this enterprise and pitfalls. We consider patterns of brain scaling, modularity, flexibility of brain organization, the “leverage,” and direction of selection on proposed dimensions. We conclude that the evidence supporting selective changes in isocortex or brain size for the isolated ability to manage social relationships is poor. Strong covariation in size and developmental duration coupled with flexible brains allow organisms to adapt in variable social and ecological environments across the life span and in evolution. PMID:22230623

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

Digit ratio (2D:4D) in primary brain tumor patients: A case-control study.

PubMed

Bunevicius, Adomas; Tamasauskas, Sarunas; Deltuva, Vytenis Pranas; Tamasauskas, Arimantas; Sliauzys, Albertas; Bunevicius, Robertas

2016-12-01

The second-to-fourth digit ratio (2D:4D) reflects prenatal estrogen and testosterone exposure, and is established in utero. Sex steroids are implicated in development and progression of primary brain tumors. To investigate whether there is a link between 2D:4D ratio and primary brain tumors, and age at presentation. Digital images of the right and left palms of 85 primary brain tumor patients (age 56.96±13.68years; 71% women) and 106 (age 54.31±13.68years; 68% women) gender and age matched controls were obtained. The most common brain tumor diagnoses were meningioma (41%), glioblastoma (20%) and pituitary adenoma (16%). Right and left 2D:4D ratios, and right minus left 2D:4D (D r-l ) were compared between patients and controls, and were correlated with age. Right and left 2D:4D ratios were significantly lower in primary brain tumor patients relative to controls (t=-4.28, p<0.001 and t=-3.69, p<0.001, respectively). The D r-l was not different between brain tumor patients and controls (p=0.27). In meningioma and glioma patients, age at presentation correlated negatively with left 2D:4D ratio (rho=-0.42, p=0.01 and rho=-0.36, p=0.02, respectively) and positively with D r-l (rho=0.45, p=0.009 and rho=0.65, p=0.04, respectively). Right and left hand 2D:4D ratios are lower in primary brain tumor patients relative to healthy individuals suggesting greater prenatal testosterone and lower prenatal estrogen exposure in brain tumor patients. Greater age at presentation is associated with greater D r-l and with lower left 2D:4D ratio of meningioma and glioma patients. Due to small sample size our results should be considered preliminary and interpreted with caution. Copyright © 2016 Elsevier Ireland Ltd. 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.

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.

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

Zinc and glutamine improve brain development in suckling mice subjected to early postnatal malnutrition.

PubMed

Ladd, Fernando V L; Ladd, Aliny A B L; Ribeiro, Antônio Augusto C M; Costa, Samuel B C; Coutinho, Bruna P; Feitosa, George André S; de Andrade, Geanne M; de Castro-Costa, Carlos Maurício; Magalhães, Carlos Emanuel C; Castro, Ibraim C; Oliveira, Bruna B; Guerrant, Richard L; Lima, Aldo Angelo M; Oriá, Reinaldo B

2010-06-01

The effect of zinc and glutamine on brain development was investigated during the lactation period in Swiss mice. Malnutrition was induced by clustering the litter size from 6-7 pups/dam (nourished control) to 12-14 pups/dam (undernourished control) following birth. Undernourished groups received daily supplementation with glutamine by subcutaneous injections starting at day 2 and continuing until day 14. Glutamine (100 mM, 40-80 microL) was used for morphological and behavioral studies. Zinc acetate was added in the drinking water (500 mg/L) to the lactating dams. Synaptophysin and myelin basic protein brain expressions were evaluated by immunoblot. Zinc serum and brain levels and hippocampal neurotransmitters were also evaluated. Zinc with or without glutamine improved weight gain as compared to untreated, undernourished controls. In addition, zinc supplementation improved cliff avoidance and head position during swim behaviors especially on days 9 and 10. Using design-based stereological methods, we found a significant increase in the volume of CA1 neuronal cells in undernourished control mice, which was not seen in mice receiving zinc or glutamine alone or in combination. Undernourished mice given glutamine showed increased CA1 layer volume as compared with the other groups, consistent with the trend toward increased number of neurons. Brain zinc levels were increased in the nourished and undernourished-glutamine treated mice as compared to the undernourished controls on day 7. Undernourished glutamine-treated mice showed increased hippocampal gamma-aminobutyric acid and synaptophysin levels on day 14. We conclude that glutamine or zinc protects against malnutrition-induced brain developmental impairments. Copyright 2010 Elsevier Inc. All rights reserved.

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.

Depletion of macrophages in CD11b diphtheria toxin receptor mice induces brain inflammation and enhances inflammatory signaling during traumatic brain injury.

PubMed

Frieler, Ryan A; Nadimpalli, Sameera; Boland, Lauren K; Xie, Angela; Kooistra, Laura J; Song, Jianrui; Chung, Yutein; Cho, Kae W; Lumeng, Carey N; Wang, Michael M; Mortensen, Richard M

2015-10-22

Immune cells have important roles during disease and are known to contribute to secondary, inflammation-induced injury after traumatic brain injury. To delineate the functional role of macrophages during traumatic brain injury, we depleted macrophages using transgenic CD11b-DTR mice and subjected them to controlled cortical impact. We found that macrophage depletion had no effect on lesion size assessed by T2-weighted MRI scans 28 days after injury. Macrophage depletion resulted in a robust increase in proinflammatory gene expression in both the ipsilateral and contralateral hemispheres after controlled cortical impact. Interestingly, this sizeable increase in inflammation did not affect lesion development. We also showed that macrophage depletion resulted in increased proinflammatory gene expression in the brain and kidney in the absence of injury. These data demonstrate that depletion of macrophages in CD11b-DTR mice can significantly modulate the inflammatory response during brain injury without affecting lesion formation. These data also reveal a potentially confounding inflammatory effect in CD11b-DTR mice that must be considered when interpreting the effects of macrophage depletion in disease models. Copyright © 2015 Elsevier B.V. All rights reserved.

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)

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

PubMed

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

2015-11-01

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. © 2015 The Author(s). Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

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.

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.

A Model of Post-Traumatic Epilepsy After Penetrating Brain Injuries: Effect of Lesion Size and Metal Fragments

PubMed Central

Kendirli, M. Tansel; Rose, Dominique T.; Bertram, Edward H.

2014-01-01

Objective Penetrating brain injury (PBI) has the highest risk for inducing post-traumatic epilepsy and retained foreign materials such as bullet fragments carry the greatest risk. This study examines the potential contribution of copper, a major component of bullets, to the development of epilepsy following PBI. Methods Anesthetized adult male rats received a penetrating injury from the dorsal cortex to the ventral hippocampus from a high speed small bit drill. In one group of animals, copper wire was inserted into the lesion. Control animals had only the lesion or the lesion plus stainless steel wire (biologically inert foreign body). From 6 to up to 11 months following the injury the rats were monitored intermittently for the development of epilepsy with video-EEG. A separate set of animals was examined for possible acute seizures in the week following the injury. Results 22 of the 23 animals with copper wire developed chronic epilepsy compared to 3 of the 20 control rats (lesion and lesion with stainless steel). Copper was associated with more extensive injury. The control rats with epilepsy had larger lesions. In the acute injury group, there was no difference in the incidence of seizures (83% lesion plus stainless steel, 70% lesion plus copper). Conclusions Copper increases the risk for epilepsy and may increase damage over time, but there were no differences between the groups in the incidence of acute post-injury seizures. Lesion size may contribute to epilepsy development in lesion only animals. Copper maybe an independent risk factor for the development of epilepsy and possible secondary injury, but lesion size also contributes to the development of epilepsy. The consequences of prolonged exposure of the brain to copper observed in these animals may have clinical implications that require further evaluation. PMID:25470332

Comparison of WBRT alone, SRS alone, and their combination in the treatment of one or more brain metastases: Review and meta-analysis.

PubMed

Khan, Muhammad; Lin, Jie; Liao, Guixiang; Li, Rong; Wang, Baiyao; Xie, Guozhu; Zheng, Jieling; Yuan, Yawei

2017-07-01

Whole brain radiotherapy has been a standard treatment of brain metastases. Stereotactic radiosurgery provides more focal and aggressive radiation and normal tissue sparing but worse local and distant control. This meta-analysis was performed to assess and compare the effectiveness of whole brain radiotherapy alone, stereotactic radiosurgery alone, and their combination in the treatment of brain metastases based on randomized controlled trial studies. Electronic databases (PubMed, MEDLINE, Embase, and Cochrane Library) were searched to identify randomized controlled trial studies that compared treatment outcome of whole brain radiotherapy and stereotactic radiosurgery. This meta-analysis was performed using the Review Manager (RevMan) software (version 5.2) that is provided by the Cochrane Collaboration. The data used were hazard ratios with 95% confidence intervals calculated for time-to-event data extracted from survival curves and local tumor control rate curves. Odds ratio with 95% confidence intervals were calculated for dichotomous data, while mean differences with 95% confidence intervals were calculated for continuous data. Fixed-effects or random-effects models were adopted according to heterogeneity. Five studies (n = 763) were included in this meta-analysis meeting the inclusion criteria. All the included studies were randomized controlled trials. The sample size ranged from 27 to 331. In total 202 (26%) patients with whole brain radiotherapy alone, 196 (26%) patients receiving stereotactic radiosurgery alone, and 365 (48%) patients were in whole brain radiotherapy plus stereotactic radiosurgery group. No significant survival benefit was observed for any treatment approach; hazard ratio was 1.19 (95% confidence interval: 0.96-1.43, p = 0.12) based on three randomized controlled trials for whole brain radiotherapy only compared to whole brain radiotherapy plus stereotactic radiosurgery and hazard ratio was 1.03 (95% confidence interval: 0.82-1.29, p = 0.81) for stereotactic radiosurgery only compared to combined approach. Local control was best achieved when whole brain radiotherapy was combined with stereotactic radiosurgery. Hazard ratio 2.05 (95% confidence interval: 1.36-3.09, p = 0.0006) and hazard ratio 1.84 (95% confidence interval: 1.26-2.70, p = 0.002) were obtained from comparing whole brain radiotherapy only and stereotactic radiosurgery only to whole brain radiotherapy + stereotactic radiosurgery, respectively. No difference in adverse events for treatment difference; odds ratio 1.16 (95% confidence interval: 0.77-1.76, p = 0.48) and odds ratio 0.92 (95% confidence interval: 0.59-1.42, p = 71) for whole brain radiotherapy + stereotactic radiosurgery versus whole brain radiotherapy only and whole brain radiotherapy + stereotactic radiosurgery versus stereotactic radiosurgery only, respectively. Adding stereotactic radiosurgery to whole brain radiotherapy provides better local control as compared to whole brain radiotherapy only and stereotactic radiosurgery only with no difference in radiation related toxicities.

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.

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.

Size-Dependent Neurotoxicity of Aluminum Oxide Particles: a Comparison Between Nano- and Micrometer Size on the Basis of Mitochondrial Oxidative Damage.

PubMed

Mirshafa, Atefeh; Nazari, Mehdi; Jahani, Daniel; Shaki, Fatemeh

2018-06-01

Aluminum nanoparticles (AlNPs) are among the most abundantly produced nanosized particles in the market. There is limited information about the potential harmful effects of aluminum oxide due to its particle size on human health. Considering the toxic effects of Al on brain as its target tissue, in this study, the toxicity of nanoparticles, microparticles, and ionic forms of Al on rat brain and isolated mitochondria was evaluated. Sixty male Wistar rats were divided into ten groups (six rats each), in which group I was the control, and the other groups were administered different doses of Al nanoparticles, Al microparticles (AlMP), and Al ionic forms (2, 4, and 8 mg/kg, i.p.) for 28 days. After 24 h, the animals were killed, brain tissue was separated, the mitochondrial fraction was isolated, and oxidative stress markers were measured. Also, mitochondrial function was assayed by MTT test. The results showed that all forms of Al particles induced ROS formation, lipid peroxidation, protein oxidation, glutathione depletion, mitochondrial dysfunction, and gait abnormalities in a dose-dependent manner. In addition, Al particles decreased mitochondrial membrane potential. These data indicated that oxidative stress might contribute to the toxicity effects of Al. Comparison of oxidative stress markers between all forms of Al revealed that the toxic effect of AlNP on brain tissue was substantially more than that caused by AlMP and bulk form. This study showed more neurotoxicity of AlNPs compared to other forms on brain oxidative damage that probably is due to more penetration into the brain.

Genetic Causes of Microcephaly and Lessons for Neuronal Development

PubMed Central

Gilmore, Edward C.; Walsh, Christopher A.

2012-01-01

The study of human developmental microcephaly is providing important insights into brain development. It has become clear that developmental microcephalies are associated with abnormalities in cellular production, and that the pathophysiology of microcephaly provides remarkable insights into how the brain generates the proper number of neurons that determine brain size. Most of the genetic causes of ‘primary’ developmental microcephaly (i.e., not associated with other syndromic features) are associated with centrosomal abnormalities. In addition to other functions, centrosomal proteins control the mitotic spindle, which is essential for normal cell proliferation during mitosis. However, the brain is often uniquely affected when microcephaly genes are mutated implying special centrosomal related functions in neuronal production. Although models explaining how this could occur have some compelling data, they are not without controversy. Interestingly, some of the microcephaly genes show evidence that they were targets of evolutionary selection in primates and human ancestors, suggesting potential evolutionary roles in controlling neuronal number and brain volume across species. Mutations in DNA repair pathway genes also lead to microcephaly. Double stranded DNA breaks appear to be a prominent type of damage that needs to be repaired during brain development, yet why defects in DNA repair affect the brain preferentially and if DNA repair relates to centrosome function, are not clearly understood. PMID:24014418

Re-evaluating the link between brain size and behavioural ecology in primates.

PubMed

Powell, Lauren E; Isler, Karin; Barton, Robert A

2017-10-25

Comparative studies have identified a wide range of behavioural and ecological correlates of relative brain size, with results differing between taxonomic groups, and even within them. In primates for example, recent studies contradict one another over whether social or ecological factors are critical. A basic assumption of such studies is that with sufficiently large samples and appropriate analysis, robust correlations indicative of selection pressures on cognition will emerge. We carried out a comprehensive re-examination of correlates of primate brain size using two large comparative datasets and phylogenetic comparative methods. We found evidence in both datasets for associations between brain size and ecological variables (home range size, diet and activity period), but little evidence for an effect of social group size, a correlation which has previously formed the empirical basis of the Social Brain Hypothesis. However, reflecting divergent results in the literature, our results exhibited instability across datasets, even when they were matched for species composition and predictor variables. We identify several potential empirical and theoretical difficulties underlying this instability and suggest that these issues raise doubts about inferring cognitive selection pressures from behavioural correlates of brain size. © 2017 The Author(s).

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)

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

Non-invasive brain stimulation to investigate language production in healthy speakers: A meta-analysis.

PubMed

Klaus, Jana; Schutter, Dennis J L G

2018-06-01

Non-invasive brain stimulation (NIBS) has become a common method to study the interrelations between the brain and language functioning. This meta-analysis examined the efficacy of transcranial magnetic stimulation (TMS) and direct current stimulation (tDCS) in the study of language production in healthy volunteers. Forty-five effect sizes from 30 studies which investigated the effects of NIBS on picture naming or verbal fluency in healthy participants were meta-analysed. Further sub-analyses investigated potential influences of stimulation type, control, target site, task, online vs. offline application, and current density of the target electrode. Random effects modelling showed a small, but reliable effect of NIBS on language production. Subsequent analyses indicated larger weighted mean effect sizes for TMS as compared to tDCS studies. No statistical differences for the other sub-analyses were observed. We conclude that NIBS is a useful method for neuroscientific studies on language production in healthy volunteers. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Brain structural and functional asymmetry in human situs inversus totalis.

PubMed

Vingerhoets, Guy; Li, Xiang; Hou, Lewis; Bogaert, Stephanie; Verhelst, Helena; Gerrits, Robin; Siugzdaite, Roma; Roberts, Neil

2018-05-01

Magnetic resonance imaging was used to investigate brain structural and functional asymmetries in 15 participants with complete visceral reversal (situs inversus totalis, SIT). Language-related brain structural and functional lateralization of SIT participants, including peri-Sylvian gray and white matter asymmetries and hemispheric language dominance, was similar to those of 15 control participants individually matched for sex, age, education, and handedness. In contrast, the SIT cohort showed reversal of the brain (Yakovlevian) torque (occipital petalia and occipital bending) compared to the control group. Secondary findings suggested different asymmetry patterns between SIT participants with (n = 6) or without (n = 9) primary ciliary dyskinesia (PCD, also known as Kartagener syndrome) although the small sample sizes warrant cautious interpretation. In particular, reversed brain torque was mainly due to the subgroup with PCD-unrelated SIT and this group also included 55% left handers, a ratio close to a random allocation of handedness. We conclude that complete visceral reversal has no effect on the lateralization of brain structural and functional asymmetries associated with language, but seems to reverse the typical direction of the brain torque in particular in participants that have SIT unrelated to PCD. The observed differences in asymmetry patterns of SIT groups with and without PCD seem to suggest that symmetry breaking of visceral laterality, brain torque, and language dominance rely on different mechanisms.

EXiO-A Brain-Controlled Lower Limb Exoskeleton for Rhesus Macaques.

PubMed

Vouga, Tristan; Zhuang, Katie Z; Olivier, Jeremy; Lebedev, Mikhail A; Nicolelis, Miguel A L; Bouri, Mohamed; Bleuler, Hannes

2017-02-01

Recent advances in the field of brain-machine interfaces (BMIs) have demonstrated enormous potential to shape the future of rehabilitation and prosthetic devices. Here, a lower-limb exoskeleton controlled by the intracortical activity of an awake behaving rhesus macaque is presented as a proof-of-concept for a locomotorBMI. A detailed description of the mechanical device, including its innovative features and first experimental results, is provided. During operation, BMI-decoded position and velocity are directly mapped onto the bipedal exoskeleton's motions, which then move the monkey's legs as the monkey remains physicallypassive. To meet the unique requirements of such an application, the exoskeleton's features include: high output torque with backdrivable actuation, size adjustability, and safe user-robot interface. In addition, a novel rope transmission is introduced and implemented. To test the performance of the exoskeleton, a mechanical assessment was conducted, which yielded quantifiable results for transparency, efficiency, stiffness, and tracking performance. Usage under both brain control and automated actuation demonstrates the device's capability to fulfill the demanding needs of this application. These results lay the groundwork for further advancement in BMI-controlled devices for primates including humans.

Neuron-specific caveolin-1 overexpression improves motor function and preserves memory in mice subjected to brain trauma.

PubMed

Egawa, Junji; Schilling, Jan M; Cui, Weihua; Posadas, Edmund; Sawada, Atsushi; Alas, Basheer; Zemljic-Harpf, Alice E; Fannon-Pavlich, McKenzie J; Mandyam, Chitra D; Roth, David M; Patel, Hemal H; Patel, Piyush M; Head, Brian P

2017-08-01

Studies in vitro and in vivo demonstrate that membrane/lipid rafts and caveolin (Cav) organize progrowth receptors, and, when overexpressed specifically in neurons, Cav-1 augments neuronal signaling and growth and improves cognitive function in adult and aged mice; however, whether neuronal Cav-1 overexpression can preserve motor and cognitive function in the brain trauma setting is unknown. Here, we generated a neuron-targeted Cav-1-overexpressing transgenic (Tg) mouse [synapsin-driven Cav-1 (SynCav1 Tg)] and subjected it to a controlled cortical impact model of brain trauma and measured biochemical, anatomic, and behavioral changes. SynCav1 Tg mice exhibited increased hippocampal expression of Cav-1 and membrane/lipid raft localization of postsynaptic density protein 95, NMDA receptor, and tropomyosin receptor kinase B. When subjected to a controlled cortical impact, SynCav1 Tg mice demonstrated preserved hippocampus-dependent fear learning and memory, improved motor function recovery, and decreased brain lesion volume compared with wild-type controls. Neuron-targeted overexpression of Cav-1 in the adult brain prevents hippocampus-dependent learning and memory deficits, restores motor function after brain trauma, and decreases brain lesion size induced by trauma. Our findings demonstrate that neuron-targeted Cav-1 can be used as a novel therapeutic strategy to restore brain function and prevent trauma-associated maladaptive plasticity.-Egawa, J., Schilling, J. M., Cui, W., Posadas, E., Sawada, A., Alas, B., Zemljic-Harpf, A. E., Fannon-Pavlich, M. J., Mandyam, C. D., Roth, D. M., Patel, H. H., Patel, P. M., Head, B. P. Neuron-specific caveolin-1 overexpression improves motor function and preserves memory in mice subjected to brain trauma. © FASEB.

The effects of rearing light level and duration differences on the optic nerve, brain, and associated structures in developing zebrafish larvae: a light and transmission electron microscope study.

PubMed

Chapman, George B; Tarboush, Rania; Connaughton, Victoria P

2012-03-01

The ultrastructure of the optic nerve, brain, and some associated structures of larval zebrafish, grown under three different light regimens were studied. Fish grown under cyclic light (control), constant dark (CD), and constant light (CL) were studied for 4 and 8 days postfertilization (dpf). We also studied the control and CD fish at 15 dpf. The brains of the control and CL fish were larger at 4 dpf than at 8 dpf. In all 4 dpf fish, the brain occupied the entire expanse between the two retinas and the optic nerve extended the shortest distance between the retina and the brain. The 15 dpf zebrafish had the smallest brain size. Groups of skeletal muscle cells associated with the optic nerves became visible in all older larvae. In the 15 dpf larvae, bulges and dilations in the optic nerve occurred as it reached the brain and optic chiasms occurred proximal to the brain. Electron microscopy yielded information about myelinated and unmyelinated axons in the optic nerve, the dimensions of neurotubules, neurofilaments, and myofilaments, including a unique variation in actin myofilaments, and a confirmation of reported myosin myofilament changes (but with dimensions). We also describe the ultrastructure of a sheath-like structure that is confluent over the optic nerve and the brain, which has not been described before in zebrafish. Also presented are images of associated fibroblasts, epithelial cells lining the mouth, cartilage plates, blood vessels, nerve bundles, and skeletal muscle cells, most of which have not been previously described in the literature. Copyright © 2012 Wiley Periodicals, Inc.

On the relationship between head circumference, brain size, prenatal long-chain PUFA/5-methyltetrahydrofolate supplementation and cognitive abilities during childhood.

PubMed

Catena, Andrés; Martínez-Zaldívar, Cristina; Diaz-Piedra, Carolina; Torres-Espínola, Francisco J; Brandi, Pilar; Pérez-García, Miguel; Decsi, Tamás; Koletzko, Berthold; Campoy, Cristina

2017-03-29

Head circumference in infants has been reported to predict brain size, total grey matter volume (GMV) and neurocognitive development. However, it is unknown whether it has predictive value on regional and subcortical brain volumes. We aimed to explore the relationship between several head circumference measurements since birth and distributions of GMV and subcortical volumes at later childhood. We examined seventy-four, Caucasian, singleton, term-born infants born to mothers randomised to receive fish oil and/or 5-methyltetrahydrofolate or placebo prenatal supplementation. We assessed head circumference at birth and at 4 and 10 years of age and cognitive abilities at 7 years of age. We obtained brain MRI at 10 years of age, on which we performed voxel-based morphometry, cortical surface extraction and subcortical segmentation. Analyses were controlled for sex, age, height, weight, family status, laterality and total intracranial volume. Prenatal supplementation did not affect head circumference at any age, cognitive abilities or total brain volumes. Head circumference at 4 years presented the highest correlation with total GMV, white matter volume and brain surface area, and was also strongly associated with GMV of frontal, temporal and occipital areas, as well as with caudate nucleus, globus pallidus, putamen and thalamus volumes. As relationships between brain volumes in childhood and several outcomes extend into adulthood, we have found that ages between 0 and 4 years as the optimal time for brain growth; postnatal factors might have the most relevant impact on structural maturation of certain cortical areas and subcortical nuclei, independent of prenatal supplementation.

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.

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.

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.

Novel Tool Selection in Left Brain-Damaged Patients With Apraxia of Tool Use: A Study of Three Cases.

PubMed

Osiurak, François; Granjon, Marine; Bonnevie, Isabelle; Brogniart, Joël; Mechtouff, Laura; Benoit, Amandine; Nighoghossian, Norbert; Lesourd, Mathieu

2018-05-01

Recent evidence indicates that some left brain-damaged (LBD) patients have difficulties to use familiar tools because of the inability to reason about physical object properties. A fundamental issue is to understand the residual capacity of those LBD patients in tool selection. Three LBD patients with tool use disorders, three right brain-damaged (RBD) patients, and six matched healthy controls performed a novel tool selection task, consisting in extracting a target out from a box by selecting the relevant tool among eight, four, or two tools. Three criteria were manipulated to make relevant and irrelevant tools (size, rigidity, shape). LBD patients selected a greater number of irrelevant tools and had more difficulties to solve the task compared to RBD patients and controls. All participants committed more errors for selecting relevant tools based on rigidity and shape than size. In some LBD patients, the difficulties persisted even in the 2-Choice condition. Our findings confirm that tool use disorders result from impaired technical reasoning, leading patients to meet difficulties in selecting tools based on their physical properties. We also go further by showing that these difficulties can decrease as the choice is reduced, at least for some properties, opening new avenues for rehabilitation programs. (JINS, 2018, 24, 524-529).

Family-based training program improves brain function, cognition, and behavior in lower socioeconomic status preschoolers

PubMed Central

Neville, Helen J.; Stevens, Courtney; Pakulak, Eric; Bell, Theodore A.; Fanning, Jessica; Klein, Scott; Isbell, Elif

2013-01-01

Using information from research on the neuroplasticity of selective attention and on the central role of successful parenting in child development, we developed and rigorously assessed a family-based training program designed to improve brain systems for selective attention in preschool children. One hundred forty-one lower socioeconomic status preschoolers enrolled in a Head Start program were randomly assigned to the training program, Head Start alone, or an active control group. Electrophysiological measures of children’s brain functions supporting selective attention, standardized measures of cognition, and parent-reported child behaviors all favored children in the treatment program relative to both control groups. Positive changes were also observed in the parents themselves. Effect sizes ranged from one-quarter to half of a standard deviation. These results lend impetus to the further development and broader implementation of evidence-based education programs that target at-risk families. PMID:23818591

Apixaban decreases brain thrombin activity in a male mouse model of acute ischemic stroke.

PubMed

Bushi, Doron; Chapman, Joab; Wohl, Anton; Stein, Efrat Shavit; Feingold, Ekaterina; Tanne, David

2018-05-14

Factor Xa (FXa) plays a critical role in the coagulation cascade by generation of thrombin. During focal ischemia thrombin levels increase in the brain tissue and cause neural damage. This study examined the hypothesis that administration of the FXa inhibitor, apixaban, following focal ischemic stroke may have therapeutic potential by decreasing brain thrombin activity and infarct volume. Male mice were divided into a treated groups that received different doses of apixaban (2, 20, 100 mg/kg administered I.P.) or saline (controls) immediately after blocking the middle cerebral artery (MCA). Thrombin activity was measured by a fluorescence assay on fresh coronal slices taken from the mice brains 24 hr following the MCA occlusion. Infarct volume was assessed using triphenyltetrazolium chloride staining. A high dose of apixaban (100 mg/kg) significantly decreased thrombin activity levels in the ipsilateral hemisphere compared to the control group (Slice#5, p = .016; Slice#6, p = .016; Slice#7, p = .016; Slice#8, p = .036; by the nonparametric Mann-Whitney test). In addition, treatment with apixaban doses of both 100 mg/kg (32 ± 8% vs. 76 ± 7% in the treatment vs. control groups respectively; p = .005 by the nonparametric Mann-Whitney test) and 20 mg/kg (43 ± 7% vs. 76 ± 7% in the treatment vs. control groups respectively; p = .019 by the nonparametric Mann-Whitney test) decreased infarct volumes in areas surrounding the ischemic core (Slices #3 and #8). No brain hemorrhages were observed either in the treated or control groups. In summary, I.P. administration of high dose of apixaban immediately after MCA occlusion decreases brain thrombin activity and reduces infarct size. © 2018 Wiley Periodicals, Inc.

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.

Genetic control of postnatal human brain growth

PubMed Central

van Dyck, Laura I.; Morrow, Eric M.

2017-01-01

Purpose of review Studies investigating postnatal brain growth disorders inform the biology underlying the development of human brain circuitry. This research is becoming increasingly important for the diagnosis and treatment of childhood neurodevelopmental disorders, including autism and related disorders. Here we review recent research on typical and abnormal postnatal brain growth and examine potential biological mechanisms. Recent findings Clinically, brain growth disorders are heralded by diverging head size for a given age and sex, but are more precisely characterized by brain imaging, postmortem analysis, and animal model studies. Recent neuroimaging and molecular biological studies on postnatal brain growth disorders have broadened our view of both typical and pathological postnatal neurodevelopment. Correlating gene and protein function with brain growth trajectories uncovers postnatal biological mechanisms, including neuronal arborization, synaptogenesis and pruning, and gliogenesis and myelination. Recent investigations of childhood neurodevelopmental and neurodegenerative disorders highlight the underlying genetic programming and experience-dependent remodeling of neural circuitry. Summary In order to understand typical and abnormal postnatal brain development, clinicians and researchers should characterize brain growth trajectories in the context of neurogenetic syndromes. Understanding mechanisms and trajectories of postnatal brain growth will aid in differentiating, diagnosing, and potentially treating neurodevelopmental disorders. PMID:27898583

Brain-region–specific alterations of the trajectories of neuronal volume growth throughout the lifespan in autism

PubMed Central

2014-01-01

Several morphometric studies have revealed smaller than normal neurons in the neocortex of autistic subjects. To test the hypothesis that abnormal neuronal growth is a marker of an autism-associated global encephalopathy, neuronal volumes were estimated in 16 brain regions, including various subcortical structures, Ammon’s horn, archicortex, cerebellum, and brainstem in 14 brains from individuals with autism 4 to 60 years of age and 14 age-matched control brains. This stereological study showed a significantly smaller volume of neuronal soma in 14 of 16 regions in the 4- to 8-year-old autistic brains than in the controls. Arbitrary classification revealed a very severe neuronal volume deficit in 14.3% of significantly altered structures, severe in 50%, moderate in 21.4%, and mild in 14.3% structures. This pattern suggests desynchronized neuronal growth in the interacting neuronal networks involved in the autistic phenotype. The comparative study of the autistic and control subject brains revealed that the number of structures with a significant volume deficit decreased from 14 in the 4- to 8-year-old autistic subjects to 4 in the 36- to 60-year-old. Neuronal volumes in 75% of the structures examined in the older adults with autism are comparable to neuronal volume in age-matched controls. This pattern suggests defects of neuronal growth in early childhood and delayed up-regulation of neuronal growth during adolescence and adulthood reducing neuron soma volume deficit in majority of examined regions. However, significant correction of neuron size but limited clinical improvements suggests that delayed correction does not restore functional deficits. PMID:24612906

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.

Focal brain lesions induced with ultraviolet irradiation.

PubMed

Nakata, Mariko; Nagasaka, Kazuaki; Shimoda, Masayuki; Takashima, Ichiro; Yamamoto, Shinya

2018-05-22

Lesion and inactivation methods have played important roles in neuroscience studies. However, traditional techniques for creating a brain lesion are highly invasive, and control of lesion size and shape using these techniques is not easy. Here, we developed a novel method for creating a lesion on the cortical surface via 365 nm ultraviolet (UV) irradiation without breaking the dura mater. We demonstrated that 2.0 mWh UV irradiation, but not the same amount of non-UV light irradiation, induced an inverted bell-shaped lesion with neuronal loss and accumulation of glial cells. Moreover, the volume of the UV irradiation-induced lesion depended on the UV light exposure amount. We further succeeded in visualizing the lesioned site in a living animal using magnetic resonance imaging (MRI). Importantly, we also observed using an optical imaging technique that the spread of neural activation evoked by adjacent cortical stimulation disappeared only at the UV-irradiated site. In summary, UV irradiation can induce a focal brain lesion with a stable shape and size in a less invasive manner than traditional lesioning methods. This method is applicable to not only neuroscientific lesion experiments but also studies of the focal brain injury recovery process.

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

Brain cortical structural differences between non-central nervous system cancer patients treated with and without chemotherapy compared to non-cancer controls: a cross-sectional pilot MRI study using clinically indicated scans

NASA Astrophysics Data System (ADS)

Shiroishi, Mark S.; Gupta, Vikash; Bigjahan, Bavrina; Cen, Steven Y.; Rashid, Faisal; Hwang, Darryl H.; Lerner, Alexander; Boyko, Orest B.; Liu, Chia-Shang Jason; Law, Meng; Thompson, Paul M.; Jahanshad, Neda

2017-11-01

Background: Increases in cancer survival have made understanding the basis of cancer-related cognitive impairment (CRCI) more important. CRCI neuroimaging studies have traditionally used dedicated research brain MRIs in breast cancer survivors with small sample sizes; little is known about other non-CNS cancers. However, there is a wealth of unused data from clinically-indicated MRIs that could be used to study CRCI. Objective: Evaluate brain cortical structural differences in those with non-CNS cancers using clinically-indicated MRIs. Design: Cross-sectional Patients: Adult non-CNS cancer and non-cancer control (C) patients who underwent clinically-indicated MRIs. Methods: Brain cortical surface area and thickness were measured using 3D T1-weighted images. An age-adjusted linear regression model was used and the Benjamini and Hochberg false discovery rate (FDR) corrected for multiple comparisons. Group comparisons were: cancer cases with chemotherapy (Ch+), cancer cases without chemotherapy (Ch-) and subgroup of lung cancer cases with and without chemotherapy vs C. Results: Sixty-four subjects were analyzed: 22 Ch+, 23 Ch- and 19 C patients. Subgroup analysis of 16 LCa was also performed. Statistically significant decreases in either cortical surface area or thickness were found in multiple ROIs primarily within the frontal and temporal lobes for all comparisons. Limitations: Several limitations were apparent including a small sample size that precluded adjustment for other covariates. Conclusions: Our preliminary results suggest that various types of non-CNS cancers, both with and without chemotherapy, may result in brain structural abnormalities. Also, there is a wealth of untapped clinical MRIs that could be used for future CRCI studies.

Comparision between Brain Atrophy and Subdural Volume to Predict Chronic Subdural Hematoma: Volumetric CT Imaging Analysis

PubMed Central

Ju, Min-Wook; Kwon, Hyon-Jo; Choi, Seung-Won; Koh, Hyeon-Song; Youm, Jin-Young; Song, Shi-Hun

2015-01-01

Objective Brain atrophy and subdural hygroma were well known factors that enlarge the subdural space, which induced formation of chronic subdural hematoma (CSDH). Thus, we identified the subdural volume that could be used to predict the rate of future CSDH after head trauma using a computed tomography (CT) volumetric analysis. Methods A single institution case-control study was conducted involving 1,186 patients who visited our hospital after head trauma from January 1, 2010 to December 31, 2014. Fifty-one patients with delayed CSDH were identified, and 50 patients with age and sex matched for control. Intracranial volume (ICV), the brain parenchyme, and the subdural space were segmented using CT image-based software. To adjust for variations in head size, volume ratios were assessed as a percentage of ICV [brain volume index (BVI), subdural volume index (SVI)]. The maximum depth of the subdural space on both sides was used to estimate the SVI. Results Before adjusting for cranium size, brain volume tended to be smaller, and subdural space volume was significantly larger in the CSDH group (p=0.138, p=0.021, respectively). The BVI and SVI were significantly different (p=0.003, p=0.001, respectively). SVI [area under the curve (AUC), 77.3%; p=0.008] was a more reliable technique for predicting CSDH than BVI (AUC, 68.1%; p=0.001). Bilateral subdural depth (sum of subdural depth on both sides) increased linearly with SVI (p<0.0001). Conclusion Subdural space volume was significantly larger in CSDH groups. SVI was a more reliable technique for predicting CSDH. Bilateral subdural depth was useful to measure SVI. PMID:27169071

Comparision between Brain Atrophy and Subdural Volume to Predict Chronic Subdural Hematoma: Volumetric CT Imaging Analysis.

PubMed

Ju, Min-Wook; Kim, Seon-Hwan; Kwon, Hyon-Jo; Choi, Seung-Won; Koh, Hyeon-Song; Youm, Jin-Young; Song, Shi-Hun

2015-10-01

Brain atrophy and subdural hygroma were well known factors that enlarge the subdural space, which induced formation of chronic subdural hematoma (CSDH). Thus, we identified the subdural volume that could be used to predict the rate of future CSDH after head trauma using a computed tomography (CT) volumetric analysis. A single institution case-control study was conducted involving 1,186 patients who visited our hospital after head trauma from January 1, 2010 to December 31, 2014. Fifty-one patients with delayed CSDH were identified, and 50 patients with age and sex matched for control. Intracranial volume (ICV), the brain parenchyme, and the subdural space were segmented using CT image-based software. To adjust for variations in head size, volume ratios were assessed as a percentage of ICV [brain volume index (BVI), subdural volume index (SVI)]. The maximum depth of the subdural space on both sides was used to estimate the SVI. Before adjusting for cranium size, brain volume tended to be smaller, and subdural space volume was significantly larger in the CSDH group (p=0.138, p=0.021, respectively). The BVI and SVI were significantly different (p=0.003, p=0.001, respectively). SVI [area under the curve (AUC), 77.3%; p=0.008] was a more reliable technique for predicting CSDH than BVI (AUC, 68.1%; p=0.001). Bilateral subdural depth (sum of subdural depth on both sides) increased linearly with SVI (p<0.0001). Subdural space volume was significantly larger in CSDH groups. SVI was a more reliable technique for predicting CSDH. Bilateral subdural depth was useful to measure SVI.

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.

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.

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.

Effect of hypnotherapy and educational intervention on brain response to visceral stimulusin the irritable bowel syndrome

PubMed Central

Lowén, Mats B.O.; Mayer, Emeran A.; Sjöberg, Martha; Tillisch, Kirsten; Naliboff, Bruce; Labus, Jennifer; Lundberg, Peter; Ström, Magnus; Engström, Maria; Walter, Susanna A.

2013-01-01

SUMMARY Background Gut directed hypnotherapy can reduce IBS symptoms but the mechanisms underlying this therapeutic effect remain unknown. Aim We determined the effect of hypnotherapy and educational intervention on brain responses to cued rectal distensions in IBS patients. Methods 44 women with moderate to severe IBS and 20 healthy controls (HCs) were included. Blood oxygen level dependent (BOLD) signals were measured by functional Magnetic Resonance Imaging (fMRI) during expectation and delivery of high (45 mmHg) and low (15 mmHg) intensity rectal distensions. Twenty-five patients were assigned to hypnotherapy (HYP) and 16 to educational intervention (EDU). 31 patients completed treatments and post treatment fMRI. Results Similar symptom reduction was achieved in both groups. Clinically successful treatment (all responders) was associated with significant BOLD attenuation during high intensity distension in the dorsal and ventral anterior insula (cluster size 142, p=0.006, and cluster size 101, p=0.005, respectively). Moreover HYP responders demonstrated a pre-post treatment BOLD attenuation in posterior insula (cluster sizes 59, p=0.05) while EDU responders had a BOLD attenuation in prefrontal cortex (cluster size 60, p=0.05). Pre-post differences for expectation conditions were almost exclusively seen in the HYP group. Following treatment, the brain response to distension was similar to that observed in HCs, suggesting that the treatment had a normalizing effect on the central processing abnormality of visceral signals in IBS. Conclusions The abnormal processing and enhanced perception of visceral stimuli in IBS can be normalized by psychological interventions. Symptom improvement in the treatment groups may be mediated by different brain mechanisms. PMID:23617618

Effect of hypnotherapy and educational intervention on brain response to visceral stimulus in the irritable bowel syndrome.

PubMed

Lowén, M B O; Mayer, E A; Sjöberg, M; Tillisch, K; Naliboff, B; Labus, J; Lundberg, P; Ström, M; Engström, M; Walter, S A

2013-06-01

Gut-directed hypnotherapy can reduce IBS symptoms, but the mechanisms underlying this therapeutic effect remain unknown. To determine the effect of hypnotherapy and educational intervention on brain responses to cued rectal distensions in IBS patients. Forty-four women with moderate-to-severe IBS and 20 healthy controls (HCs) were included. Blood oxygen level dependent (BOLD) signals were measured by functional Magnetic Resonance Imaging (fMRI) during expectation and delivery of high- (45 mmHg) and low-intensity (15 mmHg) rectal distensions. Twenty-five patients were assigned to hypnotherapy (HYP) and 16 to educational intervention (EDU). Thirty-one patients completed treatments and posttreatment fMRI. Similar symptom reduction was achieved in both groups. Clinically successful treatment (all responders) was associated with significant BOLD attenuation during high-intensity distension in the dorsal and ventral anterior insula (cluster size 142, P = 0.006, and cluster size 101, P = 0.005 respectively). Moreover HYP responders demonstrated a pre-post treatment BOLD attenuation in posterior insula (cluster sizes 59, P = 0.05) while EDU responders had a BOLD attenuation in prefrontal cortex (cluster size 60, P = 0.05). Pre-post differences for expectation conditions were almost exclusively seen in the HYP group. Following treatment, the brain response to distension was similar to that observed in HCs, suggesting that the treatment had a normalising effect on the central processing abnormality of visceral signals in IBS. The abnormal processing and enhanced perception of visceral stimuli in IBS can be normalised by psychological interventions. Symptom improvement in the treatment groups may be mediated by different brain mechanisms. NCT01815164. © 2013 John Wiley & Sons Ltd.

Thought-Controlled Nanoscale Robots in a Living Host.

PubMed

Arnon, Shachar; Dahan, Nir; Koren, Amir; Radiano, Oz; Ronen, Matan; Yannay, Tal; Giron, Jonathan; Ben-Ami, Lee; Amir, Yaniv; Hel-Or, Yacov; Friedman, Doron; Bachelet, Ido

2016-01-01

We report a new type of brain-machine interface enabling a human operator to control nanometer-size robots inside a living animal by brain activity. Recorded EEG patterns are recognized online by an algorithm, which in turn controls the state of an electromagnetic field. The field induces the local heating of billions of mechanically-actuating DNA origami robots tethered to metal nanoparticles, leading to their reversible activation and subsequent exposure of a bioactive payload. As a proof of principle we demonstrate activation of DNA robots to cause a cellular effect inside the insect Blaberus discoidalis, by a cognitively straining task. This technology enables the online switching of a bioactive molecule on and off in response to a subject's cognitive state, with potential implications to therapeutic control in disorders such as schizophrenia, depression, and attention deficits, which are among the most challenging conditions to diagnose and treat.

Thought-Controlled Nanoscale Robots in a Living Host

PubMed Central

Giron, Jonathan; Ben-Ami, Lee; Amir, Yaniv; Hel-Or, Yacov; Friedman, Doron; Bachelet, Ido

2016-01-01

We report a new type of brain-machine interface enabling a human operator to control nanometer-size robots inside a living animal by brain activity. Recorded EEG patterns are recognized online by an algorithm, which in turn controls the state of an electromagnetic field. The field induces the local heating of billions of mechanically-actuating DNA origami robots tethered to metal nanoparticles, leading to their reversible activation and subsequent exposure of a bioactive payload. As a proof of principle we demonstrate activation of DNA robots to cause a cellular effect inside the insect Blaberus discoidalis, by a cognitively straining task. This technology enables the online switching of a bioactive molecule on and off in response to a subject’s cognitive state, with potential implications to therapeutic control in disorders such as schizophrenia, depression, and attention deficits, which are among the most challenging conditions to diagnose and treat. PMID:27525806

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.

EXPRESSION OF REELIN, ITS RECEPTORS AND ITS INTRACELLULAR SIGNALING PROTEIN, DISABLED-1 (DAB-1) IN THE CANARY BRAIN: RELATIONSHIPS WITH THE SONG CONTROL SYSTEM

PubMed Central

BALTHAZART, JACQUES; VOIGT, CORNELIA; BOSERET, GÉRALDINE; BALL, GREGORY F

2008-01-01

Songbirds produce learned vocalizations that are controlled by a specialized network of neural structures, the song control system. Several nuclei in this song control system demonstrate a marked degree of adult seasonal plasticity. Nucleus volume varies seasonally based on changes in cell size or spacing, and in the case of nucleus HVC and area X on the incorporation of new neurons. Reelin, a large glycoprotein defective in reeler mice, is assumed to determine the final location of migrating neurons in the developing brain. In mammals, reelin is also expressed in the adult brain but its functions are less well characterized. We investigated the relationships between the expression of reelin and/or its receptors and the dramatic seasonal plasticity in the canary (Serinus canaria) brain. We detected a broad distribution of the reelin protein, its messenger RNA and the mRNAs encoding for the reelin receptors (VLDLR and ApoER2) as well as for its intracellular signaling protein, Dab1. These different mRNAs and proteins did not display the same neuroanatomical distribution and were not clearly associated, in an exclusive manner, with telencephalic brain areas that incorporate new neurons in adulthood. Song control nuclei were associated with a particular specialized expression of reelin and its mRNA, with the reelin signal being either denser or lighter in the song nucleus than in the surrounding tissue. The density of reelin-ir structures did not seem to be affected by four weeks of treatment with exogenous testosterone. These observations do not provide conclusive evidence that reelin plays a prominent role in the positioning of new neurons in the adult canary brain but call for additional work on this protein analyzing its expression comparatively during development and in adulthood with a better temporal resolution at critical points in the reproductive cycle when brain plasticity is known to occur. PMID:18448255

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

Thyroxine-induced changes in the glycosylation pattern and in brain and serum levels of rat alpha-fetoprotein.

PubMed

Naval, J; Calvo, M; Lampreave, F; Piñeiro, A

1986-01-01

We have studied the effect of thyroid disfunction during the postnatal period, on the serum and brain levels of rat alpha-fetoprotein (AFP) and albumin. Hypothyroidism was induced by treatment of pregnant rats and their newborn pups with 2-mercapto-1-methylimidazole(methimazole). Hyperthyroidism was provoked in newborns by daily injections of thyroxine (0.25 micrograms/g body wt) from the 3rd postnatal day weaning. Impaired growth, lower brain size, altered behaviour and morphological features observed were according to an altered thyroid status. Hypothyroid rats showed a significantly reduction in serum AFP concentration (78% of control values at 8 days of age) and a slight increase in that of albumin. level could be appreciated. Thyroxine supplementation (0.2 micrograms/rat/day) corrected most of these alterations. Hyperthyroidism induced a drastic fall in both serum and brain AFP levels (about 48% of the corresponding control values). Albumin concentration in serum was augmented significantly from the 12th postnatal day, but its brain levels did not change significantly. In hyperthyroid rats, a significant reduction (37% relative to controls) in the concanavalin A-non reactive microform of AFP, was observed. This alteration of the glycosylation pattern of AFP could be due to the inhibition by thyroxine of the activity of the hepatic enzyme GlcNAc-transferase III.

Sensitivity of the Halstead and Wechsler Test Batteries to brain damage: Evidence from Reitan's original validation sample.

PubMed

Loring, David W; Larrabee, Glenn J

2006-06-01

The Halstead-Reitan Battery has been instrumental in the development of neuropsychological practice in the United States. Although Reitan administered both the Wechsler-Bellevue Intelligence Scale and Halstead's test battery when evaluating Halstead's theory of biologic intelligence, the relative sensitivity of each test battery to brain damage continues to be an area of controversy. Because Reitan did not perform direct parametric analysis to contrast group performances, we reanalyze Reitan's original validation data from both Halstead (Reitan, 1955) and Wechsler batteries (Reitan, 1959a) and calculate effect sizes and probability levels using traditional parametric approaches. Eight of the 10 tests comprising Halstead's original Impairment Index, as well as the Impairment Index itself, statistically differentiated patients with unequivocal brain damage from controls. In addition, 13 of 14 Wechsler measures including Full-Scale IQ also differed statistically between groups (Brain Damage Full-Scale IQ = 96.2; Control Group Full Scale IQ = 112.6). We suggest that differences in the statistical properties of each battery (e.g., raw scores vs. standardized scores) likely contribute to classification characteristics including test sensitivity and specificity.

MRI study of minor physical anomaly in childhood autism implicates aberrant neurodevelopment in infancy.

PubMed

Cheung, Charlton; McAlonan, Grainne M; Fung, Yee Y; Fung, Germaine; Yu, Kevin K; Tai, Kin-Shing; Sham, Pak C; Chua, Siew E

2011-01-01

MPAs (minor physical anomalies) frequently occur in neurodevelopmental disorders because both face and brain are derived from neuroectoderm in the first trimester. Conventionally, MPAs are measured by evaluation of external appearance. Using MRI can help overcome inherent observer bias, facilitate multi-centre data acquisition, and explore how MPAs relate to brain dysmorphology in the same individual. Optical MPAs exhibit a tightly synchronized trajectory through fetal, postnatal and adult life. As head size enlarges with age, inter-orbital distance increases, and is mostly completed before age 3 years. We hypothesized that optical MPAs might afford a retrospective 'window' to early neurodevelopment; specifically, inter-orbital distance increase may represent a biomarker for early brain dysmaturation in autism. We recruited 91 children aged 7-16; 36 with an autism spectrum disorder and 55 age- and gender-matched typically developing controls. All children had normal IQ. Inter-orbital distance was measured on T1-weighted MRI scans. This value was entered into a voxel-by-voxel linear regression analysis with grey matter segmented from a bimodal MRI data-set. Age and total brain tissue volume were entered as covariates. Intra-class coefficient for measurement of the inter-orbital distance was 0.95. Inter-orbital distance was significantly increased in the autism group (p = 0.03, 2-tailed). The autism group showed a significant relationship between inter-orbital distance grey matter volume of bilateral amygdalae extending to the unci and inferior temporal poles. Greater inter-orbital distance in the autism group compared with healthy controls is consistent with infant head size expansion in autism. Inter-orbital distance positively correlated with volume of medial temporal lobe structures, suggesting a link to "social brain" dysmorphology in the autism group. We suggest these data support the role of optical MPAs as a "fossil record" of early aberrant neurodevelopment, and potential biomarker for brain dysmaturation in autism.

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

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.

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

Volumetric neuroimaging in Usher syndrome: evidence of global involvement.

PubMed

Schaefer, G B; Bodensteiner, J B; Thompson, J N; Kimberling, W J; Craft, J M

1998-08-27

Usher syndrome is a group of genetic disorders consisting of congenital sensorineural hearing loss and retinitis pigmentosa of variable onset and severity depending on the genetic type. It was suggested that the psychosis of Usher syndrome might be secondary to a metabolic degeneration involving the brain more diffusely. There have been reports of focal and diffuse atrophic changes in the supratentorial brain as well as atrophy of some of the structures of the posterior fossa. We previously performed quantitative analysis of magnetic resonance imaging studies of 19 Usher syndrome patients (12 with type I and 7 with type II) looking at the cerebellum and various cerebellar components. We found atrophy of the cerebellum in both types and sparing of cerebellar vermis lobules I-V in type II Usher syndrome patients only. We now have studied another group of 19 patients (with some overlap in the patients studied from the previous report) with Usher syndrome (8 with type I, 11 with type II). We performed quantitative volumetric measurements of various brain structures compared to age- and sex-matched controls. We found a significant decrease in intracranial volume and in size of the brain and cerebellum with a trend toward an increase in the size of the subarachnoid spaces. These data suggest that the disease process in Usher syndrome involves the entire brain and is not limited to the posterior fossa or auditory and visual systems.

Virtual reality hardware and graphic display options for brain-machine interfaces

PubMed Central

Marathe, Amar R.; Carey, Holle L.; Taylor, Dawn M.

2009-01-01

Virtual reality hardware and graphic displays are reviewed here as a development environment for brain-machine interfaces (BMIs). Two desktop stereoscopic monitors and one 2D monitor were compared in a visual depth discrimination task and in a 3D target-matching task where able-bodied individuals used actual hand movements to match a virtual hand to different target hands. Three graphic representations of the hand were compared: a plain sphere, a sphere attached to the fingertip of a realistic hand and arm, and a stylized pacman-like hand. Several subjects had great difficulty using either stereo monitor for depth perception when perspective size cues were removed. A mismatch in stereo and size cues generated inappropriate depth illusions. This phenomenon has implications for choosing target and virtual hand sizes in BMI experiments. Target matching accuracy was about as good with the 2D monitor as with either 3D monitor. However, users achieved this accuracy by exploring the boundaries of the hand in the target with carefully controlled movements. This method of determining relative depth may not be possible in BMI experiments if movement control is more limited. Intuitive depth cues, such as including a virtual arm, can significantly improve depth perception accuracy with or without stereo viewing. PMID:18006069

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.

Molecular control of brain size: Regulators of neural stem cell life, death and beyond

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

Joseph, Bertrand; Hermanson, Ola, E-mail: ola.hermanson@ki.se

2010-05-01

The proper development of the brain and other organs depends on multiple parameters, including strictly controlled expansion of specific progenitor pools. The regulation of such expansion events includes enzymatic activities that govern the correct number of specific cells to be generated via an orchestrated control of cell proliferation, cell cycle exit, differentiation, cell death etc. Certain proteins in turn exert direct control of these enzymatic activities and thus progenitor pool expansion and organ size. The members of the Cip/Kip family (p21Cip1/p27Kip1/p57Kip2) are well-known regulators of cell cycle exit that interact with and inhibit the activity of cyclin-CDK complexes, whereas membersmore » of the p53/p63/p73 family are traditionally associated with regulation of cell death. It has however become clear that the roles for these proteins are not as clear-cut as initially thought. In this review, we discuss the roles for proteins of the Cip/Kip and p53/p63/p73 families in the regulation of cell cycle control, differentiation, and death of neural stem cells. We suggest that these proteins act as molecular interfaces, or 'pilots', to assure the correct assembly of protein complexes with enzymatic activities at the right place at the right time, thereby regulating essential decisions in multiple cellular events.« less

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.

fMRI of parents of children with Asperger Syndrome: a pilot study.

PubMed

Baron-Cohen, Simon; Ring, Howard; Chitnis, Xavier; Wheelwright, Sally; Gregory, Lloyd; Williams, Steve; Brammer, Mick; Bullmore, Ed

2006-06-01

People with autism or Asperger Syndrome (AS) show altered patterns of brain activity during visual search and emotion recognition tasks. Autism and AS are genetic conditions and parents may show the 'broader autism phenotype.' (1) To test if parents of children with AS show atypical brain activity during a visual search and an empathy task; (2) to test for sex differences during these tasks at the neural level; (3) to test if parents of children with autism are hyper-masculinized, as might be predicted by the 'extreme male brain' theory. We used fMRI during a visual search task (the Embedded Figures Test (EFT)) and an emotion recognition test (the 'Reading the Mind in the Eyes' (or Eyes) test). Twelve parents of children with AS, vs. 12 sex-matched controls. Factorial analysis was used to map main effects of sex, group (parents vs. controls), and sexxgroup interaction on brain function. An ordinal ANOVA also tested for regions of brain activity where females>males>fathers=mothers, to test for parental hyper-masculinization. RESULTS ON EFT TASK: Female controls showed more activity in extrastriate cortex than male controls, and both mothers and fathers showed even less activity in this area than sex-matched controls. There were no differences in group activation between mothers and fathers of children with AS. The ordinal ANOVA identified two specific regions in visual cortex (right and left, respectively) that showed the pattern Females>Males>Fathers=Mothers, both in BA 19. RESULTS ON EYES TASK: Male controls showed more activity in the left inferior frontal gyrus than female controls, and both mothers and fathers showed even more activity in this area compared to sex-matched controls. Female controls showed greater bilateral inferior frontal activation than males. This was not seen when comparing mothers to males, or mothers to fathers. The ordinal ANOVA identified two specific regions that showed the pattern Females>Males>Mothers=Fathers: left medial temporal gyrus (BA 21) and left dorsolateral prefrontal cortex (BA 44). Parents of children with AS show atypical brain function during both visual search and emotion recognition, in the direction of hyper-masculinization of the brain. Because of the small sample size, and lack of age-matching between parents and controls, such results constitute a pilot study that needs replicating with larger samples.

Laser system refinements to reduce variability in infarct size in the rat photothrombotic stroke model

PubMed Central

Alaverdashvili, Mariam; Paterson, Phyllis G.; Bradley, Michael P.

2015-01-01

Background The rat photothrombotic stroke model can induce brain infarcts with reasonable biological variability. Nevertheless, we observed unexplained high inter-individual variability despite using a rigorous protocol. Of the three major determinants of infarct volume, photosensitive dye concentration and illumination period were strictly controlled, whereas undetected fluctuation in laser power output was suspected to account for the variability. New method The frequently utilized Diode Pumped Solid State (DPSS) lasers emitting 532 nm (green) light can exhibit fluctuations in output power due to temperature and input power alterations. The polarization properties of the Nd:YAG and Nd:YVO4 crystals commonly used in these lasers are another potential source of fluctuation, since one means of controlling output power uses a polarizer with a variable transmission axis. Thus, the properties of DPSS lasers and the relationship between power output and infarct size were explored. Results DPSS laser beam intensity showed considerable variation. Either a polarizer or a variable neutral density filter allowed adjustment of a polarized laser beam to the desired intensity. When the beam was unpolarized, the experimenter was restricted to using a variable neutral density filter. Comparison with existing method(s) Our refined approach includes continuous monitoring of DPSS laser intensity via beam sampling using a pellicle beamsplitter and photodiode sensor. This guarantees the desired beam intensity at the targeted brain area during stroke induction, with the intensity controlled either through a polarizer or variable neutral density filter. Conclusions Continuous monitoring and control of laser beam intensity is critical for ensuring consistent infarct size. PMID:25840363

Neuroanatomical Diversity of Corpus Callosum and Brain Volume in Autism: Meta-analysis, Analysis of the Autism Brain Imaging Data Exchange Project, and Simulation.

PubMed

Lefebvre, Aline; Beggiato, Anita; Bourgeron, Thomas; Toro, Roberto

2015-07-15

Patients with autism have been often reported to have a smaller corpus callosum (CC) than control subjects. We conducted a meta-analysis of the literature, analyzed the CC in 694 subjects of the Autism Brain Imaging Data Exchange project, and performed computer simulations to study the effect of different analysis strategies. Our meta-analysis suggested a group difference in CC size; however, the studies were heavily underpowered (20% power to detect Cohen's d = .3). In contrast, we did not observe significant differences in the Autism Brain Imaging Data Exchange cohort, despite having achieved 99% power. However, we observed that CC scaled nonlinearly with brain volume (BV): large brains had a proportionally smaller CC. Our simulations showed that because of this nonlinearity, CC normalization could not control for eventual BV differences, but using BV as a covariate in a linear model would. We also observed a weaker correlation of IQ and BV in cases compared with control subjects. Our simulations showed that matching populations by IQ could then induce artifactual BV differences. The lack of statistical power in the previous literature prevents us from establishing the reality of the claims of a smaller CC in autism, and our own analyses did not find any. However, the nonlinear relationship between CC and BV and the different correlation between BV and IQ in cases and control subjects may induce artifactual differences. Overall, our results highlight the necessity for open data sharing to provide a more solid ground for the discovery of neuroimaging biomarkers within the context of the wide human neuroanatomical diversity. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

To cut or not to cut? Assessing the modular structure of brain networks.

PubMed

Chang, Yu-Teng; Pantazis, Dimitrios; Leahy, Richard M

2014-05-01

A wealth of methods has been developed to identify natural divisions of brain networks into groups or modules, with one of the most prominent being modularity. Compared with the popularity of methods to detect community structure, only a few methods exist to statistically control for spurious modules, relying almost exclusively on resampling techniques. It is well known that even random networks can exhibit high modularity because of incidental concentration of edges, even though they have no underlying organizational structure. Consequently, interpretation of community structure is confounded by the lack of principled and computationally tractable approaches to statistically control for spurious modules. In this paper we show that the modularity of random networks follows a transformed version of the Tracy-Widom distribution, providing for the first time a link between module detection and random matrix theory. We compute parametric formulas for the distribution of modularity for random networks as a function of network size and edge variance, and show that we can efficiently control for false positives in brain and other real-world networks. Copyright © 2014 Elsevier Inc. All rights reserved.

Brain MRI, apoliprotein E genotype, and plasma homocysteine in American Indian Alzheimer disease patients and Indian controls.

PubMed

Weiner, Myron F; de la Plata, Carlos Marquez; Fields, B A Julie; Womack, Kyle B; Rosenberg, Roger N; Gong, Yun-Hua; Qu, Bao-Xi; Diaz-Arrastia, Ramon; Hynan, Linda S

2009-02-01

We obtained brain MRIs, plasma homocysteine levels and apolipoprotein E genotyping for 11 American Indian Alzheimer disease (AD) subjects and 10 Indian controls. We calculated white matter hyperintensity volume (WMHV), whole brain volume (WBV), and ratio of white matter hyperintensity volume to whole brain volume (WMHV/WBV). There were no significant differences between AD subjects and controls in gender, history of hypertension, diabetes, or history of high cholesterol, but hypertension and diabetes were more common among AD subjects. There was no difference between AD and control groups in age (range for all subjects was 61-89 years), % Indian heritage, waist size or body mass index. Median Indian heritage was 50% or greater in both groups. Range of education was 5-13 years in the AD group and 12-16 years in controls. Median plasma homocysteine concentration was higher in AD subjects (11 micromol/L vs. 9.8 micromol/L), but did not achieve statistical significance. Significantly more AD subjects had apolipoprotein Eepsilon4 alleles than did controls (63% vs.10%). Neuroimaging findings were not significantly different between the 2 groups, but AD subjects had greater WMHV (median 15.64 vs. 5.52 cc) and greater WMHV/WBV ratio (median 1.63 vs. 0.65 %) and a far greater range of WMHV. In combined AD subjects and controls, WBV correlated with BMI and age. WMHV and WMHV/WBV correlated inversely with MMSE scores (p = 0.001, 0.002, respectively). In addition, WMHV correlated positively with % Indian heritage (p = 0.047).

Structural brain differences in school-age children with and without single-suture craniosynostosis.

PubMed

Aldridge, Kristina; Collett, Brent R; Wallace, Erin R; Birgfeld, Craig; Austin, Jordan R; Yeh, Regina; Feil, Madison; Kapp-Simon, Kathleen A; Aylward, Elizabeth H; Cunningham, Michael L; Speltz, Matthew L

2017-04-01

OBJECTIVE Single-suture craniosynostosis (SSC), the premature fusion of a cranial suture, is characterized by dysmorphology of the craniofacial skeleton. Evidence to suggest that children with SSC are at an elevated risk of mild to moderate developmental delays and neurocognitive deficits is mounting, but the associations among premature suture fusion, neuroanatomy, and neurocognition are unexplained. The goals of this study were to determine 1) whether differences in the brain are present in young children with the 2 most common forms of SSC (sagittal and metopic) several years following surgical correction, and 2) whether the pattern of differences varies by affected suture (sagittal or metopic). Examination of differences in the brains of children with SSC several years after surgery may illuminate the growth trajectory of the brain after the potential constraint of the dysmorphic cranium has been relieved. METHODS The authors compared quantitative measures of the brain acquired from MR images obtained from children with sagittal or metopic craniosynostosis (n = 36) at 7 years of age to those obtained from a group of unaffected controls (n = 27) at the same age. The authors measured the volumes of the whole brain, cerebral cortex, cerebral white matter, cerebral cortex by lobe, and ventricles. Additionally, they measured the midsagittal area of the corpus callosum and its segments and of the cerebellar vermis and its component lobules. Measurements obtained from children with SSC and controls were compared using linear regression models. RESULTS No volume measures of the cerebrum or of the whole brain differed significantly between patients with SSC and controls (p > 0.05). However, ventricle volume was significantly increased in patients with SSC (p = 0.001), particularly in those with sagittal craniosynostosis (p < 0.001). In contrast, the area of the corpus callosum was significantly reduced in patients with metopic synostosis (p = 0.04), particularly in the posterior segments (p = 0.004). Similarly, the area of lobules VI-VII of the cerebellar vermis was reduced in patients with SSC (p = 0.03), with those with metopic craniosynostosis showing the greatest reduction (p = 0.01). CONCLUSIONS The lack of differences in overall brain size or regional differences in the size of the lobes of the cerebrum in children with metopic and sagittal synostosis suggests that the elevated risk of neurodevelopmental deficits is not likely to be associated with differences in the cerebral cortex. Instead, this study showed localized differences between sagittal and metopic craniosynostosis cases as compared with controls in the ventricles and in the midsagittal structures of the corpus callosum and the cerebellum. It remains to be tested whether these structural differences are associated with the increased risk for developmental delay and neurocognitive deficits in children with SSC.

A Wirelessly Powered Micro-Spectrometer for Neural Probe-Pin Device

NASA Technical Reports Server (NTRS)

Choi, Sang H.; Kim, Min Hyuck; Song, Kyo D.; Yoon, Hargsoon; Lee, Uhn

2015-01-01

Treatment of neurological anomalies, places stringent demands on device functionality and size. A micro-spectrometer has been developed for use as an implantable neural probe to monitor neuro-chemistry in synapses. The microspectrometer, based on a NASA-invented miniature Fresnel grating, is capable of differentiating the emission spectra from various brain tissues. The micro-spectrometer meets the size requirements, and is able to probe the neuro-chemistry and suppression voltage typically associated with a neural anomaly. This neural probe-pin device (PPD) is equipped with wireless power technology (WPT) enabling operation in a continuous manner without requiring an implanted battery. The implanted neural PPD, together with a neural electronics interface and WPT, allow real-time measurement and control/feedback for remediation of neural anomalies. The design and performance of the combined PPD/WPT device for monitoring dopamine in a rat brain will be presented to demonstrate the current level of development. Future work on this device will involve the addition of an embedded expert system capable of performing semi-autonomous management of neural functions through a routine of sensing, processing, and control.

A wirelessly powered microspectrometer for neural probe-pin device

NASA Astrophysics Data System (ADS)

Choi, Sang H.; Kim, Min H.; Song, Kyo D.; Yoon, Hargsoon; Lee, Uhn

2015-12-01

Treatment of neurological anomalies, whether done invasively or not, places stringent demands on device functionality and size. We have developed a micro-spectrometer for use as an implantable neural probe to monitor neuro-chemistry in synapses. The micro-spectrometer, based on a NASA-invented miniature Fresnel grating, is capable of differentiating the emission spectra from various brain tissues. The micro-spectrometer meets the size requirements, and is able to probe the neuro-chemistry and suppression voltage typically associated with a neural anomaly. This neural probe-pin device (PPD) is equipped with wireless power technology (WPT) to enable operation in a continuous manner without requiring an implanted battery. The implanted neural PPD, together with a neural electronics interface and WPT, enable real-time measurement and control/feedback for remediation of neural anomalies. The design and performance of the combined PPD/WPT device for monitoring dopamine in a rat brain will be presented to demonstrate the current level of development. Future work on this device will involve the addition of an embedded expert system capable of performing semi-autonomous management of neural functions through a routine of sensing, processing, and control.

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

Anatomy and aging of the amygdala and hippocampus in autism spectrum disorder: an in vivo magnetic resonance imaging study of Asperger syndrome.

PubMed

Murphy, Clodagh M; Deeley, Q; Daly, E M; Ecker, C; O'Brien, F M; Hallahan, B; Loth, E; Toal, F; Reed, S; Hales, S; Robertson, D M; Craig, M C; Mullins, D; Barker, G J; Lavender, T; Johnston, P; Murphy, K C; Murphy, D G

2012-02-01

It has been proposed that people with autism spectrum disorder (ASD) have abnormal morphometry and development of the amygdala and hippocampus (AH). However, previous reports are inconsistent, perhaps because they included people of different ASD diagnoses, ages, and health. We compared, using magnetic resonance imaging, the in vivo anatomy of the AH in 32 healthy individuals with Asperger syndrome (12-47 years) and 32 healthy controls who did not differ significantly in age or IQ. We measured bulk (gray + white matter) volume of the AH using manual tracing (MEASURE). We first compared the volume of AH between individuals with Asperger syndrome and controls and then investigated age-related differences. We compared differences in anatomy before, and after, correcting for whole brain size. There was no significant between group differences in whole brain volume. However, individuals with Asperger syndrome had a significantly larger raw bulk volume of total (P<0.01), right (P<0.01), and left amygdala (P<0.05); and when corrected for overall brain size, total (P<0.05), and right amygdala (P<0.01). There was a significant group difference in aging of left amygdala; controls, but not individuals with Asperger syndrome, had a significant age-related increase in volume (r = 0.486, P<0.01, and r = 0.007, P = 0.97, z = 1.995). There were no significant group differences in volume or age-related effects in hippocampus. Individuals with Asperger syndrome have significant differences from controls in bulk volume and aging of the amygdala. Copyright © 2011, International Society for Autism Research, Wiley-Liss, Inc.

The inner CSF–brain barrier: developmentally controlled access to the brain via intercellular junctions

PubMed Central

Whish, Sophie; Dziegielewska, Katarzyna M.; Møllgård, Kjeld; Noor, Natassya M.; Liddelow, Shane A.; Habgood, Mark D.; Richardson, Samantha J.; Saunders, Norman R.

2015-01-01

In the adult the interface between the cerebrospinal fluid and the brain is lined by the ependymal cells, which are joined by gap junctions. These intercellular connections do not provide a diffusional restrain between the two compartments. However, during development this interface, initially consisting of neuroepithelial cells and later radial glial cells, is characterized by “strap” junctions, which limit the exchange of different sized molecules between cerebrospinal fluid and the brain parenchyma. Here we provide a systematic study of permeability properties of this inner cerebrospinal fluid-brain barrier during mouse development from embryonic day, E17 until adult. Results show that at fetal stages exchange across this barrier is restricted to the smallest molecules (286Da) and the diffusional restraint is progressively removed as the brain develops. By postnatal day P20, molecules the size of plasma proteins (70 kDa) diffuse freely. Transcriptomic analysis of junctional proteins present in the cerebrospinal fluid-brain interface showed expression of adherens junctional proteins, actins, cadherins and catenins changing in a development manner consistent with the observed changes in the permeability studies. Gap junction proteins were only identified in the adult as was claudin-11. Immunohistochemistry was used to localize at the cellular level some of the adherens junctional proteins of genes identified from transcriptomic analysis. N-cadherin, β - and α-catenin immunoreactivity was detected outlining the inner CSF-brain interface from E16; most of these markers were not present in the adult ependyma. Claudin-5 was present in the apical-most part of radial glial cells and in endothelial cells in embryos, but only in endothelial cells including plexus endothelial cells in adults. Claudin-11 was only immunopositive in the adult, consistent with results obtained from transcriptomic analysis. These results provide information about physiological, molecular and morphological-related permeability changes occurring at the inner cerebrospinal fluid-brain barrier during brain development. PMID:25729345

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 model of posttraumatic epilepsy after penetrating brain injuries: effect of lesion size and metal fragments.

PubMed

Kendirli, M Tansel; Rose, Dominique T; Bertram, Edward H

2014-12-01

Penetrating brain injury (PBI) has the highest risk for inducing posttraumatic epilepsy, and those PBIs with retained foreign materials such as bullet fragments carry the greatest risk. This study examines the potential contribution of copper, a major component of bullets, to the development of epilepsy following PBI. Anesthetized adult male rats received a penetrating injury from the dorsal cortex to the ventral hippocampus from a high speed small bit drill. In one group of animals, copper wire was inserted into the lesion. Control animals had only the lesion or the lesion plus stainless steel wire (biologically inert foreign body). From 6 to up to 11 months following the injury the rats were monitored intermittently for the development of epilepsy with video-electroencephalography (EEG). A separate set of animals was examined for possible acute seizures in the week following the injury. Twenty-two of the 23 animals with copper wire developed chronic epilepsy, compared to three of the 20 control rats (lesion and lesion with stainless steel). Copper was associated with more extensive injury. The control rats with epilepsy had larger lesions. In the acute injury group, there was no difference in the incidence of seizures (83% lesion plus stainless steel, 70% lesion plus copper). Copper increases the risk for epilepsy and may increase damage over time, but there were no differences between the groups in the incidence of acute postinjury seizures. Lesion size may contribute to epilepsy development in lesion-only animals. Copper may be an independent risk factor for the development of epilepsy and possible secondary injury, but lesion size also contributes to the development of epilepsy. The consequences of prolonged exposure of the brain to copper observed in these animals may have clinical implications that require further evaluation. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

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.

An ensemble-of-classifiers based approach for early diagnosis of Alzheimer's disease: classification using structural features of brain images.

PubMed

Farhan, Saima; Fahiem, Muhammad Abuzar; Tauseef, Huma

2014-01-01

Structural brain imaging is playing a vital role in identification of changes that occur in brain associated with Alzheimer's disease. This paper proposes an automated image processing based approach for the identification of AD from MRI of the brain. The proposed approach is novel in a sense that it has higher specificity/accuracy values despite the use of smaller feature set as compared to existing approaches. Moreover, the proposed approach is capable of identifying AD patients in early stages. The dataset selected consists of 85 age and gender matched individuals from OASIS database. The features selected are volume of GM, WM, and CSF and size of hippocampus. Three different classification models (SVM, MLP, and J48) are used for identification of patients and controls. In addition, an ensemble of classifiers, based on majority voting, is adopted to overcome the error caused by an independent base classifier. Ten-fold cross validation strategy is applied for the evaluation of our scheme. Moreover, to evaluate the performance of proposed approach, individual features and combination of features are fed to individual classifiers and ensemble based classifier. Using size of left hippocampus as feature, the accuracy achieved with ensemble of classifiers is 93.75%, with 100% specificity and 87.5% sensitivity.

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.

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.

Tetherless near-infrared control of brain activity in behaving animals using fully implantable upconversion microdevices.

PubMed

Wang, Ying; Lin, Xudong; Chen, Xi; Chen, Xian; Xu, Zhen; Zhang, Wenchong; Liao, Qinghai; Duan, Xin; Wang, Xin; Liu, Ming; Wang, Feng; He, Jufang; Shi, Peng

2017-10-01

Many nanomaterials can be used as sensors or transducers in biomedical research and they form the essential components of transformative novel biotechnologies. In this study, we present an all-optical method for tetherless remote control of neural activity using fully implantable micro-devices based on upconversion technology. Upconversion nanoparticles (UCNPs) were used as transducers to convert near-infrared (NIR) energy to visible light in order to stimulate neurons expressing different opsin proteins. In our setup, UCNPs were packaged in a glass micro-optrode to form an implantable device with superb long-term biocompatibility. We showed that remotely applied NIR illumination is able to reliably trigger spiking activity in rat brains. In combination with a robotic laser projection system, the upconversion-based tetherless neural stimulation technique was implemented to modulate brain activity in various regions, including the striatum, ventral tegmental area, and visual cortex. Using this system, we were able to achieve behavioral conditioning in freely moving animals. Notably, our microscale device was at least one order of magnitude smaller in size (∼100 μm in diameter) and two orders of magnitude lighter in weight (less than 1 mg) than existing wireless optogenetic devices based on light-emitting diodes. This feature allows simultaneous implantation of multiple UCNP-optrodes to achieve modulation of brain function to control complex animal behavior. We believe that this technology not only represents a novel practical application of upconversion nanomaterials, but also opens up new possibilities for remote control of neural activity in the brains of behaving animals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nestin is essential for zebrafish brain and eye development through control of progenitor cell apoptosis.

PubMed

Chen, Hua-Ling; Yuh, Chiou-Hwa; Wu, Kenneth K

2010-02-19

Nestin is expressed in neural progenitor cells (NPC) of developing brain. Despite its wide use as an NPC marker, the function of nestin in embryo development is unclear. As nestin is conserved in zebrafish and its predicted sequence is clustered with the mammalian nestin orthologue, we used zebrafish as a model to investigate its role in embryogenesis. Injection of nestin morpholino (MO) into fertilized eggs induced time- and dose-dependent brain and eye developmental defects. Nestin morphants exhibited characteristic morphological changes including small head, small eyes and hydrocephalus. Histological examinations show reduced hind- and mid-brain size, dilated ventricle, poorly organized retina and underdeveloped lens. Injection of control nestin MO did not induce brain or eye changes. Nestin MO injection reduced expression of ascl1b (achaete-scute complex-like 1b), a marker of NPCs, without affecting its distribution. Nestin MO did not influence Elavl3/4 (Embryonic lethal, abnormal vision, Drosophila-like 3/4) (a neuronal marker), or otx2 (a midbrain neuronal marker), but severely perturbed cranial motor nerve development and axon distribution. To determine whether the developmental defects are due to excessive NPC apoptosis and/or reduced NPC proliferation, we analyzed apoptosis by TUNEL assay and acridine orange staining and proliferation by BrdU incorporation, pcna and mcm5 expressions. Excessive apoptosis was noted in hindbrain and midbrain cells. Apoptotic signals were colocalized with ascl1b. Proliferation markers were not significantly altered by nestin MO. These results suggest that nestin is essential for zebrafish brain and eye development probably through control of progenitor cell apoptosis.

A pilot randomized controlled trial of on-line interventions to improve sleep quality in adults after mild or moderate traumatic brain injury.

PubMed

Theadom, Alice; Barker-Collo, Suzanne; Jones, Kelly; Dudley, Margaret; Vincent, Norah; Feigin, Valery

2018-05-01

To explore feasibility and potential efficacy of on-line interventions for sleep quality following a traumatic brain injury (TBI). A two parallel-group, randomized controlled pilot study. Community-based. In all, 24 participants (mean age: 35.9 ± 11.8 years) who reported experiencing sleep difficulties between 3 and 36 months after a mild or moderate TBI. Participants were randomized to receive either a cognitive behaviour therapy or an education intervention on-line. Both interventions were self-completed for 20-30 minutes per week over a six-week period. The Pittsburgh Sleep Quality Index assessed self-reported sleep quality with actigraphy used as an objective measure of sleep quality. The CNS Vital Signs on-line neuropsychological test assessed cognitive functioning and the Rivermead Post-concussion Symptoms and Quality of Life after Brain Injury questionnaires were completed pre and post intervention. Both programmes demonstrated feasibility for use post TBI, with 83.3% of participants completing the interventions. The cognitive behaviour therapy group experienced significant reductions ( F = 5.47, p = 0.04) in sleep disturbance (mean individual change = -4.00) in comparison to controls post intervention (mean individual change = -1.50) with a moderate effect size of 1.17. There were no significant group differences on objective sleep quality, cognitive functioning, post-concussion symptoms or quality of life. On-line programmes designed to improve sleep are feasible for use for adults following mild-to-moderate TBI. Based on the effect size identified in this pilot study, 128 people (64 per group) would be needed to determine clinical effectiveness.

Big-brained birds survive better in nature

PubMed Central

Sol, Daniel; Székely, Tamás; Liker, András; Lefebvre, Louis

2007-01-01

Big brains are hypothesized to enhance survival of animals by facilitating flexible cognitive responses that buffer individuals against environmental stresses. Although this theory receives partial support from the finding that brain size limits the capacity of animals to behaviourally respond to environmental challenges, the hypothesis that large brains are associated with reduced mortality has never been empirically tested. Using extensive information on avian adult mortality from natural populations, we show here that species with larger brains, relative to their body size, experience lower mortality than species with smaller brains, supporting the general importance of the cognitive buffer hypothesis in the evolution of large brains. PMID:17251112

Cerebral biochemical pathways in experimental autoimmune encephalomyelitis and adjuvant arthritis: a comparative metabolomic study.

PubMed

Lutz, Norbert W; Fernandez, Carla; Pellissier, Jean-François; Cozzone, Patrick J; Béraud, Evelyne

2013-01-01

Many diseases, including brain disorders, are associated with perturbations of tissue metabolism. However, an often overlooked issue is the impact that inflammations outside the brain may have on brain metabolism. Our main goal was to study similarities and differences between brain metabolite profiles of animals suffering from experimental autoimmune encephalomyelitis (EAE) and adjuvant arthritis (AA) in Lewis rat models. Our principal objective was the determination of molecular protagonists involved in the metabolism underlying these diseases. EAE was induced by intraplantar injection of complete Freund's adjuvant (CFA) and spinal-cord homogenate (SC-H), whereas AA was induced by CFA only. Naive rats served as controls (n = 9 for each group). Two weeks after inoculation, animals were sacrificed, and brains were removed and processed for metabolomic analysis by NMR spectroscopy or for immunohistochemistry. Interestingly, both inflammatory diseases caused similar, though not identical, changes in metabolites involved in regulation of brain cell size and membrane production: among the osmolytes, taurine and the neuronal marker, N-acetylaspartate, were decreased, and the astrocyte marker, myo-inositol, slightly increased in both inoculated groups compared with controls. Also ethanolamine-containing phospholipids, sources of inflammatory agents, and several glycolytic metabolites were increased in both inoculated groups. By contrast, the amino acids, aspartate and isoleucine, were less concentrated in CFA/SC-H and control vs. CFA rats. Our results suggest that inflammatory brain metabolite profiles may indicate the existence of either cerebral (EAE) or extra-cerebral (AA) inflammation. These inflammatory processes may act through distinct pathways that converge toward similar brain metabolic profiles. Our findings open new avenues for future studies aimed at demonstrating whether brain metabolic effects provoked by AA are pain/stress-mediated and/or due to the presence of systemic proinflammatory molecules. Regardless of the nature of these mechanisms, our findings may be of interest for future clinical studies, e.g. by in-vivo magnetic resonance spectroscopy.

Mammalian neurogenesis requires Treacle-Plk1 for precise control of spindle orientation, mitotic progression, and maintenance of neural progenitor cells.

PubMed

Sakai, Daisuke; Dixon, Jill; Dixon, Michael J; Trainor, Paul A

2012-01-01

The cerebral cortex is a specialized region of the brain that processes cognitive, motor, somatosensory, auditory, and visual functions. Its characteristic architecture and size is dependent upon the number of neurons generated during embryogenesis and has been postulated to be governed by symmetric versus asymmetric cell divisions, which mediate the balance between progenitor cell maintenance and neuron differentiation, respectively. The mechanistic importance of spindle orientation remains controversial, hence there is considerable interest in understanding how neural progenitor cell mitosis is controlled during neurogenesis. We discovered that Treacle, which is encoded by the Tcof1 gene, is a novel centrosome- and kinetochore-associated protein that is critical for spindle fidelity and mitotic progression. Tcof1/Treacle loss-of-function disrupts spindle orientation and cell cycle progression, which perturbs the maintenance, proliferation, and localization of neural progenitors during cortical neurogenesis. Consistent with this, Tcof1(+/-) mice exhibit reduced brain size as a consequence of defects in neural progenitor maintenance. We determined that Treacle elicits its effect via a direct interaction with Polo-like kinase1 (Plk1), and furthermore we discovered novel in vivo roles for Plk1 in governing mitotic progression and spindle orientation in the developing mammalian cortex. Increased asymmetric cell division, however, did not promote increased neuronal differentiation. Collectively our research has therefore identified Treacle and Plk1 as novel in vivo regulators of spindle fidelity, mitotic progression, and proliferation in the maintenance and localization of neural progenitor cells. Together, Treacle and Plk1 are critically required for proper cortical neurogenesis, which has important implications in the regulation of mammalian brain size and the pathogenesis of congenital neurodevelopmental disorders such as microcephaly.

Mammalian Neurogenesis Requires Treacle-Plk1 for Precise Control of Spindle Orientation, Mitotic Progression, and Maintenance of Neural Progenitor Cells

PubMed Central

Sakai, Daisuke; Dixon, Jill; Dixon, Michael J.; Trainor, Paul A.

2012-01-01

The cerebral cortex is a specialized region of the brain that processes cognitive, motor, somatosensory, auditory, and visual functions. Its characteristic architecture and size is dependent upon the number of neurons generated during embryogenesis and has been postulated to be governed by symmetric versus asymmetric cell divisions, which mediate the balance between progenitor cell maintenance and neuron differentiation, respectively. The mechanistic importance of spindle orientation remains controversial, hence there is considerable interest in understanding how neural progenitor cell mitosis is controlled during neurogenesis. We discovered that Treacle, which is encoded by the Tcof1 gene, is a novel centrosome- and kinetochore-associated protein that is critical for spindle fidelity and mitotic progression. Tcof1/Treacle loss-of-function disrupts spindle orientation and cell cycle progression, which perturbs the maintenance, proliferation, and localization of neural progenitors during cortical neurogenesis. Consistent with this, Tcof1 +/− mice exhibit reduced brain size as a consequence of defects in neural progenitor maintenance. We determined that Treacle elicits its effect via a direct interaction with Polo-like kinase1 (Plk1), and furthermore we discovered novel in vivo roles for Plk1 in governing mitotic progression and spindle orientation in the developing mammalian cortex. Increased asymmetric cell division, however, did not promote increased neuronal differentiation. Collectively our research has therefore identified Treacle and Plk1 as novel in vivo regulators of spindle fidelity, mitotic progression, and proliferation in the maintenance and localization of neural progenitor cells. Together, Treacle and Plk1 are critically required for proper cortical neurogenesis, which has important implications in the regulation of mammalian brain size and the pathogenesis of congenital neurodevelopmental disorders such as microcephaly. PMID:22479190

Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults: a cross-sectional mega-analysis.

PubMed

Hoogman, Martine; Bralten, Janita; Hibar, Derrek P; Mennes, Maarten; Zwiers, Marcel P; Schweren, Lizanne S J; van Hulzen, Kimm J E; Medland, Sarah E; Shumskaya, Elena; Jahanshad, Neda; Zeeuw, Patrick de; Szekely, Eszter; Sudre, Gustavo; Wolfers, Thomas; Onnink, Alberdingk M H; Dammers, Janneke T; Mostert, Jeanette C; Vives-Gilabert, Yolanda; Kohls, Gregor; Oberwelland, Eileen; Seitz, Jochen; Schulte-Rüther, Martin; Ambrosino, Sara; Doyle, Alysa E; Høvik, Marie F; Dramsdahl, Margaretha; Tamm, Leanne; van Erp, Theo G M; Dale, Anders; Schork, Andrew; Conzelmann, Annette; Zierhut, Kathrin; Baur, Ramona; McCarthy, Hazel; Yoncheva, Yuliya N; Cubillo, Ana; Chantiluke, Kaylita; Mehta, Mitul A; Paloyelis, Yannis; Hohmann, Sarah; Baumeister, Sarah; Bramati, Ivanei; Mattos, Paulo; Tovar-Moll, Fernanda; Douglas, Pamela; Banaschewski, Tobias; Brandeis, Daniel; Kuntsi, Jonna; Asherson, Philip; Rubia, Katya; Kelly, Clare; Martino, Adriana Di; Milham, Michael P; Castellanos, Francisco X; Frodl, Thomas; Zentis, Mariam; Lesch, Klaus-Peter; Reif, Andreas; Pauli, Paul; Jernigan, Terry L; Haavik, Jan; Plessen, Kerstin J; Lundervold, Astri J; Hugdahl, Kenneth; Seidman, Larry J; Biederman, Joseph; Rommelse, Nanda; Heslenfeld, Dirk J; Hartman, Catharina A; Hoekstra, Pieter J; Oosterlaan, Jaap; Polier, Georg von; Konrad, Kerstin; Vilarroya, Oscar; Ramos-Quiroga, Josep Antoni; Soliva, Joan Carles; Durston, Sarah; Buitelaar, Jan K; Faraone, Stephen V; Shaw, Philip; Thompson, Paul M; Franke, Barbara

2017-04-01

Neuroimaging studies have shown structural alterations in several brain regions in children and adults with attention deficit hyperactivity disorder (ADHD). Through the formation of the international ENIGMA ADHD Working Group, we aimed to address weaknesses of previous imaging studies and meta-analyses, namely inadequate sample size and methodological heterogeneity. We aimed to investigate whether there are structural differences in children and adults with ADHD compared with those without this diagnosis. In this cross-sectional mega-analysis, we used the data from the international ENIGMA Working Group collaboration, which in the present analysis was frozen at Feb 8, 2015. Individual sites analysed structural T1-weighted MRI brain scans with harmonised protocols of individuals with ADHD compared with those who do not have this diagnosis. Our primary outcome was to assess case-control differences in subcortical structures and intracranial volume through pooling of all individual data from all cohorts in this collaboration. For this analysis, p values were significant at the false discovery rate corrected threshold of p=0·0156. Our sample comprised 1713 participants with ADHD and 1529 controls from 23 sites with a median age of 14 years (range 4-63 years). The volumes of the accumbens (Cohen's d=-0·15), amygdala (d=-0·19), caudate (d=-0·11), hippocampus (d=-0·11), putamen (d=-0·14), and intracranial volume (d=-0·10) were smaller in individuals with ADHD compared with controls in the mega-analysis. There was no difference in volume size in the pallidum (p=0·95) and thalamus (p=0·39) between people with ADHD and controls. Exploratory lifespan modelling suggested a delay of maturation and a delay of degeneration, as effect sizes were highest in most subgroups of children (<15 years) versus adults (>21 years): in the accumbens (Cohen's d=-0·19 vs -0·10), amygdala (d=-0·18 vs -0·14), caudate (d=-0·13 vs -0·07), hippocampus (d=-0·12 vs -0·06), putamen (d=-0·18 vs -0·08), and intracranial volume (d=-0·14 vs 0·01). There was no difference between children and adults for the pallidum (p=0·79) or thalamus (p=0·89). Case-control differences in adults were non-significant (all p>0·03). Psychostimulant medication use (all p>0·15) or symptom scores (all p>0·02) did not influence results, nor did the presence of comorbid psychiatric disorders (all p>0·5). With the largest dataset to date, we add new knowledge about bilateral amygdala, accumbens, and hippocampus reductions in ADHD. We extend the brain maturation delay theory for ADHD to include subcortical structures and refute medication effects on brain volume suggested by earlier meta-analyses. Lifespan analyses suggest that, in the absence of well powered longitudinal studies, the ENIGMA cross-sectional sample across six decades of ages provides a means to generate hypotheses about lifespan trajectories in brain phenotypes. National Institutes of Health. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

Eye-blink behaviors in 71 species of primates.

PubMed

Tada, Hideoki; Omori, Yasuko; Hirokawa, Kumi; Ohira, Hideki; Tomonaga, Masaki

2013-01-01

The present study was performed to investigate the associations between eye-blink behaviors and various other factors in primates. We video-recorded 141 individuals across 71 primate species and analyzed the blink rate, blink duration, and "isolated" blink ratio (i.e., blinks without eye or head movement) in relation to activity rhythms, habitat types, group size, and body size factors. The results showed close relationships between three types of eye-blink measures and body size factors. All of these measures increased as a function of body weight. In addition, diurnal primates showed more blinks than nocturnal species even after controlling for body size factors. The most important findings were the relationships between eye-blink behaviors and social factors, e.g., group size. Among diurnal primates, only the blink rate was significantly correlated even after controlling for body size factors. The blink rate increased as the group size increased. Enlargement of the neocortex is strongly correlated with group size in primate species and considered strong evidence for the social brain hypothesis. Our results suggest that spontaneous eye-blinks have acquired a role in social communication, similar to grooming, to adapt to complex social living during primate evolution.

Eye-Blink Behaviors in 71 Species of Primates

PubMed Central

Tada, Hideoki; Omori, Yasuko; Hirokawa, Kumi; Ohira, Hideki; Tomonaga, Masaki

2013-01-01

The present study was performed to investigate the associations between eye-blink behaviors and various other factors in primates. We video-recorded 141 individuals across 71 primate species and analyzed the blink rate, blink duration, and “isolated” blink ratio (i.e., blinks without eye or head movement) in relation to activity rhythms, habitat types, group size, and body size factors. The results showed close relationships between three types of eye-blink measures and body size factors. All of these measures increased as a function of body weight. In addition, diurnal primates showed more blinks than nocturnal species even after controlling for body size factors. The most important findings were the relationships between eye-blink behaviors and social factors, e.g., group size. Among diurnal primates, only the blink rate was significantly correlated even after controlling for body size factors. The blink rate increased as the group size increased. Enlargement of the neocortex is strongly correlated with group size in primate species and considered strong evidence for the social brain hypothesis. Our results suggest that spontaneous eye-blinks have acquired a role in social communication, similar to grooming, to adapt to complex social living during primate evolution. PMID:23741522

Born with an ear for dialects? Structural plasticity in the expert phonetician brain.

PubMed

Golestani, Narly; Price, Cathy J; Scott, Sophie K

2011-03-16

Are experts born with particular predispositions, or are they made through experience? We examined brain structure in expert phoneticians, individuals who are highly trained to analyze and transcribe speech. We found a positive correlation between the size of left pars opercularis and years of phonetic transcription training experience, illustrating how learning may affect brain structure. Phoneticians were also more likely to have multiple or split left transverse gyri in the auditory cortex than nonexpert controls, and the amount of phonetic transcription training did not predict auditory cortex morphology. The transverse gyri are thought to be established in utero; our results thus suggest that this gross morphological difference may have existed before the onset of phonetic training, and that its presence confers an advantage of sufficient magnitude to affect career choices. These results suggest complementary influences of domain-specific predispositions and experience-dependent brain malleability, influences that likely interact in determining not only how experience shapes the human brain but also why some individuals become engaged by certain fields of expertise.

Three-dimensional macroporous nanoelectronic networks as minimally invasive brain probes

NASA Astrophysics Data System (ADS)

Xie, Chong; Liu, Jia; Fu, Tian-Ming; Dai, Xiaochuan; Zhou, Wei; Lieber, Charles M.

2015-12-01

Direct electrical recording and stimulation of neural activity using micro-fabricated silicon and metal micro-wire probes have contributed extensively to basic neuroscience and therapeutic applications; however, the dimensional and mechanical mismatch of these probes with the brain tissue limits their stability in chronic implants and decreases the neuron-device contact. Here, we demonstrate the realization of a three-dimensional macroporous nanoelectronic brain probe that combines ultra-flexibility and subcellular feature sizes to overcome these limitations. Built-in strains controlling the local geometry of the macroporous devices are designed to optimize the neuron/probe interface and to promote integration with the brain tissue while introducing minimal mechanical perturbation. The ultra-flexible probes were implanted frozen into rodent brains and used to record multiplexed local field potentials and single-unit action potentials from the somatosensory cortex. Significantly, histology analysis revealed filling-in of neural tissue through the macroporous network and attractive neuron-probe interactions, consistent with long-term biocompatibility of the device.

Closed loop deep brain stimulation: an evolving technology.

PubMed

Hosain, Md Kamal; Kouzani, Abbas; Tye, Susannah

2014-12-01

Deep brain stimulation is an effective and safe medical treatment for a variety of neurological and psychiatric disorders including Parkinson's disease, essential tremor, dystonia, and treatment resistant obsessive compulsive disorder. A closed loop deep brain stimulation (CLDBS) system automatically adjusts stimulation parameters by the brain response in real time. The CLDBS continues to evolve due to the advancement in the brain stimulation technologies. This paper provides a study on the existing systems developed for CLDBS. It highlights the issues associated with CLDBS systems including feedback signal recording and processing, stimulation parameters setting, control algorithm, wireless telemetry, size, and power consumption. The benefits and limitations of the existing CLDBS systems are also presented. Whilst robust clinical proof of the benefits of the technology remains to be achieved, it has the potential to offer several advantages over open loop DBS. The CLDBS can improve efficiency and efficacy of therapy, eliminate lengthy start-up period for programming and adjustment, provide a personalized treatment, and make parameters setting automatic and adaptive.

Brain modularity controls the critical behavior of spontaneous activity.

PubMed

Russo, R; Herrmann, H J; de Arcangelis, L

2014-03-13

The human brain exhibits a complex structure made of scale-free highly connected modules loosely interconnected by weaker links to form a small-world network. These features appear in healthy patients whereas neurological diseases often modify this structure. An important open question concerns the role of brain modularity in sustaining the critical behaviour of spontaneous activity. Here we analyse the neuronal activity of a model, successful in reproducing on non-modular networks the scaling behaviour observed in experimental data, on a modular network implementing the main statistical features measured in human brain. We show that on a modular network, regardless the strength of the synaptic connections or the modular size and number, activity is never fully scale-free. Neuronal avalanches can invade different modules which results in an activity depression, hindering further avalanche propagation. Critical behaviour is solely recovered if inter-module connections are added, modifying the modular into a more random structure.

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

Brain Processing of Contagious Itch in Patients with Atopic Dermatitis

PubMed Central

Schut, Christina; Mochizuki, Hideki; Grossman, Shoshana K.; Lin, Andrew C.; Conklin, Christopher J.; Mohamed, Feroze B.; Gieler, Uwe; Kupfer, Joerg; Yosipovitch, Gil

2017-01-01

Several studies show that itch and scratching cannot only be induced by pruritogens like histamine or cowhage, but also by the presentation of certain (audio-) visual stimuli like pictures on crawling insects or videos showing other people scratching. This phenomenon is coined “Contagious itch” (CI). Due to the fact that CI is more profound in patients with the chronic itchy skin disease atopic dermatitis (AD), we believe that it is highly relevant to study brain processing of CI in this group. Knowledge on brain areas involved in CI in AD-patients can provide us with useful hints regarding non-invasive treatments that AD-patients could profit from when they are confronted with itch-inducing situations in daily life. Therefore, this study investigated the brain processing of CI in AD-patients. 11 AD-patients underwent fMRI scans during the presentation of an itch inducing experimental video (EV) and a non-itch inducing control video (CV). Perfusion based brain activity was measured using arterial spin labeling functional MRI. As expected, the EV compared to the CV led to an increase in itch and scratching (p < 0.05). CI led to a significant increase in brain activity in the supplementary motor area, left ventral striatum and right orbitofrontal cortex (threshold: p < 0.001; cluster size k > 50). Moreover, itch induced by watching the EV was by trend correlated with activity in memory-related regions including the temporal cortex and the (pre-) cuneus as well as the posterior operculum, a brain region involved in itch processing (threshold: p < 0.005; cluster size k > 50). These findings suggest that the fronto-striatal circuit, which is associated with the desire to scratch, might be a target region for non-invasive treatments in AD patients. PMID:28790959

Inhibition of CD147 (Cluster of Differentiation 147) Ameliorates Acute Ischemic Stroke in Mice by Reducing Thromboinflammation.

PubMed

Jin, Rong; Xiao, Adam Y; Chen, Rui; Granger, D Neil; Li, Guohong

2017-12-01

Inflammation and thrombosis currently are recognized as critical contributors to the pathogenesis of ischemic stroke. CD147 (cluster of differentiation 147), also known as extracellular matrix metalloproteinase inducer, can function as a key mediator of inflammatory and immune responses. CD147 expression is increased in the brain after cerebral ischemia, but its role in the pathogenesis of ischemic stroke remains unknown. In this study, we show that CD147 acts as a key player in ischemic stroke by driving thrombotic and inflammatory responses. Focal cerebral ischemia was induced in C57BL/6 mice by a 60-minute transient middle cerebral artery occlusion. Animals were treated with anti-CD147 function-blocking antibody (αCD147) or isotype control antibody. Blood-brain barrier permeability, thrombus formation, and microvascular patency were assessed 24 hours after ischemia. Infarct size, neurological deficits, and inflammatory cells invaded in the brain were assessed 72 hours after ischemia. CD147 expression was rapidly increased in ischemic brain endothelium after transient middle cerebral artery occlusion. Inhibition of CD147 reduced infarct size and improved functional outcome on day 3 after transient middle cerebral artery occlusion. The neuroprotective effects were associated with (1) prevented blood-brain barrier damage, (2) decreased intravascular fibrin and platelet deposition, which in turn reduced thrombosis and increased cerebral perfusion, and (3) reduced brain inflammatory cell infiltration. The underlying mechanism may include reduced NF-κB (nuclear factor κB) activation, MMP-9 (matrix metalloproteinase-9) activity, and PAI-1 (plasminogen activator inhibitor-1) expression in brain microvascular endothelial cells. Inhibition of CD147 ameliorates acute ischemic stroke by reducing thromboinflammation. CD147 might represent a novel and promising therapeutic target for ischemic stroke and possibly other thromboinflammatory disorders. © 2017 American Heart Association, Inc.

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

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

Activating Endogenous Neural Precursor Cells Using Metformin Leads to Neural Repair and Functional Recovery in a Model of Childhood Brain Injury.

PubMed

Dadwal, Parvati; Mahmud, Neemat; Sinai, Laleh; Azimi, Ashkan; Fatt, Michael; Wondisford, Fredric E; Miller, Freda D; Morshead, Cindi M

2015-08-11

The development of cell replacement strategies to repair the injured brain has gained considerable attention, with a particular interest in mobilizing endogenous neural stem and progenitor cells (known as neural precursor cells [NPCs]) to promote brain repair. Recent work demonstrated metformin, a drug used to manage type II diabetes, promotes neurogenesis. We sought to determine its role in neural repair following brain injury. We find that metformin administration activates endogenous NPCs, expanding the size of the NPC pool and promoting NPC migration and differentiation in the injured neonatal brain in a hypoxia-ischemia (H/I) injury model. Importantly, metformin treatment following H/I restores sensory-motor function. Lineage tracking reveals that metformin treatment following H/I causes an increase in the absolute number of subependyma-derived NPCs relative to untreated H/I controls in areas associated with sensory-motor function. Hence, activation of endogenous NPCs is a promising target for therapeutic intervention in childhood brain injury models. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

A Wireless 32-Channel Implantable Bidirectional Brain Machine Interface

PubMed Central

Su, Yi; Routhu, Sudhamayee; Moon, Kee S.; Lee, Sung Q.; Youm, WooSub; Ozturk, Yusuf

2016-01-01

All neural information systems (NIS) rely on sensing neural activity to supply commands and control signals for computers, machines and a variety of prosthetic devices. Invasive systems achieve a high signal-to-noise ratio (SNR) by eliminating the volume conduction problems caused by tissue and bone. An implantable brain machine interface (BMI) using intracortical electrodes provides excellent detection of a broad range of frequency oscillatory activities through the placement of a sensor in direct contact with cortex. This paper introduces a compact-sized implantable wireless 32-channel bidirectional brain machine interface (BBMI) to be used with freely-moving primates. The system is designed to monitor brain sensorimotor rhythms and present current stimuli with a configurable duration, frequency and amplitude in real time to the brain based on the brain activity report. The battery is charged via a novel ultrasonic wireless power delivery module developed for efficient delivery of power into a deeply-implanted system. The system was successfully tested through bench tests and in vivo tests on a behaving primate to record the local field potential (LFP) oscillation and stimulate the target area at the same time. PMID:27669264

Does MRI scan acceleration affect power to track brain change?

PubMed

Ching, Christopher R K; Hua, Xue; Hibar, Derrek P; Ward, Chadwick P; Gunter, Jeffrey L; Bernstein, Matt A; Jack, Clifford R; Weiner, Michael W; Thompson, Paul M

2015-01-01

The Alzheimer's Disease Neuroimaging Initiative recently implemented accelerated T1-weighted structural imaging to reduce scan times. Faster scans may reduce study costs and patient attrition by accommodating people who cannot tolerate long scan sessions. However, little is known about how scan acceleration affects the power to detect longitudinal brain change. Using tensor-based morphometry, no significant difference was detected in numerical summaries of atrophy rates from accelerated and nonaccelerated scans in subgroups of patients with Alzheimer's disease, early or late mild cognitive impairment, or healthy controls over a 6- and 12-month scan interval. Whole-brain voxelwise mapping analyses revealed some apparent regional differences in 6-month atrophy rates when comparing all subjects irrespective of diagnosis (n = 345). No such whole-brain difference was detected for the 12-month scan interval (n = 156). Effect sizes for structural brain changes were not detectably different in accelerated versus nonaccelerated data. Scan acceleration may influence brain measures but has minimal effects on tensor-based morphometry-derived atrophy measures, at least over the 6- and 12-month intervals examined here. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of Dolphins' Body and Brain Measurements with Four Other Groups of Cetaceans Reveals Great Diversity.

PubMed

Ridgway, Sam H; Carlin, Kevin P; Van Alstyne, Kaitlin R; Hanson, Alicia C; Tarpley, Raymond J

2016-01-01

We compared mature dolphins with 4 other groupings of mature cetaceans. With a large data set, we found great brain diversity among 5 different taxonomic groupings. The dolphins in our data set ranged in body mass from about 40 to 6,750 kg and in brain mass from 0.4 to 9.3 kg. Dolphin body length ranged from 1.3 to 7.6 m. In our combined data set from the 4 other groups of cetaceans, body mass ranged from about 20 to 120,000 kg and brain mass from about 0.2 to 9.2 kg, while body length varied from 1.21 to 26.8 m. Not all cetaceans have large brains relative to their body size. A few dolphins near human body size have human-sized brains. On the other hand, the absolute brain mass of some other cetaceans is only one-sixth as large. We found that brain volume relative to body mass decreases from Delphinidae to a group of Phocoenidae and Monodontidae, to a group of other odontocetes, to Balaenopteroidea, and finally to Balaenidae. We also found the same general trend when we compared brain volume relative to body length, except that the Delphinidae and Phocoenidae-Monodontidae groups do not differ significantly. The Balaenidae have the smallest relative brain mass and the lowest cerebral cortex surface area. Brain parts also vary. Relative to body mass and to body length, dolphins also have the largest cerebellums. Cortex surface area is isometric with brain size when we exclude the Balaenidae. Our data show that the brains of Balaenidae are less convoluted than those of the other cetaceans measured. Large vascular networks inside the cranial vault may help to maintain brain temperature, and these nonbrain tissues increase in volume with body mass and with body length ranging from 8 to 65% of the endocranial volume. Because endocranial vascular networks and other adnexa, such as the tentorium cerebelli, vary so much in different species, brain size measures from endocasts of some extinct cetaceans may be overestimates. Our regression of body length on endocranial adnexa might be used for better estimates of brain volume from endocasts or from endocranial volume of living species or extinct cetaceans. © 2017 The Author(s) Published by S. Karger AG, Basel.

Comparison of Dolphins' Body and Brain Measurements with Four Other Groups of Cetaceans Reveals Great Diversity

PubMed Central

Ridgway, Sam H.; Carlin, Kevin P.; Van Alstyne, Kaitlin R.; Hanson, Alicia C.; Tarpley, Raymond J.

2017-01-01

We compared mature dolphins with 4 other groupings of mature cetaceans. With a large data set, we found great brain diversity among 5 different taxonomic groupings. The dolphins in our data set ranged in body mass from about 40 to 6,750 kg and in brain mass from 0.4 to 9.3 kg. Dolphin body length ranged from 1.3 to 7.6 m. In our combined data set from the 4 other groups of cetaceans, body mass ranged from about 20 to 120,000 kg and brain mass from about 0.2 to 9.2 kg, while body length varied from 1.21 to 26.8 m. Not all cetaceans have large brains relative to their body size. A few dolphins near human body size have human-sized brains. On the other hand, the absolute brain mass of some other cetaceans is only one-sixth as large. We found that brain volume relative to body mass decreases from Delphinidae to a group of Phocoenidae and Monodontidae, to a group of other odontocetes, to Balaenopteroidea, and finally to Balaenidae. We also found the same general trend when we compared brain volume relative to body length, except that the Delphinidae and Phocoenidae-Monodontidae groups do not differ significantly. The Balaenidae have the smallest relative brain mass and the lowest cerebral cortex surface area. Brain parts also vary. Relative to body mass and to body length, dolphins also have the largest cerebellums. Cortex surface area is isometric with brain size when we exclude the Balaenidae. Our data show that the brains of Balaenidae are less convoluted than those of the other cetaceans measured. Large vascular networks inside the cranial vault may help to maintain brain temperature, and these nonbrain tissues increase in volume with body mass and with body length ranging from 8 to 65% of the endocranial volume. Because endocranial vascular networks and other adnexa, such as the tentorium cerebelli, vary so much in different species, brain size measures from endocasts of some extinct cetaceans may be overestimates. Our regression of body length on endocranial adnexa might be used for better estimates of brain volume from endocasts or from endocranial volume of living species or extinct cetaceans. PMID:28122370

Males are from Mars, and females are from Venus: sex-specific fetal brain gene expression signatures in a mouse model of maternal diet-induced obesity.

PubMed

Edlow, Andrea G; Guedj, Faycal; Pennings, Jeroen L A; Sverdlov, Deanna; Neri, Caterina; Bianchi, Diana W

2016-05-01

Maternal obesity is associated with adverse neurodevelopmental outcomes in children, including autism spectrum disorders, developmental delay, and attention-deficit hyperactivity disorder. The underlying mechanisms remain unclear. We previously identified second-trimester amniotic fluid and term cord blood gene expression patterns suggesting dysregulated brain development in fetuses of obese compared with lean women. We sought to investigate the biological significance of these findings in a mouse model of maternal diet-induced obesity. We evaluated sex-specific differences in fetal growth, brain gene expression signatures, and associated pathways. Female C57BL/6J mice were fed a 60% high-fat diet or 10% fat control diet for 12-14 weeks prior to mating. During pregnancy, obese dams continued on the high-fat diet or transitioned to the control diet. Lean dams stayed on the control diet. On embryonic day 17.5, embryos were weighed and fetal brains were snap frozen. RNA was extracted from male and female forebrains (10 per diet group per sex) and hybridized to whole-genome expression arrays. Significantly differentially expressed genes were identified using a Welch's t test with the Benjamini-Hochberg correction. Functional analyses were performed using ingenuity pathways analysis and gene set enrichment analysis. Embryos of dams on the high-fat diet were significantly smaller than controls, with males more severely affected than females (P = .01). Maternal obesity and maternal obesity with dietary change in pregnancy resulted in significantly more dysregulated genes in male vs female fetal brains (386 vs 66, P < .001). Maternal obesity with and without dietary change in pregnancy was associated with unique brain gene expression signatures for each sex, with an overlap of only 1 gene. Changing obese dams to a control diet in pregnancy resulted in more differentially expressed genes in the fetal brain than maternal obesity alone. Functional analyses identified common dysregulated pathways in both sexes, but maternal obesity and maternal dietary change affected different aspects of brain development in males compared with females. Maternal obesity is associated with sex-specific differences in fetal size and fetal brain gene expression signatures. Male fetal growth and brain gene expression may be more sensitive to environmental influences during pregnancy. Maternal diet during pregnancy has a significant impact on the embryonic brain transcriptome. It is important to consider both fetal sex and maternal diet when evaluating the effects of maternal obesity on fetal neurodevelopment. Copyright © 2016 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.

Structural Magnetic Resonance Imaging Correlates of Aggression in Psychosis: A Systematic Review and Effect Size Analysis.

PubMed

Widmayer, Sonja; Sowislo, Julia F; Jungfer, Hermann A; Borgwardt, Stefan; Lang, Undine E; Stieglitz, Rolf D; Huber, Christian G

2018-01-01

Background: Aggression in psychoses is of high clinical importance, and volumetric MRI techniques have been used to explore its structural brain correlates. Methods: We conducted a systematic review searching EMBASE, ScienceDirect, and PsycINFO through September 2017 using thesauri representing aggression, psychosis, and brain imaging. We calculated effect sizes for each study and mean Hedge's g for whole brain (WB) volume. Methodological quality was established using the PRISMA checklist (PROSPERO: CRD42014014461). Results: Our sample consisted of 12 studies with 470 patients and 155 healthy controls (HC). After subtracting subjects due to cohort overlaps, 314 patients and 96 HC remained. Qualitative analyses showed lower volumes of WB, prefrontal regions, temporal lobe, hippocampus, thalamus and cerebellum, and higher volumes of lateral ventricles, amygdala, and putamen in violent vs. non-violent people with schizophrenia. In quantitative analyses, violent persons with schizophrenia exhibited a significantly lower WB volume than HC ( p = 0.004), and also lower than non-violent persons with schizophrenia ( p = 0.007). Conclusions: We reviewed evidence for differences in brain volume correlates of aggression in persons with schizophrenia. Our results point toward a reduced whole brain volume in violent as opposed to non-violent persons with schizophrenia. However, considerable sample overlap in the literature, lack of reporting of potential confounding variables, and missing research on affective psychoses limit our explanatory power. To permit stronger conclusions, further studies evaluating structural correlates of aggression in psychotic disorders are needed.

Influence of irradiation on development of Caribbean fruit fly (diptera: tephritidae) larvae

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

Nation, J.L.; Milne, K.; Dykstra, T.M.

1995-05-01

Larvae of the Caribbean fruit fly, Anastrepha suspensa (Loew), were irradiated at hatching with 0, 5, 10, 20, 50, 75, 100 and 150 Gy doses from a Cesium-137 source and dissected for measurements of the supraesophageal ganglion (brain) and proventriculus (B/Prv) as mature third instars. Cross-sectional area of a plane through the brain and proventriculus, and simple dorsal width measurements of the two organs were evaluated as indicators of radiation exposure. Brain area, brain width, and brain/proventriculus (B/Prv) ratios were significantly different from controls in insects treated with a dose {ge}20 Gy. Detailed dissections of hatching larvae exposed to 50more » Gy revealed reductions in brain growth, small and misshapen compound eye and leg imaginal disks, and a ventral nerve cord that was elongated and sinuous. Larvae irradiated on the 1st d of each of the three instars had smaller brains, with the percentage of reduction in brain size being greater the younger the larvae were at the time of exposure. Brain and proventriculus measurements and calculated B/Prv values are indicative of irradiation in Caribbean fruit fly larvae, but the procedure may not be adaptable for routine use by quarantine inspectors. 14 refs., 4 figs., 2 tabs.« less

A dual-task home-based rehabilitation programme for improving balance control in patients with acquired brain injury: a single-blind, randomized controlled pilot study.

PubMed

Peirone, Eliana; Goria, Paolo Filiberto; Anselmino, Arianna

2014-04-01

To evaluate the safety, feasibility and effectiveness of a dual-task home-based rehabilitation programme on balance impairments among adult patients with acquired brain injury. Single-blind, randomized controlled pilot study. Single rehabilitation centre. Sixteen participants between 12 and 18 months post-acquired brain injury with balance impairments and a score <10 seconds on the One-Leg Stance Test (eyes open). All participants received 50-minutes individualised traditional physiotherapy sessions three times a week for seven weeks. In addition, the intervention group (N = 8) performed an individualised dual-task home-based programme six days a week for seven weeks. The primary outcome measure was the Balance Evaluation System Test; secondary measures were the Activities-specific Balance Confidence Scale and Goal Attainment Scaling. At the end of the pilot study, the intervention group showed significantly greater improvement in Balance Evaluation System Test scores (17.87, SD 6.05) vs. the control group (5.5, SD 3.53; P = 0.008, r = 0.63). There was no significant difference in improvement in Activities-specific Balance Confidence Scale scores between the intervention group (25.25, SD 25.51) and the control group (7.00, SD 14.73; P = 0.11, r = 0.63). There was no significant improvement in Goal Attainment Scaling scores in the intervention (19.37, SD 9.03) vs. the control group (16.28, SD 6.58; P = 0.093, r = 0.63). This pilot study shows the safety, feasibility and short-term benefit of a dual-task home-based rehabilitation programme to improve balance control in patients with acquired brain injury. A sample size of 26 participants is required for a definitive study.

Quantitative representations of an exaggerated anxiety response in the brain of female spider phobics-a parametric fMRI study.

PubMed

Zilverstand, Anna; Sorger, Bettina; Kaemingk, Anita; Goebel, Rainer

2017-06-01

We employed a novel parametric spider picture set in the context of a parametric fMRI anxiety provocation study, designed to tease apart brain regions involved in threat monitoring from regions representing an exaggerated anxiety response in spider phobics. For the stimulus set, we systematically manipulated perceived proximity of threat by varying a depicted spider's context, size, and posture. All stimuli were validated in a behavioral rating study (phobics n = 20; controls n = 20; all female). An independent group participated in a subsequent fMRI anxiety provocation study (phobics n = 7; controls n = 7; all female), in which we compared a whole-brain categorical to a whole-brain parametric analysis. Results demonstrated that the parametric analysis provided a richer characterization of the functional role of the involved brain networks. In three brain regions-the mid insula, the dorsal anterior cingulate, and the ventrolateral prefrontal cortex-activation was linearly modulated by perceived proximity specifically in the spider phobia group, indicating a quantitative representation of an exaggerated anxiety response. In other regions (e.g., the amygdala), activation was linearly modulated in both groups, suggesting a functional role in threat monitoring. Prefrontal regions, such as dorsolateral prefrontal cortex, were activated during anxiety provocation but did not show a stimulus-dependent linear modulation in either group. The results confirm that brain regions involved in anxiety processing hold a quantitative representation of a pathological anxiety response and more generally suggest that parametric fMRI designs may be a very powerful tool for clinical research in the future, particularly when developing novel brain-based interventions (e.g., neurofeedback training). Hum Brain Mapp 38:3025-3038, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Structural changes of the corpus callosum in tinnitus

PubMed Central

Diesch, Eugen; Schummer, Verena; Kramer, Martin; Rupp, Andre

2012-01-01

Objectives: In tinnitus, several brain regions seem to be structurally altered, including the medial partition of Heschl's gyrus (mHG), the site of the primary auditory cortex. The mHG is smaller in tinnitus patients than in healthy controls. The corpus callosum (CC) is the main interhemispheric commissure of the brain connecting the auditory areas of the left and the right hemisphere. Here, we investigate whether tinnitus status is associated with CC volume. Methods: The midsagittal cross-sectional area of the CC was examined in tinnitus patients and healthy controls in which an examination of the mHG had been carried out earlier. The CC was extracted and segmented into subregions which were defined according to the most common CC morphometry schemes introduced by Witelson (1989) and Hofer and Frahm (2006). Results: For both CC segmentation schemes, the CC posterior midbody was smaller in male patients than in male healthy controls and the isthmus, the anterior midbody, and the genou were larger in female patients than in female controls. With CC size normalized relative to mHG volume, the normalized CC splenium was larger in male patients than male controls and the normalized CC splenium, the isthmus and the genou were larger in female patients than female controls. Normalized CC segment size expresses callosal interconnectivity relative to auditory cortex volume. Conclusion: It may be argued that the predominant function of the CC is excitatory. The stronger callosal interconnectivity in tinnitus patients, compared to healthy controls, may facilitate the emergence and maintenance of a positive feedback loop between tinnitus generators located in the two hemispheres. PMID:22470322

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…

Engineering a High-Throughput 3-D In Vitro Glioblastoma Model

PubMed Central

Fan, Yantao; Avci, Naze G.; Nguyen, Duong T.; Dragomir, Andrei; Xu, Feng; Akay, Metin

2015-01-01

Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults because of its highly invasive behavior. The existing treatment for GBM, which involves a combination of resection, chemotherapy, and radiotherapy, has a very limited success rate with a median survival rate of <1 year. This is mainly because of the failure of early detection and effective treatment. We designed a novel 3-D GBM cell culture model based on microwells that could mimic in vitro environment and help to bypass the lack of suitable animal models for preclinical toxicity tests. Microwells were fabricated from simple and inexpensive polyethylene glycol material for the control of in vitro 3-D culture. We applied the 3-D micropatterning system to GBM (U-87) cells using the photolithography technique to control the cell spheroids’ shape, size, and thickness. Our preliminary results suggested that uniform GBM spheroids can be formed in 3-D, and the size of these GBM spheroids depends on the size of microwells. The viability of the spheroids generated in this manner was quantitatively evaluated using live/dead assay and shown to improve over 21 days. We believe that in vitro 3-D cell culture model could help to reduce the time of the preclinical brain tumor growth studies. The proposed novel platform could be useful and cost-effective for high-throughput screening of cancer drugs and assessment of treatment responses. PMID:27170911

Systematic review of physiotherapy interventions to improve gross motor capacity and performance in children and adolescents with an acquired brain injury.

PubMed

Baque, Emmah; Sakzewski, Leanne; Barber, Lee; Boyd, Roslyn N

2016-01-01

To systematically review the efficacy of physiotherapy interventions to improve gross motor capacity, performance and societal participation in children aged 5-17 years with an acquired brain injury (ABI). Randomized and non-randomized controlled trials, cohort, case series, case-control and case studies were included and classified according to grades of evidence. Methodological quality of studies was assessed using the Downs and Black (D&B) scale and quantitative data was analysed using effect sizes. Two home-based studies investigated functional strength training (one randomized controlled trial, n = 20, level 2b, D&B = 16/32 and one non-randomized self-control study, n = 19, level 4, D&B = 15/32). Four studies evaluated virtual reality including: one pilot study, n = 50, level 4, D&B = 22/32; one single-subject, non-concurrent, randomized multiple baseline study, n = 3, level 4, D&B = 15/32; one case series study, n = 2, level 4, D&B = 15/32; one case study, n = 1, level 4, D&B = 15/32. Effect sizes for the randomized controlled trial ranged between 0.30-1.29 for the Functional Reach and Timed Up and Go outcome measures. There is preliminary evidence to support the efficacy of physiotherapy interventions to improve gross motor outcomes in children with an ABI. Both functional strength training and virtual-reality based therapy are potential treatment options for clinicians to prescribe in either home or clinical settings.

Density of mushroom body synaptic complexes limits intraspecies brain miniaturization in highly polymorphic leaf-cutting ant workers

PubMed Central

Groh, Claudia; Kelber, Christina; Grübel, Kornelia; Rössler, Wolfgang

2014-01-01

Hymenoptera possess voluminous mushroom bodies (MBs), brain centres associated with sensory integration, learning and memory. The mushroom body input region (calyx) is organized in distinct synaptic complexes (microglomeruli, MG) that can be quantified to analyse body size-related phenotypic plasticity of synaptic microcircuits in these small brains. Leaf-cutting ant workers (Atta vollenweideri) exhibit an enormous size polymorphism, which makes them outstanding to investigate neuronal adaptations underlying division of labour and brain miniaturization. We particularly asked how size-related division of labour in polymorphic workers is reflected in volume and total numbers of MG in olfactory calyx subregions. Whole brains of mini, media and large workers were immunolabelled with anti-synapsin antibodies, and mushroom body volumes as well as densities and absolute numbers of MG were determined by confocal imaging and three-dimensional analyses. The total brain volume and absolute volumes of olfactory mushroom body subdivisions were positively correlated with head widths, but mini workers had significantly larger MB to total brain ratios. Interestingly, the density of olfactory MG was remarkably independent from worker size. Consequently, absolute numbers of olfactory MG still were approximately three times higher in large compared with mini workers. The results show that the maximum packing density of synaptic microcircuits may represent a species-specific limit to brain miniaturization. PMID:24807257

Glial-Specific Functions of Microcephaly Protein WDR62 and Interaction with the Mitotic Kinase AURKA Are Essential for Drosophila Brain Growth.

PubMed

Lim, Nicholas R; Shohayeb, Belal; Zaytseva, Olga; Mitchell, Naomi; Millard, S Sean; Ng, Dominic C H; Quinn, Leonie M

2017-07-11

The second most commonly mutated gene in primary microcephaly (MCPH) patients is wd40-repeat protein 62 (wdr62), but the relative contribution of WDR62 function to the growth of major brain lineages is unknown. Here, we use Drosophila models to dissect lineage-specific WDR62 function(s). Interestingly, although neural stem cell (neuroblast)-specific depletion of WDR62 significantly decreased neuroblast number, brain size was unchanged. In contrast, glial lineage-specific WDR62 depletion significantly decreased brain volume. Moreover, loss of function in glia not only decreased the glial population but also non-autonomously caused neuroblast loss. We further demonstrated that WDR62 controls brain growth through lineage-specific interactions with master mitotic signaling kinase, AURKA. Depletion of AURKA in neuroblasts drives brain overgrowth, which was suppressed by WDR62 co-depletion. In contrast, glial-specific depletion of AURKA significantly decreased brain volume, which was further decreased by WDR62 co-depletion. Thus, dissecting relative contributions of MCPH factors to individual neural lineages will be critical for understanding complex diseases such as microcephaly. Crown Copyright © 2017. Published by 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

Brain potentials during mental arithmetic: effects of extensive practice and problem difficulty.

PubMed

Pauli, P; Lutzenberger, W; Rau, H; Birbaumer, N; Rickard, T C; Yaroush, R A; Bourne, L E

1994-07-01

Recent behavioral investigations indicate that the processes underlying mental arithmetic change systematically with practice from deliberate, conscious calculation to automatic, direct retrieval of answers from memory [Bourne, L.E.Jr. and Rickard, T.C., Mental calculation: The development of a cognitive skill, Paper presented at the Interamerican Congress of Psychology, San Jose, Costa Rica, 1991: Psychol. Rev., 95 (1988) 492-527]. Results reviewed by Moscovitch and Winocur [In: The handbook of aging and cognition, Erlbaum, Hillsdale, NJ, 1992, pp. 315-372] suggest that consciously controlled processes are more dependent on frontal lobe function than are automatic processes. It is appropriate, therefore to determine whether transitions in the locus of primary brain activity occur with practice on mental calculation. In this experiment, we examine the relationship between characteristics of event-related brain potentials (ERPs) and mental arithmetic. Single-digit mental multiplication problems varying in difficulty (problem size) were used, and subjects were trained on these problems for four sessions. Problem-size and practice effects were reliably found in behavioral measures (RT). The ERP was characterized by a pronounced late positivity after task presentation followed by a slow wave, and a negativity during response indication. These components responded differentially to the practice and problem-size manipulations. Practice mainly affected topography of the amplitude of positivity and offset latency of slow wave, and problem-size mainly offset latency of slow wave and pre-response negativity. Fronto-central positivity diminished from session to session, and the focus of positivity centered finally at centro-parietal regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Alpha-Tocopherol Reduces Brain Edema and Protects Blood-Brain Barrier Integrity following Focal Cerebral Ischemia in Rats.

PubMed

Haghnejad Azar, Adel; Oryan, Shahrbanoo; Bohlooli, Shahab; Panahpour, Hamdollah

2017-01-01

This study was conducted to examine the neuroprotective effects of α-tocopherol against edema formation and disruption of the blood-brain barrier (BBB) following transient focal cerebral ischemia in rats. Ninety-six male Sprague-Dawley rats were divided into 3 major groups (n = 32 in each), namely the sham, and control and α-tocopherol-treated (30 mg/kg) ischemic groups. Transient focal cerebral ischemia (90 min) was induced by occlusion of the left middle cerebral artery. At the end of the 24-hour reperfusion period, the animals were randomly selected and used for 4 investigations (n = 8) in each of the 3 main groups: (a) assessment of neurological score and measurement of infarct size, (b) detection of brain edema formation by the wet/dry method, (c) evaluation of BBB permeability using the Evans blue (EB) extravasation technique, and (d) assessment of the malondialdehyde (MDA) and reduced glutathione (GSH) concentrations using high-performance liquid chromatography methods. Induction of cerebral ischemia in the control group produced extensive brain edema (brain water content 83.8 ± 0.11%) and EB leakage into brain parenchyma (14.58 ± 1.29 µg/g) in conjunction with reduced GSH and elevated MDA levels (5.86 ± 0.31 mmol/mg and 63.57 ± 5.42 nmol/mg, respectively). Treatment with α-tocopherol significantly lowered brain edema formation and reduced EB leakage compared with the control group (p < 0.001, 80.1 ± 0.32% and 6.66 ± 0.87 µg/g, respectively). Meanwhile, treatment with α-tocopherol retained tissue GSH levels and led to a lower MDA level (p < 0.01, 10.17 ± 0.83 mmol/mg, and p < 0.001, 26.84 ± 4.79 nmol/mg, respectively). Treatment with α-tocopherol reduced ischemic edema formation and produced protective effects on BBB function following ischemic stroke occurrence. This effect could be through increasing antioxidant activity. © 2016 S. Karger AG, Basel.

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.

Altered brain network measures in patients with primary writing tremor.

PubMed

Lenka, Abhishek; Jhunjhunwala, Ketan Ramakant; Panda, Rajanikant; Saini, Jitender; Bharath, Rose Dawn; Yadav, Ravi; Pal, Pramod Kumar

2017-10-01

Primary writing tremor (PWT) is a rare task-specific tremor, which occurs only while writing or while adopting the hand in the writing position. The basic pathophysiology of PWT has not been fully understood. The objective of this study is to explore the alterations in the resting state functional brain connectivity, if any, in patients with PWT using graph theory-based analysis. This prospective case-control study included 10 patients with PWT and 10 age and gender matched healthy controls. All subjects underwent MRI in a 3-Tesla scanner. Several parameters of small-world functional connectivity were compared between patients and healthy controls by using graph theory-based analysis. There were no significant differences in age, handedness (all right handed), gender distribution (all were males), and MMSE scores between the patients and controls. The mean age at presentation of tremor in the patient group was 51.7 ± 8.6 years, and the mean duration of tremor was 3.5 ± 1.9 years. Graph theory-based analysis revealed that patients with PWT had significantly lower clustering coefficient and higher path length compared to healthy controls suggesting alterations in small-world architecture of the brain. The clustering coefficients were lower in PWT patients in left and right medial cerebellum, right dorsolateral prefrontal cortex (DLPFC), and left posterior parietal cortex (PPC). Patients with PWT have significantly altered small-world brain connectivity in bilateral medial cerebellum, right DLPFC, and left PPC. Further studies with larger sample size are required to confirm our results.

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.

Predictors of Individual Tumor Local Control After Stereotactic Radiosurgery for Non-Small Cell Lung Cancer Brain Metastases

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

Garsa, Adam A.; Badiyan, Shahed N.; DeWees, Todd

2014-10-01

Purpose: To evaluate local control rates and predictors of individual tumor local control for brain metastases from non-small cell lung cancer (NSCLC) treated with stereotactic radiosurgery (SRS). Methods and Materials: Between June 1998 and May 2011, 401 brain metastases in 228 patients were treated with Gamma Knife single-fraction SRS. Local failure was defined as an increase in lesion size after SRS. Local control was estimated using the Kaplan-Meier method. The Cox proportional hazards model was used for univariate and multivariate analysis. Receiver operating characteristic analysis was used to identify an optimal cutpoint for conformality index relative to local control. Amore » P value <.05 was considered statistically significant. Results: Median age was 60 years (range, 27-84 years). There were 66 cerebellar metastases (16%) and 335 supratentorial metastases (84%). The median prescription dose was 20 Gy (range, 14-24 Gy). Median overall survival from time of SRS was 12.1 months. The estimated local control at 12 months was 74%. On multivariate analysis, cerebellar location (hazard ratio [HR] 1.94, P=.009), larger tumor volume (HR 1.09, P<.001), and lower conformality (HR 0.700, P=.044) were significant independent predictors of local failure. Conformality index cutpoints of 1.4-1.9 were predictive of local control, whereas a cutpoint of 1.75 was the most predictive (P=.001). The adjusted Kaplan-Meier 1-year local control for conformality index ≥1.75 was 84% versus 69% for conformality index <1.75, controlling for tumor volume and location. The 1-year adjusted local control for cerebellar lesions was 60%, compared with 77% for supratentorial lesions, controlling for tumor volume and conformality index. Conclusions: Cerebellar tumor location, lower conformality index, and larger tumor volume were significant independent predictors of local failure after SRS for brain metastases from NSCLC. These results warrant further investigation in a prospective setting.« less

Interaction between BDNF rs6265 Met allele and low family cohesion is associated with smaller left hippocampal volume in pediatric bipolar disorder.

PubMed

Zeni, Cristian Patrick; Mwangi, Benson; Cao, Bo; Hasan, Khader M; Walss-Bass, Consuelo; Zunta-Soares, Giovana; Soares, Jair C

2016-01-01

Genetic and environmental factors are implicated in the onset and evolution of pediatric bipolar disorder, and may be associated to structural brain abnormalities. The aim of our study was to assess the impact of the interaction between the Brain-Derived Neurotrophic Factor (BDNF) rs6265 polymorphism and family functioning on hippocampal volumes of children and adolescents with bipolar disorder, and typically-developing controls. We evaluated the family functioning cohesion subscale using the Family Environment Scale-Revised, genotyped the BDNF rs6265 polymorphism, and performed structural brain imaging in 29 children and adolescents with bipolar disorder, and 22 healthy controls. We did not find significant differences between patients with BD or controls in left or right hippocampus volume (p=0.44, and p=0.71, respectively). However, we detected a significant interaction between low scores on the cohesion subscale and the presence of the Met allele at BNDF on left hippocampal volume of patients with bipolar disorder (F=3.4, p=0.043). None of the factors independently (BDNF Val66Met, cohesion scores) was significantly associated with hippocampal volume differences. small sample size, cross-sectional study. These results may lead to a better understanding of the impact of the interaction between genes and environment factors on brain structures associated to bipolar disorder and its manifestations. Copyright © 2015 Elsevier B.V. All rights reserved.

A study of brain metabolism in fibromyalgia by positron emission tomography.

PubMed

Usui, Chie; Soma, Tsutomu; Hatta, Kotaro; Aratani, Satoko; Fujita, Hidetoshi; Nishioka, Kenya; Machida, Yutaka; Kuroiwa, Yoshiyuki; Nakajima, Toshihiro; Nishioka, Kusuki

2017-04-03

The aim of the present study was to determine the brain regions with altered metabolism in patients with treatment-naïve fibromyalgia (FM). We used [ 18 F] fluoro-d-glucose positron emission tomography to examine a total of 18 treatment-naïve FM patients and 18 age- and sex-matched healthy controls not suffering from pain. A voxel-by-voxel group analysis was performed using statistical parametric mapping. No significant voxel (peak)-level results were detected in this study; however, some regions were detected as significant-size clusters. There were no significant differences in brain metabolism between FM patients and controls. However, the right thalamus and left lentiform nucleus were hypermetabolic areas in FM patients with poor prognosis compared to the healthy controls. In contrast, the left insula and left lentiform nucleus were hypometabolic areas in FM patients with good prognosis compared to the healthy controls. Compared to FM patients with good prognosis, FM patients with poor prognosis showed significant hypermetabolism in the left thalamus, bilateral lentiform nucleus, and right parahippocampal gyrus. The present findings suggest an association between the metabolism in the thalamus, lentiform nucleus, and parahippocampal gyrus and prognosis in FM patients. Further study with a larger number of patients is required to confirm this association. Copyright © 2017 Elsevier Inc. All rights reserved.

Emotional recognition from dynamic facial, vocal and musical expressions following traumatic brain injury.

PubMed

Drapeau, Joanie; Gosselin, Nathalie; Peretz, Isabelle; McKerral, Michelle

2017-01-01

To assess emotion recognition from dynamic facial, vocal and musical expressions in sub-groups of adults with traumatic brain injuries (TBI) of different severities and identify possible common underlying mechanisms across domains. Forty-one adults participated in this study: 10 with moderate-severe TBI, nine with complicated mild TBI, 11 with uncomplicated mild TBI and 11 healthy controls, who were administered experimental (emotional recognition, valence-arousal) and control tasks (emotional and structural discrimination) for each domain. Recognition of fearful faces was significantly impaired in moderate-severe and in complicated mild TBI sub-groups, as compared to those with uncomplicated mild TBI and controls. Effect sizes were medium-large. Participants with lower GCS scores performed more poorly when recognizing fearful dynamic facial expressions. Emotion recognition from auditory domains was preserved following TBI, irrespective of severity. All groups performed equally on control tasks, indicating no perceptual disorders. Although emotional recognition from vocal and musical expressions was preserved, no correlation was found across auditory domains. This preliminary study may contribute to improving comprehension of emotional recognition following TBI. Future studies of larger samples could usefully include measures of functional impacts of recognition deficits for fearful facial expressions. These could help refine interventions for emotional recognition following a brain injury.

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

Dynamic pupillary exchange engages brain regions encoding social salience

PubMed Central

Harrison, Neil A.; Gray, Marcus A.; Critchley, Hugo D.

2008-01-01

Covert exchange of autonomic responses may shape social affective behavior, as observed in mirroring of pupillary responses during sadness processing. We examined how, independent of facial emotional expression, dynamic coherence between one's own and another's pupil size modulates regional brain activity. Fourteen subjects viewed pairs of eye stimuli while undergoing fMRI. Using continuous pupillometry biofeedback, the size of the observed pupils was varied, correlating positively or negatively with changes in participants’ own pupils. Viewing both static and dynamic stimuli activated right fusiform gyrus. Observing dynamically changing pupils activated STS and amygdala, regions engaged by non-static and salient facial features. Discordance between observed and observer's pupillary changes enhanced activity within bilateral anterior insula, left amygdala and anterior cingulate. In contrast, processing positively correlated pupils enhanced activity within left frontal operculum. Our findings suggest pupillary signals are monitored continuously during social interactions and that incongruent changes activate brain regions involved in tracking motivational salience and attentionally meaningful information. Naturalistically, dynamic coherence in pupillary change follows fluctuations in ambient light. Correspondingly, in social contexts discordant pupil response is likely to reflect divergence of dispositional state. Our data provide empirical evidence for an autonomically mediated extension of forward models of motor control into social interaction. PMID:19048432

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.

RELATIONSHIP BETWEEN LINGUISTIC UNITS AND MOTOR COMMANDS.

ERIC Educational Resources Information Center

FROMKIN, VICTORIA A.

ASSUMING THAT SPEECH IS THE RESULT OF A NUMBER OF DISCRETE NEUROMUSCULAR EVENTS AND THAT THE BRAIN CAN STORE ONLY A LIMITED NUMBER OF MOTOR COMMANDS WITH WHICH TO CONTROL THESE EVENTS, THE RESEARCH REPORTED IN THIS PAPER WAS DIRECTED TO A DETERMINATION OF THE SIZE AND NATURE OF THE STORED ITEMS AND AN EXPLANATION OF HOW SPEAKERS ENCODE A SEQUENCE…

An fMRI study of emotional face processing in adolescent major depression.

PubMed

Hall, Leah M J; Klimes-Dougan, Bonnie; Hunt, Ruskin H; Thomas, Kathleen M; Houri, Alaa; Noack, Emily; Mueller, Bryon A; Lim, Kelvin O; Cullen, Kathryn R

2014-10-01

Major depressive disorder (MDD) often begins during adolescence when the brain is still maturing. To better understand the neurobiological underpinnings of MDD early in development, this study examined brain function in response to emotional faces in adolescents with MDD and healthy (HC) adolescents using functional magnetic resonance imaging (fMRI). Thirty-two unmedicated adolescents with MDD and 23 healthy age- and gender-matched controls completed an fMRI task viewing happy and fearful faces. Fronto-limbic regions of interest (ROI; bilateral amygdala, insula, subgenual and rostral anterior cingulate cortices) and whole-brain analyses were conducted to examine between-group differences in brain function. ROI analyses revealed that patients had greater bilateral amygdala activity than HC in response to viewing fearful versus happy faces, which remained significant when controlling for comorbid anxiety. Whole-brain analyses revealed that adolescents with MDD had lower activation compared to HC in a right hemisphere cluster comprised of the insula, superior/middle temporal gyrus, and Heschl׳s gyrus when viewing fearful faces. Brain activity in the subgenual anterior cingulate cortex was inversely correlated with depression severity. Limitations include a cross-sectional design with a modest sample size and use of a limited range of emotional stimuli. Results replicate previous studies that suggest emotion processing in adolescent MDD is associated with abnormalities within fronto-limbic brain regions. Findings implicate elevated amygdalar arousal to negative stimuli in adolescents with depression and provide new evidence for a deficit in functioning of the saliency network, which may be a future target for early intervention and MDD treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

Long-term outcome of gamma knife radiosurgery for metastatic brain tumors originating from lung cancer

PubMed Central

Bir, Shyamal C.; Ambekar, Sudheer; Bollam, Papireddy; Nanda, Anil

2014-01-01

Background: Gamma knife radiosurgery (GKRS) has emerged as an important treatment option for metastasis brain tumors (MBTs). However, the long-term outcome of GKRS on MBTs originating from lung carcinoma is not well understood. The treatment of MBTs derived from lung cancer with GKRS at our institution is reviewed. Methods: We performed a retrospective review (2000-2013) of 173 patients with MBTs from lung cancer who received GKRS. Out of 173 patients, 38 patients had recurrent tumors after microsurgical resection and whole brain radiotherapy (WBT). Results: GKRS in MBTs metastasized from lung carcinoma showed significant variations in tumor growth control (decreased in 79 [45.7%] patients, arrested growth in 54 [31.2%] patients, and increased tumor size in 40 [23.1%] patients). The median survival in the study population was 14 months. Overall survival after 3 years was 25%, whereas progression-free survival after 3 years was 45%. The predictive factors for improving survival in the patients with MBTs were recursive partitioning analysis (RPA) class I (P = 0.005), absence of hydrocephalus (P = 0.001), Karnofsky performance scale (KPS) >70 (P = 0.007), age ≤65 (P = 0.041), tumor size ≤3 cm (P = 0.023), controlled primary tumor (P = 0.049), and single number of MBTS (P = 0.044). Conclusion: Long-term follow-up revealed that GKRS offers a high rate of tumor control and good overall survival period in both new and recurrent patients with MBTs originating from lung carcinoma. Thus, GKRS is an effective treatment option for new patients with MBTs from lung cancer, as well as an adjuvant therapy in patients with recurrent MBTs derived from lung cancer. PMID:25289169

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.

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.

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

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.

Abnormalities in emotion processing within cortical and subcortical regions in criminal psychopaths: evidence from a functional magnetic resonance imaging study using pictures with emotional content.

PubMed

Müller, Jürgen L; Sommer, Monika; Wagner, Verena; Lange, Kirsten; Taschler, Heidrun; Röder, Christian H; Schuierer, Gerhardt; Klein, Helmfried E; Hajak, Göran

2003-07-15

Neurobiology of psychopathy is important for our understanding of current neuropsychiatric questions. Despite a growing interest in biological research in psychopathy, its neural underpinning remains obscure. We used functional magnetic resonance imaging to study the influence of affective contents on brain activation in psychopaths. Series containing positive and negative pictures from the International Affective Picture System were shown to six male psychopaths and six male control subjects while 100 whole-brain echo-planar-imaging measurements were acquired. Differences in brain activation were evaluated using BrainVoyager software 4.6. In psychopaths, increased activation through negative contents was found right-sided in prefrontal regions and amygdala. Activation was reduced right-sided in the subgenual cingulate and the temporal gyrus, and left-sided in the dorsal cingulate and the parahippocampal gyrus. Increased activation through positive contents was found left-sided in the orbitofrontal regions. Activation was reduced in right medial frontal and medial temporal regions. These findings underline the hypotheses that psychopathy is neurobiologically reflected by dysregulation and disturbed functional connectivity of emotion-related brain regions. These findings may be interpreted within a framework including prefrontal regions that provide top-down control to and regulate bottom-up signals from limbic areas. Because of the small sample size, the results of this study have to be regarded as preliminary.

Recent trends in the development of nanophytobioactive compounds and delivery systems for their possible role in reducing oxidative stress in Parkinson's disease models.

PubMed

Ganesan, Palanivel; Ko, Hyun-Myung; Kim, In-Su; Choi, Dong-Kug

2015-01-01

Oxidative stress plays a very critical role in neurodegenerative diseases, such as Parkinson's disease (PD), which is the second most common neurodegenerative disease among elderly people worldwide. Increasing evidence has suggested that phytobioactive compounds show enhanced benefits in cell and animal models of PD. Curcumin, resveratrol, ginsenosides, quercetin, and catechin are phyto-derived bioactive compounds with important roles in the prevention and treatment of PD. However, in vivo studies suggest that their concentrations are very low to cross blood-brain barrier thereby it limits bioavailability, stability, and dissolution at target sites in the brain. To overcome these problems, nanophytomedicine with the controlled size of 1-100 nm is used to maximize efficiency in the treatment of PD. Nanosizing of phytobioactive compounds enhances the permeability into the brain with maximized efficiency and stability. Several nanodelivery techniques, including solid lipid nanoparticles, nanostructured lipid carriers, nanoliposomes, and nanoniosomes can be used for controlled delivery of nanobioactive compounds to brain. Nanocompounds, such as ginsenosides (19.9 nm) synthesized using a nanoemulsion technique, showed enhanced bioavailability in the rat brain. Here, we discuss the most recent trends and applications in PD, including 1) the role of phytobioactive compounds in reducing oxidative stress and their bioavailability; 2) the role of nanotechnology in reducing oxidative stress during PD; 3) nanodelivery systems; and 4) various nanophytobioactive compounds and their role in PD.

Alterations of whole-brain cortical area and thickness in mild cognitive impairment and Alzheimer's disease.

PubMed

Li, Chuanming; Wang, Jian; Gui, Li; Zheng, Jian; Liu, Chen; Du, Hanjian

2011-01-01

Gray matter volume and density of several brain regions, determined by magnetic resonance imaging (MRI), are decreased in Alzheimer's disease (AD). Animal studies have indicated that changes in cortical area size is relevant to thinking and behavior, but alterations of cortical area and thickness in the brains of individuals with AD or its likely precursor, mild cognitive impairment (MCI), have not been reported. In this study, 25 MCI subjects, 30 AD subjects, and 30 age-matched normal controls were recruited for brain MRI scans and Functional Activities Questionnaire (FAQ) assessments. Based on the model using FreeSurfer software, two brain lobes were divided into various regions according to the Desikan-Killiany atlas and the cortical area and thickness of every region was compared and analyzed. We found a significant increase in cortical area of several regions in the frontal and temporal cortices, which correlated negatively with MMSE scores, and a significant decrease in cortical area of several regions in the parietal cortex and the cingulate gyrus in AD subjects. Increased cortical area was also seen in some regions of the frontal and temporal cortices in MCI subjects, whereas the cortical thickness of the same regions was decreased. Our observations suggest characteristic differences of the cortical area and thickness in MCI, AD, and normal control subjects, and these changes may help diagnose both MCI and AD.

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.

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

Cognitive and Occupational Function in Survivors of Adolescent Cancer.

PubMed

Nugent, Bethany D; Bender, Catherine M; Sereika, Susan M; Tersak, Jean M; Rosenzweig, Margaret

2018-02-01

Adolescents with cancer have unique developmental considerations. These include brain development, particularly in the frontal lobe, and a focus on completing education and entering the workforce. Cancer and treatment at this stage may prove to uniquely affect survivors' experience of cognitive and occupational function. An exploratory, cross-sectional, descriptive comparative study was employed to describe cognitive and occupational function in adult survivors of adolescent cancer (diagnosed between the ages of 15 and 21 years) and explore differences in age- and gender-matched controls. In total, 23 survivors and 14 controls participated in the study. While significant differences were not found between the groups on measures of cognitive and occupational function, several small and medium effect sizes were found suggesting that survivors may have greater difficulty than controls. Two small effect sizes were found in measures of neuropsychological performance (the Digit Vigilance test [d = 0.396] and Stroop test [d = 0.226]). Small and medium effect sizes ranging from 0.269 to 0.605 were found for aspects of perceived and total cognitive function. A small effect size was also found in work output (d = 0.367). While we did not find significant differences in cognitive or occupational function between survivors and controls, the effect sizes observed point to the need for future research. Future work using a larger sample size and longitudinal design are needed to further explore cognitive and occupational function in this vulnerable and understudied population and assist in the understanding of patterns of change over time.

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).

Pilot Study on Long Term Effects of HZE Exposure on the Canine Brain

NASA Astrophysics Data System (ADS)

Budinger, T.; Brennan, K.; Pearlstein, R.

A ground-based pilot experiment was initiated in December 1992 to evaluate the long term effects on health and aging after HZE cosmic radiation of the canine brain. Six adult male beagle dogs (1 yr) from the UC Davis breeding colony at the Laboratory for Energy Related Health Research were researched in this study. Iron nuclei at 600 MeV/amu (180 keV/mm) were used to irradiate the whole brain. The fluence of 3 x 106 iron nuclei/ cm2 mimics the HZE exposure (all > He) for a 2- year mission to Mars. The HZE irradiation was a fully stripped iron particle beam at the LBNL BEVALAC. Using a Raster Scanner we were able to spread the beam to deliver a uniform dose over the brain. The total dose to the brain was 200 cGy. Four dogs were whole brain irradiated with iron and two dogs served as litter-mate controls. The control dogs received a similar amount of background neutron irradiation as the irradiated dogs. One of the control dogs died suddenly 3/98 of intestinal cancer unrelated to the brain irradiation. That brain was not harvested before autolysis had prevented analysis. Periodic PET metabolism and yearly MRI studies have been done on these dog's brain since irradiation. All dogs had yearly physical, neurological and blood chemistry work-ups. PET imaging was performed with the Donner 600-crystal high-resolution PET (2.6 mm resolution) and with the commercial PET, CTI/Siemens ECAT 951 PET Scanner (5 mm resolution). NMR imaging is performed with the 1 5T GE Signa at UCSF using T spoiled gradient imaging.1 sequences for T1 contrast at 1 mm resolution as well as a T2 weighted spin echo imaging sequence at 1 mm resolution. A major goal of this work is to present an accurate method for measuring surface areas and volumes of the irradiated vs the non-irradiated canine brain using MRI data which are isotropic in resolution at the 1 mm level. This allows us to monitor the changes in brain size with aging and radiation exposure. Nine years post irradiation, these dog brains (+ 3 additional age-matched controls) were in-situ perfused with 4% paraformaldehyde/01.M phosphate buffer. The brain was removed and fixed in the same fixative for 2 weeks. Brain sections were embedded in parafin and cut at 6 or 12 μm thickness. Histology included H&E, Luxol fast blue and Silver staining. Immunochemistry included Amyloidprecursor protein. There was no marked increase in amyloid plaque formation in the irradiated dogs. Imaging and histology results will be presented at the COSPAR conference.

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

Joint source based analysis of multiple brain structures in studying major depressive disorder

NASA Astrophysics Data System (ADS)

Ramezani, Mahdi; Rasoulian, Abtin; Hollenstein, Tom; Harkness, Kate; Johnsrude, Ingrid; Abolmaesumi, Purang

2014-03-01

We propose a joint Source-Based Analysis (jSBA) framework to identify brain structural variations in patients with Major Depressive Disorder (MDD). In this framework, features representing position, orientation and size (i.e. pose), shape, and local tissue composition are extracted. Subsequently, simultaneous analysis of these features within a joint analysis method is performed to generate the basis sources that show signi cant di erences between subjects with MDD and those in healthy control. Moreover, in a cross-validation leave- one-out experiment, we use a Fisher Linear Discriminant (FLD) classi er to identify individuals within the MDD group. Results show that we can classify the MDD subjects with an accuracy of 76% solely based on the information gathered from the joint analysis of pose, shape, and tissue composition in multiple brain structures.

Effect of intravenous administration of D-lysergic acid diethylamide on initiation of protein synthesis in a cell-free system derived from brain.

PubMed

Cosgrove, J W; Brown, I R

1984-05-01

An initiating cell-free protein synthesis system derived from brain was utilized to demonstrate that the intravenous injection of D-lysergic acid diethylamide (LSD) to rabbits resulted in a lesion at the initiation stage of brain protein synthesis. Three inhibitors of initiation, edeine, poly(I), and aurintricarboxylic acid were used to demonstrate a reduction in initiation-dependent amino acid incorporation in the brain cell-free system. One hour after LSD injection, there was also a measurable decrease in the formation of 40S and 80S initiation complexes in vitro, using either [35S]methionine or [35S]Met-tRNAf. Analysis of the methionine pool size after LSD administration indicated there was no change in methionine levels. Analysis of the formation of initiation complexes in the brain cell-free protein synthesis system prepared 6 h after LSD administration indicated that there was a return to control levels at this time. The effects of LSD on steps in the initiation process are thus reversible.

Functional abnormalities in normally appearing athletes following mild traumatic brain injury: a functional MRI study

PubMed Central

Slobounov, Semyon M.; Zhang, K.; Pennell, D.; Ray, W.; Johnson, B.; Sebastianelli, W.

2010-01-01

Memory problems are one of the most common symptoms of sport-related mild traumatic brain injury (MTBI), known as concussion. Surprisingly, little research has examined spatial memory in concussed athletes given its importance in athletic environments. Here, we combine functional magnetic resonance imaging (fMRI) with a virtual reality (VR) paradigm designed to investigate the possibility of residual functional deficits in recently concussed but asymptomatic individuals. Specifically, we report performance of spatial memory navigation tasks in a VR environment and fMRI data in 15 athletes suffering from MTBI and 15 neurologically normal, athletically active age matched controls. No differences in performance were observed between these two groups of subjects in terms of success rate (94 and 92%) and time to complete the spatial memory navigation tasks (mean = 19.5 and 19.7 s). Whole brain analysis revealed that similar brain activation patterns were observed during both encoding and retrieval among the groups. However, concussed athletes showed larger cortical networks with additional increases in activity outside of the shared region of interest (ROI) during encoding. Quantitative analysis of blood oxygen level dependent (BOLD) signal revealed that concussed individuals had a significantly larger cluster size during encoding at parietal cortex, right dorsolateral prefrontal cortex, and right hippocampus. In addition, there was a significantly larger BOLD signal percent change at the right hippocampus. Neither cluster size nor BOLD signal percent change at shared ROIs was different between groups during retrieval. These major findings are discussed with respect to current hypotheses regarding the neural mechanism responsible for alteration of brain functions in a clinical setting. PMID:20039023

Application of optical coherence tomography for in vivo monitoring of the meningeal lymphatic vessels during opening of blood-brain barrier: mechanisms of brain clearing

NASA Astrophysics Data System (ADS)

Semyachkina-Glushkovskaya, Oxana; Abdurashitov, Arkady; Dubrovsky, Alexander; Bragin, Denis; Bragina, Olga; Shushunova, Nataliya; Maslyakova, Galina; Navolokin, Nikita; Bucharskaya, Alla; Tuchin, Valery; Kurths, Juergen; Shirokov, Alexander

2017-12-01

The meningeal lymphatic vessels were discovered 2 years ago as the drainage system involved in the mechanisms underlying the clearance of waste products from the brain. The blood-brain barrier (BBB) is a gatekeeper that strongly controls the movement of different molecules from the blood into the brain. We know the scenarios during the opening of the BBB, but there is extremely limited information on how the brain clears the substances that cross the BBB. Here, using the model of sound-induced opening of the BBB, we clearly show how the brain clears dextran after it crosses the BBB via the meningeal lymphatic vessels. We first demonstrate successful application of optical coherence tomography (OCT) for imaging of the lymphatic vessels in the meninges after opening of the BBB, which might be a new useful strategy for noninvasive analysis of lymphatic drainage in daily clinical practice. Also, we give information about the depth and size of the meningeal lymphatic vessels in mice. These new fundamental data with the applied focus on the OCT shed light on the mechanisms of brain clearance and the role of lymphatic drainage in these processes that could serve as an informative platform for a development of therapy and diagnostics of diseases associated with injuries of the BBB such as stroke, brain trauma, glioma, depression, or Alzheimer disease.

Effects on birds of fenthion aerial application for mosquito control

USGS Publications Warehouse

DeWeese, L.R.; McEwen, L.C.; Settimi, L.A.; Deblinger, R.D.

1983-01-01

Effects on birds of an aerial application of fenthion, a potent organophosphorus cholinesterase (ChE)-inhibiting insecticide, were assessed on four study sites 1.8 to 3.6 km2 in size. These sites were located within 121.5 km2 of wet meadows treated with 47 g of fenthion (AI) per ha in ultralow- volume formulation. Assessment methods were searches for sick or dead birds, measurements of brain ChE activity in specimens found dead or collected alive at different time intervals, and counts of bird populations. After treatment, 99 birds and 15 mammals were found sick or dead; 106 of these were on one site. Brain ChE activity in dead birds was depressed sufficiently to indicate that death was caused by an anti-ChE substance. Brain ChE activity in three common bird species collected alive showed the greatest reduction 2 days postspray. Two of these species had ChE activity that was still significantly (P<0.05) depressed 15 days postspray. Bird populations declined most where mortality was heaviest. Fenthion sprayed for mosquito control was life threatening to many birds inhabiting treated meadows.

Magnetic resonance imaging-three-dimensional printing technology fabricates customized scaffolds for brain tissue engineering

PubMed Central

Fu, Feng; Qin, Zhe; Xu, Chao; Chen, Xu-yi; Li, Rui-xin; Wang, Li-na; Peng, Ding-wei; Sun, Hong-tao; Tu, Yue; Chen, Chong; Zhang, Sai; Zhao, Ming-liang; Li, Xiao-hong

2017-01-01

Conventional fabrication methods lack the ability to control both macro- and micro-structures of generated scaffolds. Three-dimensional printing is a solid free-form fabrication method that provides novel ways to create customized scaffolds with high precision and accuracy. In this study, an electrically controlled cortical impactor was used to induce randomized brain tissue defects. The overall shape of scaffolds was designed using rat-specific anatomical data obtained from magnetic resonance imaging, and the internal structure was created by computer-aided design. As the result of limitations arising from insufficient resolution of the manufacturing process, we magnified the size of the cavity model prototype five-fold to successfully fabricate customized collagen-chitosan scaffolds using three-dimensional printing. Results demonstrated that scaffolds have three-dimensional porous structures, high porosity, highly specific surface areas, pore connectivity and good internal characteristics. Neural stem cells co-cultured with scaffolds showed good viability, indicating good biocompatibility and biodegradability. This technique may be a promising new strategy for regenerating complex damaged brain tissues, and helps pave the way toward personalized medicine. PMID:28553343

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).

Males are from Mars, females are from Venus: sex-specific fetal brain gene expression signatures in a mouse model of maternal diet-induced obesity

PubMed Central

EDLOW, Andrea G.; GUEDJ, Faycal; PENNINGS, Jeroen L.A.; SVERDLOV, Deanna; NERI, Caterina; BIANCHI, Diana W.

2016-01-01

BACKGROUND Maternal obesity is associated with adverse neurodevelopmental outcomes in children, including autism spectrum disorders, developmental delay, and attention deficit hyperactivity disorder. The underlying mechanisms remain unclear. We previously identified second trimester amniotic fluid and term cord blood gene expression patterns suggesting dysregulated brain development in fetuses of obese compared to lean women. OBJECTIVES We sought to investigate the biological significance of these findings in a mouse model of maternal diet-induced obesity. We evaluated sex-specific differences in fetal growth, brain gene expression signatures and associated pathways. STUDY DESIGN Female C57BL/6J mice were fed a 60% high-fat diet or 10% fat control diet for 12–14 weeks prior to mating. During pregnancy, obese dams continued on the high-fat diet (HFD/HFD), or transitioned to the CD (HFD/CD). Lean dams stayed on the control diet. On embryonic day 17.5, embryos were weighed and fetal brains were snap frozen. RNA was extracted from male and female forebrains (10/diet group/sex) and hybridized to whole genome expression arrays. Significantly differentially expressed genes were identified using Welch’s t-test with the Benjamini-Hochberg correction. Functional analyses were performed using Ingenuity Pathways Analysis and Gene Set Enrichment Analysis. RESULTS Embryos of HFD/HFD dams were significantly smaller than controls, with males more severely affected than females (p=0.01). Maternal obesity and maternal obesity with dietary change in pregnancy resulted in significantly more dysregulated genes in male versus female fetal brains (386 vs 66, p<0.001). Maternal obesity with and without dietary change in pregnancy was associated with unique brain gene expression signatures for each sex, with overlap of only one gene. Changing obese dams to a control diet in pregnancy resulted in more differentially expressed genes in the fetal brain than maternal obesity alone. Functional analyses identified common dysregulated pathways in both sexes, but maternal obesity and maternal dietary change affected different aspects of brain development in males compared to females. CONCLUSIONS Maternal obesity is associated with sex-specific differences in fetal size and fetal brain gene expression signatures. Male fetal growth and brain gene expression may be more sensitive to environmental influences during pregnancy. Maternal diet during pregnancy significantly impacts the embryonic brain transcriptome. It is important to consider both fetal sex and maternal diet when evaluating the effects of maternal obesity on fetal neurodevelopment. PMID:26945603

On the growth and form of cortical convolutions

NASA Astrophysics Data System (ADS)

Tallinen, Tuomas; Chung, Jun Young; Rousseau, François; Girard, Nadine; Lefèvre, Julien; Mahadevan, L.

2016-06-01

The rapid growth of the human cortex during development is accompanied by the folding of the brain into a highly convoluted structure. Recent studies have focused on the genetic and cellular regulation of cortical growth, but understanding the formation of the gyral and sulcal convolutions also requires consideration of the geometry and physical shaping of the growing brain. To study this, we use magnetic resonance images to build a 3D-printed layered gel mimic of the developing smooth fetal brain; when immersed in a solvent, the outer layer swells relative to the core, mimicking cortical growth. This relative growth puts the outer layer into mechanical compression and leads to sulci and gyri similar to those in fetal brains. Starting with the same initial geometry, we also build numerical simulations of the brain modelled as a soft tissue with a growing cortex, and show that this also produces the characteristic patterns of convolutions over a realistic developmental course. All together, our results show that although many molecular determinants control the tangential expansion of the cortex, the size, shape, placement and orientation of the folds arise through iterations and variations of an elementary mechanical instability modulated by early fetal brain geometry.

Role of Caspase-9 Gene Ex5+32 G>A (rs1052576) Variant in Susceptibility to Primary Brain Tumors.

PubMed

Ozdogan, Selcuk; Kafadar, Ali; Yilmaz, Seda Gulec; Timirci-Kahraman, Ozlem; Gormus, Uzay; Isbir, Turgay

2017-09-01

This study is the first to evaluate the relationship of caspase-9 (CASP-9) gene polymorphism with the risk for primary brain tumor development. The study group included 43 glioma and 27 meningioma patients and 76 healthy individuals. CASP-9 gene Ex5+32 G>A (rs1052576) polymorphism was analyzed by real-time polymerase chain reaction (RT-PCR). Individuals with the CASP-9 GG genotype had significantly decreased risk of developing a glioma brain tumor (p=0.024). Additionally, the GA genotype was significantly lower in patients with glioma than the control group (p=0.019). A significantly decreased risk of developing glioma was found in the A allele carrier group (p=0.024). However, there was no statistically significant relationship between CASP-9 polymorphism and brain meningioma (p=0.493). CASP-9 (rs1052576) mutant A allele seems to be a protective factor for glioma brain tumor. Future studies with a larger sample size will clarify the possible roles of CASP-9 gene in the etiology and progression of primary brain tumors. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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

Local Brain Activity Differences Between Herpes Zoster and Postherpetic Neuralgia Patients: A Resting-State Functional MRI Study.

PubMed

Cao, Song; Li, Ying; Deng, Wenwen; Qin, Bangyong; Zhang, Yi; Xie, Peng; Yuan, Jie; Yu, Buwei; Yu, Tian

2017-07-01

Herpes zoster (HZ) can develop into postherpetic neuralgia (PHN), both of which are painful diseases. PHN patients suffer chronic pain and emotional disorders. Previous studies showed that the PHN brain displayed abnormal activity and structural change, but the difference in brain activity between HZ and PHN is still not known. To identify regional brain activity changes in HZ and PHN brains with resting-state functional magnetic resonance imaging (rs-fMRI) technique, and to observe the differences between HZ and PHN patients. Observational study. University hospital. Regional homogeneity (ReHo) and fractional aptitude of low-frequency fluctuation (fALFF) methods were employed to analysis resting-state brain activity. Seventy-three age and gender matched patients (50 HZ, 23 PHN) and 55 healthy controls were enrolled. ReHo and fALFF changes were analyzed to detect the functional abnormality in HZ and PHN brains. Compared with healthy controls, HZ and PHN patients exhibited abnormal ReHo and fALFF values in classic pain-related brain regions (such as the frontal lobe, thalamus, insular, and cerebellum) as well as the brainstem, limbic lobe, and temporal lobe. When HZ developed to PHN, the activity in the vast area of the cerebellum significantly increased while that of some regions in the occipital lobe, temporal lobe, parietal lobe, and limbic lobe showed an apparent decrease. (a) Relatively short pain duration (mean 12.2 months) and small sample size (n = 23) for PHN group. (b) Comparisons at different time points (with paired t-tests) for each patient may minimize individual differences. HZ and PHN induced local brain activity changed in the pain matrix, brainstem, and limbic system. HZ chronification induced functional change in the cerebellum, occipital lobe, temporal lobe, parietal lobe, and limbic lobe. These brain activity changes may be correlated with HZ-PHN transition. Herpes zoster, postherpetic neuralgia, resting-state fMRI (rs-fMRI), regional homogeneity (ReHo), fractional aptitude of low-frequency fluctuation (fALFF).

Developmentally stable whole-brain volume reductions and developmentally sensitive caudate and putamen volume alterations in those with attention-deficit/hyperactivity disorder and their unaffected siblings.

PubMed

Greven, Corina U; Bralten, Janita; Mennes, Maarten; O'Dwyer, Laurence; van Hulzen, Kimm J E; Rommelse, Nanda; Schweren, Lizanne J S; Hoekstra, Pieter J; Hartman, Catharina A; Heslenfeld, Dirk; Oosterlaan, Jaap; Faraone, Stephen V; Franke, Barbara; Zwiers, Marcel P; Arias-Vasquez, Alejandro; Buitelaar, Jan K

2015-05-01

Attention-deficit/hyperactivity disorder (ADHD) is a heritable neurodevelopmental disorder. It has been linked to reductions in total brain volume and subcortical abnormalities. However, owing to heterogeneity within and between studies and limited sample sizes, findings on the neuroanatomical substrates of ADHD have shown considerable variability. Moreover, it remains unclear whether neuroanatomical alterations linked to ADHD are also present in the unaffected siblings of those with ADHD. To examine whether ADHD is linked to alterations in whole-brain and subcortical volumes and to study familial underpinnings of brain volumetric alterations in ADHD. In this cross-sectional study, we included participants from the large and carefully phenotyped Dutch NeuroIMAGE sample (collected from September 2009-December 2012) consisting of 307 participants with ADHD, 169 of their unaffected siblings, and 196 typically developing control individuals (mean age, 17.21 years; age range, 8-30 years). Whole-brain volumes (total brain and gray and white matter volumes) and volumes of subcortical regions (nucleus accumbens, amygdala, caudate nucleus, globus pallidus, hippocampus, putamen, thalamus, and brainstem) were derived from structural magnetic resonance imaging scans using automated tissue segmentation. Regression analyses revealed that relative to control individuals, participants with ADHD had a 2.5% smaller total brain (β = -31.92; 95% CI, -52.69 to -11.16; P = .0027) and a 3% smaller total gray matter volume (β = -22.51; 95% CI, -35.07 to -9.96; P = .0005), while total white matter volume was unaltered (β = -10.10; 95% CI, -20.73 to 0.53; P = .06). Unaffected siblings had total brain and total gray matter volumes intermediate to participants with ADHD and control individuals. Significant age-by-diagnosis interactions showed that older age was linked to smaller caudate (P < .001) and putamen (P = .01) volumes (both corrected for total brain volume) in control individuals, whereas age was unrelated to these volumes in participants with ADHD and their unaffected siblings. Attention-deficit/hyperactivity disorder was not significantly related to the other subcortical volumes. Global differences in gray matter volume may be due to alterations in the general mechanisms underlying normal brain development in ADHD. The age-by-diagnosis interaction in the caudate and putamen supports the relevance of different brain developmental trajectories in participants with ADHD vs control individuals and supports the role of subcortical basal ganglia alterations in the pathophysiology of ADHD. Alterations in total gray matter and caudate and putamen volumes in unaffected siblings suggest that these volumes are linked to familial risk for ADHD.

Neonatal stimulation of 5-HT(2) receptors reduces androgen receptor expression in the rat anteroventral periventricular nucleus and sexually dimorphic preoptic area.

PubMed

Dakin, C L; Wilson, C A; Kalló, I; Coen, C W; Davies, D C

2008-05-01

Masculinization of the brain is dependent upon a perinatal surge in testosterone. It also requires a transient decrease in hypothalamic 5-HT concentration and turnover and an increase in androgen receptor (AR) expression during the second postnatal week. We have previously shown that increasing 5-HT activity over this period in male or androgenized female rats feminizes their adult behaviour and also feminizes the size of their anteroventral periventricular nucleus (AVPV) and sexually dimorphic nucleus of the preoptic area (SDN-POA). To investigate the role of 5-HT in sexual differentiation of the brain, 5-HT activity was raised over postnatal days 8-16 in male, female and androgenized female rats by daily administration of the 5-HT(2) receptor agonist (-)[2,5 dimethoxy-4-iodophenyl]-2-amino propane hydrochloride [(-)DOI]. By postnatal day 18, the size of the AVPV and SDN-POA was sexually dimorphic; their sizes were feminized by (-)DOI treatment. In the absence of (-)DOI treatment, there were significantly more AR-immunoreactive cells in the AVPV of males, and in the SDN-POA of males and androgenized females, than in those of females on postnatal day 18. (-)DOI treatment reduced the number of AR-immunoreactive cells in the AVPV and SDN-POA of males and androgenized females, but not of females, by postnatal day 18. These results suggest that 5-HT(2) receptor activation can influence sexual differentiation of the brain by controlling AR expression.

Effects of biological and technical factors on brain and muscle cholinesterases in Nile tilapia, Oreochromis niloticus: implications for biomonitoring neurotoxic contaminations.

PubMed

Pathiratne, A; Chandrasekera, L W H U; De Seram, P K C

2008-02-01

Influence of body length, body weight, gender, sexual maturity, and tissue storage on brain and muscle cholinesterases (ChE) in Nile tilapia was evaluated considering its potential use in biomonitoring neurotoxic contaminations in tropical environments. Results show that ChE activities in both tissues decreased significantly with increased total length (4-24.5 cm) or body weight (1-186 g) of the fish and the relationships were curvilinear. Comparisons of the slopes and elevations of the regression lines of the logarithmic ChE and body size relationships of males with those of females indicated that gender had no significant effect on the body size-specific ChE activities. Response of the ChE of sexually mature males to chlorpyrifos exposure was similar to that of females. Gonadal maturity stage of this fish does not seem to influence ChE activities. Storage of tissues at -80 degrees C for 28 days had no significant effect on ChE activities in the control fish and the fish exposed to carbofuran. However, a partial reactivation of brain ChE activities was observed in the fish exposed to carbosulfan after 28 days of storage. The results emphasize the importance of consideration of body size of the fish and storage time of the tissues in order to formulate accurate conclusions about the neurotoxic chemical exposure when ChE of the fish is used in biomonitoring programs.

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

Brain Aneurysm

MedlinePlus

A brain aneurysm is an abnormal bulge or "ballooning" in the wall of an artery in the brain. They are sometimes called berry aneurysms because they ... often the size of a small berry. Most brain aneurysms produce no symptoms until they become large, ...

Large-scale mapping of cortical alterations in 22q11.2 deletion syndrome: Convergence with idiopathic psychosis and effects of deletion size.

PubMed

Sun, Daqiang; Ching, Christopher R K; Lin, Amy; Forsyth, Jennifer K; Kushan, Leila; Vajdi, Ariana; Jalbrzikowski, Maria; Hansen, Laura; Villalon-Reina, Julio E; Qu, Xiaoping; Jonas, Rachel K; van Amelsvoort, Therese; Bakker, Geor; Kates, Wendy R; Antshel, Kevin M; Fremont, Wanda; Campbell, Linda E; McCabe, Kathryn L; Daly, Eileen; Gudbrandsen, Maria; Murphy, Clodagh M; Murphy, Declan; Craig, Michael; Vorstman, Jacob; Fiksinski, Ania; Koops, Sanne; Ruparel, Kosha; Roalf, David R; Gur, Raquel E; Schmitt, J Eric; Simon, Tony J; Goodrich-Hunsaker, Naomi J; Durdle, Courtney A; Bassett, Anne S; Chow, Eva W C; Butcher, Nancy J; Vila-Rodriguez, Fidel; Doherty, Joanne; Cunningham, Adam; van den Bree, Marianne B M; Linden, David E J; Moss, Hayley; Owen, Michael J; Murphy, Kieran C; McDonald-McGinn, Donna M; Emanuel, Beverly; van Erp, Theo G M; Turner, Jessica A; Thompson, Paul M; Bearden, Carrie E

2018-06-13

The 22q11.2 deletion (22q11DS) is a common chromosomal microdeletion and a potent risk factor for psychotic illness. Prior studies reported widespread cortical changes in 22q11DS, but were generally underpowered to characterize neuroanatomic abnormalities associated with psychosis in 22q11DS, and/or neuroanatomic effects of variability in deletion size. To address these issues, we developed the ENIGMA (Enhancing Neuro Imaging Genetics Through Meta-Analysis) 22q11.2 Working Group, representing the largest analysis of brain structural alterations in 22q11DS to date. The imaging data were collected from 10 centers worldwide, including 474 subjects with 22q11DS (age = 18.2 ± 8.6; 46.9% female) and 315 typically developing, matched controls (age = 18.0 ± 9.2; 45.9% female). Compared to controls, 22q11DS individuals showed thicker cortical gray matter overall (left/right hemispheres: Cohen's d = 0.61/0.65), but focal thickness reduction in temporal and cingulate cortex. Cortical surface area (SA), however, showed pervasive reductions in 22q11DS (left/right hemispheres: d = -1.01/-1.02). 22q11DS cases vs. controls were classified with 93.8% accuracy based on these neuroanatomic patterns. Comparison of 22q11DS-psychosis to idiopathic schizophrenia (ENIGMA-Schizophrenia Working Group) revealed significant convergence of affected brain regions, particularly in fronto-temporal cortex. Finally, cortical SA was significantly greater in 22q11DS cases with smaller 1.5 Mb deletions, relative to those with typical 3 Mb deletions. We found a robust neuroanatomic signature of 22q11DS, and the first evidence that deletion size impacts brain structure. Psychotic illness in this highly penetrant deletion was associated with similar neuroanatomic abnormalities to idiopathic schizophrenia. These consistent cross-site findings highlight the homogeneity of this single genetic etiology, and support the suitability of 22q11DS as a biological model of schizophrenia.

Cortical Abnormalities Associated With Pediatric and Adult Obsessive-Compulsive Disorder: Findings From the ENIGMA Obsessive-Compulsive Disorder Working Group.

PubMed

Boedhoe, Premika S W; Schmaal, Lianne; Abe, Yoshinari; Alonso, Pino; Ameis, Stephanie H; Anticevic, Alan; Arnold, Paul D; Batistuzzo, Marcelo C; Benedetti, Francesco; Beucke, Jan C; Bollettini, Irene; Bose, Anushree; Brem, Silvia; Calvo, Anna; Calvo, Rosa; Cheng, Yuqi; Cho, Kang Ik K; Ciullo, Valentina; Dallaspezia, Sara; Denys, Damiaan; Feusner, Jamie D; Fitzgerald, Kate D; Fouche, Jean-Paul; Fridgeirsson, Egill A; Gruner, Patricia; Hanna, Gregory L; Hibar, Derrek P; Hoexter, Marcelo Q; Hu, Hao; Huyser, Chaim; Jahanshad, Neda; James, Anthony; Kathmann, Norbert; Kaufmann, Christian; Koch, Kathrin; Kwon, Jun Soo; Lazaro, Luisa; Lochner, Christine; Marsh, Rachel; Martínez-Zalacaín, Ignacio; Mataix-Cols, David; Menchón, José M; Minuzzi, Luciano; Morer, Astrid; Nakamae, Takashi; Nakao, Tomohiro; Narayanaswamy, Janardhanan C; Nishida, Seiji; Nurmi, Erika; O'Neill, Joseph; Piacentini, John; Piras, Fabrizio; Piras, Federica; Reddy, Y C Janardhan; Reess, Tim J; Sakai, Yuki; Sato, Joao R; Simpson, H Blair; Soreni, Noam; Soriano-Mas, Carles; Spalletta, Gianfranco; Stevens, Michael C; Szeszko, Philip R; Tolin, David F; van Wingen, Guido A; Venkatasubramanian, Ganesan; Walitza, Susanne; Wang, Zhen; Yun, Je-Yeon; Thompson, Paul M; Stein, Dan J; van den Heuvel, Odile A

2018-05-01

Brain imaging studies of structural abnormalities in OCD have yielded inconsistent results, partly because of limited statistical power, clinical heterogeneity, and methodological differences. The authors conducted meta- and mega-analyses comprising the largest study of cortical morphometry in OCD ever undertaken. T 1 -weighted MRI scans of 1,905 OCD patients and 1,760 healthy controls from 27 sites worldwide were processed locally using FreeSurfer to assess cortical thickness and surface area. Effect sizes for differences between patients and controls, and associations with clinical characteristics, were calculated using linear regression models controlling for age, sex, site, and intracranial volume. In adult OCD patients versus controls, we found a significantly lower surface area for the transverse temporal cortex and a thinner inferior parietal cortex. Medicated adult OCD patients also showed thinner cortices throughout the brain. In pediatric OCD patients compared with controls, we found significantly thinner inferior and superior parietal cortices, but none of the regions analyzed showed significant differences in surface area. However, medicated pediatric OCD patients had lower surface area in frontal regions. Cohen's d effect sizes varied from -0.10 to -0.33. The parietal cortex was consistently implicated in both adults and children with OCD. More widespread cortical thickness abnormalities were found in medicated adult OCD patients, and more pronounced surface area deficits (mainly in frontal regions) were found in medicated pediatric OCD patients. These cortical measures represent distinct morphological features and may be differentially affected during different stages of development and illness, and possibly moderated by disease profile and medication.

Short progressive muscle relaxation or motor coordination training does not increase performance in a brain-computer interface based on sensorimotor rhythms (SMR).

PubMed

Botrel, L; Acqualagna, L; Blankertz, B; Kübler, A

2017-11-01

Brain computer interfaces (BCIs) allow for controlling devices through modulation of sensorimotor rhythms (SMR), yet a profound number of users is unable to achieve sufficient accuracy. Here, we investigated if visuo-motor coordination (VMC) training or Jacobsen's progressive muscle relaxation (PMR) prior to BCI use would increase later performance compared to a control group who performed a reading task (CG). Running the study in two different BCI-labs, we achieved a joint sample size of N=154 naïve participants. No significant effect of either intervention (VMC, PMR, control) was found on resulting BCI performance. Relaxation level and visuo-motor performance were associated with later BCI performance in one BCI-lab but not in the other. These mixed results do not indicate a strong potential of VMC or PMR for boosting performance. Yet further research with different training parameters or experimental designs is needed to complete the picture. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Visuomotor Dissociation in Cerebral Scaling of Size.

PubMed

Potgieser, Adriaan R E; de Jong, Bauke M

2016-01-01

Estimating size and distance is crucial in effective visuomotor control. The concept of an internal coordinate system implies that visual and motor size parameters are scaled onto a common template. To dissociate perceptual and motor components in such scaling, we performed an fMRI experiment in which 16 right-handed subjects copied geometric figures while the result of drawing remained out of sight. Either the size of the example figure varied while maintaining a constant size of drawing (visual incongruity) or the size of the examples remained constant while subjects were instructed to make changes in size (motor incongruity). These incongruent were compared to congruent conditions. Statistical Parametric Mapping (SPM8) revealed brain activations related to size incongruity in the dorsolateral prefrontal and inferior parietal cortex, pre-SMA / anterior cingulate and anterior insula, dominant in the right hemisphere. This pattern represented simultaneous use of a 'resized' virtual template and actual picture information requiring spatial working memory, early-stage attention shifting and inhibitory control. Activations were strongest in motor incongruity while right pre-dorsal premotor activation specifically occurred in this condition. Visual incongruity additionally relied on a ventral visual pathway. Left ventral premotor activation occurred in all variably sized drawing while constant visuomotor size, compared to congruent size variation, uniquely activated the lateral occipital cortex additional to superior parietal regions. These results highlight size as a fundamental parameter in both general hand movement and movement guided by objects perceived in the context of surrounding 3D space.

[Morphological changes of neurons and neuroglial cells in the brain of senescence-accelerated prone 1 (SAMP1) mice].

PubMed

Khudoerkov, R M; Sal'kov, V N; Sal'nikova, O V; Sobolev, V B

2014-01-01

Computerized morphometry was used to examine the sizes of neuronal bodies and the compactness of arrangement of neurons and neuroglial cells in layers III and V of the sensorimotor cortex in senescence-accelerated prone 1 (SAMP1) mice (an experimental group) and senescence-accelerated-resistant strain 1 (SAMR1) ones (a control group). In the SAMP1 mice as compared to the SAMR1 ones, the neuronal body sizes were significantly unchanged; the compactness of their arrangement decreased by 17 and 20% in layers III and V, respectively; that of neuroglial cells significantly increased by 14% in layer III only. In the SAMP1 mice versus the SAMR1 ones, the glial index rose by 36% in layer III and by 24% in layer V. During simulation of physiological aging, the sizes of neuronal bodies were shown to be virtually unchanged in the cerebral cortex; the compactness of their arrangement (cell counts) moderately reduced and that of neuroglial cells increased, which caused a rise in the glioneuronal index that was indicative of the enhanced supporting function of neuroglial cells during the physiological aging of brain structures.

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

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.

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.

Brain-controlled applications using dynamic P300 speller matrices.

PubMed

Halder, Sebastian; Pinegger, Andreas; Käthner, Ivo; Wriessnegger, Selina C; Faller, Josef; Pires Antunes, João B; Müller-Putz, Gernot R; Kübler, Andrea

2015-01-01

Access to the world wide web and multimedia content is an important aspect of life. We present a web browser and a multimedia user interface adapted for control with a brain-computer interface (BCI) which can be used by severely motor impaired persons. The web browser dynamically determines the most efficient P300 BCI matrix size to select the links on the current website. This enables control of the web browser with fewer commands and smaller matrices. The multimedia player was based on an existing software. Both applications were evaluated with a sample of ten healthy participants and three end-users. All participants used a visual P300 BCI with face-stimuli for control. The healthy participants completed the multimedia player task with 90% accuracy and the web browsing task with 85% accuracy. The end-users completed the tasks with 62% and 58% accuracy. All healthy participants and two out of three end-users reported that they felt to be in control of the system. In this study we presented a multimedia application and an efficient web browser implemented for control with a BCI. Both applications provide access to important areas of modern information retrieval and entertainment. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

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

Open-label adjunctive creatine for female adolescents with SSRI-resistant major depressive disorder: a 31-phosphorus magnetic resonance spectroscopy study.

PubMed

Kondo, Douglas G; Sung, Young-Hoon; Hellem, Tracy L; Fiedler, Kristen K; Shi, Xianfeng; Jeong, Eun-Kee; Renshaw, Perry F

2011-12-01

Adolescent major depressive disorder (MDD) is a life-threatening brain disease with limited interventions. Treatment resistance is common, and the illness burden is disproportionately borne by females. 31-Phosphorus magnetic resonance spectroscopy ((31)P MRS) is a translational method for in vivo measurement of brain energy metabolites. We recruited 5 female adolescents who had been on fluoxetine (Prozac®) for ≥ 8 weeks, but continued meet diagnostic criteria for MDD with a Children's Depression Rating Scale-Revised (CDRS-R) raw score ≥ 40. Treatment response was measured with the CDRS-R. (31)P MRS brain scans were performed at baseline, and repeated following adjunctive creatine 4 g daily for 8 weeks. For comparison, 10 healthy female adolescents underwent identical brain scans performed 8 weeks apart. The mean CDRS-R score declined from 69 to 30.6, a decrease of 56%. Participants experienced no Serious Adverse Events, suicide attempts, hospitalizations or intentional self-harm. There were no unresolved treatment-emergent adverse effects or laboratory abnormalities. MDD participants' baseline CDRS-R score was correlated with baseline pH (p=0.04), and was negatively correlated with beta-nucleoside triphosphate (β-NTP) concentration (p=0.03). Compared to healthy controls, creatine-treated adolescents demonstrated a significant increase in brain Phosphocreatine (PCr) concentration (p=0.02) on follow-up (31)P MRS brain scans. Lack of placebo control; and small sample size. Further study of creatine as an adjunctive treatment for adolescents with SSRI-resistant MDD is warranted. Copyright © 2011 Elsevier B.V. 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.

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

Serum levels of natriuretic peptides in children with various types of loading conditions.

PubMed

Eerola, Anneli; Jokinen, Eero; Pihkala, Jaana I

2009-06-01

To evaluate the influence of volume overload of the left (LV) and right ventricle (RV) and pressure overload of LV and restrictive physiology on levels of N-terminal proatriopeptide (ANPN) and N-terminal pro-brain natriuretic peptide (NT-proBNP). We studied 41 children with atrial septal defect (ASD), 35 with patent ductus arteriosus (PDA), 27 with coarctation of the aorta (CoA), 25 with restrictive physiology caused by Mulibrey nanism, and 64 control children. We measured serum concentrations of natriuretic peptides and evaluated ventricular size and function with echocardiography. In patients with ASD, PDA, and Mulibrey nanism, levels of both ANPN and NT-proBNP were higher than in controls but in children with CoA, only ANPN levels were higher. ANPN levels correlated with RV size in ASD and NT-proBNP levels with LV size in PDA. In patients with restriction, NT-proBNP levels correlated negatively with LV size. Correlation between echo measurements and levels of natriuretic peptides varied according to loading condition. Measurement of natriuretic peptide levels provides a supplemental method for non-invasive haemodynamic evaluation of children's heart disease.

Corticalization of motor control in humans is a consequence of brain scaling in primate evolution.

PubMed

Herculano-Houzel, Suzana; Kaas, Jon H; de Oliveira-Souza, Ricardo

2016-02-15

Control over spinal and brainstem somatomotor neurons is exerted by two sets of descending fibers, corticospinal/pyramidal and extrapyramidal. Although in nonhuman primates the effect of bilateral pyramidal lesions is mostly limited to an impairment of the independent use of digits in skilled manual actions, similar injuries in humans result in the locked-in syndrome, a state of mutism and quadriplegia in which communication can be established only by residual vertical eye movements. This behavioral contrast makes humans appear to be outliers compared with other primates because of our almost total dependence on the corticospinal/pyramidal system for the effectuation of movement. Here we propose, instead, that an increasing preponderance of the corticospinal/pyramidal system over motor control is an expected consequence of increasing brain size in primates because of the faster scaling of the number of neurons in the primary motor cortex over the brainstem and spinal cord motor neuron pools, explaining the apparent uniqueness of the corticalization of motor control in humans. © 2015 Wiley Periodicals, Inc.

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.

A pilot randomized trial of two cognitive rehabilitation interventions for mild cognitive impairment: caregiver outcomes.

PubMed

Cuc, Andrea V; Locke, Dona E C; Duncan, Noah; Fields, Julie A; Snyder, Charlene Hoffman; Hanna, Sherrie; Lunde, Angela; Smith, Glenn E; Chandler, Melanie

2017-12-01

This study aims to provide effect size estimates of the impact of two cognitive rehabilitation interventions provided to patients with mild cognitive impairment: computerized brain fitness exercise and memory support system on support partners' outcomes of depression, anxiety, quality of life, and partner burden. A randomized controlled pilot trial was performed. At 6 months, the partners from both treatment groups showed stable to improved depression scores, while partners in an untreated control group showed worsening depression over 6 months. There were no statistically significant differences on anxiety, quality of life, or burden outcomes in this small pilot trial; however, effect sizes were moderate, suggesting that the sample sizes in this pilot study were not adequate to detect statistical significance. Either form of cognitive rehabilitation may help partners' mood, compared with providing no treatment. However, effect size estimates related to other partner outcomes (i.e., burden, quality of life, and anxiety) suggest that follow-up efficacy trials will need sample sizes of at least 30-100 people per group to accurately determine significance. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

[Neuroprotective effect of naloxone in brain damage caused by repeated febrile seizure].

PubMed

Shan, Ying; Qin, Jiong; Chang, Xing-zhi; Yang, Zhi-xian

2004-04-01

The brain damage caused by repeated febrile seizure (FS) during developing age is harmful to the intellectual development of children. So how to decrease the related damage is a very important issue. The main purpose of the present study was to find out whether the non-specific opiate antagonist naloxone at low dose has the neuroprotective effect on seizure-induced brain damage. Warm water induced rat FS model was developed in this study. Forty-seven rats were randomly divided into two groups: normal control group (n = 10) and hyperthermic seizure groups (n = 37). The latter was further divided into FS control group (n = 13) and naloxone-treated group (n = 24). The dose of naloxone is different in two naloxone-treated groups (12/each group), in one group the dose was 1 mg/kg, in the other one 2 mg/kg. Seven febrile seizures were induced in each rat of hyperthermic seizure groups with the interval of 2 days. The rats were weighed and injected intraperitoneally with naloxone once the FS occurred in naloxone-treated group, while the rats of the other groups were injected with 0.9% sodium chloride. Latency, duration and grade of FS in different groups were observed and compared. HE-staining and the electron microscopy (EM) were used to detect the morphologic and ultrastructural changes of hippocampal neurons. In naloxone-treated group, the rats' FS duration and FS grade (5.02 +/- 0.63, 2.63 +/- 0.72) were significantly lower (t = 5.508, P < 0.01; t = 8.439, P < 0.01) than those in FS control group (7.70 +/- 2.25 min, 4.52 +/- 0.49), although no significant gap was observed on FS latency between them. In FS control group, HE-staining pattern of hippocampal CA(1) and CA(2) showed lots of disordered neurons with confused polarity and vacuoles formed. Nuclei were with various size, some rounded and some oblong. While in naloxone-treated groups, the arrangement of neurons was regular, only a small quantity of neurons had changed polarity and vacuoles formed. Most nuclei were oblong and in the same size. In hippocampal CA(1) region and dentate gyrus of rats from FS control group, EM showed that the most mitochondrion volumes obviously increased with vacuoles formed, the matrix condensed, the ridge obscured or disappeared, apoptosis body emerged. Minor to moderate dilation of rough endoplasmic reticulum and Golgi's complex was also observed. However, in naloxone-treated groups, the number of neurons with swollen mitochondrion and endoplasmic reticulum was much fewer than that in FS control group. No apoptosis body was observed. The comparison between them showed much lighter brain damage in naloxone-treated groups than in FS control group. Although low-dose naloxone could not totally stop the occurrence of febrile seizure, it could lighten the brain damage resulted from repeated FS to some extent.

Prospective study of a community reintegration programme for patients with acquired chronic brain injury: effects on caregivers' emotional burden and family functioning.

PubMed

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

2011-01-01

To examine the effects of a residential community reintegration programme for patients with psychosocial problems due to acquired chronic brain injury on caregivers' emotional burden and family functioning. A prospective cohort study with waiting list control and 1-year follow-up. Forty-one caregivers of which 28 female. Mean age was 48 ± 8.3 years and 33 caregivers were parents. A structured residential treatment programme was offered to the patients directed at domestic life, work, leisure time and social interactions. The Involvement Evaluation Questionnaire for Brain Injury (IEQ-BI) for emotional burden, the General Health Questionnaire (GHQ) for psychological health and the Family Assessment Device (FAD) for family functioning were used. There was an overall significant effect of Time for all outcome measures (MANOVA T(2 )= 9.1, F(15,317) = 64.1, p = 0.000). The effect sizes were moderate for three IEQ-BI sub-scales (partial η(2 )= 0.12-0.17) and small for two sub-scales (partial η(2 )= 0.05-0.09). The effect size for GHQ was moderate (partial η(2 )= 0.11). As for FAD no significant time effects were present (partial η(2 )= 0.00-0.04). Emotional burden and psychological health of the caregivers improved significantly when patients with acquired brain injury and psychosocial problems followed a residential community reintegration programme. Family dynamics remained stable.

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

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.

Increased postischemic brain injury in mice deficient in uracil-DNA glycosylase

PubMed Central

Endres, Matthias; Biniszkiewicz, Detlev; Sobol, Robert W.; Harms, Christoph; Ahmadi, Michael; Lipski, Andreas; Katchanov, Juri; Mergenthaler, Philipp; Dirnagl, Ulrich; Wilson, Samuel H.; Meisel, Andreas; Jaenisch, Rudolf

2004-01-01

Uracil-DNA glycosylase (UNG) is involved in base excision repair of aberrant uracil residues in nuclear and mitochondrial DNA. Ung knockout mice generated by gene targeting are viable, fertile, and phenotypically normal and have regular mutation rates. However, when exposed to a nitric oxide donor, Ung–/– fibroblasts show an increase in the uracil/cytosine ratio in the genome and augmented cell death. After combined oxygen-glucose deprivation, Ung–/– primary cortical neurons have increased vulnerability to cell death, which is associated with early mitochondrial dysfunction. In vivo, UNG expression and activity are low in brains of naive WT mice but increase significantly after reversible middle cerebral artery occlusion and reperfusion. Moreover, major increases in infarct size are observed in Ung–/– mice compared with littermate control mice. In conclusion, our results provide compelling evidence that UNG is of major importance for tissue repair after brain ischemia. PMID:15199406

Encephalization quotients and life-history traits in the Sirenia

USGS Publications Warehouse

O'Shea, T.J.; Reep, R.L.

1990-01-01

Relative brain size in the Sirenia is unusually small. Encephalization quotients are 0.27 for Florida manatees (Trichechus manatus) and 0.38 for dugongs (Dugong dugon). Estimates for Steller's sea cow (Hydrodamalis gigas) range from 0.12 to 0.19. These values are among the lowest known for Recent mammals, and seemingly have changed little since the Eocene. A body plan specialized for the aquatic environment does not account for low encephalization quotients; values are substantially less than predicted based on cetacean or pinniped allometry. Life-history, ecological, and behavioral traits of the Sirenia are typical of relatively large-brained species. Low quality food and a low metabolic rate, however, are characteristic of the Sirenia and other small-brained mammals. Acting through prolonged postnatal growth, selection also likely favored large body size in the Sirenia without a correlated increase in brain size.

Organ size control via hydraulically gated oscillations.

PubMed

Ruiz-Herrero, Teresa; Alessandri, Kévin; Gurchenkov, Basile V; Nassoy, Pierre; Mahadevan, L

2017-12-01

Hollow vesicular tissues of various sizes and shapes arise in biological organs such as ears, guts, hearts, brains and even entire organisms. Regulating their size and shape is crucial for their function. Although chemical signaling has been thought to play a role in the regulation of cellular processes that feed into larger scales, it is increasingly recognized that mechanical forces are involved in the modulation of size and shape at larger length scales. Motivated by a variety of examples of tissue cyst formation and size control that show simultaneous growth and size oscillations, we create a minimal theoretical framework for the growth and dynamics of a soft, fluid-permeable, spherical shell. We show that these shells can relieve internal pressure by bursting intermittently, shrinking and re-growing, providing a simple mechanism by which hydraulically gated oscillations can regulate size. To test our theory, we develop an in vitro experimental set-up to monitor the growth and oscillations of a hollow tissue spheroid growing freely or when confined. A simple generalization of our theory to account for irreversible deformations allows us to explain the time scales and the amplitudes of oscillations in terms of the geometry and mechanical properties of the tissue shells. Taken together, our theory and experimental observations show how soft hydraulics can regulate the size of growing tissue shells. © 2017. Published by The Company of Biologists Ltd.

Neurologic manifestations of major electrolyte abnormalities.

PubMed

Diringer, M

2017-01-01

The brain operates in an extraordinarily intricate environment which demands precise regulation of electrolytes. Tight control over their concentrations and gradients across cellular compartments is essential and when these relationships are disturbed neurologic manifestations may develop. Perturbations of sodium are the electrolyte disturbances that most often lead to neurologic manifestations. Alterations in extracellular fluid sodium concentrations produce water shifts that lead to brain swelling or shrinkage. If marked or rapid they can result in profound changes in brain function which are proportional to the degree of cerebral edema or contraction. Adaptive mechanisms quickly respond to changes in cell size by either increasing or decreasing intracellular osmoles in order to restore size to normal. Unless cerebral edema has been severe or prolonged, correction of sodium disturbances usually restores function to normal. If the rate of correction is too rapid or overcorrection occurs, however, new neurologic manifestations may appear as a result of osmotic demyelination syndrome. Disturbances of magnesium, phosphate and calcium all may contribute to alterations in sensorium. Hypomagnesemia and hypocalcemia can lead to weakness, muscle spasms, and tetany; the weakness from hypophosphatemia and hypomagnesemia can impair respiratory function. Seizures can be seen in cases with very low concentrations of sodium, magnesium, calcium, and phosphate. © 2017 Elsevier B.V. All rights reserved.

Progesterone Treatment Shows Benefit in a Pediatric Model of Moderate to Severe Bilateral Brain Injury

PubMed Central

Geddes, Rastafa I.; Sribnick, Eric A.; Sayeed, Iqbal; Stein, Donald G.

2014-01-01

Purpose Controlled cortical impact (CCI) models in adult and aged Sprague-Dawley (SD) rats have been used extensively to study medial prefrontal cortex (mPFC) injury and the effects of post-injury progesterone treatment, but the hormone's effects after traumatic brain injury (TBI) in juvenile animals have not been determined. In the present proof-of-concept study we investigated whether progesterone had neuroprotective effects in a pediatric model of moderate to severe bilateral brain injury. Methods Twenty-eight-day old (PND 28) male Sprague Dawley rats received sham (n = 24) or CCI (n = 47) injury and were given progesterone (4, 8, or 16 mg/kg per 100 g body weight) or vehicle injections on post-injury days (PID) 1–7, subjected to behavioral testing from PID 9–27, and analyzed for lesion size at PID 28. Results The 8 and 16 mg/kg doses of progesterone were observed to be most beneficial in reducing the effect of CCI on lesion size and behavior in PND 28 male SD rats. Conclusion Our findings suggest that a midline CCI injury to the frontal cortex will reliably produce a moderate TBI comparable to what is seen in the adult male rat and that progesterone can ameliorate the injury-induced deficits. PMID:24489882

Recent trends in the development of nanophytobioactive compounds and delivery systems for their possible role in reducing oxidative stress in Parkinson’s disease models

PubMed Central

Ganesan, Palanivel; Ko, Hyun-Myung; Kim, In-Su; Choi, Dong-Kug

2015-01-01

Oxidative stress plays a very critical role in neurodegenerative diseases, such as Parkinson’s disease (PD), which is the second most common neurodegenerative disease among elderly people worldwide. Increasing evidence has suggested that phytobioactive compounds show enhanced benefits in cell and animal models of PD. Curcumin, resveratrol, ginsenosides, quercetin, and catechin are phyto-derived bioactive compounds with important roles in the prevention and treatment of PD. However, in vivo studies suggest that their concentrations are very low to cross blood–brain barrier thereby it limits bioavailability, stability, and dissolution at target sites in the brain. To overcome these problems, nanophytomedicine with the controlled size of 1–100 nm is used to maximize efficiency in the treatment of PD. Nanosizing of phytobioactive compounds enhances the permeability into the brain with maximized efficiency and stability. Several nanodelivery techniques, including solid lipid nanoparticles, nanostructured lipid carriers, nanoliposomes, and nanoniosomes can be used for controlled delivery of nanobioactive compounds to brain. Nanocompounds, such as ginsenosides (19.9 nm) synthesized using a nanoemulsion technique, showed enhanced bioavailability in the rat brain. Here, we discuss the most recent trends and applications in PD, including 1) the role of phytobioactive compounds in reducing oxidative stress and their bioavailability; 2) the role of nanotechnology in reducing oxidative stress during PD; 3) nanodelivery systems; and 4) various nanophytobioactive compounds and their role in PD. PMID:26604750

Exercise ameliorates neurocognitive impairments in a translational model of pediatric radiotherapy.

PubMed

Sahnoune, Iman; Inoue, Taeko; Kesler, Shelli R; Rodgers, Shaefali P; Sabek, Omaima M; Pedersen, Steen E; Zawaski, Janice A; Nelson, Katharine H; Ris, M Douglas; Leasure, J Leigh; Gaber, M Waleed

2018-04-09

While cranial radiation therapy (CRT) is an effective treatment, healthy areas surrounding irradiation sites are negatively affected. Frontal lobe functions involving attention, processing speed, and inhibition control are impaired. These deficits appear months to years after CRT and impair quality of life. Exercise has been shown to rejuvenate the brain and aid in recovery post-injury through its effects on neurogenesis and cognition. We developed a juvenile rodent CRT model that reproduces neurocognitive deficits. Next, we utilized the model to test whether exercise ameliorates these deficits. Fischer rats (31 days old) were irradiated with a fractionated dose of 4 Gy × 5 days, trained and tested at 6, 9, and 12 months post-CRT using 5-choice serial reaction time task. After testing, fixed rat brains were imaged using diffusion tensor imaging and immunohistochemistry. CRT caused early and lasting impairments in task acquisition, accuracy, and latency to correct response, as well as causing stunting of growth and changes in brain volume and diffusion. Exercising after irradiation improved acquisition, behavioral control, and processing speed, mitigated the stunting of brain size, and increased brain fiber numbers compared with sedentary CRT values. Further, exercise partially restored global connectome organization, including assortativity and characteristic path length, and while it did not improve the specific regional connections that were lowered by CRT, it appeared to remodel these connections by increasing connectivity between alternate regional pairs. Our data strongly suggest that exercise may be useful in combination with interventions aimed at improving cognitive outcome following pediatric CRT.

Regional homogeneity associated with overgeneral autobiographical memory of first-episode treatment-naive patients with major depressive disorder in the orbitofrontal cortex: A resting-state fMRI study.

PubMed

Liu, Yansong; Zhao, Xudong; Cheng, Zaohuo; Zhang, Fuquan; Chang, Jun; Wang, Haosen; Xie, Rukui; Wang, Zhiqiang; Cao, Leiming; Wang, Guoqiang

2017-02-01

Overgeneral autobiographical memory (OGM) is involved in the onset and maintenance of depression. Recent studies have shown correlations between OGM and alterations of some brain regions by using task-state functional magnetic resonance imaging (fMRI). However, the correlation between OGM and spontaneous brain activity in depression remains unclear. The purpose of this study was to determine whether patients with major depressive disorder (MDD) show abnormal regional homogeneity (ReHo) and, if so, whether the brain areas with abnormal ReHo are associated with OGM. Twenty five patients with MDD and 25 age-matched, sex-matched, and education-matched healthy controls underwent resting-state fMRI. All participants were also assessed by 17-item Hamilton Depression Rating Scale and autobiographical memory test. The ReHo method was used to analyze regional synchronization of spontaneous neuronal activity. Patients with MDD, compared to healthy controls, exhibited extensive ReHo abnormalities in some brain regions, including the frontal, temporal, and occipital cortex. Moreover, ReHo value of the orbitofrontal cortex was negatively correlated with OGM scores in patients with MDD. The sample size of this study was relatively small, and the influence of physiological noise was not completely excluded. These results suggest that abnormal ReHo of spontaneous brain activity in the orbitofrontal cortex may be involved in the pathophysiology of OGM in patients with MDD. Copyright © 2016 Elsevier B.V. All rights reserved.

A systematic review of peer mentoring interventions for people with traumatic brain injury.

PubMed

Morris, Richard Pg; Fletcher-Smith, Joanna C; Radford, Kathryn A

2017-08-01

This systematic review sought evidence concerning the effectiveness of peer mentoring for people with traumatic brain injury. Fourteen electronic databases were searched, including PsycINFO, MEDLINE, CINAHL, EMBASE and the Cochrane Library, from inception to September 21 2016. Ten grey literature databases, PROSPERO, two trials registers, reference lists and author citations were also searched. Studies which employed a model of one-to-one peer mentoring between traumatic brain injury survivors were included. Two reviewers independently screened all titles and abstracts before screening full texts of shortlisted studies. A third reviewer resolved disagreements. Two reviewers independently extracted data and assessed studies for quality and risk of bias. The search returned 753 records, including one identified through hand searching. 495 records remained after removal of duplicates and 459 were excluded after screening. Full texts were assessed for the remaining 36 studies and six met the inclusion criteria. All were conducted in the United States between 1996 and 2012 and employed a variety of designs including two randomised controlled trials. A total of 288 people with traumatic brain injury participated in the studies. No significant improvements in social activity level or social network size were found, but significant improvements were shown in areas including behavioural control, mood, coping and quality of life. There is limited evidence for the effectiveness of peer mentoring after traumatic brain injury. The available evidence comes from small-scale studies, of variable quality, without detailed information on the content of sessions or the 'active ingredient' of the interventions.

Syllabic encoding during overt speech production in Cantonese: Evidence from temporal brain responses.

PubMed

Wong, Andus Wing-Kuen; Wang, Jie; Ng, Tin-Yan; Chen, Hsuan-Chih

2016-10-01

The time course of phonological encoding in overt Cantonese disyllabic word production was investigated using a picture-word interference task with concurrent recording of the event-related brain potentials (ERPs). Participants were asked to name aloud individually presented pictures and ignore a distracting Chinese character. Participants' naming responses were faster, relative to an unrelated control, when the distractor overlapped with the target's word-initial or word-final syllables. Furthermore, ERP waves in the syllable-related conditions were more positive-going than those in the unrelated control conditions from 500ms to 650ms post target onset (i.e., a late positivity). The mean and peak amplitudes of this late positivity correlated with the size of phonological facilitation. More importantly, the onset of the late positivity associated with word-initial syllable priming was 44ms earlier than that associated with word-final syllable priming, suggesting that phonological encoding in overt speech runs incrementally and the encoding duration for one syllable unit is approximately 44ms. Although the size of effective phonological units might vary across languages, as suggested by previous speech production studies, the present data indicate that the incremental nature of phonological encoding is a universal mechanism. Copyright © 2016 Elsevier B.V. All rights reserved.

Effectiveness and feasibility of Socratic feedback to increase awareness of deficits in patients with acquired brain injury: Four single-case experimental design (SCED) studies.

PubMed

Schrijnemaekers, Anne-Claire M C; Winkens, Ieke; Rasquin, Sascha M C; Verhaeg, Annette; Ponds, Rudolf W H M; van Heugten, Caroline M

2018-06-29

To investigate the effectiveness and feasibility of a Socratic feedback programme to improve awareness of deficits in patients with acquired brain injury (ABI). Rehabilitation centre. Four patients with ABI with awareness problems. A series of single-case experimental design studies with random intervention starting points (A-B + maintenance design). Rate of trainer-feedback and self-control behaviour on everyday tasks, patient competency rating scale (PCRS), self-regulating skills interview (SRSI), hospital anxiety and depression scale. All patients needed less trainer feedback, the change was significant in 3 out of 4. One patient increased in overt self-corrective behaviour. SRSI performance increased in all patients (medium to strong effect size), and PCRS performance increased in two patients (medium and strong effect size). Mood and anxiety levels were elevated in one patient at the beginning of the training and decreased to normal levels at the end of the training. The feasibility of the programme was scored 9 out of 10. The Socratic feedback method is a promising intervention for improving awareness of deficits in patients with ABI. Controlled studies with larger populations are needed to draw more solid conclusions about the effect of this method.

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.

Laser technique for anatomical-functional study of the medial prefrontal cortex of the brain

NASA Astrophysics Data System (ADS)

Sanchez-Huerta, Laura; Hernandez, Adan; Ayala, Griselda; Marroquin, Javier; Silva, Adriana B.; Khotiaintsev, Konstantin S.; Svirid, Vladimir A.; Flores, Gonzalo; Khotiaintsev, Sergei N.

1999-05-01

The brain represents one of the most complex systems that we know yet. In its study, non-destructive methods -- in particular, behavioral studies play an important role. By alteration of brain functioning (e.g. by pharmacological means) and observation of consequent behavior changes an important information on brain organization and functioning is obtained. For inducing local alterations, permanent brain lesions are employed. However, for correct results this technique has to be quasi-non-destructive, i.e. not to affect the normal brain function. Hence, the lesions should be very small, accurate and applied precisely over the structure (e.g. the brain nucleus) of interest. These specifications are difficult to meet with the existing techniques for brain lesions -- specifically, neurotoxical, mechanical and electrical means because they result in too extensive damage. In this paper, we present new laser technique for quasi-non- destructive anatomical-functional mapping in vivo of the medial prefrontal cortex (MPFC) of the rat. The technique is based on producing of small-size, well-controlled laser- induced lesions over some areas of the MPFC. The anesthetized animals are subjected to stereotactic surgery and certain points of the MPFC are exposed the confined radiation of the 10 W cw CO2 laser. Subsequent behavioral changes observed in neonatal and adult animals as well as histological data prove effectiveness of this technology for anatomical- functional studies of the brain by areas, and as a treatment method for some pathologies.

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.

Maternal obesity increases inflammation and exacerbates damage following neonatal hypoxic-ischaemic brain injury in rats.

PubMed

Teo, Jonathan D; Morris, Margaret J; Jones, Nicole M

2017-07-01

In humans, maternal obesity is associated with an increase in the incidence of birth related difficulties. However, the impact of maternal obesity on the severity of brain injury in offspring is not known. Recent studies have found evidence of increased glial response and inflammatory mediators in the brains as a result of obesity in humans and rodents. We hypothesised that hypoxic-ischaemic (HI) brain injury is greater in neonatal offspring from obese rat mothers compared to lean controls. Female Sprague Dawley rats were randomly allocated to high fat (HFD, n=8) or chow (n=4) diet and mated with lean male rats. On postnatal day 7 (P7), male and female pups were randomly assigned to HI injury or control (C) groups. HI injury was induced by occlusion of the right carotid artery followed by 3h exposure to 8% oxygen, at 37°C. Control pups were removed from the mother for the same duration under ambient conditions. Righting behaviour was measured on day 1 and 7 following HI. The extent of brain injury was quantified in brain sections from P14 pups using cresyl violet staining and the difference in volume between brain hemispheres was measured. Before mating, HFD mothers were 11% heavier than Chow mothers (p<0.05, t-test). Righting reflex was delayed in offspring from HFD-fed mothers compared to the Chow mothers. The Chow-HI pups showed a loss in ipsilateral brain tissue, while the HFD-HI group had significantly greater loss. No significant difference was detected in brain volume between the HFD-C and Chow-C pups. When analysed on a per litter basis, the size of the injury was significantly correlated with maternal weight. Similar observations were made with neuronal staining showing a greater loss of neurons in the brain of offspring from HFD-mothers following HI compared to Chow. Astrocytes appeared to more hypertrophic and a greater number of microglia were present in the injured hemisphere in offspring from mothers on HFD. HI caused an increase in the proportion of amoeboid microglia and exposure to maternal HFD exacerbated this response. In the contralateral hemisphere, offspring exposed to maternal HFD displayed a reduced proportion of ramified microglia. Our data clearly demonstrate that maternal obesity can exacerbate the severity of brain damage caused by HI in neonatal offspring. Given that previous studies have shown enhanced inflammatory responses in offspring of obese mothers, these factors including gliosis and microglial infiltration are likely to contribute to enhanced brain injury. Copyright © 2016 Elsevier Inc. All rights reserved.

Two way controls of apoptotic regulators consign DmArgonaute-1 a better clasp on it

PubMed Central

Bag, Indira; SNCVL, Pushpavalli; Garikapati, Koteswara Rao; Bhadra, Utpal

2018-01-01

Argonaute family proteins are well conserved among all organisms. Its role in mitotic cell cycle progression and apoptotic cell elimination is poorly understood. Earlier we have established the contribution of Ago-1 in cell cycle control related to G2/M cyclin in Drosophila. Here we have extended our study in understanding the relationship of Ago-1 in regulating apoptosis during Drosophila development. Apoptosis play a critical role in controlling organ shape and size during development of multi cellular organism. Multifarious regulatory pathways control apoptosis during development among which highly conserved JNK (c-Jun N-terminal kinase) pathway play a crucial role. Here we have over expressed Ago-1 in Drosophila eye and brain by employing UAS (upstream activation sequence)-GAL4 system under the expression of eye and brain specific driver. Over expression of Ago-1 resulted in reduced number of ommatidia in the eye and produced smaller size brain in adult and larval Drosophila. A drastic reversal of the phenotype towards normal was observed upon introduction of a single copy of the dominant negative mutation of basket (bsk, Drosophila homolog of JNK) indicating an active and physical involvement of the bsk with Ago-1 in inducing developmental apoptotic process. Further study showed that Ago-1 stimulates phosphorylation of JNK through transforming growth factor-β activated kinase 1- hemipterous (Tak1-hep) axis of JNK pathway. JNK phosphorylation results in up regulation of pro-apoptotic genes head involution defective (hid), grim & reaper (rpr) and induces activation of Drosophila caspases (cysteinyl aspartate proteinases);DRONC (Death regulator Nedd2-like caspase), ICE (alternatively Drice, Death related ICE-like caspase) and DCP1 (Death caspase-1) by inhibiting apoptotic inhibitor protein DIAP1 (Death-associated inhibitor of apoptosis 1). Further, Ago-1 also inhibits miR-14 expression to trigger apoptosis. Our findings propose that Ago-1 acts as a key regulator in controlling cell death, tumor regression and stress response in metazoan providing a constructive bridge between RNAi machinery and cell death. PMID:29385168

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.

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.

The BRAIN TRIAL: a randomised, placebo controlled trial of a Bradykinin B2 receptor antagonist (Anatibant) in patients with traumatic brain injury.

PubMed

Shakur, Haleema; Andrews, Peter; Asser, Toomas; Balica, Laura; Boeriu, Cristian; Quintero, Juan Diego Ciro; Dewan, Yashbir; Druwé, Patrick; Fletcher, Olivia; Frost, Chris; Hartzenberg, Bennie; Mantilla, Jorge Mejia; Murillo-Cabezas, Francisco; Pachl, Jan; Ravi, Ramalingam R; Rätsep, Indrek; Sampaio, Cristina; Singh, Manmohan; Svoboda, Petr; Roberts, Ian

2009-12-03

Cerebral oedema is associated with significant neurological damage in patients with traumatic brain injury. Bradykinin is an inflammatory mediator that may contribute to cerebral oedema by increasing the permeability of the blood-brain barrier. We evaluated the safety and effectiveness of the non-peptide bradykinin B2 receptor antagonist Anatibant in the treatment of patients with traumatic brain injury. During the course of the trial, funding was withdrawn by the sponsor. Adults with traumatic brain injury and a Glasgow Coma Scale score of 12 or less, who had a CT scan showing an intracranial abnormality consistent with trauma, and were within eight hours of their injury were randomly allocated to low, medium or high dose Anatibant or to placebo. Outcomes were Serious Adverse Events (SAE), mortality 15 days following injury and in-hospital morbidity assessed by the Glasgow Coma Scale (GCS), the Disability Rating Scale (DRS) and a modified version of the Oxford Handicap Scale (HIREOS). 228 patients out of a planned sample size of 400 patients were randomised. The risk of experiencing one or more SAEs was 26.4% (43/163) in the combined Anatibant treated group, compared to 19.3% (11/57) in the placebo group (relative risk = 1.37; 95% CI 0.76 to 2.46). All cause mortality in the Anatibant treated group was 19% and in the placebo group 15.8% (relative risk 1.20, 95% CI 0.61 to 2.36). The mean GCS at discharge was 12.48 in the Anatibant treated group and 13.0 in the placebo group. Mean DRS was 11.18 Anatibant versus 9.73 placebo, and mean HIREOS was 3.94 Anatibant versus 3.54 placebo. The differences between the mean levels for GCS, DRS and HIREOS in the Anatibant and placebo groups, when adjusted for baseline GCS, showed a non-significant trend for worse outcomes in all three measures. This trial did not reach the planned sample size of 400 patients and consequently, the study power to detect an increase in the risk of serious adverse events was reduced. This trial provides no reliable evidence of benefit or harm and a larger trial would be needed to establish safety and effectiveness. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN23625128.

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.

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.

Effect of the Mediterranean diet on cognition and brain morphology and function: a systematic review of randomized controlled trials.

PubMed

Radd-Vagenas, Sue; Duffy, Shantel L; Naismith, Sharon L; Brew, Bruce J; Flood, Victoria M; Fiatarone Singh, Maria A

2018-03-01

Observational studies of the Mediterranean diet suggest cognitive benefits, potentially reducing dementia risk. We performed the first published review to our knowledge of randomized controlled trials (RCTs) investigating Mediterranean diet effects on cognition or brain morphology and function, with an additional focus on intervention diet quality and its relation to "traditional" Mediterranean dietary patterns. We searched 9 databases from inception (final update December 2017) for RCTs testing a Mediterranean compared with alternate diet for cognitive or brain morphology and function outcomes. Analyses were based on 66 cognitive tests and 1 brain function outcome from 5 included studies (n = 1888 participants). The prescribed Mediterranean diets varied considerably between studies, particularly with regards to quantitative food advice. Only 8/66 (12.1%) of individual cognitive outcomes at trial level significantly favored a Mediterranean diet for cognitive performance, with effect sizes (ESs) ranging from small (0.32) to large (1.66), whereas 2 outcomes favored controls. Data limitations precluded a meta-analysis. Of 8 domain composite cognitive scores from 2 studies, the 3 (Memory, Frontal, and Global function) from PREDIMED (PREvención con DIeta MEDiterránea) were significant, with ESs ranging from 0.39 to 1.29. A posttest comparison at a second PREDIMED site found that the Mediterranean diet modulates the effect of several genotypes associated with dementia risk for some cognitive outcomes, with mixed results. Finally, the risk of low-plasma brain-derived neurotrophic factor was reduced by 78% (OR = 0.22; 95% CI: 0.05, 0.90) in those who consumed a Mediterranean diet compared to control diet at 3 y in this trial. There was no benefit of the Mediterranean diet for incident cognitive impairment or dementia. Five RCTs of the Mediterranean diet and cognition have been published to date. The data are mostly nonsignificant, with small ESs. However, the significant improvements in cognitive domain composites in the most robustly designed study warrant additional research.

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.

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.

Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group

PubMed Central

Schmaal, L; Hibar, D P; Sämann, P G; Hall, G B; Baune, B T; Jahanshad, N; Cheung, J W; van Erp, T G M; Bos, D; Ikram, M A; Vernooij, M W; Niessen, W J; Tiemeier, H; Hofman, A; Wittfeld, K; Grabe, H J; Janowitz, D; Bülow, R; Selonke, M; Völzke, H; Grotegerd, D; Dannlowski, U; Arolt, V; Opel, N; Heindel, W; Kugel, H; Hoehn, D; Czisch, M; Couvy-Duchesne, B; Rentería, M E; Strike, L T; Wright, M J; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Martin, N G; Gillespie, N A; Goya-Maldonado, R; Gruber, O; Krämer, B; Hatton, S N; Lagopoulos, J; Hickie, I B; Frodl, T; Carballedo, A; Frey, E M; van Velzen, L S; Penninx, B W J H; van Tol, M-J; van der Wee, N J; Davey, C G; Harrison, B J; Mwangi, B; Cao, B; Soares, J C; Veer, I M; Walter, H; Schoepf, D; Zurowski, B; Konrad, C; Schramm, E; Normann, C; Schnell, K; Sacchet, M D; Gotlib, I H; MacQueen, G M; Godlewska, B R; Nickson, T; McIntosh, A M; Papmeyer, M; Whalley, H C; Hall, J; Sussmann, J E; Li, M; Walter, M; Aftanas, L; Brack, I; Bokhan, N A; Thompson, P M; Veltman, D J

2017-01-01

The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: −0.10 to −0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: −0.26 to −0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life. PMID:27137745

Disorder-specific volumetric brain difference in adolescent major depressive disorder and bipolar depression.

PubMed

MacMaster, Frank P; Carrey, Normand; Langevin, Lisa Marie; Jaworska, Natalia; Crawford, Susan

2014-03-01

Structural abnormalities in frontal, limbic and subcortical regions have been noted in adults with both major depressive disorder (MDD) and bipolar disorder (BD). In the current study, we examined regional brain morphology in youth with MDD and BD as compared to controls. Regional brain volumes were measured in 32 MDD subjects (15.7 ± 2.1 years), 14 BD subjects (16.0 ± 2.4 years) and 22 healthy controls (16.0 ± 2.8 years) using magnetic resonance imaging (MRI). Regions of interest included the hippocampus, dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), caudate, putamen and thalamus. Volumetric differences between groups were significant (F26,80 = 1.80, p = 0.02). Post-hoc analyses indicated that individuals with MDD showed reduced left hippocampus volumes (p = 0.048) as well as right ACC white and gray matter volumes (p = 0.003; p = 0.01) compared to controls. BD participants also displayed reduced left hippocampal and right/left putamen volumes compared to controls (p < 0.001; p = 0.015; p = 0.046 respectively). Interestingly, right and left ACC white matter volumes were smaller in MDD than in BD participants (p = 0.019; p = 0.045 respectively). No volumetric group differences were observed for the DLPFC and thalamus. Discriminant analysis was able to correctly classify 81.0 % of subjects as having BD or as MDD based on imaging data. Confirmation and extension of our findings requires larger sample sizes. Our findings provide new evidence of distinct, specific regional brain volumetric differences between MDD and BD that may be used to distinguish the two disorders.

Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group.

PubMed

Schmaal, L; Hibar, D P; Sämann, P G; Hall, G B; Baune, B T; Jahanshad, N; Cheung, J W; van Erp, T G M; Bos, D; Ikram, M A; Vernooij, M W; Niessen, W J; Tiemeier, H; Hofman, A; Wittfeld, K; Grabe, H J; Janowitz, D; Bülow, R; Selonke, M; Völzke, H; Grotegerd, D; Dannlowski, U; Arolt, V; Opel, N; Heindel, W; Kugel, H; Hoehn, D; Czisch, M; Couvy-Duchesne, B; Rentería, M E; Strike, L T; Wright, M J; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Martin, N G; Gillespie, N A; Goya-Maldonado, R; Gruber, O; Krämer, B; Hatton, S N; Lagopoulos, J; Hickie, I B; Frodl, T; Carballedo, A; Frey, E M; van Velzen, L S; Penninx, B W J H; van Tol, M-J; van der Wee, N J; Davey, C G; Harrison, B J; Mwangi, B; Cao, B; Soares, J C; Veer, I M; Walter, H; Schoepf, D; Zurowski, B; Konrad, C; Schramm, E; Normann, C; Schnell, K; Sacchet, M D; Gotlib, I H; MacQueen, G M; Godlewska, B R; Nickson, T; McIntosh, A M; Papmeyer, M; Whalley, H C; Hall, J; Sussmann, J E; Li, M; Walter, M; Aftanas, L; Brack, I; Bokhan, N A; Thompson, P M; Veltman, D J

2017-06-01

The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.

A Preliminary Comparison of Motor Learning Across Different Non-invasive Brain Stimulation Paradigms Shows No Consistent Modulations.

PubMed

Lopez-Alonso, Virginia; Liew, Sook-Lei; Fernández Del Olmo, Miguel; Cheeran, Binith; Sandrini, Marco; Abe, Mitsunari; Cohen, Leonardo G

2018-01-01

Non-invasive brain stimulation (NIBS) has been widely explored as a way to safely modulate brain activity and alter human performance for nearly three decades. Research using NIBS has grown exponentially within the last decade with promising results across a variety of clinical and healthy populations. However, recent work has shown high inter-individual variability and a lack of reproducibility of previous results. Here, we conducted a small preliminary study to explore the effects of three of the most commonly used excitatory NIBS paradigms over the primary motor cortex (M1) on motor learning (Sequential Visuomotor Isometric Pinch Force Tracking Task) and secondarily relate changes in motor learning to changes in cortical excitability (MEP amplitude and SICI). We compared anodal transcranial direct current stimulation (tDCS), paired associative stimulation (PAS 25 ), and intermittent theta burst stimulation (iTBS), along with a sham tDCS control condition. Stimulation was applied prior to motor learning. Participants ( n = 28) were randomized into one of the four groups and were trained on a skilled motor task. Motor learning was measured immediately after training (online), 1 day after training (consolidation), and 1 week after training (retention). We did not find consistent differential effects on motor learning or cortical excitability across groups. Within the boundaries of our small sample sizes, we then assessed effect sizes across the NIBS groups that could help power future studies. These results, which require replication with larger samples, are consistent with previous reports of small and variable effect sizes of these interventions on motor learning.

A Preliminary Comparison of Motor Learning Across Different Non-invasive Brain Stimulation Paradigms Shows No Consistent Modulations

PubMed Central

Lopez-Alonso, Virginia; Liew, Sook-Lei; Fernández del Olmo, Miguel; Cheeran, Binith; Sandrini, Marco; Abe, Mitsunari; Cohen, Leonardo G.

2018-01-01

Non-invasive brain stimulation (NIBS) has been widely explored as a way to safely modulate brain activity and alter human performance for nearly three decades. Research using NIBS has grown exponentially within the last decade with promising results across a variety of clinical and healthy populations. However, recent work has shown high inter-individual variability and a lack of reproducibility of previous results. Here, we conducted a small preliminary study to explore the effects of three of the most commonly used excitatory NIBS paradigms over the primary motor cortex (M1) on motor learning (Sequential Visuomotor Isometric Pinch Force Tracking Task) and secondarily relate changes in motor learning to changes in cortical excitability (MEP amplitude and SICI). We compared anodal transcranial direct current stimulation (tDCS), paired associative stimulation (PAS25), and intermittent theta burst stimulation (iTBS), along with a sham tDCS control condition. Stimulation was applied prior to motor learning. Participants (n = 28) were randomized into one of the four groups and were trained on a skilled motor task. Motor learning was measured immediately after training (online), 1 day after training (consolidation), and 1 week after training (retention). We did not find consistent differential effects on motor learning or cortical excitability across groups. Within the boundaries of our small sample sizes, we then assessed effect sizes across the NIBS groups that could help power future studies. These results, which require replication with larger samples, are consistent with previous reports of small and variable effect sizes of these interventions on motor learning. PMID:29740271

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

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.

Silymarin improves the behavioural, biochemical and histoarchitecture alterations in focal ischemic rats: a comparative evaluation with piracetam and protocatachuic acid.

PubMed

Muley, Milind M; Thakare, Vishnu N; Patil, Rajesh R; Kshirsagar, Ajay D; Naik, Suresh R

2012-08-01

Comparative neuroprotective potential of silymarin, piracetam and protocatechuic acid ethyl ester (PCA) was evaluated in focal ischemic rats. Various pharmacological, biochemical (lipid peroxidation, reduced glutathione, catalase, nitrite content, brain water content) and behavioural (memory impairment, motor control, neurological score) including infarct size and histopathological alterations were evaluated. Silymarin (200mg/kg) and PCA treatment significantly improved behavioural, biochemical and histopathological changes, and reduced water content and infarct size. However, piracetam only improved behavioural and histopathological changes, reduced water content and infarct size. The findings indicate that silymarin exhibits neuroprotective activity better than PCA and piracetam in focal ischemia/reperfusion reflected by its better restoration of behavioural and antioxidant profile. Copyright © 2012 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.

Implanted Miniaturized Antenna for Brain Computer Interface Applications: Analysis and Design

PubMed Central

Zhao, Yujuan; Rennaker, Robert L.; Hutchens, Chris; Ibrahim, Tamer S.

2014-01-01

Implantable Brain Computer Interfaces (BCIs) are designed to provide real-time control signals for prosthetic devices, study brain function, and/or restore sensory information lost as a result of injury or disease. Using Radio Frequency (RF) to wirelessly power a BCI could widely extend the number of applications and increase chronic in-vivo viability. However, due to the limited size and the electromagnetic loss of human brain tissues, implanted miniaturized antennas suffer low radiation efficiency. This work presents simulations, analysis and designs of implanted antennas for a wireless implantable RF-powered brain computer interface application. The results show that thin (on the order of 100 micrometers thickness) biocompatible insulating layers can significantly impact the antenna performance. The proper selection of the dielectric properties of the biocompatible insulating layers and the implantation position inside human brain tissues can facilitate efficient RF power reception by the implanted antenna. While the results show that the effects of the human head shape on implanted antenna performance is somewhat negligible, the constitutive properties of the brain tissues surrounding the implanted antenna can significantly impact the electrical characteristics (input impedance, and operational frequency) of the implanted antenna. Three miniaturized antenna designs are simulated and demonstrate that maximum RF power of up to 1.8 milli-Watts can be received at 2 GHz when the antenna implanted around the dura, without violating the Specific Absorption Rate (SAR) limits. PMID:25079941

Learning performance and brain structure of artificially-reared honey bees fed with different quantities of food

PubMed Central

Spaethe, Johannes; Steffan-Dewenter, Ingolf; Härtel, Stephan

2017-01-01

Background Artificial rearing of honey bee larvae is an established method which enables to fully standardize the rearing environment and to manipulate the supplied diet to the brood. However, there are no studies which compare learning performance or neuroanatomic differences of artificially-reared (in-lab) bees in comparison with their in-hive reared counterparts. Methods Here we tested how different quantities of food during larval development affect body size, brain morphology and learning ability of adult honey bees. We used in-lab rearing to be able to manipulate the total quantity of food consumed during larval development. After hatching, a subset of the bees was taken for which we made 3D reconstructions of the brains using confocal laser-scanning microscopy. Learning ability and memory formation of the remaining bees was tested in a differential olfactory conditioning experiment. Finally, we evaluated how bees reared with different quantities of artificial diet compared to in-hive reared bees. Results Thorax and head size of in-lab reared honey bees, when fed the standard diet of 160 µl or less, were slightly smaller than hive bees. The brain structure analyses showed that artificially reared bees had smaller mushroom body (MB) lateral calyces than their in-hive counterparts, independently of the quantity of food they received. However, they showed the same total brain size and the same associative learning ability as in-hive reared bees. In terms of mid-term memory, but not early long-term memory, they performed even better than the in-hive control. Discussion We have demonstrated that bees that are reared artificially (according to the Aupinel protocol) and kept in lab-conditions perform the same or even better than their in-hive sisters in an olfactory conditioning experiment even though their lateral calyces were consistently smaller at emergence. The applied combination of experimental manipulation during the larval phase plus subsequent behavioral and neuro-anatomic analyses is a powerful tool for basic and applied honey bee research. PMID:29085743

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.

Detection of reduced interhemispheric cortical communication during task execution in multiple sclerosis patients using functional near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Jimenez, Jon J.; Yang, Runze; Nathoo, Nabeela; Varshney, Vishal P.; Golestani, Ali-Mohammad; Goodyear, Bradley G.; Metz, Luanne M.; Dunn, Jeff F.

2014-07-01

Multiple sclerosis (MS) impairs brain activity through demyelination and loss of axons. Increased brain activity is accompanied by increases in microvascular hemoglobin oxygen saturation (oxygenation) and total hemoglobin, which can be measured using functional near-infrared spectroscopy (fNIRS). Due to the potentially reduced size and integrity of the white matter tracts within the corpus callosum, it may be expected that MS patients have reduced functional communication between the left and right sides of the brain; this could potentially be an indicator of disease progression. To assess interhemispheric communication in MS, we used fNIRS during a unilateral motor task and the resting state. The magnitude of the change in hemoglobin parameters in the motor cortex was significantly reduced in MS patients during the motor task relative to healthy control subjects. There was also a significant decrease in interhemispheric communication between the motor cortices (expressed as coherence) in MS patients compared to controls during the motor task, but not during the resting state. fNIRS assessment of interhemispheric coherence during task execution may be a useful marker in disorders with white matter damage or axonal loss, including MS.

Neuroprotective effect of p-coumaric acid in mice with cerebral ischemia reperfusion injuries.

PubMed

Sakamula, Romgase; Thong-Asa, Wachiryah

2018-06-01

Cerebral ischemia reperfusion (IR) is associated with neuronal death, which leads to disability and cognitive decline. The pathomechanism occurs because ischemia is exacerbated during the reperfusion period. Neuronal damage susceptibility depends on the affected brain areas and the duration of ischemia. Prevention and supplementation to neurons may help them endure during IR and further benefit them in rehabilitation. We investigated the protective effect of p-coumaric acid (PC) on cerebral IR injuries in mice. We randomly divided 30 male ICR mice into 3 groups of Sham (received vehicle and not induced IR), Control-IR (received vehicle and induced IR) and PC-IR (received 100 mg/kg PC and induced IR). We orally administered vehicle or 100 mg/kg of p-coumaric acid for 2 weeks before inducing the cerebral IR injuries by using 30 min of a bilateral common carotid artery occlusion followed by a 45-min reperfusion. We induced the IR condition in the Control-IR and PC-IR groups but not the Sham group, and only the PC-IR group received p-coumaric acid. After IR induction, we sacrificed all the mice and collected their brain tissues to evaluate their oxidative statuses, whole brain infarctions and vulnerable neuronal deaths. We studied the whole-brain infarction volume by 2, 3, 5-triethyltetrazoliumchloride staining of sections. We performed a histological investigation of the vulnerable neuronal population in the dorsal hippocampus by staining brain sections with 0.1% cresyl violet. The results indicated that IR caused significant increases in calcium and malondialdehyde (MDA) levels, whole brain infarction volume and hippocampal neuronal death. Pretreatment with p-coumaric acid significantly reduced MDA levels, whole-brain infarction volume and hippocampal neuronal death together and increased catalase and superoxide dismutase activities. We conclude here that pretreating animals with p-coumaric acid can prevent IR-induced brain oxidative stress, infarction size and neuronal vulnerability to death in cerebral IR injuries.

Glibenclamide reduces secondary brain damage after experimental traumatic brain injury.

PubMed

Zweckberger, K; Hackenberg, K; Jung, C S; Hertle, D N; Kiening, K L; Unterberg, A W; Sakowitz, O W

2014-07-11

Following traumatic brain injury (TBI) SUR1-regulated NCCa-ATP (SUR1/TRPM4) channels are transcriptionally up-regulated in ischemic astrocytes, neurons, and capillaries. ATP depletion results in depolarization and opening of the channel leading to cytotoxic edema. Glibenclamide is an inhibitor of SUR-1 and, thus, might prevent cytotoxic edema and secondary brain damage following TBI. Anesthetized adult Sprague-Dawley rats underwent parietal craniotomy and were subjected to controlled cortical impact injury (CCI). Glibenclamide was administered as a bolus injection 15min after CCI injury and continuously via osmotic pumps throughout 7days. In an acute trial (180min) mean arterial blood pressure, heart rate, intracranial pressure, encephalographic activity, and cerebral metabolism were monitored. Brain water content was assessed gravimetrically 24h after CCI injury and contusion volumes were measured by MRI scanning technique at 8h, 24h, 72h, and 7d post injury. Throughout the entire time of observation neurological function was quantified using the "beam-walking" test. Glibenclamide-treated animals showed a significant reduction in the development of brain tissue water content(80.47%±0.37% (glibenclamide) vs. 80.83%±0.44% (control); p<0.05; n=14). Contusion sizes increased continuously within 72h following CCI injury, but glibenclamide-treated animals had significantly smaller volumes at any time-points, like 172.53±38.74mm(3) (glibenclamide) vs. 299.20±64.02mm(3) (control) (p<0.01; n=10; 24h) or 211.10±41.03mm(3) (glibenclamide) vs. 309.76±19.45mm(3) (control) (p<0.05; n=10; 72h), respectively. An effect on acute parameters, however, could not be detected, most likely because of the up-regulation of the channel within 3-6h after injury. Furthermore, there was no significant effect on motor function assessed by the beam-walking test throughout 7days. In accordance to these results and the available literature, glibenclamide seems to have promising potency in the treatment of TBI. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Very Early Brain Damage Leads to Remodeling of the Working Memory System in Adulthood: A Combined fMRI/Tractography Study

PubMed Central

Karolis, Vyacheslav; Caldinelli, Chiara; Brittain, Philip J.; Kroll, Jasmin; Rodríguez-Toscano, Elisa; Tesse, Marcello; Colquhoun, Matthew; Howes, Oliver; Dell'Acqua, Flavio; Thiebaut de Schotten, Michel; Murray, Robin M.; Williams, Steven C.R.; Nosarti, Chiara

2015-01-01

The human brain can adapt to overcome injury even years after an initial insult. One hypothesis states that early brain injury survivors, by taking advantage of critical periods of high plasticity during childhood, should recover more successfully than those who suffer injury later in life. This hypothesis has been challenged by recent studies showing worse cognitive outcome in individuals with early brain injury, compared with individuals with later brain injury, with working memory particularly affected. We invited individuals who suffered perinatal brain injury (PBI) for an fMRI/diffusion MRI tractography study of working memory and hypothesized that, 30 years after the initial injury, working memory deficits in the PBI group would remain, despite compensatory activation in areas outside the typical working memory network. Furthermore we hypothesized that the amount of functional reorganization would be related to the level of injury to the dorsal cingulum tract, which connects medial frontal and parietal working memory structures. We found that adults who suffered PBI did not significantly differ from controls in working memory performance. They exhibited less activation in classic frontoparietal working memory areas and a relative overactivation of bilateral perisylvian cortex compared with controls. Structurally, the dorsal cingulum volume and hindrance-modulated orientational anisotropy was significantly reduced in the PBI group. Furthermore there was uniquely in the PBI group a significant negative correlation between the volume of this tract and activation in the bilateral perisylvian cortex and a positive correlation between this activation and task performance. This provides the first evidence of compensatory plasticity of the working memory network following PBI. SIGNIFICANCE STATEMENT Here we used the example of perinatal brain injury (PBI) associated with very preterm birth to study the brain's ability to adapt to injury sustained early in life. In adulthood, individuals with PBI did not show significant deficits in working memory, but exhibited less activation in typical frontoparietal working memory areas. They also showed a relative overactivation of nontask-specific brain areas (perisylvian cortex) compared with controls, and such activation was negatively correlated with the size of white matter pathways involved in working memory (dorsal cingulum). Furthermore, this “extra” activation was associated with better working memory performance and could represent a novel compensatory mechanism following PBI. Such information could inform the development of neuroscience-based cognitive interventions following PBI. PMID:26631462

Voluntary Exercise Preconditioning Activates Multiple Antiapoptotic Mechanisms and Improves Neurological Recovery after Experimental Traumatic Brain Injury

PubMed Central

Zhao, Zaorui; Sabirzhanov, Boris; Wu, Junfang; Faden, Alan I.

2015-01-01

Abstract Physical activity can attenuate neuronal loss, reduce neuroinflammation, and facilitate recovery after brain injury. However, little is known about the mechanisms of exercise-induced neuroprotection after traumatic brain injury (TBI) or its modulation of post-traumatic neuronal cell death. Voluntary exercise, using a running wheel, was conducted for 4 weeks immediately preceding (preconditioning) moderate-level controlled cortical impact (CCI), a well-established experimental TBI model in mice. Compared to nonexercised controls, exercise preconditioning (pre-exercise) improved recovery of sensorimotor performance in the beam walk task, as well as cognitive/affective functions in the Morris water maze, novel object recognition, and tail-suspension tests. Further, pre-exercise reduced lesion size, attenuated neuronal loss in the hippocampus, cortex, and thalamus, and decreased microglial activation in the cortex. In addition, exercise preconditioning activated the brain-derived neurotrophic factor pathway before trauma and amplified the injury-dependent increase in heat shock protein 70 expression, thus attenuating key apoptotic pathways. The latter include reduction in CCI-induced up-regulation of proapoptotic B-cell lymphoma 2 (Bcl-2)-homology 3–only Bcl-2 family molecules (Bid, Puma), decreased mitochondria permeabilization with attenuated release of cytochrome c and apoptosis-inducing factor (AIF), reduced AIF translocation to the nucleus, and attenuated caspase activation. Given these neuroprotective actions, voluntary physical exercise may serve to limit the consequences of TBI. PMID:25419789

A novel approach to quantify different iron forms in ex-vivo human brain tissue

NASA Astrophysics Data System (ADS)

Kumar, Pravin; Bulk, Marjolein; Webb, Andrew; van der Weerd, Louise; Oosterkamp, Tjerk H.; Huber, Martina; Bossoni, Lucia

2016-12-01

We propose a novel combination of methods to study the physical properties of ferric ions and iron-oxide nanoparticles in post-mortem human brain, based on the combination of Electron Paramagnetic Resonance (EPR) and SQUID magnetometry. By means of EPR, we derive the concentration of the low molecular weight iron pool, as well as the product of its electron spin relaxation times. Additionally, by SQUID magnetometry we identify iron mineralization products ascribable to a magnetite/maghemite phase and a ferrihydrite (ferritin) phase. We further derive the concentration of magnetite/maghemite and of ferritin nanoparticles. To test out the new combined methodology, we studied brain tissue of an Alzheimer’s patient and a healthy control. Finally, we estimate that the size of the magnetite/maghemite nanoparticles, whose magnetic moments are blocked at room temperature, exceeds 40-50 nm, which is not compatible with the ferritin protein, the core of which is typically 6-8 nm. We believe that this methodology could be beneficial in the study of neurodegenerative diseases such as Alzheimer’s Disease which are characterized by abnormal iron accumulation in the brain.

Self-Assembly of Gold Nanoparticles Shows Microenvironment-Mediated Dynamic Switching and Enhanced Brain Tumor Targeting

PubMed Central

Feng, Qishuai; Shen, Yajing; Fu, Yingjie; Muroski, Megan E.; Zhang, Peng; Wang, Qiaoyue; Xu, Chang; Lesniak, Maciej S.; Li, Gang; Cheng, Yu

2017-01-01

Inorganic nanoparticles with unique physical properties have been explored as nanomedicines for brain tumor treatment. However, the clinical applications of the inorganic formulations are often hindered by the biological barriers and failure to be bioeliminated. The size of the nanoparticle is an essential design parameter which plays a significant role to affect the tumor targeting and biodistribution. Here, we report a feasible approach for the assembly of gold nanoparticles into ~80 nm nanospheres as a drug delivery platform for enhanced retention in brain tumors with the ability to be dynamically switched into the single formulation for excretion. These nanoassemblies can target epidermal growth factor receptors on cancer cells and are responsive to tumor microenvironmental characteristics, including high vascular permeability and acidic and redox conditions. Anticancer drug release was controlled by a pH-responsive mechanism. Intracellular L-glutathione (GSH) triggered the complete breakdown of nanoassemblies to single gold nanoparticles. Furthermore, in vivo studies have shown that nanospheres display enhanced tumor-targeting efficiency and therapeutic effects relative to single-nanoparticle formulations. Hence, gold nanoassemblies present an effective targeting strategy for brain tumor treatment. PMID:28638474

A miniaturized neuroprosthesis suitable for implantation into the brain

NASA Technical Reports Server (NTRS)

Mojarradi, Mohammad; Binkley, David; Blalock, Benjamin; Andersen, Richard; Ulshoefer, Norbert; Johnson, Travis; Del Castillo, Linda

2003-01-01

This paper presents current research on a miniaturized neuroprosthesis suitable for implantation into the brain. The prosthesis is a heterogeneous integration of a 100-element microelectromechanical system (MEMS) electrode array, front-end complementary metal-oxide-semiconductor (CMOS) integrated circuit for neural signal preamplification, filtering, multiplexing and analog-to-digital conversion, and a second CMOS integrated circuit for wireless transmission of neural data and conditioning of wireless power. The prosthesis is intended for applications where neural signals are processed and decoded to permit the control of artificial or paralyzed limbs. This research, if successful, will allow implantation of the electronics into the brain, or subcutaneously on the skull, and eliminate all external signal and power wiring. The neuroprosthetic system design has strict size and power constraints with each of the front-end preamplifier channels fitting within the 400 x 400-microm pitch of the 100-element MEMS electrode array and power dissipation resulting in less than a 1 degree C temperature rise for the surrounding brain tissue. We describe the measured performance of initial micropower low-noise CMOS preamplifiers for the neuroprosthetic.

Laser Desorption/Ionization Mass Spectrometric Imaging of Endogenous Lipids from Rat Brain Tissue Implanted with Silver Nanoparticles

NASA Astrophysics Data System (ADS)

Muller, Ludovic; Baldwin, Kathrine; Barbacci, Damon C.; Jackson, Shelley N.; Roux, Aurélie; Balaban, Carey D.; Brinson, Bruce E.; McCully, Michael I.; Lewis, Ernest K.; Schultz, J. Albert; Woods, Amina S.

2017-08-01

Mass spectrometry imaging (MSI) of tissue implanted with silver nanoparticulate (AgNP) matrix generates reproducible imaging of lipids in rodent models of disease and injury. Gas-phase production and acceleration of size-selected 8 nm AgNP is followed by controlled ion beam rastering and soft landing implantation of 500 eV AgNP into tissue. Focused 337 nm laser desorption produces high quality images for most lipid classes in rat brain tissue (in positive mode: galactoceramides, diacylglycerols, ceramides, phosphatidylcholines, cholesteryl ester, and cholesterol, and in negative ion mode: phosphatidylethanolamides, sulfatides, phosphatidylinositol, and sphingomyelins). Image reproducibility in serial sections of brain tissue is achieved within <10% tolerance by selecting argentated instead of alkali cationized ions. The imaging of brain tissues spotted with pure standards was used to demonstrate that Ag cationized ceramide and diacylglycerol ions are from intact, endogenous species. In contrast, almost all Ag cationized fatty acid ions are a result of fragmentations of numerous lipid types having the fatty acid as a subunit. Almost no argentated intact fatty acid ions come from the pure fatty acid standard on tissue.

Self-Assembly of Gold Nanoparticles Shows Microenvironment-Mediated Dynamic Switching and Enhanced Brain Tumor Targeting.

PubMed

Feng, Qishuai; Shen, Yajing; Fu, Yingjie; Muroski, Megan E; Zhang, Peng; Wang, Qiaoyue; Xu, Chang; Lesniak, Maciej S; Li, Gang; Cheng, Yu

2017-01-01

Inorganic nanoparticles with unique physical properties have been explored as nanomedicines for brain tumor treatment. However, the clinical applications of the inorganic formulations are often hindered by the biological barriers and failure to be bioeliminated. The size of the nanoparticle is an essential design parameter which plays a significant role to affect the tumor targeting and biodistribution. Here, we report a feasible approach for the assembly of gold nanoparticles into ~80 nm nanospheres as a drug delivery platform for enhanced retention in brain tumors with the ability to be dynamically switched into the single formulation for excretion. These nanoassemblies can target epidermal growth factor receptors on cancer cells and are responsive to tumor microenvironmental characteristics, including high vascular permeability and acidic and redox conditions. Anticancer drug release was controlled by a pH-responsive mechanism. Intracellular L-glutathione (GSH) triggered the complete breakdown of nanoassemblies to single gold nanoparticles. Furthermore, in vivo studies have shown that nanospheres display enhanced tumor-targeting efficiency and therapeutic effects relative to single-nanoparticle formulations. Hence, gold nanoassemblies present an effective targeting strategy for brain tumor treatment.

Continuous nicotinamide administration improves behavioral recovery and reduces lesion size following bilateral frontal controlled cortical impact injury.

PubMed

Vonder Haar, Cole; Anderson, Gail D; Hoane, Michael R

2011-10-31

Previous research has demonstrated considerable preclinical efficacy of nicotinamide (NAM; vitamin B(3)) in animal models of TBI with systemic dosing at 50 and 500 mg/kg yielding improvements on sensory, motor, cognitive and histological measures. The current study aimed to utilize a more specific dosing paradigm in a clinically relevant delivery mechanism: continuously secreting subcutaneous pumps. A bilateral frontal controlled cortical impact (CCI) or sham surgery was performed and rats were treated with NAM (150 mg/kg day) or saline (1 ml/kg) pumps 30 min after CCI, continuing until seven days post-CCI. Rats were given a loading dose of NAM (50mg/kg) or saline (1 ml/kg) following pump implant. Rats received behavioral testing (bilateral tactile adhesive removal, locomotor placing task and Morris water maze) starting on day two post-CCI and were sacrificed at 31 days post-CCI and brains were stained to examine lesion size. NAM-treated rats had reductions in sensory, motor and cognitive behavioral deficits compared to vehicle-treated rats. Specifically, NAM-treated rats significantly improved on the bilateral tactile adhesive removal task, locomotor placing task and the reference memory paradigm of the Morris water maze. Lesion size was also significantly reduced in the NAM-treated group. The results from this study indicate that at the current dose, NAM produces beneficial effects on recovery from a bilateral frontal brain injury and that it may be a relevant compound to be explored in human studies. Copyright © 2011 Elsevier B.V. All rights reserved.

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.

Pupil size signals mental effort deployed during multiple object tracking and predicts brain activity in the dorsal attention network and the locus coeruleus.

PubMed

Alnæs, Dag; Sneve, Markus Handal; Espeseth, Thomas; Endestad, Tor; van de Pavert, Steven Harry Pieter; Laeng, Bruno

2014-04-01

Attentional effort relates to the allocation of limited-capacity attentional resources to meet current task demands and involves the activation of top-down attentional systems in the brain. Pupillometry is a sensitive measure of this intensity aspect of top-down attentional control. Studies relate pupillary changes in response to cognitive processing to activity in the locus coeruleus (LC), which is the main hub of the brain's noradrenergic system and it is thought to modulate the operations of the brain's attentional systems. In the present study, participants performed a visual divided attention task known as multiple object tracking (MOT) while their pupil sizes were recorded by use of an infrared eye tracker and then were tested again with the same paradigm while brain activity was recorded using fMRI. We hypothesized that the individual pupil dilations, as an index of individual differences in mental effort, as originally proposed by Kahneman (1973), would be a better predictor of LC activity than the number of tracked objects during MOT. The current results support our hypothesis, since we observed pupil-related activity in the LC. Moreover, the changes in the pupil correlated with activity in the superior colliculus and the right thalamus, as well as cortical activity in the dorsal attention network, which previous studies have shown to be strongly activated during visual tracking of multiple targets. Follow-up pupillometric analyses of the MOT task in the same individuals also revealed that individual differences to cognitive load can be remarkably stable over a lag of several years. To our knowledge this is the first study using pupil dilations as an index of attentional effort in the MOT task and also relating these to functional changes in the brain that directly implicate the LC-NE system in the allocation of processing resources.

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.

Aberrant topological patterns of brain structural network in temporal lobe epilepsy.

PubMed

Yasuda, Clarissa Lin; Chen, Zhang; Beltramini, Guilherme Coco; Coan, Ana Carolina; Morita, Marcia Elisabete; Kubota, Bruno; Bergo, Felipe; Beaulieu, Christian; Cendes, Fernando; Gross, Donald William

2015-12-01

Although altered large-scale brain network organization in patients with temporal lobe epilepsy (TLE) has been shown using morphologic measurements such as cortical thickness, these studies, have not included critical subcortical structures (such as hippocampus and amygdala) and have had relatively small sample sizes. Here, we investigated differences in topological organization of the brain volumetric networks between patients with right TLE (RTLE) and left TLE (LTLE) with unilateral hippocampal atrophy. We performed a cross-sectional analysis of 86 LTLE patients, 70 RTLE patients, and 116 controls. RTLE and LTLE groups were balanced for gender (p = 0.64), seizure frequency (Mann-Whitney U test, p = 0.94), age (p = 0.39), age of seizure onset (p = 0.21), and duration of disease (p = 0.69). Brain networks were constructed by thresholding correlation matrices of volumes from 80 cortical/subcortical regions (parcellated with Freesurfer v5.3 https://surfer.nmr.mgh.harvard.edu/) that were then analyzed using graph theoretical approaches. We identified reduced cortical/subcortical connectivity including bilateral hippocampus in both TLE groups, with the most significant interregional correlation increases occurring within the limbic system in LTLE and contralateral hemisphere in RTLE. Both TLE groups demonstrated less optimal topological organization, with decreased global efficiency and increased local efficiency and clustering coefficient. LTLE also displayed a more pronounced network disruption. Contrary to controls, hub nodes in both TLE groups were not distributed across whole brain, but rather found primarily in the paralimbic/limbic and temporal association cortices. Regions with increased centrality were concentrated in occipital lobes for LTLE and contralateral limbic/temporal areas for RTLE. These findings provide first evidence of altered topological organization of the whole brain volumetric network in TLE, with disruption of the coordinated patterns of cortical/subcortical morphology. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Abnormal functional global and local brain connectivity in female patients with anorexia nervosa

PubMed Central

Geisler, Daniel; Borchardt, Viola; Lord, Anton R.; Boehm, Ilka; Ritschel, Franziska; Zwipp, Johannes; Clas, Sabine; King, Joseph A.; Wolff-Stephan, Silvia; Roessner, Veit; Walter, Martin; Ehrlich, Stefan

2016-01-01

Background Previous resting-state functional connectivity studies in patients with anorexia nervosa used independent component analysis or seed-based connectivity analysis to probe specific brain networks. Instead, modelling the entire brain as a complex network allows determination of graph-theoretical metrics, which describe global and local properties of how brain networks are organized and how they interact. Methods To determine differences in network properties between female patients with acute anorexia nervosa and pairwise matched healthy controls, we used resting-state fMRI and computed well-established global and local graph metrics across a range of network densities. Results Our analyses included 35 patients and 35 controls. We found that the global functional network structure in patients with anorexia nervosa is characterized by increases in both characteristic path length (longer average routes between nodes) and assortativity (more nodes with a similar connectedness link together). Accordingly, we found locally decreased connectivity strength and increased path length in the posterior insula and thalamus. Limitations The present results may be limited to the methods applied during preprocessing and network construction. Conclusion We demonstrated anorexia nervosa–related changes in the network configuration for, to our knowledge, the first time using resting-state fMRI and graph-theoretical measures. Our findings revealed an altered global brain network architecture accompanied by local degradations indicating wide-scale disturbance in information flow across brain networks in patients with acute anorexia nervosa. Reduced local network efficiency in the thalamus and posterior insula may reflect a mechanism that helps explain the impaired integration of visuospatial and homeostatic signals in patients with this disorder, which is thought to be linked to abnormal representations of body size and hunger. PMID:26252451

Abnormal functional global and local brain connectivity in female patients with anorexia nervosa.

PubMed

Geisler, Daniel; Borchardt, Viola; Lord, Anton R; Boehm, Ilka; Ritschel, Franziska; Zwipp, Johannes; Clas, Sabine; King, Joseph A; Wolff-Stephan, Silvia; Roessner, Veit; Walter, Martin; Ehrlich, Stefan

2016-01-01

Previous resting-state functional connectivity studies in patients with anorexia nervosa used independent component analysis or seed-based connectivity analysis to probe specific brain networks. Instead, modelling the entire brain as a complex network allows determination of graph-theoretical metrics, which describe global and local properties of how brain networks are organized and how they interact. To determine differences in network properties between female patients with acute anorexia nervosa and pairwise matched healthy controls, we used resting-state fMRI and computed well-established global and local graph metrics across a range of network densities. Our analyses included 35 patients and 35 controls. We found that the global functional network structure in patients with anorexia nervosa is characterized by increases in both characteristic path length (longer average routes between nodes) and assortativity (more nodes with a similar connectedness link together). Accordingly, we found locally decreased connectivity strength and increased path length in the posterior insula and thalamus. The present results may be limited to the methods applied during preprocessing and network construction. We demonstrated anorexia nervosa-related changes in the network configuration for, to our knowledge, the first time using resting-state fMRI and graph-theoretical measures. Our findings revealed an altered global brain network architecture accompanied by local degradations indicating wide-scale disturbance in information flow across brain networks in patients with acute anorexia nervosa. Reduced local network efficiency in the thalamus and posterior insula may reflect a mechanism that helps explain the impaired integration of visuospatial and homeostatic signals in patients with this disorder, which is thought to be linked to abnormal representations of body size and hunger.

Disaster-Proofing Senior Leadership: Preventing Technological Failure in Future Nano-War

DTIC Science & Technology

2009-02-01

phenomenon beyond Globalization 3.0, where the empowered individual becomes the empowered machine-enhanced human or cyborg in 50 to 100 years. This merging...gain control of their bodies, could turn into superhuman cyborg - like upgrades. Further, the ability to understand and replicate brain functions in...The implications of nano-enhanced humans and cyborgs on the battlefield are legion. With ubiquitous sensing via the quantum dot-sized sensor nets

Correlations between ventricular enlargement and gray and white matter volumes of cortex, thalamus, striatum, and internal capsule in schizophrenia.

PubMed

Horga, Guillermo; Bernacer, Javier; Dusi, Nicola; Entis, Jonathan; Chu, Kingwai; Hazlett, Erin A; Haznedar, M Mehmet; Kemether, Eileen; Byne, William; Buchsbaum, Monte S

2011-10-01

Ventricular enlargement is one of the most consistent abnormal structural brain findings in schizophrenia and has been used to infer brain shrinkage. However, whether ventricular enlargement is related to local overlying cortex and/or adjacent subcortical structures or whether it is related to brain volume change globally has not been assessed. We systematically assessed interrelations of ventricular volumes with gray and white matter volumes of 40 Brodmann areas (BAs), the thalamus and its medial dorsal nucleus and pulvinar, the internal capsule, caudate and putamen. We acquired structural MRI ( patients with schizophrenia (n = 64) and healthy controls (n = 56)) and diffusion tensor fractional anisotropy (FA) (untreated schizophrenia n = 19, controls n = 32). Volumes were assessed by manual tracing of central structures and a semi-automated parcellation of BAs. Patients with schizophrenia had increased ventricular size associated with decreased cortical gray matter volumes widely across the brain; a similar but less pronounced pattern was seen in normal controls; local correlations (e.g. temporal horn with temporal lobe volume) were not appreciably higher than non-local correlations (e.g. temporal horn with prefrontal volume). White matter regions adjacent to the ventricles similarly did not reveal strong regional relationships. FA and center of mass of the anterior limb of the internal capsule also appeared differentially influenced by ventricular volume but findings were similarly not regional. Taken together, these findings indicate that ventricular enlargement is globally interrelated with gray matter volume diminution but not directly correlated with volume loss in the immediately adjacent caudate, putamen, or internal capsule.

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

Rare-earth Nanoparticle-induced Cytotoxicity on Spatial Cognition Memory of Mouse Brain.

PubMed

Lin, Cai-Hou; Liu, Gui-Fen; Chen, Jing; Chen, Yan; Lin, Ru-Hui; He, Hong-Xing; Chen, Jian-Ping

2017-11-20

Luminescent rare-earth-based nanoparticles have been increasingly used in nanomedicine due to their excellent physicochemical properties, such as biomedical imaging agents, drug carriers, and biomarkers. However, biological safety of the rare-earth-based nanomedicine is of great significance for future development in practical applications. In particular, biological effects of rare-earth nanoparticles on human's central nervous system are still unclear. This study aimed to investigate the potential toxicity of rare-earth nanoparticles in nervous system function in the case of continuous exposure. Adult ICR mice were randomly divided into seven groups, including control group (receiving 0.9% normal saline) and six experimental groups (10 mice in each group). Luminescent rare-earth-based nanoparticles were synthesized by a reported co-precipitation method. Two different sizes of the nanoparticles were obtained, and then exposed to ICR mice through caudal vein injection at 0.5, 1.0, and 1.5 mg/kg body weight in each day for 7 days. Next, a Morris water maze test was employed to evaluate impaired behaviors of their spatial recognition memory. Finally, histopathological examination was implemented to study how the nanoparticles can affect the brain tissue of the ICR mice. Two different sizes of rare-earth nanoparticles have been successfully obtained, and their physical properties including luminescence spectra and nanoparticle sizes have been characterized. In these experiments, the rare-earth nanoparticles were taken up in the mouse liver using the magnetic resonance imaging characterization. Most importantly, the experimental results of the Morris water maze tests and histopathological analysis clearly showed that rare-earth nanoparticles could induce toxicity on mouse brain and impair the behaviors of spatial recognition memory. Finally, the mechanism of adenosine triphosphate quenching by the rare-earth nanoparticles was provided to illustrate the toxicity on the mouse brain. This study suggested that long-term exposure of high-dose bare rare-earth nanoparticles caused an obvious damage on the spatial recognition memory in the mice.

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.

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.

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.

Proprioceptive Distance Cues Restore Perfect Size Constancy in Grasping, but Not Perception, When Vision Is Limited.

PubMed

Chen, Juan; Sperandio, Irene; Goodale, Melvyn Alan

2018-03-19

Our brain integrates information from multiple modalities in the control of behavior. When information from one sensory source is compromised, information from another source can compensate for the loss. What is not clear is whether the nature of this multisensory integration and the re-weighting of different sources of sensory information are the same across different control systems. Here, we investigated whether proprioceptive distance information (position sense of body parts) can compensate for the loss of visual distance cues that support size constancy in perception (mediated by the ventral visual stream) [1, 2] versus size constancy in grasping (mediated by the dorsal visual stream) [3-6], in which the real-world size of an object is computed despite changes in viewing distance. We found that there was perfect size constancy in both perception and grasping in a full-viewing condition (lights on, binocular viewing) and that size constancy in both tasks was dramatically disrupted in the restricted-viewing condition (lights off; monocular viewing of the same but luminescent object through a 1-mm pinhole). Importantly, in the restricted-viewing condition, proprioceptive cues about viewing distance originating from the non-grasping limb (experiment 1) or the inclination of the torso and/or the elbow angle of the grasping limb (experiment 2) compensated for the loss of visual distance cues to enable a complete restoration of size constancy in grasping but only a modest improvement of size constancy in perception. This suggests that the weighting of different sources of sensory information varies as a function of the control system being used. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

Combined effects of marijuana and nicotine on memory performance and hippocampal volume.

PubMed

Filbey, Francesca M; McQueeny, Tim; Kadamangudi, Shrinath; Bice, Collette; Ketcherside, Ariel

2015-10-15

Combined use of marijuana (MJ) and tobacco is highly prevalent in today's population. Individual use of either substance is linked to structural brain changes and altered cognitive function, especially with consistent reports of hippocampal volume deficits and poorer memory performance. However, the combined effects of MJ and tobacco on hippocampal structure and on learning and memory processes remain unknown. In this study, we examined both the individual and combined effects of MJ and tobacco on hippocampal volumes and memory performance in four groups of adults taken from two larger studies: MJ-only users (n=36), nicotine-only (Nic-only, n=19), combined marijuana and nicotine users (MJ+Nic, n=19) and non-using healthy controls (n=16). Total bilateral hippocampal volumes and memory performance (WMS-III logical memory) were compared across groups controlling for total brain size and recent alcohol use. Results found MJ and MJ+Nic groups had smaller total hippocampal volumes compared to Nic-only and controls. No significant difference between groups was found between immediate and delayed story recall. However, the controls showed a trend for larger hippocampal volumes being associated with better memory scores, while MJ+Nic users showed a unique inversion, whereby smaller hippocampal volume was associated with better memory. Overall, results suggest abnormalities in the brain-behavior relationships underlying memory processes with combined use of marijuana and nicotine use. Further research will need to address these complex interactions between MJ and nicotine. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Cortical magnetic resonance imaging findings in familial pediatric bipolar disorder.

PubMed

Chang, Kiki; Barnea-Goraly, Naama; Karchemskiy, Asya; Simeonova, Diana Iorgova; Barnes, Patrick; Ketter, Terence; Reiss, Allan L

2005-08-01

Morphometric magnetic resonance imaging (MRI) studies of pediatric bipolar disorder (BD) have not reported on gray matter volumes but have reported increased lateral ventricular size and presence of white matter hyperintensities (WMH). We studied gray matter volume, ventricular-to-brain ratios (VBR), and number of WMH in patients with familial, pediatric BD compared with control subjects. Twenty subjects with BD (aged 14.6 +/- 2.8 years; 4 female) according to the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia, each with a parent with BD, and 20 age-, gender-, and intelligence quotient-matched healthy control subjects (aged 14.1 +/- 2.8 years; 4 female) were scanned at 3 T. Most subjects were taking psychotropic medications. A high-resolution T1-weighted spoiled gradient echo three-dimensional MRI sequence was analyzed by BrainImage for volumetric measurements, and T2-weighted images were read by a neuroradiologist to determine presence of WMH. After covarying for age and total brain volume, there were no significant differences between subjects with BD and control subjects in volume of cerebral (p = .09) or prefrontal gray matter (p = .34). Subjects with BD did not have elevated numbers of WMH or greater VBR when compared with control subjects. Children and adolescents with familial BD do not seem to have decreased cerebral grey matter or increased numbers of WMH, dissimilar to findings in adults with BD. Gray matter decreases and development of WMH might be later sequelae of BD or unique to adult-onset BD.

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.

Event-related brain potentials and cognitive processes related to perceptual-motor information transmission.

PubMed

Kopp, Bruno; Wessel, Karl

2010-05-01

In the present study, event-related potentials (ERPs) were recorded to investigate cognitive processes related to the partial transmission of information from stimulus recognition to response preparation. Participants classified two-dimensional visual stimuli with dimensions size and form. One feature combination was designated as the go-target, whereas the other three feature combinations served as no-go distractors. Size discriminability was manipulated across three experimental conditions. N2c and P3a amplitudes were enhanced in response to those distractors that shared the feature from the faster dimension with the target. Moreover, N2c and P3a amplitudes showed a crossover effect: Size distractors evoked more pronounced ERPs under high size discriminability, but form distractors elicited enhanced ERPs under low size discriminability. These results suggest that partial perceptual-motor transmission of information is accompanied by acts of cognitive control and by shifts of attention between the sources of conflicting information. Selection negativity findings imply adaptive allocation of visual feature-based attention across the two stimulus dimensions.

4D MEMRI atlas of neonatal FVB/N mouse brain development.

PubMed

Szulc, Kamila U; Lerch, Jason P; Nieman, Brian J; Bartelle, Benjamin B; Friedel, Miriam; Suero-Abreu, Giselle A; Watson, Charles; Joyner, Alexandra L; Turnbull, Daniel H

2015-09-01

The widespread use of the mouse as a model system to study brain development has created the need for noninvasive neuroimaging methods that can be applied to early postnatal mice. The goal of this study was to optimize in vivo three- (3D) and four-dimensional (4D) manganese (Mn)-enhanced MRI (MEMRI) approaches for acquiring and analyzing data from the developing mouse brain. The combination of custom, stage-dependent holders and self-gated (motion-correcting) 3D MRI sequences enabled the acquisition of high-resolution (100-μm isotropic), motion artifact-free brain images with a high level of contrast due to Mn-enhancement of numerous brain regions and nuclei. We acquired high-quality longitudinal brain images from two groups of FVB/N strain mice, six mice per group, each mouse imaged on alternate odd or even days (6 3D MEMRI images at each day) covering the developmental stages between postnatal days 1 to 11. The effects of Mn-exposure, anesthesia and MRI were assessed, showing small but significant transient effects on body weight and brain volume, which recovered with time and did not result in significant morphological differences when compared to controls. Metrics derived from deformation-based morphometry (DBM) were used for quantitative analysis of changes in volume and position of a number of brain regions. The cerebellum, a brain region undergoing significant changes in size and patterning at early postnatal stages, was analyzed in detail to demonstrate the spatiotemporal characterization made possible by this new atlas of mouse brain development. These results show that MEMRI is a powerful tool for quantitative analysis of mouse brain development, with great potential for in vivo phenotype analysis in mouse models of neurodevelopmental diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

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…

Preliminary evidence of altered neural response during intertemporal choice of losses in adult attention-deficit hyperactivity disorder.

PubMed

Tanaka, Saori C; Yahata, Noriaki; Todokoro, Ayako; Kawakubo, Yuki; Kano, Yukiko; Nishimura, Yukika; Ishii-Takahashi, Ayaka; Ohtake, Fumio; Kasai, Kiyoto

2018-04-30

Impulsive behaviours are common symptoms of attention-deficit hyperactivity disorder (ADHD). Although previous studies have suggested functional models of impulsive behaviour, a full explanation of impulsivity in ADHD remains elusive. To investigate the detailed mechanisms behind impulsive behaviour in ADHD, we applied an economic intertemporal choice task involving gains and losses to adults with ADHD and healthy controls and measured brain activity by functional magnetic resonance imaging. In the intertemporal choice of future gains, we observed no behavioural or neural difference between the two groups. In the intertemporal choice of future losses, adults with ADHD exhibited higher discount rates than the control participants. Furthermore, a comparison of brain activity representing the sensitivity of future loss in the two groups revealed significantly lower activity in the striatum and higher activity in the amygdala in adults with ADHD than in controls. Our preliminary findings suggest that an altered size sensitivity to future loss is involved in apparent impulsive choice behaviour in adults with ADHD and shed light on the multifaceted impulsivity underlying ADHD.

Preliminary fMRI findings on the effects of event rate in adults with ADHD.

PubMed

Kooistra, Libbe; van der Meere, Jaap J; Edwards, Jodi D; Kaplan, Bonnie J; Crawford, Susan; Goodyear, Bradley G

2010-05-01

Inhibition problems in attention deficit hyperactivity disorder (ADHD) are sensitive to stimulus event rate. This pilot study explores the neural basis of this increased susceptibility to event rate in ADHD. Event-related functional magnetic resonance imaging was used in conjunction with the administration of a fast (1.5 s) and a slow (7 s) Go/No-Go task. Brain activity patterns and reaction times of ten young male adults with ADHD (two of whom were in partial remission) and ten healthy male controls were compared. The ADHD group responded slower than controls with greater variability but with similar number of errors. Accurate response inhibition in the ADHD group in the slow condition was associated with widespread fronto-striatal activation, including the thalamus. For correct Go trials only, the ADHD group compared with controls showed substantial under-activation in the slow condition. The observed abnormal brain activation in the slow condition in adults with ADHD supports a fronto-striatal etiology, and underlines a presumed activation regulation deficit. Larger sample sizes to further validate these preliminary findings are needed.

Systematic Review of Prenatal Cocaine Exposure and Adolescent Development

PubMed Central

Buckingham-Howes, Stacy; Berger, Sarah Shafer; Scaletti, Laura A.

2013-01-01

BACKGROUND AND OBJECTIVE: Previous research found that prenatal cocaine exposure (PCE) may increase children's vulnerability to behavior and cognition problems. Maturational changes in brain and social development make adolescence an ideal time to reexamine associations. The objective was to conduct a systematic review of published studies examining associations between PCE and adolescent development (behavior, cognition/school outcomes, physiologic responses, and brain morphology/functioning). METHODS: Articles were obtained from PubMed, PsycInfo, Web of Science, and CINAHL databases through July 2012 with search terms: prenatal drug, substance, or cocaine exposure; adolescence/adolescent; and in utero substance/drug exposure. Criteria for inclusion were nonexposed comparison group, human adolescents aged 11 to 19, peer-reviewed, English-language, and adolescent outcomes. RESULTS: Twenty-seven studies representing 9 cohorts met the criteria. Four outcome categories were identified: behavior, cognition/school performance, brain structure/function, and physiologic responses. Eleven examined behavior; 7 found small but significant differences favoring nonexposed adolescents, with small effect sizes. Eight examined cognition/school performance; 6 reported significantly lower scores on language and memory tasks among adolescents with PCE, with varying effect sizes varied. Eight examined brain structure/function and reported morphologic differences with few functional differences. Three examined physiologic responses with discordant findings. Most studies controlled for other prenatal exposures, caregiving environment, and violence exposure; few examined mechanisms. CONCLUSIONS: Consistent with findings among younger children, PCE increases the risk for small but significantly less favorable adolescent functioning. Although the clinical importance of differences is often unknown, the caregiving environment and violence exposure pose additional threats. Future research should investigate mechanisms linking PCE with adolescent functioning. PMID:23713107

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

Tracking the pathway of diesel exhaust particles from the nose to the brain by X-ray florescence analysis

NASA Astrophysics Data System (ADS)

Matsui, Yasuto; Sakai, Nobumitsu; Tsuda, Akira; Terada, Yasuko; Takaoka, Masaki; Fujimaki, Hidekazu; Uchiyama, Iwao

2009-08-01

Studies have shown that exposure to nano-sized particles (< 50 nm) result in their translocation to the central nervous system through the olfactory nerve. Translocation commonly occurs via inhalation, ingestion and skin uptake. Little information is available on the specific pathway of cellular localization of nano-sized particles in the olfactory bulb. The nano-sized particles entrance into the postsynaptics cell is of particular interest because the mitral cell projects to the central nucleus of the amygdala and the piriform cortex. Therefore, our objective in this follow-up study has been to determine whether or not the mitral cells project nano-sized particles to the brain. Nano-sized particles in this study were generated using diesel exhaust. Lab mice were exposed for a period of 4 weeks. We employed synchrotron radiation (SPring-8, Japan) to determine the concentration levels of metal in the olfactory neuron pathway. Metal levels were assayed by mapping, using X-ray fluorescence analysis. The major metal components measured in the filter that collected the inhaled diesel exhaust particles were calcium, copper, iron, nickel and zinc. Our studies reveal an increase in the amount of nano-sized particles in the glomerular layer as well as in the neurons in the olfactory epithelium. Higher levels of nickel and iron were found in the olfactory epithelium's lamina propria mucosae in comparison to that in the control group. Higher levels of iron also were observed in the glomerular layer. Our studies do not clarify the specifics of metal adhesion and detachment. This remains to be one of the key issues requiring further clarification.

Working memory deficit in patients with restless legs syndrome: an event-related potential study.

PubMed

Kim, Sung Min; Choi, Jeong Woo; Lee, Chany; Lee, Byeong Uk; Koo, Yong Seo; Kim, Kyung Hwan; Jung, Ki-Young

2014-07-01

The aim of this study was to investigate whether there is a working memory (WM) deficit in restless legs syndrome (RLS) patients, by studying the Sternberg WM task of event-related potential (ERP). Thirteen drug-naive RLS patients and 13 healthy age-matched controls with no sleep disturbances participated in the present study. P300 ERP was recorded during Sternberg WM task using digits as mnemonic items. P300 amplitudes and reaction times were compared between groups (RLS vs. control) considering brain regions (frontal, central, and parietal) and memory load sizes (two, three, and four) as within-subject factors. Clinical and sleep-related variables were correlated with P300 amplitude. The reaction time in RLS patients was significantly longer than controls over all memory load sizes. The P300 amplitude at parietal regions in RLS patients was significantly lower than in controls regardless of memory load sizes, which was significantly negatively correlated with duration of RLS history in RLS patients. Our study suggests that patients with severe RLS have WM deficits. Furthermore, negative correlation of P300 amplitudes with the duration of RLS illness suggests that cerebral cortical dysfunction in RLS patients results from repeated RLS symptom attacks. Copyright © 2014 Elsevier B.V. All rights reserved.

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

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.

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

Default mode network in young people with familial risk for psychosis--the Oulu Brain and Mind study.

PubMed

Jukuri, Tuomas; Kiviniemi, Vesa; Nikkinen, Juha; Miettunen, Jouko; Mäki, Pirjo; Jääskeläinen, Erika; Mukkala, Sari; Koivukangas, Jenni; Nordström, Tanja; Taanila, Anja; Moilanen, Irma; Heinimaa, Markus; Barnett, Jennifer H; Jones, Peter B; Murray, Graham K; Veijola, Juha

2013-02-01

The default mode network (DMN) is active in the brain at rest and de-activated during cognitive tasks. Abnormal function in the DMN has been reported in people with schizophrenia but it is not known whether this applies also to people with a familial risk for psychosis (FR). We compared the activity of the DMN between FR participants and controls. We conducted a resting state functional MRI (R-fMRI) in 72 young adults without psychosis and with a history of psychosis in one or both parents (FR group) and 72 age matched controls without parental psychosis, and without current psychosis or a current prodromal syndrome. Both groups were drawn from the Northern Finland Birth Cohort 1986 (Oulu Brain and Mind study). Parental psychosis was established using the Finnish hospital discharge register. We pre-processed R-fMRI data using independent component analysis followed by a dual regression approach to assess differences between the groups. The FR vs. Control group differences were assessed using non-parametric permutation tests utilizing threshold-free cluster enhancement and correcting for multiple comparisons (p<0.05). FR participants demonstrated significantly lower activity compared with controls in the posterior cingulate cortex, the central node of the DMN. The size of the region was 41 mm(3). The activity of the DMN differed between FR and control groups. This suggests that familial risk for psychotic disorders may be mediated through genetic effects on connectivity in the posterior cingulate cortex. Copyright © 2012 Elsevier B.V. All rights reserved.

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.

Brain volumes in psychotic youth with schizophrenia and mood disorders

PubMed Central

El-Sayed, Mohamed; Steen, R. Grant; Poe, Michele D.; Bethea, T. Carter; Gerig, Guido; Lieberman, Jeffrey; Sikich, Linmarie

2010-01-01

Background We sought to test the hypothesis that deficits in grey matter volume are characteristic of psychotic youth with early-onset schizophrenia-spectrum disorders (EOSS) but not of psychotic youth with early-onset mood disorders (EOMD). Methods We used magnetic resonance imaging to examine brain volume in 24 psychotic youth (13 male, 11 female) with EOSS (n = 12) or EOMD (n = 12) and 17 healthy controls (10 male, 7 female). We measured the volume of grey and white matter using an automated segmentation program. Results After adjustment for age and intracranial volume, whole brain volume was lower in the EOSS patients than in the healthy controls (p = 0.001) and EOMD patients (p = 0.002). The EOSS patients had a deficit in grey matter volume (p = 0.005), especially in the frontal (p = 0.003) and parietal (p = 0.006) lobes, with no significant differences in white matter volume. Limitations The main limitations of our study were its small sample size and the inclusion of patients with depression and mania in the affective group. Conclusion Adolescents with EOSS have grey matter deficits compared with healthy controls and psychotic adolescents with EOMD. Our results suggest that grey matter deficits are not generally associated with psychosis but may be specifically associated with schizophrenia. Larger studies with consistent methods are needed to reconcile the contradictory findings among imaging studies involving psychotic youth. PMID:20569649

Dietary Slowly Digestible Starch Triggers the Gut-Brain Axis in Obese Rats with Accompanied Reduced Food Intake.

PubMed

Hasek, Like Y; Phillips, Robert J; Zhang, Genyi; Kinzig, Kimberly P; Kim, Choon Young; Powley, Terry L; Hamaker, Bruce R

2018-03-01

Slowly digestible starch (SDS), as a functional carbohydrate providing a slow and sustained glucose release, may be able to modulate food intake through activation of the gut-brain axis. Diet-induced obese rats were used to test the effect on feeding behavior of high-fat (HF) diets containing an SDS, fabricated to digest into the ileum, as compared to rapidly digestible starch (RDS). Ingestion of the HF-SDS diet over an 11-week period reduced daily food intake, through smaller meal size, to the same level as a lean body control group, while the group consuming the HF-RDS diet remained at a high food intake. Expression levels (mRNA) of the hypothalamic orexigenic neuropeptide Y (NPY) and Agouti-related peptide (AgRP) were significantly reduced, and the anorexigenic corticotropin-releasing hormone (CRH) was increased, in the HF-SDS fed group compared to the HF-RDS group, and to the level of the lean control group. SDS with digestion into the ileum reduced daily food intake and paralleled suppressed expression of appetite-stimulating neuropeptide genes associated with the gut-brain axis. This novel finding suggests further exploration involving a clinical study and potential development of SDS-based functional foods as an approach to obesity control. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Altered brain network modules induce helplessness in major depressive disorder.

PubMed

Peng, Daihui; Shi, Feng; Shen, Ting; Peng, Ziwen; Zhang, Chen; Liu, Xiaohua; Qiu, Meihui; Liu, Jun; Jiang, Kaida; Fang, Yiru; Shen, Dinggang

2014-10-01

The abnormal brain functional connectivity (FC) has been assumed to be a pathophysiological aspect of major depressive disorder (MDD). However, it is poorly understood, regarding the underlying patterns of global FC network and their relationships with the clinical characteristics of MDD. Resting-state functional magnetic resonance imaging data were acquired from 16 first episode, medication-naïve MDD patients and 16 healthy control subjects. The global FC network was constructed using 90 brain regions. The global topological patterns, e.g., small-worldness and modularity, and their relationships with depressive characteristics were investigated. Furthermore, the participant coefficient and module degree of MDD patients were measured to reflect the regional roles in module network, and the impairment of FC was examined by network based statistic. Small-world property was not altered in MDD. However, MDD patients exhibited 5 atypically reorganized modules compared to the controls. A positive relationship was also found among MDD patients between the intra-module I and helplessness factor evaluated via the Hamilton Depression Scale. Specifically, eight regions exhibited the abnormal participant coefficient or module degree, e.g., left superior orbital frontal cortex and right amygdala. The decreased FC was identified among the sub-network of 24 brain regions, e.g., frontal cortex, supplementary motor area, amygdala, thalamus, and hippocampus. The limited size of MDD samples precluded meaningful study of distinct clinical characteristics in relation to aberrant FC. The results revealed altered patterns of brain module network at the global level in MDD patients, which might contribute to the feelings of helplessness. Copyright © 2014 Elsevier B.V. All rights reserved.

Altered brain network modules induce helplessness in major depressive disorder

PubMed Central

Peng, Daihui; Shi, Feng; Shen, Ting; Peng, Ziwen; Zhang, Chen; Liu, Xiaohua; Qiu, Meihui; Liu, Jun; Jiang, Kaida; Shen, Dinggang

2017-01-01

Objective The abnormal brain functional connectivity (FC) has been assumed to be a pathophysiological aspect of major depressive disorder (MDD). However, it is poorly understood, regarding the underlying patterns of global FC network and their relationships with the clinical characteristics of MDD. Methods Resting-state functional magnetic resonance imaging data were acquired from 16 first episode, medication-naïve MDD patients and 16 healthy control subjects. The global FC network was constructed using 90 brain regions. The global topological patterns, e.g., small-worldness and modularity, and their relationships with depressive characteristics were investigated. Furthermore, the participant coefficient and module degree of MDD patients were measured to reflect the regional roles in module network, and the impairment of FC was examined by network based statistic. Results Small-world property was not altered in MDD. However, MDD patients exhibited 5 atypically reorganized modules compared to the controls. A positive relationship was also found among MDD patients between the intra-module I and helplessness factor evaluated via the Hamilton Depression Scale. Specifically, eight regions exhibited the abnormal participant coefficient or module degree, e.g., left superior orbital frontal cortex and right amygdala. The decreased FC was identified among the sub-network of 24 brain regions, e.g., frontal cortex, supplementary motor area, amygdala, thalamus, and hippocampus. Limitation The limited size of MDD samples precluded meaningful study of distinct clinical characteristics in relation to aberrant FC. Conclusions The results revealed altered patterns of brain module network at the global level in MDD patients, which might contribute to the feelings of helplessness. PMID:25033474

The association between regular cannabis exposure and alterations of human brain morphology: an updated review of the literature.

PubMed

Lorenzetti, Valentina; Solowij, Nadia; Fornito, Alex; Lubman, Dan Ian; Yucel, Murat

2014-01-01

Cannabis is the most widely used illicit drug worldwide, though it is unclear whether its regular use is associated with persistent alterations in brain morphology. This review examines evidence from human structural neuroimaging investigations of regular cannabis users and focuses on achieving three main objectives. These include examining whether the literature to date provides evidence that alteration of brain morphology in regular cannabis users: i) is apparent, compared to non-cannabis using controls; ii) is associated with patterns of cannabis use; and with iii) measures of psychopathology and neurocognitive performance. The published findings indicate that regular cannabis use is associated with alterations in medial temporal, frontal and cerebellar brain regions. Greater brain morphological alterations were evident among samples that used at higher doses for longer periods. However, the evidence for an association between brain morphology and cannabis use parameters was mixed. Further, there is poor evidence for an association between measures of brain morphology and of psychopathology symptoms/neurocognitive performance. Overall, numerous methodological issues characterize the literature to date. These include investigation of small sample sizes, heterogeneity across studies in sample characteristics (e.g., sex, comorbidity) and in employed imaging techniques, as well as the examination of only a limited number of brain regions. These factors make it difficult to draw firm conclusions from the existing findings. Nevertheless, this review supports the notion that regular cannabis use is associated with alterations of brain morphology, and highlights the need to consider particular methodological issues when planning future cannabis research.

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

Comparative analysis of cortical layering and supragranular layer enlargement in rodent carnivore and primate species.

PubMed

Hutsler, Jeffrey J; Lee, Dong-Geun; Porter, Kristin K

2005-08-02

The mammalian cerebral cortex is composed of individual layers characterized by the cell types they contain and their afferent and efferent connections. The current study examined the raw, and size-normalized, laminar thicknesses in three cortical regions (somatosensory, motor, and premotor) of fourteen species from three orders of mammals: primates, carnivores, and rodents. The proportional size of the pyramidal cell layers (supra- and infragranular) varied between orders but was similar within orders despite wide variance in absolute cortical thickness. Further, supragranular layer thickness was largest in primates (46 +/- 3 percent), followed by carnivores (36 +/- 3 percent), and then rodents (19 +/- 4 percent), suggesting a distinct difference in the proportion of cortex devoted to corticocortical connectivity across these orders. Although measures of supragranular layer thickness are highly correlated with measures of overall brain size, such associations are not present when independent contrasts are used to control for phylogenetic inertia. Interestingly, neurogenesis time span remains strongly associated with supragranular layer thickness despite size normalization and controlling for phylogenetic inertia. Such layering differences between orders, and similarities amongst species within an order, suggest that supragranular layer expansion may have occurred early in mammalian evolution and may be related to ontogenetic variables such as neurogenesis time span rather than measures of overall size.

Thermal magnetic resonance: physics considerations and electromagnetic field simulations up to 23.5 Tesla (1GHz).

PubMed

Winter, Lukas; Oezerdem, Celal; Hoffmann, Werner; van de Lindt, Tessa; Periquito, Joao; Ji, Yiyi; Ghadjar, Pirus; Budach, Volker; Wust, Peter; Niendorf, Thoralf

2015-09-22

Glioblastoma multiforme is the most common and most aggressive malign brain tumor. The 5-year survival rate after tumor resection and adjuvant chemoradiation is only 10 %, with almost all recurrences occurring in the initially treated site. Attempts to improve local control using a higher radiation dose were not successful so that alternative additive treatments are urgently needed. Given the strong rationale for hyperthermia as part of a multimodal treatment for patients with glioblastoma, non-invasive radio frequency (RF) hyperthermia might significantly improve treatment results. A non-invasive applicator was constructed utilizing the magnetic resonance (MR) spin excitation frequency for controlled RF hyperthermia and MR imaging in an integrated system, which we refer to as thermal MR. Applicator designs at RF frequencies 300 MHz, 500 MHz and 1GHz were investigated and examined for absolute applicable thermal dose and temperature hotspot size. Electromagnetic field (EMF) and temperature simulations were performed in human voxel models. RF heating experiments were conducted at 300 MHz and 500 MHz to characterize the applicator performance and validate the simulations. The feasibility of thermal MR was demonstrated at 7.0 T. The temperature could be increased by ~11 °C in 3 min in the center of a head sized phantom. Modification of the RF phases allowed steering of a temperature hotspot to a deliberately selected location. RF heating was monitored using the integrated system for MR thermometry and high spatial resolution MRI. EMF and thermal simulations demonstrated that local RF hyperthermia using the integrated system is feasible to reach a maximum temperature in the center of the human brain of 46.8 °C after 3 min of RF heating while surface temperatures stayed below 41 °C. Using higher RF frequencies reduces the size of the temperature hotspot significantly. The opportunities and capabilities of thermal magnetic resonance for RF hyperthermia interventions of intracranial lesions are intriguing. Employing such systems as an alternative additive treatment for glioblastoma multiforme might be able to improve local control by "fighting fire with fire". Interventions are not limited to the human brain and might include temperature driven targeted drug and MR contrast agent delivery and help to understand temperature dependent bio- and physiological processes in-vivo.

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.

How functional connectivity between emotion regulation structures can be disrupted: preliminary evidence from adolescents with moderate to severe traumatic brain injury.

PubMed

Newsome, Mary R; Scheibel, Randall S; Mayer, Andrew R; Chu, Zili D; Wilde, Elisabeth A; Hanten, Gerri; Steinberg, Joel L; Lin, Xiaodi; Li, Xiaoqi; Merkley, Tricia L; Hunter, Jill V; Vasquez, Ana C; Cook, Lori; Lu, Hanzhang; Vinton, Kami; Levin, Harvey S

2013-09-01

Outcome of moderate to severe traumatic brain injury (TBI) includes impaired emotion regulation. Emotion regulation has been associated with amygdala and rostral anterior cingulate (rACC). However, functional connectivity between the two structures after injury has not been reported. A preliminary examination of functional connectivity of rACC and right amygdala was conducted in adolescents 2 to 3 years after moderate to severe TBI and in typically developing (TD)control adolescents, with the hypothesis that the TBI adolescents would demonstrate altered functional connectivity in the two regions. Functional connectivity was determined by correlating fluctuations in the blood oxygen level dependent(BOLD) signal of the rACC and right amygdala with that of other brain regions. In the TBI adolescents, the rACC was found to be significantly less functionally connected to medial prefrontal cortices and to right temporal regions near the amygdala (height threshold T = 2.5, cluster level p < .05, FDR corrected), while the right amygdala showed a trend in reduced functional connectivity with the rACC (height threshold T = 2.5, cluster level p = .06, FDR corrected). Data suggest disrupted functional connectivity in emotion regulation regions. Limitations include small sample sizes. Studies with larger sample sizes are necessary to characterize the persistent neural damage resulting from moderate to severe TBI during development.

Isolation and characterization of neural stem cells from dystrophic mdx mouse

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

Annese, Tiziana; Corsi, Patrizia; Ruggieri, Simona

The blood-brain barrier (BBB) is altered in mdx mouse, an animal model to study Duchenne muscular dystrophy (DMD). Our previous work demonstrated that perivascular glial endfeet control the selective exchanges between blood and neuropil as well as the BBB development and integrity; the alterations of dystrophin and dystrophin-associated protein complex (DAPs) in the glial cells of mdx mouse, parallel damages of the BBB and increase in vascular permeability. The aim of this study was to improve our knowledge about brain cellular components in the mdx mouse through the isolation, for the first time, of the adult neural stem cells (ANSCs).more » We characterized them by FACS, electron microscopy, confocal immunofluorescence microscopy, Real Time-PCR and western blotting, and we studied the expression of the DAPs aquaporin-4 (AQP4), potassium channel Kir4.1, α- and β-dystroglycan (αDG, βDG), α-syntrophin (αSyn), and short dystrophin isoform Dp71 proteins. The results showed that the mdx ANSCs expressed CD133 and Nestin receptor as the control ones, but showed a reduction in Notch receptor and altered cell proliferation with an increment in the apoptotic nuclei. Ultrastructurally, they appeared 50% size reduced compared to control ones, with a few cytoplasmic organelles. Moreover, the mdx ANSCs are devoid in full length dystrophin 427, and they expressed post-transcriptional reduction in the Dp71 in parallel with the ubiquitin proteasome activation, and decrement of DAPs proteins which appeared diffused in the cytoplasm and not polarized on the stem cells plasmamembrane, as prevalently observed in the controls. Overall, these results indicate that structural and molecular alterations affect the neural stem cells in the dystrophic brain, whose increased apoptosis and reduced Dp71 and DAPs proteins expression, together with loss in Dp427 dystrophin, could be responsible of the altered mdx glial maintenance and differentiation and consequent failure in the vessels barrier control occurring in the adult dystrophic brain.« less

Effects of insulin-like growth factor 1 on pathologic processes in the cuprizone model of multiple sclerosis

NASA Astrophysics Data System (ADS)

Fedorishin, D.; Sorokina, I.; Tolstikova, T.; Akulov, A.; Glazacheva, V.; Nemirovich-Danchenko, N.; Khodanovich, M.; Yarnykh, V.

2017-08-01

The study aims to evaluate the effect of insulin-like growth factor 1 (IGF-1) on the demyelination and astrogliosis using the cuprizone murine model. Demyelination was induced in 14 adult male mice by 0.3% cuprizone in drinking water. Five animals from the cuprizone-treated group received subcutaneous injections of IGF-1. Seven animals were used as a control group. The extent of demyelination was evaluated as a decrease in the size of the corpus callosum on T2-weighted images that were received using an 11.7T animal MRI scanner. Brain sections were immunohistochemically stained for glial fibrillary acidic protein (GFAP), a marker of astrocytes. It was revealed that the cuprizone caused extensive demyelination and astroglyosis. IGF-1 treatment restored the size of the corpus callosum and the number of astrocytes in the corpus callosum and the anterior commissure to the control level.

Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial

PubMed Central

Smith, Stephen M.; de Jager, Celeste A.; Whitbread, Philippa; Johnston, Carole; Agacinski, Grzegorz; Oulhaj, Abderrahim; Bradley, Kevin M.; Jacoby, Robin

2010-01-01

Background An increased rate of brain atrophy is often observed in older subjects, in particular those who suffer from cognitive decline. Homocysteine is a risk factor for brain atrophy, cognitive impairment and dementia. Plasma concentrations of homocysteine can be lowered by dietary administration of B vitamins. Objective To determine whether supplementation with B vitamins that lower levels of plasma total homocysteine can slow the rate of brain atrophy in subjects with mild cognitive impairment in a randomised controlled trial (VITACOG, ISRCTN 94410159). Methods and Findings Single-center, randomized, double-blind controlled trial of high-dose folic acid, vitamins B6 and B12 in 271 individuals (of 646 screened) over 70 y old with mild cognitive impairment. A subset (187) volunteered to have cranial MRI scans at the start and finish of the study. Participants were randomly assigned to two groups of equal size, one treated with folic acid (0.8 mg/d), vitamin B12 (0.5 mg/d) and vitamin B6 (20 mg/d), the other with placebo; treatment was for 24 months. The main outcome measure was the change in the rate of atrophy of the whole brain assessed by serial volumetric MRI scans. Results A total of 168 participants (85 in active treatment group; 83 receiving placebo) completed the MRI section of the trial. The mean rate of brain atrophy per year was 0.76% [95% CI, 0.63–0.90] in the active treatment group and 1.08% [0.94–1.22] in the placebo group (P = 0.001). The treatment response was related to baseline homocysteine levels: the rate of atrophy in participants with homocysteine >13 µmol/L was 53% lower in the active treatment group (P = 0.001). A greater rate of atrophy was associated with a lower final cognitive test scores. There was no difference in serious adverse events according to treatment category. Conclusions and Significance The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins. Sixteen percent of those over 70 y old have mild cognitive impairment and half of these develop Alzheimer's disease. Since accelerated brain atrophy is a characteristic of subjects with mild cognitive impairment who convert to Alzheimer's disease, trials are needed to see if the same treatment will delay the development of Alzheimer's disease. Trial Registration Controlled-Trials.com ISRCTN94410159 PMID:20838622

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.

Size-Dependent Deposition, Translocation, and Microglial Activation of Inhaled Silver Nanoparticles in the Rodent Nose and Brain

PubMed Central

Patchin, Esther Shin; Anderson, Donald S.; Silva, Rona M.; Uyeminami, Dale L.; Scott, Grace M.; Guo, Ting; Van Winkle, Laura S.; Pinkerton, Kent E.

2016-01-01

Background: Silver nanoparticles (AgNP) are present in personal, commercial, and industrial products, which are often aerosolized. Current understanding of the deposition, translocation, and health-related impacts of AgNP inhalation is limited. Objectives: We determined a) the deposition and retention of inhaled Ag in the nasal cavity from nose-only exposure; b) the timing for Ag translocation to and retention/clearance in the olfactory bulb (OB); and c) whether the presence of Ag in the OB affects microglial activity. Methods: Male Sprague-Dawley rats were exposed nose-only to citrate-buffered 20- or 110-nm AgNP (C20 or C110, respectively) or citrate buffer alone for 6 hr. The nasal cavity and OB were examined for the presence of Ag and for biological responses up to 56 days post-exposure (8 weeks). Results: The highest nasal Ag deposition was observed on Day 0 for both AgNP sizes. Inhalation of aerosolized C20 resulted in rapid translocation of Ag to the OB and in microglial activation at Days 0, 1, and 7. In contrast, inhalation of C110 resulted in a gradual but progressive transport of Ag to and retention in the OB, with a trend for microglial activation to variably be above control. Conclusions: The results of this study show that after rats experienced a 6-hr inhalation exposure to 20- and 110-nm AgNP at a single point in time, Ag deposition in the nose, the rate of translocation to the brain, and subsequent microglial activation in the OB differed depending on AgNP size and time since exposure. Citation: Patchin ES, Anderson DS, Silva RM, Uyeminami DL, Scott GM, Guo T, Van Winkle LS, Pinkerton KE. 2016. Size-dependent deposition, translocation, and microglial activation of inhaled silver nanoparticles in the rodent nose and brain. Environ Health Perspect 124:1870–1875; http://dx.doi.org/10.1289/EHP234 PMID:27152509

Affective context interferes with cognitive control in unipolar depression: An fMRI investigation

PubMed Central

Dichter, Gabriel S.; Felder, Jennifer N.; Smoski, Moria J.

2009-01-01

Background Unipolar major depressive disorder (MDD) is characterized by aberrant amygdala responses to sad stimuli and poor cognitive control, but the interactive effects of these impairments are poorly understood. Aim To evaluate brain activation in MDD in response to cognitive control stimuli embedded within sad and neutral contexts. Method Fourteen adults with MDD and fifteen matched controls participated in a mixed block/event-related functional magnetic resonance imaging (fMRI) task that presented oddball target stimuli embedded within blocks of sad or neutral images. Results Target events activated similar prefrontal brain regions in both groups. However, responses to target events embedded within blocks of emotional images revealed a clear group dissociation. During neutral blocks, the control group demonstrated greater activation to targets in the midfrontal gyrus and anterior cingulate relative to the MDD group, replicating previous findings of prefrontal hypo-activation in MDD samples to cognitive control stimuli. However, during sad blocks, the MDD group demonstrated greater activation in a number of prefrontal regions, including the mid-, inferior, and orbito-frontal gyri and the anterior cingulate, suggesting that relatively more prefrontal brain activation was required to disengage from the sad images to respond to the target events. Limitations A larger sample size would have provided greater statistical power, and more standardized stimuli would have increased external validity. Conclusions This double dissociation of prefrontal responses to target events embedded within neutral and sad context suggests that MDD impacts not only responses to affective events, but extends to other cognitive processes carried out in the context of affective engagement. This implies that emotional reactivity to sad events in MDD may impact functioning more broadly than previously understood. PMID:18706701

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…

Dolphin social intelligence: complex alliance relationships in bottlenose dolphins and a consideration of selective environments for extreme brain size evolution in mammals.

PubMed

Connor, Richard C

2007-04-29

Bottlenose dolphins in Shark Bay, Australia, live in a large, unbounded society with a fission-fusion grouping pattern. Potential cognitive demands include the need to develop social strategies involving the recognition of a large number of individuals and their relationships with others. Patterns of alliance affiliation among males may be more complex than are currently known for any non-human, with individuals participating in 2-3 levels of shifting alliances. Males mediate alliance relationships with gentle contact behaviours such as petting, but synchrony also plays an important role in affiliative interactions. In general, selection for social intelligence in the context of shifting alliances will depend on the extent to which there are strategic options and risk. Extreme brain size evolution may have occurred more than once in the toothed whales, reaching peaks in the dolphin family and the sperm whale. All three 'peaks' of large brain size evolution in mammals (odontocetes, humans and elephants) shared a common selective environment: extreme mutual dependence based on external threats from predators or conspecific groups. In this context, social competition, and consequently selection for greater cognitive abilities and large brain size, was intense.

Three-dimensional mapping of the lateral ventricles in autism

PubMed Central

Vidal, Christine N.; Nicolsonln, Rob; Boire, Jean-Yves; Barra, Vincent; DeVito, Timothy J.; Hayashi, Kiralee M.; Geaga, Jennifer A.; Drost, Dick J.; Williamson, Peter C.; Rajakumar, Nagalingam; Toga, Arthur W.; Thompson, Paul M.

2009-01-01

In this study, a computational mapping technique was used to examine the three-dimensional profile of the lateral ventricles in autism. T1-weighted three-dimensional magnetic resonance images of the brain were acquired from 20 males with autism (age: 10.1 ± 3.5 years) and 22 male control subjects (age: 10.7 ± 2.5 years). The lateral ventricles were delineated manually and ventricular volumes were compared between the two groups. Ventricular traces were also converted into statistical three-dimensional maps, based on anatomical surface meshes. These maps were used to visualize regional morphological differences in the thickness of the lateral ventricles between patients and controls. Although ventricular volumes measured using traditional methods did not differ significantly between groups, statistical surface maps revealed subtle, highly localized reductions in ventricular size in patients with autism in the left frontal and occipital horns. These localized reductions in the lateral ventricles may result from exaggerated brain growth early in life. PMID:18502618

Combining glial cell line-derived neurotrophic factor gene delivery (AdGDNF) with L-arginine decreases contusion size but not behavioral deficits after traumatic brain injury.

PubMed

Degeorge, M L; Marlowe, D; Werner, E; Soderstrom, K E; Stock, M; Mueller, A; Bohn, M C; Kozlowski, D A

2011-07-27

Our laboratory has previously demonstrated that viral administration of glial cell line-derived neurotrophic factor (AdGDNF), one week prior to a controlled cortical impact (CCI) over the forelimb sensorimotor cortex of the rat (FL-SMC) is neuroprotective, but does not significantly enhance recovery of sensorimotor function. One possible explanation for this discrepancy is that although protected, neurons may not have been functional due to enduring metabolic deficiencies. Additionally, metabolic events following TBI may interfere with expression of therapeutic proteins administered to the injured brain via gene therapy. The current study focused on enhancing the metabolic function of the brain by increasing cerebral blood flow (CBF) with l-arginine in conjunction with administration of AdGDNF immediately following CCI. An adenoviral vector harboring human GDNF was injected unilaterally into FL-SMC of the rat immediately following a unilateral CCI over the FL-SMC. Within 30min of the CCI and AdGDNF injections, some animals were injected with l-arginine (i.v.). Tests of forelimb function and asymmetry were administered for 4weeks post-injury. Animals were sacrificed and contusion size and GDNF protein expression measured. This study demonstrated that rats treated with AdGDNF and l-arginine post-CCI had a significantly smaller contusion than injured rats who did not receive any treatment, or injured rats treated with either AdGDNF or l-arginine alone. Nevertheless, no amelioration of behavioral deficits was seen. These findings suggest that AdGDNF alone following a CCI was not therapeutic and although combining it with l-arginine decreased contusion size, it did not enhance behavioral recovery. Copyright © 2011 Elsevier B.V. All rights reserved.

Reduced intestinal brain-derived neurotrophic factor increases vagal sensory innervation of the intestine and enhances satiation.

PubMed

Biddinger, Jessica E; Fox, Edward A

2014-07-30

Brain-derived neurotrophic factor (BDNF) is produced by developing and mature gastrointestinal (GI) tissues that are heavily innervated by autonomic neurons and may therefore control their development or function. To begin investigating this hypothesis, we compared the morphology, distribution, and density of intraganglionic laminar endings (IGLEs), the predominant vagal GI afferent, in mice with reduced intestinal BDNF (INT-BDNF(-/-)) and controls. Contrary to expectations of reduced development, IGLE density and longitudinal axon bundle number in the intestine of INT-BDNF(-/-) mice were increased, but stomach IGLEs were normal. INT-BDNF(-/-) mice also exhibited increased vagal sensory neuron numbers, suggesting that their survival was enhanced. To determine whether increased intestinal IGLE density or other changes to gut innervation in INT-BDNF(-/-) mice altered feeding behavior, meal pattern and microstructural analyses were performed. INT-BDNF(-/-) mice ate meals of much shorter duration than controls, resulting in reduced meal size. Increased suppression of feeding in INT-BDNF(-/-) mice during the late phase of a scheduled meal suggested that increased satiation signaling contributed to reduced meal duration and size. Furthermore, INT-BDNF(-/-) mice demonstrated increases in total daily intermeal interval and satiety ratio, suggesting that satiety signaling was augmented. Compensatory responses maintained normal daily food intake and body weight in INT-BDNF(-/-) mice. These findings suggest a target organ-derived neurotrophin suppresses development of that organ's sensory innervation and sensory neuron survival and demonstrate a role for BDNF produced by peripheral tissues in short-term controls of feeding, likely through its regulation of development or function of gut innervation, possibly including augmented intestinal IGLE innervation. Copyright © 2014 the authors 0270-6474/14/3410379-15$15.00/0.

Enzyme-linked DNA dendrimer nanosensors for acetylcholine

PubMed Central

Walsh, Ryan; Morales, Jennifer M.; Skipwith, Christopher G.; Ruckh, Timothy T.; Clark, Heather A.

2015-01-01

It is currently difficult to measure small dynamics of molecules in the brain with high spatial and temporal resolution while connecting them to the bigger picture of brain function. A step towards understanding the underlying neural networks of the brain is the ability to sense discrete changes of acetylcholine within a synapse. Here we show an efficient method for generating acetylcholine-detecting nanosensors based on DNA dendrimer scaffolds that incorporate butyrylcholinesterase and fluorescein in a nanoscale arrangement. These nanosensors are selective for acetylcholine and reversibly respond to levels of acetylcholine in the neurophysiological range. This DNA dendrimer architecture has the potential to overcome current obstacles to sensing in the synaptic environment, including the nanoscale size constraints of the synapse and the ability to quantify the spatio-temporal fluctuations of neurotransmitter release. By combining the control of nanosensor architecture with the strategic placement of fluorescent reporters and enzymes, this novel nanosensor platform can facilitate the development of new selective imaging tools for neuroscience. PMID:26442999

Enzyme-linked DNA dendrimer nanosensors for acetylcholine.

PubMed

Walsh, Ryan; Morales, Jennifer M; Skipwith, Christopher G; Ruckh, Timothy T; Clark, Heather A

2015-10-07

It is currently difficult to measure small dynamics of molecules in the brain with high spatial and temporal resolution while connecting them to the bigger picture of brain function. A step towards understanding the underlying neural networks of the brain is the ability to sense discrete changes of acetylcholine within a synapse. Here we show an efficient method for generating acetylcholine-detecting nanosensors based on DNA dendrimer scaffolds that incorporate butyrylcholinesterase and fluorescein in a nanoscale arrangement. These nanosensors are selective for acetylcholine and reversibly respond to levels of acetylcholine in the neurophysiological range. This DNA dendrimer architecture has the potential to overcome current obstacles to sensing in the synaptic environment, including the nanoscale size constraints of the synapse and the ability to quantify the spatio-temporal fluctuations of neurotransmitter release. By combining the control of nanosensor architecture with the strategic placement of fluorescent reporters and enzymes, this novel nanosensor platform can facilitate the development of new selective imaging tools for neuroscience.

Enzyme-linked DNA dendrimer nanosensors for acetylcholine

NASA Astrophysics Data System (ADS)

Walsh, Ryan; Morales, Jennifer M.; Skipwith, Christopher G.; Ruckh, Timothy T.; Clark, Heather A.

2015-10-01

It is currently difficult to measure small dynamics of molecules in the brain with high spatial and temporal resolution while connecting them to the bigger picture of brain function. A step towards understanding the underlying neural networks of the brain is the ability to sense discrete changes of acetylcholine within a synapse. Here we show an efficient method for generating acetylcholine-detecting nanosensors based on DNA dendrimer scaffolds that incorporate butyrylcholinesterase and fluorescein in a nanoscale arrangement. These nanosensors are selective for acetylcholine and reversibly respond to levels of acetylcholine in the neurophysiological range. This DNA dendrimer architecture has the potential to overcome current obstacles to sensing in the synaptic environment, including the nanoscale size constraints of the synapse and the ability to quantify the spatio-temporal fluctuations of neurotransmitter release. By combining the control of nanosensor architecture with the strategic placement of fluorescent reporters and enzymes, this novel nanosensor platform can facilitate the development of new selective imaging tools for neuroscience.

Altered proliferation and networks in neural cells derived from idiopathic autistic individuals.

PubMed

Marchetto, Maria C; Belinson, Haim; Tian, Yuan; Freitas, Beatriz C; Fu, Chen; Vadodaria, Krishna; Beltrao-Braga, Patricia; Trujillo, Cleber A; Mendes, Ana P D; Padmanabhan, Krishnan; Nunez, Yanelli; Ou, Jing; Ghosh, Himanish; Wright, Rebecca; Brennand, Kristen; Pierce, Karen; Eichenfield, Lawrence; Pramparo, Tiziano; Eyler, Lisa; Barnes, Cynthia C; Courchesne, Eric; Geschwind, Daniel H; Gage, Fred H; Wynshaw-Boris, Anthony; Muotri, Alysson R

2017-06-01

Autism spectrum disorders (ASD) are common, complex and heterogeneous neurodevelopmental disorders. Cellular and molecular mechanisms responsible for ASD pathogenesis have been proposed based on genetic studies, brain pathology and imaging, but a major impediment to testing ASD hypotheses is the lack of human cell models. Here, we reprogrammed fibroblasts to generate induced pluripotent stem cells, neural progenitor cells (NPCs) and neurons from ASD individuals with early brain overgrowth and non-ASD controls with normal brain size. ASD-derived NPCs display increased cell proliferation because of dysregulation of a β-catenin/BRN2 transcriptional cascade. ASD-derived neurons display abnormal neurogenesis and reduced synaptogenesis leading to functional defects in neuronal networks. Interestingly, defects in neuronal networks could be rescued by insulin growth factor 1 (IGF-1), a drug that is currently in clinical trials for ASD. This work demonstrates that selection of ASD subjects based on endophenotypes unraveled biologically relevant pathway disruption and revealed a potential cellular mechanism for the therapeutic effect of IGF-1.

Increased CSF aquaporin-4, and interleukin-6 levels in dogs with idiopathic communicating internal hydrocephalus and a decrease after ventriculo-peritoneal shunting.

PubMed

Schmidt, Martin J; Rummel, Christoph; Hauer, Jessica; Kolecka, Malgorzata; Ondreka, Nele; McClure, Vanessa; Roth, Joachim

2016-06-29

Studies in animal models, in which internal hydrocephalus has been induced by obstructing the cerebrospinal fluid pathways, have documented an up-regulation of the concentrations of aquaporin-4 (AQP4) in the brain. In this study, the concentrations of aquaporin-1 (AQP1), AQP1, AQP4 and interleukin-6 (IL-6) were determined in the CSF of dogs with idiopathic communicating hydrocephalus before and after the reduction of intraventricular volume following ventriculo-peritoneal shunt (VP-shunt) treatment. The concentrations of AQP4 and IL-6 were increased in the cerebrospinal fluid of dogs with hydrocephalus compared to controls. Both parameters significantly decreased after surgical treatment, accompanied by decrease of ventricular size and the clinical recovery of the dogs. AQP1 was not detectable in CSF. Brain AQP4 up-regulation might be a compensatory response in dogs with hydrocephalus. Future determination of AQP4 at the mRNA and protein level in brain tissue is warranted to substantiate this hypothesis.

Comparison of Automated Brain Volume Measures obtained with NeuroQuant and FreeSurfer.

PubMed

Ochs, Alfred L; Ross, David E; Zannoni, Megan D; Abildskov, Tracy J; Bigler, Erin D

2015-01-01

To examine intermethod reliabilities and differences between FreeSurfer and the FDA-cleared congener, NeuroQuant, both fully automated methods for structural brain MRI measurements. MRI scans from 20 normal control subjects, 20 Alzheimer's disease patients, and 20 mild traumatically brain-injured patients were analyzed with NeuroQuant and with FreeSurfer. Intermethod reliability was evaluated. Pairwise correlation coefficients, intraclass correlation coefficients, and effect size differences were computed. NeuroQuant versus FreeSurfer measures showed excellent to good intermethod reliability for the 21 regions evaluated (r: .63 to .99/ICC: .62 to .99/ES: -.33 to 2.08) except for the pallidum (r/ICC/ES = .31/.29/-2.2) and cerebellar white matter (r/ICC/ES = .31/.31/.08). Volumes reported by NeuroQuant were generally larger than those reported by FreeSurfer with the whole brain parenchyma volume reported by NeuroQuant 6.50% larger than the volume reported by FreeSurfer. There was no systematic difference in results between the 3 subgroups. NeuroQuant and FreeSurfer showed good to excellent intermethod reliability in volumetric measurements for all brain regions examined with the only exceptions being the pallidum and cerebellar white matter. This finding was robust for normal individuals, patients with Alzheimer's disease, and patients with mild traumatic brain injury. Copyright © 2015 by the American Society of Neuroimaging.

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.

Volumetric structural brain abnormalities in men with schizophrenia or antisocial personality disorder.

PubMed

Barkataki, Ian; Kumari, Veena; Das, Mrigendra; Taylor, Pamela; Sharma, Tonmoy

2006-05-15

Brain abnormalities are found in association with antisocial personality disorder and schizophrenia, the two mental disorders most implicated in violent behaviour. Structural magnetic resonance imaging was used to investigate the whole brain, cerebellum, temporal lobe, lateral ventricles, caudate nucleus, putamen, thalamus, hippocampus, amygdala and the prefrontal, pre-motor, sensorimotor, occipito-parietal regions in 13 men with antisocial personality disorder, 13 men with schizophrenia and a history of violence, 15 men with schizophrenia without violent history and 15 healthy non-violent men. Compared to controls, the antisocial personality disorder group displayed reductions in whole brain volume and temporal lobe as well as increases in putamen volume. Both schizophrenia groups regardless of violence history exhibited increased lateral ventricle volume, while the schizophrenia group with violent history showed further abnormalities including reduced whole brain and hippocampal volumes and increased putamen size. The findings suggest that individuals with antisocial personality disorder as well as those with schizophrenia and a history of violence have common neural abnormalities, but also show neuro-anatomical differences. The processes by which they came to apparently common ground may, however, differ. The finding of temporal lobe reductions prevalent among those with antisocial personality disorder and hippocampal reduction in the violent men with schizophrenia contributes support for the importance of this region in mediating violent behaviour.

Animal models of cerebral ischemia

NASA Astrophysics Data System (ADS)

Khodanovich, M. Yu.; Kisel, A. A.

2015-11-01

Cerebral ischemia remains one of the most frequent causes of death and disability worldwide. Animal models are necessary to understand complex molecular mechanisms of brain damage as well as for the development of new therapies for stroke. This review considers a certain range of animal models of cerebral ischemia, including several types of focal and global ischemia. Since animal models vary in specificity for the human disease which they reproduce, the complexity of surgery, infarct size, reliability of reproduction for statistical analysis, and adequate models need to be chosen according to the aim of a study. The reproduction of a particular animal model needs to be evaluated using appropriate tools, including the behavioral assessment of injury and non-invasive and post-mortem control of brain damage. These problems also have been summarized in the review.

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.

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.

Normal variation in early parental sensitivity predicts child structural brain development.

PubMed

Kok, Rianne; Thijssen, Sandra; Bakermans-Kranenburg, Marian J; Jaddoe, Vincent W V; Verhulst, Frank C; White, Tonya; van IJzendoorn, Marinus H; Tiemeier, Henning

2015-10-01

Early caregiving can have an impact on brain structure and function in children. The influence of extreme caregiving experiences has been demonstrated, but studies on the influence of normal variation in parenting quality are scarce. Moreover, no studies to date have included the role of both maternal and paternal sensitivity in child brain maturation. This study examined the prospective relation between mothers' and fathers' sensitive caregiving in early childhood and brain structure later in childhood. Participants were enrolled in a population-based prenatal cohort. For 191 families, maternal and paternal sensitivity was repeatedly observed when the child was between 1 year and 4 years of age. Head circumference was assessed at 6 weeks, and brain structure was assessed using magnetic resonance imaging (MRI) measurements at 8 years of age. Higher levels of parental sensitivity in early childhood were associated with larger total brain volume (adjusted β = 0.15, p = .01) and gray matter volume (adjusted β = 0.16, p = .01) at 8 years, controlling for infant head size. Higher levels of maternal sensitivity in early childhood were associated with a larger gray matter volume (adjusted β = 0.13, p = .04) at 8 years, independent of infant head circumference. Associations with maternal versus paternal sensitivity were not significantly different. Normal variation in caregiving quality is related to markers of more optimal brain development in children. The results illustrate the important role of both mothers and fathers in child brain development. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Small Worldness in Dense and Weighted Connectomes

NASA Astrophysics Data System (ADS)

Colon-Perez, Luis; Couret, Michelle; Triplett, William; Price, Catherine; Mareci, Thomas

2016-05-01

The human brain is a heterogeneous network of connected functional regions; however, most brain network studies assume that all brain connections can be described in a framework of binary connections. The brain is a complex structure of white matter tracts connected by a wide range of tract sizes, which suggests a broad range of connection strengths. Therefore, the assumption that the connections are binary yields an incomplete picture of the brain. Various thresholding methods have been used to remove spurious connections and reduce the graph density in binary networks. But these thresholds are arbitrary and make problematic the comparison of networks created at different thresholds. The heterogeneity of connection strengths can be represented in graph theory by applying weights to the network edges. Using our recently introduced edge weight parameter, we estimated the topological brain network organization using a complimentary weighted connectivity framework to the traditional framework of a binary network. To examine the reproducibility of brain networks in a controlled condition, we studied the topological network organization of a single healthy individual by acquiring 10 repeated diffusion-weighted magnetic resonance image datasets, over a one-month period on the same scanner, and analyzing these networks with deterministic tractography. We applied a threshold to both the binary and weighted networks and determined that the extra degree of freedom that comes with the framework of weighting network connectivity provides a robust result as any threshold level. The proposed weighted connectivity framework provides a stable result and is able to demonstrate the small world property of brain networks in situations where the binary framework is inadequate and unable to demonstrate this network property.

Zebrafish: a model animal for analyzing the impact of environmental pollutants on muscle and brain mitochondrial bioenergetics.

PubMed

Bourdineaud, Jean-Paul; Rossignol, R; Brèthes, D

2013-01-01

Mercury, anthropogenic release of uranium (U), and nanoparticles constitute hazardous environmental pollutants able to accumulate along the aquatic food chain with severe risk for animal and human health. The impact of such pollutants on living organisms has been up to now approached by classical toxicology in which huge doses of toxic compounds, environmentally irrelevant, are displayed through routes that never occur in the lifespan of organisms (for instance injecting a bolus of mercury to an animal although the main route is through prey and fish eating). We wanted to address the effect of such pollutants on the muscle and brain mitochondrial bioenergetics under realistic conditions, at unprecedented low doses, using an aquatic model animal, the zebrafish Danio rerio. We developed an original method to measure brain mitochondrial respiration: a single brain was put in 1.5 mL conical tube containing a respiratory buffer. Brains were gently homogenized by 13 strokes with a conical plastic pestle, and the homogenates were immediately used for respiration measurements. Skinned muscle fibers were prepared by saponin permeabilization. Zebrafish were contaminated with food containing 13 μg of methylmercury (MeHg)/g, an environmentally relevant dose. In permeabilized muscle fibers, we observed a strong inhibition of both state 3 mitochondrial respiration and cytochrome c oxidase activity after 49 days of MeHg exposure. We measured a dramatic decrease in the rate of ATP release by skinned muscle fibers. Contrarily to muscles, brain mitochondrial respiration was not modified by MeHg exposure although brain accumulated twice as much MeHg than muscles. When zebrafish were exposed to 30 μg/L of waterborne U, the basal mitochondrial respiratory control ratio was decreased in muscles after 28 days of exposure. This was due to an increase of the inner mitochondrial membrane permeability. The impact of a daily ration of food containing gold nanoparticles of two sizes (12 and 50 nm) was investigated at a very low dose for 60 days (40 ng gold/fish/day). Mitochondrial dysfunctions appeared in brain and muscle for both tested sizes. In conclusion, at low environmental doses, dietary or waterborne heavy metals impinged on zebrafish tissue mitochondrial respiration. Due to its incredible simplicity avoiding tedious and time-consuming mitochondria isolation, our one-pot method allowing brain respiratory analysis should give colleagues the incentive to use zebrafish brain as a model in bioenergetics. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy. Copyright © 2012 Elsevier Ltd. All rights reserved.

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.

The rat: a laboratory model for studies of the diving response

PubMed Central

Gan, Qi; Juric, Rajko

2010-01-01

Underwater submersion in mammals induces apnea, parasympathetically mediated bradycardia, and sympathetically mediated peripheral vasoconstriction. These effects are collectively termed the diving response, potentially the most powerful autonomic reflex known. Although these physiological responses are directed by neurons in the brain, study of neural control of the diving response has been hampered since 1) it is difficult to study the brains of animals while they are underwater, 2) feral marine mammals are usually large and have brains of variable size, and 3) there are but few references on the brains of naturally diving species. Similar responses are elicited in anesthetized rodents after stimulation of their nasal mucosa, but this nasopharyngeal reflex has not been compared directly with natural diving behavior in the rat. In the present study, we compared hemodynamic responses elicited in awake rats during volitional underwater submersion with those of rats swimming on the water's surface, rats involuntarily submerged, and rats either anesthetized or decerebrate and stimulated nasally with ammonia vapors. We show that the hemodynamic changes to voluntary diving in the rat are similar to those of naturally diving marine mammals. We also show that the responses of voluntary diving rats are 1) significantly different from those seen during swimming, 2) generally similar to those elicited in trained rats involuntarily “dunked” underwater, and 3) generally different from those seen from dunking naive rats underwater. Nasal stimulation of anesthetized rats differed most from the hemodynamic variables of rats trained to dive voluntarily. We propose that the rat trained to dive underwater is an excellent laboratory model to study neural control of the mammalian diving response, and also suggest that some investigations may be done with nasal stimulation of decerebrate preparations to decipher such control. PMID:20093670

THR-18, a 18-mer peptide derived from PAI-1, is neuroprotective and improves thrombolysis by tPA in rat stroke models.

PubMed

Krakovsky, M; Polianski, V; Nimrod, A; Higazi, A; Leker, R R; Lamensdorf, I

2011-11-01

The thrombolytic treatment of stroke is limited by a narrow therapeutic time window and is associated with significant adverse side effects. To improve this situation, the modulation of tissue-type plasminogen activator (tPA) activity by a synthetic plasminogen activator inhibitor-1-derived 18-mer peptide (THR-18) was examined in two models of stroke in rats. In the first model (thromboembolic), stroke was induced by intra-carotid injection of micro-clots to rats, and tPA (6 mg/kg) was intravenously infused for 30 minutes with or without THR-18 (1 mg/kg) at 4 hours post-induction. In the second model [transient middle cerebral artery occlusion (tMCAO)], stroke was induced for 2 hours by a transient mechanical occlusion. tPA and/or THR-18 (0.02, 0.1, and 1 mg/kg) were intravenously infused for 60 minutes at the time of reperfusion. In the thromboembolic model, cerebral blood flow, measured before and up to 5.5 hours post-induction, revealed that tPA administration caused reperfusion of flow at 30 minutes post-infusion. Later on, an additional increase in reperfusion was seen in the tPA+THR-18 group, and not with tPA alone. In both models, the frequency of intracranial hemorrhage in the tPA-treated group was found to be significantly higher than the control, and this tPA effect was attenuated by THR-18. In the thromboembolic study, infarct size and brain edema were similar in the control and tPA-treated rats. However, the combination of tPA and THR-18 caused a statistically significant reduction in both parameters (infarct size 17.8 versus 25.0%, brain edema 5 versus 8%, tPA+THR-18 versus control, respectively). In the tMCAO mechanical model, infarct size and brain edema were both increased by tPA treatment as compared to the control group, and this increase was markedly diminished by THR-18 co-administration. Neurobehavioral assessment of the tMCAO animals performed at 72 hours post-stroke induction revealed significant improvements (P<0.05-0.01) in neuroscores in all groups of animals treated with peptide-tPA, as compared to the tPA monotherapy group. A significant (P<0.05) improvement in the neurological outcome was also seen in the THR-18 monoterapy group, as compared to the control animals, thus demonstrating a clear neuroprotective effect by the peptide on its own. The results support the use of THR-18 together with tPA in the thrombolytic therapy of stroke, in order to achieve better patency, less tPA-induced damage, and possibly a widening of tPA therapeutic time window.

Role of the Axon Initial Segment in the Control of Spontaneous Frequency of Nigral Dopaminergic Neurons In Vivo.

PubMed

Meza, Rodrigo C; López-Jury, Luciana; Canavier, Carmen C; Henny, Pablo

2018-01-17

The spontaneous tonic discharge activity of nigral dopamine neurons plays a fundamental role in dopaminergic signaling. To investigate the role of neuronal morphology and architecture with respect to spontaneous activity in this population, we visualized the 3D structure of the axon initial segment (AIS) along with the entire somatodendritic domain of adult male mouse dopaminergic neurons, previously recorded in vivo We observed a positive correlation of the firing rate with both proximity and size of the AIS. Computational modeling showed that the size of the AIS, but not its position within the somatodendritic domain, is the major causal determinant of the tonic firing rate in the intact model, by virtue of the higher intrinsic frequency of the isolated AIS. Further mechanistic analysis of the relationship between neuronal morphology and firing rate showed that dopaminergic neurons function as a coupled oscillator whose frequency of discharge results from a compromise between AIS and somatodendritic oscillators. Thus, morphology plays a critical role in setting the basal tonic firing rate, which in turn could control striatal dopaminergic signaling that mediates motivation and movement. SIGNIFICANCE STATEMENT The frequency at which nigral dopamine neurons discharge action potentials sets baseline dopamine levels in the brain, which enables activity in motor, cognitive, and motivational systems. Here, we demonstrate that the size of the axon initial segment, a subcellular compartment responsible for initiating action potentials, is a key determinant of the firing rate in these neurons. The axon initial segment and all the molecular components that underlie its critical function may provide a novel target for the regulation of dopamine levels in the brain. Copyright © 2018 the authors 0270-6474/18/380733-12$15.00/0.

Subthalamic nucleus deep brain stimulation improves somatosensory function in Parkinson's disease.

PubMed

Aman, Joshua E; Abosch, Aviva; Bebler, Maggie; Lu, Chia-Hao; Konczak, Jürgen

2014-02-01

An established treatment for the motor symptoms of Parkinson's disease (PD) is deep brain stimulation (DBS) of the subthalamic nucleus (STN). Mounting evidence suggests that PD is also associated with somatosensory deficits, yet the effect of STN-DBS on somatosensory processing is largely unknown. This study investigated whether STN-DBS affects somatosensory processing, specifically the processing of tactile and proprioceptive cues, by systematically examining the accuracy of haptic perception of object size. (Haptic perception refers to one's ability to extract object features such as shape and size by active touch.) Without vision, 13 PD patients with implanted STN-DBS and 13 healthy controls haptically explored the heights of 2 successively presented 3-dimensional (3D) blocks using a precision grip. Participants verbally indicated which block was taller and then used their nonprobing hand to motorically match the perceived size of the comparison block. Patients were tested during ON and OFF stimulation, following a 12-hour medication washout period. First, when compared to controls, the PD group's haptic discrimination threshold during OFF stimulation was elevated by 192% and mean hand aperture error was increased by 105%. Second, DBS lowered the haptic discrimination threshold by 26% and aperture error decreased by 20%. Third, during DBS ON, probing with the motorically more affected hand decreased haptic precision compared to probing with the less affected hand. This study offers the first evidence that STN-DBS improves haptic precision, further indicating that somatosensory function is improved by STN-DBS. We conclude that DBS-related improvements are not explained by improvements in motor function alone, but rather by enhanced somatosensory processing. © 2013 Movement Disorder Society.

Neurobiology of KB220Z-Glutaminergic-Dopaminergic Optimization Complex [GDOC] as a Liquid Nano: Clinical Activation of Brain in a Highly Functional Clinician Improving Focus, Motivation and Overall Sensory Input Following Chronic Intake.

PubMed

Duquette, Lucien L; Mattiace, Frank; Blum, Kenneth; Waite, Roger L; Boland, Teresa; McLaughlin, Thomas; Dushaj, Kristina; Febo, Marcelo; Badgaiyan, Rajendra D

2016-01-01

With neurogenetic and epigenetic tools utilized in research and neuroimaging, we are unraveling the mysteries of brain function, especially as it relates to Reward Deficiency (RDS). We encourage the development of pharmaceuticals or nutraceuticals that promote a reduction in dopamine resistance and balance brain neurochemistry, leading to dopamine homeostasis. We disclose self-assessment of a highly functional professional under work-related stress following KB220Z use, a liquid (aqua) nano glutaminergic-dopaminergic optimization complex (GDOC). Subject took GDOC for one month. Subject self-administered GDOC using one-half-ounce twice a day. During first three days, unique brain activation occurred; resembling white noise after 30 minutes and sensation was strong for 45 minutes and then dissipated. He described effect as if his eyesight improved slightly and pointed out that his sense of smell and sleep greatly improved. Subject experienced a calming effect similar to meditation that could be linked to dopamine release. He also reported control of going over the edge after a hard day's work, which was coupled with a slight increase in energy, increased motivation to work, increased focus and multi-tasking, with clearer purpose of task at hand. Subject felt less inhibited in a social setting and suggested Syndrome that GDOC increased his Behavior Activating System (reward), while having a decrease in the Behavior Inhibition System (caution). These results and other related studies reveal an improved mood, work-related focus, and sleep. These effects as a subjective feeling of brain activation maybe due to direct or indirect dopaminergic interaction. While this case is encouraging, we must await more research in a larger randomized placebo-controlled study to map the role of GDOC, especially in a nano-sized product, to determine the possible effects on circuit inhibitory control and memory banks and the induction of dopamine homeostasis independent of either hypo- or hyper-dopaminergic traits/states.

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.

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.

Feasibility of a Cognitive Behavioral Intervention to Manage Fatigue in Individuals With Traumatic Brain Injury: A Pilot Study.

PubMed

Raina, Ketki D; Morse, Jennifer Q; Chisholm, Denise; Leibold, Mary Lou; Shen, Jennifer; Whyte, Ellen

2016-01-01

To evaluate the feasibility of conducting a randomized clinical trial of an Internet-based manualized intervention to teach individuals with traumatic brain injury to manage their fatigue. Community dwelling. Forty-one participants randomized to Maximizing Energy (MAX) intervention group (n = 20) and Health Education group (n = 21). The experimental group (MAX intervention) received an 8-week program that combined education and Problem-Solving Therapy to teach individuals to manage fatigue-related problems. The attention control group received health education. Primary outcome measures pertained to the feasibility of conducting the trial. Secondary outcomes were fatigue impact and fatigue severity assessed at baseline and postintervention. Of the 65 participants referred, 41 were enrolled (63% recruitment rate), of which 3 withdrew (92% retention rate). Participants in the experimental and control groups completed their homework 75% and 85% of the time, respectively, and were equally engaged in the sessions. Participants in the experimental group were able to learn and implement the MAX intervention steps. Effect sizes for all measures ranged from small (-0.17) to medium (-0.58) in favor of the intervention group. Findings from the study suggest that the MAX intervention is feasible to administer to individuals with post-traumatic brain injury fatigue.

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.

Warnings and caveats in brain controllability.

PubMed

Tu, Chengyi; Rocha, Rodrigo P; Corbetta, Maurizio; Zampieri, Sandro; Zorzi, Marco; Suweis, S

2018-08-01

A recent article by Gu et al. (Nat. Commun. 6, 2015) proposed to characterize brain networks, quantified using anatomical diffusion imaging, in terms of their "controllability", drawing on concepts and methods of control theory. They reported that brain activity is controllable from a single node, and that the topology of brain networks provides an explanation for the types of control roles that different regions play in the brain. In this work, we first briefly review the framework of control theory applied to complex networks. We then show contrasting results on brain controllability through the analysis of five different datasets and numerical simulations. We find that brain networks are not controllable (in a statistical significant way) by one single region. Additionally, we show that random null models, with no biological resemblance to brain network architecture, produce the same type of relationship observed by Gu et al. between the average/modal controllability and weighted degree. Finally, we find that resting state networks defined with fMRI cannot be attributed specific control roles. In summary, our study highlights some warning and caveats in the brain controllability framework. Copyright © 2018 Elsevier Inc. All rights reserved.

Control-related systems in the human brain

PubMed Central

Power, Jonathan D; Petersen, Steven E

2013-01-01

A fundamental question in cognitive neuroscience is how the human brain self-organizes to perform tasks. Multiple accounts of this self-organization are currently influential and in this article we survey one of these accounts. We begin by introducing a psychological model of task control and several neuroimaging signals it predicts. We then discuss where such signals are found across tasks with emphasis on brain regions where multiple control signals are present. We then present results derived from spontaneous task-free functional connectivity between control-related regions that dovetail with distinctions made by control signals present in these regions, leading to a proposal that there are at least two task control systems in the brain. This prompts consideration of whether and how such control systems distinguish themselves from other brain regions in a whole-brain context. We present evidence from whole-brain networks that such distinctions do occur and that control systems comprise some of the basic system-level organizational elements of the human brain. We close with observations from the whole-brain networks that may suggest parsimony between multiple accounts of cognitive control. PMID:23347645

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...

Increased Brain Glucose Uptake After 12 Weeks of Aerobic High-Intensity Interval Training in Young and Older Adults.

PubMed

Robinson, Matthew M; Lowe, Val J; Nair, K Sreekumaran

2018-01-01

Aerobic exercise training can increase brain volume and blood flow, but the impact on brain metabolism is less known. We determined whether high-intensity interval training (HIIT) increases brain metabolism by measuring brain glucose uptake in younger and older adults. Brain glucose uptake was measured before and after HIIT or a sedentary (SED) control period within a larger exercise study. Study procedures were performed at the Mayo Clinic in Rochester, MN. Participants were younger (18 to 30 years) or older (65 to 80 years) SED adults who were free of major medical conditions. Group sizes were 15 for HIIT (nine younger and six older) and 12 for SED (six younger and six older). Participants completed 12 weeks of HIIT or SED. HIIT was 3 days per week of 4 × 4 minute intervals at over 90% of peak aerobic capacity (VO2peak) with 2 days per week of treadmill walking at 70% VO2peak. Resting brain glucose uptake was measured using 18F-fluorodeoxyglucose positron emission tomography scans at baseline and at week 12. Scans were performed at 96 hours after exercise. VO2peak was measured by indirect calorimetry. Glucose uptake increased significantly in the parietal-temporal and caudate regions after HIIT compared with SED. The gains with HIIT were not observed in all brain regions. VO2peak was increased for all participants after HIIT and did not change with SED. We demonstrate that brain glucose metabolism increased after 12 weeks of HIIT in adults in regions where it is reduced in Alzheimer's disease. Copyright © 2017 Endocrine Society

Brain morphology in children with nevoid basal cell carcinoma syndrome.

PubMed

Shiohama, Tadashi; Fujii, Katsunori; Miyashita, Toshiyuki; Mizuochi, Hiromi; Uchikawa, Hideki; Shimojo, Naoki

2017-04-01

Brain morphology is tightly regulated by diverse signaling pathways. Hedgehog signaling is a candidate pathway considered responsible for regulating brain morphology. Nevoid basal cell carcinoma syndrome (NBCCS), caused by a PTCH1 mutation in the hedgehog signaling pathway, occasionally exhibits macrocephaly and medulloblastoma. Although cerebellar enlargement occurs in ptch1 heterozygous-deficient mice, its impact on human brain development remains unknown. We investigated the brain morphological characteristics of children with NBCCS. We evaluated brain T1-weighted images from nine children with NBCCS and 15 age-matched normal control (NC) children (mean [standard deviation], 12.2 [2.8] vs. 11.6 [2.3] years old). The diameters of the cerebrum, corpus callosum, and brain stem and the cerebellar volume were compared using two-tailed t-tests with Welch's correction. The transverse diameters (150.4 [9.9] vs. 136.0 [5.5] mm, P = 0.002) and longitudinal diameters (165.4 [8.0] vs. 151.3 [8.7] mm, P = 0.0007) of the cerebrum, cross-sectional area of the cerebellar vermis (18.7 [2.6] vs. 11.8 [1.7] cm 2 , P = 0.0001), and total volume of the cerebellar hemispheres (185.1 [13.0] vs. 131.9 [10.4] cm 3 , P = 0.0001) were significantly larger in the children with NBCCS than in NC children. Thinning of the corpus callosum and ventricular enlargement were also confirmed in children with NBCCS. We demonstrate that, on examination of the brain morphology, an increase in the size of the cerebrum, cerebellum, and cerebral ventricles is revealed in children with NBCCS compared to NC children. This suggests that constitutively active hedgehog signaling affects human brain morphology and the PI3K/AKT and RAS/MAPK pathways. © 2017 Wiley Periodicals, Inc.

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.

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 the direct effects of deep brain stimulation using embedded axon models

NASA Astrophysics Data System (ADS)

Sotiropoulos, Stamatios N.; Steinmetz, Peter N.

2007-06-01

To better understand the spatial extent of the direct effects of deep brain stimulation (DBS) on neurons, we implemented a geometrically realistic finite element electrical model incorporating anisotropic and inhomogenous conductivities. The model included the subthalamic nucleus (STN), substantia nigra (SN), zona incerta (ZI), fields of Forel H2 (FF), internal capsule (IC) and Medtronic 3387/3389 electrode. To quantify the effects of stimulation, we extended previous studies by using multi-compartment axon models with geometry and orientation consistent with anatomical features of the brain regions of interest. Simulation of axonal firing produced a map of relative changes in axonal activation. Voltage-controlled stimulation, with clinically typical parameters at the dorso-lateral STN, caused axon activation up to 4 mm from the target. This activation occurred within the FF, IC, SN and ZI with current intensities close to the average injected during DBS (3 mA). A sensitivity analysis of model parameters (fiber size, fiber orientation, degree of inhomogeneity, degree of anisotropy, electrode configuration) revealed that the FF and IC were consistently activated. Direct activation of axons outside the STN suggests that other brain regions may be involved in the beneficial effects of DBS when treating Parkinsonian symptoms.

Abnormal small-world brain functional networks in obsessive-compulsive disorder patients with poor insight.

PubMed

Lei, Hui; Cui, Yan; Fan, Jie; Zhang, Xiaocui; Zhong, Mingtian; Yi, Jinyao; Cai, Lin; Yao, Dezhong; Zhu, Xiongzhao

2017-09-01

There are limited data on neurobiological correlates of poor insight in obsessive-compulsive disorder (OCD). This study explored whether specific changes occur in small-world network (SWN) properties in the brain functional network of OCD patients with poor insight. Resting-state electroencephalograms (EEGs) were recorded for 12 medication-free OCD patients with poor insight, 50 medication-free OCD patients with good insight, and 36 healthy controls. Both of the OCD groups exhibited topological alterations in the brain functional network characterized by abnormal small-world parameters at the beta band. However, the alterations at the theta band only existed in the OCD patients with poor insight. A relatively small sample size. Subjects were naïve to medications and those with Axis I comorbidity were excluded, perhaps limiting generalizability. Disrupted functional integrity at the beta bands of the brain functional network may be related to OCD, while disrupted functional integrity at the theta band may be associated with poor insight in OCD patients, thus this study might provide novel insight into our understanding of the pathophysiology of OCD. Copyright © 2017 Elsevier B.V. All rights reserved.

Effectiveness of cognitive rehabilitation following acquired brain injury: a meta-analytic re-examination of Cicerone et al.'s (2000, 2005) systematic reviews.

PubMed

Rohling, Martin L; Faust, Mark E; Beverly, Brenda; Demakis, George

2009-01-01

The present study provides a meta-analysis of cognitive rehabilitation literature (K = 115, N = 2,014) that was originally reviewed by K. D. Cicerone et al. (2000, 2005) for the purpose of providing evidence-based practice guidelines for persons with acquired brain injury. The analysis yielded a small treatment effect size (ES = .30, d(+) statistic) directly attributable to cognitive rehabilitation. A larger treatment effect (ES = .71) was found for single-group pretest to posttest outcomes; however, modest improvement was observed for nontreatment control groups as well (ES = .41). Correction for this effect, which was not attributable to cognitive treatments, resulted in the small, but significant, overall estimate. Treatment effects were moderated by cognitive domain treated, time postinjury, type of brain injury, and age. The meta-analysis revealed sufficient evidence for the effectiveness of attention training after traumatic brain injury and of language and visuospatial training for aphasia and neglect syndromes after stroke. Results provide important quantitative documentation of effective treatments, complementing recent systematic reviews. Findings also highlight gaps in the scientific evidence supporting cognitive rehabilitation, thereby indicating future research directions. (c) 2009 APA, all rights reserved.

Neuroprotection by glutamate oxaloacetate transaminase in ischemic stroke: an experimental study.

PubMed

Campos, Francisco; Sobrino, Tomás; Ramos-Cabrer, Pedro; Argibay, Bárbara; Agulla, Jesús; Pérez-Mato, María; Rodríguez-González, Raquel; Brea, David; Castillo, José

2011-06-01

As ischemic stroke is associated with an excessive release of glutamate into the neuronal extracellular space, a decrease in blood glutamate levels could provide a mechanism to remove it from the brain tissue, by increasing the brain-blood gradient. In this regard, the ability of glutamate oxaloacetate transaminase (GOT) to metabolize glutamate in blood could represent a potential neuroprotective tool for ischemic stroke. This study aimed to determine the neuroprotective effects of GOT in an animal model of cerebral ischemia by means of a middle cerebral arterial occlusion (MCAO) following the Stroke Therapy Academic Industry Roundtable (STAIR) group guidelines. In this animal model, oxaloacetate-mediated GOT activation inhibited the increase of blood and cerebral glutamate after MCAO. This effect is reflected in a reduction of infarct size, smaller edema volume, and lower sensorimotor deficits with respect to controls. Magnetic resonance spectroscopy confirmed that the increase of glutamate levels in the brain parenchyma after MCAO is inhibited after oxaloacetate-mediated GOT activation. These findings show the capacity of the GOT to remove glutamate from the brain by means of blood glutamate degradation, and suggest the applicability of this enzyme as an efficient and novel neuroprotective tool against ischemic stroke.

A novel approach to quantify different iron forms in ex-vivo human brain tissue

PubMed Central

Kumar, Pravin; Bulk, Marjolein; Webb, Andrew; van der Weerd, Louise; Oosterkamp, Tjerk H.; Huber, Martina; Bossoni, Lucia

2016-01-01

We propose a novel combination of methods to study the physical properties of ferric ions and iron-oxide nanoparticles in post-mortem human brain, based on the combination of Electron Paramagnetic Resonance (EPR) and SQUID magnetometry. By means of EPR, we derive the concentration of the low molecular weight iron pool, as well as the product of its electron spin relaxation times. Additionally, by SQUID magnetometry we identify iron mineralization products ascribable to a magnetite/maghemite phase and a ferrihydrite (ferritin) phase. We further derive the concentration of magnetite/maghemite and of ferritin nanoparticles. To test out the new combined methodology, we studied brain tissue of an Alzheimer’s patient and a healthy control. Finally, we estimate that the size of the magnetite/maghemite nanoparticles, whose magnetic moments are blocked at room temperature, exceeds 40–50 nm, which is not compatible with the ferritin protein, the core of which is typically 6–8 nm. We believe that this methodology could be beneficial in the study of neurodegenerative diseases such as Alzheimer’s Disease which are characterized by abnormal iron accumulation in the brain. PMID:27941952

Sex Differences in Gray Matter Changes and Brain-Behavior Relationships in Patients with Stimulant Dependence.

PubMed

Regner, Michael F; Dalwani, Manish; Yamamoto, Dorothy; Perry, Robert I; Sakai, Joseph T; Honce, Justin M; Tanabe, Jody

2015-12-01

To investigate whether sex modulates the effects of stimulant dependence on gray matter volume (GMV) in patients who have achieved long-term abstinence and to characterize how sex modulates GMV according to specific behavioral measures, such as dependence symptom count, behavioral approach, and impulsivity. Colorado Multiple Institutional Review Board approval and informed consent were obtained. In this prospective parallel group study, 127 age- and sex-matched participants (68 control subjects [28 women, 40 men] and 59 patients with stimulant dependence [28 women, 31 men]) underwent T1-weighted spoiled gradient-echo inversion recovery magnetic resonance imaging of the brain at 3 T. Images were segmented by using voxel-based morphometric software. After adjustment for age, education, and head size, the effects of group according to sex on GMV and main effects were analyzed throughout the whole brain by using an analysis of covariance family-wise cluster corrected for multiple comparisons, with a threshold P value of less than .05. Dependence symptom count and behavioral measurements were correlated with GMV in the whole brain and in five a priori regions of interest. The effects of group according to sex on GMV were significant in numerous regions (P < .001). Compared with female control subjects, women with stimulant dependence had significantly lower GMV in widespread brain regions (P < .001). There were no significant differences in GMV between male control subjects and men with stimulant dependence (P = .625). Dependence symptom count negatively correlated with GMV in the nucleus accumbens in women (left: r = -0.364, P = .047; right: r = -0.407, P = .031) but not in men (left: r = -0.063, P = .737; right: r = -0.174, P = .349). Behavioral approach (P = .002) and impulsivity (P = .013) correlated negatively with frontal and temporal GMV changes in women with stimulant dependence but not in the other groups. Vast changes in GMV were observed in women with stimulant dependence after prolonged abstinence, but were not observed in men. Sexual dimorphism in drug-related neuroanatomic changes and brain-behavior relationships may be mechanisms underlying the difference in clinical profiles of addiction between women and men.

Comparison of brain volume abnormalities between ADHD and conduct disorder in adolescence

PubMed Central

Stevens, Michael C.; Haney-Caron, Emily

2012-01-01

Background Previous studies of brain structure abnormalities in conduct disorder and attention-deficit/hyperactivity disorder (ADHD) samples have been limited owing to cross-comorbidity, preventing clear understanding of which structural brain abnormalities might be specific to or shared by each disorder. To our knowledge, this study was the first direct comparison of grey and white matter volumes in diagnostically “pure” (i.e., no comorbidities) conduct disorder and ADHD samples. Methods Groups of adolescents with noncormobid conduct disorder and with noncomorbid, combined-subtype ADHD were compared with age- and sex-matched controls using DARTEL voxel-based analysis of T1-weighted brain structure images. Analysis of variance with post hoc analyses compared whole brain grey and white matter volumes among the groups. Results We included 24 adolescents in each study group. There was an overall 13% reduction in grey matter volume in adolescents with conduct disorder, reflecting numerous frontal, temporal, parietal and subcortical deficits. The same grey matter regions typically were not abnormal in those with ADHD. Deficits in frontal lobe regions previously identified in studies of patients with ADHD either were not detected, or group differences from controls were not as strong as those between the conduct disorder and control groups. White matter volume measurements did not differentiate conduct disorder and ADHD. Limitations Our modest sample sizes prevented meaningful examination of individual features of ADHD or conduct disorder, such as aggression, callousness, or hyperactive versus inattentive symptom subtypes. Conclusion The evidence supports theories of frontotemporal abnormalities in adolescents with conduct disorder, but raises questions about the prominence of frontal lobe and striatal structural abnormalities in those with noncomorbid, combined-subtype ADHD. The latter point is clinically important, given the widely held belief that ADHD is associated with numerous frontal lobe structural deficits, a conclusion that is not strongly supported following direct comparison of diagnostically pure groups. The results are important for future etiological studies, particularly those seeking to identify how early expression of specific brain structure abnormalities could potentiate the risk for antisocial behaviour. PMID:22663946

Does body mass play a role in the regulation of food intake?

PubMed

Speakman, John R; Stubbs, R James; Mercer, Julian G

2002-11-01

It is widely believed that body fatness (and hence total body mass) is regulated by a lipostatic feedback system. This system is suggested to involve at least one peripheral signalling compound, which signals to the brain the current size of body fat stores. In the brain the level of the signal is compared with a desirable target level, and food intake and energy expenditure are then regulated to effect changes in the size of body fat stores. There is considerable support for this theory at several different levels of investigation. Patterns of body-mass change in subjects forced into energy imbalance seem to demonstrate homeostasis, and long-term changes in body mass are minor compared with the potential changes that might result from energy imbalance. Molecular studies of signalling compounds have suggested a putative lipostatic signal (leptin) and a complex network of downstream processing events in the brain, polymorphisms of which lead to disruption of body-mass regulation. This network of neuropeptides provides a rich seam of potential pharmaceutical targets for the control of obesity. Despite this consistent explanation for the observed phenomena at several different levels of enquiry, there are alternative explanations. In the present paper we explore the possibility that the existence of lipostatic regulation of body fatness is an illusion generated by the links between body mass and energy expenditure and responses to energy imbalance that are independent of body mass. Using computer-based models of temporal patterns in energy balance we show that common patterns of change in body mass following perturbation can be adequately explained by this 'non-lipostatic' model. This model has some important implications for the interpretations that we place on the molecular events in the brain, and ultimately in the search for pharmaceutical agents for alleviation of obesity.

Central nervous system abnormalities in Fanconi anaemia: patterns and frequency on magnetic resonance imaging

PubMed Central

Alston, Robert; Wright, Neville B; Chandler, Kate; Bonney, Denise; Wynn, Robert F; Will, Andrew M; Punekar, Maqsood; Loughran, Sean; Kilday, John-Paul; Schindler, Detlev; Patel, Leena; Meyer, Stefan

2015-01-01

Objective: Fanconi anaemia (FA) is an inherited disease associated with congenital and developmental abnormalities resulting from the disruption of a multigenic DNA damage response pathway. This study aimed to define the MRI appearances of the brain in patients with FA in correlation with their genetic and clinical features. Methods: A review of the brain MRI in 20 patients with FA was performed. Pituitary size and frequencies of the radiological findings of individuals with FA and age-matched controls were determined. Results: Abnormalities were identified in 18 (90%) patients with FA, the commonest being a small pituitary (68%, p < 0.01 females and p < 0.001 males). In five cases (25%, p = 0.02), the pituitary morphology was also abnormal. Posterior fossa abnormalities were seen in six cases (30%, p = 0.01) including Chiari I malformation (n = 3), Dandy–Walker variant (n = 2) and cerebellar atrophy (n = 2). Six patients (30%, p = 0.01) had morphological structural variation of the corpus callosum (CC). Conclusion: The incidence of central nervous system (CNS) abnormalities in FA is higher than previously reported, with a midline predominance that points to impact in the early stages of CNS development. MRI brain imaging is important for endocrine assessment and pre-transplant evaluation and can make an important contribution to clinical decision-making. Advances in knowledge: The incidence of brain structural abnormalities in FA is higher than previously reported, with abnormalities of the posterior fossa, CC and pituitary being common. There is an association with gender and reduction in pituitary size which does not strongly correlate with biochemically evident endocrine abnormality. PMID:26369989

Facilitating return to work through early specialist health-based interventions (FRESH): protocol for a feasibility randomised controlled trial.

PubMed

Radford, Kathryn A; Phillips, Julie; Jones, Trevor; Gibson, Ali; Sutton, Chris; Watkins, Caroline; Sach, Tracey; Duley, Lelia; Walker, Marion; Drummond, Avril; Hoffman, Karen; O'Connor, Rory; Forshaw, Denise; Shakespeare, David

2015-01-01

Over one million people sustain traumatic brain injury each year in the UK and more than 10 % of these are moderate or severe injuries, resulting in cognitive and psychological problems that affect the ability to work. Returning to work is a primary rehabilitation goal but fewer than half of traumatic brain injury survivors achieve this. Work is a recognised health service outcome, yet UK service provision varies widely and there is little robust evidence to inform rehabilitation practice. A single-centre cohort comparison suggested better work outcomes may be achieved through early occupational therapy targeted at job retention. This study aims to determine whether this intervention can be delivered in three new trauma centres and to conduct a feasibility, randomised controlled trial to determine whether its effects and cost effectiveness can be measured to inform a definitive trial. Mixed methods study, including feasibility randomised controlled trial, embedded qualitative studies and feasibility economic evaluation will recruit 102 people with traumatic brain injury and their nominated carers from three English UK National Health Service (NHS) trauma centres. Participants will be randomised to receive either usual NHS rehabilitation or usual rehabilitation plus early specialist traumatic brain injury vocational rehabilitation delivered by an occupational therapist. The primary objective is to assess the feasibility of conducting a definitive trial; secondary objectives include measurement of protocol integrity (inclusion/exclusion criteria, intervention adherence, reasons for non-adherence) recruitment rate, the proportion of eligible patients recruited, reasons for non-recruitment, spectrum of TBI severity, proportion of and reasons for loss to follow-up, completeness of data collection, gains in face-to-face V s postal data collection and the most appropriate methods of measuring primary outcomes (return to work, retention) to determine the sample size for a larger trial. To our knowledge, this is the first feasibility randomised controlled trial of a vocational rehabilitation health intervention specific to traumatic brain injury. The results will inform the design of a definitive trial. The trial is registered ISRCTN Number 38581822.

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

Genetic neuropathology of obsessive psychiatric syndromes

PubMed Central

Jaffe, A E; Deep-Soboslay, A; Tao, R; Hauptman, D T; Kaye, W H; Arango, V; Weinberger, D R; Hyde, T M; Kleinman, J E

2014-01-01

Anorexia nervosa (AN), bulimia nervosa (BN) and obsessive-compulsive disorder (OCD) are complex psychiatric disorders with shared obsessive features, thought to arise from the interaction of multiple genes of small effect with environmental factors. Potential candidate genes for AN, BN and OCD have been identified through clinical association and neuroimaging studies; however, recent genome-wide association studies of eating disorders (ED) so far have failed to report significant findings. In addition, few, if any, studies have interrogated postmortem brain tissue for evidence of expression quantitative trait loci (eQTLs) associated with candidate genes, which has particular promise as an approach to elucidating molecular mechanisms of association. We therefore selected single-nucleotide polymorphisms (SNPs) based on candidate gene studies for AN, BN and OCD from the literature, and examined the association of these SNPs with gene expression across the lifespan in prefrontal cortex of a nonpsychiatric control cohort (N=268). Several risk-predisposing SNPs were significantly associated with gene expression among control subjects. We then measured gene expression in the prefrontal cortex of cases previously diagnosed with obsessive psychiatric disorders, for example, ED (N=15) and OCD/obsessive-compulsive personality disorder or tics (OCD/OCPD/Tic; N=16), and nonpsychiatric controls (N=102) and identified 6 and 286 genes that were differentially expressed between ED compared with controls and OCD cases compared with controls, respectively (false discovery rate (FDR) <5%). However, none of the clinical risk SNPs were among the eQTLs and none were significantly associated with gene expression within the broad obsessive cohort, suggesting larger sample sizes or other brain regions may be required to identify candidate molecular mechanisms of clinical association in postmortem brain data sets. PMID:25180571

Genetic neuropathology of obsessive psychiatric syndromes.

PubMed

Jaffe, A E; Deep-Soboslay, A; Tao, R; Hauptman, D T; Kaye, W H; Arango, V; Weinberger, D R; Hyde, T M; Kleinman, J E

2014-09-02

Anorexia nervosa (AN), bulimia nervosa (BN) and obsessive-compulsive disorder (OCD) are complex psychiatric disorders with shared obsessive features, thought to arise from the interaction of multiple genes of small effect with environmental factors. Potential candidate genes for AN, BN and OCD have been identified through clinical association and neuroimaging studies; however, recent genome-wide association studies of eating disorders (ED) so far have failed to report significant findings. In addition, few, if any, studies have interrogated postmortem brain tissue for evidence of expression quantitative trait loci (eQTLs) associated with candidate genes, which has particular promise as an approach to elucidating molecular mechanisms of association. We therefore selected single-nucleotide polymorphisms (SNPs) based on candidate gene studies for AN, BN and OCD from the literature, and examined the association of these SNPs with gene expression across the lifespan in prefrontal cortex of a nonpsychiatric control cohort (N=268). Several risk-predisposing SNPs were significantly associated with gene expression among control subjects. We then measured gene expression in the prefrontal cortex of cases previously diagnosed with obsessive psychiatric disorders, for example, ED (N=15) and OCD/obsessive-compulsive personality disorder or tics (OCD/OCPD/Tic; N=16), and nonpsychiatric controls (N=102) and identified 6 and 286 genes that were differentially expressed between ED compared with controls and OCD cases compared with controls, respectively (false discovery rate (FDR) <5%). However, none of the clinical risk SNPs were among the eQTLs and none were significantly associated with gene expression within the broad obsessive cohort, suggesting larger sample sizes or other brain regions may be required to identify candidate molecular mechanisms of clinical association in postmortem brain data sets.

Prediction error and somatosensory insula activation in women recovered from anorexia nervosa

PubMed Central

Frank, Guido K.W.; Collier, Shaleise; Shott, Megan E.; O’Reilly, Randall C.

2016-01-01

Background Previous research in patients with anorexia nervosa showed heightened brain response during a taste reward conditioning task and heightened sensitivity to rewarding and punishing stimuli. Here we tested the hypothesis that individuals recovered from anorexia nervosa would also experience greater brain activation during this task as well as higher sensitivity to salient stimuli than controls. Methods Women recovered from restricting-type anorexia nervosa and healthy control women underwent fMRI during application of a prediction error taste reward learning paradigm. Results Twenty-four women recovered from anorexia nervosa (mean age 30.3 ± 8.1 yr) and 24 control women (mean age 27.4 ± 6.3 yr) took part in this study. The recovered anorexia nervosa group showed greater left posterior insula activation for the prediction error model analysis than the control group (family-wise error– and small volume–corrected p < 0.05). A group × condition analysis found greater posterior insula response in women recovered from anorexia nervosa than controls for unexpected stimulus omission, but not for unexpected receipt. Sensitivity to punishment was elevated in women recovered from anorexia nervosa. Limitations This was a cross-sectional study, and the sample size was modest. Conclusion Anorexia nervosa after recovery is associated with heightened prediction error–related brain response in the posterior insula as well as greater response to unexpected reward stimulus omission. This finding, together with behaviourally increased sensitivity to punishment, could indicate that individuals recovered from anorexia nervosa are particularly responsive to punishment. The posterior insula processes somatosensory stimuli, including unexpected bodily states, and greater response could indicate altered perception or integration of unexpected or maybe unwanted bodily feelings. Whether those findings develop during the ill state or whether they are biological traits requires further study. PMID:26836623

Prediction error and somatosensory insula activation in women recovered from anorexia nervosa.

PubMed

Frank, Guido K W; Collier, Shaleise; Shott, Megan E; O'Reilly, Randall C

2016-08-01

Previous research in patients with anorexia nervosa showed heightened brain response during a taste reward conditioning task and heightened sensitivity to rewarding and punishing stimuli. Here we tested the hypothesis that individuals recovered from anorexia nervosa would also experience greater brain activation during this task as well as higher sensitivity to salient stimuli than controls. Women recovered from restricting-type anorexia nervosa and healthy control women underwent fMRI during application of a prediction error taste reward learning paradigm. Twenty-four women recovered from anorexia nervosa (mean age 30.3 ± 8.1 yr) and 24 control women (mean age 27.4 ± 6.3 yr) took part in this study. The recovered anorexia nervosa group showed greater left posterior insula activation for the prediction error model analysis than the control group (family-wise error- and small volume-corrected p < 0.05). A group × condition analysis found greater posterior insula response in women recovered from anorexia nervosa than controls for unexpected stimulus omission, but not for unexpected receipt. Sensitivity to punishment was elevated in women recovered from anorexia nervosa. This was a cross-sectional study, and the sample size was modest. Anorexia nervosa after recovery is associated with heightened prediction error-related brain response in the posterior insula as well as greater response to unexpected reward stimulus omission. This finding, together with behaviourally increased sensitivity to punishment, could indicate that individuals recovered from anorexia nervosa are particularly responsive to punishment. The posterior insula processes somatosensory stimuli, including unexpected bodily states, and greater response could indicate altered perception or integration of unexpected or maybe unwanted bodily feelings. Whether those findings develop during the ill state or whether they are biological traits requires further study.

Diffuse traumatic axonal injury in mice induces complex behavioural alterations that are normalized by neutralization of interleukin-1β.

PubMed

Ekmark-Lewén, Sara; Flygt, Johanna; Fridgeirsdottir, Gudrun A; Kiwanuka, Olivia; Hånell, Anders; Meyerson, Bengt J; Mir, Anis K; Gram, Hermann; Lewén, Anders; Clausen, Fredrik; Hillered, Lars; Marklund, Niklas

2016-04-01

Widespread traumatic axonal injury (TAI) results in brain network dysfunction, which commonly leads to persisting cognitive and behavioural impairments following traumatic brain injury (TBI). TBI induces a complex neuroinflammatory response, frequently located at sites of axonal pathology. The role of the pro-inflammatory cytokine interleukin (IL)-1β has not been established in TAI. An IL-1β-neutralizing or a control antibody was administered intraperitoneally at 30 min following central fluid percussion injury (cFPI), a mouse model of widespread TAI. Mice subjected to moderate cFPI (n = 41) were compared with sham-injured controls (n = 20) and untreated, naive mice (n = 9). The anti-IL-1β antibody reached the target brain regions in adequate therapeutic concentrations (up to ~30 μg/brain tissue) at 24 h post-injury in both cFPI (n = 5) and sham-injured (n = 3) mice, with lower concentrations at 72 h post-injury (up to ~18 μg/g brain tissue in three cFPI mice). Functional outcome was analysed with the multivariate concentric square field (MCSF) test at 2 and 9 days post-injury, and the Morris water maze (MWM) at 14-21 days post-injury. Following TAI, the IL-1β-neutralizing antibody resulted in an improved behavioural outcome, including normalized behavioural profiles in the MCSF test. The performance in the MWM probe (memory) trial was improved, although not in the learning trials. The IL-1β-neutralizing treatment did not influence cerebral ventricle size or the number of microglia/macrophages. These findings support the hypothesis that IL-1β is an important contributor to the processes causing complex cognitive and behavioural disturbances following TAI. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Anti-inflammatory effects of vinpocetine on the functional expression of nuclear factor-kappa B and tumor necrosis factor-alpha in a rat model of cerebral ischemia-reperfusion injury.

PubMed

Wang, Hongxin; Zhang, Kan; Zhao, Lan; Tang, Jiangwei; Gao, Luyan; Wei, Zhongping

2014-04-30

The restoration of blood flow to the brain after ischemic stroke prevents further, extensive damage but can result in reperfusion injury. The inflammation response is one of many factors involved in cerebral ischemia-reperfusion injury. This study investigated the use of vinpocetine, a drug used to treat cognitive impairment, to explore its effects on inflammation in a rat model of cerebral ischemia-reperfusion. Wistar rats were randomly assigned to a control group, (n=40) a cerebral ischemia-reperfusion group (n=52) and a vinpocetine cerebral ischemia-reperfusion group (n=52). A model of middle cerebral artery occlusion was induced for 2h followed by reperfusion and the infarct size was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining 6h, 24h, 3 days, and 7 days after reperfusion. The dry-wet weight method was used to measure brain water content and evaluate the extent of brain edema. Immunohistochemistry and in-situ hybridization were used to detect the expression of NF-κB and TNF-α. The NF-κB levels in ischemic brain tissue increased 6h after reperfusion and the TNF-α levels increased at 24h, both reached their peaks at day 3 then decreased gradually, but remained above the controls at day 7. Vinpocetine decreased the levels of NF-κB and TNF-α 24h and 3 days after reperfusion. NF-κB and TNF-α is associated with changes in brain edema and infarct volume. Vinpocetine decreases the expression of NF-κB and TNF-α and inhibits the inflammatory response after cerebral ischemia-reperfusion. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Altered fractional amplitude of low frequency fluctuation in premenstrual syndrome: A resting state fMRI study.

PubMed

Liao, Hai; Duan, Gaoxiong; Liu, Peng; Liu, Yanfei; Pang, Yong; Liu, Huimei; Tang, Lijun; Tao, Jien; Wen, Danhong; Li, Shasha; Liang, Lingyan; Deng, Demao

2017-08-15

Premenstrual syndrome (PMS) is becoming highly prevalent among female and is characterized by emotional, physical and behavior symptoms. Previous evidence suggested functional dysregulation of female brain was expected to be involved in the etiology of PMS. The aim of present study was to evaluate the alterations of spontaneous brain activity in PMS patients based on functional magnetic resonance imaging (fMRI). 20 PMS patients and 21 healthy controls underwent resting-state fMRI scanning during luteal phase. All participants were asked to complete a prospective daily record of severity of problems (DRSP) questionnaire. Compared with healthy controls, the results showed that PMS patients had increased fALFF in bilateral precuneus, left hippocampus and left inferior temporal cortex, and decreased fALFF in bilateral anterior cingulate cortex (ACC) and cerebellum at luteal phase. Moreover, the DRSP scores of PMS patients were negatively correlated with the mean fALFF in ACC and positively correlated with the fALFF in precuneus. (1) the study did not investigate whether or not abnormal brain activity differences between groups in mid-follicular phase, and within-group changes. between phases.(2) it was relatively limited sample size and the participants were young; (3) fALFF could not provide us with more holistic information of brain network;(4) the comparisons of PMS and premenstrual dysphoric disorder (PMDD) were not involved in the study. The present study shows abnormal spontaneous brain activity in PMS patients revealed by fALFF, which could provide neuroimaging evidence to further improve our understanding of the underlying neural mechanism of PMS. Copyright © 2017. Published by Elsevier B.V.

Restoration of motor function following spinal cord injury via optimal control of intraspinal microstimulation: toward a next generation closed-loop neural prosthesis

PubMed Central

Grahn, Peter J.; Mallory, Grant W.; Berry, B. Michael; Hachmann, Jan T.; Lobel, Darlene A.; Lujan, J. Luis

2014-01-01

Movement is planned and coordinated by the brain and carried out by contracting muscles acting on specific joints. Motor commands initiated in the brain travel through descending pathways in the spinal cord to effector motor neurons before reaching target muscles. Damage to these pathways by spinal cord injury (SCI) can result in paralysis below the injury level. However, the planning and coordination centers of the brain, as well as peripheral nerves and the muscles that they act upon, remain functional. Neuroprosthetic devices can restore motor function following SCI by direct electrical stimulation of the neuromuscular system. Unfortunately, conventional neuroprosthetic techniques are limited by a myriad of factors that include, but are not limited to, a lack of characterization of non-linear input/output system dynamics, mechanical coupling, limited number of degrees of freedom, high power consumption, large device size, and rapid onset of muscle fatigue. Wireless multi-channel closed-loop neuroprostheses that integrate command signals from the brain with sensor-based feedback from the environment and the system's state offer the possibility of increasing device performance, ultimately improving quality of life for people with SCI. In this manuscript, we review neuroprosthetic technology for improving functional restoration following SCI and describe brain-machine interfaces suitable for control of neuroprosthetic systems with multiple degrees of freedom. Additionally, we discuss novel stimulation paradigms that can improve synergy with higher planning centers and improve fatigue-resistant activation of paralyzed muscles. In the near future, integration of these technologies will provide SCI survivors with versatile closed-loop neuroprosthetic systems for restoring function to paralyzed muscles. PMID:25278830

[Alterations of glial fibrillary acidic protein in rat brain after gamma knife irradiation].

PubMed

Ma, Z M; Jiang, B; Ma, J R

2001-08-28

To study glial fibrillary acidic protein (GFAP) immunoreactivity in different time and water content of the rat brain treated with gamma knife radiotherapy and to understand the alteration course of the brain lesion after a single high dose radiosurgical treatment. In the brains of the normal rats were irradiated by gamma knife with 160 Gy-high dose. The irradiated rats were then killed on the 1st day, 7th day, 14th day, and 28th day after radiotherapy, respectively. The positive cells of GFAP in brain tissue were detected by immunostaining; the water content of the brain tissue was measured by microgravimetry. The histological study of the irradiated brain tissue was performed with H.E. and examined under light microscope. The numbers of GFAP-positive astrocytes began to increase on the 1st day after gamma knife irradiation. It was enlarged markedly in the number and size of GFAP-stained astrocytes over the irradiated areas. Up to the 28th day, circumscribed necrosis foci (4 mm in diameter) was seen in the central area of the target. In the brain tissue around the necrosis, GFAP-positive astrocytes significantly increased (P < 0.01, compared with the control group). The swelling of cells in irradiated region was observed on the 1st day; after irradiation endothelial cells degenerated and red blood cells escaped from blood vessel on the 7th day; leakage of Evans blue dye was observed in the target region on the 14th day. There was a significant decrease of specific gravity in the irradiated brain tissue the 14th and 28th day after irradiation. The results suggest that GFAP can be used as a marker for the radiation-induced brain injury. The brain edema and disruption of brain-blood barrier can be occurred during the acute stage after irradiation.

Biopersistence of silver nanoparticles in tissues from Sprague–Dawley rats

PubMed Central

2013-01-01

Silver nanoparticles are known to be distributed in many tissues after oral or inhalation exposure. Thus, understanding the tissue clearance of such distributed nanoparticles is very important to understand the behavior of silver nanoparticles in vivo. For risk assessment purposes, easy clearance indicates a lower overall cumulative toxicity. Accordingly, to investigate the clearance of tissue silver concentrations following oral silver nanoparticle exposure, Sprague–Dawley rats were assigned to 3 groups: control, low dose (100 mg/kg body weight), and high dose (500 mg/kg body weight), and exposed to two different sizes of silver nanoparticles (average diameter 10 and 25 nm) over 28 days. Thereafter, the rats were allowed to recover for 4 months. Regardless of the silver nanoparticle size, the silver content in most tissues gradually decreased during the 4-month recovery period, indicating tissue clearance of the accumulated silver. The exceptions were the silver concentrations in the brain and testes, which did not clear well, even after the 4-month recovery period, indicating an obstruction in transporting the accumulated silver out of these tissues. Therefore, the results showed that the size of the silver nanoparticles did not affect their tissue distribution. Furthermore, biological barriers, such as the blood–brain barrier and blood-testis barrier, seemed to play an important role in the silver clearance from these tissues. PMID:24059869

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)

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…

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

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.

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.

Widespread Volumetric Reductions in Schizophrenia and Schizoaffective Patients Displaying Compromised Cognitive Abilities.

PubMed

Van Rheenen, Tamsyn E; Cropley, Vanessa; Zalesky, Andrew; Bousman, Chad; Wells, Ruth; Bruggemann, Jason; Sundram, Suresh; Weinberg, Danielle; Lenroot, Roshel K; Pereira, Avril; Shannon Weickert, Cynthia; Weickert, Thomas W; Pantelis, Christos

2018-04-06

Progress toward understanding brain mechanisms in psychosis is hampered by failures to account for within-group heterogeneity that exists across neuropsychological domains. We recently identified distinct cognitive subgroups that might assist in identifying more biologically meaningful subtypes of psychosis. In the present study, we examined whether underlying structural brain abnormalities differentiate these cognitively derived subgroups. 1.5T T1 weighted structural scans were acquired for 168 healthy controls and 220 patients with schizophrenia/schizoaffective disorder. Based on previous work, 47 patients were categorized as being cognitively compromised (impaired premorbid and current IQ), 100 as cognitively deteriorated (normal premorbid IQ, impaired current IQ), and 73 as putatively cognitively preserved (premorbid and current IQ within 1 SD of controls). Global, subcortical and cortical volume, thickness, and surface area measures were compared among groups. Whole cortex, subcortical, and regional volume and thickness reductions were evident in all subgroups compared to controls, with the largest effect sizes in the compromised group. This subgroup also showed abnormalities in regions not seen in the other patient groups, including smaller left superior and middle frontal areas, left anterior and inferior temporal areas and right lateral medial and inferior frontal, occipital lobe and superior temporal areas. This pattern of more prominent brain structural abnormalities in the group with the most marked cognitive impairments-both currently and putatively prior to illness onset, is consistent with the concept of schizophrenia as a progressive neurodevelopmental disorder. In this group, neurodevelopmental and neurodegenerative factors may be important for cognitive function.

Statistical testing and power analysis for brain-wide association study.

PubMed

Gong, Weikang; Wan, Lin; Lu, Wenlian; Ma, Liang; Cheng, Fan; Cheng, Wei; Grünewald, Stefan; Feng, Jianfeng

2018-04-05

The identification of connexel-wise associations, which involves examining functional connectivities between pairwise voxels across the whole brain, is both statistically and computationally challenging. Although such a connexel-wise methodology has recently been adopted by brain-wide association studies (BWAS) to identify connectivity changes in several mental disorders, such as schizophrenia, autism and depression, the multiple correction and power analysis methods designed specifically for connexel-wise analysis are still lacking. Therefore, we herein report the development of a rigorous statistical framework for connexel-wise significance testing based on the Gaussian random field theory. It includes controlling the family-wise error rate (FWER) of multiple hypothesis testings using topological inference methods, and calculating power and sample size for a connexel-wise study. Our theoretical framework can control the false-positive rate accurately, as validated empirically using two resting-state fMRI datasets. Compared with Bonferroni correction and false discovery rate (FDR), it can reduce false-positive rate and increase statistical power by appropriately utilizing the spatial information of fMRI data. Importantly, our method bypasses the need of non-parametric permutation to correct for multiple comparison, thus, it can efficiently tackle large datasets with high resolution fMRI images. The utility of our method is shown in a case-control study. Our approach can identify altered functional connectivities in a major depression disorder dataset, whereas existing methods fail. A software package is available at https://github.com/weikanggong/BWAS. Copyright © 2018 Elsevier B.V. All rights reserved.

Dysfunctional Incidental Olfaction in Mild Cognitive Impairment (MCI): An Electroencephalography (EEG) Study

PubMed Central

Walla, Peter; Duregger, Cornelia; Deecke, Lüder; Dal-Bianco, Peter

2011-01-01

Our study provides evidence that Mild Cognitive Impairment (MCI) is associated with olfactory dysfunction on both conscious and non-conscious levels. MCI patients and age-matched controls underwent a face processing task during which sympathy decisions had to be made via button presses. Incidentally, some of the faces were associated with a simultaneously presented odour. Although attention was paid to faces, brain activities were analysed with respect to odour versus no-odour conditions. Behavioural differences were found related to overall face recognition performance, but these were not statistically significant. However, odour-related neurophysiology differed between both groups. Normal controls demonstrated brain activity differences between odour and no-odour conditions that resemble difference activity patterns in healthy young participants as described in a previous magnetoencephalography (MEG) study [1]. They showed odour-related activity patterns between about 160 ms and 320 ms after stimulus onset and between about 640 ms and 720 ms. On the other hand, the patient group did not show any such difference activities. Based on previous research we interpret the early odour-related brain activity pattern in controls as being associated with subliminal olfaction and the later activity pattern with conscious olfaction. None of these were found in MCI patients, although it has to be emphasised that our sample size was rather small. We confirm previous findings about olfactory related dysfunction in patients with MCI and conclude from our findings that even subliminal odour-related information processing is impaired. PMID:24962612

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.

SAD-B kinase regulates pre-synaptic vesicular dynamics at hippocampal Schaffer collateral synapses and affects contextual fear memory.

PubMed

Watabe, Ayako M; Nagase, Masashi; Hagiwara, Akari; Hida, Yamato; Tsuji, Megumi; Ochiai, Toshitaka; Kato, Fusao; Ohtsuka, Toshihisa

2016-01-01

Synapses of amphids defective (SAD)-A/B kinases control various steps in neuronal development and differentiation, such as axon specifications and maturation in central and peripheral nervous systems. At mature pre-synaptic terminals, SAD-B is associated with synaptic vesicles and the active zone cytomatrix; however, how SAD-B regulates neurotransmission and synaptic plasticity in vivo remains unclear. Thus, we used SAD-B knockout (KO) mice to study the function of this pre-synaptic kinase in the brain. We found that the paired-pulse ratio was significantly enhanced at Shaffer collateral synapses in the hippocampal CA1 region in SAD-B KO mice compared with wild-type littermates. We also found that the frequency of the miniature excitatory post-synaptic current was decreased in SAD-B KO mice. Moreover, synaptic depression following prolonged low-frequency synaptic stimulation was significantly enhanced in SAD-B KO mice. These results suggest that SAD-B kinase regulates vesicular release probability at pre-synaptic terminals and is involved in vesicular trafficking and/or regulation of the readily releasable pool size. Finally, we found that hippocampus-dependent contextual fear learning was significantly impaired in SAD-B KO mice. These observations suggest that SAD-B kinase plays pivotal roles in controlling vesicular release properties and regulating hippocampal function in the mature brain. Synapses of amphids defective (SAD)-A/B kinases control various steps in neuronal development and differentiation, but their roles in mature brains were only partially known. Here, we demonstrated, at mature pre-synaptic terminals, that SAD-B regulates vesicular release probability and synaptic plasticity. Moreover, hippocampus-dependent contextual fear learning was significantly impaired in SAD-B KO mice, suggesting that SAD-B kinase plays pivotal roles in controlling vesicular release properties and regulating hippocampal function in the mature brain. © 2015 International Society for Neurochemistry.

Conservation law for self-paced movements.

PubMed

Huh, Dongsung; Sejnowski, Terrence J

2016-08-02

Optimal control models of biological movements introduce external task factors to specify the pace of movements. Here, we present the dual to the principle of optimality based on a conserved quantity, called "drive," that represents the influence of internal motivation level on movement pace. Optimal control and drive conservation provide equivalent descriptions for the regularities observed within individual movements. For regularities across movements, drive conservation predicts a previously unidentified scaling law between the overall size and speed of various self-paced hand movements in the absence of any external tasks, which we confirmed with psychophysical experiments. Drive can be interpreted as a high-level control variable that sets the overall pace of movements and may be represented in the brain as the tonic levels of neuromodulators that control the level of internal motivation, thus providing insights into how internal states affect biological motor control.